Ilaris®
Musculoskeletal disorders
: often - back pain.
Digestive system disorders
: uncommon - gastroesophageal reflux disease.
General disorders and reactions at the injection site
: often - general weakness/fatigue.
Reactions at the injection site
were observed in 1.2% of patients treated with Ilaris® in clinical studies.
Changes in laboratory parameters
General blood analysis
A decrease in white blood cell count <0.8x109/L lower limit of normal was observed in 6.7% of patients treated with Ilaris® compared to 1.4% of patients treated with triamcinolone. A decrease in absolute neutrophil count below 1 x 109/L was observed in 2% of patients in comparative studies of gouty arthritis. Isolated cases of a decrease in the number of neutrophils below 0.5 x 109 /l were also observed.
In 12.7% of cases, during therapy with canakinumab, a slight and transient decrease in platelet count (ranging from 75 x109/l) to the lower limit of normal was observed (with the comparison drug this decrease was observed in 7.7% of cases).
Uric acid
During canakinumab therapy, a transient increase in uric acid concentrations (approximately 0.6 mg/dL) is observed. The drug Ilaris® does not reduce the ability of anti-gout drugs to reduce the concentration of uric acid when used together.
Aspartate aminotransferase/alanine aminotransferase (AST/ALT)
During therapy with canakinumab, a mild to moderate increase in AST/ALT activity may develop.
Triglycerides
During canakinumab therapy, on average, there was an increase in plasma triglyceride concentrations by 33.5 mg/dL, and in the triamcinolone group there was a slight decrease of 3.1 mg/dL. An increase in triglyceride concentrations of more than 5 times (compared to the upper limit of normal) was observed in 2.4% of cases in the canakinumab group and in 0.7% of cases in the triamcinolone group. The clinical significance of this observation is unknown.
Cryopyrin-associated periodic syndrome
Infectious and parasitic diseases
: very often - nasopharyngitis; often - urinary tract infections; upper respiratory tract infections, viral infection.
Nervous system disorders
: very often - dizziness/vertigo*.
Skin and subcutaneous tissue disorders
: very often - reaction at the injection site**.
*Symptoms of vertigo, in some cases, were considered serious AEs; all episodes of vertigo resolved despite continued drug therapy.
**Adverse event (AE) was identified using a physician questionnaire.
In long-term, open-label dose escalation studies, there was an increase in the incidence of infectious diseases (gastroenteritis, respiratory tract infections and upper respiratory tract infections), nausea and dizziness in the group of patients receiving doses of the drug 600 mg or 8 mg/kg, compared with groups receiving other doses of the drug.
Changes in laboratory parameters
General blood analysis
When using the drug in clinical studies in patients with CAPS, an increase in hemoglobin and a decrease in the number of leukocytes, neutrophils and platelets were observed. However, these changes were probably associated with a decrease in the severity of the inflammatory process during drug therapy and had no clinical significance.
Liver enzymes
In rare cases, in patients with CAPS treated with the drug, an increase in the activity of “liver” transaminases was observed.
Bilirubin
In a number of cases, during drug therapy in patients with CAPS, an asymptomatic slight increase in the content of bilirubin in the blood serum was observed, not accompanied by an increase in the activity of “liver” transaminases.
sJIA
Infectious and parasitic diseases
: very often - infections (in particular, nasopharyngitis, viral infections of the upper respiratory tract, pneumonia, rhinitis, pharyngitis, tonsillitis, sinusitis, urinary tract infections, gastroenteritis, viral infection).
Digestive system disorders
: very often - pain in the upper abdomen.
Skin and subcutaneous tissue disorders
: very often - a reaction at the injection site of mild severity*, often - a reaction at the injection site of moderate severity*.
* - did not lead to termination of the study.
Changes in laboratory parameters
General blood analysis
A decrease in the number of leukocytes <0.8x109/l lower limit of normal was observed in 10.4% of patients treated with Ilaris®, compared with 4.0% in the placebo group.
A transient decrease in absolute neutrophil count <1 x 109/L was observed in 6.0% of patients treated with Ilaris®, compared to 2.0% in the placebo group. There was one case of a decrease in the absolute number of neutrophils <0.5x109/l during treatment with Ilaris®.
Moderate and transient decreases ranging from 75 x109/L to the lower limit of normal in platelets were observed in 6.3% of patients receiving Ilaris®, compared with 2.0% in the placebo group.
Liver enzymes
A threefold increase in ALT and/or AST compared to the upper limit of normal was observed in 4.1% of patients treated with Ilaris®, compared to 2.0% in the placebo group. During subsequent examination, normalization of indicators was noted.
Hypersensitivity reactions
When using the drug Ilaris® in clinical studies, adverse events were reported, which were regarded by doctors as hypersensitivity reactions. In most cases, these reactions were mild. When using the drug, the development of anaphylactoid or anaphylactic reactions was not observed. However, when prescribing Ilaris®, the risk of developing severe hypersensitivity reactions, which can occur when injecting drugs of protein origin, cannot be excluded. In patients treated with Ilaris® for gouty arthritis, CAPS and sJIA, antibodies to the drug were detected in 1.5%, 3% and 2% of cases, respectively. There was no relationship between the formation of antibodies, clinical response and the development of adverse events.
Use in patients aged < 18 years
(patients with CAPS)
In children aged 2 to 17 years, there were no clinically significant differences in the safety and tolerability of Ilaris®, including the overall incidence and severity of infections, compared with the general patient population. Upper respiratory tract infections were most common in children.
Use in patients >
65 years of age
There were no differences in the safety profile of the drug in this group of patients.
The patient should be informed of the need to consult a doctor in case of severe adverse reactions, including those not specified in the instructions.
Ilaris (Canakinumab)
Marketing authorization holder: NOVARTIS PHARMA, AG (Switzerland)
Manufactured by: NOVARTIS PHARMA STEIN, AG (Switzerland)
ATX code: L04AC08 (Canakinumab)
Active substance: canakinumab (canakinumab) Rec.INN registered by WHO
Release form, packaging and composition of the drug Ilaris®
Lyophilisate for preparing a solution for subcutaneous administration in the form of a white powder; reconstituted solution: slightly opalescent, slightly yellow to slightly brown or brownish-yellow.
| 1 fl. | |
| canakinumab | 150 mg |
Excipients: sucrose, L-histidine, L-histidine hydrochloride monohydrate, polysorbate 80.
Colorless glass bottles with a capacity of 6 ml (1) – cardboard packs×.
× the pack can be sealed with a transparent sticker.
Clinical and pharmacological group: Immunosuppressive drug. Monoclonal antibodies to interleukin-1 beta
Pharmacotherapeutic group: Immunosuppressive agent – monoclonal antibodies to interleukin-1 beta
pharmachologic effect
Immunosuppressant, monoclonal antibodies to interleukin-1β.
Canakinumab is a fully human IgG1/kappa isotype monoclonal antibody to interleukin-1β (IL-1β). Canakinumab binds with high affinity to human IL-1β, thereby preventing the interaction of IL-1β with its receptors, IL-1β-induced gene activation and the production of inflammatory mediators such as IL-6 and COX-2.
In patients with gouty arthritis and various phenotypes of cryopyrin-associated periodic syndrome (CAPS), including familial cold autoinflammatory syndrome/familial cold urticaria (Family Cold Autoinflammatory Syndrome/Familial Cold Urticaria, FCAS/FCU), Mackle syndrome Wales (Muckle-Wells Syndrome, MWS) and multisystemic infantile inflammatory disease/chronic infantile neurological cutaneous and articular syndrome (Neonatal onset multisystemic inflammatory disease/Chronic infantile neurological cutaneous and articular, NOMID/CINCA), canakinumab reduces the severity of local and systemic inflammatory reactions, caused by excess production of IL-1β. When used in patients with an acute attack of gouty arthritis, the concentration of laboratory markers of inflammation (C-reactive protein (CRP), serum amyloid A (SAA)) decreases, and signs of inflammation of the affected joint (pain, swelling, redness) disappear within a short time.
When using canakinumab in patients with various CAPS phenotypes, there is a decrease within the first day of the following manifestations of the disease: fever, fatigue, skin rash, arthralgia, myalgia, headache/migraine, conjunctivitis, weakness, as well as a decrease (within several days) production of inflammatory markers, including both CRP and CAA, and leads to normalization of the number of leukocytes and platelets (if they are increased).
Pharmacokinetics
In adult patients with various CAPS phenotypes, after a single subcutaneous administration of canakinumab at a dose of 150 mg, the Tmax of canakinumab is approximately 7 days. With subcutaneous administration of canakinumab, the absolute bioavailability is 63% (population pharmacokinetic analysis).
Cmax in blood plasma and AUC increase proportionally to the dose in the dose range from 0.30 to 10.0 mg/kg with intravenous infusion or with subcutaneous administration at a dose of 150 mg to 300 mg.
There was no significant difference in the pharmacokinetic properties of canakinumab in patients with gouty arthritis and different CAPS phenotypes.
The Vss of canakinumab varies with body weight. For a typical gouty arthritis patient weighing 93 kg, Vss is 7.92 L. For patients with different phenotypes, CAPS Vss is 6.01 L in a typical patient weighing 70 kg.
With subcutaneous administration of the drug for 6 months (dose of 150 mg) every 8 weeks, the accumulation coefficient of canakinumab is 1.3, every 12 weeks – 1.1.
The average final T1/2 is 26 days. The clearance of canakinumab varies depending on body weight. For a typical patient with gouty arthritis weighing 93 kg, the clearance is 0.23 l/day. For patients with different CAPS phenotypes, the clearance is 0.17 L/day in a typical patient weighing 70 kg.
Indications of the active substances of the drug Ilaris®
Acute gouty arthritis: treatment of acute attacks of gouty arthritis and prevention of the development of new attacks in the event of ineffectiveness, intolerance or contraindications to the use of NSAIDs and/or colchicine and when it is impossible to carry out therapy with repeated courses of GCS.
Cryopyrin-associated periodic syndrome (CAPS) in adults and children aged 4 years and older weighing >15 kg, including: familial cold autoinflammatory syndrome (FCAS)/familial cold urticaria (FCU); Muckle-Wales syndrome (MWS); infantile multisystem inflammatory disease (NOMID)/chronic infantile neurological cutaneous articular syndrome (CINCA).
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