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.
