Comparative effectiveness and survival of infliximab, adalimumab, and etanercept for rheumatoid arthritis patients in the Hellenic Registry of Biologics: Low rates of remission and 5-year drug survival
Introduction
Anti-TNFα agents are the most commonly used class of biologic agents for the treatment of active rheumatoid arthritis (RA) [1]. Among different anti-TNFα drugs, adalimumab, etanercept, and infliximab are the three most widely used. Although these agents differ in their mode of action, pharmacokinetics, and immunogenicity, it is not clear whether clinical outcomes also differ. This is due to paucity of head-to-head randomized controlled trials (RCTs) and the conflicting results of observational studies.
Information about the comparative effectiveness and safety of TNFα inhibitors can guide treatment decisions in clinical practice. Data from meta-analyses of RCTs have been used for indirect comparison of TNFα-inhibitors. A systematic review of RCTs and prospective cohort studies demonstrated comparable effectiveness of the three TNFα inhibitors, adalimumab, etanercept, and infliximab [2]. A network meta-analysis based on RCTs of biologics in RA concluded that there were no significant differences in efficacy measures between anti-TNFα agents though etanercept was safer than adalimumab and infliximab [3]. A more recent similar analysis showed that although the odds for serious infections were comparable between the three TNFα inhibitors, withdrawals due to adverse events were more likely with infliximab [4].
Results from observational studies provide complementary information to those of RCTs regarding long-term drug efficacy and safety [5]. In most European registries of RA patients, differential drug response rates in favor of etanercept and adalimumab as compared to infliximab have been observed [6], [7]. In contrast, the Portuguese and the US CORRONA registries reported comparable effectiveness of adalimumab, etanercept, and infliximab, although in the latter study, infliximab was associated with higher survival rates [8], [9]. In terms of safety, two retrospective studies in the US have reported a higher risk for serious infections with infliximab compared to etanercept and adalimumab [10], [11]. Moreover, treatment with etanercept was associated with lower risk for serious infections compared to adalimumab and infliximab in the DREAM registry [12], while drug discontinuations due to adverse events were significantly lower for etanercept than for infliximab in the RADIUS [13] and the BIOBADASER [14] registries.
Data on the comparative efficacy and safety of different anti-TNFα agents in southern European RA patients are limited [8], [15], [16]. This is important in view of the variations in disease severity across different ethnic backgrounds and clinical settings [17]. In this paper, we report on effectiveness, survival, and safety profile of three anti-TNF agents, namely infliximab, adalimumab, and etanercept, in a Greek RA population from the Hellenic Registry of Biological Therapies. We also evaluate predictors of clinically important outcomes, such as major treatment responses, drug withdrawal, and serious infections.
Section snippets
Study design
The Hellenic Registry of Biologic Therapies is a nationwide, prospective, observational cohort of patients with inflammatory arthritides. Patients are enrolled by participating rheumatologists from seven academic and national health system rheumatology centers located at five different regions across the country. The registry was founded in 2004 and is under the auspices of the Hellenic Society for Rheumatology (HSR). Patients have an unrestricted access to anti-TNFα agents based on the
Participants
By 31/12/2009, 2216 patients who received 3113 treatment courses had been registered. A total of 1188 patients were excluded due to diagnoses other than RA (n = 943), or treatment with DMARDs only (n = 167), or biologic agent other than TNFα inhibitor (n = 78). Thus, 1028 patients who received 1297 treatments with infliximab (n = 560), adalimumab (n = 435), and etanercept (n = 302) were analyzed (Table 1). All treatments were consecutive courses of the first (n = 1028), second (n = 233), and
Discussion
This is the first report of the Hellenic Registry of Biologic Therapies on long-term efficacy and safety of anti-TNFα treatment with infliximab, adalimumab, and etanercept in RA patients. Our main finding is that, although treatment responses were comparable between the three agents, disease remission rates were lowest for infliximab, intermediate for etanercept, and highest for adalimumab. Moreover, drug survival was lowest for infliximab due to increased safety-related withdrawals compared to
Conclusion
This is a report from a large Mediterranean cohort of RA patients on the comparative effectiveness and safety of the three most widely used anti-TNFα agents during a long-term follow-up. Our data are in line with most European registries showing a differential long-term drug survival between infliximab, adalimumab, and etanercept, mostly due to adverse events. Yet, the most clinically important finding for a chronic disease like RA is that overall 5 years anti-TNFα survival in real life is less
Acknowledgments
We would like to thank Hellenic Rheumatology Society for the support.
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Role of funding source: This work was supported in part by the Hellenic Rheumatology Society through unrestricted grants from Shering-Plough, Abbott, Wyeth, Bristol Myers Squibb and Roche companies. Those companies had no role in study design, collection, analysis and interpretation of the data, in the writing of the manuscript and in the decision to submit the manuscript for publication.