A pilot trial of Canakinumab (Ilaris), an IL-1β Receptor antagonist, in the treatment of patients with sporadic Inclusion Body Myositis (sIBM) (P3.444)

Objective: Study the effect of Canakinumab in sIBM. Background: In sIBM inflammatory mediators may chronically enhance degeneration. Because IL-1β co-localizes with Amyloid Precursor Protein and upregulates in-vitro amyloid aggregates, targeting IL-1β may arrest disease progression. Anakinra, an IL-1-Receptor antagonist, was ineffective (Kosmidis et al, 2013); Canakinumab, a monoclonal antibody against IL-1β, approved for some autoinflammatory diseases, is more target-specifc. Design/Methods: Five ambulatory sIBM patients, age 45–80 (mean 63,4), and disease duration 5–29 (mean 16) years, participated after signing informed consent, in an open-labelled study with 150 mg Canakinumab [4 bimonthly, then monthly, subcutaneous injections] for 6–18 (mean 11.4) months. Patients were examined bimonthly with manual dynamometer (QMT) in 12 proximal and distal muscles and with Grip-Force (GF). Efficacy was defined as >15% increased strength over one year. Effect on disease progression was tested in two patients with available QMT data from the Anakinra study. Results: Patient 1 showed 37.1% increase QMT and 13% GF by month 9; patient 2 showed 6.5% reduction in QMT and 1.6% GF after 15 months, denoting stability; patient 3 dropped-out at month 6 because of 23% loss in QMT and 32.35 % GF with worsening respiratory and bulbar functions; patient 4 dropped-out at month 10 because of continuing worsening, evidenced by 18% reduction in QMT and 20% GF; patient 5 showed 30.4% loss in QMT and 20.8% GF after 18 months. No effect on disease progression was noted in those patients with prior QMT data. Conclusions: In this open-label study, Canakinumab showed small benefits in 2 of 5 sIBM patients over one-year, but was ineffective in 2 others and worsened one. The results suggest that Canakinumab may benefit a small patient subset, highlighting the heterogeneous nature of sIBM. A controlled trial testing different doses and frequency of administration may be warranted. Disclosure: Dr. KOSMIDIS has nothing to disclose. Dr. PIKAZIS has nothing to disclose. Dr. Vlachoyiannopoulos has nothing to disclose. Dr. Tzioufas has nothing to disclose. Dr. Dalakas has nothing to disclose.