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

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, Helen Lachmann, Philip Hawkins, Simon Gibbs, Mark Offer, Jean-Marie Berthelot, Christian Jorgensen, Sylvie Fabre, Eric Hachulla, Sandrine Morell-Dubois, Pierre-Yves Hatron, Pierre Quartier, Richard Mouy, Isabelle Koné-Paut, Sandrine Lacassagne, Isabelle Marie, Tu-Anh Tran, Jasmin Kuemmerle-Deschner, Sandra Hansmann, Joachim Riethmueller, Nicolay Tzaribachev, Richa Chaturvedi, Shalini Srivastava, Sudeep Khanna, Ripunjaya Mohanty, Prasanna Kumar Mishra, Judith Smith, Howard Rowley, Benjamin Brooks, Anna Huttenlocher, Kimberley Smuda, Daniel Stoppenbach, Kieron Leslie, Amy Gilliam, Erin Mathes, Kanade Shinkai, Toby Maurer, Patrick Unemori, 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, Helen Lachmann, Philip Hawkins, Simon Gibbs, Mark Offer, Jean-Marie Berthelot, Christian Jorgensen, Sylvie Fabre, Eric Hachulla, Sandrine Morell-Dubois, Pierre-Yves Hatron, Pierre Quartier, Richard Mouy, Isabelle Koné-Paut, Sandrine Lacassagne, Isabelle Marie, Tu-Anh Tran, Jasmin Kuemmerle-Deschner, Sandra Hansmann, Joachim Riethmueller, Nicolay Tzaribachev, Richa Chaturvedi, Shalini Srivastava, Sudeep Khanna, Ripunjaya Mohanty, Prasanna Kumar Mishra, Judith Smith, Howard Rowley, Benjamin Brooks, Anna Huttenlocher, Kimberley Smuda, Daniel Stoppenbach, Kieron Leslie, Amy Gilliam, Erin Mathes, Kanade Shinkai, Toby Maurer, Patrick Unemori

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.

Figures

Figure 1
Figure 1
Physicians' (a) and patients' (b) assessmentsa of disease activity and individual symptoms over the study. aGlobal disease activity and symptoms were assessed by using a 5-point scale. *n = 33 for end of part 1.
Figure 2
Figure 2
Interleukin (IL)-6 (a) and serum amyloid A (SAA) levels (b) over the course of the study by treatment group.a Data are presented as median (interquartile range) *1 week after the start of part 1. Upper limit of normal range for SAA was 10 mg/L.
Figure 3
Figure 3
SF-36a domain scores at baseline and at the ends of part 1 and 3 in adults. aData are presented as the mean.

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