Long-term efficacy and safety of canakinumab in patients with mevalonate kinase deficiency: results from the randomised Phase 3 CLUSTER trial

Objectives. To evaluate the long-term efficacy and safety of canakinumab in patients with mevalonate kinase deficiency during the open label extension (weeks 41-113) of the randomized controlled CLUSTER trial. Methods. During a 72-week period, patients received open-label canakinumab 150 or 300 mg, every 4 or 8 weeks. The disease activity was evaluated every 8 weeks using physician global assessment and counting the number of flares. Concentrations of CRP and serum amyloid A protein were measured. The safety was studied by determination and classification of observed adverse events. The safety and efficacy were analysed separately in three subgroups of patients receiving a cumulative dose of less than <35 mg/kg, >= 35 to <70 mg/kg or >= 70 mg/kg. Results Of the 74 patients who started the CLUSTER study, 66 entered Epoch 4 and 65 completed it. During the 72-week period, 42 (64%) patients experienced no flares, while 13 (20%) had one flare, as compared with a median of 12 flares per year reported at baseline. Low physician global assessment scores were seen at the end of the study for all groups with >90% reporting minimal disease activity or none at all. Median CRP concentrations were consistently equal or lower than 10 mg/l, while median serum amyloid A concentrations remained only slightly above the normal range of 10 mg/l. The study showed no new or unexpected adverse events. Conclusion Canakinumab proved effective to control disease activity and prevent flares in mevalonate kinase deficiency during the 72-week study period. No new safety concerns were reported.

Automated summary

The study evaluated the long-term efficacy and safety of canakinumab in patients with mevalonate kinase deficiency during the open label extension of the CLUSTER trial. Canakinumab effectively controlled disease activity and prevented flares in these patients over a 72-week period. No new safety concerns were reported, and the majority of patients experienced minimal or no disease activity at the end of the study.