Efficacy and safety of rozanolixizumab in patients with muscle-specific tyrosine kinase autoantibody-positive generalised myasthenia gravis : a subgroup analysis of the randomised, double-blind, placebo-controlled, adaptive phase III MycarinG study
Habib, A.A. (University of California)
Sacconi, S. (Université Côte d'Azur)
Cortés-Vicente, Elena (Institut de Recerca Sant Pau)
Mahuwala, Z.K. (University of Kentucky)
Mantegazza, Renato (Istituto Nazionale Neurologico Carlo Besta)
Vissing, John (University of Copenhagen)
Wiendl, Heinz (University Hospital Münster)
Bril, V. (University Health Network)
Antonini, Giovanni (Sapienza University of Rome)
Grosskreutz, Julian (University of Lübeck)
Pascuzzi, Robert M. (Indiana University Health)
Utsugisawa, Kimiaki (Hanamaki General Hospital)
Vu, Tuan H. (University of South Florida Morsani College of Medicine)
Boehnlein, Marion (UCB Pharma. Monheim am Rhein)
Greve, Bernhard (UCB Pharma. Monheim am Rhein)
Woltering, Franz (UCB Pharma. Monheim am Rhein)
Universitat Autònoma de Barcelona. Departament de Medicina

Date:	2024
Abstract:	Background: Muscle-specific tyrosine kinase (MuSK) autoantibody-positive (Ab+) generalised myasthenia gravis (gMG) is a rare and frequently severe subtype of gMG. Objectives: To assess the efficacy and safety of rozanolixizumab in the subgroup of patients with MuSK Ab+ gMG in the MycarinG study. Design: A randomised, double-blind, placebo-controlled phase III study. Methods: Patients with acetylcholine receptor (AChR) Ab+ or MuSK Ab+ gMG (aged ⩾18 years, Myasthenia Gravis Foundation of America Disease Class II-IVa, Myasthenia Gravis Activities of Daily Living [MG-‍ADL] score ⩾3. 0 [non-ocular symptoms], Quantitative Myasthenia Gravis score ⩾11. 0) were randomly assigned (1:1:1) to receive once-weekly subcutaneous infusions of rozanolixizumab 7 mg/kg, rozanolixizumab 10 mg/kg or placebo for 6 weeks, followed by an 8-week observation period. Randomisation was stratified by AChR and MuSK autoantibody status. The primary study endpoint was change from baseline to Day 43 in MG-ADL score. Treatment-emergent adverse events (TEAEs) were also assessed. Results: Overall, 200 patients were randomised, of whom 21 had MuSK Ab+ gMG and received rozanolixizumab 7 mg/kg (n = 5), 10 mg/kg (n = 8) or placebo (n = 8). In patients with MuSK Ab+ gMG, reductions from baseline to Day 43 in MG-ADL scores were observed: rozanolixizumab 7 mg/kg least squares mean (LSM) change (standard error), -7. 28 (1. 94); 10 mg/kg, -4. 16 (1. 78); and placebo, 2. 28 (1. 95). Rozanolixizumab 7 mg/kg LSM difference from placebo was -9. 56 (97. 5% confidence interval: -15. 25, -3. 87); 10 mg/kg, -6. 45 (-11. 03, -1. 86). TEAEs were experienced by four (80. 0%), five (62. 5%) and three (37. 5%) patients with MuSK Ab+ gMG receiving rozanolixizumab 7 mg/kg, 10 mg/kg and placebo, respectively. No patients experienced serious TEAEs. No deaths occurred. Conclusion: This subgroup analysis of adult patients with MuSK Ab+ gMG enrolled in the MycarinG study supports the use of rozanolixizumab as an effective treatment option for patients with gMG who have MuSK autoantibodies. Trial registration: ClinicalTrials. gov: NCT03971422 (https://clinicaltrials. gov/study/NCT03971422); EU Clinical Trials Register: EudraCT 2019-000968-18 (https://www. clinicaltrials‌register. eu/ctr-search/trial/2019-000968-18/GB).
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Muscle-specific tyrosine kinase ; Muscle-specific tyrosine kinase autoantibody positive ; Myasthenia gravis ; Rozanolixizumab
Published in:	Therapeutic Advances in Neurological Disorders, Vol. 17 (1-12 2024) , ISSN 1756-2864

DOI: 10.1177/17562864241273036
PMID: 39297052

16 p, 1.1 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles