INTRODUCTION: To assess the efficacy and safety of the subcutaneous (s.c.) secukinumab 150 mg with loading (150 mg) or without loading (150 mg no-load) regimen through 104 weeks in patients with active psoriatic arthritis (PsA) in the FUTURE 4 (NCT02294227) study. METHODS: Patients with PsA (N = 341) were randomized to s.c. secukinumab 150 mg, 150 mg no-load or placebo at baseline, weeks 1, 2, 3 and every 4 weeks thereafter. All placebo patients were reassigned to secukinumab 150 mg no-load at either week 16 (non-responders) or week 24 (responders). The primary end point was ACR20 at week 16. Patients could have their dose escalated from 150 to 300 mg based on their physician's decision starting at week 36. Pre- and post-escalation ACR and PASI responses were also assessed. RESULTS: A total of 95.6% (326/341), 84.5% (288/341) and 79.8% (272/341) patients completed 16, 52 and 104 weeks of treatment, respectively. The primary end point was met; ACR20 response rate at week 16 was 41.2% and 39.8% with the 150 mg and 150 mg no-load groups, respectively, versus placebo (18.4%; adjusted P value = 0.0003 for both treatment arms). Efficacy responses observed at week 16 in both treatment regimens were sustained up to week 52 and 104, with many patients continuing to show improvements up to week 104. After dose escalation to 300 mg, the proportion of patients with non-/low-level ACR/PASI response decreased with increasing proportions of patients having higher ACR/PASI responses. No new or unexpected safety signals were reported. CONCLUSION: The secukinumab 150 mg or 150 mg no-load regimen demonstrated significant and sustained improvements in the signs and symptoms of psoriatic arthritis through 104 weeks; the loading regimen was associated with numerically higher and earlier responses for some high-hurdle end points. Improved efficacy was observed upon dose escalation from 150 to 300 mg. The safety profile was consistent with previous reports. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02294227. FUNDING: Novartis Pharma AG, Basel, Switzerland.

Altoona Centre for Clinical Research Duncansville PA USA

Barts Health NHS Trust London UK

Hamburger Rheuma Forschungszentrum 2 Hamburg Germany

Institute of Rheumatology and Department of Rheumatology Charles University Prague Czech Republic

Novartis Pharma AG Basel Switzerland

Novartis Pharmaceutical Corporation East Hanover NJ USA

Specjalistyczne Gabinety Lekarskie DERMED Anna Kaszuba Lodz Poland

University of Queensland Brisbane Australia

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Kang EJ, Kavanaugh A. Psoriatic arthritis: latest treatments and their place in therapy. Ther Adv Chronic Dis. 2015;6(4):194–203. doi: 10.1177/2040622315582354. PubMed DOI PMC

Weger W. Current status and new developments in the treatment of psoriasis and psoriatic arthritis with biological agents. Br J Pharmacol. 2010;160(4):810–820. doi: 10.1111/j.1476-5381.2010.00702.x. PubMed DOI PMC

Ritchlin CT, Kavanaugh A, Gladman DD, Mease PJ, Helliwell P, Boehncke W-H, et al. Treatment recommendations for psoriatic arthritis. Ann Rheum Dis. 2009;68(9):1387–1394. doi: 10.1136/ard.2008.094946. PubMed DOI PMC

Mease PJ, Armstrong AW. Managing patients with psoriatic disease: the diagnosis and pharmacologic treatment of psoriatic arthritis in patients with psoriasis. Drugs. 2014;74(4):423–441. doi: 10.1007/s40265-014-0191-y. PubMed DOI PMC

Gossec L, Smolen JS, Ramiro S, de Wit M, Cutolo M, Dougados M, et al. European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update. Ann Rheum Dis. 2016;75(3):499–510. doi: 10.1136/annrheumdis-2015-208337. PubMed DOI

Coates LC, On behalf of BSRCAC, Standards A, Guidelines Working G, the B. Tillett W, et al. The 2012 BSR and BHPR guideline for the treatment of psoriatic arthritis with biologics. Rheumatology. 2013;52(10):1754–1757. doi: 10.1093/rheumatology/ket187. PubMed DOI

Singh JA, Guyatt G, Ogdie A, Gladman DD, Deal C, Deodhar A, et al. 2018 American College of Rheumatology/National Psoriasis Foundation guideline for the treatment of psoriatic arthritis. Arthritis Care Res (Hoboken) 2019;71(1):2–29. doi: 10.1002/acr.23789. PubMed DOI PMC

Costa L, Perricone C, Chimenti MS, Del Puente A, Caso P, Peluso R, et al. Switching between biological treatments in psoriatic arthritis: a review of the evidence. Drugs R&D. 2017;17(4):509–522. doi: 10.1007/s40268-017-0215-7. PubMed DOI PMC

McInnes IB, Mease PJ, Kirkham B, Kavanaugh A, Ritchlin CT, Rahman P, et al. Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015;386(9999):1137–1146. doi: 10.1016/S0140-6736(15)61134-5. PubMed DOI

Strand V, Mease P, Gossec L, Elkayam O, van den Bosch F, Zuazo J, et al. Secukinumab improves patient-reported outcomes in subjects with active psoriatic arthritis: results from a randomised phase III trial (FUTURE 1) Ann Rheum Dis. 2017;76(1):203–207. doi: 10.1136/annrheumdis-2015-209055. PubMed DOI

Mease PJ, Kavanaugh A, Reimold A, Tahir H, Rech J, Hall S, et al. Secukinumab in the treatment of psoriatic arthritis: efficacy and safety results through 3 years from the year 1 extension of the randomised phase III FUTURE 1 trial. RMD Open. 2018;4(2):e000723. doi: 10.1136/rmdopen-2018-000723. PubMed DOI PMC

Nash P, Mease PJ, McInnes IB, Rahman P, Ritchlin CT, Blanco R, et al. Efficacy and safety of secukinumab administration by autoinjector in patients with psoriatic arthritis: results from a randomized, placebo-controlled trial (FUTURE 3) Arthritis Res Ther. 2018;20(1):47. doi: 10.1186/s13075-018-1551-x. PubMed DOI PMC

Mease P, van der Heijde D, Landewe R, Mpofu S, Rahman P, Tahir H, et al. Secukinumab improves active psoriatic arthritis symptoms and inhibits radiographic progression: primary results from the randomised, double-blind, phase III FUTURE 5 study. Ann Rheum Dis. 2018;77(6):890–897. PubMed PMC

Mease PJ, KA, Reimold A, Tahir H, Rech J, Hall S, Geusens P, Pascale P, Delicha EM, Pricop L, Mpofu S. Secukinumab provides sustained improvements in the signs and symptoms in psoriatic arthritis: final 5 year efficacy and safety results from a phase 3 trial [abstract]. Arthritis Rheumatol. 2018;70(suppl 10). PubMed PMC

Kavanaugh A, McInnes IB, Mease PJ, Hall S, Chinoy H, Kivitz AJ, et al. Efficacy of subcutaneous secukinumab in patients with active psoriatic arthritis stratified by prior tumor necrosis factor inhibitor use: results from the randomized placebo-controlled FUTURE 2 study. J Rheumatol. 2016;43(9):1713–1717. doi: 10.3899/jrheum.160275. PubMed DOI

World’s Medical Association; 2019. https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/. Accessed 15 Apr 2019.

McInnes IB KA, Nash P, Rahman P, Rech J, Kirkham B, Navarra SV, Ding K, Ilsley E, Pricop L. Secukinumab provides sustained improvements in the signs and symptoms of active psoriatic arthritis: long-term (4-year) data from a phase 3 study [abstract]. Arthritis Rheumatol. 2018;70(suppl 10).

Mease PJ, McInnes IB, Kirkham B, Kavanaugh A, Rahman P, van der Heijde D, et al. Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N Engl J Med. 2015;373(14):1329–1339. doi: 10.1056/NEJMoa1412679. PubMed DOI

Efficacy and Safety of Intravenous Secukinumab for the Treatment of Active Psoriatic Arthritis: Results From a Randomized, Placebo-Controlled Phase 3 Study

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ClinicalTrials.gov
NCT02294227