New biologic: Rilonacept (Arcalyst), a regeneron Interleukin-1 blocker was recently approved for the treatment of cryopyrin-associated periodic syndromes (CAPS).
Interleukin-1 blocker approved for the treatment of cryopyrin-associated periodic syndromes (CAPS)
Efficacy. The efficacy of rilonacept was evaluated in a 2-part randomized, double-blind, placebo-controlled trial. In Part A, patients received a 320-mg loading dose of rilonacept followed by rilonacept 160 mg/wk or placebo for 6 weeks. In Part B, all patients received rilonacept 160 mg/wk for 9 weeks and were then randomized to either rilonacept 160 mg/wk or placebo for an additional 9 weeks. The trial also included a 24-week, open-label treatment extension phase; enrolled patients received rilonacept 160 mg/wk. For both parts of the study, patients completed a daily questionnaire to rate the severity (0, none; to 10, very severe) of CAPS-related symptoms. Researchers evaluated the mean symptom score change from baseline to the completion of treatment. The mean change from baseline to end point among rilonacept recipients in Part A of the trial was –2.4 versus a –0.5 reduction among patients who received placebo. The mean change among patients who received rilonacept in Part B of the trial was +0.1 versus a +0.9 difference among patients who received placebo. Most patients indicated improvement in symptom scores within several days of initiating rilonacept therapy. Patients' C-reactive protein (CRP) and serum amyloid A (SAA) levels were assessed in Part A of the trial. Rilonacept was associated with a 20-mg/L reduction from baseline in mean CRP level versus a 2-mg/L reduction with placebo. Mean SAA levels were reduced by 56 mg/L among patients treated with rilonacept versus no change among those who received placebo. Reductions in mean symptom scores, serum CRP, and serum SAA levels were maintained for ≤1 year among patients who received rilonacept in the extension phase.
Safety. The blocking of IL-1 can interfere with immune response to infections. Some patients receiving rilonacept have experienced serious, life-threatening infections. Patients with active or chronic infections should not be treated with rilonacept. Patients should receive all recommended vaccinations before initiating rilonacept treatment; live vaccines should not be administered concurrently with rilonacept. The most common adverse events associated with rilonacept include injection-site reactions, respiratory tract infections, sinusitis, cough, and hypoesthesia.
Dosing. The recommended dose of rilonacept for patients aged ≥18 years is a 320-mg loading dose (delivered as two 2-mL subcutaneous [SC] injections of 160 mg on the same day, administered in different injection sites), followed by 160 mg/wk administered as a single 2-mL SC injection. The recommended dose of rilonacept for patients aged 12 to 17 years is a 4.4-mg/kg loading dose (maximum, 320 mg), delivered as 1 or 2 SC injections (maximum single-injection volume, 2 mL). Pediatric patients should then be treated with 2.2 mg/kg/wk delivered as a single SC injection (up to 2 mL).