WASHINGTON, DC—Cycling to a different tumor necrosis factor alpha inhibitor (TNFi) after treatment failure in patients with rheumatoid arthritis (RA) can be effective, according to a review and meta-analysis of randomized controlled trials (RCTs) reported at the 2016 ACR/ARHP Annual Meeting.
In fact, cycling to a different TNFi can be considered prior to swapping to another therapy with a different mode of action, “suggesting that many patients fail a specific agent and not TNFi as a class,” noted Maria A. Lopez-Olivo, MD, MSc, PhD, of the section of rheumatology and clinical immunology, at The University of Texas MD Anderson Cancer Center, Houston, TX.
Noting that “up to one-third of the patients who receive TNFi lose responsiveness over time,” the study authors compared the efficacy of various approaches by searching electronic databases (MEDLINE, EMBASE, Cochrane Library, and Web of Sciences) and clinicaltrials.gov and other websites for unpublished records.
“The search was broad in scope to capture all available evidence,” Dr. Lopez-Olivo stated.
Two independent reviewers performed the selection process. Included were “studies evaluating the efficacy and safety of targeted therapies in RA that included only adult patients with failure to respond to at least one TNFi.”
Excluded were non-randomized studies; RCTs with no separate data for TNFi failures or those that evaluated retreatments (e.g., rituximab or tocilizumab vs. placebo after one or two cycles of rituximab or tocilizumab); studies with insufficient data to evaluate the outcomes of interest; and those that compared a brand-name product with a biosimilar, with no control group.
The outcomes included ACR50 (50% improvement per American College of Rheumatology criteria), serious adverse events (AEs), and study withdrawals.
Of 33,741 citations, 19 studies with multiple publications were identified, for an article count of 76. Mean age ranged between 45.1 and 58.2 years; the majority were female (82%) with a disease duration ranging between 8.6 and 13.2 years and a baseline disability score ranging from 1.1 to 1.9.
In patients failing any other TNFi, cycling strategies included golimumab, certolizumab, adalimumab, etanercept, or infliximab, while swapping strategies included rituximab, tocilizumab, abatacept, or tofacitinib.
“Four studies were head-to-head comparisons; one compared two different doses of tocilizumab combined with methotrexate with tocilizumab monotherapy; one compared non-TNFi plus TNFi versus TNFi only; and the remaining studies compared a targeted agent combined with a disease modifying anti-rheumatic drug (DMARD) versus DMARD monotherapy (with or without placebo),” the authors reported.
Of the studies, 3 (n=898) were suitable for direct meta-analysis for the cycling strategy, as were 4 (n=1,774) for the swapping strategy.
This analysis showed that when an alternative TNFi was used in combination with a DMARD, ACR50 response rates significantly improved at 12 to 24 weeks vs. the DMARD alone group (pooled for all TNFi = RR 2.6 [95% CI 1.6, 4.3]).
Improvements were also observed with each swapping strategy; pooled RR including rituximab, abatacept, tocilizumab, or tofacitinib was 6.1 (95% CI 4.1 to 8.9).
No differences were observed in the rates of withdrawals due to AEs or serious AEs between groups for any of the strategies.