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

Abstract

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).1Objectives: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 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 mg BID (N=133)PBO(N=136)Tofacitinib5 mg BIDPBOp valueTofacitinib5 mg BIDPBO→tofacitinib5 mg 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 errorConclusion: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.