Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Comparative Effectiveness of Biological Treatment Options Following Tumor Necrosis Factor Inhibitor Failure in Rheumatoid Arthritis: Systematic Review and Indirect Pairwise Meta-Analysis.
Schoels1, Monika, Wong2, John B., Aletaha3, Daniel, Smolen4, Josef S.
2nd Department of Internal Medicine, Hietzing Hospital, Vienna, Austria; Div. of Clinical Decision Making, Informatics and Telemedicine, Tufts University School of Medicine, Boston, MA
Div. of Clinical Decision Making, Informatics and Telemedicine, Tufts University School of Medicine, Boston, MA
Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Austria
Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Austria; 2nd Department of Internal Medicine, Hietzing Hospital, Vienna, Austria
The optimal treatment for rheumatoid arthritis (RA) patients who fail tumor necrosis factor a inhibitors (TNFi) remains uncertain; direct randomized controlled trials comparing therapeutic options are lacking. Therefore, we indirectly compared drug efficacy and safety of biologic agents following inadequate response to TNFi. Additionally, we investigated the dependence of success rates on the number of previously failed TNFi.
We performed a systematic literature search and retrieved randomized controlled trials (RCTs) that enrolled patients who had experienced TNFi failure. After assessing the heterogeneity of trial populations at baseline, we performed an indirect meta-analysis with pairwise comparisons of drug efficacy and safety using a random effects model. We used published clinical trial data on abatacept (ABA), rituximab (RTX), and tocilizumab (TOC) to perform the analyses; for golimumab (GOL), we obtained ACR20, 50 and 70 response rates in the subpopulation of patients treated with concomitant methotrexate (MTX) for 24 weeks to match the other trials. We derived odds ratios (OR) for ACR response and ascertained risk differences (RD) for adverse events, serious adverse events and infection rates. In sub-analyses, we investigated whether multiple previous TNFi failures diminished the clinical response when compared to the efficacy of biologicals after one TNFi.
In four RCTs with 24 week follow-up, direct comparisons of abatacept, golimumab, rituximab, and tocilizumab versus placebo showed statistically significant mean odds ratios for ACR20 (point estimates ranging from 3.38.9), ACR50 (5.510.2) and ACR70 (4.113.5). The risk for adverse events, serious adverse events, and serious infections was non-significant compared with placebo. Indirect pairwise comparisons of the four biologic agents showed no statistically significant differences in ACR50 and ACR70 outcomes. Golimumab had a significantly lower ACR20 response (OR 0.560.59) but significantly fewer adverse events (RD 0.130.18). Drug efficacy outcomes following multiple previous TNFi failures did not differ significantly from patients with a history of 1 TNFi (data for comparison was available for golimumab and tocilizumab, Figure).
Figure. Response rates of GOL (left column) and TOC (right column). ACR20 (top panel), 50 (middle panel), and 70 (lower panel) of patients that had previously failed 2 (p2) and 3 (p3) TNFi, when compared to drug response rates after failure of 1 TNFi (p1)
In patients refractory to one or more TNFi, new biological agents provide significant improvement with good safety. In the absence of head-to-head trials, adjusted indirect meta-analysis enables evaluation of the comparative effectiveness and safety of biologics with each other and reveals similar effects of all biologicals.
To cite this abstract, please use the following information:
Schoels, Monika, Wong, John B., Aletaha, Daniel, Smolen, Josef S.; Comparative Effectiveness of Biological Treatment Options Following Tumor Necrosis Factor Inhibitor Failure in Rheumatoid Arthritis: Systematic Review and Indirect Pairwise Meta-Analysis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1795