Rheumatoid Arthritis

Biologic treatments for rheumatoid arthritis: anti-TNF, anti IL-6, anti B-cell and anti T cell

Biologic treatments are antibodies which are designed to destroy or limit key proteins and cells that drive RA. There are several different types of biological treatments for RA including:

  • anti-TNF,
  • anti IL-6,
  • anti B-cell and
  • anti-T cell

These work in different ways.

1. Anti-TNF therapy works by blocking the action of TNF (tumour necrosis factor), a molecule responsible for increasing levels of inflammation in people with rheumatoid arthritis.
2. Anti IL-6 therapy (tocilizumab) blocks another important protein that drives inflammation and is responsible for a lot of the flu-like symptoms that affects some people with RA.
3. Anti B-cell therapy (rituximab - trade name MabThera) removes antibody-producing white blood cells called B-cells which play an important role in inflammatory reactions that can lead to joint inflammation, deformity and loss of function.
4. Anti-T cell therapy (abatacept) stops certain white cells talking to each other and becoming activated and inflammatory.
 
Most of these drugs are given in combination with the conventional DMARDs already mentioned (methotrexate etc).

There are lots of different types of anti-TNF drugs including: Infliximab (Remicade) etanercept (Enbrel), adalimumab (Humira), certolizumab pegol (Cimzia) and golimumab (Simponi) some are given by intravenous drip and others as injections.
 
The anti IL-6 treatment tocilizumab (Actemra) is self-injected once a week, although can be given as a drip every four weeks if preferred.

B-cell depleting therapy rituximab is given by intravenous drip in a hospital clinic. A steroid injection is usually given first. Usually two intravenous infusions are given 2 weeks apart. This treatment is repeated at six months and then only repeated if/when there are signs that improvement is wearing off, which can be anything from 6 months to 3 years later. 

Anti-T cell therapy abatacept (Orencia) is taken as weekly self-injections or monthly as a drip in the hospital if preferred.
 
Only a minority of patients with RA will have these drugs, as they are only used when standard drugs are either not tolerated or are not effective and are only given to people who fulfil specific criteria set out by the National Institute for Health and Care Excellence (NICE). These include a person's level of disease activity, as measured by their erythrocyte sedimentation rate (ESR), and non-response to other disease modifying anti-rheumatic drugs (DMARDs)

You can listen to, watch or read Professor Robert Moots introduction to biologic treatments. 

Professor Robert Moots explains about biologic treatments for rheumatoid arthritis.

Professor Robert Moots explains about biologic treatments for rheumatoid arthritis.

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I'm Robert Moots. I'm Professor of Rheumatology at the University of Liverpool and a consultant rheumatologist. I'm going to talk with you now about biologic treatments for rheumatoid arthritis. And there's a group of drugs that have been developed really as designer drugs, particularly to inhibit certain parts of the process that cause inflammation, and that's what causes rheumatoid arthritis. First of all, we have to remember that before the biologic drugs, all of the drugs that we used to treat rheumatoid arthritis, we really didn't fully understand why they worked. We know that they could help disease, but we didn't really know fully why. And also because in many ways they're crude drugs, they also had lots of potential side effects. 

Over recent years however we've learnt much more about what causes rheumatoid arthritis, and as we've learnt these things we've been able to design new drugs that specifically inhibit important parts of the pathways that cause the inflammation. The first drugs that were developed in this way were the TNF alpha blockers. TNF stands for tumour necrosis factor, and this is an important chemical that causes inflammation and is particularly high in rheumatoid arthritis. What we learnt is that if we inhibit this chemical, patients get better. And there are three drugs that are available at the moment that do this. First of all infliximab, then etanercept and adalimumab. So they're very complicated names, but the bottom line is that they neutralise this inflammation chemical and this can help get people better.

So let's consider these individually. First of all infliximab. This is a protein like the others, but an antibody. And the antibody is made up of a tiny fragment of part of a mouse antibody coupled to a human antibody. And this drug is given by intravenous infusion. So patients have to go in and have a drip gradually going though into the vein over a period of a few hours. And once patients are stable on this treatment, the drug is given every eight weeks. The other drug, adalimumab, is also an antibody, but it's a fully human antibody and therefore people are a bit less prone to develop an intolerance to it, which I'll explain in a minute. The third drug, etanercept, also a protein, is coupled, is a human antibody coupled to the natural receptor for TNF alpha. So adalimumab and etanercept are actually given by the patient as an injection under the skin, a subcutaneous injection. Etanercept is given once a week, and adalimumab is given once a fortnight. 

These drugs are also known by their trade names. Infliximab is also known as Remicade. Adalimumab as Humira, which is much easier to pronounce. And etanercept is also known as Enbrel. We know that all three of these TNF blockers work very well. In fact these have become the gold standard for treating rheumatoid arthritis because they give the best results. However, it's important to know that not everybody with rheumatoid arthritis needs a TNF alpha blocker. Patients with milder disease can do perfectly well on simple drugs. And at the moment in the United Kingdom we have to reserve the TNF blockers for people who have got bad disease and who have also not responded to the simple drugs, including methotrexate. But if you're in that situation, you're not responding to the simple drugs and you do have bad disease, then you will be eligible to have this treatment. TNF blockers are given by rheumatologists, and it's important that their delivery is supervised by a rheumatologist from a hospital.

As I've mentioned, these drugs give the best chance of responding if your disease is bad. But also, like any drug, there is always a risk of a side effect. The side effects that we know about which are likely in some patients on a TNF blocker re

Anti-TNF and B-cell treatments
Some of the people we interviewed were currently on the 'biological' drugs (including four who took part in the original clinical trials) and others were considering it. In those who were using it their quality of life had improved - less inflammation and stiffness, less fatigue and in some cases less pain, so giving them greater mobility, energy and strength. Some people said they had had only minor flare ups of their RA since starting anti-TNF. 

Sandra was not responding to treatment and her symptoms were getting worse. She describes how her...

Sandra was not responding to treatment and her symptoms were getting worse. She describes how her...

Age at interview: 51
Sex: Female
Age at diagnosis: 51
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Each time I was given a new drug, I was told well this is really good, this is really good and we will get there but having then been on the three drugs for quite a while it was obvious by my blood results that the inflammation was just not going down. In between times I was having steroid injections and the only time I got any relief was for a week or two after the steroid injections but then each time I had a steroid injection, it seemed that the relief from the pain and some of the swelling was lasting a shorter and shorter time.
 
I was in hospital in the November. Yes and by the time I’d had a week in the hospital I was, and I’d had the steroid injections so I was feeling a lot better and that lasted about a month. And then it flared up probably worse than ever so I was then seen by the Consultant again in the December and he then suggested that I, the way forward was to start anti TNF’s. He assessed me and said that I met the criteria and then I had to wait about six weeks to see the specialist nurse to be re-assessed by her.
 
How did he assess you?
 
He did my DAS score which is when they obviously check all your joints for swelling and for pain so he counted that up. He listened to the way my life was and the lethargy side of things which was just extreme and he looked at my blood results as well which was still showing high levels of inflammation.
 
So those are the sort of points that meet the criteria?
 
Yes, yeah, you have to, I believe, be on a certain level with all those things so you do have to be quite bad to meet the criteria. And then it has to be, you have to be assessed again to make sure that, that perhaps just wasn’t a short flare up I presume and that you are still meeting the criteria when you are checked by the second person.
 
So that’s the specialist nurse?
 
Yes, yes
 
And she does something similar or?
 
Exactly the same. Yes she did exactly the same tests.
 
Do you have to fill in a questionnaire or?
 
Not really a questionnaire but part of it is they score regarding how much you can do at home and how you rate your daily life if you like. So that will include how well you’re coping with the pain and how much lethargy you get and you score yourself sort of nought to ten as to how you’re actually feeling with it or…
 
And how were you scoring at that time, do you remember?
 
I can’t remember which way round they do it, whether nought’s the worst or ten’s the worst but if ten was the worst, I was scoring about an eight.
 
And how were you feeling emotionally at that time, given that your life has changed?
 
Mm, desperate. Yeah, absolutely desperate. I felt that initially I was told you know, methotrexate would work for me and then I’d, well you’d added in another drug and another drug and nothing had. In the meantime I was getting very worried about my job; I was struggling to do things at home. In fact there was, well most things I couldn’t do at home, I couldn’t cook a meal, I couldn’t wash and dry my hair, I was struggling to drive, I was struggling with daily hygiene, life was just one big struggle and I was constantly feeling absolutely exhausted and it didn’t matter how much I rested or how much I slept, I didn’t ever feel refreshed and ever feel that I’d got some energy.

 

Talks about why they changed her medication to an anti-TNF treatment and the changes it has made...

Talks about why they changed her medication to an anti-TNF treatment and the changes it has made...

Age at interview: 37
Sex: Female
Age at diagnosis: 30
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I was put on anti-TNF about four months ago. I had gone back on my methotrexate after my second child was born. When was that, probably about four months after she was born and I thought great, you know, back on the methotrexate. I understand that is going to work. And it did work. It was really strange. It worked well for about eight months and then I just suddenly, I started to get a flare up and I couldn't quite understand it, and joints swollen, very tired. You think oh no, here we go again. 

Went to my GP. Got seen by the hospital and they increased my methotrexate and it still didn't work. And it is awful, because you think well this is my lifeline. This is my drug that always works. And in actual fact it took me a while to be seen. As my symptoms got worse and worse, I was off work. I was off sick, because I couldn't move very well. And I think you have go through certain criteria don't you to qualify for anti-TNF because of the cost, so they had to basically test me on the other two. DMARD isn't it. So methotrexate wasn't working so they added Leflunomide and Hydroxychloroquine. They didn't do anything, except that my hair started to fall out. 

And then eventually they referred me, after, I must have had about five steroid injections because I was just so inflamed yes, about five steroid injections over' I used to have one a month. I used to be begging for it. And yes, so five steroid injections. Tried the other two DMARDS. They finally referred me to the anti-TNF clinic. 

There was a really, really brilliant registrar at the hospital who referred me. Who I kept seeing. She was wonderful. And anti-TNF, yes the anti-TNF people in the clinic and they sort of did my tender joint count, when they see how many limbs are inflamed. It was funny because I actually had steroid cover. I still had steroids on board when they saw me and I thought I was doing pretty well, but obviously I was still very inflamed. So I qualified for it on that level. And I started it so it is Humira or adalimumab. They seem to give them really strange names. And it worked fantastically. It worked within two weeks and I have been on it ever since.

And so it has made a change to your life, your every day life? 

Absolutely. I am able, because I don't think there is anything, I do remember with me, each time I have had my flare ups I have always got small babies, which is a nightmare. And I can't get on the floor with them. I mean, it is the basics, before I wasn't able to get on the floor with my baby, you know, trying to get onto the floor was just impossible. You know, playing with her was impossible. And anti-TNF has, you know, has enabled me to have a normal life. You wouldn't really think there was anything, anything wrong with me. It is, I mean it has made a huge difference.

The effects of anti-TNF often begin very soon after the first treatment (unlike DMARD treatment) and people felt the initial benefits of reduced swelling and increased mobility within 24 hours or a week. The full effects can take several months to develop, but generally enabled people to plan things in advance and know they would be able to participate. One woman felt it had increased the length of her active day because she was less tired.

She was almost housebound because of her RA. Doctors started her on etanercept (Enbrel) and...

She was almost housebound because of her RA. Doctors started her on etanercept (Enbrel) and...

Age at interview: 26
Sex: Female
Age at diagnosis: 22
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The reason I started that because everything else wouldn't work the, I've been on various different medications and none of them worked, or they would work for a small period of time and then it would just, just slide back down again, and, I started in, it would be about September of last year, and, the previous six months that was when I was particularly bad, and we'd booked a holiday actually which we had to cancel due to it 'cause it's just, I just couldn't go and the doctors had said, “You're just at the point where nothing else is working so we're gonna put you on this medication.” and they explained that it lowers your immune system and, so it's combating the over-activeness of your immune system that causes your joints to flair up and that, and I was given quite a lot of information actually and they do, make you understand how it works and what the side effects are and, because you have to be quite careful if you get a cold or anything you have to, you have to stop taking it because it can, because it lowers your immune system, you know, you can't just carry on taking it 'cause you'll just make yourself ill. So there, there's quite a lot of information that you have to have and you do have to understand it and how it works 'cause if you don't you can, you can make yourself ill yourself by taking it when you shouldn't, so the information was quite plentiful really and it, what was explained and I think they make you understand it because you need to but then when they, I think, they do, they didn't try to say, oh it's gonna be an absolute miracle cure because they don't want to sort of get your hopes up luckily it did it completely, completely changed me life, going on it, but they said, “Look this is the situation a lot of people have been on various sort of medications and nothing's worked and they've tried this and it has completely turned around,” which it did do, luckily [laughs].

Which drug are you taking?

It's etanercept.

About it was, it, was about six months before I started and I couldn't, I couldn't walk very far I was, mostly sort of housebound really 'cause my partner works so obviously he wasn't, you know, I was sort of in the house really and I'd, very severe pains in my feet so I couldn't walk very far, very stiff, swollen knees, hips, I needed help off the chair, and help in and out of the bath and, just, you, I couldn't do anything really I would try to get up and about as much as possible because I knew that if I just sort of stayed in bed or, I'd sort of sat on the sofa all day it just made it worse so I did sort of try and get up as much as possible but, you know, you, I couldn't do anything that you would normally do, I couldn't go out shopping or I couldn't, [sighs] go out for, I mean I tried to sort of go out for small walks but, even that was quite difficult as well and that was for about six months and I had to stop work completely and not do a lot during those six months. and then, when I started taking the anti-TNF drugs it was about two weeks and I felt better, and, less tired and just, just generally better and then, four weeks later, no it's about six weeks later and we'd, we went to America and we did, well we went to Disneyworld and I walked round Disneyworld for two weeks without any problems, so in, within a space of about six weeks I was completely different, so it really, it's a good [laughs] very good drug [laughs].

After being a bit concerned before her first anti-TNF alpha treatment she felt the effects...

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After being a bit concerned before her first anti-TNF alpha treatment she felt the effects...

Age at interview: 49
Sex: Female
Age at diagnosis: 33
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So I had my first appointment in September 2002  and I was absolutely, I think I probably felt, I knew the reports of what the anti-TNF, you know, the good reports, and that to people, the good effects people had felt and I was slightly concerned myself that I would be one of the percentage that it wouldn't work. So I went slightly, hoping that it would work for me but, yes, it was a dramatic change that day. You know, I had, sort of everyone was very good. It was, you know, the staff were wonderful. You know, very nice environment. That night I felt completely different, which was very exciting. 

We went to Stratford-on-Avon that evening and I actually quite late in the evening, walked a distance which I would find quite difficult during the day, but at night-time I would find it very difficult the distance I walked. So it was wonderful. It was a wonderful experience. And I think it's probably, from a pain point of view, it's got better, you know, as time's gone on.

I was quite surprised really that, I was quite prepared for it not to, because previous treatments take time, previous medication you take there's a time lapse between you taking it, whether there is an effect or not an effect. So we, we've had to be very patient or we've had to be previously but this was immediate. This was immediate.  

Felt the effects of Enbrel straight away and has less inflammation and more strength.

Felt the effects of Enbrel straight away and has less inflammation and more strength.

Age at interview: 37
Sex: Female
Age at diagnosis: 27
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The treatment that I am on is supposed to make me feel loads better. I had my first injection nearly four weeks ago of the anti-TNF and by the following morning I could actually get my wedding ring back on which I hadn't been able to do for so long because my fingers were so big. I actually saw my consultant yesterday and I said to him 'I've never known to have wrist bones.

I can actually feel the bones back in my wrists again where the inflammation is just going down so quickly'. And he's seen such a difference in me in four weeks that I'm thinking another four weeks on 'This could be great!' I just want it to work so badly [laugh]. So I'm looking forward rather than backwards. I'm hoping that it's just going to get better. I hope.

I was told that it's, they call it, like, the miracle drug and as much as I wanted to think 'Yes, next week, I'm going to be walking further than I've walked for years', but I also, although my fingers went down the next morning and people were saying 'How do you feel? How do you feel? Do you feel really good?', I was like 'Oh, I feel alright, I feel the same' because I could feel the difference but I had this thing that if I admitted I felt the difference, I would jinx it, it would go wrong. Something would go wrong somewhere.

So although I'm feeling, I am feeling a lot better and so much stronger, I, I frightened myself the other day when I picked [son] up from the floor. I have never done that since he was born. I've always had to have him at arm's, like at hand level, and I actually lifted him from the floor. He fell and hurt himself and I lifted him up and before I realised what I had done I had actually lifted him up. And he weighs a ton and I was amazed [laugh]. Yeah, shocked, cos that's, it's given me a strength that I didn't have, I haven't had for such a long time.

The effects of the anti-TNF were noticeable after a week.

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The effects of the anti-TNF were noticeable after a week.

Age at interview: 29
Sex: Female
Age at diagnosis: 25
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When, when I first had it done, the lady who was doing it said all the people that had recently had this noticed the effect straight away, you know, the same day and when I got home I kept willing for it to happen and it didn't and I didn't feel no different and for that weekend, I had it done on a Friday and that weekend I felt very depressed 'cos I felt no different but after, I would say after about a week I did notice that the pain was a lot better and, but the real test was to reduce my steroids and if there was still no pain that meant it was working. And that's what I did, and it did work and I've hardly had any pain since being on this infliximab.

Sometimes, the benefits of anti-TNF therapy were experienced as gradual and subtle rather than in a swift and observable way. Sandra indicated that she noted the benefits of Cimzia after about twelve weeks but it has not made a significant impact on her lethargy.

Emma talks about the benefits she has experienced since using Cimzia and describes the...

Emma talks about the benefits she has experienced since using Cimzia and describes the...

Age at interview: 24
Sex: Female
Age at diagnosis: 21
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I first started it with an open mind but obviously I had to take the two injections for 3 months and they said there might be improvement within sort of between 3 to 6 months but I’d have to wait that long to see the benefit from it. And I think because it is quite a slow process of it working you don’t realise just how much better you are until quite far down the line. When you realise I can get up in the morning and I’m not as stiff as I used to be. I can actually wear high heeled shoes for a limited amount of time. I can. I have joined a gym.
 
It’s just little things that you can do on a regular basis that you weren’t able to do before. So it’s not like one day you wake up and everything is perfect and you’re all back to normal. It is how you manage to start doing things again that you weren’t able to do before.
 
Ok so it’s a very gradual and slow process.
 
It’s a very gradual process.
 
So there just comes a point where you start, you realise that you can do all these things that you were not doing before?
 
[Uh huh] I think it’s good to mark your achievements as well. I mean this summer just gone I walked a Race for Life and for me doing that considering what I was like last year is amazing. I wouldn’t have been able to do it last year. That’s how bad my feet were. Obviously I’ve had lots of like little injections along the way of steroids and things to alleviate flare ups but considering where I am at the moment to where I was this time last year it’s a huge improvement.
 
So how long was that walk that you did?
 
I think it was 5 kilometers.
 
Five kilometres?
 
I think it was about, yeah three miles, five km I think.
 
Tell me how you were last year because I mean you said that you had sort of pain, you were unable to walk. In comparison how far were you able to walk?
 
The best way to compare it is if I am at work. Last year doing a 12-hour shift I would come home and my ankles would be swollen, my toes would be swollen. They were painful. I had to come home, lift my feet. My partner, bless him, used to rub my feet for me. I used to use a lot of sort of cooling or heat alternatives to try and ease the pain. And that was after work this time last year. Whereas now if I finish a 12-hour shift they may be slightly swollen but that’s probably because of how long I spend on my feet but the pain. I wouldn’t say there’s a pain. I’d say it was more of a dull ache that I know I’ve been on my feet but it’s manageable and I could come home from a 12-hour shift and go out. I could, I can do other things. I don’t have to come home and sit and put my feet up. I know I can carry on for a little bit longer.

 

Taking the anti-TNF medication
Infliximab is infused through an intravenous drip over about 2 hours in hospital as a day patient. One woman enjoyed these sessions in a 'lovely environment' and liked meeting other people with RA. Another now received it every 7 weeks as she noticed the effects wearing off and her symptoms were worse in the last week before her next infusion. When taking part in a clinical trial for Simponi, Pat was selected to have the drug in injection and later in infusion form She experienced side effects when having infusions and also she felt uncomfortable with the lack of privacy in the hospital.

Having the anti-TNF infusion every 8 weeks in hospital is a good experience, she enjoys meeting...

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Having the anti-TNF infusion every 8 weeks in hospital is a good experience, she enjoys meeting...

Age at interview: 49
Sex: Female
Age at diagnosis: 33
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Yeah, I have the infusion once every 8 weeks. And it's, it's like a little club really. I mean it's nice actually. It's, it's a very nice environment, it's very relaxed which is great. If, if you feel relaxed then you don't mind coming. Yet, I feel it, I feel I need, well probably as time has gone on, I don't desperately need the drug at that moment of time. I think the effects of it after six weeks I would feel that, you know, the symptoms were coming back slightly. 

The last two infusions I think I haven't felt like that. So it's just, you know, I don't feel, previously I've felt I knew when the appointment was coming. I don't feel like that quite so much at the minute. But the environment is lovely. It's relaxed. It's a nice place, you know, to come. You meet the same people and it's, you know, it's a pleasant experience which is good. So it's very positive.

Yeah, it's, I'm glad I've done what I've done. You know, it's, but it's very positive what you hear, it's good. These sessions are good, that we do it all together, that, you know, you meet people, you can talk people and maybe it's little counselling sessions for us all. You know, maybe it's a way of us sort of coping with what we have, maybe.

And how many people, you know, sort of are at these sessions?

Well there were six of us today, five of us today. I mean, either sort of four of five, six. And you can talk, you know, across and whatever and you meet people from sort of early on to very late to sort of it, rheumatoid arthritis is very individual.

Pat preferred Simponi injections to infusions because the latter gave her headaches. She found...

Pat preferred Simponi injections to infusions because the latter gave her headaches. She found...

Age at interview: 54
Sex: Female
Age at diagnosis: 25
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Well, obviously I, she said, “You’ve been chosen to have the fusion,” and I thought… I didn’t like that very much, not for any particular reason, it was it was just a ward in a hospital and it just wasn’t, it was just really dreary.

 
It’s like six, seven people sitting with drips in and if you don’t like looking at other people with drips in, it wasn’t very cosy, you know. I thought it could have been more of a living room set up. If it was only a bit more colourful but it wasn’t you know. I used to dread going really cos I thought, “Aw to sit in here for, but it’s like, they put a saline solution through and then they gave you an antihistamine so you don’t have no reaction and then the drip goes through so it can be two hours or more, you know from start to finish really, so.
 
And it’s not a nice environment?
 
No I didn’t think so actually, because I thought they maybe, they could have had little, little like curtains across, you know, each others chair cos we’re all strangers and we all were having things you just, it was, you know, it made you sleepy sometimes, everyone was looking at you and, I just thought, ‘Oh no, I would rather have a curtain and sit on me own really,’ you know and it was a very dreary hospital room obviously, you know, but yeah that, that was the only thing. I just thought it could have been a bit more cheery, maybe cheery is the word.
 
And how did you feel afterwards?
 
The first one, they gave me antihistamine, I was really on Cloud Nine, floating cos I’d never taken an antihistamine in me life so I was really, really drowsy to the fact the nurse who was on charge, he said, “Why don’t you go and lie on the bed.” [Laughs].
 
There was a bed in the ward, I kept, I said, “I keep falling asleep,” then it clicked on that it was the antihistamine really so that was OK and then the headache. I’d say instant headache when the Golimumab started to go through, definitely like a headache that could last up to four hours... each time of the fusion, it was a headache.
 
And after four hours you would...?
 
Yeah well it, it kind of just go off but it was just, you know, one of those headaches that’s in your head and you know it’s there. You can still do your, come home and do your meal and things but you knew it was there kind of this headache but as soon as that drip started with the drug, definitely headache.
 
And you didn’t have a headache when you were using the pen?
 
No, no, no
 
So it’s different?
 
Yeah I’d say so. The pen’s sort of quick and maybe, I don’t know, is that a smaller dose or something? It goes by your weight [I’ll have a little drink] it goes by your weight doesn’t it really?

 

A nurse teaches patients to do the subcutaneous injections of Enbrel, Humira, Simponi or Cimizia and most people find injecting easy and not painful. A 37 year old woman's husband gave her the Enbrel injections twice a week. Another woman injects Humira herself in a similar way but checks carefully because one batch she had been dispensed was out of date. Pat couldn’t do the Simponi injection herself and asked her husband to do them for her.

Her husband helps her by injecting the Enbrel twice a week.

Her husband helps her by injecting the Enbrel twice a week.

Age at interview: 37
Sex: Female
Age at diagnosis: 27
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But these injections are working wonderfully and my husband's having great fun doing them for me [laughs].

Right, so, he, how often do you have to have them?

Twice a week, in the tops of the legs and it's, it's really good, you get a complete pack with everything in it that you have to do, but the unfortunate thing is I can't crack the tops off the needles, I can't take the tops off the little bottle that you have to use the syringe to put the stuff in so, it was agreed that [husband] could do it for me. So he makes this up for me on a Monday and a Thursday and then injects me with it and he's loving it [laughter]. He can inflict some pain on me.

Injects Humira Anti-TNF into her leg every two weeks but one batch she was given was out of date.

Injects Humira Anti-TNF into her leg every two weeks but one batch she was given was out of date.

Age at interview: 21
Sex: Female
Age at diagnosis: 12
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I inject it every other week and it goes into my thigh or my stomach I'm told but I'm not going to try that because that makes me feel ill to think of it there, so in my thigh and I alternative the legs and that's it's, it's strange injecting myself because it's something I've never done before but it's all pre-done in a, in the syringe so you just take the lid off and remember to squeeze the air out because the time that I didn't gave me a big bruise in my leg.

It was funny, I had it all ready, just about to inject and I checked the expiry date 'cos I remembered the rheumatology nurse saying, 'Always look at the date, look at the name and look at the date and make sure it's the right thing you're putting in your leg'.  So I looked at the date and I thought, and it was something like the 30th of the 4th 03. And I thought, 'That's fine'. And then I thought, 'Wait a minute, it's the 5th'. And I thought, 'Well, I don't know what to do. I don't know, do I take it?' I looked in the fridge, that's all I had. And I thought, 'Do I take it? Do I leave it?'  

So I phoned up to check and my rheumatology nurse said, 'Don't do it. I'll phone the pharmacy.'

People commented on the features of prefilled syringes and how important these are for people with painful and restricted mobility on their hands. Christine, Sandra and Emma have noted that the Cimzia prefilled syringes makes it easier for someone with RA to use and control with either one or two hands, depending on grip strength and control.

Christine finds the Cimzia prefilled syringe very easy to use. To some extent, it was the...

Christine finds the Cimzia prefilled syringe very easy to use. To some extent, it was the...

Age at interview: 73
Sex: Female
Age at diagnosis: 67
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When I was in the hospital and she came up and she spent the whole afternoon with me with a load of injection things telling me the ins and outs of each of them and the reason I chose Cimzia, one of the reasons I chose Cimzia is that the top, as you take the injection out of the packet… the top is like a pen top with the If you can imagine here, it’s like yeah, it’s got a nice big loop on it and at the time my hands were bad and I thought, ‘Ah, that’s alright because I can get a finger in there and pull on,’ whereas some of these little tiny caps are very difficult to pull off.So that’s a reason I, and that’s the only reason; to me they were much of a muchness but it was the ease of getting the cap off and when you push the syringe to get and make sure the liquid was up to the needle, you know, you’ve got a great big, I’ll show you later, they’ve got, you’ve got a nice big rubber thing to hold on to and if your hands are not good you need that. So that is why and you know, she said, “There’s not a lot of difference in them but they’ve all got this, some have got this, somes got something else,” and I said, “What do you think of those?” she said, “It’s a very good one.” So Cimzia it was.
 
So they were offering you what we call the biological new therapies, or, Rituximab or?
 
I don’t know what they, I can’t remember what they were called now but again she offered, they were all there, in a, you know and she told me the whys and wherefores but the best one for getting the top off which, not being funny, if you’re going to inject yourself, you’ve got to be able to get to the needle haven’t you? [laughs] And if you can’t [claps] well you’re done so I, I’m quite independent, I can go upstairs and I sit on the bed, one, one month, one fortnight I do one leg and one the other. No problems whatsoever.

 

Cimzia was described as a ‘thick liquid’ and painful to inject but people found that taking the injection out of the fridge at least thirty minutes before injecting helps.

Christine leaves her Cimzia injection out of the fridge for well over half an hour before injecting.

Christine leaves her Cimzia injection out of the fridge for well over half an hour before injecting.

Age at interview: 73
Sex: Female
Age at diagnosis: 67
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Some people have described Cimzia as being a very thick liquid…?

 
You must let it warm up. It’s got to be kept in the fridge, oh when I’m unhooked I’ll show you, it’s got to be kept in the fridge. And they say have it a room temperature for at least half an hour. Well I try and leave it a bit longer than that. As soon as I come down on the Monday, every other Monday morning, I take it out of the fridge, sometimes I’ll leave a note for [name] to say, “When you get up, you take it out of the fridge,” and then by the time I’ve been down and had my breakfast and cup of tea, taken me tablets and what have you, gone back upstairs and had a shower and what have you, it’s sometimes even an hour. So then it’s, but I think possibly if you didn’t let it warm up at room temperature it would be thick.But it does not appear thick when it’s been out of the fridge for a while.

 

Emma finds it too painful to inject herself so a colleague at the hospital does the Cimzia...

Emma finds it too painful to inject herself so a colleague at the hospital does the Cimzia...

Age at interview: 24
Sex: Female
Age at diagnosis: 21
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Yeah it comes in an injection form. When I first started on it [Cimzia] I had to have two injections at the same time every two weeks. So it was like a, to get my dosage up to the right level. Once I’d had three months worth of that then I went on to one injection every two weeks. I personally can’t do it myself [laugh]. I take it into work and my colleagues do it for me. I find it’s quite a difficult thing to do because it’s quite a thick solution. And I just, I can’t brace myself to do it myself [laugh].
 
You use a pen don’t you?
 
It’s quite a large sort of needle.
 
Ok so it’s not a pen?
 
Syringe. So it’s not like a pen one. It’s quite a large one with a syringe and a sort of pusher on it, plunger on it. It’s very well adapted for people with rheumatoid in their hands actually, very easily, you know, removable handles and things like that.
 
And it is under the skin? It’s subcutaneous. Is it painful when the liquid is going in?
 
Yes.
 
So maybe that is a put off?
 
Slightly but I mean it’s once every two weeks. There seems to be a lot of solution and it’s quite thick so I find it’s the burning pain rather than anything. It doesn’t last for very long. It’s only when you are having it done. Because it’s quite thick it’s difficult to get in and sort of have to grin and bear it whilst you have it but it’s done within a matter of seconds.

 

Anti-TNF clinic
Patients on anti-TNF and B-cell therapy attend a special clinic; the anti-TNF (or biologics) clinic where the medical staff monitors the person's progress on the new drug, discuss any problems, and try to spot possible adverse effects of the medication. The occasional extra clinic visit is needed because detailed forms have to be completed on each patient to enter details on to a national registry which is a requirement from NICE for these drugs to be available. People on the new treatments said that on average they attended the anti-TNF clinic every three to four months in addition to going to the rheumatologist clinic. They pointed out that they tend to see the same health staff at both clinics (with the exception of the anti-TNF nurse). (See also Regular Monitoring of RA and other diagnostic tests.)

Sandra talks about how often she is seen on the anti-TNF clinic and describes the care she...

Sandra talks about how often she is seen on the anti-TNF clinic and describes the care she...

Age at interview: 51
Sex: Female
Age at diagnosis: 51
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I think I started on the Cimzia and then was reviewed after about ten weeks by my Specialist Nurse to see how I was getting on with that. Because I’d been on the methotrexate, you have monthly blood tests anyway so that was no different, I carried on having my monthly blood test done and then when she reviewed me she again did the DAS score which is when they test your joints for swellings and pain and again looked at my blood results to see how; it was then showing that the inflammation was reducing.
 
After the first month or?
 
No I’d, it was about ten, I’d tried taking Cimzia for about ten weeks… that I saw her and then I think I was reviewed again about three, three months later. And then this time it’ll be six months before, six months gap between being seen.
 
I think, all the care I’ve been given has been excellent. My only frustration is getting follow up appointments.
 
Follow up?
 
Whereas you would see the specialist nurse or you’d see the Consultant and he’d say, “I want to review you in two months’ time,” and then you’d go out to make that appointment and it’s going to be three months’ time and to wait that extra month is a long time. So I think that has been my, my biggest frustration, is, is being told we will review you in two months or three months but then because of the appointments being so full, always adding another month on. But they are very good that there is the, the Helpline number which I have used so you know, if you are getting desperate you can phone up and, and speak to somebody and I do feel that I’m listened to. The hospital, when I was admitted I can’t fault it at all. It was absolutely fantastic. I think I needed to go in and it was also very, very useful for me in particular being with other people that had either rheumatoid or very similar conditions. It was quite nice to shuffle down the corridor with other people that were also working and walking at your pace rather than you constantly trying to keep up with people. And just experiences and tips of how to cope with doing different things, just, just your daily things – just getting yourself up and washed and dressed and doing your hair and invariably there was somebody that sort of said, “Oh I find it easier doing, doing it this way,” and that was really, really useful.

 

Pearl describes the quality of care she receives at her anti-TNF clinic.

Pearl describes the quality of care she receives at her anti-TNF clinic.

Age at interview: 60
Sex: Female
Age at diagnosis: 40
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Yeah you can see the rheumatoid nurse. You can make an appointment yourself. You can see her any time. You can ring up or you can ring and for, you know, advice or, you know, if there is any problems you can always ring. So you’re not stuck on your own, you know. You can always ask questions and yeah.
 
Have you ever had difficulties in reaching someone from the medical team?
 
No, no. If I can’t get through then they get back to me and they do get back to you, you know, and arrange an appointment, yeah. They are good, yeah.
 
So you feel that you are well supported in that?
 
Yeah, yeah. If I have a problem I just. You know I know it’s on the end of the phone I can get it sorted.
 
Have you called them? Have you ever called them?
 
I have yeah, you know, when I’ve had flare ups and such and they make appointments to see the professor. You know they do that sort of thing or I can go in and they’ll give me a steroid injection. But that’s a good thing about it being on the Simponi I haven’t had a steroid injection since I’ve been on it as well. So, you know, that is a real good thing. Yeah.
 
But based on your experience what do you think they should improve regarding the consultation? Do you think there is still room for improvement?
 
I don’t think so.
 
No?
 
No with the professor [name], he is really, he is a person you can sit and talk to. He’ll, when he talks to you, you know, he bends over to you. And he asks, you know, ‘Is there anything I can do for you to make you feel better?’ He’s that sort of a man. He’s not like your typical doctor, you know, he understands and he cares. I couldn’t really think of anything to make it, to make it better. You know they are all very good.
 
Ok.
 
And they are all good with me. Its first names, you know or, ‘You’re ok Pearl.’ And you feel like part of, like part of a family basically because they ask you how you are and they know you when you go. I’ve been going since 1991 so, I mean, it’s been a lot of the same faces so. You know.
 
You said something very important when you said that they understand and they care?
 
Yeah you get that. You get that feeling. It’s not you’re going in as a number and you are going through to see a doctor who doesn’t really know you but I’ve known the professor [name] and he knows me. So…
 
So it’s more of a personal?
 
Yeah, yeah
 
Yeah kind of involvement.
 
Yeah and you don’t have to go in and explain everything because he understands where you are up to. So and that’s, that’s a good thing about it. You’re not seeing somebody different all the time which does happen. It does happen and they don’t know anything about you, you know.
 
You have had this continuation of care since you were diagnosed?
 
Yeah. Even when you’re going in to make your appointment, you know the girl on the desk I’ve known, you know, I know her first name. ‘How is your family? How is your dad?’ and all this, you know, and that all makes a big difference. Yeah.
 
For you to feel more kind of comfortable

Talks about her hospital appointments, including her anti-TNF clinic and the type of tests she...

Talks about her hospital appointments, including her anti-TNF clinic and the type of tests she...

Age at interview: 26
Sex: Female
Age at diagnosis: 22
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I see my doctor about every six months, but I also see the anti-TNF nurse, about every three months, so you've got that alongside, and then I've blood tests about every four weeks because obviously they need to monitor what's going on. So you, it's not a case of it's a medication where they'll put, you, they put you on it and, and tell you to go home, there is quite a lot of monitoring that you have to do alongside it because it is a quite a powerful, powerful drug so you do have to make a lot of hospital [laughs] visits but, you know, that's part and parcel of, feeling better is that you, you do have to make more hospital visits to, to enable you to, for that medication to run smoothly for you.

Do you know what they are checking with the blood test? What are they looking for?

It's the change in your white blood cells isn't it? [laughs].

They check for your, I don't know what the count is, the rheumatoid factor?

So when, before I was on anti-TNF drugs, I had a rheumatoid factor of about a hundred and twenty and, obviously when you, you've start medication it starts to work that will go down so they can, they can tell by that how, how bad you are feeling 'cause it does reflect I mean in some people it doesn't but it's, in a lot of people it does reflect 'cause I could tell when I was feeling rubbish by looking at my rheumatoid factor [laughs] 'cause it was always very high so, they, they'll look for that and monitor that as well, but they, they ask you as well when you go for going to the hospital they, you know, they check all your joints regularly and see if any are particularly inflamed, and they'll also tell you how you ask you how you are feeling generally as well so that's always monitored.

In which way?

Sort of how, how you're feeling in terms of sort of tiredness or just, just general wellbeing as well.

They'll check all your joints and, and, and see whether they're inflamed but and, they'll ask you about how you're feeling but no other tests no.

If you have any questions or if you need any advice can you ask, can you phone anybody?

Yeah, you can phone the hospital whenever you want. Yeah so, and you can speak to, I can speak to the, the person who I see at the hospital any time I want so.

That's your consultant or your nurse?

The nurse, if I want to I, if I wanted to speak to my doctor I could do as well so, you know, help is there if you, if you need to ask any questions or anything and you can just speak to someone straightaway, so.

Information and advice
Knowing the implications of taking any new treatment was important for interviewees. Many people pointed out that rheumatologists and nurses did their best to ensure that patients understood all the facts about their new drugs before they started on them. Several people also visited the site provided by the drug manufacturer on the Internet and found it very useful and informative. (See also Finding information about RA).

She read as much about anti-TNF as possible to make a decision and to calm her fears before she...

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She read as much about anti-TNF as possible to make a decision and to calm her fears before she...

Age at interview: 49
Sex: Female
Age at diagnosis: 33
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Here I am 2002 and considering another sort of drug therapy because I think what I'm taking at the moment is actually not particularly that effective in a way, it's, I feel my mind and my body are out of synch. You know my mind is racing and I want to do things but my body is not doing what I want to do. I'm having my first infusion tomorrow of anti-TNF. I am not sure whether I'm going with it because I feel I have to try something else. I've read, I've looked on the website I've got, I've gleaned, you know got information from it.  It is all very well documented so obviously you know all that happens in a trial and it's pretty scary stuff, that you know it all.  

So whereas I think when I took methotrexate six years ago, I think the documentation on the drugs was not there and now you have it all on a plate, so you know all the bad and all the good and all the whatever. So probably with us being very well informed now it's actually, it's not so easy to, I think we've always wanted to be informed but may be with the whole wealth of information it's, you realise that the drugs you take are extremely potent drugs and it puts into question, you have to weigh up.  

Tomorrow I'm, it's I know what, they did voice concerns about lymph cancer and skin cancer with anti -TNF. If I had a choice in the whole scheme of life, I obviously don't want to be on medication to be quite honest, but I am. And possibly if I've got a chance of me physically doing more if this is what it does then I, you know, I think the chances, I think the odds are just in favour of doing it really. I'm not overly, I'm not overly delighted with it but then it's I think I have to do it, really I think I do for my family. I think I have to do it. If I can sort of walk slightly better or without pain then I think, you know I want to do that.

I think it's a chance I probably have to take. It's pretty well monitored so if there's any problems, you know they'll sort of jump in but I think methotrexate, as I say it's not so. I think any trial that takes place now, you know it all you have all the evidence there so we're very well informed, you know it all, whereas I think, methotrexate, it wasn't quite the same or maybe I didn't chose read all the information, so this seems slightly more scarier than, oh I don't know, I didn't what to go on methotrexate, either. But tomorrow it will come and I'll see really. You know I'm sort of anticipating whatever with slight sort of, slight, well very big concerns really, but I think it has to be done really.  

Information and access to specialist advice is very important to people on the 'biologics' treatments. As part of their action these treatments do modify the immune system (which is why they work in RA), and some of the people we interviewed indicated that they experience more frequent colds and infections than before. Several people said that judging whether or not to take their medication when ill was most important. All those on biologics treatments said that they have been given a helpline number by their anti-TNF clinic. They feel reassured that, if needed, they can have access to specialist help and advice but several said that it is not always easy to speak to their nurse/doctor on same the day. 

She was 'amazed' to be given lots of information and advice about her anti-TNF medication. Says...

She was 'amazed' to be given lots of information and advice about her anti-TNF medication. Says...

Age at interview: 37
Sex: Female
Age at diagnosis: 30
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How much information they gave you about the Humira?

Quite a lot actually. I was amazed it was so different from the Methotrexate where you get sort of this, you know, you get like a photocopied sheet don't you with things on it. You know, information on it. But with Humira I suppose because, you know, it is a big company, big bucks, you get, you know, everything sort embossed and you know, you get a little calendar when it is due and yes, I got a lot of information actually and it was easy to understand as well, you know.

As usual I Googled and I you know, I started looking at the disadvantages of it, but then I worked out that I don't really have a choice, because if I want to get on with my life, then this is the drug I need to take. You know, there are side effects with any drugs. I mean look at the side effects of paracetamol. So, yes'

And what did you find out regarding sort of side effects?

I mean I suppose the biggest one is you increase your risks of other infections. And if you catch infections they could be a lot more long lasting so you have to be quite astute at thinking hang on I have had this cough for two weeks now. I need to go down to the GP's, perhaps start some antibiotics. Rather than before you would have just got over it. I noticed that. It is niggly things but nothing major. 

I think there is an increased risk of lymphoma isn't there? Which is fun. But I think it is about 1% or something, you know, I am more probably at risk of getting run over by a bus really, so' You have to take it in context. It is, it sounds dramatic, but it has actually given me my life back. You know, the fortnightly injection is enabling me to have a really good life and I have reduced my analgesics as well. Halved those, so' yes. It is good stuff.

Okay so it seems that you are not terribly sort of concerned about long term effects? Would you say that? Or have you put it into perspective?

I think I have put it in perspective. Because I am concerned. I think sometimes if you find me [coughs] if you find looking through the BNF about the side effects of everything. And I do sometimes think oh God I don't want this, that and the other. But you have got to get it in context. If I am not on it I am not going to have a life. You know, the Methotrexate is not working and Methotrexate has, you know, side effects. They all do. But you have to get it in context. I mean, I think I look quite well. I think I have' you know, my friends can't believe how well I look, and one of my friends said to me a couple of days ago, 'Oh you look as though there is nothing wrong with you.' Which I thought was great. But no the anti-TNF is wonderful stuff.

Pearl indicates that since starting on anti-TNF therapy she has more frequent colds and has to...

Pearl indicates that since starting on anti-TNF therapy she has more frequent colds and has to...

Age at interview: 60
Sex: Female
Age at diagnosis: 40
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I do get chest infections [cough] a lot. Excuse me. That’s the only thing, rarely, you know. I think it’s with the low immune system they say you pick, you’re picking infections up.
 
So you have noticed that you get more?
 
Yeah I get more chest infections, yeah, yeah.
 
Do they go on their own or in some cases do you need to take antibiotics?
 
Yeah all the time.
 
Really?
 
Yeah because I got this. I only got this Friday. Saturday it was really bad, Sunday and I had to go to the doctor’s on Monday and he gave me antibiotics because the crackling was on the chest and that’s only in a couple of days, yeah.
 
And you think it is because of your immune system is weak…?
 
I think so yeah.
 
And how often do you get these?
 
I get them every year. I get maybe two a year, not a lot but it’s just that and I’ll get them every year where before I didn’t, you know. I didn’t. Excuse me.
 
Have you noticed any other side effects apart from the chest infections following?
 
No, no. that’s the only thing is the chest infections and for two months I had the headaches which they’ve gone. So I don’t know whether that was a bit of a flare up of the arthritis and I’ve had it in my head because I get it in my jaw and you get that same tightness, you know when it tightens up so it could have been a bit of a flare up as well we had.

 

Sandra was advised by her anti-TNF team to avoid sunlight exposure and to seek medical help if...

Sandra was advised by her anti-TNF team to avoid sunlight exposure and to seek medical help if...

Age at interview: 51
Sex: Female
Age at diagnosis: 51
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They warn you about sunlight as well… and certainly I have found that if the sun is out at all, I’m not talking about going on, on holiday to a really hot place but just in this country, if the sun is out and there’s the slightest bit of warmth in the sun, it feels like my face is absolutely on fire so I usually wear total sunblock now and if I go out in the sun it’s for very, very short periods with total sunblock or I sit in the shade and I do need to keep covered.

 
You need to keep covered? Why? Is the skin more sensitive?
 
Yes it is, yes it is. I think methotrexate has the same effect as well that it can make you more photosensitive.
 
Any other counter indication?
 
Risk of infection. They do warn you that if you start showing any signs of infections, sore throats, fevers, coughs and things like that, you should be aware that actually potentially you could get unwell quite quickly. Therefore you should ‘err on the side of caution’ and get things checked out earlier on than perhaps you would normally.
 
But did they talk to you in terms of side effects or potential side effects?
 
They say you can be more at risk of skin cancers and they gave me a booklet to read of which there are loads of potentially quite worrying side effects. It, I do feel that the side effects that are listed, and there’s pages of them, could easily put you off taking the drug. But for me I felt I had no choice because my quality of life was so poor at that time to me it was worth those risks.

 

Pregnancy and biologic treatments
Young women commented that doctors and nurses at their anti-TNF clinic routinely remind them of the need to avoid a pregnancy while on the anti-TNF and B-cell therapy drugs. Moreover, those women also taking methotrexate were told that they would need to 'wash' this drug off their system before conception. Several women said that they have a very difficult choice to make between being taken off drugs which are controlling their RA and having a child.   

Professor Robert Moots advices and informs about biologic drugs and pregnancy.

Professor Robert Moots advices and informs about biologic drugs and pregnancy.

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It's very important that we think about how these biologic drugs can have an impact on our lives. I think the important thing to remember is that rheumatoid arthritis is much more common in women, and in many women pregnancy is clearly an issue to consider. Obviously if one wishes to get pregnant and to go through pregnancy, the absolutely safest way is to not be on any drugs at all. On the other hand, we know that bad rheumatoid arthritis can make it very hard to become pregnant. And there's a variety of reasons for this. So it's important to consider how we might manage pregnancy in patients with bad rheumatoid arthritis, and the biologic drugs can be very helpful for this. 

First of all, if a woman wants to become pregnant it's important to get the disease as well controlled as possible. And this might involve using a TNF blocker. Once the disease has become well controlled, then it's probably safe to try and get pregnant. But clearly during the pregnancy we want to try and avoid taking drugs where possible. So we tend not to recommend having a TNF blocker during pregnancy. But on the other hand, there are many women that have got pregnant on a TNF blocker and who've ended up staying on the drug through pregnancy without any problems either to them or to the baby. So whilst we think it probably will end up to be okay staying on these drugs through pregnancy, it's clearly premature to say that it really is safe. So we would recommend that you'd stop the drug either as soon as you realised you'd got pregnant or ideally just before you conceived. If you end up getting pregnant whilst taking it, then clearly it's important you discuss this with your rheumatologist. 

For rituximab it's probably a similar situation. But as we don't have quite the same experience we would tend to recommend that women don't get pregnant when they've had a cycle of this until it's washed out of the system. I think the other thing that's very important to remember is that all of the biologic drugs work even better when they're given together with methotrexate. Now methotrexate is a drug that we clearly want to avoid in pregnancy. So that's another reason why if you're wishing to get pregnant it's important to think about in advance, and I think ideally to plan this with advice from your rheumatologist, who'll be in a good position to help you.

At every opportunity, her consultant raises the issue of the importance of not getting pregnant...

At every opportunity, her consultant raises the issue of the importance of not getting pregnant...

Age at interview: 26
Sex: Female
Age at diagnosis: 22
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Did they say anything about risk during pregnancy or...?

Yeah my, my doctor always mentions it [laughs] every time because she's petrified of people getting pregnant but she mentions it every time I go over the like, 'No I'm not having children.' but yeah they always talk about the risks of getting pregnant and anything so they say when, if you do want children obviously you need to let them know first and then they can plan, she'd always said, 'If you, if you wanted to have a child you need to plan it and they would take you off the medication and they would plan a course of what to do and, during that period.' So, they do explain that that's quite an important thing that, that you shouldn't' mmm.

And you are taking contraceptives any contraception?

Yeah.

Okay, and do you have any kind of plans to, to have a child?

No, no. Because I'd, I don't wanna come off the medication so [laughs] that again far outweighs the coming off the medication, I'd rather not so, I don't want to have a child because of that reason, and it's not a major thing for me I don't particularly crave for having a family anyway so, but it, you know? It would be, if someone wanted to have a child it would be quite difficult. I would suspect be, a decision to make because obviously, you can't be on that medication whilst you, whilst you're pregnant, so'

I think that would be a difficult situation.

Is this something you have discussed with your partner?

Yeah, yeah we've discussed it, but I mean it's never been, he's not, he doesn't want children and I, not, I'm not particularly that fussed I've never been, desperate to have children so it wasn't a big, a major decision to make but if for someone who wanted a family I would suspect it would be, so.

Emma and her partner would like children in the future. At present, they are very careful to...

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Emma and her partner would like children in the future. At present, they are very careful to...

Age at interview: 24
Sex: Female
Age at diagnosis: 21
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I’ve asked that a couple of times and a few people have said to wait until nearer the time and we’ll go through it in detail. But someone has explained to me I would have to come off all of my medication for about 6 to 9 months before I think about trying to get pregnant. And I think that would be the hardest time because if I do manage to get pregnant I’d be, I’ve heard that lots of people from professionals and non professionals that hormones from pregnancy actually alleviate some of the symptoms from rheumatoid so it would obviously just be the period when I’m coming off my medication. But there are alternative things that they can give me that are safe while I am trying to get pregnant that I could use instead. But as I’ve said, I don’t know in great detail but I know there are options and it is possible and I’ve heard a few stories where there have been successes.
 
And they’ve also told me if I do get caught pregnant whilst I’m still on my medication there’s a high risk of the pregnancy failing or having a severely disabled child because of the Methotrexate. I’m fully aware of that which I think was good of them to tell me so soon.
 
And what form of contraceptive are you using?
 
I use Microgyn on myself and we use condoms as well.
 
I think we’ve talked about your worries regarding pregnancy?
 
Yeah. That still gets me worried. [Ha ha] It’s always on my mind. It’s a huge worry.
 
And what have your consultant and specialist nurse said about it?
 
Just explained, you know, there have been good cases. People have been able to get pregnant whilst on this medication and, you know, there’s ways around it. You might find it slightly difficult but it’s possible. And I think, I mean I know I want children further down the line. I know that so it’s. I just don’t know how difficult it’s going to be. And I think not knowing is worse. I’d rather just know it would be difficult. Know it’s possible. Know I can do it.
 
And as I say it can be quite upsetting in case it doesn’t work out but I mean there’s no point thinking like that. You have to think positive. You have to think, ‘It’s not yet. We’ll cross that bridge when we get there.’ There are ways around it. I have been told that and they will help me through it. I think that’s a big thing as well. I know I will be monitored closely and I know I will be given advice and things like that.

Concerns
Both people who were taking the 'biologics' drugs and those considering it, had concerns that it is relatively new, with little yet known about possible longer term side effects. Side effects after the infliximab infusion that one woman mentioned were indigestion, feeling tired and having a 'very low mood' for the first two days and about two days of itchiness the following week. Those on Enbrel and Humira mentioned a red mark or rash around the actual injection site that could last up to two weeks. One young woman reported a headache the first time she injected Enbrel. Pearl who is on Simponi injections had headaches that have now disappeared. Pat also reported headaches after Simponi infusions and nausea when injecting it. Sandra has noted that since on Cimzia she needs to used a sun blocking cream when going out otherwise, her face feels really hot.

Emma has developed an irregular heart rhythm; a listed side-effect of using Cimzia. She is having...

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Emma has developed an irregular heart rhythm; a listed side-effect of using Cimzia. She is having...

Age at interview: 24
Sex: Female
Age at diagnosis: 21
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Personally yes. I’ve actually developed SVT which is sinus ventricular tachycardia which is an irregular heart rhythm from it. It’s not definite because some people are born with a pre-disposition to it but I’ve, I’ve had two attacks of SVT since I started on the injection. So I’ve been to see cardiologists and I’m having a procedure to stop that up in [city].
 
Will you continue with Cimzia?
 
Yup. I will continue with it. This is why I am having a procedure on my heart because the injections are working so well I really want to continue them. Obviously I don’t like having the irregular heart rhythm and it’s quite a horrible feeling. You never know when it’s going to happen which is why I am having the procedure on my heart to stop it happening again ever.
 
Do you have any concerns in the long term or do you just sort of balance the benefits and?
 
I think not knowing what the long term side effects of Cimzia is, kind of frustrates me in a way. I’d rather just know what and deal with them but I can’t look at that because I have to look at what benefits I’ve received on it so far and just be thankful that it’s worked for me. So whatever is down the line I’ll have to deal with when it comes really.

 

Several people were more concerned about the side effects of methotrexate than that of their anti-TNF medication because they were experiencing severe side effects like nausea, sickness or hair loss. Two young women have decided to stop methotrexate and continue with their anti-TNF drug alone. Christine was on methotrexate for a relatively short period but has developed severe breathing problems that she attributes to this medication.

She couldn't cope with the side effects of methotrexate and stopped taking it. One of her...

She couldn't cope with the side effects of methotrexate and stopped taking it. One of her...

Age at interview: 22
Sex: Female
Age at diagnosis: 11
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But when I actually went on my last hospital visit, I discussed it with them and said, 'Overall, I'm not happy being on it.' I know, and I do feel the difference when I'm on methotrexate, in conjunction with Enbrel it does help my joints, but then I can't deal with the sickness and the headaches as well. I'd rather try and deal with just a bit more swelling than usual, than have to deal with sickness and headaches every day.

You were sick every day?

Feeling sick every day. And then there were times where I was actually sick. I also felt that my appetite was very suppressed on methotrexate. And just, in general, didn't feel too well. 

The only thing I'd say about the Enbrel, is that I've heard it's very common but I permanently have a sore throat. Sort of get blocked nose and things which, it, for a while I feel like I've got a cold coming on. You know, it, it's just some part and parcel of the drug and I'd rather suffer with minor side effects like that, than have the full swing of the arthritis so.

I'd much rather deal with that every day than not having the drugs, so.

And were you given anti-sickness [coughs] sorry, anti-sickness tablets, or, did they help?

I've had anti-sickness tablets but I've never noticed a difference with them. I, they've never helped. I had folic acid with the methotrexate as well and I never noticed a difference with that either. So, I've no, they've never made a difference.

And when you told your consultant that you were not happy with taking, with taking it, what was his or her response?

A lot of the time it's depending on which consultant I've seen. Some consultants have sort of scared me a bit and said, 'You know, your arthritis will spiral if you don't.' Because methotrexate works very well with Enbrel. They work very well together. Which I got confused about, because when I was originally told about Enbrel, I was told it was this wonder drug, in fact, they've known cases of people to have done anything between four to twelve injections and it's almost like blasted it out of their system, and they've been fine. 

And then you obviously hear about people who've been on it for a long time and. I'd sort of argue back and said, 'Well, if it's such a good drug, why does it need backing up with something else?' You know, and yes, I agree, it does help if you take it but, at the same time, I've made that decision that I can't deal with the sickness and the headaches every day. It interferes with my day to day life too much. 

So I think it depends on what consultant you see. The, the last one I saw, he was very good and sort of said, 'You know, it's your decision. If you're happy to live with the degree of swelling and activity that's going on with Enbrel at the moment, then that's up to you. That's absolutely fine.' And he was very good about it.

So I've decided to stay off the methotrexate. Just for my own, just help me feel better from day to day really.

So how long have you been off the, the drug?

I've been off it for about six weeks now.

Six weeks.

And it has shown in my blood test results, the activity's a little bit higher, but I have sort of a line where, there's what I can deal with and there's what I can't deal with and this level of swelling, I can deal with, I will learn to cope with it. And I'd rather cope with that t

She is more concern about the side effects of methotrexate than the anti-TNF drugs. Besides she...

She is more concern about the side effects of methotrexate than the anti-TNF drugs. Besides she...

Age at interview: 22
Sex: Female
Age at diagnosis: 5
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OK. Do you have any concerns about taking it?

Its no because with the anti-TNF medications they're not' I mean I've taken the, the two already. I know all the side effects and to me the side effects of the anti-TNF aren't as bad as what you can get with say obviously methotrexate. And so with me side effects are this big thing, like if I see something on the side effects list that says like a sickness and stuff. I'm going to get that, that's just me. I get it into my head, 'I'm going to get that.' And obviously I'm probably worried like I could take methotrexate again now and I might not get any side effects, like I did before. So I research a lot. But I'm not really concerned about it because obviously I'm at the stage now, where I will try anything, just to see if it works, because anything is better, than being in pain constantly. So obviously if it doesn't work, then there'll be other options. But I will just, I mean I'm not going to be stubborn and say, 'No, I'm not trying to because I've research and this it says blah, blah, blah on the you know, information packs or whatever.' I will try it at the moment just because anything is better than like I am now.

Several people worried about still taking a range of other drugs and one woman had been able to reduce her painkillers, steroid and sleeping tablets since starting anti-TNF treatment. Those who had not been receiving anti-TNF treatment for long still hoped to reduce their other medications over time. Sandra, however, has asked for the reduction of her other medications to be postponed because she feels anxious that her stiffness and pain will come back.

Infliximab enabled her to reduce the other medication.

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Infliximab enabled her to reduce the other medication.

Age at interview: 29
Sex: Female
Age at diagnosis: 25
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In February they put me forward to go on a new drug called infliximab and that only got agreed in July this year. And I started taking it in July and I've got to say that is has worked. So, I've still got to take a lot of tablets, I'm still taking methotrexate which I take 20 by injection, 20mg by injection and I still have to take an anti-inflammatory and I'm still on painkillers, but whereas before I was on them every 4 hours and then taking amitriptyline to go to sleep at night, it's just taking them as and when now, it's not half as much.

And I find that I'm sleeping at night with no painkillers and no amitriptyline which helps you sleep. I haven't taken that at all since, in that first week I did but since then I haven't taken nothing like that. But they said in time that they can start getting me off a lot of my other medication as well. And I still take steroids which is the big problem 'cos my bone density's very low but they don't know if it was a problem with the steroids or whether it was something I had before.

And when you said you reduced your steroids down to three, what were you on to begin with?

I was on, I was on 15 but then I was on 7.5 for a long time. So I went from 7.5 to 3.5 and they want me to stick at 3.5 until I've been on infliximab for at least 6 months.

So did you choose to take the dosage down?

Yes. Apparently I should have done it anyway but no-one did tell me so I did it myself. 'Cos I, I needed to know that it was working and the only way I'd know is if I wasn't on so many steroids 'cos whilst I'm on steroids I'm very good but if they take me down then the pain starts so I knew then if I got down to 3, 3.5 and I had no pain then I knew that the Infliximab was working.

Many people felt that this new treatment was their best option - having not responded well to other medication or suffered unpleasant side effects. They chose to 'live for today' with a better quality of life rather than worry about potential problems in the future. One young woman said that now she feels more positive than before about life in general, because she is on a treatment that is controlling her RA.

Says that the benefits of her treatment outweigh any concerns she might have about side effects...

Says that the benefits of her treatment outweigh any concerns she might have about side effects...

Age at interview: 26
Sex: Female
Age at diagnosis: 22
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Did you have any questions about this drug or this treatment before you started?

I did have questions about it because obviously it's quite a powerful drug so, but I think, when you're in a situation where you can't do anything and someone says to you, 'Well this is, this is one option, and it's been it, you know, it's been trialled with people and where it hasn't work, where other drugs haven't worked with them it's been very successful.' You do have questions, but at the end of the day what you're thinking in the back of the mind is actually if it works, you know, the side effects are irrelevant because you can't actually have much of a life anyway if you don't have it, so you do have quite a lot of questions but they're only as a sort of matter of course if you know what I mean? You like [laughs] you're so desperate to take something that's gonna work that that actually that far outweighs any kind of doubt in your mind about what other side effects are and, and things so, you, all you're thinking about is I want something that works [laughs].

If you're in a situation where you, you can't go out and you can't do things and, even the littlest things take hours, and, you know, you would take anything, you know, the side effects are, you, they're immaterial really because if you don't take it then you'll just end up housebound so, it doesn't really, the side effects are not really if, a major concern [laughs].

But did they talk to you about that?

Yeah, yeah they went through the side effects

Says that she has a more positive outlook on life since starting on Enbrel because she knows her...

Says that she has a more positive outlook on life since starting on Enbrel because she knows her...

Age at interview: 22
Sex: Female
Age at diagnosis: 11
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Okay. So, is there an emotional side to your illness?

There is I mean, I'm the same as anyone else. I do get my down moments where I think, 'Why have I got this?' And I do feel that I have my teenage years robbed of me, because I, I'd never stepped foot in a club. There's a lot of things I haven't done that normal teenagers have done. 

But I'm certainly more positive now than what I used to be, and I do believe that's because of the drug I'm on. Because although it's there, it's not in your face as much and so I've had that. I can go out and do things more now that I want to do. I have my limitations but I can do them, whereas before, I couldn't do them in the first place at all. So I'm certainly more positive now that what I was. 

I do find if there's a situation that's cropped up that's upsetting, or something, I tend to get more emotional maybe than somebody else, so someone will have to go, 'Boo.' And I'll probably cry. You know, I do cry at things a lot more which, I've been told is when I've been to hospital you get given questionnaires when we go, and they ask you a lot of questions about how you feel emotionally, especially from day to day. 

And admittedly, I'll admit I can get down about things quite quickly but when it comes to the arthritis, I feel quite positive that it's being managed now and my outlook is better than what it was. I'm very positive compared to what I was before. So I, like I say, I think myself lucky compared to what it could have been. 

And I, you know, if I'm having a down moment I think to myself, 'There's people out there far worse than what you are.' You know, cancer patients and things like that. You know, I think the same goes, arthritis can ruin your life, but it won't take your life or something like that, you know. And, well I don't even know if it will ruin my life, motto, that gets on with it [laughs].

I try to anyway.

So what have you done within these last three years that you were unable to do before?

I've been holding down a part time job, at this farm shop. But it's the general mobility from day to day that has changed the most. Something so simple as getting in and out of the car which, you know, admittedly still is a struggle now, but before it would take ages to get in and out of the car. Getting out of the bath. 

The only thing I'll say that I can't do still to this day, is squat or bend or kneel on my knees. I haven't been able to do that for about eleven years, or since I was diagnosed actually. And it's amazing how something like that can really affect, you know, you think about it, if you drop something on the floor you'd think, 'I can't squat for that. I have to bend my whole body.' But I do work round that but it just general mobility, getting up in the morning, not being as stiff and as swollen and everything else. It is far better than what it was. I can also go out for longer periods of time. 

I mean, when my arthritis was particularly bad, this was just before I was put on the Enbrel, I couldn't walk by myself. I was either supported by my mum and dad. I couldn't even use the crutches because my elbows were swollen, so I couldn't even use crutches to get around.

People who started to use anti-TNF drugs as part of a clinical trial were initially uncertain about their chances of securing funding to continue using this therapy. This was particularly difficult for people whose quality of life has been significantly improved by anti-TNF therapy.

Linda's RA has responded very well to Simponi, but she is unsure whether her PCT will provide the...

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Linda's RA has responded very well to Simponi, but she is unsure whether her PCT will provide the...

Age at interview: 44
Sex: Female
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And do you have any concerns if they take you off the drug?
 
Yeah
 
What are your concerns?
 
Because I know it sounds crazy and you think the weather doesn’t affect but the bad weather is coming on now to December, January, February. That’s the worst months for flare ups and pain because they tend to be worse in the winter than they do in the summer. And it worries me that I’d say by January by the time the drug has left your body that are my attacks are going to be more severe because, you know, taking it off me or, you know, what will happen basically. I’ll go back to the way I was which I don’t want to go back because, you know, I don’t have to take time off work or, you know.
 
Were you taking time off work before?
 
It was more they had to work around me. I’m not making, I’m not getting allowances made for my day-to-day duties where, you know, say I was having a flare up first thing in the morning then I’d be running late. So I was working around the days I could do things. I did go to work but it was taking longer to get into work or I’d have shorter days because, you know, my wrists were really sore so I didn’t want to do too much. So it was, although I wasn’t taking actual time off it was working within the limits with what I could do whereas now I’m not making any adjustments to my days really.
 
And how are your employers and?
 
Well they are fine. But as I say I’m not really bothering them if you know what I mean because I’m actually. I call in myself that it’s remission. It’s temporarily slowing it down, that’s the way I feel it’s slowed down so I feel like, you know, it’s just on an even keel at the moment. I’m not expecting flare ups or, you know, whereas you think, ‘Well I haven’t had one for a while I’m due to, you know, it’ll kick off soon.’ I’m not getting any warning signals that it’s going to, you know, start getting the pains or the tingling, you know, in my wrists and it’s just I feel it’s settled. So I am worried that, you know, you saying about ‘concerns’ I am concerned that once the drug stops that it’s going to be unsettled again and I’ll have more flare ups. Which, you know, I don’t know, I can’t do anything about that but that is worrying me.
 
What have they said?
 
The hospital?
 
The hospital said about an alternative?
 
Well they haven’t because obviously I’m, it’s coming to, because the trial is coming to an end I will, I think by November I’ll be, I think next time I go in November they’ll know which, you know, and where I’m going to. Obviously I’ve got to go back to the clinic then and so obviously it will be another doctor I will see and they’ll take it from there as to what the next step is supposed to be once I’ve been taken off the trial. So I don’t know until I see them in about November.
 
So they haven’t explained or told you about it?
 
No not really. They just said, that they’d wrote off because I’ve done so well on it is there any way I could be kept. You know, because of the benefits, you know, it’s improved. For me it’s improved… you know it really has improved my quality of life because I’m not relying on anyone to do anything for me. I can get on with my own, you k

Limitations of anti-TNF and B-cell therapy drugs

Professor Moots talks about the limitations of anti-TNF therapy.

Professor Moots talks about the limitations of anti-TNF therapy.

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I think the other thing that's important to bear in mind is what your expectation of a response would be. I've mentioned about how good these biologic drugs can be, but it's important to bear in mind that they don't work for everybody, and also what they do is to suppress inflammation. And we must remember that rheumatoid arthritis can cause problems in a variety of ways. First of all, the pain and the stiffness that patients get can be due to the inflammation, and if we suppress the inflammation this will help get rid of those symptoms, reduce the pain and the stiffness. But on the other hand, patients with rheumatoid arthritis can get pain because the joints have been damaged. What we can't do at the moment is reverse damage. So if you have bad rheumatoid, you've got very damaged joints and there isn't much inflammation going on, you will not really expect to receive much benefit from a biologic drug. And I think these drugs are best given earlier on to try and prevent damage. But on the other hand, it's often hard to tell whether your pain is due to inflammation or damage. In some situations it's a matter of waiting and seeing how much better you can get with a drug. But I think it's always important to bear in mind that one of these new biologic drugs, like any drug to treat rheumatoid arthritis, may really have no effect at all.

Joint damage in those who had had severe rheumatoid arthritis for many years cannot be reversed. Despite feeling better on anti-TNF medication several respondents were still impaired and needed joint replacements.

Feels better on anti-TNF medication with increased mobility and energy but still has extensive...

Feels better on anti-TNF medication with increased mobility and energy but still has extensive...

Age at interview: 53
Sex: Female
Age at diagnosis: 30
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But the being able to feel on this new drug better than I had been before, being able to get out of bed in the morning and walk as good as I'm going to walk for the rest of the day, instead of hobbling around, bent over like a little old lady was just great. I mean and, you just felt that you had so much more energy because you weren't battling against such pain all the time.  

I have been on the drug since December 2000 and it just is, it's just made such a difference to my life. It just has enabled me to get on with my life and yes I'm still in pain, I can't, and I, I've since had a knee, a total knee replacement last November because I've had the disease for so long I've got a lot of damage and the drug actually does help to reduce the damage but I'm, you know, I'm so advanced that it's, it would have to be a real miracle drug to try and reverse as much damage as I have.  

So I still can't walk any further or stand up for any length, any length of time but I do have less pain and less stiffness and I certainly think that I would have had to have had a shoulder replacement by now if I hadn't been on that drug.  

She explains that her anti-TNF drug is working well and that at present she prefers drug therapy...

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She explains that her anti-TNF drug is working well and that at present she prefers drug therapy...

Age at interview: 25
Sex: Female
Age at diagnosis: 13
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I think Humira must be close to two years. And before that I was on Etanercept, and that was since 2003. And they kind of assessed me and found that wasn't really effective as it, as it should be. So they tried me on the Humira, which seems to be working, like it's controlling the disease in my joints at the moment. But the damage that's been done in my feet is from the inflammation that's kind of attacked the joint over the years. So that's, that's damage that's been done since sort of 13. All the inflammation is kind of eating away at the cartilage if you like. And now the, the bone in, the bone here is kind of rubbing against the bone in my foot, and that's what's causing so much pain and the reason why I need ankle fusion or ankle replacement.

[laugh] But my alternative to drug therapy is surgery. And I've been to see surgeons at the [hospital]. So I've seen [doctor], who deals with ankle replacement surgery and [doctor], who deals with ankle fusion surgery. And that was last year. And I, at the time I said, 'Look, no. Thank you for sort of informing me but I'm not at the stage where I really want to have surgery.' Because, you know, you get complications with surgery, don't you? And like ankle replacement, you risk amputation if you get an infection. And you might have to have it done every ten years. And like ankle fusion is good. It, it gets rid of the pain pretty much. But then you, you kind of have a permanent limp and that puts pressure on other joints. And I don't know, it's, it's not something I really want to go into at the moment. And I'm moving to France in August. So I wouldn't want to have surgery before I go there and get any complications and then have to put that off. Because my heart's completely set on doing that now. So'

And how are you feeling with Humira?

Yes. No side effects, not that I know of anyway. Yes, okay. Apart, as I say apart from really the damage that's already there from years gone by, it's, there's no sort of serious inflammation. My hands aren't boiling hot. No, it's pretty good.

In some cases, the effectiveness of anti-TNF drugs might wear off or the body stops tolerating it. One 22 year old girl was on Enbrel for about three years, briefly on Humira and then back on Enbrel but both drugs no longer work for her. She will try influximab next.  

She has tried Enbrel and Humira but both drugs are not longer effective on her RA. At the time of...

She has tried Enbrel and Humira but both drugs are not longer effective on her RA. At the time of...

Age at interview: 22
Sex: Female
Age at diagnosis: 5
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And then in September of 2003, they had me in hospital to start me off on the Enbrel. I had twenty swollen joints at that time. So what they did is they started me off and I had like the first dose. And then I had a week of hydro, hydrotherapy and physio. And then I'd go home for the weekend. And they'd have me, they'd have me back for another week of the second dose. And then more hydrotherapy and physiotherapy.

And within two weeks, the twenty swollen joints actually reduced to like three. Everything just stopped aching. Everything, it worked really, really well.

I think I was on Enbrel for three years, until it started rejecting me. And the only reason it was rejecting, like my body was getting immune to it was because I kept getting tonsillitis. So I'd have tonsillitis, have my penicillin course, it would go away. And then like two or three weeks later, I would get tonsillitis again. 

When you say that it worked very well for like about three years '?

Yes it did very well for about two or three years. 

Tell me, tell me about that period, what were you able to do and'?

I was able to most things. I could walk without aids, obviously not long distance still because my hips were, my hips were stuck. So I'd still use wheelchair for long, long distance. But I could walk around the house. I could walk the stairs. Could I walk the stairs? Yeah, I could walk the stairs. I could you know, walk from say the car into the cinema, into the actual cinema, back out again and things like that. I could probably walk from my house to the corner shop just down the road, which was you know, quite good. And when we went into town shopping I could get out of the wheelchair, into each shop that we went into and look around and walk around and stuff like that. So it was, it did work. Very, very well. And then obviously it's, my body started to, "Hmm okay, we're used to this one now, we're going to stop. We're going to reject it." So they had Humira which they switched me to. I think I was on, I think it started to work at first, but it didn't work as well as the Enbrel first did. So I was only on Humira, for about a year and half, two years. And then they recently switched me back to Enbrel in June of this year. Oh no July of this year because by the time, you know, they got everything sort it out. So in July, I went back into Enbrel. It kind of worked to start with. And I then I think that my body thought, well no you've had this before, we don't want you to benefit from it. So it didn't work. I had a bit of a break. 

Obviously, now like this I'm still taking it. It's not doing as good a job as it did the first time around. But I think it's taking the twinge away from the pain. So now they want to try me on Infliximab, which is obviously the last anti-TNF medication they're got on the market, at the moment. Which has to be taken with methotrexate, unfortunately. 

Yes we saw the doctors in the hospital that I go to now, in [city]. A couple of weeks ago. He explained that they had the influximab was the last anti-TNF medication that you can get on the market. And he explained that it's intravenously and that they do it on the clinic. And you have one dose and two weeks later you come back and have the second dose. And they can usually tell if it works after two doses. Everybody gets a reaction after two doses. And obviously sometimes really, really good and sometimes not as good as you would've hoped. And you need more but usually you, you can, you get a kind of an idea if it's going to work after the first two doses.

Yo

Although Pat felt better on Simponi, test results showed that the level of disease was unchanged....

Although Pat felt better on Simponi, test results showed that the level of disease was unchanged....

Age at interview: 54
Sex: Female
Age at diagnosis: 25
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Well the plan was to go on Rituximab after I’d stopped the trial drug, I can’t remember what date it was now but in between the start date of the Rituximab I had this ulcer under me foot and it was infected you see, so then when I rang them she said, “You can’t have Rituximab or while you’ve got any infection, while you’re taking antibiotics, while you’ve got any, you know, the podiatrist said it was a chronic ulcer and was 4mm deep so it’d had been quite sore so I’m none the wiser of what I’m supposed to be doing at the moment really. So as I say, me bloods have come back again today so it’s increased from 28 to 58 again in a month but yeah, so I’ll, so it’s definitely not under control at the moment, is it really?
 
What it was, just a basic talk and saying, “Well, you know, it’s probably a flare up,” and that, that was about it. I had two, I had a steroid injection in me shoulder and one in the top of me thigh and that was probably it really till they said, “Well if you meet the criteria for Rituximab but we’ll take it from there, so that’s really about it. I haven’t really been.
 
And meeting the criteria, what does that mean?
 
I think I’ve got to be active arthritis, maybe still got to be active which it was at the time. I think basically that you’ve got to have tried certain things and your arthritis is still active enough. I haven’t actually decided if I want Rituximab being honest. They, they’ve put it forward to me and one of the doctors who came up to see me on the trial basis. She said, “I don’t know why you have never ever been given it ever before”. She said, “I just can’t believe you’ve never been offered it actually”. She was very surprised they’d never offered to me that so. Anyway that’s been the next thing, is that but I don’t… what’s frightening me is if I take it and then I’ve got to have all this flare up again, if they say I’m, it’s not working and that’s me worst nightmare at the moment is I don’t want to go through all that pain again. I’d rather stay as I am and cope with it than have the flare up I did have but I wouldn’t like to experience again just, just yet anyway really.
 
So I, the experience that you had with the Golimumab?
 
When I came off the Golimumab and the flare up was just like day one when I was, you know, when I first began. And I don’t really want to go through that at the moment. Not this year, not this side of Christmas anyway. I really don’t want to go through all that.
 
And have they given you information about Rituximab?
 
Mm I had a leaflet through. I did ask the nurse the other week. I said so, so basically a giant booster then really, like a giant steroid kind of, but it’s not a steroid really, it’s just like big, probably lift in other ways. It’s not cure; it’s probably a few months at a time. She said , “It takes,” and did she say, “it takes a few weeks to get into your system but once it’s in, it’s there for about six months or whenever my arthritis is, is starting to creep again and then you’ll do it again so it’s always going to be monitored in that case really”. I just feel it’s just more chemicals which I’m not, I don’t feel, I can’t say I’m looking forward to going on it actually at the moment, I don’t know why. I’m just not very positive about it at all. They’ve assured me it’s really good and it will do me w

Those who had had RA for a long time felt that these new treatments had brightened the outlook for people with newly diagnosed RA and hoped that trials in patients in the early stages of RA would investigate whether the damaging inflammation could be halted.

The new treatments becoming available make her optimistic for the future for people with early RA.

The new treatments becoming available make her optimistic for the future for people with early RA.

Age at interview: 53
Sex: Female
Age at diagnosis: 30
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So I really feel optimistic for the first time ever that we have now got a range of biological drugs and we've got more in the pipeline that are coming through that over the next few years will come onto the market which will really give people with this disease hope that they will not have to go a life, through a lifetime of operations and ghastly pain and so on as I have been. And one of the things that I'm campaigning for is for a big trial to be done with people who have early RA because the small number of people with early RA who've been put onto these drugs and this is outside of the guidelines, the NICE guidelines, they're showing really good results. You, if you hit it hard in that first year after diagnosis with the new biological drugs then you have a real chance of putting the disease into remission or, you know, controlling it to a very large degree. And my goodness me, what a difference when I think back to what my father went through, it's just a huge progress and it's reassuring that there is this research going on.

B-cell therapy rituximab

Professor Robert Moots discusses a new drug called rituximab (Mabthera).

Professor Robert Moots discusses a new drug called rituximab (Mabthera).

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But if another TNF blocker doesn't work, we now have a new drug called rituximab, or Mabthera, which can be very helpful in this situation. I'm going to say a little bit about rituximab now. 

Rituximab is a protein. In fact it's an antibody that's delivered by an intravenous drip. This drug was first discovered or developed to treat patients with forms of leukaemia or lymphoma, because the drug works by depleting or killing a certain type of white blood cell. What we've learnt subsequently is that these white cells that rituximab depletes are also important in causing rheumatoid arthritis. So if we deplete these cells, the idea is that the arthritis gets better. And clinical trials have shown quite clearly that this is indeed the case. In fact, what's even more important is that we know that rituximab or Mabthera can be very effective even in patients that have tried and not responded to a TNF blocker. So there's a very important place for this drug. And on the whole we tend to use it for people that have got bad disease, that have tried a TNF blocker and haven't responded. 

Now rituximab/Mabthera is given by two intravenous infusions. And that means coming into hospital, usually for a day case, but sometimes to stay overnight, to have a slow infusion of the drug. You can then go home, and then two weeks later come back for your second infusion, which can actually be given much faster than the first one. When patients have had a cycle, and that means two infusions of rituximab, there can be a beneficial effect that can last as long as a year. And some patients can actually go into remission or at least get a lot better and without any other treatment stay well for up to a year. But the usual time for people to respond is approximately about six months. And then if your disease starts to come back again, as is usually the case, the cycle of rituximab can be repeated. And this can go on through a number of cycles. Have the infusions, improve, flare up, and then have the two infusions again. And clearly there's a big advantage in getting better without drugs after a single cycle and then having that cycle repeated.

Now there are some potential issues with rituximab. We know that it works well. It doesn't work well in everybody, like any drug, but it can work well in a lot of people. The types of problems people can get with rituximab are short-term and longer-term problems. In the short term a few patients can develop reactions to the drug, so there can be a nasty allergic reaction during the infusion. And that's why it's important to have this drug in a hospital, where doctors and nurses can help stop that reaction if it happens. Otherwise, patients on rituximab in the long term may be a little bit more susceptible to infections, just like we find in patients with almost any other drug used to treat rheumatoid arthritis. But the benefits I think are actually very high, because in patients that fail on a TNF blocker it's difficult to find other drugs that are likely to be effective, and rituximab can be highly effective in these patients. Also the risk of a side effect is actually very low. And I think this is something that we give now to lots of patients with rheumatoid arthritis, and we're finding that we're getting very good responses. So this is an extra weapon we've got in our armament of drugs to fight the disease.

Some patients do not respond to or, cannot tolerate anti-TNF therapy and for those patients rituximab is appropriate. One respondent had her first infusion of rituximab three months previously. She had already tried Enbrel and Humira. Pat has been offered rituximab following her lack of response to Simponi.

She started on B-cell therapy rituximab in October 2007. Previously she has tried two anti-TNF...

She started on B-cell therapy rituximab in October 2007. Previously she has tried two anti-TNF...

Age at interview: 40
Sex: Female
Age at diagnosis: 38
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Then, because those weren't working on their own, they tried me with the Humira injections. They did work for a little while but then, after a while, they just didn't seem to do very much so. 

Then they changed then to the etanercept for six months, and they did the trial on that for six months, and, to start with, my hands and my knees started going down. I wasn't having as many problems with my neck but then, unfortunately, that went the same way as the Humira and they had to stop that as well. And then in November of last year, they decided to put me on' I can't remember.

Rituximab.

Sorry. Yeah. Rituximab infusions. They started those at the end of October, beginning of November, about two months ago it started to work. My hands started to go down, I wasn't having any problems with my neck. 

Yeah. Like it's mainly in my hands and my knee, really, that get inflamed. Every morning, when I wake up, my hands, well, you couldn't move, I couldn't move my knuckles, to start with. Mind you, they are usually a little bit stiff in the morning even though this has started to work. It's a lot better than it was. But as I said, it's started to go back down. But my neck, when it flares I, I can't move it at all, it, it, sort of, goes into my shoulder and my neck so I have to take diazepam to try and calm that down, on top of everything else, but that hasn't actually flared since I've been on rituximab.

They said they were hoping it would work better because it works in a different way to the humira and the etanercept so they were hoping that this one would, I, because it coats the right B cells, or whatever, cells, but hopefully, over a longer period. It might work better than the other ones. They said it wouldn't perform miracles, but it could make my life a lot more bearable with it. I suppose I didn't really get my hopes up too high because I had with the Humira, originally, so. But it did, when it did start to work it was good. I was waking up in the morning and I could move my fingers, before I couldn't for a few hours, and my neck, my neck was fine as well. 

But I have problems with my ankles, they start to swell as well now, so they're sort of a bit. Painful every now and again. But that has lessened, slightly, as well, since they've put me on the rituximab.

If you have to, kind of, summarise it, would you say that you have been noticing some improvement.

Yeah. Definitely. Yeah.

Since you were put on rituximab?

Yeah.

Anything that hasn't improved that has remained the same?

My hip. My right hip, actually, that's, that has actually got worse but the rest of my joints have actually got better, even though my inflammation levels are going back up, it's not as bad as it was when they first put me on rituximab, so. 

They do a follow-up after three months, that's why I'm seeing them at the end of January (2008) so, because it will be three months, and they, basically, see how you've been getting on. I have to have pre-clinic bloods done as well so they know exactly what's going on the week before I have the appointment, as well, so they've got all the information they need there for it.

Okay, and you have had regular blood tests?

Yes. Every two weeks, for the last two years.

Says that her care team at the anti-TNF clinic has prepared her for the possibility that...

Says that her care team at the anti-TNF clinic has prepared her for the possibility that...

Age at interview: 40
Sex: Female
Age at diagnosis: 38
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But they have said that if the ritux., the, this one, the.

Rituximab

Rituximab, yeah. Doesn't work then it will get the definite guinea pig stage. And there are other things.

What?

There are other things that are on, sort of, trial, totally that they might be able to try me on, but they haven't elaborated on that. Obviously, because I've not been on this one for very long, they want to see how this goes and then, if not, then discuss something else. But I have said if this doesn't work then, then I would be, at the moment, I'd be willing to try something else but, sometimes, some days you just think, 'Why doesn't everybody just go away and leave me alone?' But other days, you think, 'Well, yeah, it's got to be worth it' [laughs].

So they have prepared you for the possibility that it might not work?

Yes. Yes, they do. Yeah, they, they do that, as well, yeah. I'm usually a pessimist but with Humira I was very optimistic and, unfortunately, it didn't work for me and I came down to earth with rather a large bump with that one, but I, by the time they put me on to the etanercept I was, 'Well, if it works, brilliant, if it doesn't, so what? I've tried it.' So, that was why I tried this one as well. So, it's worth trying it.

Last reviewed August 2016.

Last update August 2016.

 

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