Authors' objectives:

The aim of this report was to assess the use of etanercept, infliximab and adalimumab for the treatment of rheumatoid arthritis.

Authors' results and conclusions: Etanercept: Etanercept as single drug therapy didn t prove to be better than MTX during a Cochrane systematic review published in 2003. When compared to placebo, etanercept showed better ACR20 response rates (20% improvement in the ACR index, one of the indexes most widely used to assess the impact of rheumatoid arthritis (RA)) after six months with a 40% absolute increase in benefits. In another study where 686 patients were randomized to receive MTX plus etanercept or each drug separately, a better ACR20 response rate was observed in the combination therapy group (85% vs 75% and 76% for single drug therapy with MTX and etanercept, respectively). Combination therapy with both drugs was also more effective at attaining a higher rate of disease remission as well as in the radiographic findings. Infliximab: Infliximab proved to be more effective than placebo in studies conducted after six and twelve months of treatment in combination with MTX. It showed better ACR20 response rates with a 25% absolute benefit. In another study where 1,049 patients were randomized to receive MTX plus infliximab or MTX plus placebo, those patients treated with infliximab showed better ACR response rates and better radiographic and quality of life scores. The absolute benefit for the group treated with infliximab was between 9 and 13%. Adalimumab: Adalimumab proved to be better than placebo in a study that randomized 644 patients who had had a poor response to disease modifying anti-rheumatic drugs (DMARDs). The group treated with adalimumab reached an ACR20 response between 35.8 and 53.4% of the cases, depending on the dose used. While in the placebo group, this response was obtained only in19%. When assessing the effectiveness of adding adalimumab to MTX therapy, this combination therapy proved to be more effective than any of the two drugs separately, with an absolute increase in benefits (as per ACR50) between 16% and 21%. Adverse effects: Due to the interaction of these drugs with the immune system, there is fear that they may increase the risk of severe infections, malignancies and autoimmune events. There was an increase in the risk of severe infections; especially tuberculosis (TB) and lymphoma in adverse effect follow-up studies and drug surveillance programs. Because of the increase in the risk of TB, it is recommended to screen its presence and, if necessary, to administer treatment or prophylaxis prior to starting anti-TNF Contraindications against the use of these drugs include heart failure Class III-IV, active or latent TB and other active infections such as HIV, recent history of malignancies, specially lymphoma; multiple sclerosis or optical neuritis; history of anaphylaxis with the use of this drug or concomitant use of anakinra.

Authors' recommendations: Three biological agents have proved to be better than placebo in the management of active RA. None of them proved to be better than MTX when used as single drug therapy. Combination of any of these three drugs with MTX has proved to be more beneficial than MTX administered alone. Special care should be taken in the surveillance of severe infections, autoimmunity and neoplasias in patients treated with these drugs, especially screening for TB prior to starting therapy. These are drugs with a potentially high cost for health systems. In those countries where studies were conducted on their cost-effectiveness, these treatments did not prove to be cost-effective or their cost-effectiveness was at the limit of internationally accepted standards. That is why, in countries where these drugs are covered, they are specifically used in those selected subgroups of patients with active RA who have not adequately responded to conventional treatment with MTX or who have not tolerated it.

Authors' methods: Overview

Project Status: Completed

URL for project: http://www.iecs.org.ar/

Year Published: 2006

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Argentina

Organisation Name: Institute for Clinical Effectiveness and Health Policy

Contact Address: Dr. Emilio Ravignani 2024, Buenos Aires - Argentina, C1414 CABA

Contact Name: info@iecs.org.ar

Contact Email: info@iecs.org.ar

Copyright: Institute for Clinical Effectiveness and Health Policy (IECS)