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: Cryopyrin-associated periodic syndromes Ilaris is indicated for the treatment of cryopyrin-associated periodic syndromes (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. Tumour necrosis factor receptor associated periodic syndrome (TRAPS) Ilaris is indicated for the treatment of tumour necrosis factor (TNF) receptor associated periodic syndrome (TRAPS). Hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD) Ilaris is indicated for the treatment of hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD). Familial Mediterranean fever (FMF) Ilaris is indicated for the treatment of Familial Mediterranean Fever (FMF). It is recommended that Ilaris be given in combination with colchicine, if appropriate. Ilaris is also indicated for the treatment of: 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. Gouty arthritis Ilaris is indicated for the symptomatic treatment of adult patients with frequent gouty arthritis attacks (at least 3 attacks in the previous 12 months) in whom non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine are contraindicated, are not tolerated, or do not provide an adequate response, and in whom repeated courses of corticosteroids are not appropriate (see section 5.1).

For CAPS, TRAPS, HIDS/MKD, FMF and Still’s disease, the treatment is to be initiated and supervised by a specialist physician experienced in the diagnosis and treatment of the relevant indication. For gouty arthritis, the physician needs to be experienced in the use of biologics and Ilaris is to be administered by a healthcare professional. Posology CAPS: Adults, adolescents and children aged 2 years and older The recommended starting dose of canakinumab for CAPS patients is: Adults, adolescents and children = 4 years of age: • 150 mg for patients with body weight > 40 kg • 2 mg/kg for patients with body weight = 15 kg and = 40 kg • 4 mg/kg for patients with body weight = 7.5 kg and < 15 kg Children 2 to < 4 years of age: • 4 mg/kg for patients with body weight = 7.5 kg This is administered every eight weeks as a single dose via subcutaneous injection. For patients with a starting dose of 150 mg or 2 mg/kg, if a satisfactory clinical response (resolution of rash and other generalised inflammatory symptoms) has not been achieved 7 days after treatment start, a second dose of canakinumab at 150 mg or 2 mg/kg can be considered. If a full treatment response is subsequently achieved, the intensified dosing regimen of 300 mg or 4 mg/kg every 8 weeks needs to be maintained. If a satisfactory clinical response has not been achieved 7 days after this increased dose, a third dose of canakinumab at 300 mg or 4 mg/kg can be considered. If a full treatment response is subsequently achieved, maintaining the intensified dosing regimen of 600 mg or 8 mg/kg every 8 weeks is to be considered, based on individual clinical judgement. For patients with a starting dose of 4 mg/kg, if a satisfactory clinical response has not been achieved 7 days after treatment start, a second dose of canakinumab 4 mg/kg can be considered. If a full treatment response is subsequently achieved, maintaining the intensified dosing regimen of 8 mg/kg every 8 weeks is to be considered, based on individual clinical judgement. Clinical experience with dosing at intervals of less than 4 weeks or at doses above 600 mg or 8 mg/kg is limited. TRAPS, HIDS/MKD and FMF: Adults, adolescents and children aged 2 years and older The recommended starting dose of canakinumab in TRAPS, HIDS/MKD and FMF patients is: • 150 mg for patients with body weight > 40 kg • 2 mg/kg for patients with body weight = 7.5 kg and = 40 kg This is administered every four weeks as a single dose via subcutaneous injection. If a satisfactory clinical response has not been achieved 7 days after treatment start, a second dose of canakinumab at 150 mg or 2 mg/kg can be considered. If a full CAPS in adults and children = 4 years of age = 15 kg Maintenance dose: 150 mg or 2 mg/kg every 8 weeks Additional dose of 150 mg or 2 mg/kg can be considered 150 mg or 2 mg/kg Additional dose of 300 mg or 4 mg/kg can be considered Maintenance dose 4 mg/kg every 8 weeks Additional dose of 4 mg/kg can be considered Satisfactory clinical response after 7 days? Satisfactory clinical response after 7 days? Maintenance dose: 300 mg or 4 mg/kg every 8 weeks If full treatment response after 7 days, maintenance dose: 600 mg or 8 mg/kg every 8 weeks Satisfactory clinical response after 7 days? 4 mg/kg CAPS in children 2-< 4 years of age or children = 4 years of age = 7.5 kg and < 15 kg If full treatment response after 7 days, maintenance dose: 8 mg/kg every 8 weeks Yes No No No Yes Yes treatment response is subsequently achieved, the intensified dosing regimen of 300 mg (or 4 mg/kg for patients weighing = 40 kg) every 4 weeks needs to be maintained. In patients without clinical improvement, it is recommended that the treating physician reconsiders continued treatment with canakinumab. Still’s disease (SJIA and AOSD) The recommended dose of canakinumab for patients with Still’s disease with body weight = 7.5 kg is 4 mg/kg (up to a maximum of 300 mg) administered every four weeks via subcutaneous injection. In patients without clinical improvement, it is recommended that the treating physician reconsiders continued treatment with canakinumab. Gouty arthritis Management of hyperuricaemia with appropriate urate lowering therapy (ULT) needs to be instituted or optimised. Canakinumab needs to be used as an on-demand therapy to treat gouty arthritis attacks. The recommended dose of canakinumab for adult patients with gouty arthritis is 150 mg administered subcutaneously as a single dose during an attack. For maximum effect, administration of canakinumab as soon as possible after the onset of a gouty TRAPS, HIDS/MKD and FMF patients with body weight > 40 kg Maintenance dose: 150 mg every 4 weeks Additional dose of 150 mg can be considered 150 mg Maintenance dose 2 mg/kg every 4 weeks Additional dose of 2 mg/kg can be considered Satisfactory clinical response after 7 days? Satisfactory clinical response after 7 days? 2 mg/kg TRAPS, HIDS/MKD and FMF patients with body weight =7.5 kg and =40 kg If full treatment response is achieved, maintenance dose: 4 mg/kg every 4 weeks No No Yes Yes If full treatment response is achieved, maintenance dose: 300 mg every 4 weeks arthritis attack is recommended. It is recommended that patients who do not respond to initial treatment are not re- treated with canakinumab. In patients who respond and require re-treatment, there needs to be an interval of at least 12 weeks before a new dose of canakinumab may be administered (see section 5.2). Missed doses If an injection is missed in patients with CAPS, TRAPS, HIDS/MKD, FMF or Still’s disease (AOSD or SJIA), it is to be administered as soon as possible without waiting until the next scheduled dose. Subsequent doses are to be administered at the recommended intervals. Special populations Paediatric population CAPS, TRAPS, HIDS/MKD and FMF The safety and efficacy of canakinumab in CAPS, TRAPS, HIDS/MKD and FMF patients under 2 years of age have not been established. Currently available data are described in sections 4.8, 5.1 and 5.2 but no recommendation on a posology can be made. SJIA The safety and efficacy of canakinumab in SJIA patients under 2 years of age have not been established. No data are available. Gouty arthritis There is no relevant use of canakinumab in the paediatric population in the indication gouty arthritis. Elderly No dose adjustment is required. Hepatic impairment Canakinumab has not been studied in patients with hepatic impairment. No recommendation on a posology can be made. Renal impairment No dose adjustment is needed in patients with renal impairment. However, clinical experience in such patients is limited. Patient Card All prescribers of Ilaris shall be familiar with the SmPC and inform the patients/caregivers about the Patient Card explaining what to do should they experience any symptom of infection or macrophage activation syndrome (MAS), or in case of vaccinations prior to treatment. The physician will provide the Patient Card to each patient/caregiver. Method of administration For subcutaneous use. The following are suitable injection sites: upper thigh, abdomen, upper arm or buttocks. It is recommended to select a different injection site each time the product is injected to avoid soreness. Broken skin and areas which are bruised or covered by a rash must be avoided. Injection into scar tissue must be avoided as this may result in insufficient exposure to canakinumab. Each vial is for single use in a single patient, for a single dose. CAPS, TRAPS, HIDS/MKD, FMF and Still’s disease (AOSD and SJIA) After proper training in the correct injection technique, patients or their caregivers may inject canakinumab if the physician determines that it is appropriate and with medical follow-up as necessary (see section 6.6). For instructions on reconstitution of the medicinal product before administration, see section 6.6.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Active, severe infections (see section 4.4).

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Infections Canakinumab is associated with an increased incidence of serious infections. Patients must be monitored carefully for signs and symptoms of infections during and after treatment with canakinumab (see section 4.8). Physicians need to exercise caution when administering canakinumab to patients with infections, a history of recurring infections, or underlying conditions which may predispose them to infections. Treatment of CAPS, TRAPS, HIDS/MKD, FMF and Still’s disease (SJIA and AOSD) Canakinumab must not be initiated or continued in patients during an active infection requiring medical intervention. Treatment of gouty arthritis Canakinumab must not be administered during an active infection. Concomitant use of canakinumab with tumour necrosis factor (TNF) inhibitors is not recommended because this may increase the risk of serious infections (see section 4.5). Isolated cases of unusual or opportunistic infections (including aspergillosis, atypical mycobacterial infections, herpes zoster) have been reported during canakinumab treatment. The causal relationship of canakinumab to these events cannot be excluded. Tuberculosis screening In approximately 12% of CAPS patients tested with a PPD (purified protein derivative) skin test in clinical trials, follow-up testing yielded a positive test result while treated with canakinumab without clinical evidence of a latent or active tuberculosis infection. It is unknown whether the use of interleukin-1 (IL-1) inhibitors such as canakinumab increases the risk of reactivation of tuberculosis. Before initiation of therapy, all patients must be evaluated for both active and latent tuberculosis infection. Particularly in adult patients, it is recommended that this evaluation includes a detailed medical history. Appropriate screening tests (e.g. tuberculin skin test, interferon gamma release assay or chest X-ray) are recommended to be performed in all patients (local recommendations may apply). Patients must be monitored closely for signs and symptoms of tuberculosis during and after treatment with canakinumab. All patients are to be instructed to seek medical advice if signs or symptoms suggestive of tuberculosis (e.g. persistent cough, weight loss, subfebrile temperature) appear during canakinumab therapy. In the event of conversion from a negative to a positive PPD test, especially in high-risk patients, alternative means of screening for a tuberculosis infection can be considered. Neutropenia and leukopenia Neutropenia (absolute neutrophil count [ANC] < 1.5 x 109/l) and leukopenia have been observed with medicinal products that inhibit IL-1, including canakinumab. Treatment with canakinumab is not to be initiated in patients with neutropenia or leukopenia. It is recommended that white blood cell (WBC) counts including neutrophil counts be assessed prior to initiating treatment and again after 1 to 2 months. For chronic or repeated therapies, it is also recommended to assess WBC counts periodically during treatment. If a patient becomes neutropenic or leukopenic, the WBC counts need to be monitored closely and treatment discontinuation considered. Malignancies Malignancy events have been reported in patients treated with canakinumab. The risk for the development of malignancies with anti-interleukin (IL)-1 therapy is unknown. Hypersensitivity reactions Hypersensitivity reactions with canakinumab therapy have been reported. The majority of these events were mild in severity. During clinical development of canakinumab in over 2 600 patients, no anaphylactoid or anaphylactic reactions attributable to treatment with canakinumab were reported. However, the risk of severe hypersensitivity reactions, which is not uncommon for injectable proteins, cannot be excluded (see section 4.3). Hepatic function Transient and asymptomatic cases of elevations of serum transaminases or bilirubin have been reported in clinical trials (see section 4.8). Vaccinations No data are available on the risk of secondary transmission of infection by live (attenuated) vaccines in patients receiving canakinumab. Therefore, live vaccines must not be given concurrently with canakinumab unless the benefits clearly outweigh the risks (see section 4.5). Prior to initiation of canakinumab therapy it is recommended that adult and paediatric patients receive all vaccinations, as appropriate, including pneumococcal vaccine and inactivated influenza vaccine (see section 4.5). Mutation in NLRP3 gene in CAPS patients Clinical experience in CAPS patients without a confirmed mutation in the NLRP3 gene is limited. Macrophage activation syndrome in patients with Still’s disease (SJIA and AOSD) Macrophage activation syndrome (MAS) is a known, life-threatening disorder that may develop in patients with rheumatic conditions, in particular Still’s disease. If MAS occurs, or is suspected, evaluation and treatment need to be started as early as possible. Physicians need to be attentive to symptoms of infection or worsening of Still’s disease, as these are known triggers for MAS. Based on clinical trial experience, canakinumab does not appear to increase the incidence of MAS in Still’s disease patients, but no definitive conclusion can be made. Drug reaction with eosinophilia and systemic symptoms (DRESS) Drug reaction with eosinophilia and systemic symptoms (DRESS) has rarely been reported in patients treated with Ilaris, predominantly in patients with systemic juvenile idiopathic arthritis (sJIA). Patients with DRESS may require hospitalization, as this condition may be fatal. If signs and symptoms of DRESS are present and an alternative aetiology cannot be established, Ilaris must not be re-administered and a different treatment considered. Polysorbate 80 content This medicinal product contains 0.6 mg of polysorbate 80 in each vial. Polysorbates may cause allergic reactions. The patient/caregiver needs to be instructed to tell the doctor if they or their child have/has any known allergies.

Women of childbearing potential / Contraception in males and females It is recommended that women use effective contraceptives during treatment with canakinumab and for up to 3 months after the last dose. Pregnancy There is a limited amount of data from the use of canakinumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). The risk for the foetus/mother is unknown. It is therefore recommended that women who are pregnant or who desire to become pregnant only be treated after a thorough benefit-risk evaluation. Animal studies indicate that canakinumab crosses the placenta and is detectable in the foetus. No human data are available, but as canakinumab is an immunoglobulin of the G class (IgG1), human transplacental transfer is expected. The clinical impact of this is unknown. However, administration of live vaccines to newborn infants exposed to canakinumab in utero is not recommended for 16 weeks following the mother’s last dose of canakinumab before childbirth. It is recommended that women who received canakinumab during pregnancy be instructed to inform the baby’s healthcare professional before any vaccinations are given to their newborn infant. Breast-feeding It is unknown whether canakinumab is excreted in human milk. It is therefore recommended that the decision whether to breast-feed during canakinumab therapy only be taken after a thorough benefit-risk evaluation. Animal studies have shown that a murine anti-murine IL-1 beta antibody had no undesirable effects on development in nursing mouse pups and that the antibody was transferred to them (see section 5.3). Fertility Formal studies of the potential effect of canakinumab on human fertility have not been conducted. Canakinumab had no effect on male fertility parameters in marmosets (C. jacchus). A murine anti-murine IL-1 beta antibody had no undesirable effects on fertility in male or female mice (see section 5.3).

Ilaris has minor influence on the ability to drive and use machines. Treatment with Ilaris may result in dizziness/vertigo or asthenia (see section 4.8). Patients who experience such symptoms during Ilaris treatment need to wait for this to resolve completely before performing tasks that require judgement or motor skills.

Summary of the safety profile The most frequent adverse reactions were infections predominantly of the upper respiratory tract. No impact on the type or frequency of adverse reactions was seen with longer-term treatment. Hypersensitivity reactions have been reported in patients treated with canakinumab (see sections 4.3 and 4.4). Opportunistic infections have been reported in patients treated with canakinumab (see section 4.4). Tabulated list of adverse reactions Adverse reactions are listed according to MedDRA system organ class. Within each system organ class, the adverse reactions are ranked by frequency category with the most common first. Frequency categories are defined using the following convention: very common (= 1/10); common (= 1/100 to < 1/10); uncommon (= 1/1 000 to < 1/100); rare (= 1/10 000 to < 1/1 000); very rare (< 1/10 000); not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Table 1 Tabulated list of adverse reactions MedDRA System Organ Class Indications: CAPS, TRAPS, HIDS/MKD, FMF, SJIA, gouty arthritis Infections and infestations Very common Respiratory tract infections (including pneumonia, bronchitis, influenza, viral infection, sinusitis, rhinitis, pharyngitis, tonsillitis, nasopharyngitis, upper respiratory tract infection) Ear infection Cellulitis Gastroenteritis Urinary tract infection Common Vulvovaginal candidiasis Nervous system disorders Common Dizziness/vertigo Gastrointestinal disorders Very common Upper abdominal pain 1 Uncommon Gastro-oesophageal reflux disease 2 Skin and subcutaneous tissue disorders Very common Injection site reaction Musculoskeletal and connective tissue disorders Very common Arthralgia 1 Common Musculoskeletal pain 1 Back pain 2 General disorders and administration site conditions Common Fatigue/asthenia 2 Investigations Very common Creatinine renal clearance decreased 1,3 Proteinuria 1,4 Leukopenia 1,5 Common Neutropenia 5 Uncommon Platelet count decreased 5 1 In SJIA 2 In gouty arthritis 3 Based on estimated creatinine clearance, most were transient 4 Most represented transient trace to 1+ positive urinary protein by dipstick 5 See further information below Still’s Disease (SJIA and AOSD) SJIA pooled analysis and AOSD A total of 445 SJIA patients aged 2 to < 20 years received canakinumab in clinical trials, including 321 patients aged 2 to < 12 years, 88 patients aged 12 to < 16 years, and 36 patients aged 16 to < 20 years. A pooled safety analysis of all SJIA patients showed that in the subset of young adult SJIA patients aged 16 to < 20 years, the safety profile of canakinumab was consistent with what was observed in SJIA patients less than 16 years of age. The safety profile of canakinumab in AOSD patients in a randomised, double blind placebo-controlled study (GDE01T) in 36 adult patients (aged 22 to 70 years) was similar to what was observed in SJIA patients. Description of selected adverse reactions 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. 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. Platelets 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 Haematology In the overall SJIA programme, transient decreased white blood cell (WBC) counts = 0.8 x LLN were reported in 33 patients (16.5%). In the overall SJIA programme, transient decreases in absolute neutrophil count (ANC) to less than 1 x 109/l were reported in 12 patients (6.0%). In the overall SJIA programme, 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%). Laboratory abnormalities in gouty arthritis patients Haematology Decreased white blood cell counts (WBC) = 0.8 x lower limit of normal (LLN) were reported in 6.7% of patients treated with canakinumab compared to 1.4% treated with triamcinolone acetonide. Decreases in absolute neutrophil counts (ANC) to less than 1 x 109/l were reported in 2% of patients in the comparative trials. Isolated cases of ANC counts < 0.5 x 109/l were also observed (see section 4.4). Mild (< LLN and > 75 x 109/l) and transient decreases in platelet counts were observed at a higher incidence (12.7%) with canakinumab in the active-controlled clinical studies versus the comparator (7.7%) in gouty arthritis patients. Uric acid Increases in uric acid level (0.7 mg/dl at 12 weeks and 0.5 mg/dl at 24 weeks) were observed after canakinumab treatment in comparative trials in gouty arthritis. In another study, among patients who were starting on ULT, increases in uric acid were not observed. Uric acid increases were not observed in clinical trials in non-gouty arthritis populations (see section 5.1). ALT/AST Mean and median increases in alanine transaminase (ALT) of 3.0 U/l and 2.0 U/l, respectively, and in aspartate transaminase (AST) of 2.7 U/l and 2.0 U/l, respectively, from baseline to end of study were seen in the canakinumab-treated groups versus the triamcinolone acetonide-treated group(s), however the incidence of clinically significant changes (= 3 x the upper limit of normal) was greater for patients treated with triamcinolone acetonide (2.5% for both AST and ALT) compared with canakinumab-treated patients (1.6% for ALT and 0.8% for AST). Triglycerides In active-controlled gouty arthritis trials, there was a mean increase in triglycerides of 33.5 mg/dl in canakinumab-treated patients compared with a modest decrease of -3.1 mg/dl with triamcinolone acetonide. The incidence of patients with triglyceride elevations > 5 x upper limit of normal (ULN) was 2.4% with canakinumab and 0.7% with triamcinolone acetonide. The clinical significance of this observation is unknown. Long term data from observational study A total of 243 CAPS patients (85 paediatric patients aged = 2 to = 17 years and 158 adult patients aged = 18 years) were treated with canakinumab in routine clinical practice in a long-term registry study (mean of 3.8 years of canakinumab exposure). The safety profile of canakinumab observed following long-term treatment in this setting was consistent with what has been observed in interventional studies in CAPS patients. Paediatric population There were 80 paediatric CAPS patients (2-17 years of age) who received canakinumab in the interventional studies. Overall, there were no clinically meaningful differences in the safety and tolerability profile of canakinumab in paediatric patients compared to the overall CAPS population (comprised of adult and paediatric patients, N=211), including the overall frequency and severity of infectious episodes. Infections of the upper respiratory tract were the most frequently reported infection events. Additionally, 6 paediatric patients under the age of 2 years were evaluated in a small open-label clinical study. The safety profile of canakinumab appeared similar to that in patients aged 2 years and above. There were 102 TRAPS, HIDS/MKD and FMF patients (2-17 years of age) who received canakinumab in a 16-week study. Overall, there were no clinically meaningful differences in the safety and tolerability profile of canakinumab in paediatric patients compared to the overall population. Elderly population There is no significant difference in safety profile observed in patients = 65 years of age. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Reported experience with is limited. In early clinical trials, patients and healthy volunteers received doses as high as 10 mg/kg, administered intravenously or subcutaneously, without evidence of acute toxicity. In case of , it is recommended for the patient to be monitored for any signs or symptoms of adverse reactions, and appropriate symptomatic treatment instituted immediately.

Pharmacotherapeutic group: Immunosuppressants, interleukin inhibitors, ATC code: L04AC08 Mechanism of action Canakinumab is a human monoclonal anti-human interleukin-1 beta (IL-1 beta) antibody of the IgG1/? isotype. Canakinumab binds with high affinity specifically to human IL-1 beta and neutralises the biological activity of human IL-1 beta by blocking its

CAPS Absorption The peak serum canakinumab concentration (Cmax) occurred approximately 7 days following single subcutaneous administration of 150 mg in adult CAPS patients. The mean terminal half-life was 26 days. Mean values for Cmax and area under the curve extrapolated to infinity (AUCinf) after a single subcutaneous dose of 150 mg in a typical adult CAPS patient (70 kg) were 15.9 µg/ml and 708 µg*d/ml. The absolute bioavailability of subcutaneously administered canakinumab was estimated to be 66%. Exposure parameters (such as AUC and Cmax) increased in proportion to dose over the dose range of 0.30 to 10.0 mg/kg given as intravenous infusion or from 150 to 600 mg as subcutaneous injection. Predicted steady-state exposure values (Cmin,ss, Cmax,ss, AUC,ss,8w) after 150 mg subcutaneous administration (or 2 mg/kg, respectively) every 8 weeks were slightly higher in the weight category 40-70 kg (6.6 µg/ml, 24.3 µg/ml, 767 µg*d/ml) compared to the weight categories < 40 kg (4.0 µg/ml, 19.9 µg/ml, 566 µg*d/ml) and > 70 kg (4.6 µg/ml, 17.8 µg/ml, 545 µg*d/ml). The expected accumulation ratio was 1.3-fold following 6 months of subcutaneous administration of 150 mg canakinumab every 8 weeks. Distribution Canakinumab binds to serum IL-1 beta. The distribution volume (Vss) of canakinumab varied according to body weight. It was estimated to be 6.2 litres in a CAPS patient of body weight 70 kg. Elimination The apparent clearance (CL/F) of canakinumab increases with body weight. It was estimated to be 0.17 l/d in a CAPS patient of body weight 70 kg and 0.11 l/d in a SJIA patient of body weight 33 kg. After accounting for body weight differences, no clinically significant differences in the of canakinumab were observed between CAPS and SJIA patients. There was no indication of accelerated clearance or time-dependent change in the of canakinumab following repeated administration. No gender or age-related pharmacokinetic differences were observed after correction for body weight. TRAPS, HIDS/MKD and FMF Bioavailability in TRAPS, HIDS/MKD and FMF patients has not been determined independently. Apparent clearance (CL/F) in the TRAPS, HIDS/MKD and FMF population at body weight of 55 kg (0.14 l/d) was comparable to CAPS population at body weight of 70 kg (0.17 l/d). The apparent volume of distribution (V/F) was 4.96 l at body weight of 55 kg. After repeated subcutaneous administration of 150 mg every 4 weeks, canakinumab minimal concentration at week 16 (Cmin) was estimated to be 15.4 ± 6.6 µg/ml. The estimated steady state AUCtau was 636.7 ± 260.2 µg*d/ml. Still’s disease (SJIA and AOSD) Bioavailability in SJIA patients has not been determined independently. Apparent clearance per kg body weight (CL/F per kg) was comparable between the SJIA and CAPS population (0.004 l/d per kg). The apparent volume of distribution per kg (V/F per kg) was 0.14 l/kg. Sparse pharmacokinetics (PK) data in AOSD patients suggest similar PK of canakinumab as compared to SJIA and other patient populations. After repeated administration of 4 mg/kg every 4 weeks the accumulation ratio of canakinumab was 1.6 fold in SJIA patients. Steady state was reached after 110 days. The overall predicted mean (±SD) for Cmin,ss, Cmax,ss and AUC,ss4w were 14.7±8.8 µg/ml, 36.5 ± 14.9 µg/ml and 696.1 ± 326.5 µg*d/ml, respectively. The AUCss4w in each age group was 692, 615, 707 and 742 µg*d/ml for 2-3, 4-5, 6-11, and 12-19 years old, respectively. When stratified by weight, a lower (30-40%) median of exposure for Cmin,ss (11.4 vs 19 µg/ml) and AUCss (594 vs 880 µg*d/ml) for the lower bodyweight category (= 40 kg) vs the higher bodyweight category (> 40 kg) was observed. Based on the population pharmacokinetic modelling analysis, the pharmacokinetics of canakinumab in young adult SJIA patients aged 16 to 20 years were similar to those in patients less than 16 years of age. Predicted canakinumab steady state exposures at a dose level of 4 mg/kg (maximum 300 mg) in patients over the age of 20 years were comparable to those in SJIA patients younger than 20 years of age. Gouty arthritis population Bioavailability in gouty arthritis patients has not been determined independently. Apparent clearance per kg body weight (CL/F per kg) was comparable between the gouty arthritis and CAPS population (0.004 l/d/kg). Mean exposure in a typical gouty arthritis patient (93 kg) after a single subcutaneous 150 mg dose (Cmax: 10.8 µg/ml and AUCinf: 495 µg*d/ml) was lower than in a typical 70 kg CAPS patient (15.9 µg/ml and 708 µg*d/ml). This is consistent with the observed increase in CL/F with body weight. The expected accumulation ratio was 1.1-fold following subcutaneous administration of 150 mg canakinumab every 12 weeks. Paediatric population Peak concentrations of canakinumab occurred between 2 to 7 days (Tmax) following single subcutaneous administration of canakinumab 150 mg or 2 mg/kg in paediatric patients 4 years of age and older. The terminal half-life ranged from 22.9 to 25.7 days, similar to the observed in adults. Based on the population pharmacokinetic modelling analysis, the pharmacokinetics of canakinumab in children aged 2 to < 4 years were similar to those in patients 4 years of age and older. Subcutaneous absorption rate was estimated to decrease with age and appeared to be fastest in the youngest patients. Accordingly, Tmax was shorter (3.6 days) in younger SJIA patients (2-3 years) compared to older SJIA patients (12-19 years; Tmax 6 days). Bioavailability (AUCss) was not affected. An additional pharmacokinetics analysis showed that the pharmacokinetics of canakinumab in 6 paediatric CAPS patients under the age of 2 years were similar to the pharmacokinetics in paediatric patients 2-4 years of age. Based on the population pharmacokinetic modelling analysis, the expected exposures after a dose of 2 mg/kg were comparable across the CAPS paediatric age groups, but were approximately 40% lower in paediatric patients of very low body weight (e.g. 10 kg) than in adult patients (150 mg dose). This is consistent with the observations of higher exposure in higher body weight groups in CAPS patients. In TRAPS, HIDS/MKD and FMF, exposure parameters (trough concentrations) were comparable across age groups from 2 to < 20 years old following subcutaneous administration of canakinumab 2 mg/kg every 4 weeks. are similar in CAPS, TRAPS, HIDS/MKD, FMF and SJIA paediatric populations. Elderly population No change in pharmacokinetic parameters based on clearance or volume of distribution were observed between elderly patients and adult patients < 65 years of age.

Non-clinical data reveal no special hazard for humans based on conventional studies of cross-reactivity, repeated dose toxicity, immunotoxicity, toxicity to reproduction and development. Formal carcinogenicity studies have not been conducted with canakinumab.

Sucrose Histidine Histidine hydrochloride monohydrate Polysorbate 80 (E 433)

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

3 years. After reconstitution, from a microbiological point of view, the product must be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C - 8°C.

Store in a refrigerator (2°C - 8°C). Do not freeze. Store in the original package in order to protect from light. For storage conditions after reconstitution of the medicinal product, see section 6.3.

Powder for solution for injection in a vial (type I glass) with a stopper (coated chlorobutyl rubber) and flip-off cap (aluminium). Packs containing 1 vial or multipacks containing 4 (4x1) vials. Not all pack sizes may be marketed.

Ilaris 150 mg powder for solution for injection is supplied in a single-use vial for individual use. Instructions for reconstitution Using aseptic technique, reconstitute each vial of canakinumab at room temperature (typically 15°C to 25°C) by slowly injecting 1 ml water for injections with a 1 ml syringe and an 18 G x 2 inch (50 mm) needle. Swirl the vial slowly at an angle of about 45° for approximately 1 minute and allow to stand for about 5 minutes. Then gently turn the vial upside down and back again ten times. If possible, avoid touching the rubber stopper with your fingers. Allow to stand for about 15 minutes at room temperature to obtain a clear to opalescent solution. Do not shake. Do not use if particles are present in the solution. Tap the side of the vial to remove any residual liquid from the stopper. The solution needs to be practically free of visible particles and clear to opalescent. The solution needs to be colourless or may have a slight brownish-yellow tint. If the solution has a distinctly brown discolouration it must not be used. If not used immediately after reconstitution, the solution needs to be kept at 2°C to 8°C and used within 24 hours. Instructions for administration Carefully withdraw the required volume depending on the dose to be administered (0.1 ml to 1 ml) and subcutaneously inject using a 27 G x 0.5 inch (13 mm) needle. Disposal Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Feb. 16, 2026

spc-doc_PLGB 00101-1092.pdf

Bulk SPC upload Feb2026