Ulrich Mrowietz1, Craig L Leonardi2, Giampiero Girolomoni3, Darryl Toth4, Akimichi Morita5, Shyamal A Balki6, Jacek C Szepietowski7, Pascaline Regnault8, Helen Thurston8, Charis Papavassilis8. 1. Psoriasis Center, Department of Dermatology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany. Electronic address: umrowietz@dermatology.uni-kiel.de. 2. Saint Louis University School of Medicine, St Louis, Missouri. 3. Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy. 4. XLR8 Medical Research, Windsor, Ontario, Canada. 5. Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. 6. Shree Hospital and Critical Care Center, Nagpur, India. 7. Department of Dermatology, Venereology, and Allergology, Wroclaw Medical University, Wroclaw, Poland. 8. Novartis Pharma AG, Basel, Switzerland.
Abstract
BACKGROUND: Secukinumab has demonstrated high, sustained efficacy in psoriasis to 52 weeks on a fixed-interval regimen. OBJECTIVE: We sought to compare a retreatment-as-needed versus a fixed-interval regimen. METHODS: In this double-blind study, adults with moderate to severe plaque psoriasis were randomized 1:1 to subcutaneous secukinumab at 300 mg (n = 484) or 150 mg (n = 482) weekly from baseline until week 4, and at week 8. At week 12, patients achieving 75% or more improvement from baseline Psoriasis Area and Severity Index score (PASI 75) were rerandomized to 2 dose levels of secukinumab retreatment as needed (n = 217, 300 mg; n = 206, 150 mg) or fixed interval (n = 217; n = 203). Primary end point was noninferiority of retreatment as needed versus fixed interval for maintaining PASI 75 to week 52. RESULTS: Secukinumab induced high responses by week 12 (84.4%-91.1% PASI 75 responders). From week 12 to week 52, more patients on fixed interval (78.2%, 300 mg; 62.1%, 150 mg) maintained PASI 75 versus retreatment as needed (67.7%; 52.4%); statistical noninferiority of retreatment as needed was not established. Overall safety, including very low incidences of treatment-emergent anti-drug antibodies (<0.5%), was similar between regimens. LIMITATIONS: The primary end point was developed without any known precedent. CONCLUSION: Secukinumab fixed interval showed clear benefit versus the study-specified retreatment-as-needed regimen for maintaining efficacy. Both regimens exhibited safety consistent with previous trials. The potential of retreatment as needed with secukinumab warrants further investigation.
RCT Entities:
BACKGROUND:Secukinumab has demonstrated high, sustained efficacy in psoriasis to 52 weeks on a fixed-interval regimen. OBJECTIVE: We sought to compare a retreatment-as-needed versus a fixed-interval regimen. METHODS: In this double-blind study, adults with moderate to severe plaque psoriasis were randomized 1:1 to subcutaneous secukinumab at 300 mg (n = 484) or 150 mg (n = 482) weekly from baseline until week 4, and at week 8. At week 12, patients achieving 75% or more improvement from baseline Psoriasis Area and Severity Index score (PASI 75) were rerandomized to 2 dose levels of secukinumab retreatment as needed (n = 217, 300 mg; n = 206, 150 mg) or fixed interval (n = 217; n = 203). Primary end point was noninferiority of retreatment as needed versus fixed interval for maintaining PASI 75 to week 52. RESULTS:Secukinumab induced high responses by week 12 (84.4%-91.1% PASI 75 responders). From week 12 to week 52, more patients on fixed interval (78.2%, 300 mg; 62.1%, 150 mg) maintained PASI 75 versus retreatment as needed (67.7%; 52.4%); statistical noninferiority of retreatment as needed was not established. Overall safety, including very low incidences of treatment-emergent anti-drug antibodies (<0.5%), was similar between regimens. LIMITATIONS: The primary end point was developed without any known precedent. CONCLUSION:Secukinumab fixed interval showed clear benefit versus the study-specified retreatment-as-needed regimen for maintaining efficacy. Both regimens exhibited safety consistent with previous trials. The potential of retreatment as needed with secukinumab warrants further investigation.
Authors: Vivaswath S Ayyar; Jong Bong Lee; Weirong Wang; Meghan Pryor; Yanli Zhuang; Thomas Wilde; An Vermeulen Journal: Front Pharmacol Date: 2022-04-25 Impact factor: 5.988
Authors: Marie Masson Regnault; Jason Shourick; Fatma Jendoubi; Marie Tauber; Carle Paul Journal: Am J Clin Dermatol Date: 2022-04-30 Impact factor: 6.233