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 persons 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.

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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.

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

Age at interview 51

Gender Female

Age at diagnosis 51

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

Age at interview 37

Gender Female

Age at diagnosis 30

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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…

Age at interview 26

Gender Female

Age at diagnosis 22

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

Age at interview 49

Gender Female

Age at diagnosis 33

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

Age at interview 37

Gender Female

Age at diagnosis 27

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

Age at interview 29

Gender Female

Age at diagnosis 25

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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…

Age at interview 24

Gender Female

Age at diagnosis 21

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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…

Age at interview 49

Gender Female

Age at diagnosis 33

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

Age at interview 54

Gender Female

Age at diagnosis 25

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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 womans 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.

Age at interview 37

Gender Female

Age at diagnosis 27

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Injects Humira Anti-TNF into her leg every two weeks but one batch she was given was out of date.

Age at interview 21

Gender Female

Age at diagnosis 12

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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…

Age at interview 73

Gender Female

Age at diagnosis 67

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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.

Age at interview 73

Gender Female

Age at diagnosis 67

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

Age at interview 24

Gender Female

Age at diagnosis 21

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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 persons 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.)

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

Age at interview 51

Gender Female

Age at diagnosis 51

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

Age at interview 60

Gender Female

Age at diagnosis 40

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

Age at interview 26

Gender Female

Age at diagnosis 22

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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…

Age at interview 49

Gender Female

Age at diagnosis 33

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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…

Age at interview 37

Gender Female

Age at diagnosis 30

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

Age at interview 60

Gender Female

Age at diagnosis 40

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

Age at interview 51

Gender Female

Age at diagnosis 51

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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.

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

Age at interview 26

Gender Female

Age at diagnosis 22

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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

Gender Female

Age at diagnosis 21

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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…

Age at interview 24

Gender Female

Age at diagnosis 21

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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…

Age at interview 22

Gender Female

Age at diagnosis 11

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

Age at interview 22

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Age at diagnosis 5

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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.

Age at interview 29

Gender Female

Age at diagnosis 25

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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.

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

Age at interview 26

Gender Female

Age at diagnosis 22

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

Age at interview 22

Gender Female

Age at diagnosis 11

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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…

Age at interview 44

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Limitations of anti-TNF and B-cell therapy drugs

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

Age at interview 49

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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.

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

Age at interview 53

Gender Female

Age at diagnosis 30

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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

Gender Female

Age at diagnosis 13

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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…

Age at interview 22

Gender Female

Age at diagnosis 5

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

Age at interview 54

Gender Female

Age at diagnosis 25

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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.

Age at interview 53

Gender Female

Age at diagnosis 30

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B-cell therapy rituximab

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

Age at interview 49

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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.

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

Age at interview 40

Gender Female

Age at diagnosis 38

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

Age at interview 40

Gender Female

Age at diagnosis 38

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