POS0895 EFFECT OF TOFACITINIB ON PATIENT-REPORTED OUTCOMES IN PATIENTS WITH ACTIVE ANKYLOSING SPONDYLITIS: RESULTS FROM A PHASE 3 TRIAL
Authors: V. Navarro-Compán, J. C. C. Wei, F. Van den Bosch, M. Magrey, L. Wang, D. Fleishaker, J. C. Cappelleri, C. Wang, J. Wu, O. Dina, L. Fallon, V. Strand
Journal: Annals of the Rheumatic Diseases (2021)

Background: Ankylosing spondylitis (AS) can significantly impact quality of life. Tofacitinib is an oral Janus kinase inhibitor under investigation for the treatment of adult patients (pts) with AS. The safety/efficacy (including pt-reported outcomes [PROs]) of tofacitinib in pts with AS was assessed in a Phase 3 trial ( NCT03502616 ). 1 Objectives: To evaluate the effect of tofacitinib on pt-reported pain, fatigue, overall health and work productivity in pts with active AS enrolled in the Phase 3 trial. Methods: Pts with an inadequate clinical response or intolerance to ≥2 oral NSAIDs were randomised in a double-blind fashion to tofacitinib 5 mg twice daily (BID) or placebo (PBO) for 16 weeks. At Week (W)16, all pts received open-label tofacitinib 5 mg BID up to W48. Least squares (LS) mean changes from baseline (Δ) up to W48 are reported for the following outcomes: pt assessment of nocturnal spinal pain, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Short Form-36 Health Survey version 2 (SF-36v2; W16 and W48 only), and Work Productivity and Activity Impairment Questionnaire (WPAI; W16 and W48 only). Results: At W16, there were greater improvements from baseline in pain (total back pain [previously published 1 ] and nocturnal spinal pain) and fatigue (FACIT-F total score; experience and impact domain scores) with tofacitinib vs PBO (p≤0.05; Table 1); improvements were observed as early as W2. Also, improvements in SF-36v2 physical component summary (PCS) (Table 1), and physical functioning, role-physical, bodily pain, general health and social functioning domains (Figure 1) were greater with tofacitinib vs PBO at W16 (p≤0.05). Similarly, improvements in WPAI scores at W16 were greater with tofacitinib vs PBO (p≤0.05), except for % work time missed (Table 1). Improvements with tofacitinib continued up to W48 (Table 1/Figure 1). Generally, pts receiving PBO who advanced to tofacitinib at W16 reported similar improvements after switching to tofacitinib (Table 1/Figure 1). Table 1. PROs at baseline and Δ at W16 and W48 Baseline, mean (SD) [N1] Δ, W16, LS mean (SE ) Δ, W48, LS mean (SE ) Tofacitinib 5 mg BID (N=133 ) PBO (N=136 ) Tofacitinib 5 mg BID PBO p value Tofacitinib 5 mg BID PBO → tofacitinib 5 mg BID Nocturnal spinal pain a 6.8 (1.9) 6.8 (1.9) -2.67 (0.20) -0.84 (0.20) &lt;0.0001 -3.52 (0.23) -3.01 (0.23) FACIT-F total score a,b 27.2 (10.7) 27.4 (9.3) 6.54 (0.80) 3.12 (0.79) 0.0008 9.54 (0.90) 7.35 (0.89) FACIT-F experience domain a 8.9 (4.3) 8.7 (4.0) 2.85 (0.36) 1.29 (0.36) 0.0007 4.22 (0.40) 3.40 (0.40) FACIT-F impact domain a 18.3 (6.9) 18.8 (5.9) 3.68 (0.49) 1.81 (0.49) 0.0028 5.32 (0.54) 3.95 (0.54) SF-36v2 PCS b,c 33.5 (7.3) 33.1 (7.0) [135] 6.69 (0.59) 3.14 (0.59) &lt;0.0001 8.81 (0.720) 7.39 (0.71) SF-36v2 MCS c 39.4 (11.1) 39.8 (12.7) [135] 3.45 (0.91) 2.13 (0.92) 0.2529 7.07 (0.93) 6.35 (0.92) WPAI c % activity impairment 56.5 (23.4) 56.0 (21.4) -19.03 (1.97) -5.63 (1.97) &lt;0.0001 -27.37 (2.34) -19.77 (2.31) % work time missed 9.9 (22.4) [81] 11.5 (24.6) [88] -3.65 (2.66) 0.88 (2.62) 0.1784 -8.10 (2.14) -5.79 (2.05) % impairment while working 48.4 (26.3) [79] 49.6 (22.2) [85] -19.83 (2.27) -6.94 (2.30) &lt;0.0001 -25.35 (2.77) -23.00 (2.66) % overall work impairment 50.8 (27.4) [79] 53.5 (23.1) [85] -21.49 (2.51) -7.64 (2.56) &lt;0.0001 -27.63 (3.01) -23.22 (2.90) a MMRM b Global type I error-controlled endpoint c Analysis of covariance model for W16 and MMRM for W48 MCS, mental component summary; MMRM, Mixed Model for Repeated Measures; N, number of pts in full analysis set; N1, number of pts included in the analysis (if different from N); SD, standard deviation; SE, standard error Conclusion: In pts with active AS, improvements in spinal pain, fatigue, overall health and work productivity were greater with tofacitinib vs PBO at W16; improvements continued up to W48. These PRO findings support the primary efficacy results of this Phase 3 trial, 1 and add to the overall understanding of the benefit/risk profile of tofacitinib in patients with AS. References: [1]Deodhar et al. Arthritis Rheumatol 2020; 72 (S10): Abs L11. Acknowledgements: Study sponsored by Pfizer Inc. Medical writing support was provided by Emma Mitchell, CMC Connect, and funded by Pfizer Inc. Disclosure of Interests: Victoria Navarro-Compán Speakers bureau: AbbVie, Eli Lilly, Janssen, MSD, Novartis, Pfizer Inc, UCB, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer Inc, UCB, Grant/research support from: AbbVie, Novartis, James Cheng-Chung Wei Speakers bureau: Eli Lilly, Janssen, Novartis, Pfizer Inc, Consultant of: Eli Lilly, Novartis, Pfizer Inc, Grant/research support from: AbbVie, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, UCB, Filip van den Bosch Shareholder of: AbbVie, Celgene, Eli Lilly, Galapagos, Gilead, Merck, Novartis, Pfizer Inc, UCB, Marina Magrey: None declared, Lisy Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Dona Fleishaker Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Cunshan Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph Wu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Oluwaseyi Dina Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lara Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Vibeke Strand Consultant of: AbbVie, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Corrona, Eli Lilly, Galapagos, Genentech/Roche, Gilead, GSK, Ichnos, Inmedix, Janssen, Kiniksa, Merck, Myriad Genetics, Novartis, Pfizer Inc, Regeneron, Samsung, Sandoz, Sanofi, Scipher, SetPoint Medical, UCB