ATLANTA – Canakinumab was safe, well tolerated, and highly effective in the long-term treatment of cryopyrin-associated periodic syndromes in pediatric patients in an open-label phase III extension study.
Treatment of cryopyrin-associated periodic syndromes (CAPS) in 47 patients, aged 3-17 years, who were enrolled in the study was associated with a rapid and sustained clinical and biochemical remission across varying disease severity phenotypes.
Five of the children had familial cold auto-inflammatory syndrome (FCAS), 23 had Muckle-Wells syndrome (MWS), and 18 had chronic infantile neurologic, cutaneous, and articular syndrome/neonatal-onset multisystem inflammatory disease (CINCA/NOMID). One patient was found to not have a CAPS disease phenotype, reported Dr. Jasmin B. Kuemmerle-Deschner at the annual meeting of the American College of Rheumatology.
Of the 47 patients, 38 had not previously been treated with the human interleukin-1 beta monoclonal antibody, and 9 were "rolled over" from earlier phase II or III studies. Of the 38 canakinumab-naive patients, 68% achieved a complete response based on physician global assessment of disease activity and skin assessment, plus normalization of C-reactive protein (CRP) and lowering of serum amyloid A (SAA) to less than 10 mg/L for both measures. More than 80% of the canakinumab-naive patients were relapse-free after a median of 290 days of exposure to treatment, and normal CRP and SAA levels were also maintained throughout the study period in the rollover patients, said Dr. Kuemmerle-Deschner, a pediatric rheumatologist at Universitaetsklinikum Tuebingen (Germany).
The response in the treatment-naive patients was rapid, with levels of CRP and SAA decreasing within 7 days from 14.8 to 2.5 mg/L, and from 40.6 to 7.4 mg/L, respectively, she noted.
Also of note was that 8 of the 11 patients who had an incomplete response within 7 days developed a complete response by 14 days, and the remaining patients – all of whom had the most severe disease phenotype (CINCA/NOMID) – had a partial response, she said.
All patients were treated with 150 mg (or 2 mg/kg for those weighing 40 kg or less) of subcutaneous canakinumab once every 8 weeks. Patients who did not have a complete response were allowed dose adjustments, including an additional dose of 300 mg or 4 mg/kg for those weighing 40 kg or less, or more frequent dosing. Dose adjustments were required in 17 patients, including all of the patients with NOMID; those patients required mean doses of 5.8 mg/kg, compared with 5.5 mg/kg in the MWS patients, and 2.7 mg/kg in the FCAS patients.
Adverse events were generally mild or moderate and transient, and they included abdominal pain, pyrexia, headache, nasopharyngitis, and rhinitis.
"It was remarkable that 92% of patients had no injections-site reaction, and only 8% patients reported mild reaction," Dr. Kuemmerle-Deschner said.
Serious adverse events occurred in six patients, and included nephrotic syndrome, bronchitis, pneumonia, and appendicitis, which occurred in one patient each, and tonsillitis, which occurred in two patients. Only one patient withdrew from the study because of an adverse event.
The findings of this study show that canakinumab, for which earlier phase II and III studies demonstrated high efficacy for treating CAPS, also has long-term safety, tolerability, and efficacy, Dr. Kuemmerle-Deschner said.
"Canakinumab led to rapid and sustained response in the majority of patients," she said, noting that importantly, children with severe CAPS phenotypes required dose adjustment and higher overall doses to sustain remission.
Dr. Kuemmerle-Deschner disclosed that she has received research grants and consulting fees from Novartis Pharmaceuticals, the maker of canakinumab (Ilaris).