Tofacitinib, An Oral Janus Kinase Inhibitor: Post-Hoc Analyses Of Efficacy And Safety Of Monotherapy Versus Combination Therapy In A Phase 3 Rheumatoid Arthritis Population

Background Tofacitinib is a novel oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). Phase (P) 2 and 3 studies demonstrated tofacitinib is effective and has a manageable safety profile as both monotherapy and in combination with nonbiologic disease-modifying antirheumatic drugs (DMARDs). Objectives To assess whether there are relative differences in efficacy or safety between mono- and combination therapy in RA patients (pts) with an inadequate response (IR) to DMARDs. Methods Pooled tofacitinib data from three combination therapy P3 studies (≈2100 pts) (ORAL Sync, Standard and Scan) were compared to one monotherapy P3 study (≈600 pts) (ORAL Solo), all DMARD IR pts. The proportion of pts achieving ACR20, 50 and 70, DAS28-4(ESR) (DAS)-defined remission and low disease activity (LDA) (DAS Results Demographic and baseline (BL) disease characteristics of pts across the four studies were generally similar, except geographic region of enrolment; the highest level of mean BL values of joint counts, CRP, HAQ and DAS were seen in the monotherapy study (DAS 6.69 vs 6.29-6.46 with monotherapy vs combination therapy, respectively). In the efficacy and safety analyses (Figure), point estimates for the ORs ranged from 1.0–1.3 for rates of ACR20/50/70, LDA, HAQ and AEs, 1.9 for DAS-defined remission and 0.5 for d/c due to AEs and SAEs. Across all endpoints, the CIs included 1, indicating similar response and risk rates for tofacitinib mono- and combination therapy. Image/graph Conclusions In this meta-analysis, no statistically significant differences in efficacy or safety endpoints were observed with tofacitinib administered as monotherapy or in combination with DMARDs in DMARD IR pts. A randomised clinical trial directly comparing mono- and combination therapy is warranted to confirm these results. Disclosure of Interest E. Keystone: None Declared, R. Fleischmann: None Declared, R. van Vollenhoven Grant/research support from: AbbVie, BMS, GSK, MSD, Pfizer, Roche, UCB, Consultant for: AbbVie, BMS, GSK, MSD, Pfizer, Roche, UCB, J. Kremer: None Declared, D. Gruben Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., J. Bradley Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., R. Riese Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., C. Mebus Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., G. Wallenstein Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., S. Zwillich Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., B. Benda Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., S. Krishnaswami: None Declared