Efficacy of Biologicals in the Treatment of Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic multisystem disease. A characteristic feature of RA is persistent inflammatory synovitis, usually involving the peripheral joints in a symmetric distribution. The prevalence of RA is approximately 0.8% of the population (range: 0.3–2.1%); women are affected approximately 3 times more often than men. The current therapeutic approach is to start a disease-modifying agent early in the illness to prevent eventual joint damage. Older disease-modifying anti-rheumatic drugs include methotrexate, sulphasalazine and hydroxychloroquine. Newer ones such as leflunomide and cyclosporin are also used. A recent advance in the management of rheumatoid arthritis is the use of biological agents, which block certain key molecules involved in the pathogenesis of the illness. They include tumour-necrosis-factor-α-blocking agents such as infliximab, etanercept and adalimumab, the anti-CD-20 agent, rituximab, and CTLA-4 Ig abatacept. The present study was planned with the aim of evaluating the efficacy of such newer biological therapies in refractory RA at various time points. Databases including Medline, Embase and the Cochrane Library were searched for all relevant studies up to January 2007. A total of 26 studies were included in present meta-analysis. The method of DerSimonian and Laird [Control Clin Trials 1986;7:177–188] was used to calculated a pooled odds ratio (OR) for the American College of Rheumatology (ACR) criteria 20, 50 and 70, at 24, 54 and 96 weeks. The overall pooled OR were found to be significantly more than the placebo at all 3 time points for all 3 criteria (ACR 20, 50 70). In conclusion, biologicals as a group are highly effective in the treatment of RA. Biologicals were efficacious both in treatment naïve and methotrexate-refractory patients.

Therapy of B-cell malignancies by anti–HLA-DR humanized monoclonal antibody, IMMU-114, is mediated through hyperactivation of ERK and JNK MAP kinase signaling pathways

“…24 In patients with more aggressive histologic lymphoma subtypes, rituximab therapy has an approximately 30% overall response rate, 25 but combined with CHOP chemotherapy, improved objective responses and durations compared with CHOP alone, making R-CHOP a standard protocol for the treatment of diffuse large B-cell lymphoma. [26][27][28][29] Rituximab's success has led to an expansion of its use in a variety of diseases [30][31][32][33][34][35][36] and has generated an ongoing effort to improve on the efficacy of rituximab treatments for B-cell malignancies. Efforts include the development of humanized anti-CD20 mAbs, 12,37 combining mAbs with other biologic agents, eg, interleukin-2 26 and interferon, 38 combining mAb therapy with chemotherapy, as was done with CHOP, 39,40 and the use of mAbs that target antigens other than CD20.…”

Comparison of Certolizumab Pegol with Other Anticytokine Agents for Treatment of Rheumatoid Arthritis: A Multiple-treatment Bayesian Metaanalysis

“…Therefore, only indirect comparisons (vs a common comparator) 8 make it possible to assess the differences possibly existing between antirheumatic biotherapies. Some recently published studies used multiple-treatment metaanalyses to compare the first marketed anti-TNF-α agents (infliximab, etanercept, adalimumab) either between them 9,10 or with another biological agent (abatacept, anakinra, or rituximab) 11,12,13 . Regarding the clinical efficacy of CZP, it still has not been compared with that of other anticytokine biotherapies [anti-TNF-α, anti-interleukin 1 and 6] in a mixed-treatment comparison.…”

Mucosal healing predicts long-term outcome of maintenance therapy with infliximab in Crohnʼs disease

“…[4][5][6] A beneficial impact of early disease-modifying treatment on diseaseassociated damage has been demonstrated in rheumatoid arthritis but not in CD. 7 Corticosteroids are not diseasemodifying in CD. 12,13 Azathioprine and methotrexate have been shown to induce MH in patients with CD who experience long-term remission but their effect on the natural history of the disease and on the need for surgery remains largely unknown.…”