Abstract
Background/Aims
SKIPPAIN (NCT03136861) is the first randomised controlled study involving a biological disease-modifying anti-rheumatic drug, with a primary endpoint of spinal pain at Week 8 in patients with axial spondyloarthritis (axSpA; ankylosing spondylitis [AS] and non-radiographic [nr]-axSpA). We present the 24-week results of secukinumab in reducing spinal pain and disease activity following step-up dosing.
Methods
This double-blind, placebo-controlled Phase 3b study enrolled patients (aged ≥18 years) with active disease (BASDAI ≥4; average spinal pain numerical rating scale [NRS] score >4 at baseline; inadequate response to ≥ 2 non-steroidal anti-inflammatory drugs ≥4 weeks). Patients were randomised (3:1) to subcutaneous secukinumab 150 mg or placebo weekly followed by every 4 weeks (Q4W) from Week 4. At Week 8, placebo patients were re-randomised to secukinumab 150 or 300 mg Q4W. Patients originally randomised to secukinumab 150 mg were classified as responders or non-responders (spinal pain NRS score <4 or ≥ 4, respectively) at Week 8. Responders were re-assigned to continue doubleblind secukinumab 150 mg Q4W (Arm A1). Non-responders were re-randomised to double-blind secukinumab 150 mg (Arm A2) or a step-up dose of 300 mg (Arm A3) Q4W. Treatment was up to Week 24. Primary endpoint: proportion of patients achieving an average spinal pain score <4 on a 0-10 NRS with secukinumab vs placebo at Week 8.
Results
380 axSpA patients (269/380 [70.8%] AS; 111/380 [29.2%] nr-axSpA) were randomised to secukinumab 150 mg (N = 285) or placebo (N = 95). The primary endpoint was met (proportion of spinal pain NRS [average] score responders: 32% vs 20%; odds ratio [95% confidence interval] 1.9 [1.1-3.3] favouring secukinumab vs placebo; P < 0.05). Further reductions in spinal pain occurred at Week 24, especially in those initially randomised to placebo and switched to active drug. Pronounced improvements were observed in other disease activity measurements (Table 1). Numerically, more patients achieved ASDAS low disease activity at Week 24 post-secukinumab dose escalation (Arm A3) vs those remaining on the same dose (Arm A2).
Conclusion
Secukinumab provided rapid, significant improvement in spinal pain and led to low disease activity in axSpA patients. Secukinumab dose escalation might be beneficial for patients not responding fully to the starting dose. P188 Table 1:Spinal pain and ASDAS-CRP scores at Weeks 8 and 24Week 8SEC 150 mg (N = 285)PBO (N = 95)Change from baseline in spinal pain NRS score (total), mean (SD) [n]-2.6 (2.5) [279]-1.5 (2.2) [92]Change from baseline in ASDAS-CRP score, mean (SD) [n]-1.2 (1.0) [271]-0.5 (0.8) [89]Week 24Active treatment group (SEC treatment starting at baseline)PBO switchers group (SEC treatment starting at Week 8)Arm A1 (SEC 150 R-150) N = 90Arm A2 (SEC 150 NR-150) N = 94Arm A3 (SEC 150 NR-300) N = 94Arm B1 (PBO-SEC 150) N = 45Arm B2 (PBO-SEC 300) N = 44Change from Week 8 in spinal pain NRS score (total), mean (SD) [n]-0.4 (1.5) [88]-2.1 (2.2) [93]-1.9 (2.2) [91]-2.5 (2.6) [45]-2.9 (2.6) [43]Change from baseline in ASDAS-CRP score, mean (SD) [n]-2.2 (1.0) [86]-1.2 (1.0) [93]-1.5 (1.0) [92]-1.5 (1.1) [44]-1.8 (0.9) [43]Arm A1=SEC responder to SEC 150 mg at Week 8 (SEC 150 R-150); Arm A2=SEC non-responder to SEC 150 mg at Week 8 (SEC 150 NR-150); Arm A3=SEC non-responder to SEC 300 mg at Week 8 (SEC 150 NR-300); Arm B1=Placebo patients to SEC 150 mg (PBO-SEC 150); Arm B2=Placebo patients to SEC 300 mg (PBO-SEC 300). ASDAS-CRP, Ankylosing Spondylitis Disease Activity Score using C-reactive protein; N, total number of patients randomised; n, number of evaluable patients; NR, non-responders; NRS, numerical rating scale; PBO, placebo; R, responders; SD, standard deviation; SEC, secukinumab.
Disclosure
H. Marzo-Ortega: Consultancies; AbbVie, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB. Member of speakers’ bureau; AbbVie, Celgene, Janssen, Lilly, Novartis, Pfizer, Takeda, UCB. Grants/research support; Janssen, Novartis. C. Perella: Corporate appointments; Employee of Novartis. Shareholder/stock ownership; Novartis Stock. D. Poddubnyy: Consultancies; Consultant/speaker for: AbbVie, BMS, Lilly, MSD, Novartis, Pfizer, Roche, UCB. Grants/research support; AbbVie, MSD, Novartis, Pfizer. E. Pournara: Corporate appointments; Employee of Novartis. Shareholder/stock ownership; Novartis Stock. A. Zielińska: Consultancies; Novartis, Pfizer. A. Baranauskaite: Consultancies; AbbVie. Member of speakers’ bureau; Novartis, AbbVie, Amgen, Roche, KRKA. S. Sadhu: Corporate appointments; Employee of Novartis. B. Schulz: Corporate appointments; Employee of Novartis. M. Rissler: Corporate appointments; Employee of Novartis. Shareholder/stock ownership; Novartis Stock.
The Efficacy of Lingual Laser Frenectomy in Pediatric OSAS: A Randomized Double-Blinded and Controlled Clinical Study
