Background Tofacitinib is an oral JAK inhibitor for the treatment of RA. In clinical practice, a proportion of patients (pts) with RA may not be candidates for treatment with the conventional synthetic DMARD (csDMARD) methotrexate (MTX).1
Objectives To evaluate tofacitinib 5 or 10 mg BID efficacy and safety using pooled data from 8 Phase (P) 2 and 6 P3 trials in RA pts who were (1) inadequate responders (IR)/intolerant to csDMARDs, but did not have an IR or intolerance to MTX or biologic DMARDs (ie, non-MTX csDMARD-IR population) or (2) pts with an IR/intolerance to any csDMARD including MTX but not bDMARD-IR (ie, 2nd-line population).
Methods Month 3 efficacy outcomes included proportions of pts achieving ACR20/50/70 responses, and Disease Activity Score 28-4(ESR) (DAS28-4[ESR])<2.6 (remission), as well as change from baseline in DAS28-4(ESR) and Health Assessment Questionnaire-Disability Index (HAQ-DI) scores. No multiplicity adjustments were made. Crude incidence rates (CIR; unique pts with events/100 pt-years) based on adverse event (AE) reporting through Month 24 were calculated for treatment-emergent AEs (TEAEs), serious AEs (SAEs), discontinuations (DCs) due to AEs and AEs of special interest.
Results In the P2/3 tofacitinib RA trials, prior csDMARDs received by the non-MTX csDMARD-IR and 2nd-line populations, respectively were: chloroquine (17.7% and 37.2%), hydroxychloroquine (13.7% and 22.7%), leflunomide (19.4% and 20.9%), MTX (7.3% and 93.3%), sulfasalazine (31.1% and 27.1%) and others (8.0% and 11.1%); pts may have received >1 prior csDMARD. The non-MTX csDMARD-IR population included 208, 247 and 82 pts receiving tofacitinib 5 and 10 mg BID or placebo (PBO), respectively; the 2nd-line population comprised 1206, 1266 and 856 pts, respectively. Baseline characteristics were generally similar between populations except for mean RA duration (5.2–7.2 years, non-MTX csDMARD-IR pts; 8.2–8.5 years, 2nd-line pts). Most pts were female (80.3–85.4%), mean age range was 49.7–52.5 years and mean DAS28-4(ESR) score ranged from 6.2–6.5. Tofacitinib 5 and 10 mg BID achieved higher ACR responses and greater changes from baseline in DAS28-4(ESR) and HAQ-DI scores vs PBO at Month 3 in both populations (Table). Numerically higher proportions of non-MTX csDMARD-IR pts achieved efficacy outcomes vs 2nd-line population. CIRs for SAEs, DCs due to AEs and AEs of special interest were similar across groups; CIRs for TEAEs were higher with PBO vs tofacitinib. AE frequency was generally lower in the non-MTX csDMARD-IR population vs 2nd-line population.
Conclusions This analysis indicates that tofacitinib is associated with similar efficacy and safety outcomes between csDMARD-IR (including MTX-IR) pts and those who are csDMARD-IR but not MTX-IR. This suggests a favourable tofacitinib benefit/risk profile for RA pts who have a contraindication to or refuse treatment with MTX and failed other csDMARDs.
Lopez-Olivo MA et al. Cochrane Database Syst Rev 2014; CD000957.
Acknowledgements This study was sponsored by Pfizer Inc. Editorial support was provided by K Nicholson of CMC and was funded by Pfizer Inc.
Disclosure of Interest J. Tesser Grant/research support from: Pfizer Inc, Consultant for: Pfizer Inc, A. Gül Consultant for: AbbVie, Bristol-Myers Squibb, MSD, Novartis, Pfizer Inc, Roche, Servier, UCB, Xoma, E. Olech Grant/research support from: AbbVie, Amgen, Celgene, Genentech, Janssen, Regeneron, Sanofi-Aventis, UCB, Vertex Pharmaceuticals, Consultant for: AbbVie, Amgen, Celgene, Genentech, Janssen, Regeneron, Sanofi-Aventis, UCB, Vertex Pharmaceuticals, K. Oelke Grant/research support from: Novartis, Consultant for: Novartis, Speakers bureau: Amgen, AbbVie, Bristol-Myers Squibb, Pfizer Inc, Crescendo Biosciences, UCB, T. Lukic Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Murray Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Zhang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Takiya Shareholder of: Pfizer Inc, Consultant for: Pfizer Inc