Background and ObjectivesFive-tumour necrosis factor (TNF)-blockers (infliximab, etanercept, adalimumab, certolizumab pegol and golimumab) are available for treatment of rheumatoid arthritis. Only few clinical trials compare one TNF-blocker to another. Hence, a systematic review is required to indirectly compare the substances. The aim of our study is to estimate the efficacy and the safety of TNF-blockers in the treatment of rheumatoid arthritis (RA) and indirectly compare all five currently available blockers by combining the results from included randomized clinical trials (RCT).MethodsA systematic literature review was conducted using databases including: MEDLINE, SCOPUS (including EMBASE), Cochrane library and electronic search alerts. Only articles reporting double-blind RCTs of TNF-blockers vs. placebo, with or without concomitant methotrexate (MTX), in treatment of RA were selected. Data collected were information of patients, interventions, controls, outcomes, study methods and eventual sources of bias.ResultsForty-one articles reporting on 26 RCTs were included in the systematic review and meta-analysis. Five RCTs studied infliximab, seven etanercept, eight adalimumab, three golimumab and three certolizumab. TNF-blockers were more efficacious than placebo at all time points but were comparable to MTX. TNF-blocker and MTX combination was superior to either MTX or TNF-blocker alone. Increasing doses did not improve the efficacy. TNF-blockers were relatively safe compared to either MTX or placebo.ConclusionsNo single substance clearly rose above others in efficacy, but the results of the safety analyses suggest that etanercept might be the safest alternative. Interestingly, MTX performs nearly identically considering both efficacy and safety aspects with a margin of costs.

All available TNF-inhibitors showed similar treatment responses with or without csDMARDs. Adalimumab was associated with better drug survival when compared to infliximab.

Background and ObjectivesEconomic evaluations provide information to aid the optimal utilization of limited healthcare resources. Costs of biologics for Rheumatoid arthritis (RA) are remarkably high, which makes these agents an important target for economic evaluations. This systematic review aims to identify existing studies examining the cost-effectiveness of biologics for RA, assess their quality and report their results systematically.MethodsA literature search covering Medline, Scopus, Cochrane library, ACP Journal club and Web of Science was performed in March 2013. The cost-utility analyses (CUAs) of one or more available biological drugs for the treatment of RA in adults were included. Two independent investigators systematically collected information and assessed the quality of the studies. To enable the comparison of the results, all costs were converted to 2013 euro.ResultsOf the 4890 references found in the literature search, 41 CUAs were included in the current systematic review. While considering only direct costs, the incremental cost-effectiveness ratio (ICER) of the tumor necrosis factor inhibitors (TNFi) ranged from 39,000 to 1 273,000 €/quality adjusted life year (QALY) gained in comparison to conventional disease-modifying antirheumatic drugs (cDMARDs) in cDMARD naïve patients. Among patients with an insufficient response to cDMARDs, biologics were associated with ICERs ranging from 12,000 to 708,000 €/QALY. Rituximab was found to be the most cost-effective alternative compared to other biologics among the patients with an insufficient response to TNFi.ConclusionsWhen 35,000 €/QALY is considered as a threshold for the ICER, TNFis do not seem to be cost-effective among cDMARD naïve patients and patients with an insufficient response to cDMARDs. With thresholds of 50,000 to 100,000 €/QALY biologics might be cost-effective among patients with an inadequate response to cDMARDs. Standardization of multiattribute utility instruments and a validated standard conversion method for missing utility measures would enable better comparison between CUAs.

Our results provide some reassurance of the safety of biologic treatments in the treatment of RA.