Background Methotrexate (MTX) is considered the anchor drug in RA, both as monotherapy, as well as for its ability to increase the efficacy of biologic agents when used in combination . Some RA patients have to discontinue DMARD therapy. Thus, it is important to define the optimal biological monotherapy in RA patients.
Objectives To review the evidence for short-term efficacy and safety of biologic monotherapy in RA. The aim was to define the optimal biological monotherapy in RA patients without concomitant use of any DMARD therapy.
Methods Systematic review and Network Meta-Analysis of RCTs with DMARD inadequate responders (IR) and DMARD naïve RA patients, comparing biologic agents in monotherapy with either placebo (no DMARD) or DMARD, were considered eligible for inclusion. The co-primary outcomes were the number of patients achieving an ACR50 response, and the number discontinuing therapy due to adverse events (AE)  preferably after 6 months (3-12 months), respectively. The network meta-analysis was based on mixed-effects logistic regression (GLMM modelled in SAS) ; combining statistical inference from both direct and indirect comparisons of the treatment effects between biologics. All dosages applied for all of the nine biologics. Results are reported as odds ratios (OR [95%CI]). For sensitivity, in terms of the included patients, we compared DMARD IR responder trials with DMARD Naïve trials.
Results From the literature search 27 individual studies (7,938 patients) were included: abatacept [Aba:1], adalimumab [Ada:5], anakinra [Ana:2], certolizumab [Cer:2], etanercept [Eta:6], golimumab [Gol:3], infliximab [Inf:1], rituximab [Rit:1] and tocilizumab [Toc:6]. The network only included one ‘closed loop’ with biologics head-to-head: ADACTA (Toc vs. Ada) . Benefit (ACR50): Ana was statistically less likely than Ada, Eta, Gol, and Toc, respectively, to have a clinical response (p<0.05). The odds for responding was statistically higher (p<0.05) for Toc compared to Aba (3.9[1.2;12.4]), Ada (2.1[1.2;3.6]), and Inf (7.7[1.8;32.4]), respectively. Finally, Eta was statistically more likely to result in a response than Inf (5.6[1.3;23.9]). Harm (Withdrawal d/t AEs): Gol seemed less likely to cause withdrawal from side effects (p<0.05) compared to Ada (0.4[0.1;0.9]), Ana (0.3[0.1;0.8]), Cer (0.3[0.1;1.0]), Inf (0.2[0.1;1.0]), and Toc (0.4[0.1;0.8]). For sensitivity, the ACR50 estimates were compared with the direct comparison of Ada vs. Toc ; the model apparently did not build on incoherence, as data from the ADACTA study reported a comparable effect size (OR=2.3 [1.5; 3.7]).
Conclusions All biologics are not equal. In RA patients who need biologic therapy without concomitant use of DMARDs, some biologics are better than others with respect to ACR50 responses.
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Acknowledgements Musculoskeletal Statistics Unit, The Parker Institute receives support via research grants from the Oak Foundation.
Disclosure of Interest R. Christensen Grant/research support from: This particular study, including both the protocol and subsequent manuscript, has been supported by a grant from Roche; the grant was provided as an unrestricted grant to Musculoskeletal Statistics Unit, The Parker Institute., Speakers bureau: Abbott, BMS, Pfizer, Roche, MSD, Expanscience, Biogen Idec, Ipsen, Novartis, Bayer, S. Tarp: None Declared, D. Furst: None Declared, M. Østergaard: None Declared, T. Lorenzen: None Declared, M. Hansen: None Declared, J. Singh: None Declared, E. Choy: None Declared, M. Boers: None Declared, M. Suarez-Almazor: None Declared, B. Ejbjerg: None Declared, L. Kristensen: None Declared, H. Bliddal: None Declared
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