P190 Secukinumab improves back pain, morning stiffness, fatigue and physical function in tumour necrosis factor inhibitor-naive patients with non-radiographic axial spondyloarthritis: results from a randomised controlled Phase 3 study
Authors: Marzo-Ortega Helena , Deodhar Atul , Blanco Ricardo Alonso , Kameda Hideto , Kivitz Alan , Poddubnyy Denis , Magrey Marina N , Wang Jianyuan , Haemmerle Sibylle , Shete Abhijit , Braun Jürgen 
Published: April 2021

Abstract
Background/Aims
Patients with non-radiographic axial spondyloarthritis (nr-axSpA) suffer from comparable disease burden to patients with ankylosing spondylitis (AS)/radiographic axSpA, including inflammatory back pain, morning stiffness, fatigue and reduced spinal mobility. Secukinumab 150 mg has demonstrated sustained improvement in signs and symptoms in patients with AS over 4 years. This post-hoc analysis evaluates the effect of secukinumab on back pain, morning stiffness, fatigue and physical function in tumour necrosis factor inhibitor-naive (TNFi-naive) patients with nr-axSpA from the PREVENT study (NCT02696031).
Methods
Patients with nr-axSpA receiving either subcutaneous secukinumab 150 mg with loading dose (LD), without loading dose (NL) or placebo (PBO) were included. Patients with inadequate response to treatment could switch to open-label secukinumab 150 mg or standard of care (TNFi) after Week 20 based on clinical judgement of disease activity. Nocturnal back pain scores (VAS [0-100]; ASAS outcome component), morning stiffness (overall level; VAS [0-10] ASAS outcome component), FACIT-Fatigue and SF-36 PCS scores were assessed. Continuous values were imputed as mixed-effects model repeated measures for mean change from baseline through Week 16 and as observed at Week 52. Minimal clinically important difference (MCID) was assessed using non-responder imputation through Week 16 and as observed at Week 52.
Results
Overall, 501 TNFi-naive patients were included (LD, N = 164; NL, N = 166; PBO, N = 171). Up to 64% of PBO and approximately of 50% secukinumab-treated patients switched to open-label secukinumab 150 mg between Week 20 and Week 52. Secukinumab-treated patients vs PBO (P &lt; 0.05) demonstrated a higher mean reduction from baseline in nocturnal back pain and morning stiffness at Weeks 4 and 16, which was sustained at Week 52 (Table 1). Improvements in secukinumab-treated patients vs PBO (P &lt; 0.05) were reported in FACIT-Fatigue and SF-36 PCS scores from baseline at Weeks 16 and 52 (Table 1). At Week 16, a higher proportion of secukinumab-treated patients met the MCID criteria vs PBO (P &lt; 0.05) across efficacy assessments, which was sustained at Week 52.
Conclusion
Secukinumab provided clinically meaningful improvement in back pain, morning stiffness, fatigue and physical function in TNFi-naive patients with nr-axSpA over 52 weeks.
Disclosure
H. Marzo-Ortega: Consultancies; H.M-O. is a consultant for AbbVie, Celgene, Janssen, Lilly, Novartis, Pfizer and UCB. Member of speakers’ bureau; H.M-O. is a member of speakers' buraeu for AbbVie, Celgene, Janssen, Lilly, Novartis, Pfizer, Takeda and UCB. Grants/research support; H.M-O. has received research support from Janssen and Novartis. A. Deodhar: Consultancies; A.D. is a consultant for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen, Novartis, Pfizer and UCB. Grants/research support; A.D. has received grant/research support from AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer and UCB. R. Alonso Blanco: Consultancies; R.A.B. has received consultancy fees from AbbVie, Pfizer, Roche, Bristol Myers Squibb, Janssen, UCB Pharma and MSD. Member of speakers’ bureau; R.A.B. is a member of the speakers' bureau for AbbVie, Pfizer, Roche, Bristol Myers Squibb, Janssen, UCB Pharma, MSD and Lilly. Grants/research support; R.A.B. has received grant/research support from AbbVie, MSD and Roche. H. Kameda: Consultancies; H.K. is a consultant for AbbVie, Asahi-Kasei, Astellas, Eli Lilly, Gilead Sciences, Janssen, Novartis, Sanofi and UCB. Member of speakers’ bureau; H.K. has received speakers' bureau fees from: AbbVie, Asahi-Kasei, BMS, Chugai, Eisai, Eli Lilly, Janssen, Mitsubishi-Tanabe, Novartis and Pfizer. Grants/research support; H.K. has received grant/research support from AbbVie, Asahi-Kasei, Chugai, Eisai, Mitsubishi-Tanabe and Novartis. A. Kivitz: Consultancies; A.K. has received consultancy fees from AbbVie, Boehringer Ingelheim, Flexion, Janssen, Pfizer, Sanofi, Regeneron, Sun Pharma Advanced Research and Gilead Sciences. Shareholder/stock ownership; A.K. is a shareholder of Pfizer, Sanofi, GlaxoSmithKline, Gilead Sciences and Novartis. Member of speakers’ bureau; A.K. is a member of the speakers' bureau for Celgene, Merck, Lilly, Novartis, Pfizer, Sanofi, Genzyme, Flexion and AbbVie. D. Poddubnyy: Consultancies; D.P. has received consultancy fees from AbbVie, BMS, Eli Lilly, MSD, Novartis, Pfizer, UCB and Roche. Honoraria; D.P. has received speaker fees from AbbVie, BMS, Lilly, MSD, Novartis, Pfizer, UCB and Roche. Grants/research support; D.P. has received research grants from AbbVie, MSD, Novartis and Pfizer. M. Magrey: Consultancies; M.M. is a consultant for Eli Lily and Novartis. Grants/research support; M.M. has received grant/research support from AbbVie, UCB and Amgen. J. Wang: Corporate appointments; J.W. is an employee of Novartis. S. Haemmerle: Corporate appointments; S.H. is an employee of Novartis. Shareholder/stock ownership; S.H. has ownership of Novartis stock. A. Shete: Corporate appointments; A.S. is an employee of Novartis. Shareholder/stock ownership; A.S. is a shareholder of Novartis. J. Braun: Consultancies; J.B. is a consultant for AbbVie (Abbott), Amgen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, UCB pharma and Eli Lilly. Member of speakers’ bureau; J.B. has received speakers' bureau fees from AbbVie (Abbott), Amgen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, UCB and Eli Lilly. Grants/research support; J.B. has received research support from AbbVie (Abbott), Amgen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Centocor, Chugai, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, UCB and Eli Lilly. P190 Table 1:Mean change from baseline up to Week 52 in the TNFi-naive populationEndpointsWeekSecukinumab LD (N = 164)Secukinumab NL (N = 166)PBO(N = 171)Nocturnal back painaBLd70.81 (17.86)70.86 (16.03)70.29 (14.67)4e-24.35 (2.00)§-23.07 (1.99)‡-16.67 (1.96)16e-30.93 (2.23)†-31.91 (2.22)†-20.27 (2.19)52f-40.9 (31.03)-43.3 (29.93)-Overall level of morning stiffnessaBLd7.59 (1.66)7.31 (1.95)7.11 (1.60)4e-2.62 (0.20)§-2.49 (0.20)§-1.73 (0.20)16e-3.30 (0.22)†-3.34 (0.22)†-2.20 (0.22)52f-4.55 (3.00)-4.52 (2.74)-FACIT-Fatigueb,cBLd21.79 (9.28)24.85 (10.60)23.96 (9.87)16e9.10 (0.74)†8.61 (0.74)§5.25 (0.73)52f11.97 (11.70)11.05 (10.95-SF-36 PCSb,cBLd32.88 (7.72)33.83 (7.06)33.68 (6.69)16e7.17 (0.61)†6.66 (0.61)§4.26 (0.60)52f10.04 (10.78)9.06 (9.60)-†P&lt;0.001,§P &lt; 0.01 and‡P &lt; 0.05 vs PBO.aAt Week 52, number of evaluable patients was 139 for LD and 146 for NL groups; number of patients switched to open-label secukinumab 150 mg was 67 for LD and 68 for NL groups for both pain and morning stiffness;bAt Week 52, number of evaluable patients was 146 for LD and 154 for NL groups; number of patients switched to open-label secukinumab 150 mg were 69 for LD and 71 for NL groups for fatigue and physical function;cFACIT-Fatigue and SF-36 PCS was assessed at baseline and Weeks 16 and 52;dMean (SD) presented at BL (as observed);eMean change from BL (SE) using MMRM at Weeks 4 and 16. For continuous variables, MMRM analysis was only conducted until Week 20.fMean change from BL (SD) as observed at Week 52. BL, baseline; FACIT, Functional Assessment of Chronic Illness Therapy; LD, with loading dose; MMRM, mixed-effects model repeated measures; N, number of randomised patients; n, number of evaluable patients; NA, not available; NL, without loading dose; PBO, placebo; SD, standard deviation; SE, standard error; SF36 PCS, Short Form-36 Physical Component Summary; TNFi, tumour necrosis factor inhibitor.