Iain B McInnes1, Frank Behrens2, Philip J Mease3, Arthur Kavanaugh4, Christopher Ritchlin5, Peter Nash6, Jordi Gratacós Masmitja7, Philippe Goupille8, Tatiana Korotaeva9, Alice B Gottlieb10, Ruvie Martin11, Kevin Ding11, Pascale Pellet12, Shephard Mpofu12, Luminita Pricop11. 1. Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. Electronic address: iain.mcinnes@glasgow.ac.uk. 2. Rheumatology University Hospital and Fraunhofer Institute for Molecular Biology and Applied Ecology, Branch for Translational Medicine and Pharmacology and Fraunhofer Cluster of Excellence for Immune-Mediated Diseases, Goethe University, Frankfurt, Germany. 3. Swedish Medical Centre, Providence St Joseph Health and University of Washington, Seattle, WA, USA. 4. Rheumatology, Allergy, Immunology Division, University of California San Diego, School of Medicine, La Jolla, CA, USA. 5. Allergy, Immunology and Rheumatology Division, University of Rochester, Rochester, NY, USA. 6. Department of Medicine, Griffith University, Brisbane, QLD, Australia. 7. Rheumatology Department, University Hospital Parc Taulí, Sabadell, Universitat Autònoma de Barcelona, Spain. 8. Department of Rheumatology and INSERM-CIC1415, University Hospital of Tours, EA 7501 GICC, University of Tours, Tours, France. 9. Research Institute of Rheumatology n.a. V A Nasonova, Moscow, Russia. 10. Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 11. Novartis Pharmaceuticals, East Hanover, NJ, USA. 12. Novartis Pharma, Basel, Switzerland.
Abstract
BACKGROUND: Head-to-head trials in psoriatic arthritis are helpful in guiding clinical decision making. The EXCEED study evaluated the efficacy and safety of secukinumab versus adalimumab as first-line biological monotherapy for 52 weeks in patients with active psoriatic arthritis, with a musculoskeletal primary endpoint of American College of Rheumatology (ACR) 20 response. METHODS: This parallel-group, double-blind, active-controlled, phase-3b, multicentre (168 sites in 26 countries) trial enrolled patients aged at least 18 years with active psoriatic arthritis. Eligible patients were randomly assigned (1:1) by means of interactive response technology to receive secukinumab or adalimumab. Patients, investigators, site personnel, and those doing the assessments (except independent study drug administrators) were masked to study assignment. 300 mg secukinumab was administered subcutaneously at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks until week 48 as a pre-filled syringe. Adalimumab was administered every 2 weeks from baseline until week 50 as 40 mg per 0·4 mL citrate free subcutaneous injection. The primary outcome was the proportion of patients with at least 20% improvement in the ACR response criteria (ACR20) at week 52. Patients were analysed according to the treatment to which they were randomly assigned. Safety analyses included all safety data reported up to and including the week 52 visit for each patient who received at least one dose of study drug. The trial is registered at ClinicalTrials.gov, NCT02745080. FINDINGS:Between April 3, 2017 and Aug 23, 2018, we randomly assigned 853 patients to receivesecukinumab (n=426) or adalimumab (n=427). 709 (83%) of 853 patients completed week 52 of the study, of whom 691 (81%) received the last study treatment at week 50. 61 (14%) of 426 patients in the secukinumab group discontinued treatment by week 52 versus 101 (24%) of 427 patients in the adalimumab group. The primary endpoint of superiority of secukinumab versus adalimumab for ACR20 response at week 52 was not met. 67% of patients in the secukinumab group achieved an ACR20 response at week 52 versus 62% of patients in the adalimumab group (OR 1·30, 95% CI 0·98-1·72; p=0·0719). The safety profiles of secukinumab and adalimumab were consistent with previous reports. Seven (2%) of 426 patients in the secukinumab group and six (1%) of 427 patients in the adalimumab group had serious infections. One death was reported in the secukinumab group due to colon cancer and was assessed as not related to the study drug by the investigator. INTERPRETATION:Secukinumab did not meet statistical significance for superiority versus adalimumab in the primary endpoint of ACR20 response at week 52. However, secukinumab was associated with a higher treatment retention rate than adalimumab. This study provides comparative data on two biological agents with different mechanisms of action, which could help guide clinical decision making in the management of patients with psoriatic arthritis. FUNDING: Novartis Pharma.
RCT Entities:
BACKGROUND: Head-to-head trials in psoriatic arthritis are helpful in guiding clinical decision making. The EXCEED study evaluated the efficacy and safety of secukinumab versus adalimumabas first-line biological monotherapy for 52 weeks in patients with active psoriatic arthritis, with a musculoskeletal primary endpoint of American College of Rheumatology (ACR) 20 response. METHODS: This parallel-group, double-blind, active-controlled, phase-3b, multicentre (168 sites in 26 countries) trial enrolled patients aged at least 18 years with active psoriatic arthritis. Eligible patients were randomly assigned (1:1) by means of interactive response technology to receive secukinumab or adalimumab. Patients, investigators, site personnel, and those doing the assessments (except independent study drug administrators) were masked to study assignment. 300 mg secukinumab was administered subcutaneously at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks until week 48 as a pre-filled syringe. Adalimumab was administered every 2 weeks from baseline until week 50 as 40 mg per 0·4 mL citrate free subcutaneous injection. The primary outcome was the proportion of patients with at least 20% improvement in the ACR response criteria (ACR20) at week 52. Patients were analysed according to the treatment to which they were randomly assigned. Safety analyses included all safety data reported up to and including the week 52 visit for each patient who received at least one dose of study drug. The trial is registered at ClinicalTrials.gov, NCT02745080. FINDINGS: Between April 3, 2017 and Aug 23, 2018, we randomly assigned 853 patients to receive secukinumab (n=426) or adalimumab (n=427). 709 (83%) of 853 patients completed week 52 of the study, of whom 691 (81%) received the last study treatment at week 50. 61 (14%) of 426 patients in the secukinumab group discontinued treatment by week 52 versus 101 (24%) of 427 patients in the adalimumab group. The primary endpoint of superiority of secukinumab versus adalimumab for ACR20 response at week 52 was not met. 67% of patients in the secukinumab group achieved an ACR20 response at week 52 versus 62% of patients in the adalimumab group (OR 1·30, 95% CI 0·98-1·72; p=0·0719). The safety profiles of secukinumab and adalimumab were consistent with previous reports. Seven (2%) of 426 patients in the secukinumab group and six (1%) of 427 patients in the adalimumab group had serious infections. One death was reported in the secukinumab group due to colon cancer and was assessed as not related to the study drug by the investigator. INTERPRETATION:Secukinumab did not meet statistical significance for superiority versus adalimumab in the primary endpoint of ACR20 response at week 52. However, secukinumab was associated with a higher treatment retention rate than adalimumab. This study provides comparative data on two biological agents with different mechanisms of action, which could help guide clinical decision making in the management of patients with psoriatic arthritis. FUNDING: Novartis Pharma.
Authors: Laura C Coates; Enrique R Soriano; Nadia Corp; Heidi Bertheussen; Kristina Callis Duffin; Cristiano B Campanholo; Jeffrey Chau; Lihi Eder; Daniel G Fernández-Ávila; Oliver FitzGerald; Amit Garg; Dafna D Gladman; Niti Goel; Philip S Helliwell; M Elaine Husni; Deepak R Jadon; Arnon Katz; Dhruvkumar Laheru; John Latella; Ying-Ying Leung; Christine Lindsay; Ennio Lubrano; Luis Daniel Mazzuoccolo; Philip J Mease; Denis O'Sullivan; Alexis Ogdie; Wendy Olsder; Penelope Esther Palominos; Lori Schick; Ingrid Steinkoenig; Maarten de Wit; D A van der Windt; Arthur Kavanaugh Journal: Nat Rev Rheumatol Date: 2022-06-27 Impact factor: 32.286
Authors: A B Gottlieb; J F Merola; K Reich; F Behrens; P Nash; C E M Griffiths; W Bao; P Pellet; L Pricop; I B McInnes Journal: Br J Dermatol Date: 2021-07-14 Impact factor: 11.113
Authors: A Prior-Español; C Sánchez-Piedra; J Campos; F J Manero; C Pérez-García; C Bohórquez; N Busquets-Pérez; J M Blanco-Madrigal; C Díaz-Torne; F Sánchez-Alonso; L Mateo; S Holgado-Pérez Journal: Sci Rep Date: 2021-05-27 Impact factor: 4.379