Key safety profile data for ILARIS in the treatment of adult-onset Still’s disease (AOSD) and systemic juvenile idiopathic arthritis (SJIA).
- This data from the phase II CONSIDER study showed that the overall safety findings were consistent with the known profile of Ilaris1
- The safety analyses were based on all patients randomised who received at least one dose of the study drug1
- Within the first 12-week- period of this trial, two patients experienced an SAE, both of them under treatment with Ilaris (increased liver enzymes and patellofemoral pain syndrome leading to hospitalisation)1
- A further seven SAEs were observed in the second period of the study (between weeks 12 and 24): two in Ilaris-exposed patients (deep vein thrombosis and hypotonia) and the other five in one patient treated with placebo (fracture at MCP 5, hand fracture, removal of a medical device at MCP 5, upper abdominal pain and acute cholecystitis)1
- Due to premature termination of the study, observation time was limited to a maximum of 27 months (reached only by one patient)1
- Primary endpoint of the study (proportion of patients with a clinically relevant reduction of the articular manifestation measure by change in disease activity score) was not met1
- This data provides long-term (up to 5 years) safety on a pooled population from Ilaris’ clinical programme in SJIA3
- Overall, the median duration of exposure (canakinumab and placebo) in was 3.5 years3
- Long-term use of Ilaris was well tolerated and consistent with the safety profile that has been reported in other Ilaris trials3
- Infections were the most common adverse events (AEs)3
- Despite disease control, new macrophage activation syndrome (MAS) events occurred while on Ilaris therapy3
Tabulated list of adverse reactions
CAPS, TRAPS, HIDS/MKD, FMF, SJIA
|Infections and infestations|
|Very common||Respiratory tract infections (including pneumonia, bronchitis, influenza, viral infection, sinusitis, rhinitis, pharyngitis, tonsillitis, nasopharyngitis, upper respiratory tract infection) (see ‘Laboratory anomalies’ below)
Urinary tract infection
|Nervous system disorders|
|Very common||Upper abdominal pain*|
|Skin and subcutaneous tissue disorders|
|Very common||Injection site reaction|
|Musculoskeletal and connective tissue disorders|
|Very common||Creatinine renal clearance decreased*†
Leukopenia (see "Laboratory anomalies" below)
|Common||Neutropenia (see "Laboratory anomalies" below)|
|Uncommon||Platelet count decreased (see "Laboratory anomalies" below)|
Adapted from ILARIS® (canakinumab) Summary of Product Characteristics.2
Canakinumab is contraindicated in active, severe infections. Canakinumab should not be initiated or continued in patients during an active infection requiring medical intervention.
As canakinumab is associated with an increased incidence of serious infections, patients should be monitored carefully for signs and symptoms of infections during and after treatment with canakinumab.
Long-term data and laboratory abnormalities in CAPS patients
During clinical trials with canakinumab in CAPS patients mean values for haemoglobin increased and those for white blood cell, neutrophils and platelets decreased.
Elevations of transaminases have been observed rarely in CAPS patients.
Asymptomatic and mild elevations of serum bilirubin have been observed in CAPS patients treated with canakinumab without concomitant elevations of transaminases.
In the long-term, open-label studies with dose escalation, events of infections (gastroenteritis, respiratory tract infection, upper respiratory tract infection), vomiting and dizziness were more frequently reported in the 600 mg or 8 mg/kg dose group than in other dose groups.
Treatment with canakinumab should not be initiated in patients with neutropenia or leukopenia. For further information, please visit the SmPC.2
Laboratory abnormalities in TRAPS, HIDS/MKD and FMF patients
Neutrophils: Although ≥ Grade 2 reductions in neutrophil count occurred in 6.5% of patients (common) and Grade 1 reductions occurred in 9.5% of patients, the reductions are generally transient and neutropenia-associated infection has not been identified as an adverse reaction.
Although reductions in platelet count (≥ Grade 2) occurred in 0.6% of patients, bleeding has not been identified as an adverse reaction. Mild and transient Grade 1 reduction in platelets occurred in 15.9% of patients without any associated bleeding adverse events.
Laboratory abnormalities in SJIA patients
In the overall SJIA programme, transient decreased white blood cell (WBC) counts ≤ 0.8 x LLN were reported in 33 patients (16.5%). Transient decreases in absolute neutrophil count (ANC) to less than 1 x 109/l were reported in 12 patients (6.0%). Transient decreases in platelet counts (< LLN) were observed in 19 patients (9.5%).
ALT/AST: In the overall SJIA programme, high ALT and/or AST > 3 x upper limit of normal (ULN) were reported in 19 patients (9.5%).
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
- ILARIS should be given in combination with colchicine, if appropriate.
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.
†Based on estimated creatinine clearance, most were transient.
‡Most represented transient trace to 1+ positive urinary protein by dipstick.
AE, adverse event; ANC, absolute neutrophil count; AOSD, adult-onset Still’s disease; CAPS, cryopyrin-associated periodic syndromes; CINCA, chronic infantile neurological, cutaneous, articular syndrome; FCAS, familial cold autoinflammatory syndrome; FCU, familial cold urticaria; FMF, familial Mediterranean fever; HIDS, hyperimmunoglobulin D syndrome; LLN, lower limit normal; MAS, macrophage activation syndrome; MedDRA PT, Medical Dictionary for Regulatory Activities preferred term; MKD, mevalonate kinase deficiency; MWS, Muckle-Wells syndrome; NOMID, neonatal-onset multisystem inflammatory disease; NSAID, non-steroidal anti-inflammatory drug; SJIA, systemic juvenile idiopathic arthritis; TRAPS, tumour necrosis factor receptor-associated periodic syndrome; WBC, white blood cell count.
- Kedor C, et al. Ann Rheum Dis 2020;79(8):1090–1097 and supplementary appendix.
- ILARIS® (canakinumab) Summary of Product Characteristics.
- Ruperto N, et al. Ann Rheum Dis 2018;77(12):1710–1719.