Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Rilonacept: Long-Term Safety Profile in Patients with Cryopyrin-Associated Periodic Syndromes (CAPS)
Hoffman1, Hal M., Nadler2, Douglas R., Brooks2, Warren P., Weinstein2, Steven P.
IL1-b inhibition with weekly rilonacept (IL-1 Trap) provided marked, durable improvement in clinical and laboratory signs and symptoms associated with CAPS (Familial Cold Auto-inflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS)) while exhibiting a generally well-tolerated profile during a 24-wk double-blind, placebo-controlled pivotal study and a subsequent single arm, 24-wk, open-label extension (OLE) study. The results described herein report on the safety profile in patients throughout the OLE and subsequent 64-week long term extension (LTE).
Patients enrolled into the consecutive OLE and LTE by either continuing from the pivotal study (44 patients) or entering directly (57 patients). All patients received SC rilonacept 160 mg/week (for a maximum of 112 wks). Safety assessments were performed at baseline and periodically throughout the study, including physical examinations, vital signs, documentation of adverse events (AEs), routine laboratory tests, and assays to detect anti-rilonacept antibodies.
Safety data were available for 104 pts with more than 125 patient exposure years (mean age 43.6 years; 66.3% female). The most common treatment-emergent AEs were injection-site reactions (erythema, swelling, pruritis, bruising), which occurred in 60.6% of patients; these were mild to moderate in severity and did not cause patient withdrawal. The most common treatment-emergent infections were: nasopharyngitis (10.6%), sinusitis (11.5%), upper RTIs (11.5%), UTIs (8.7%) and bronchitis (6.7%) which occurred in 32.7% of patients. None of the serious AEs (sciatica, cholelithiasis, hyponatremia, hypokalemia, pulmonary embolism, GI reflux, renal colic) were considered drug-related. During the OLE/LTE, one patient withdrew due to pregnancy and one due to chronic sinusitis. One death occurred due to pneumococcal meningitis and one to coronary atherosclerosis, respectively; the causes of death were assessed by the treating physician and considered not to be treatment-related. Through Week 56 (up to 80 weeks of rilonacept treatment) small to modest mean reductions in platelet (67K/mm3) counts occurred, but levels were stable throughout and did not fall below reference range. Mean neutrophil counts decreased (-1.9 K/mm3); no patients reported with neutropenia (<1.0 K neutrophils/mm3). Small and expected increases (16.9 mg/dL) in mean total cholesterol occurred. Change in weight and BMI was 2.9kg and 1.0 kg/m2, respectively, at Week 72. Other vital signs were without notable changes. Among the 96 patients who received at least 6 weeks of treatment through Week 72 of the OLE, 39 (40.6%) and 20 (20.8%), respectively, were anti-rilonacept Ab positive or positive at last assessment. Titers were generally low to moderate and had no apparent impact on rilonacept levels.
Rilonacept is generally well tolerated in both the long- and short-term when administered as a weekly SC injection of 160 mg.
To cite this abstract, please use the following information:
Hoffman, Hal M., Nadler, Douglas R., Brooks, Warren P., Weinstein, Steven P.; Rilonacept: Long-Term Safety Profile in Patients with Cryopyrin-Associated Periodic Syndromes (CAPS) [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1237