POS0895\u2005EFFECT OF TOFACITINIB ON PATIENT-REPORTED OUTCOMES IN PATIENTS WITH ACTIVE ANKYLOSING SPONDYLITIS: RESULTS FROM A PHASE 3 TRIAL

Abstract

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).1To 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.Pts with an inadequate clinical response or intolerance to ≥2 oral NSAIDs were randomised in a double-blind fashion to tofacitinib 5\u2009mg twice daily (BID) or placebo (PBO) for 16 weeks. At Week (W)16, all pts received open-label tofacitinib 5\u2009mg 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).At W16, there were greater improvements from baseline in pain (total back pain [previously published1] 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 W48Baseline,mean (SD) [N1]Δ, W16,LS mean (SE)Δ, W48,LS mean (SE)Tofacitinib5\u2009mg BID (N=133)PBO(N=136)Tofacitinib5\u2009mg BIDPBOp valueTofacitinib5\u2009mg BIDPBO→tofacitinib5\u2009mg BIDNocturnalspinal paina6.8 (1.9)6.8 (1.9)-2.67 (0.20)-0.84 (0.20)<0.0001-3.52 (0.23)-3.01 (0.23)FACIT-Ftotal scorea,b27.2 (10.7)27.4 (9.3)6.54 (0.80)3.12 (0.79)0.00089.54 (0.90)7.35 (0.89)FACIT-F experience domaina8.9 (4.3)8.7 (4.0)2.85 (0.36)1.29 (0.36)0.00074.22 (0.40)3.40 (0.40)FACIT-Fimpactdomaina18.3 (6.9)18.8 (5.9)3.68 (0.49)1.81 (0.49)0.00285.32 (0.54)3.95 (0.54)SF-36v2 PCSb,c33.5 (7.3)33.1 (7.0) [135]6.69 (0.59)3.14 (0.59)<0.00018.81 (0.720)7.39 (0.71)SF-36v2 MCSc39.4 (11.1)39.8 (12.7) [135]3.45 (0.91)2.13 (0.92)0.25297.07 (0.93)6.35 (0.92)WPAIc% activity impairment56.5 (23.4)56.0 (21.4)-19.03 (1.97)-5.63 (1.97)<0.0001-27.37 (2.34)-19.77 (2.31)% work time missed9.9 (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 working48.4 (26.3) [79]49.6 (22.2) [85]-19.83 (2.27)-6.94 (2.30)<0.0001-25.35 (2.77)-23.00 (2.66)% overall work impairment50.8 (27.4) [79]53.5 (23.1) [85]-21.49 (2.51)-7.64 (2.56)<0.0001-27.63 (3.01)-23.22 (2.90)aMMRMbGlobal type I error-controlled endpointcAnalysis of covariance model for W16 and MMRM for W48MCS, 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 errorIn 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.[1]Deodhar et al. Arthritis Rheumatol 2020; 72 (S10): Abs L11.Study sponsored by Pfizer Inc. Medical writing support was provided by Emma Mitchell, CMC Connect, and funded by Pfizer Inc.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