SAT0252 Clinical and functional response to tofacitinib and adalimumab in patients with rheumatoid arthritis: probability plot analysis of results from the oral strategy trial
Authors: T. Takeuchi, J. S. Smolen, R. Fleischmann, N. Iikuni, H. Fan, K. Soma, E. Akylbekova, T. Hirose
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). ORAL Strategy (NCT02187055), a 12-month, global, Phase 3b/4 study, demonstrated that in patients with RA and an inadequate response to methotrexate (MTX), tofacitinib + MTX was non-inferior to adalimumab + MTX, while tofacitinib monotherapy was not non-inferior to either combination based on American College of Rheumatology (ACR)50 response rates at Month 6.<sup>1</sup> <h3>Objectives:</h3> To assess clinical and functional efficacy across treatments in the ORAL Strategy trial using cumulative probability plots. <h3>Methods:</h3> Efficacy was evaluated between patients who received tofacitinib 5 mg twice daily (BID) as monotherapy (N=384), tofacitinib 5 mg BID + MTX (N=376) and adalimumab 40 mg subcutaneously once every 2 weeks + MTX (N=386) based on ACR responses and changes from baseline in Health Assessment Questionnaire-Disability Index (ΔHAQ-DI) score at Month 12. Cumulative probability plots for ACR-n (where ACR is the % improvement from baseline in ACR components, and n represents the mimimum % achieved by each patient) and ΔHAQ-DI are presented. The area under the curve (AUC) was calculated for ACR-n up to Month 12 (in months), and an analysis of covariance model was used to assess treatment effects in terms of the AUC of ACR-n at Month 12; there was no adjustment for multiplicity for this post hoc analysis. <h3>Results:</h3> The cumulative probability plots of ACR responses at Month 12 indicated that the proportion of patients who achieved responses of ACR20, ACR50 and ACR70 was similar for tofacitinib + MTX and adalimumab + MTX, but was numerically smaller for tofacitinib monotherapy (figure, A). Responses of approximately ≥ACR80 were achieved by a similar proportion of patients in each treatment group. Least squares mean (standard error) AUC of ACR-n up to Month 12 (in months) was similar for tofacitinib + MTX (437 [35]) and adalimumab + MTX (402 [35]), but was smaller for tofacitinib monotherapy (319 [35]; p&lt;0.05). The cumulative probability plots of ΔHAQ-DI suggested that, in general, reductions from baseline in HAQ-DI were similar across treatment groups (figure, B), although a slightly higher proportion of patients who received tofacitinib monotherapy reported an increase in HAQ-DI vs other treatments. Figure 1 Cumulative probability plot of A) ACR response and B) VHAQ-DI at Month 12 Two outlets for ACR response are not shown: tofacitinib 5 mg BID monotherapy, ACR-n-1700, cumulative probability-0.0003; adailmumab 40 mg SC Q2W + MTX, ACR-n-463, cumulative probability-0.003 <h3>Conclusions:</h3> These data support the primary ORAL Strategy findings,<sup>1</sup> indicating that in patients with RA, clinical efficacy, based on ACR response, was generally similar for tofacitinib + MTX and adalimumab + MTX, while a smaller proportion of patients who received tofacitinib monotherapy achieved ACR response in general, and particularly for &lt;ACR80. Functional efficacy, based on ΔHAQ-DI, was generally similar across all treatment groups. Cumulative probability analyses for CDAI will be further evaluated. <h3>Reference</h3> [1]Fleischmann R, et al. Lancet2017;390:457–68. <h3>Acknowledgements:</h3> Study sponsored by Pfizer Inc. Medical writing support was provided by A MacLachlan of CMC and funded by Pfizer Inc. <h3>Disclosure of Interest:</h3> T. Takeuchi Grant/research support from: AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, Teijin, Consultant for: AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, Teijin, Speakers bureau: AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, Teijin, J. Smolen Grant/research support from: AbbVie, Eli Lilly, Janssen, MSD, Pfizer Inc, Roche, Consultant for: AbbVie, Amgen, AstraZeneca, Astro, Celgene, Celtrion, Eli Lilly, GSK, ILTOO, Janssen, MedImmune, MSD, Novartis-Sandoz, Pfizer Inc, Roche, Samsung, Sanofi, UCB, Speakers bureau: AbbVie, Amgen, AstraZeneca, Astro, Celgene, Celtrion, Eli Lilly, GSK, ILTOO, Janssen, MedImmune, MSD, Novartis-Sandoz, Pfizer Inc, Roche, Samsung, Sanofi, UCB, R. Fleischmann Consultant for: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celltrion, Eli Lilly, Genentech, GSK, Janssen, Novartis, Pfizer Inc, Sanofi-Aventis, UCB, N. Iikuni Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, H. Fan Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, K. Soma Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, E. Akylbekova Consultant for: Pfizer Inc, Employee of: IQVIA, T. Hirose Shareholder of: Pfizer Japan Inc, Employee of: Pfizer Japan Inc