Ilaris (Canakinumab) in the Schnitzler Syndrome

Summary

Schnitzler syndrome:

Schnitzler syndrome is a rare disabling autoinflammatory syndrome characterized by a chronic urticarial rash and monoclonal gammopathy, accompanied by intermittent fever, arthralgia or arthritis or bone pain. Diagnostic criteria have been established. The disease never remits spontaneously. Although there is no standard of care, there have been promising developments in therapeutic options, especially anti-interleukin-1 therapy. Anakinra, a synthetic analogue of the endogenous interleukin-1 receptor antagonist, has caused rapid clinical remission in 24 patients with Schnitzler syndrome. However, to sustain remission, continuous daily administration (100 mg sc) is required. The level of monoclonal protein does not decrease. Side effects of anakinra include painful injection site reactions and neutropenia.

Interleukin-1 and the autoinflammatory diseases:

As a key proinflammatory cytokine mediating local and systemic responses to infection and tissue injury, interleukin-1 can induce a range of responses, including fever, pain sensitization, bone and cartilage destruction, and the acute-phase inflammatory response. The so-called autoinflammatory diseases are mediated entirely by interleukin-1; reducing interleukin-1 activity brings about a rapid and sustained remission. Autoinflammatory diseases include relatively uncommon disorders such as familial Mediterranean fever, adult and juvenile Still's disease, the hyper-IG D syndrome, Behçet's syndrome, the cryoporin-associated periodic syndrome (CAPS), deficiency of the interleukin-1 receptor antagonist (DIRA) and Schnitzler's syndrome. Some common conditions such as gout and type 2 diabetes, are also likely to be autoinflammatory diseases.

Canakinumab:

Canakinumab (Ilaris, Novartis Pharma) is a fully human anti-interleukin-1-bèta monoclonal antibody. Treatment with subcutaneous canakinumab (150 mg) once every 8 weeks was associated with a rapid remission of symptoms in the great majority of children and adults with CAPS. Serum inflammatory markers quickly returned to normal. In general, the side effects seen in this small study (35 patients) were not serious, though suspected infections ware significantly more prevalent in patients receiving canakinumab than in those receiving placebo. The prolonged duration of action of canakinumab and low incidence of injection-site reactions may confer certain advantages over other interleukin-1 inhibitors (anakinra and rilonacept), since both are frequently associated with injection-site reactions, and both require more frequent administration (daily for anakinra and weekly for rilonacept).

Canakinumab was approved for the treatment of CAPS by the US Food and Drug Administration in June 2009 and by the European Medicines Agency in October 2009.

Canakinumab is currently being evaluated for its potential in the treatment of systemic-onset juvenile idiopathic arthritis, diabetes mellitus, and difficult-to-treat gouty arthritis.

Conditions

• Schnitzler Syndrome

Interventions

DRUG

Ilaris

* Canakinumab 150 mg (or 2 mg/kg for patients weighing \<40kg) every 8 weeks over a 6 months treatment period (i.e., weeks 0, 8, 16 and 24). * At Day 7, patients who show an improvement, but not a clinical remission, will be given another 150 mg (or 2 mg/kg for patients weighing \<40 kg) injection and continue at 300 mg (or 4 mg/kg for patients weighing \<40 kg) every 8 weeks beginning at Week 8. * Patients who show no improvement of symptoms and signs of Schnitzler's syndrome will not receive any additional canakinumab dose and will be offered corticosteroid therapy. These patients will return for a follow-up visit 2 weeks later (Day 21) for safety reasons and will be discontinued from the trial. * If a patient flares twice during the study, physician may optionally change the dosing frequency to every 4 weeks.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven

  lead OTHER

Principal Investigators

• Steven Vanderschueren, MD, PhD · General Internal Medicine, UZ Gasthuisberg, Leuven

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-05-31

Primary Completion

2011-08-31

Completion

2012-05-31

Countries

• Belgium

Study Locations