Rheumatoid arthritis: biologics in second-line therapy show benefit

The German Institute for Quality and Efficiency in Health Care (IQWiG) examined 9 biotechnologically produced drugs for the treatment of adults with rheumatoid arthritis in whom prior pharmacological treatment had failed. According to the findings, for each drug the data provide proof, an indication, or at least a hint of a benefit in relation to at least one outcome criterion. This is the conclusion of the final report published by IQWiG on 26 August 2013.

In comparison to the preliminary report, additional data and studies confirm the positive effect of biologics. However, there is a lack of long-term data and robust direct comparisons of biologics with each other to be able to assess which of these drugs are better or less suited in second-line therapy.

Alleviation of pain and prevention of damage to joints

Rheumatoid arthritis is an autoimmune disease and the most common form of chronic inflammatory joint disease (0.5 to 1% of the EU population). Patients suffer from pain, fatigue and exhaustion, depressive moods, as well as functional limitations; these symptoms are accompanied by a loss of quality of life, independence and participation in social and occupational activities. The primary aim of treatment is thus to eradicate the symptoms of disease as far as possible and delay or prevent the destruction of joints (remission).

Nine biologics in second-line therapy

Disease-modifying antirheumatic drugs (DMARDs), among others, are used in the pharmacological treatment of rheumatoid arthritis, which, in contrast to anti-inflammatory drugs, intervene with the disease mechanism itself. Biotechnologically produced DMARDs (bDMARDs), called biologics, are harvested from living cell cultures.

The bDMARDs intervene at different points of the inflammation process via different mechanisms. Most of them inhibit the tumour-necrosis factor (TNF)-?, a factor that influences the inflammation process. According to treatment recommendations, the administration of a bDMARD is indicated as second-line therapy for patients in whom prior therapy failed to achieve the desired success or had no effect at all.

Nine such drugs were available in 2010 at the time IQWiG was commissioned to conduct the present benefit assessment: abatacept (trade name: Orencia), adalimumab (Humira), anakinra (Kineret), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi), infliximab (Remicade), rituximab (MabThera), and tocilizumab (RoActemra).
Treatment in placebo groups discontinued more frequently

A total of 35 studies were relevant for the present benefit assessment; however, some only reported results for subpopulations. In nearly all studies patients received the cytostatic drug methotrexate (MTX), which is used as basic therapy in inflammatory-rheumatoid diseases. One patient group additionally received a biologic; the control group mostly received placebo.