LB0003 Tofacitinib with and without methotrexate versus adalimumab with methotrexate for the treatment of rheumatoid arthritis: results from oral strategy, a phase 3b/4 randomised trial

Background Tofacitinib is an oral JAK inhibitor for the treatment of RA. There is no direct comparison of tofacitinib monotherapy vs tofacitinib +MTX in MTX inadequate responders (IR) and limited data comparing tofacitinib (±MTX) vs adalimumab (ADA) +MTX in patients (pts) with RA. Objectives To compare efficacy and safety of tofacitinib monotherapy, tofacitinib+MTX, and ADA+MTX in a head-to-head, non-inferiority trial in MTX-IR pts. Methods In this randomised, triple-dummy, active-controlled, 1-year, Phase 3b/4 trial (ORAL Strategy; NCT02187055), pts had active RA (≥4 tender/painful joints on motion and ≥4 swollen joints [28-joint count] at baseline [BL]) inadequately controlled with MTX. Pts were randomised 1:1:1 to receive tofacitinib 5 mg twice daily (5 mg mono BID), tofacitinib 5 mg BID +MTX (5 mg BID+MTX) or subcutaneous ADA 40 mg every other week +MTX (ADA+MTX); MTX dose: 15–25 mg/wk. The primary endpoint was ACR50 at Month (Mo) 6. Non-inferiority between treatments was declared if the lower bound of 98.34% two-sided confidence intervals of the difference of ACR50 response at Mo 6 was larger than -13% (based on meta analysis of ADA trials 1 ), and superiority if it was larger than 0%. Other endpoints included: ACR20/50/70 and least-squares mean changes from BL in SDAI, DAS28-4(ESR) and HAQ-DI at Mos 6 and 12. Safety was assessed throughout the trial. Results 1146 pts were randomised and treated (5 mg mono BID: n=384; 5 mg BID+MTX: n=376; ADA+MTX: n=386). Demographics and BL disease characteristics were similar across groups. Most pts were female (82.7–83.1%), white (75.9–77.1%), with a mean age of 49.7–50.7 years, median disease duration of 5.4–6.1 years and mean HAQ-DI score of 1.6. Across groups, 80.2–81.6% of pts completed the study. ACR50 response rate at Mo 6 was 38.3% for 5 mg mono BID, 46.0% for 5 mg BID+MTX and 43.8% for ADA+MTX. Non-inferiority was demonstrated for 5 mg BID+MTX vs ADA+MTX (P Conclusions Tofacitinib 5 mg BID+MTX was as effective as ADA+MTX in MTX-IR pts with RA. However, clinical outcomes of all 3 regimens, including tofacitinib 5 mg BID monotherapy, were comparable. There were no new or unexpected safety issues. References Machado et al. Rev Bras Reumatol 2013;53:419–430. Acknowledgements This study was funded by Pfizer Inc. Editorial support provided by D Binks of CMC. Disclosure of Interest R. Fleischmann Grant/research support from: Abbott, Amgen, Astellas, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Genentech, Eli Lilly, Janssen, Novartis, Pfizer Inc, Regeneron Pharmaceuticals Inc., Sanofi Aventis, Roche, UCB, Consultant for: Abbott, Akros, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Eli Lilly, Janssen, Novartis, Pfizer Inc, Sanofi Aventis, UCB, E. Mysler Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Medimmune, Pfizer Inc and Roche, Consultant for: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Medimmune, Pfizer Inc and Roche, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Medimmune, Pfizer Inc and Roche, S. Hall Consultant for: Pfizer Inc, Celgene, Roche, AbbVie, Eli Lilly, Janssen, A. Kivitz Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Genentech and Pfizer Inc, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Genentech and Pfizer Inc, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Genentech, and Pfizer Inc, R. Moots Grant/research support from: Biogen, Bristol-Myers Squibb, Chugai, Novartis, Pfizer, Roche, Sandoz, UCB Pharma, Consultant for: Biogen, Bristol-Myers Squibb, Chugai, Novartis, Pfizer, Roche, Sandoz, UCB Pharma, Speakers bureau: Biogen, Bristol-Myers Squibb, Chugai, Novartis, Pfizer, Roche, Sandoz, UCB Pharma, Z. Luo Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Tatulych Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, R. DeMasi Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, K. Soma Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, R. Zhang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Takiya Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Mojcik Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Krishnaswami Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Menon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Smolen Grant/research support from: AbbVie, Janssen, Lilly, MSD, Pfizer Inc, and Roche, Consultant for: AbbVie, Amgen, AstraZeneca, Astro, Celgene, Celtrion, Glaxo, ILTOO, Janssen, Lilly, MedImmune, MSD, Novartis-Sandoz, Pfizer Inc, Roche, Samsung, Sanofi, and UCB, Speakers bureau: AbbVie, Amgen, AstraZeneca, Astro, Celgene, Celtrion, Glaxo, ILTOO, Janssen, Lilly, MedImmune, MSD, Novartis-Sandoz, Pfizer Inc, Roche, Samsung, Sanofi, and UCB