Long-term efficacy and safety of canakinumab in patients with colchicine-resistant familial Mediterranean fever: results from the randomised phase III CLUSTER trial

Abstract

ObjectivesTo evaluate the long-term efficacy and safety of canakinumab to treat patients with colchicine-resistant familial Mediterranean fever (crFMF) during Epoch 4 (weeks 41 to 113) of the CLUSTER study.MethodsPatients received open-label canakinumab 150 or 300 mg, every 4 or 8 weeks during a 72-week period. We evaluated disease activity every 8 weeks using the physician global assessment (PGA) of disease activity, counting the number of flares, and measuring concentrations of C reactive protein (CRP) and serum amyloid A (SAA). Safety was studied by determination and classification of observed adverse events (AEs). We analysed safety and efficacy separately in two subgroups of patients receiving a cumulative dose of less than 2700 mg, or equal or more than 2700 mg.ResultsOf the 61 patients that started the CLUSTER study, 60 entered Epoch 4 and 57 completed it. During the 72-week period, 35/60 (58.3%) patients experienced no flares, and 23/60 (38.3%) had one flare, as compared with a median of 17.5 flares per year reported at baseline. PGA scores indicated no disease activity for the majority of patients throughout the study. Median CRP concentrations were always lower than 10 mg/L, while median SAA concentrations remained over the limit of normal (10 mg/L) but under the 30 mg/L threshold. No new or unexpected AEs were reported.ConclusioncrFMF patients treated with canakinumab during 72 weeks experienced a minimal incidence of flares and good control of clinical disease activity, with no new safety concerns reported.

IL-1 Inhibitors in the Treatment of Monogenic Periodic Fever Syndromes: From the Past to the Future Perspectives

“…Substantial changes in median creatinine clearance values were not observed during the study and thus, it has not been elucidated whether canakinumab treatment can also prevent amyloidosis and renal complications. No SAEs were reported during the study period and in conclusion, the canakinumab treatment was shown to bear a potential of controlling disease in FMF patients as a long-term therapy ( 46 ).…”

“…A CLUSTER study, a 16-week randomised phase III clinical trial with 72-week open-label period presented by Ozen et al ( 46 ) also measured the long-term treatment responses to canakinumab in colchicine-resistant FMF patients. In this 72-week long study, 61 patients were enrolled.…”

Ergebnisse der systematischen Literatursuche als Grundlage für die „evidenzbasierten Therapieempfehlungen für FMF-Patienten mit unzureichendem Ansprechen bzw. Unverträglichkeit auf Kolchizin“ der Gesellschaft für Kinder- und Jugendrheumatologie und der Deutschen Gesellschaft für Rheumatologie

“…So liegen für den Einsatz von Rilonacept, Anakinra und Canakinumab bei Patienten mit hoher Krankheitsaktivität eines FMF trotz adäquat dosierter Kolchizin-Therapie mittlerweile publizierte Ergebnisse randomisierter kontrollierter Studien vor. Für Canakinumab gibt es auch bereits recht positive 72-Wochen-Daten [ 131 ].…”

Correspondence on ‘Long-term efficacy and safety of canakinumab in patients with colchicine-resistant familial Mediterranean fever: results from the randomised phase III CLUSTER trial’

“…We read with great interest the article "Long-term efficacy and safety of canakinumab in patients with colchicine-resistant familial Mediterranean fever: results from the randomised phase III CLUSTER trial" by Özen et al 1 This article makes a remarkable contribution to treatment in patients with colchicineresistant familial Mediterranean fever (FMF), which shows a great remission rate with minimal side effects. However, there are some aspects that need to be clarified and discussed.…”