Τίτλος:
Trial of canakinumab, an IL-1β receptor antagonist, in patients with inclusion body myositis
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
ObjectiveTo assess whether canakinumab, a monoclonal antibody against IL-1β approved for autoinflammatory diseases, is effective as target-specific therapy in patients with sporadic inclusion body myositis (sIBM).MethodsBecause in sIBM IL-1β colocalizes with amyloid precursor protein and upregulates amyloid aggregates enhancing degeneration, targeting IL-1β with canakinumab may arrest disease progression. On this basis, 5 ambulatory patients with sIBM participated in an institutional review board-approved open-labeled study with 150 mg canakinumab [4 bimonthly, then monthly subcutaneous injections] for a mean period of 15.8 months. Patients were assessed bimonthly with a manual dynamometer in 12 proximal and distal muscles and with grip force (GF) in both hands. Total muscle strength (TMS) was expressed in kilograms. Efficacy was defined as >15% increased strength after 12 months.ResultsPatient 1 stopped at month 5 because of 23% loss in TMS and 32.35% in GF; patient 2 showed 37.1% increase in TMS and 13% in GF by month 9; patient 3 exhibited 26.7% reduction in TMS and 10% in GF at month 33; patient 4 showed 6.5% reduction in TMS and 1.6% in GF after 15 months, denoting relative stability; and patient 5 showed 30.4% loss in TMS and 20.8% in GF after 18 months. In patients 2 and 4, in whom 3-year longitudinal data were available, no effect on disease progression was noted.ConclusionsIn this long-term, open-label study, canakinumab showed small, but not clinically appreciable, stabilizing benefits in 2 of 5 patients with sIBM over 1 year, was ineffective in 2 others, and might have worsened one. No patient improved.Classification of evidenceThis study provides Class IV evidence that canakinumab was ineffective for patients with sIBM. © 2019 American Academy of Neurology.
Συγγραφείς:
Kosmidis, M.L.
Pikazis, D.
Vlachoyiannopoulos, P.
Tzioufas, A.G.
Dalakas, M.C.
Περιοδικό:
Neurology® Neuroimmunology and Neuroinflammation
Εκδότης:
Lippincott Williams and Wilkins
Λέξεις-κλειδιά:
amyloid precursor protein; canakinumab; interleukin 1beta; canakinumab; IL1B protein, human; interleukin 1beta; monoclonal antibody, adult; aged; ambulatory care; Article; clinical article; disease exacerbation; drug approval; drug efficacy; female; human; inclusion body myositis; male; middle aged; muscle strength; open study; priority journal; protein aggregation; sporadic inclusion body myositis; sporadic inclusion body myositis; case report; drug effect; hand strength; inclusion body myositis; subcutaneous drug administration; treatment outcome; very elderly, Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Disease Progression; Female; Hand Strength; Humans; Injections, Subcutaneous; Interleukin-1beta; Male; Middle Aged; Muscle Strength; Myositis, Inclusion Body; Treatment Outcome
DOI:
10.1212/NXI.0000000000000581
