To describe the efficacy, safety, and exposure-response relationship of canakinumab in a subgroup of patients with systemic juvenile idiopathic arthritis (SJIA) aged ≥16 years, representative of ...adult-onset Still's disease (AOSD) patients, and to compare this subgroup with those of children and young adolescents with SJIA by pooling clinical data collected during the development programme of canakinumab.
Safety and efficacy data on canakinumab-treated patients were pooled from 4 SJIA studies (NCT00426218, NCT00886769, NCT00889863, and NCT00891046). In the majority of patients, canakinumab was administered at 4 mg/kg every 4 weeks. Efficacy parameters (adapted American College of Rheumatology aACR paediatric and juvenile idiopathic arthritis JIA ACR responses), quality of life, C-reactive protein levels, safety, and exposure-response relationship were assessed over 12 weeks in 3 age groups (children 2-<12, young adolescents 12-<16 and older adolescents and young adults ≥16 years).
Efficacy outcomes were analysed in 216 children, 56 young adolescents and 29 older adolescents and young adults. Efficacy parameters across 3 age groups were largely comparable. At Day 15, at least 50% of patients from each age group exhibited aACR ≥70 and ACR responses. The safety profile of canakinumab was similar across age groups. One death was reported.
Pooled analyses from SJIA studies indicate that older adolescents and young adults SJIA patients show similar efficacy, safety, and exposure-response relationship on a weight-based dosing regimen as observed in children and adolescent SJIA patients. These analyses suggest that canakinumab may be an effective therapy in young adults with Still's disease.
To assess the long-term safety and efficacy of canakinumab in Japanese patients with cryopyrin-associated periodic syndrome (CAPS).
In this open-label phase 3 study, Japanese patients aged ≥2 years ...with CAPS received canakinumab 2-8 mg/kg subcutaneously every 8 weeks. The duration of the core treatment phase was 24 weeks followed by 22 months extension phase. The primary objective was the proportion of patients free of clinical and serologic relapse at week 24.
The study enrolled 19 Japanese patients (median age, 14 years; range, 2-48 years) with CAPS MWS, 7 (36.8%); NOMID, 12 (63.2%) for a median of 109 weeks. Fifteen patients (79%) achieved a complete response by day 15, 18 (94.7%) by week 24 and all by week 48. At the end of the study, 18 (95%) were free from relapse and 11 (57.9%) were assessed as having no disease activity by the PGA. Thirteen (68%) patients (MWS, 4; NOMID, 9) had their canakinumab dose increased during the trial. All patients experienced at least one adverse event (AE), the most common being infections (100%) and 5 (26.3%) reported serious AEs. No deaths were reported and the only patient who discontinued the study early withdrew consent.
Regular canakinumab treatment every 8 weeks at dose levels from 2-8 mg/kg, based on the clinical need, represents a successful strategy to induce rapid and complete response while maintain long-term disease control in Japanese patients with CAPS. The safety profile of canakinumab was consistent with that observed from previous studies.
Cryopyrin-associated periodic syndrome (CAPS), a rare hereditary auto-inflammatory disease, is associated with mutations in the NLRP3 gene resulting in elevated interleukin-1β (IL-1 β) release. CAPS ...generally occurs in early childhood with most patients presenting with periodic fever, skin rash, osteoarthropathy, aseptic meningitis, sensorineural hearing loss and optic neuritis. Canakinumab, a fully human anti-IL-1β monoclonal antibody which binds selectively to IL-1β, has demonstrated good efficacy with CAPS. This is the first study to evaluate the safety and efficacy of canakinumab in Japanese patients with CAPS.
In this open-label study, 19 Japanese CAPS patients aged ≥2 years received canakinumab either 150 mg s.c. or 2 mg/kg for patients with a body weight ≤ 40 kg every 8 weeks for 24 weeks. The primary objective was to assess the proportion of patients who were free of relapse at week 24.
A complete response was achieved in 18 (94.7%) patients with some requiring a dose and/or a frequency adjustment to attain full clinical response. The majority of patients (14/18; 77.8%) were in remission, i.e. free of relapse at week 24. Auto-inflammatory disease activity as assessed by physician's global assessment declined from baseline to end of the study (score of absent in 10.5% at baseline versus 31.6% at end of the study). Two patients had serious adverse events (SAEs), which resolved with standard treatment. One patient reported a mild injection-site reaction. No malignancies or deaths were reported during the study.
Canakinumab 150 mg s.c. every 8 weeks was well-tolerated, highly efficacious and offered a convenient dosing regimen for treating Japanese patients with CAPS.
To assess the effect of canakinumab, a fully human anti-interleukin-1β antibody, on symptoms and health-related quality of life (HRQoL) in patients with cryopyrin-associated periodic syndrome (CAPS).
...In this 48-week, phase 3 study, patients with CAPS received canakinumab 150 mg subcutaneously at 8-week intervals. All patients (n = 35) received canakinumab during weeks 1 through 8; weeks 9 through 24 constituted a double-blind placebo-controlled withdrawal phase, and weeks 24 through 48 constituted an open-label phase in which all patients received canakinumab. Patient and physician assessments of symptoms, levels of inflammatory markers, and HRQoL were performed.
Rapid symptom remission was achieved, with 89% of patients having no or minimal disease activity on day 8. Responses were sustained in patients receiving 8-weekly canakinumab. Responses were lost during the placebo-controlled phase in the placebo group and were regained on resuming canakinumab therapy in the open-label phase. Clinical responses were accompanied by decreases in serum levels of C-reactive protein, serum amyloid A protein, and interleukin-6. HRQoL scores at baseline were considerably below those of the general population. Improvements in all 36-item Short-Form Health Survey (SF-36) domain scores were evident by day 8. Scores approached or exceeded those of the general U.S. population by week 8 and remained stable during canakinumab therapy. Improvements in bodily pain and role-physical were particularly marked, increasing by more than 25 points from baseline to week 8. Therapy was generally well tolerated.
Canakinumab, 150 mg, 8-weekly, induced rapid and sustained remission of symptoms in patients with CAPS, accompanied by substantial improvements in HRQoL.
Clintrials.gov NCT00465985.
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