POS0631 COMPARATIVE EFFICACY OF COMBINATION THERAPY WITH BIOLOGIC OR TARGET SYNTHETIC DRUGS FOR RHEUMATOID ARTHRITIS: A BAYESIAN NETWORK META-ANALYSIS
Authors: F. Cacciapaglia, V. Venerito, S. Stano, M. Fornaro, G. Lopalco, F. Iannone
Journal: Annals of the Rheumatic Diseases (2021)

Background: Biologic agents and small molecules have shown long term benefit when added in patients with active RA non-responders to conventional DMARDs treatment (1). In head-to-head trials only adalimumab was compared to other drugs in combination with methotrexate, with some evidence of superiority but no data on multiple comparisons have been reported (2). The availability of biosimilar agents led in clinical practice to prefer mainly the cheaper one, so the choice of the most effective treatment remains a clinical unmet need (3). Objectives: To assess the relative efficacy of different therapeutic strategies for achieving ACR50 response at 24 weeks of treatment in patients with active RA, based on direct and indirect evidence. Methods: We performed systematic reviews of MEDLINE, EMBASE, and Cochrane Library databases, searching for all published phase 3 Randomised Controlled Trials (RCTs) comparing adalimumab originator to its biosimilars, abatacept, baricitinib, certolizumab pegol, tofacitinib or upadacitinib, combined to MTX, in patients with active RA inadequate responders to previous conventional DMARDs. American College of Rheumatology (ACR) 50% response at 24 weeks of treatment had to be evaluated both in adalimumab branch and in examined drug branch. Bayesian fixed-effect network meta-analysis was performed to combine the direct and indirect evidence using the WinBUGS 1.4 software (MRC Biostatistics Unit, Cambridge, UK). Results: Eleven RCTs evaluating 6’004 patients were included in the analysis, namely originator (1) and biosimilars (2) adalimumab, abatacept (3), baricitinib (4), certolizumab pegol (5), tofacitinib (6) and upadacitinib (7). Convergence was reached at n.100’000 iterations. Upadacitinib seems to be more effective than both originator and biosimilar adalimumab in achieving ACR 50 (OR 1.65 95% CI 1.25-2.14 and OR 1.22 95%CI 1.10-2.18; see Figure 1). Similarly, tofacitinib was more effective of originator adalimumab (OR 1.25 95%CI 1.01-155). Upadacitinib was ranked first among treatments with a probability of being the agent more likely to induce ACR 50 response of 86.3%. In this regard tofacitinib had a probability of 4.8%, hence it was ranked second among treatments. Figure 1. Caterpillar plot OR for ACR50 at 24 weeks (originator [1] and biosimilars [2] adalimumab; abatacept [3]; baricitinib [4]; certolizumab pegol [5]; tofacitinib [6]; upadacitinib [7]). Conclusion: Although patients with active RA and inadequate response to MTX have different therapeutic combination of biologics or small molecules options, the best relative efficacy in terms of ACR50 response after 24 weeks of treatment is for upadacitinib 15 mg/day. References: [1]Smolen JS, et al. Annals of the Rheumatic Diseases 2020;79:685-699. [2]Combe B, Lukas C. Joint Bone Spine, 2020,105004. [3]Caporali R, et al. Biomed Res Int. 2018 Sep 9;2018:3878953. Disclosure of Interests: Fabio Cacciapaglia Speakers bureau: Roche, Pfizer, Eli Lilly, MSD, UCB, BMS, Abbvie, Vincenzo Venerito: None declared, Stefano Stano: None declared, Marco Fornaro: None declared, Giuseppe Lopalco Speakers bureau: Celgene, BMS, Abbvie, Novartis, Florenzo Iannone Speakers bureau: Roche, Pfizer, Eli Lilly, MSD, UCB, BMS, Abbvie, Novartis, Celgene