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. 2015 May;21(5):409-23.
doi: 10.18553/jmcp.2015.21.5.409.

Comparative Efficacy of Novel DMARDs as Monotherapy and in Combination with Methotrexate in Rheumatoid Arthritis Patients with Inadequate Response to Conventional DMARDs: A Network Meta-Analysis

Felicity Buckley  1 , Axel Finckh, Tom W J Huizinga, Fred Dejonckheere, Jeroen P Jansen
Affiliations

Comparative Efficacy of Novel DMARDs as Monotherapy and in Combination with Methotrexate in Rheumatoid Arthritis Patients with Inadequate Response to Conventional DMARDs: A Network Meta-Analysis

Felicity Buckley et al. J Manag Care Spec Pharm. 2015 May.

Abstract

Background: Given the availability of a number of alternative biologic treatment options and other novel disease-modifying antirheumatic drugs (DMARDs) for the treatment of patients with rheumatoid arthritis (RA), clinicians are faced with an increasingly challenging choice regarding optimal treatment. Biologics are usually combined with traditional DMARDs, primarily methotrexate (MTX), but some biologics and tofacitinib (together referred to in this article as novel DMARDs) have been shown to be efficacious as monotherapy as well. In real-world practice, approximately one-third of RA patients receiving biologics are on monotherapy, primarily because of intolerance of, or noncompliance with, MTX. Limited data, however, are available analyzing the effectiveness of monotherapy compared with combination therapy across novel DMARDs.

Objective: To compare American College of Rheumatology (ACR) responses to approved novel DMARDs used as monotherapy or as combination therapy with methotrexate (MTX) at 24 weeks in RA patients who have shown inadequate response to conventional DMARDs (DMARD-IR).

Methods: Through a systematic review of the literature, we identified randomized controlled trials that assessed approved novel DMARDs used as monotherapy or as combination therapy with MTX in DMARD-IR RA patients. Twenty-eight RCTs were identified that evaluated abatacept, anakinra, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, tocilizumab, or tofacitinib. ACR responses at 24 weeks were extracted and combined by means of Bayesian network meta-analyses.

Results: With the exception of anakinra plus MTX, which was less efficacious, most novel DMARDs, when used in combination with MTX, demonstrated comparable ACR responses. When novel DMARDs were used as monotherapies, greater ACR20/50/70 responses were observed with tocilizumab than with anti-tumor necrosis factor agents (aTNF) or tofacitinib. Furthermore, ACR20/50/70 responses with tocilizumab plus MTX were similar to those with tocilizumab monotherapy (odds ratio [OR] for the indirect comparison = 1.08, 95% credible interval [CrI] = 0.40-2.84; OR = 1.24, CrI = 0.44-3.61; OR = 0.95, CrI = 0.33-2.72, respectively), whereas greater responses were observed with aTNF plus MTX than with aTNF monotherapy (OR = 2.41, CrI = 0.51-11.61; OR = 2.85, CrI = 0.51-17.67; OR = 1.28, CrI = 0.21-8.42, respectively). Relative efficacy estimates for the indirect comparison of tofacitinib plus MTX with tofacitinib monotherapy were very uncertain.

Conclusions: Results suggest that in combination with MTX most of the available novel DMARDs have similar levels of efficacy in DMARD-IR patients. As monotherapy, however, tocilizumab displayed higher ACR responses than aTNF or tofacitinib. ACR responses with tocilizumab plus MTX were similar to those with tocilizumab as monotherapy, whereas aTNF in combination with MTX demonstrated greater ACR responses than aTNF as monotherapy.

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Conflict of interest statement

This research was supported by F. Hoffmann-La Roche Ltd. Buckley, Finckh, Huizinga, and Jansen have served as consultants for Roche. Dejonckheere is an employee of F. Hoffmann-La Roche.

Buckley and Jansen were responsible for study design, systematic review, analysis and interpretation of data, and writing the manuscript. Finckh and Huizinga were responsible for interpretation of data and writing the manuscript. Dejonckheere contributed to study design and writing the manuscript. All authors participated equally in revising and approving the final manuscript.

Figures

FIGURE 1
FIGURE 1
Flow Diagram of Study Identification and Selection
FIGURE 2
FIGURE 2
Network of RCTs Evaluating Agents for DMARD-IR RA Patients in Terms of ACR20/50/70 Response at 24 Weeks
FIGURE 3
FIGURE 3
Probability of ACR20/50/70 Response with 95% CrI for Different Classes of Biologic Treatment with and Without MTX
See this image and copyright information in PMC

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