Biologics treatments: anti-TNF and b-cell therapy

There are two currently licensed biologic treatments: TNF inhibitors and b-cell therapy rituximab. These work in different ways. 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. B-cell therapy rituximab (trade name MabThera) removes antibody-producing white blood cells called B-cells. B-cells play an important role in inflammatory reactions that can lead to joint inflammation, deformity and loss of function.

Five different anti-TNF drugs can be used. Infliximab (Remicade) is given in an intravenous drip every 8 weeks and usually taken in combination with methotrexate. The others are injected subcutaneously (beneath the skin): etanercept (Enbrel) usually once a week, adalimumab (Humira) usually every 2 weeks, certolizumab (Cimzia) and golimumab (Simponi) two new TNFi drugs that are both self injected under the skin.

A new biologic therapy; abatacept (Orencia), that works in a totally different way, inhibiting the activation of certain white blood cells, has not been approved by  NICE (National Institute for Clinical Excellence). The present cost (2007) of anti-TNF treatment is between £9,000 and £18,000 per patient per year.

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 course of rituximab cost around £3,500. This treatment is repeated only if/when there are signs that improvement is wearing off, which can be anything from 6 months to 3 years later. 

These new therapies are only considered for a minority of patients who fulfil specific criteria set out by the National Institute of Clinical 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) and the hospital and the Primary Care Trust (PCT) have to agree funding before the drug is used.  A minority of patients with RA will require these drugs, employed when standard drugs are either not tolerated or are not effective.

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

Professor Robert Moots explains about biologic treatments for rheumatoid arthritis.

Anti-TNF and B-cell treatments

Access to anti-TNF and B-cell therapies is limited to those who fail to respond to other treatments and those who have particularly bad disease. Presently reported waiting time for anti-TNF treatment vary from five months to a year. Seventeen of the people we interviewed were currently on the 'biologics' 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. Five 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 RA was assessed by two specialists before being given anti-TNF therapy.

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

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 provided the necessary information but did not promise any 'magic cure'. She made significant improvement within two weeks.

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

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

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

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 improvements as a slow process.

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 the other patients.

Pat preferred Simponi injections to infusions because the latter gave her headaches. She found the lack of privacy in the hospital uncomfortable.

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.

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

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 features of the syringe that helped her decide for this anti-TNF medication.

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.

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

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.)

Sandra talks about how often she is seen on the anti-TNF clinic and describes the care she receives as excellent. But her only frustration is the setting up of follow up appointments.

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

Talks about her hospital appointments, including her anti-TNF clinic and the type of tests she has done. She says that there is a lot of monitoring because the anti-TNF is a 'powerful' drug.

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 started. Felt she had to try this new treatment.

Information and access to specialist advice is very important to people on the 'biologics' treatments. Anti-TNF drugs and B-cell therapy do lower the immune system and some of the respondents indicated that they experience more frequent colds and infections than before. Several respondents said that assessing correctly whether or not to take their medication when ill was most important. All respondents on the biologics treatments indicated 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 that she put her concerns about side effects of Humira into perspective.

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

Sandra was advised by her anti-TNF team to avoid sunlight exposure and to seek medical help if she gets infections such as colds or sore throats.

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.

At every opportunity, her consultant raises the issue of the importance of not getting pregnant while on Enbrel. She and her husband have decided not to have any children.

Emma and her partner would like children in the future. At present, they are very careful to avoid an unplanned pregnancy and Emma is on the contraceptive pill and her partner uses a condom.

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 a procedure to correct that and says she will continue using the anti-TNF drug because it is working so well for her but, she finds it frustrating not to know more about long-term side-effects.

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 consultants accepted her decision but another warned her that Enbrel on its own was less effective.

She is more concern about the side effects of methotrexate than the anti-TNF drugs. Besides she will try anything to alleviate her condition.

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.

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 because she didn't have “much of a life anyway”.

Says that she has a more positive outlook on life since starting on Enbrel because she knows her RA is under control and talks about what she is able to do since starting on anti-TNF medication.

People who started to use anti-TNF drugs as part of a clinical trial were initially uncertain about their chances of securing funding from their PCT 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 funds for her to continue on it once the trial is over. She is particularly worried about the impact a deterioration of her symptoms can have on her work life.

Limitations of anti-TNF and B-cell therapy drugs

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

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 joint damage.

She explains that her anti-TNF drug is working well and that at present she prefers drug therapy to surgery because she is moving to France. Ankle damage is the result of years of inflammation.

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 the interview she was due to start on influximab.

Although Pat felt better on Simponi, test results showed that the level of disease was unchanged. She has been offered B cell therapy– rituximab but she is apprehensive about trying a new drug.

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.

B-cell therapy rituximab

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

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 drugs. She has noticed some improvement in her condition since starting on rituximab.

Says that her care team at the anti-TNF clinic has prepared her for the possibility that rituximab might not work and that she too has more 'realistic' expectations.