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

Abstract

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.

TRIAL REGISTRATION:

NCT02059291. https://clinicaltrials.gov.

• Authors: Jerold Jeyaratnam, Anna Simon, Inmaculada Calvo, Tamas Constantin, Anna Shcherbina, Michael Hofer, Marco Gattorno, Alberto Martini, Brigitte Bader-Meunier, Bas Vastert, Jeremy Levy, Elise Dekker, Fabrizio de Benedetti, Joost Frenkel
• Journal: Rheumatology (Oxford, England) (Rheumatology (Oxford)) Vol. 61 Issue 5 Pg. 2088-2094 (05 05 2022) ISSN: 1462-0332 [Electronic] England
• PMID: 34554243 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Serum Amyloid A Protein
• canakinumab

Topics

• Antibodies, Monoclonal (adverse effects)
• Antibodies, Monoclonal, Humanized (adverse effects)
• Double-Blind Method
• Humans
• Mevalonate Kinase Deficiency (drug therapy)
• Serum Amyloid A Protein
• Treatment Outcome