Date: Sunday, November 13, 2016
Session Title: Rheumatoid Arthritis – Small Molecules, Biologics and Gene Therapy - Poster I
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: EULAR, ACR and treat-to-target guidelines recommend switching treatment in inadequate responders (IRs) to alternative therapy by Week (Wk) 12.1-3 Although any biological (b)DMARD can be initiated in conventional synthetic (cs)DMARD IRs, many practitioners use a TNF inhibitor (TNFi) for primary biologic treatment. For TNFi IRs, an immediate switch to a second TNFi may be proposed despite there being no blinded, prospective clinical trials demonstrating the efficacy and safety of the immediate use of a second TNFi. EXXELERATE is the first randomized controlled trial (RCT) to address immediate switching to another TNFi, in a TNFi IR patient (pt) population.
Methods: EXXELERATE (NCT01500278) was a 104-wk randomized, investigator-blind, parallel-group, head-to-head superiority study comparing the early (Wk 12)- and later (Wk 104)-term efficacy and safety of certolizumab pegol (CZP)+MTX vs adalimumab (ADA)+MTX (Figure). Pts were randomized 1:1 to CZP+MTX or ADA+MTX. At Wk 12, pts were classified as responders (achieving either DAS28[ESR] ≤3.2 or a DAS28[ESR] reduction from baseline [BL] of ≥1.2), or non-responders (NRs). NRs originally randomized to CZP were switched to ADA, while NRs to ADA were switched to CZP (Figure). A pre-defined exploratory objective assessed early- and later-term efficacy of switching to a second TNFi using ACR20/50/70, low disease activity (LDA) and remission (REM). The safety of switching TNFi without a washout period was assessed by monitoring all TEAEs occurring after treatment switch and within 70 days of the final dose of initial study drug.
Results: At BL, 457 pts were randomized to CZP and 458 to ADA. Of the 122 pts who switched and continued after Wk 12, 65 CZP NRs were switched to ADA and 57 ADA NRs switched to CZP. Clinical improvement was observed in a considerable proportion of pts (Table); 33 pts (55.9%) switching to CZP and 40 pts (60.6%) switching to ADA responded 12 wks later (Wk 24) by achieving DAS28(ESR) ≤3.2 or a DAS28(ESR) reduction from Wk 12 of ≥1.2 and were classed as secondary responders. Further improvements in various measures of clinical efficacy were observed, though less so than the level achieved by primary responders (Table). A similar proportion of ADA to CZP and CZP to ADA pts reported TEAEs occurring after treatment switch and within 70 days of the final dose of initial study drug (n=24, 40.7%; n=30, 45.5%). There were no reported serious infectious events (SIEs).
Conclusion: EXXELERATE demonstrated that efficacy can be achieved using a second TNFi in a proven primary TNFi failure pt population. Furthermore, these results expand current RCT data by providing, in a controlled setting, clinical evidence for the safety of an immediate switch from one TNFi to another without a washout period, and demonstrating no increase in SIEs. References: 1. Smolen J. Ann Rheum Dis 2015;75(1):3–15; 2. Singh J. Arthritis Rheumatol 2016;68(1):1–26; 3. Smolen J. Ann Rheum Dis 2014;73(3):492–502
To cite this abstract in AMA style:Fleischmann R, Burmester GR, Combe B, Curtis JR, Hall S, Haraoui B, van Vollenhoven R, Cioffi C, Ecoffet C, Ionescu L, Gervitz L, Peterson L, Smolen J. Efficacy and Safety of Switching Between Certolizumab Pegol and Adalimumab after Primary Anti-TNF Treatment Failure: 2-Year Results from a Randomized, Investigator-Blind, Superiority Head-to-Head Study [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/efficacy-and-safety-of-switching-between-certolizumab-pegol-and-adalimumab-after-primary-anti-tnf-treatment-failure-2-year-results-from-a-randomized-investigator-blind-superiority-head-to-head-stud/. Accessed May 27, 2023.
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