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. 

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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. 

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.

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.

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.

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.

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.

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.

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 and other diagnostic tests.)

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).

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. 

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.   

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.

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.

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.

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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.

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.

Limitations of anti-TNF and B-cell therapy drugs

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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.

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.  

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.

B-cell therapy rituximab

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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.

Last reviewed August 2016.

Last update August 2016.

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