Efficacy and safety of rilonacept (interleukin‐1 trap) in patients with cryopyrin‐associated periodic syndromes: Results from two sequential placebo‐controlled studies

Abstract

Objective. To assess the efficacy and safety of rilonacept (Interleukin-1 [IL-1] Trap), a long-acting and potent inhibitor of IL-1, in patients with cryopyrinassociated periodic syndromes (CAPS), including familial cold autoinflammatory syndrome (FCAS) and Muckle-Wells syndrome (MWS).Methods. Forty-seven adult patients with CAPS, as defined by mutations in the causative NLRP3 (CIAS1) gene and pathognomonic symptoms, were enrolled in 2 consecutive phase III studies. Study 1 involved a 6-week randomized double-blind comparison of weekly subcutaneous injections of rilonacept (160 mg) versus placebo. Study 2 consisted of 9 weeks of single-blind treatment with rilonacept (part A), followed by a 9-week, randomized, double-blind, placebo-controlled withdrawal procedure (part B). Primary efficacy was evaluated using a validated composite key symptom score.Results. Forty-four patients completed both studies. In study 1, rilonacept therapy reduced the group mean composite symptom score by 84%, compared with 13% with placebo therapy (primary end point; P < 0.0001 versus placebo). Rilonacept also significantly improved all other efficacy end points in study 1 (numbers of multisymptom and single-symptom disease flare days, single-symptom scores, physician's and patient's global assessments of disease activity, limitations in daily activities, and C-reactive protein and serum amyloid A [SAA] levels). In study 2 part B, rilonacept was superior to placebo for maintaining the improvements seen with rilonacept therapy, as shown by all efficacy parameters (primary end point; P < 0.0001 versus placebo). Rilonacept was generally well tolerated; the most common adverse events were injection site reactions.Conclusion. Treatment with weekly rilonacept provided marked and lasting improvement in the clinical signs and symptoms of CAPS, and normalized the levels of SAA from those associated with risk of developing amyloidosis. Rilonacept exhibited a generally favorable safety and tolerability profile.Cryopyrin-associated periodic syndromes (CAPS) are a group of inherited inflammatory disorClinicalTrials.gov identifier: NCT00288704.

Acquired cold urticaria: Clinical features, particular phenotypes, and disease course in a tertiary care center cohort

“…4,17,18 Importantly, the presence of other family members with similar symptoms should always be ruled out in patients with ACU, because specific treatments (eg, antieinterleukin-1) have demonstrated effectiveness in the management of familial cold-induced urticaria syndromes. [19][20][21] Moreover, regardless of the prescribed treatment, self-limited evolution can be seen in some patients with ACU. In the present study, almost 26% of the patients experienced complete symptom resolution (and therefore no need for treatment) during the surveillance period, with a mean disease duration until resolution of 5.1 years.…”

Advances in the pathogenesis and treatment of systemic juvenile idiopathic arthritis

“…In this study, rilonacept significantly reduced symptom scores, CRP and serum amyloid A levels, and the physician and patient global assessment of disease compared with placebo. Rilonacept was well tolerated, with the most common adverse effect being injection site reactions (58). A more recent, small, placebo-controlled study also found rilonacept promising in the treatment of Familial Mediterranean Fever, another genetic autoinflammatory syndrome in which IL-1 is an important mediator of disease (59).…”

The Inflammasomes in Kidney Disease

“…50,51 DISEASE ENTITIES INVOLVING THE INFLAMMASOME-CASPASE-1-IL-1〉/IL-18 AXIS Several human autoinflammatory syndromes are directly related to variations in inflammasome or IL-1-related genes ( Table 2). The cryopyrin-associated periodic syndromes encompass MuckleWells syndrome, familial cold autoinflammatory syndrome, and chronic infantile neurologic cutaneous and ar- [52][53][54] The deficiency of IL-1 receptor (IL-1R) antagonist syndrome is also associated with increased circulating IL-1␤ levels. 55 Although none of these diseases is known to directly affect the kidney, a role for NLRP3 or IL-1 signaling in renal pathology cannot be excluded.…”