Infliximab efficacy in rheumatoid arthritis after an inadequate response to etanercept or adalimumab: results of a target-driven active switch study. (November 2014)

• Record Type: Journal Article
• Authors: Fleischmann, Roy; Goldman, John A.; Leirisalo-Repo, Marjatta; Zanetakis, Ellen; El-Kadi, Hisham; Kellner, Herbert; Bolce, Rebecca; DeHoratius, Raphael; Wang, Jim; Decktor, Dennis
• Is Part Of: Current medical research and opinion. Volume 30:Number 11(2014:Nov.)
• Page Start: 2139
• Page End: 2149
• Publication Date: 2014-11
• Subjects: Clinical medicine -- Periodicals; Therapeutics -- Periodicals; 615.5
• DOI: 10.1185/03007995.2014.942416
• Languages: English
• ISSNs: 0300-7995

Abstract

<abstract> <title>Abstract</title> <sec id="ss1"> <title>Objective:</title> <p>Evaluate efficacy of infliximab with response-driven dosing in patients with active RA.</p> </sec> <sec id="ss2"> <title>Research design and methods:</title> <p>Patients (<italic>n</italic> = 203) with active RA despite methotrexate + etanercept/adalimumab, participated in this active-infliximab-switch study. Infliximab 3 mg/kg was infused at Weeks 0, 2, 6, 14, and 22 with escalation to 5 or 7 mg/kg depending on EULAR response at Weeks 14 and 22. The primary endpoint was EULAR response at Week 10. Safety was assessed through Week 30. Infliximab levels and antibodies to infliximab (ATI) were measured at Weeks 0, 6, 14, and 26.</p> </sec> <sec id="ss3"> <title>Clinical trial registration:</title> <p>NCT 00714493, EudraCT 2007-003288-36.</p> </sec> <sec id="ss4"> <title>Results:</title> <p>Of 197 evaluable patients, 120/77 previously received etanercept/adalimumab. Baseline mean (SD) swollen and tender joint counts were 17.3 (10.54) and 30.2 (16.89), respectively; mean DAS28-ESR was 6.19 (0.981). At Week 10, 98 (49.7%; 95% CI: 42.6%, 56.9%) patients achieved EULAR response, with a significantly improved DAS28-ESR score (mean [SD] change −1.1 [1.15]; <italic>p</italic> < 0.001). EULAR response was achieved by 41.7%/62.3% of patients previously receiving etanercept/adalimumab (<italic>p</italic> = 0.006). At Week 26, 51.8% (95% CI: 44.6%, 58.9%) of patients achieved or maintained EULAR response. Infliximab dose was escalated in 100 patients, 52% of whom achieved EULAR response at Week 26. Median serum concentration levels at Week 26 showed that dose escalation helped EULAR non-responders achieve levels similar to or higher than the levels seen in responders. ATI were associated with lower serum concentrations of infliximab, consistent with lower efficacy rates among ATI-positive patients.</p> </sec> <sec id="ss5"> <title>Conclusion:</title> <p>Infliximab, in treat-to-target settings with individual dose escalation, demonstrated significant efficacy at Weeks 10 and 26 in patients switched to infliximab after inadequate response to etanercept/adalimumab. The observed efficacy indicated that the switch to infliximab and ability to increase dose in a targeted fashion were beneficial.</p> </sec> <sec id="ss6"> <title>Key limitations:</title> <p>Given the relatively short duration of study follow-up, these safety findings require confirmation in a longer-term study.</p> </sec> </abstract>