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Key efficacy data for ILARIS in the treatment of adult-onset Still’s disease (AOSD) and systemic juvenile idiopathic arthritis (SJIA).
Over two-thirds of AOSD patients receiving ILARIS demonstrated an improvement from baseline in disease activity at Week 12 vs less than half receiving placebo (p=0.18)*1
The primary endpoint was the proportion of patients who demonstrated an improvement from baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28-ESR) of >1.2 at Week 12.1
Please note, statistical significance was not met.
Adapted from Kedor C, et al. 2020.1
Study design: Kedor C, et al. 20201
The phase II Canakinumab for Treatment of Adult-Onset Still’s Disease to Achieve Reduction of Arthritic Manifestation (CONSIDER) study was performed as a multicentre, double-blind, randomised, placebo-controlled trial in patients with AOSD and active joint involvement (tender and swollen joint counts of ≥4 each). AOSD patients were treated with canakinumab (4 mg/kg, maximum 300 mg subcutaneous every 4 weeks, n=18) or placebo (n=17) (1:1 ratio). The primary endpoint was the proportion of patients with a clinically relevant reduction in disease activity at week 12 as determined by the change in disease activity score (ΔDAS28>1.2).
*Patients with AOSD and active joint involvement (tender and swollen joint counts of ≥4 each) were treated with canakinumab (4 mg/kg, maximum 300 mg subcutaneous every 4 weeks) or placebo.1
ILARIS can help patients with SJIA achieve fast and lasting disease control2–4
By Day 15, >8 out of 10 SJIA patients receiving ILARIS achieved an aACR30 response† (vs 10% placebo)‡3,4
A third of SIJA patients receiving ILARIS achieved an aACR100 with just one dose by Day 15 (vs 0% placebo)‡3,4
Adapted from Ruperto N et al. 2012 (Trial 1).3
Over half of SJIA patients receiving ILARIS achieved an aACR90 response after 32 weeks of open-label treatment§¶3
Adapted from Ruperto N et al. 2012 (Trial 1).3
Lasting relief was maintained for up to 3 years in the LTE study‖2
Adapted from Ruperto N et al. 2016 (Trial 1).2
Ruperto N, et al. 20123
Randomised, double-blind, placebo-controlled, 4-week study assessing the short-term efficacy of canakinumab in 84 patients randomised to receive a single dose of 4 mg/kg (up to 300 mg) canakinumab (n=43) or placebo (n=41). The primary objective was the proportion of patients who achieved a minimum 30% improvement in the paediatric American College of Rheumatology (ACR) response criterion adapted to include absence of fever. Canakinumab treatment improved all paediatric ACR response scores as compared to placebo at days 15 and 29.
Ruperto N, et al. 20162
This study reported the long-term efficacy and safety of canakinumab in patients with SJIA with active systemic features and arthritis at baseline, who were enrolled from the previously reported pivotal phase III studies, and followed for up to 5 years. In trial 1 of 1-month duration, a single canakinumab dose or placebo was administered. Patients from trial 1 could enter the two-part trial 2 where canakinumab-naïve patients and patients from a Phase II trial were additionally enrolled. Trial 2 was a randomised withdrawal study, with an open-label lead in part I up to 32 weeks.
*Treatment difference for all ACR scores was significant (p≤0.0001).4
†In the Phase I/II study, treatment with canakinumab has a rapid onset of action, with disappearance or clinically significant improvement of symptoms within one day of dosing.3aACR response: Percentage improvement (at least 30%, 50%, 70%, 90%, 100%) in at least 3 of the 6 response variables and worsening of >30% in no more than 1 of the 6 variables, including absence of fever. The disease activity components include C-reactive protein (CRP) level, number of joints with active arthritis, number of joints with limited range of motion, physician’s global assessment of disease activity, parent’s global assessment of patient’s overall well-being, and functional ability (Childhood Health Assessment Questionnaire–Disability Index [CHAQ-DI]).3
‡SJIA patients aged 2–19 were randomised to receive a single dose of either ILARIS (4 mg/kg up to 300 mg) or placebo and followed for 29 days before enrolment to a subsequent trial.3
§In trial 2, graph shows the rates of aJIA-ACR responses at the end of the 32-week, open-label phase which included data from the last observation of patients who had had a response.3
¶The primary objective was to determine whether at least 25% of the patients who were being treated with glucocorticoids could have their dose tapered. Trial 2 of this study enrolled SJIA patients aged 2–19 to receive open-label ILARIS (4 mg/kg up to 300 mg) every 4 weeks for 12–32 weeks.3
‖Primary analysis included intent-to-treat population from trial 2 based on observed data with all discontinuations at different timepoints counted as missing and with missing data imputed using last observation carried forward. 5-year LTE study of the 2 pivotal Phase III trials to evaluate the long-term efficacy and safety of ILARIS in SJIA patients. 144 of the 177 patients (81%) enrolled in the core studies entered the LTE. 58% discontinued, with higher discontinuation rates in late responders (81%) vs early responders (29%). No new safety findings were observed.2
Indications4
Periodic fever syndromes
ILARIS is indicated for the treatment of the following autoinflammatory periodic fever syndromes in adults, adolescents and children aged 2 years and older:
- CAPS, including:
- Muckle-Wells syndrome (MWS)
- Neonatal-onset multisystem inflammatory disease (NOMID)/chronic infantile neurological, cutaneous, articular syndrome (CINCA)
- Severe forms of familial cold autoinflammatory syndrome (FCAS)/familial cold urticaria (FCU) presenting with signs and symptoms beyond cold-induced urticarial skin rash
- TRAPS
- HIDS/MKD
- FMF
- ILARIS should be given in combination with colchicine, if appropriate.
Still’s disease
ILARIS is indicated for the treatment of active Still’s disease including adult-onset Still’s disease (AOSD) and systemic juvenile idiopathic arthritis (SJIA) in patients aged 2 years and older who have responded inadequately to previous therapy with non-steroidal anti-inflammatory drugs (NSAIDs) and systemic corticosteroids. ILARIS can be given as monotherapy or in combination with methotrexate.
aACR response, adapted American College of Rheumatology response; ACR, American College of Rheumatology; aJIA-ACR response, adapted juvenile idiopathic arthritis American College of Rheumatology response; AOSD, adult-onset Still’s disease; bDMARD, biologic disease-modifying antirheumatic drug; CAPS, cryopyrin-associated periodic syndromes; CHAQ-DI, Childhood Health Assessment Questionnaire–Disability Index; CINCA, chronic infantile neurological, cutaneous, articular syndrome; CRP, C-reactive protein; DAS28-ESR, disease activity score 28-joint count with ESR; ESR, erythrocyte sedimentation rate; FCAS, familial cold autoinflammatory syndrome; FCU, familial cold urticaria; FMF, familial Mediterranean fever; HIDS, hyperimmunoglobulin D syndrome; LTE, long-term extension; MKD, mevalonate kinase deficiency; MWS, Muckle-Wells syndrome; NOMID, neonatal-onset multisystem inflammatory disease; NSAID, non-steroidal anti-inflammatory drug; RITA, Rare Immunodeficiency, Autoinflammatory and Autoimmune Disease Network; SJIA, systemic juvenile idiopathic arthritis; TRAPS, tumour necrosis factor receptor-associated periodic syndrome.
References
- Kedor C, et al. Ann Rheum Dis 2020;79(8):1090–1097.
- Ruperto N, et al. Ann Rheum Dis 2016;75:265–266.
- Ruperto N, et al. N Engl J Med 2012;367(25):2396–2406.
- ILARIS® (canakinumab) Summary of Product Characteristics.
