Cimzia (certolizumab pegol)

Professor Peter C. Taylor MA, PhD, FRCP Kennedy Institute of Rheumatology Division,
Imperial College London
Original article: 27/10/2010
Reviewed: N/A
Next review due: 27/10/2013

What is Cimzia (certolizumab pegol)?

Cimzia is a small protein-based drug, which is a part of an antibody molecule, administered by subcutaneous (meaning under the skin) injection, that blocks the activity of soluble tumour necrosis factor (TNF), a major mediator of inflammation and joint damage in rheumatoid arthritis. The Cimzia molecule comprises a chemical called PEGOL which is attached to the protein component that blocks TNF.  Because the protein component is small in size and weight it would soon be cleared from the body after injection. By undergoing a process known as PEGylation, when the PEGOL is added to the protein that neutralises harmful TNF, the resulting molecule lasts longer in the body and so only needs to be injected once every two weeks. There are several other examples of PEGylated protein drugs that have been in use for a long time, such as PEGylated interferon treatment for Hepatitis C infection.

Why has this drug been prescribed?

Cimzia is one of several drugs in a class of therapeutics that work by neutralising TNF (these drugs are often referred to as ‘anti-TNF' drugs). Cimzia has been tested in clinical trials and is usually prescribed in rheumatoid patients with severe and active disease that has not been adequately controlled by a trial of at least two standard disease modifying anti-rheumatic drugs (DMARDs), one of which must be methotrexate, either used in combination or separately. As in the case of other anti-TNF drugs, Cimzia works most effectively in those patients able to take once-weekly methotrexate in addition to Cimzia. In the important clinical trials that were undertaken before Cimzia became available in the clinic, about 60% of patients taking Cimzia together with background methotrexate therapy were found to have a clinically meaningful benefit. The range of benefits included reductions in the numbers of swollen and tender joints and reduction in pain and fatigue.

Another consistent finding in clinical trials was that there is a very low frequency of injection site reactions and discomfort with Cimzia, with over 98% of patients in trials reporting no problems. The reason for this very low rate of injection site discomfort is not fully understood but it has been suggested that it may be explained in part by the PEGOL in the Cimzia molecule.

How is the drug administered?

The drug is given by self administered subcutaneous injection once every two weeks. When the drug is first started, a “loading dose” is given for the first three times the drug is used and this may help to speed up the onset of benefit. For the first three occasions that the drug is administered, two separate injections are required for each of the three visits. These have the potential advantage that a nurse can give the first dose and also show the patient what to do, and then can watch the patient give the second dose. Once this has been done for a total of three times, then only a single injection is required once a fortnight.

The injection can be administered with a syringe that has been especially designed by ‘OXO Good Grips’, the company that makes specialist kitchen equipment and utensils, to be very easy to use for patients with a range of hand function. It is particularly easy to use even if there is marked hand disability. You will be shown the syringe and different ways in which you can use it, finding the most comfortable and convenient way to suit you, when you are taught how to inject Cimzia.

As in the case of other anti-TNF drugs, Cimzia works most effectively in those patients able to take once weekly methotrexate in addition to Cimzia. However, Cimzia can also be given on its own without the need for methotrexate treatment at the same time if there have been side-effects to methotrexate or other reasons why it should not be used.

How does the drug work?

Like other anti-TNFs, Cimzia works by neutralising a chemical known as TNF which is produced in high amounts in the rheumatoid joint. TNF is a cause of many of the features of rheumatoid arthritis including inflammation, which is seen as swelling, tenderness and heat, as well as damage to joints that occurs if the inflammation caused by TNF is not adequately switched off. In clinical trials, improvements (such as reduced fatigue and pain and a reduction in the number of swollen, painful joints) were observed as early as 1 week after the first injection and the size of improvement in those patients responding continued to increase with further injections up to 12 weeks.

What are the potential side-effects?

Most patients will experience no or very minor side-effects at all with Cimzia. Very few patients (less than 2%) experience injection site pain or reactions. Otherwise, the side-effects that can occur with Cimzia are very similar to those that can arise with any anti-TNF treatment. Because TNF can play a role in immune defence against infection in healthy people as well as having a harmful role in the features of arthritis in rheumatoid, a minority of patients may experience infections more readily than if they were not on Cimzia. However, only a very small proportion of patients would be expected to get serious infectious complications requiring an admission to hospital. If you do develop symptoms of an infection, such as a cough productive of coloured sputum and a temperature, it is best to get in touch with your GP and rheumatology practice straight away. It may be necessary to miss your next dose of Cimzia and your GP or rheumatologist will decide whether antibiotics or other treatment will be necessary.

If you require joint surgery, your rheumatologist may advise that you stop Cimzia temporarily around the time of surgery to minimise the small risk of infectious complications or any problems with wound healing.

How can I reduce the risk of infection?

Many infections can be avoided by careful hand washing or using an antibacterial hand wash after going out or travelling.  Some foods contain live bacteria and are best avoided when on biologics. A particular example would be unpasteurised soft cheeses.

Can you have alcohol with this drug?

There is no reason to abstain from alcohol if you take Cimzia but, as many patients will also be taking methotrexate and/or other DMARDs, it is important to take alcohol only in moderation and after discussion with your specialist. For the majority of patients on methotrexate a modest alcohol intake is fine but it will depend on the individual and on your blood monitoring tests for liver function.

What is the monitoring for Cimzia/how often?

Patients on Cimzia need to be assessed at regular intervals to ensure that there is an adequate response. This will usually be about 12 weeks after starting the drug. After that, frequency of clinic follow-up will depend on how well disease activity has been managed. For some patients a twice-yearly check up will be fine whereas others will need to be seen more often. Most will be seen every 4-6 months. With respect to safety monitoring, no special tests are required for Cimzia itself but most patients will also be on other DMARDs and some of these (such as methotrexate and sulfasalazine) require blood monitoring tests at regular intervals. Your physician will advise you about this. It is very helpful to carry a booklet which records your blood test results so that these are available to both your GP and specialist when you visit.

Immunisations

As with other anti-TNF treatments, you are advised not to have immunisation with any live vaccines (for example yellow fever) while on the biologic treatment. However, it is alright to have non-live vaccines such as flu, and indeed patients with rheumatoid arthritis are encouraged to do so.

Shingles

Shingles can occur in individuals who have had previous chicken pox, as the virus that causes it can remain in nerve cells in a dormant state. Shingles is reported to occur more frequently in patients on anti-TNF although less so in patients on Enbrel than with Remicade or Humira. It is not yet known how frequently it occurs in Cimzia treated patients but it is assumed that there may be a small increased risk. In the event of an itchy, painful blistering rash of shingles type occurring over one area of the body you should report to your GP as soon as possible as there are medications which can help settle it down if taken early. Your rheumatologist or GP will be able to advise on whether Cimzia needs to be stopped temporarily as in the case of other infectious complications.

Effects on fertility/pregnancy

Cimzia is not known to have any detrimental effects on fertility. Indeed by controlling inflammation associated with arthritis, and perhaps by other mechanisms also, anti-TNFs in general may even enhance fertility but at this time more information is needed to understand its safety during pregnancy. If you are planning a pregnancy it is very important to talk to your specialist nurse or doctor who can give advice about drugs for your arthritis. Methotrexate needs to be discontinued prior to conception. If your arthritis is poorly controlled at the time you would like to become pregnant, then your specialist will discuss which drugs you can safely continue. If it is possible to control the arthritis without continuing anti-TNF, that is ideal. There is some information on use of injectable anti-TNF in pregnancy and many women have had healthy babies after taking self-injected anti-TNF throughout. Some women with Crohn’s disease have taken Cimzia through pregnancy very safely. Cimzia is different from other anti-TNFs in that it does not travel from the maternal blood across the placenta to a baby growing in the womb. Therefore, if an anti-TNF is required in pregnancy Cimzia would be a good choice. But this must be discussed very carefully with your specialist in the light of your other medication and overall activity of your disease.

Current licence

Cimzia is approved in the European Union for the treatment of patients with moderate to severe active rheumatoid arthritis who have failed to respond to treatment with other disease-modifying anti-rheumatic drugs (DMARDs). Additionally, Cimzia can also be considered as monotherapy (taken on its own without background once-weekly methotrexate) in patients where the use of methotrexate is considered inappropriate.

Other issues

At the time of writing, (June 2010) Cimzia is supplied on the basis of a so called “patient access scheme” which means that the first 12 weeks of drug are supplied free of charge to the primary care trust. The consequence of this is that your rheumatologist will be able to determine whether this drug works for you without cost over the first 12 weeks.

Conclusion

Cimzia is a biologic anti-TNF made by a new approach to antibody treatments that involves PEGylation of the part of an antibody that neutralises harmful, soluble TNF. The result of PEGylation is that the drug remains effective in the body for longer and therefore only has to be given by subcutaneous injection once every two weeks. The clinical trials show that Cimzia works rapidly in the majority of patients with early improvements in swollen and tender joints as well as pain, fatigue and physical function. Very few patients taking Cimzia experience injection site pain or reactions.

References available on request

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