Biological therapies for arthritis: anti-TNF, B-cell therapy and anti-IL therapy

A paediatric rheumatologist explains what biologics are.

Age at interview 49

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Biologics are the latest ‘kids on the block’ in arthritis. They’ve been used many years in adult arthritis. In paediatric arthritis we have to wait a while, they’ve been tested in adults before we can test in children. But we now have quite a number available. Biologics are much more targeted treatments and working much more specifically on the agents that are causing the problem. So one of the big players in the inflammation is TNF it’s called tumour necrosis factor and the key, the first biologic that was licensed for use in juvenile arthritis is etanercept (or Enbrel), and it’s an anti-TNF agent. We’ve now got many more and they have, they vary in which type of juvenile arthritis they’re more effective in sobut most young people will go on etanercept first and after that then depending on their type of arthritis, but infliximab, tozilizumab is primarily with the systemics and adalimumab are the key ones used in the UK at the moment, but every year they’re increasing the number and again they are the, they have really changed our management of arthritis. So ten years ago we would have several young people in wheelchairs in our clinics and everything. I haven’t seen a wheelchair in my clinic for a long time with someone with arthritis because of these much more effective treatments. So every year we’re seeing advances which is great, and as I say ten years ago the pattern of the arthritis was very different to what it is now.

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Biological therapies are a newer type of DMARDs (disease-modifying anti-rheumatic drugs) that work by blocking the immune response that causes arthritis.
The immune system is the body’s system for stopping illness and disease. When an illness enters our body, a response from the immune system is triggered to fight it off. Arthritis is an auto-immune condition, which means the immune system cant tell the difference between healthy body tissue and harmful things such as infection, so it starts attacking normal body tissues by mistake. In certain types of arthritis, the immune system triggers the body to overproduce:
  • Tumour necrosis factor (TNF), a chemical in the blood
  • B-cells, a type of white blood cell
  • Interleukins or ILs, a protein
TNF, B-cells and ILs all cause inflammation in the joints in people with certain types of arthritis. Biological therapies work by blocking these. So for example anti-TNFs are a group of drugs which block the production of TNF.
B-cell treatments remove B-cells from the blood and anti-IL treatments remove interleukins.
People are normally given biologic treatments because their DMARDs (such as methotrexate) are not working well. David Z described biological therapy as “the next stage on” from the DMARDs.
Some biological therapies are injected. Others are given to the person via a drip (infusion) in hospital.

Anti-TNF medication

The most common anti-TNF medications currently used to treat young people with arthritis are etanercept (Enbrel), infliximab and adalimumab (Humira).
Some of the people we spoke to said that they benefited lots from taking anti-TNF medication. Elizabeth said adalimumab (Humira) stopped her from “hurting all over”. Jessica’s mum described etanercept (Enbrel) as “life-changing”. She said that Jessica went from being somebody who could hardly move to somebody who could “participate in life”.

Sarah said Enbrel (etanercept) completely and utterly changed my life. She became more mobile,…

Age at interview 22

Gender Female

Age at diagnosis 11

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But the medication itself I’ve now been put on to the Enbrel, an anti-TNF which, to be honest, has completely and utterly changed my life, to what it was before. It will be two years, three years, sorry, in February, this February coming, I’ve been on it. The day that the lady that came out to give me the injections, she sat through, and went through how to do them, and what to expect next.

At the time, I was very ill in bed. I could not move. I was, actually, being carried by my mum and dad around upstairs, through every joint being swollen. And I did this injection that night, two hours later.

I walked to the bathroom on my own.

For the next couple of days after that, things started to go down, joints started to sort of recede, as it were, and I was doing the 25 milligrams twice a week, at that point. And from then on, things got much better. I’m currently taking the 50 milligrams once a week. As anybody else that has taken Enbrel (etanercept) will know, it makes you very sore where you inject and I find it easier just to do it once a week.

I now do it in my stomach, I alternate between my legs and stomach, because I find I get very sore and bruised on my legs if I do it there constantly.

Things aren’t brilliant, but they’re nowhere near as bad as they were. I have far more mobility now. I can drive my car, which I couldn’t do before. I’m also holding down a part time job, at the moment.

And it’s amazing, when you’ve spent day in day out not being able to do anything, not being able to go anywhere, how it can affect your life.

Yeah, it’s just, I’ve absolutely, miracle drug. It, it’s what they say it is I know that it is the drug that’s doing it. I haven’t actually fought this off myself at all. It originally it was juvenile arthritis. I should have grown out of it, late teenage years.

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People sometimes said that their anti-TNF medication worked for a certain amount of time but then stopped working. Doctors might then try the person on a different type of anti-TNF medication.

Melissa took Enbrel (etanercept) for three years. At first Melissa was able to get out of her…

Age at interview 22

Gender 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 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 own penicillin course, it would go away. And then like two or three weeks later, I would get tonsillitis again.

OK. When you say that it worked very well for about three years?

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

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

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 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.

OK.

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 i. 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.

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Some of the people we talked to said that anti-TNF medication caused no side effects. Others felt like they got ill more than others. Anti-TNFs work by suppressing (or weakening) the immune system (they are ‘immunosuppressants’) so people who take it become more prone to infections.
People who experienced side effects after taking etanercept noticed a number of changes. Elly said her cuts took longer to heal. Sarah said she had a permanently sore throat and blocked nose. She said that these were “minor side effects” compared to the “full swing of arthritis”.
People also reported side effects after taking adalimumab. Catherine said that it might have given her headaches and stomach aches. Michelle said she got a red, itchy patch on her leg where she injected it.
Etanercept and adalimumab are taken as subcutaneous injections (injections just under the skin). Some people injected themselves at home. They used a syringe or a pen device. Others were injected by parents or healthcare professionals. Some people said that the syringe hurt more. Others said the pen device hurt more. Sometimes people felt no pain at all, or said that the medication stung more than the needle going in. Adalimumab sometimes stings more than etanercept. Sometimes the area which was injected became red, swollen, sore or bruised. To help prevent this people alternated which leg was injected. Sometimes people injected the skin of their stomach because it hurt less. Catherine used a bag of peas to numb where she was going to inject. Beth had pressure applied to her leg after her injection to help with the pain.
People who took adalimumab could use a ready-made syringe which contained the medication. People who took etanercept (Enbrel) had to mix the medicine and put it in a syringe themselves.

Humira stops Elizabeth from hurting all over. She does not like needles but she looks forward to…

Age at interview 18

Gender Female

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In terms of the medications you’re on, what are you on now?

I’m on prednisolone steroids, 5 milligrams, which I’ve been on for about a year, no just over a year. And I’m on Humira (adalimumab) injections 40 milligrams every fortnight, which are really good. I just took one this morning.

Did you?

And I’m on leflunomide 10 milligrams which I take every night. And I’m not on methotrexate at the moment.

Okay so what, what makes the Humira good?

I don’t really know what it does in technical terms but I’ve had it, I first had it when I was about 13 and I think I was one of the first children to really have it cos they just gave it to the older people. But I have it every two weeks and near the end of the two weeks everything starts to hurt for no reason.

All over?

Yeah, all over, like I’d be taking the same medication but it wouldn’t work and I’d just, it would just start to seize up and I’d think, right this weekend you know, it’s time to take Humira. Take Humira and then in about 2 days I will just feel better. So I, and the thing about me is I don’t like needles, I’d never inject myself unless I had to, and I look forward to it, you know it’s quite a weird thing but I really like it.

Okay.
That’s also one of the things that worries me, if they suddenly say you can’t have it any more. Cos it’s, it is a very expensive drug but oh you know, coming off of it oh no, I don’t know.

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People sometimes took methotrexate with anti-TNF medication. However, some people preferred to take anti-TNF medication on its own, especially if the methotrexate gave them side effects (see DMARDs). In some cases, methotrexate has to be given with certain biologics, such as infliximab.

Adalimumab in combination with methotrexate, was shown in a recent trial (2015) to be an effective therapy in children and adolescents with JIA-associated uveitis. The trial outcomes directly led to the changes in commissioning guidelines and resulted in NHS England approving the use of adalimumab in children with uveitis that threatens their sight, and for whom other treatments have proven ineffective.

B-cell therapy and anti-IL treatments

Rituximab is the only the type of B-cell therapy available and is used for people with rheumatoid factor positive polyarthritis JIA or adults with rheumatoid arthritis (RA). Tocilizumab and anakinra are anti-IL treatments used to treat people with systemic JIA and adult RA.
Ryan was put on a tocilizumab clinical trial without taking an anti-TNF treatment first, but others were given B-cell therapy after trying anti-TNF medication and finding it did not help. Kyrun tried 6 different anti-TNFs but each one only worked for a month. He then tried tocilizumab and has been on it for a year. When Ryan was given tocilizumab he said that the number of joints affected by arthritis went down from eleven to three. He could also walk short distances again.
Lucy took anakinra and hardly noticed that she has arthritis.

Tocilizumab is taken as a drip (infusion) in hospital. Ryan was not allowed to eat for 24 hours before he had his drip. He said he was so hungry he felt sick. Kerrie said that the first time she had a drip it felt “daunting”. She was in a room with lots of people having drips. She could eat and drink as normal.

Cat described what happens when she goes for an infusion.

Age at interview 24

Gender Female

Age at diagnosis 14

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So I’ll have to go into hospital first thing in the morning, they clerk you in which basically means they fill out a load of forms and just check that you’re well enough to have the, have the medication because it; the way it works is it kills off certain types of your white blood cells which fight infection so for a short period of time after you have the infusion your immune system’s quite low. So you need to be well enough to be able to cope with that. It’s actually a drug they give to certain types of cancer patients as well so that’s sort of the, the, the strength of the, of the medication. Then they put what’s called a cannula into your vein so, which is small plastic tube, they use a needle to put it in but the needle doesn’t stay in your hand or anything so it doesn’t really hurt.

The plastic tube stays in your vein and they attach that to the drip so you have a bag with the medication in and a tube that then attaches to the tube in your hand, and they start it and it just goes in slowly for six hours something like that, five/six hours. They start it off slowly and then gradually increase the pace so the first half of the infusion goes really slowly and then it and then it gets quicker because some people have reactions to it, allergic reactions or they spike a bit of a temperature or something like that so if they start it off slowly they can monitor you and then if you’re doing alright then they can speed it up. I’ve never really had any problems so far. And then they, you stay for half an hour after it’s done just to check you’re OK and then you can go home. So it’s just boring [laughs] but you’re in an out on a day so and you don’t have to think about it again for six months.

Yeah I bring a lot of magazines and I always try and take someone with me but always a different person every time because I appreciate how boring it is and because they give you; one of the drugs they give you before they give you the infusion is Piriton [chlorphenamine maleate] which is like an anti-allergy thing that you can take for hay fever and that kind of thing just to kind of try and prevent any allergic reaction to it. It makes you really drowsy so a lot of the time I fall asleep and so whatever person has come with me to, to have the, have the infusion ends up sat there just by themselves for a few hours so I do try and rotate my friends and family round.

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Lucy takes anakinra for her systemic JIA and injects the medication.

Lucy injects her stomach with anakinra. She prefers to inject herself because she can control…

Age at interview 10

Gender Female

Age at diagnosis 7

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Anakinra OK and that’s the one that goes in your stomach?

Yup.

You mentioned that you had it in your leg before.

Yeah

Why did you put it in your stomach now rather than have it in the other leg?

Because if there is, there’s less muscles in your stomach and then it doesn’t hurt as much.

In this, up here, because there’s more fat.

OK so on your, the top of the leg, on the thigh?

Yeah

And when it comes to your stomach whereabouts in your stomach do you put it?

In just in the middle not like near my belly button whatever.

Not near your belly button?

No just like the two sides.

OK. I’m assuming that somebody shows you how to do the injection? Who was that?

It was our, I can’t remember the name, it was my nurse. It was like she showed you how to do it but Mum, she showed Mummy how to do it first.

OK so did the person come to the house or did you have to go to them?

And I was in the hospital then so in the end they came here.

A lot of young people are injected by their mums or sometimes dads so I was surprised to learn that you know you’re ten years old and you’re doing it yourself. So I was wondering if your mum or dad had ever injected you?

Yeah Mummy injected me like about three times and then that was it and I prefer to do it myself.

You mean you decided? Is it better that you do it yourself?

Yeah

Why’s it better?

Because I just can get control of where it is and all that so I

Are you, who’s better? You or your Mum at giving these injections?

Me

Who hurts less?

Me

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Steroids for arthritis

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