Cycling of tumor necrosis factor inhibitors versus switching to different mechanism of action therapy in rheumatoid arthritis patients with inadequate response to tumor necrosis factor inhibitors: a Bayesian network meta-analysis

Abstract

Introduction: For patients with rheumatoid arthritis (RA) with an inadequate response to tumor necrosis factor inhibitors (TNFi), main options include cycling onto a different TNFi or switching to a biologic/targeted synthetic disease-modifying antirheumatic drug with a different mechanism of action (MOA). This network meta-analysis (NMA) assessed comparative clinical efficacy of cycling versus switching. Methods: We conducted a literature search in MEDLINE, Embase, and Cochrane Library. Outcomes included proportion of patients with 20%, 50%, or 70% response to American College of Rheumatology criteria (ACR20/ACR50/ACR70 response), Disease Activity Score in 28 joints (DAS28) score below 2.6 or between 2.6 and 3.2, mean change in DAS28 score, mean reduction in and proportion of patients achieving a clinically meaningful reduction (⩾0.22) in Health Assessment Questionnaire score, number of serious adverse events (AEs), and withdrawals for any reason/due to AEs/lack of treatment efficacy. To account for the wide range of study populations and designs, we developed three models to conduct the NMA: fixed-effect, random-effects, and hierarchical Bayesian. PROSPERO ID: CRD42019122993. Results: We identified nine randomized controlled trials and 16 observational studies. The fixed-effect model suggested a 0.99 probability that switch was the better strategy for increasing odds of a clinically meaningful improvement in ACR50 [odds ratio (OR): 1.35 (95% credible interval (CI): 0.96–1.81)]. The fixed-effect model also suggested that switch was associated with lower rates of withdrawal for any reasons [OR: 0.53 (95% CI: 0.40–0.68)]. The random-effects and hierarchical Bayesian models suggested additional uncertainty as they considered more variability than the fixed-effect model. Discussion: Results suggest that switching to a drug with a different MOA is more effective and associated with lower rates of withdrawal than cycling to a different TNFi after failure of first-line TNFi. Further trials that directly compare cycling with switching are warranted to better assess comparative efficacy. Plain language summary Assessment of the effectiveness of different drug treatment strategies in patients with rheumatoid arthritis: an analysis of the published literature Rheumatoid arthritis (RA) is a chronic disease in which inflammation affects joints along with the entire body; this may cause significant pain, joint damage, physical disability, a decreased quality of life, and an increased risk of death. Tumor necrosis factor inhibitors (TNFis) are a common choice as first-line drugs to treat RA. Although they are effective in many patients, therapy with a TNFi is not successful within the first year of treatment in approximately one-third of patients due to either a lack of efficacy or safety issues. When TNFi therapy is unsuccessful, the options are to “cycle” to another TNFi or to “switch” to another drug with a different mechanism of action (MOA). Further studies are needed to help doctors decide the best treatment strategy for their patients when treatment with an initial TNFi fails. This study analyzed 25 published studies in which patients were either “cycled” to another TNFi or “switched” to a drug with a different MOA after unsuccessful treatment with an initial TNFi. The results showed that “switching” to a drug with a different MOA was a better treatment strategy than “cycling” to another TNFi; “switching” increased the chance of clinically meaningful improvement in disease status and lowered the chance of having to stop treatment for any reason.

The RA-BE-REAL Multinational, Prospective, Observational Study in Patients with Rheumatoid Arthritis Receiving Baricitinib, Targeted Synthetic, or Biologic Disease-Modifying Therapies: a 6-Month Interim Analysis

“…This treatment approach is supported by the recent European Alliance of Associations for Rheumatology guidelines, which propose that if a ts/bDMARD has failed, treatment with another ts/bDMARD should be considered, whereas if a TNFi therapy has failed, patients may receive an agent with another mechanism of action or a second TNFi [ 2 ]. However, a network meta-analysis comparing cycling (i.e., using another agent with the same mode of action) versus switching (i.e., using agents with different modes of action) among RA treatments found that the latter approach was associated with improved clinical outcomes and lower withdrawal rates [ 28 ].…”

Comparative effectiveness of TNF inhibitor vs IL-6 receptor inhibitor as monotherapy or combination therapy with methotrexate in biologic-experienced patients with rheumatoid arthritis: An analysis from the CorEvitas RA Registry

“…The current analysis had some important differences compared with other studies, which had suggested better outcomes when patients were switched to a different class of biologics after a TNFi failure rather than rechallenged with another TNFi (i.e., cycling) [33][34][35][36]. In our study, CDAI was the primary outcome, whereas in some similar analyses, persistence was used as an outcome [33,34,36]; there were only 6 months of follow-up; and approximately one-third of the TNFi initiators and more than half of the IL-6Ri initiators were on their second treatment switch.…”

“…There was a high proportion of patients who had prior TNFi exposure (88.8%-92.1%) in our study. Literature suggests that a better treatment response would occur when switching from a TNFi to an alternative mechanism of action therapy [33][34][35][36]. Since many patients initiating a TNFi had already failed another TNFi in our b/ts-experienced cohort, we investigated for a potential selection bias in patients who received a follow-on TNFi.…”

ACCP-negative rheumatoid arthritis – clinical and immunological features

“…Серонегативность по АЦЦП коррелировала с повышением риска развития инфекций на фоне лечения ТЦЗ [176]. Клинически и экономически более оправданным вариантом коррекции терапии при неэффективности иФНО-α является переход к ГИБП с альтернативным механизмом действия [177][178][179][180][181][182]. При сравнении РТМ и ТЦЗ их эффективность после потери эффекта иФНО-α была сопоставима [183].…”