Abstract
Background/Aims
MAXIMISE, the first randomised controlled trial evaluating efficacy of a biologic for psoriatic arthritis (PsA) axial manifestations, showed that secukinumab 300 and 150 mg provided rapid and significant improvement in ASAS20 responses through Week 12. We report the effect of secukinumab on clinical and imaging outcomes through 52 weeks.
Methods
This Phase 3, double-blind, multicentre trial included 498 patients (≥18 years) with PsA who fulfilled CASPAR criteria presenting with spinal pain VAS ≥40/100, BASDAI ≥4 and inadequate response to ≥ 2 non-steroidal anti-inflammatory drugs. Patients were randomised to secukinumab 300 mg (N = 167), 150 mg (N = 165) or placebo (N = 166) weekly for 4 weeks and every 4 weeks thereafter. At Week 12, placebo patients were re-randomised to secukinumab 300/150 mg. The primary endpoint was ASAS20 with secukinumab 300 mg at Week 12. Exploratory assessments at Week 52 included ASAS20/40, BASDAI50, spinal pain (VAS) and improvement in Berlin magnetic resonance imaging (MRI) score for spine and sacroiliac joints.
Results
The primary endpoint was met. ASAS20/40 responses at Week 12 were 62.9%/43.6% (secukinumab 300 mg) and 66.3%/39.5% (secukinumab 150 mg) versus 31.2%/12.2% (placebo), respectively (P < 0.0001). ASAS20/40 responses improved further with secukinumab 300/150 mg from baseline through 52 weeks. 74.1%/74.7% and 63.0%/50.6% of placebo patients, re-randomised at Week 12 to secukinumab 300/150 mg, achieved ASAS20/40 at Week 52. At baseline, 59.5% (secukinumab 300 mg), 54.2% (secukinumab 150 mg) and 64.2% (placebo) of patients had positive MRI scores for the sacroiliac joints and/or the spine. Reductions in Berlin MRI scores for the entire spine and sacroiliac joints were sustained with secukinumab 300/150 mg from baseline through 52 weeks (Table 1). 64.6%, 69.1% and 33.6% of patients with inflammatory back pain at baseline, confirmed by ASAS, Calin et al. and Berlin criteria in the secukinumab 300 mg, 150 mg and placebo groups, respectively, achieved ASAS20 at Week 12. P184 Table 1:Endpoints at Week 52CriteriaSecukinumab 300 mg SC (N = 164)Secukinumab 150 mg SC (N = 157)Placebo to secukinumab 300 mg SC (N = 81)Placebo to secukinumab 150 mg SC (N = 80)Clinical endpointsASAS20, % responders (n/M)a75.5 (123/163)77.3 (119/154)74.1 (60/81)74.7 (59/79)ASAS40, % responders (n/M)a62.6 (102/163)60.4 (93/154)63.0 (51/81)50.6 (40/79)BASDAI50, % responders (n/M)b68.3 (95/139)58.5 (83/142)55.6 (40/72)54.1 (40/74)Spinal pain VAS, mean change from BL (SD), nb-42.4 (27.0), 140-43.8 (26.2), 142-43.1 (25.0), 72-36.4 (25.2), 74Imaging endpointBerlin MRI score for entire spine, mean change from BL (SD), nb-0.6 (2.3), 121-0.3 (1.3), 124-0.8 (2.7), 63-0.4 (1.3), 60Berlin MRI score for SIJ, mean change from BL (SD), nb-0.7 (2.2), 122-0.5 (1.7), 122-0.9 (2.4), 63-1.0 (2.7), 59N=total number of patients in the group; n=number of patients with response; M=number of evaluable patients. aIntermediate missing data as well as any data missing in the case of study discontinuation is imputed using LOCF; bObserved data. Patients with initial placebo treatment were re-randomised to secukinumab 300 or 150 mg at Week 12. ASAS, Assessment of SpondyloArthritis International Society; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BL, baseline; LOCF, last observation carried forward; MRI, magnetic resonance imaging; SC, subcutaneous; SD, standard deviation; SIJ, sacroiliac joints; VAS, visual analogue scale.
Conclusion
Secukinumab improved signs and symptoms of axial disease (ASAS20/40) through 52 weeks with reduced inflammatory MRI lesions in the spine and sacroiliac joints in PsA patients with axial manifestations. Efficacy at Week 52 was comparable in patients who switched at Week 12 from placebo to secukinumab 300/150 mg.
Disclosure
X. Baraliakos: Consultancies; AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB, Werfen. Member of speakers’ bureau; AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB. Grants/research support; AbbVie, Novartis. L. Gossec: Consultancies; AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB. Grants/research support; Lilly, Mylan, Pfizer, Sandoz. E. Pournara: Corporate appointments; Employee of Novartis. Shareholder/stock ownership; Novartis stock. S. Jeka: Grants/research support; AbbVie, Pfizer, Roche, Novartis, MSD, Sandoz, Lilly, Egis, UCB, Celgene. R. Blanco: Consultancies; AbbVie, Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma, MSD. Grants/research support; AbbVie, MSD, Roche. S. D'Angelo: Consultancies; AbbVie, Biogen, BMS, Celgene, Lilly, MSD, Novartis, UCB. Member of speakers’ bureau; AbbVie, BMS, Celgene, Lilly, Novartis, Pfizer, Sanofi. G. Schett: Honoraria; AbbVie, BMS, Celgene, Janssen, Lilly, Novartis, Roche, UCB. B. Schulz: Corporate appointments; Employee of Novartis. M. Rissler: Corporate appointments; Employee of Novartis. Shareholder/stock ownership; Novartis stock. D. Whyms: Corporate appointments; Employee of Novartis. C. Perella: Corporate appointments; Employee of Novartis. Shareholder/stock ownership; Novartis stock. L.C. Coates: Consultancies; : AbbVie, Amgen, Biogen, Celgene, Pfizer, UCB, Boehringer Ingelheim, Novartis, Lilly, Janssen, Sun Pharma, Prothena, Gilead. Grants/research support; AbbVie, Janssen, Lilly, Novartis, Pfizer, Amgen.
Occult axial involvement in patients with psoriatic arthritis mutilans: a case report
