Abatacept in biologic-naïve patients and TNF inadequate responders: clinical data in focus.
BACKGROUND
Advances in the understanding of rheumatoid arthritis (RA) immunopathogenesis support the hypothesis for a 'window of opportunity' for therapeutic intervention in RA and the need for rapid and effective treatment strategies, with the ultimate goal of alleviating symptoms and halting progressive joint damage. Biologic therapies targeting pro-inflammatory cytokines have significantly improved the outlook for patients with RA; however, some patients still experience inadequate treatment responses. Recently, therapeutic agents targeting alternative pathways have been developed. One such therapy--abatacept--targets T-cell activation and is approved in the United States for treatment of moderate-to-severe RA and juvenile idiopathic arthritis.


OBJECTIVE
To overview the efficacy and safety of abatacept in the treatment of adult patients with active RA and an inadequate response to methotrexate (MTX) or tumor necrosis factor (TNF) antagonists. SEARCH METHODOLOGY: A comprehensive literature search was performed using the National Library of Medicine (MEDLINE), EMBASE and BIOSIS databases (restricted to articles in the English language posted between January 2000 and February 2007). The search terms 'CTLA-4Ig', 'abatacept' and 'ORENCIA' were used, and data from randomized clinical trials were summarized.


RESULTS
Abatacept provided clinically meaningful improvements in the signs and symptoms of RA in both MTX and TNF antagonist inadequate responders in Phase II and III studies. Health-related quality of life was also improved with abatacept, which demonstrated an acceptable safety and tolerability profile in both patient populations. Additionally, when assessed in patients with an inadequate response to MTX, abatacept inhibited structural damage progression.


CONCLUSIONS
Although longer-term data are required and differing study designs preclude direct comparisons with other RA therapies, results of clinical trials to date suggest that abatacept has an acceptable safety profile and is an effective treatment option for patients with RA, whether treating biologic-naïve patients or those who have already had an inadequate response to TNF antagonists.
Sherrer
Yvonne
Y
Center for Rheumatology, Immunology and Arthritis, Fort Lauderdale, FL 33334, USA. YRSherrer@AOL.com
D000069594:Abatacept; D000328:Adult; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D018501:Antirheumatic Agents; D018796:Immunoconjugates; D014409:Tumor Necrosis Factor-alpha; D000069594:Abatacept