Sustained remission of symptoms and improved health-related quality of life in patients with cryopyrin-associated periodic syndrome treated with canakinumab: results of a double-blind placebo-controlled randomized withdrawal study.

Abstract

INTRODUCTION:

To assess the effect of canakinumab, a fully human anti-interleukin-1β antibody, on symptoms and health-related quality of life (HRQoL) in patients with cryopyrin-associated periodic syndrome (CAPS).

METHODS:

In this 48-week, phase 3 study, patients with CAPS received canakinumab 150 mg subcutaneously at 8-week intervals. All patients (n = 35) received canakinumab during weeks 1 through 8; weeks 9 through 24 constituted a double-blind placebo-controlled withdrawal phase, and weeks 24 through 48 constituted an open-label phase in which all patients received canakinumab. Patient and physician assessments of symptoms, levels of inflammatory markers, and HRQoL were performed.

RESULTS:

Rapid symptom remission was achieved, with 89% of patients having no or minimal disease activity on day 8. Responses were sustained in patients receiving 8-weekly canakinumab. Responses were lost during the placebo-controlled phase in the placebo group and were regained on resuming canakinumab therapy in the open-label phase. Clinical responses were accompanied by decreases in serum levels of C-reactive protein, serum amyloid A protein, and interleukin-6. HRQoL scores at baseline were considerably below those of the general population. Improvements in all 36-item Short-Form Health Survey (SF-36) domain scores were evident by day 8. Scores approached or exceeded those of the general U.S. population by week 8 and remained stable during canakinumab therapy. Improvements in bodily pain and role-physical were particularly marked, increasing by more than 25 points from baseline to week 8. Therapy was generally well tolerated.

CONCLUSIONS:

Canakinumab, 150 mg, 8-weekly, induced rapid and sustained remission of symptoms in patients with CAPS, accompanied by substantial improvements in HRQoL.

TRIAL REGISTRATION:

Clintrials.gov NCT00465985.

• Authors: Isabelle Koné-Paut, Helen J Lachmann, Jasmin B Kuemmerle-Deschner, Eric Hachulla, Kieron S Leslie, Richard Mouy, Alberto Ferreira, Karine Lheritier, Neha Patel, Ralph Preiss, Philip N Hawkins, Canakinumab in CAPS Study Group
• Journal: Arthritis research & therapy (Arthritis Res Ther) Vol. 13 Issue 6 Pg. R202 ( 2011) ISSN: 1478-6362 [Electronic] England
• PMID: 22152723 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Interleukin-1beta
• Interleukin-6
• Serum Amyloid A Protein
• canakinumab
• C-Reactive Protein

Topics

• Adolescent
• Adult
• Aged
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized
• C-Reactive Protein (metabolism)
• Child
• Child, Preschool
• Cryopyrin-Associated Periodic Syndromes (blood, drug therapy, pathology)
• Double-Blind Method
• Drug Administration Schedule
• Female
• Health Status
• Humans
• Interleukin-1beta (antagonists & inhibitors)
• Interleukin-6 (blood)
• Male
• Middle Aged
• Quality of Life
• Remission Induction
• Serum Amyloid A Protein (metabolism)
• Surveys and Questionnaires
• Treatment Outcome
• Young Adult