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 (MKD) during the open label extension (weeks 41-113) of the randomised 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 (PGA) and counting the number of flares. Concentrations of C reactive protein (CRP) and serum amyloid A (SAA) 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 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 PGA 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 SAA 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 MKD during the 72-week study period. No new safety concerns were reported. Clinical trial registration number NCT02059291.