Session Information
Date: Tuesday, October 23, 2018
Title: Spondyloarthritis Including Psoriatic Arthritis – Clinical Poster III: Treatment
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose:
Secukinumab, a fully human monoclonal antibody that selectively neutralizes IL-17A, has demonstrated efficacy for patients with psoriatic arthritis (PsA) in multiple phase 3 clinical trials.1–4 To improve and standardize the assessment of PsA outcomes, the PsA core domain set, initially implemented in 2006,5 has been updated by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and endorsed by Outcome Measures in Rheumatology (OMERACT)6 in 2016. The updated PsA core domains are: musculoskeletal disease activity (arthritis, enthesitis, dactylitis, and spine symptoms), skin disease activity (psoriasis and nail psoriasis), pain, patient global assessment, physical function, fatigue, health-related quality of life, and systemic inflammation; structural damage assessment is recommended at least once in the development program of PsA medications. Here we report the efficacy of secukinumab vs placebo across individual PsA core domains, using pooled data from 4 phase 3 FUTURE studies.
Methods:
Patients with active PsA participated in the phase 3 clinical trials FUTURE 2, 3, 4, and 5 (397, 414, 341, and 996 patients, respectively).1–4 Data were pooled from the studies using secukinumab dosed at 150 mg (load vs no load), 300 mg, or placebo at the end of the 16-week double-blind period, and efficacy evaluated according to the updated GRAPPA-OMERACT PsA core domains. Core domains were assessed using multiple instruments (Table 1) with improvement defined as percentage of patients achieving ≥ 50% improvement (joints), complete resolution (arthritis, enthesitis, dactylitis), or minimal clinically important difference in PsA where known and/or least squares mean change from baseline (patient-reported outcomes). Axial data are from MEASURE 2 (not assessed in FUTURE studies).
Results:
2049 patients were included, of whom 461 received secukinumab 300 mg, 572 received secukinumab 150 mg, 335 received secukinumab 150 mg no load, and 681 received placebo. Baseline demographics and disease characteristics were broadly similar in all treatment groups. Efficacy results for each core domain are provided in Table 1.
Conclusion:
Secukinumab demonstrated efficacy across GRAPPA-OMERACT PsA core domains in the phase 3 clinical trials program using multiple instruments and thresholds to measure improvement. Secukinumab 300 mg had the greatest efficacy across domains vs placebo. Our results indicate that secukinumab improves both the disease manifestations and life impact of PsA as demonstrated using the PsA core domain set.
References:
1. McInnes IB, et al. Rheumatology. 2017;56:1993-2003; 2. Nash P, et al. Arthritis Res Ther. 2018;20: 47; 3. Kivitz A, et al. PANLAR 2018 [abstract 364]; 4. Mease PJ, et al. ACR 2017 [abstract 17L]; 5. Gladman DD, et al. J Rheumatol. 2007;34:1167-70; 6. Orbai AM, et al. Ann Rheum Dis. 2017;76:673-80.
Table 1. Pooled efficacy results across GRAPPA-OMERACT PsA core domains.
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Improvement in Patients With PsA at Week 16 in FUTURE Trialsa
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PsA Core Domains
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Measures and Improvement Definitions, n/M (%)
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Secukinumab 300 mg n = 461
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Secukinumab 150 mg n = 572
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Secukinumab 150 mg, no load n = 335
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Placebo
n = 681
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Inner circle domains (should be measured in all PsA clinical trials)
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Musculoskeletal disease activity – Arthritis – Enthesitis – Dactylitis
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SJC76, ≥ 50% improvement
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314/444 (70.7)
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353/551 (64.1)
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201/323 (62.2)
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258/626 (41.2)
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SJC76 resolution
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158/444 (35.6)
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151/551 (27.4)
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77/323 (23.8)b
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104/626 (16.6)
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TJC78, ≥ 50% improvement
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289/444 (65.1)
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316/551 (57.4)
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183/323 (56.7)
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204/626 (32.6)
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TJC78 resolution
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89/444 (20.0)
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80/551 (14.5)
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32/323 (9.9)c
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35/626 (5.6)
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LEI resolution
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151/284 (53.2)
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166/374 (44.4)
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80/195 (41.0)d
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125/431 (29.0)
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LDI resolution
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107/174 (61.5)
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98/188 (52.1)
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74/141 (52.5)e
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76/231 (32.9)
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Skin disease activity
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PASI75
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151/214 (70.6)
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175/306 (57.2)
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95/171 (55.6)
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34/326 (10.4)
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IGA 0/1
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112/214 (52.3)
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125/306 (40.8)
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55/171 (32.2)
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25/326 (7.7)
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Pain
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PsA pain, mean change from BLf,g
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−19.75 (n = 440)
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−15.94 (n = 545)
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−15.44 (n = 320)
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−4.46 (n = 616)
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PsA pain VAS, ≥ 3 points improvementg
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313/440 (71.1)
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403/545 (73.9)
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229/319 (71.8)
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331/617 (53.6)
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Patient global
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PGA, mean change from BLf,g
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−20.04 (n = 440)
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−15.92 (n = 545)
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−14.60 (n = 320)
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−5.31 (n = 616)
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Physical function
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HAQ-DI, MCID = 0.3
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262/459 (57.1)
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281/571 (49.2)
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172/335 (51.3)
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226/680 (33.2)
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HAQ-DI, mean change from BLf
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−0.48 (n = 438)
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−0.36 (n = 544)
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−0.40 (n = 320)
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−0.16 (n = 615)
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HRQOL
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SF-36 PCS, MCID ≥ 2.5, %
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65.9
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59.4
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61.8
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42.0
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SF-36 MCS, MCID ≥ 2.5, %
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48.4h
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50.0h
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49.9h
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40.4
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PsAQOL, mean change from BLf
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−3.65 (n = 443)
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−3.26 (n = 548)
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−3.16 (n = 319)
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−1.20 (n = 622)
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Fatigue
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FACIT-Fatigue, mean change from BLf,g
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1.13 (n = 442)i
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0.63 (n = 546)j
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−0.29 (n = 319)k
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1.18 (n = 621)
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Systemic inflammation
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Elevated CRP (> 10 mg/L) resolution
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83/111 (74.8)
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86/134 (64.2)
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52/ 75 (69.3)
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55/154 (35.7)
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Middle circle domains (important but not required in all PsA clinical trials)
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Participation
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WPAI-GH, mean change from BLf
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−13.98 (n = 283)
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−10.85 (n = 392)
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−13.39 (n = 186)
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−4.62 (n = 417)
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Structural damage
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No structural progression at week 24l
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191/217 (88.0)
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170/213 (79.8)m
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176/210 (83.8)n
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218/296 (73.6)
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Improvement in Patients With Ankylosing Spondylitis at Week 16 in MEASURE 2a,o
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Secukinumab 150 mg
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Placebo
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Spine symptoms
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BASDAI, mean change from BL
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−2.19p
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−0.85
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a All P values vs placebo were P < .0001 except where indicated. All P values were for hypothesis generation. No adjustment was made for multiple comparisons. b P = .0073. c P = .0139. d P = .0066. e P = .0003. f Least squares mean change from BL; n is the number of patients with measures at both baseline and week 16 visit. g No MCID has been defined in PsA. h P < .01. i P = .9213. j P = .2581. k P = .0136. l Defined as a change from baseline vdH-mTSS of ≤ 0.5. Data shown are from the FUTURE 5 study. m P = .1027. n P = .0053. o Baeten D, et al. N Engl J Med. 2015;373:2534-2548. p P < .001.
BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BL, baseline; CRP, C-reactive protein; FACIT-Fatigue, Functional Assessment of Chronic Illness Therapy-Fatigue; HAQ-DI, Health Assessment Questionnaire-Disability Index; HRQOL, health-related quality of life; IGA, Investigator’s Global Assessment; LDI, Leeds Dactylitis Index; LEI, Leeds Enthesitis Index; MCID, minimal clinically important difference; MCS, mental component summary; PASI75/90, 75%/90% reduction in the Psoriasis Area and Severity Index; PCS, physical component summary; PGA, patient global assessment; PsA, psoriatic arthritis; PsAQOL, psoriatic arthritis–specific quality of life; SJC76, swollen joint count based on 76 joints; TJC78, tender joint count based on 78 joints; VAS, 100-mm visual analogue scale; vdH-mTSS, van der Heijde-modified Total Sharp Score; WPAI-GH, Work Productivity and Activity Impairment Questionnaire: General Health.
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To cite this abstract in AMA style:
Orbai AM, McInnes IB, Coates LC, Husni ME, Gladman DD, Gossec L, Pricop L, Chambenoit O, Meng X, Mease PJ. Secukinumab Improves Grappa-Omeract Core Domains of Psoriatic Arthritis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/secukinumab-improves-grappa-omeract-core-domains-of-psoriatic-arthritis/. Accessed .« Back to 2018 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/secukinumab-improves-grappa-omeract-core-domains-of-psoriatic-arthritis/