Ilaris

Dosage Forms & Strengths

powder for injection

• 180mg/vial (150mg/mL after reconstitution)

Cryopyrin-Associated Periodic Syndrome

Indicated for treatment of cryopyrin-associated periodic syndrome (CAPS), including familial old autoinflammatory syndrome and Muckle-Wells syndrome in adults and children

>40 kg: 150 mg SC q8wk

15-40 kg: 2 mg/kg SC q8wk; may increase to 3 mg/kg if inadequate response 

Tumor Necrosis Factor Receptor-Associated Periodic Syndrome

Indicated for the treatment of Tumor Necrosis Factor (TNF) receptor Associated Periodic Syndrome (TRAPS) in adult and pediatric patients

150 mg SC q4wk; may increase to 300 mg q4wk if the clinical response is not adequate

Hyperimmunoglobulin D Syndrome/Mevalonate Kinase Deficiency

Indicated for the treatment of hyperimmunoglobulin D (Hyper-IgD) Syndrome (HIDS) (HIDS)/mevalonate kinase deficiency (MKD) in adult and pediatric patients

150 mg SC q4wk; may increase to 300 mg q4wk if the clinical response is not adequate

Familial Mediterranean Fever

Indicated for the treatment of Familial Mediterranean Fever (FMF) in adult and pediatric patients

150 mg SC q4wk; may increase to 300 mg q4wk if the clinical response is not adequate

Still Disease (Orphan)

Orphan designation for treatment of adult-onset Still disease

Sponsor

• Novartis Pharmaceuticals Corporation; One Health Plaza; East Hanover, New Jersey 07936

Dosage Forms & Strengths

powder for injection

• 180mg/vial (150mg/mL after reconstitution)

Cryopyrin-Associated Periodic Syndrome

Indicated for treatment of cryopyrin-associated periodic syndrome, including familial old autoinflammatory syndrome and Muckle-Wells syndrome in adults and children

<4 years

• Safety and efficacy not established

≥4 Years

• 15-40 kg: 2 mg/kg SC q8wk 
• ≥40 kg: 150 mg SC q8wk

Tumor Necrosis Factor Receptor-Associated Periodic Syndrome

Indicated for the treatment of Tumor Necrosis Factor (TNF) receptor Associated Periodic Syndrome (TRAPS) in adult and pediatric patients

≤40 kg: 2 mg/kg SC q4wk; may increase to 4 mg/kg q4wk if the clinical response is not adequate 

>40 kg: 150 mg SC q4wk; may increase to 300 mg q4wk if the clinical response is not adequate

Hyperimmunoglobulin D Syndrome/Mevalonate Kinase Deficiency

Indicated for the treatment of hyperimmunoglobulin D (Hyper-IgD) Syndrome (HIDS) (HIDS)/mevalonate kinase deficiency (MKD) in adult and pediatric patients

≤40 kg: 2 mg/kg SC q4wk; may increase to 4 mg/kg q4wk if the clinical response is not adequate 

>40 kg: 150 mg SC q4wk; may increase to 300 mg q4wk if the clinical response is not adequate

Familial Mediterranean Fever

Indicated for the treatment of Familial Mediterranean Fever (FMF) in adult and pediatric patients

≤40 kg: 2 mg/kg SC q4wk; may increase to 4 mg/kg q4wk if the clinical response is not adequate 

>40 kg: 150 mg SC q4wk; may increase to 300 mg q4wk if the clinical response is not adequate

Systemic Juvenile Idiopathic Arthritis

Indicated for active SJIA

<2 years: Safety and efficacy not established

≥2 years and weight ≥7.5 kg: 4 mg/kg SC qMonth; not to exceed 300 mg/dose

Pregnancy: The limited human data from postmarketing reports on use of therapy in pregnant women are not sufficient to inform a drug associated risk; monoclonal antibodies, such as canakinumab, are transported across the placenta in a linear fashion as pregnancy progresses; therefore, potential fetal exposure is likely to be greater during the second and third trimesters of pregnancy

Lactation: There is no information regarding the presence of canakinumab in human milk, the effects on the breastfed infant, or the effects on milk production. Human IgG is known to be present in human milk; the effects of canakinumab in breast milk and possible systemic exposure in the breastfed infant are unknown; the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed infant from therapy or from underlying maternal condition

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. Especially tell your healthcare provider if you take:

• Medicines that affect your immune system 
• IL-1 blocking agents such as Kineret (anakinra), Arcalyst (rilonacept) 
• Tumor Necrosis Factor (TNF) inhibitors such as Enbrel (etanercept) 
• Humira (adalimumab), or Remicade (infliximab) 
• Medicines that can affect enzyme metabolism. Ask your healthcare provider if you are not sure.

Ask your healthcare provider or pharmacist for a list of these medicines, if you are not sure.

Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.

Before you take Ilaris, tell your healthcare provider if you:

• think you have an infection 
• are being treated for an infection 
• have signs of an infection, such as fever, cough, or flu-like symptoms 
• have a history of infections that keep coming back
• have or have had HIV, Hepatitis B, or Hepatitis C
• have an immune system problem. People with these conditions have a higher chance for infections. 
• have tuberculosis (TB), or if you have been in close contact with someone who has or has had tuberculosis 
• are scheduled to receive any immunizations (vaccines). You should not get ‘live vaccines’ if you take Ilaris. 
• are pregnant or planning to become pregnant. It is not known if Ilaris will harm your unborn baby. Tell your healthcare provider right away if you become pregnant while taking Ilaris. 
• are breastfeeding or planning to breastfeed. It is not known if Ilaris passes into your breast milk. You and your healthcare provider should decide if you will take Ilaris or breastfeed. You should not do both.

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements.

Dosage for the treatment of CAPS

The recommended dose of Ilaris for the treatment of cryopyrin-associated periodic syndromes (CAPS) in people who weigh more than 40 kg (88 pounds) is 150 mg every eight weeks.

You should not use this medicine if you are allergic to canakinumab.

Tell your doctor if you have ever had tuberculosis, if anyone in your household has tuberculosis, or if you have recently traveled to an area where tuberculosis is common.

Make sure you are current on all vaccines before you begin treatment with canakinumab.

To make sure canakinumab is safe for you, tell your doctor if you have:

• an active infection;

• a history of low white blood cell counts;

• a weak immune system;

• a history of HIV, hepatitis B, or hepatitis C;

• a history of recurrent infections; or

• if you are scheduled to receive any vaccine.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether canakinumab passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Treatment with canakinumab may increase your risk of developing cancer. Talk to your doctor about your individual risk.

Storage

Parenteral

2–8°C in original carton to protect from light.1

Following reconstitution, store at room temperature, protect from light, and use within 60 minutes or store at 2–8°C and use within 4 hours.1

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Canakinumab injection is used to treat cryopyrin-associated periodic syndromes (CAPS). This also includes familial cold auto-inflammatory syndrome (FCAS) and Muckle-Wells syndrome (MWS). CAPS is a rare, inherited disease of the immune system. It occurs when the body produces too much of a chemical called interleukin-1 beta. This chemical causes inflammation, and patients with CAPS may have a fever, headache, skin rash, joint or muscle pain, or unusual tiredness or weakness.

Canakinumab helps prevent inflammation by keeping the interleukin-1 beta from working properly. This medicine also treats adults and children with other autoinflammatory periodic fever syndromes, such as tumor necrosis factor receptor associated periodic syndrome (TRAPS), hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD), and familial Mediterranean fever (FMF).

Canakinumab is also used to treat active systemic juvenile idiopathic arthritis (SJIA) in children 2 years of age and older.

This medicine is to be given only by or under the direct supervision of a doctor.

It is very important that your doctor check your or your child's progress at regular visits to make sure that this medicine is working properly.

You will need to have a skin test for tuberculosis before you or your child start using this medicine. Tell your doctor if you or anyone in your home has ever had a positive reaction to a tuberculosis test.

Your body's ability to fight an infection may be reduced while you are being treated with canakinumab. It is very important that you call your doctor right away if you or your child have a fever, chills, cough, hoarseness, lower back or side pain, or painful or difficult urination.

Using this medicine may increase your risk of cancer. Talk to your doctor if you have concerns about this risk.

Canakinumab may cause allergic reactions. Tell your doctor right away if you have a rash, itching, lightheadedness or dizziness, swelling of the face, tongue, and throat, trouble breathing or swallowing, or chest pain after you or your child receive the medicine.

Do not get any immunizations (vaccines), especially the live vaccines (eg, nasal flu virus vaccine) without your doctor's approval while you are being treated with this medicine.

This medicine may cause a life-threatening condition called macrophage activation syndrome (MAS). This usually occurs in patients with rheumatic conditions, including SJIA, and must be treated immediately. Tell your doctor right away if you have a fever that lasts longer than 3 days, a cough that does not go away, redness in one part of your body, or warm feeling or swelling of your skin.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time this medicine (Ilaris) is refilled. If you have any questions about this medicine, please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Review Date: October 4, 2017

Confirmed hypersensitivity to the active substance or to any of the excipients [see Warnings and Precautions (5.3) and Adverse Reactions (6.2)].

Approximately 570 patients have been treated with Ilaris in interventional trials in CAPS, TRAPS, HIDS/MKD, FMF or SJIA. These clinical trials included approximately 350 children up to 17 years of age. The most frequently reported adverse drug reactions were infections predominantly of the upper respiratory tract. The majority of the events were mild to moderate although serious infections were observed.

Opportunistic infections have also been reported in patients treated with Ilaris [see Warnings and Precautions (5.1)].

     Clinical Trials Experience 

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Treatment of Periodic Fever Syndromes: CAPS, TRAPS, HIDS/MKD, and FMF

Treatment of CAPS

The data described herein reflect exposure to Ilaris in 104 adult and pediatric CAPS patients, including 20 FCAS, 72 MWS, 10 MWS/NOMID (Neonatal Onset Multisystem Inflammatory Disorder) overlap, 1 non-FCAS non-MWS, and 1 misdiagnosed in placebo-controlled (35 patients) and uncontrolled trials. Sixty-two patients were exposed to Ilaris for at least 6 months, 56 for at least 1 year, and 4 for at least 3 years. A total of 9 serious adverse reactions were reported for CAPS patients. Among these were vertigo (2 patients), infections (3 patients), including intra-abdominal abscess following appendectomy (1 patient). The most commonly reported adverse reactions associated with Ilaris treatment in greater than 10% of the CAPS patients were nasopharyngitis, diarrhea, influenza, rhinitis, nausea, headache, bronchitis, gastroenteritis, pharyngitis, weight increased, musculoskeletal pain, and vertigo. One patient discontinued treatment due to potential infection. 

CAPS Study 1 investigated the safety of Ilaris in an 8-week, open-label period (Part 1), followed by a 24-week, randomized withdrawal period (Part 2), followed by a 16-week, open-label period (Part 3). All patients were treated with Ilaris 150 mg subcutaneously or 2 mg/kg if body weight was greater than or equal to 15 kg and less than or equal to 40 kg (see Table 1). 

Since all CAPS patients received Ilaris in Part 1, there are no controlled data on adverse events (AEs). Data in Table 1 are for all AEs for all CAPS patients receiving canakinumab. In CAPS Study 1, no pattern was observed for any type or frequency of adverse events throughout the three study periods.

Vertigo

Vertigo has been reported in 9% to 14% of patients in CAPS studies, exclusively in MWS patients, and reported as a serious adverse event in two cases. All events resolved with continued treatment with Ilaris. 

Injection-Site Reactions

In CAPS Study 1, subcutaneous injection-site reactions were observed in 9% of patients in Part 1 with mild tolerability reactions; in Part 2, one patient each (7%) had a mild or a moderate tolerability reaction and, in Part 3, one patient had a mild local tolerability reaction. No severe injection-site reactions were reported and none led to discontinuation of treatment. 

Treatment of TRAPS, HIDS/MKD, and FMF

A Phase III trial (TRAPS, HIDS/MKD, and FMF Study 1) investigated the safety of Ilaris in 3 cohorts (TRAPS, HIDS/MKD, and FMF) as follows: a 12-week screening period (Part 1), followed by a 16-week, randomized, double-blind, placebo-controlled parallel-arm treatment period (Part 2), followed by a 24-week randomized withdrawal period (Part 3), followed by a 72-week, open-label treatment period (Part 4). All patients randomized to treatment with Ilaris in Part 2 received 150 mg subcutaneously every 4 weeks if body weight was greater than 40 kg (or 2 mg/kg every 4 weeks if body weight was less than or equal to 40 kg). 

In Part 2 of the TRAPS, HIDS/MKD, and FMF Study 1, initially 90 patients were randomized to Ilaris treatment and 91 patients were randomized to placebo. Of patients randomized to Ilaris, 55.6% remained on the initial dose through week 16 with 6.7% receiving an additional Ilaris dose between Day 7 and Day 15. Of the patients randomized to placebo, 9.9% remained on placebo through Week 16 with 28.6% switching to active treatment with Ilaris by Day 15.

Overall, there were 43 TRAPS, 68 HIDS/MKD, and 58 FMF patients in the safety set with a cumulative canakinumab exposure of 47.61 patient-years. The cumulative exposure in the placebo group was 8.03 patient-years.

In Part 2 of the TRAPS, HIDS/MKD, and FMF Study 1, a total of 22 TRAPS patients aged 3 to 76 years of age, 37 HIDS/MKD patients aged 2 to 43 years of age, and 31 FMF patients aged 2 to 60 years of age were initially randomized to treatment with Ilaris 150 mg every four weeks in the placebo-controlled period of the clinical trial. In addition, 4 non-randomized patients (2 FMF patients of age 20 and 29 years with non-exon 10 mutations and 2 HIDS/MKD patients both of 1 year of age) received open-label treatment in Part 2.

The most commonly reported adverse reactions (greater than or equal to 10%) associated with Ilaris treatment in TRAPS, HIDS/MKD, and FMF patients were injection-site reactions and nasopharyngitis. The reported adverse reactions (greater than or equal to 3%) associated with Ilaris treatment in TRAPS, HIDS/MKD, and FMF patients were injection-site reactions (10.1%), and infections including nasopharyngitis (10.7%), upper respiratory tract infection (7.1%), rhinitis (5.3%), gastroenteritis (3.0%), and pharyngitis (3.0%). Serious infections (e.g., conjunctivitis, pneumonia, pharyngitis, pharyngotonsillitis) were observed in approximately 2.4% (0.03 per 100 patient-days) of patients receiving Ilaris in Part 2 of the TRAPS, HIDS/MKD, and FMF Study 1.

In the Ilaris treatment group, 1 TRAPS patient discontinued treatment due to adverse events, 2 HIDS/MKD patients discontinued treatment due to adverse events, and no FMF patients discontinued treatment due to an adverse event.

Injection-Site Reactions

In the TRAPS, HIDS/MKD, and FMF Study 1, subcutaneous injection-site reactions were observed in 10.1% of patients in Part 2 who had a mild or a moderate tolerability reaction. No severe injection-site reactions were reported and none led to discontinuation of treatment.

Treatment of SJIA

A total of 201 SJIA patients aged 2 to less than 20 years have received Ilaris in clinical trials. The safety of Ilaris compared to placebo was investigated in two phase 3 studies [see Clinical Studies (14.2)]. Patients in SJIA Study 1 received a single dose of Ilaris 4 mg/kg (n=43) or placebo (n=41) via subcutaneous injection and were assessed at Day 15 for the efficacy endpoints and had a safety analysis up to Day 29. SJIA Study 2 was a two-part study with an open-label, single-arm active treatment period (Part I) followed by a randomized, double-blind, placebo-controlled, event-driven withdrawal design (Part II). Overall, 177 patients were enrolled into the study and received Ilaris 4 mg/kg (up to 300 mg maximum) in Part I, and 100 patients received Ilaris 4 mg/kg (up to 300 mg maximum) every 4 weeks or placebo in Part II. Adverse drug reactions listed in Table 2 showed higher rates than placebo from both trials. The adverse drug reactions associated with Ilaris treatment in greater than 10% of SJIA patients were infections, abdominal pain, and injection-site reactions. Serious infections (e.g., pneumonia, varicella, gastroenteritis, measles, sepsis, otitis media, sinusitis, adenovirus, lymph node abscess, pharyngitis) were observed in approximately 4% to 5% (0.02 to 0.17 per 100 patient-days) of patients receiving Ilaris in both studies.

Adverse reactions are listed according to MedDRA version 15.0 system organ class. 

n= number of patients

^IR=Exposure adjusted incidence rate per 100 patient-days

*No injection-site reaction led to study discontinuation

      Hypersensitivity 

During clinical trials, no anaphylactic reactions have been reported. In CAPS trials one patient discontinued and in TRAPS, HIDS/MKD, FMF, and SJIA trials no patients discontinued due to hypersensitivity reactions. Ilaris should not be administered to any patients with known clinical hypersensitivity to Ilaris [see Contraindications (4) and Warnings and Precautions (5.3)].

      Immunogenicity

A biosensor binding assay or a bridging immunoassay was used to detect antibodies directed against canakinumab in patients who received Ilaris. Antibodies against Ilaris were observed in approximately 1.5% and 3.1% of the patients treated with Ilaris for CAPS and SJIA, respectively. No neutralizing antibodies were detected. No apparent correlation of antibody development to clinical response or adverse events was observed. The CAPS clinical studies employed the biosensor binding assay, and most of the SJIA clinical studies employed the bridging assay. The data obtained in an assay are highly dependent on several factors including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, underlying disease, and the number of patients tested. For these reasons, comparison of the incidence of antibodies to canakinumab between the CAPS and SJIA clinical studies or with the incidence of antibodies to other products may be misleading.

No TRAPS, HIDS/MKD and FMF patients treated with Ilaris doses of 150 mg and 300 mg over 16 weeks of treatment tested positive for anti-canakinumab antibodies.

      Laboratory Findings

Hematology

TRAPS, HIDS/MKD, and FMF

Overall, in the TRAPS, HIDS/MKD, and FMF Study 1, neutrophil count decreased (greater than or equal to Grade 2) was reported in 6.5% of patients and platelet count decreased (greater than or equal to Grade 2) was reported in 0.6% of patients.

SJIA

During clinical trials with Ilaris, mean values decreased for white blood cells, neutrophils and platelets.

In the randomized, placebo-controlled portion of SJIA Study 2, decreased white blood cell counts (WBC) less than or equal to 0.8 times lower limit of normal (LLN) were reported in 5 patients (10.4%) in the Ilaris group compared to 2 (4.0%) in the placebo group. Transient decreases in absolute neutrophil count (ANC) to less than 1x109/L were reported in 3 patients (6.0%) in the Ilaris group compared to 1 patient (2.0%) in the placebo group. One case of ANC less than 0.5x109/L was observed in the Ilaris group and none in the placebo group.

Mild (less than LLN and greater than 75x109/L) and transient decreases in platelet counts were observed in 3 (6.3%) Ilaris-treated patients versus 1 (2.0%) placebo-treated patient.

Hepatic Transaminases

Elevations of transaminases have been observed in patients treated with Ilaris.

In the randomized, placebo-controlled portion of SJIA Study 2, high ALT and/or AST greater than or equal to 3 times upper limit of normal (ULN) were reported in 2 (4.1%) Ilaris-treated patients and 1 (2.0%) placebo patient. All patients had normal values at the next visit.

Bilirubin

Asymptomatic and mild elevations of serum bilirubin have been observed in patients treated with Ilaris without concomitant elevations of transaminases.

      Pregnancy

Risk Summary

The limited human data from postmarketing reports on use of Ilaris in pregnant women are not sufficient to inform a drug-associated risk. Monoclonal antibodies, such as canakinumab, are transported across the placenta in a linear fashion as pregnancy progresses; therefore, potential fetal exposure is likely to be greater during the second and third trimesters of pregnancy. In animal embryo-fetal development studies with marmoset monkeys, there was no evidence of embryotoxicity or fetal malformations with subcutaneous administration of canakinumab during the period of organogenesis and later in gestation at doses that produced exposures approximately 11 times the exposure at the maximum recommended human dose (MRHD) and greater. Delays in fetal skeletal development were observed in marmoset monkeys following prenatal exposure to Ilaris at concentrations approximately 11 times the MRHD and greater. Similar delays in fetal skeletal development were observed in mice administered a murine analog of Ilaris during the period of organogenesis. Delays in skeletal ossification are changes from the expected ossification state in an otherwise normal structure/bone: these findings are generally reversible or transitory and not detrimental to postnatal survival [see Animal Data].

The estimated background risk of major birth defects and miscarriage for the indicated population(s) are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Animal Data

In embryo-fetal development studies, pregnant marmoset monkeys received canakinumab from gestation days 25 to 140 at doses that produced exposures approximately 11 times that achieved with MRHD and greater (on a plasma area under the curve (AUC) basis with maternal subcutaneous doses of 15, 50, or 150 mg/kg twice weekly). Ilaris did not elicit any evidence of embryotoxicity or fetal malformations. There were increases in the incidence of incomplete ossification of the terminal caudal vertebra and misaligned and/or bipartite vertebra in fetuses at all dose levels when compared to concurrent controls suggestive of delay in skeletal development in the marmoset. Since Ilaris does not cross-react with mouse or rat IL-1β, pregnant mice were subcutaneously administered a murine analog of Ilaris at doses of 15, 50, or 150 mg/kg during the period of organogenesis on gestation days 6, 11, and 17. The incidence of incomplete ossification of the parietal and frontal skull bones of fetuses was increased in a dose-dependent manner at all dose levels tested.

      Lactation

Risk Summary

There is no information regarding the presence of canakinumab in human milk, the effects on the breastfed infant, or the effects on milk production. Human IgG is known to be present in human milk. The effects of canakinumab in breast milk and possible systemic exposure in the breastfed infant are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Ilaris and any potential adverse effects on the breastfed infant from canakinumab or from the underlying maternal condition.

      Pediatric Use 

The CAPS trials with Ilaris included a total of 23 pediatric patients with an age range from 4 years to 17 years (11 adolescents were treated subcutaneously with 150 mg, and 12 children were treated with 2 mg/kg based on body weight greater than or equal to 15 kg and less than or equal to 40 kg). The majority of patients achieved improvement in clinical symptoms and objective markers of inflammation (e.g., Serum Amyloid A and C-Reactive Protein). Overall, the efficacy and safety of Ilaris in pediatric and adult patients were comparable. Infections of the upper respiratory tract were the most frequently reported infection. The safety and effectiveness of Ilaris in CAPS patients under 4 years of age has not been established [see Clinical Pharmacology (12.3)].

The safety and efficacy of Ilaris in SJIA patients under 2 years of age have not been established [see Clinical Pharmacology (12.3)].

The TRAPS, HIDS/MKD, and FMF trial included a total of 102 pediatric patients (TRAPS, HIDS/MKD and FMF patients) with an age range from 2 to 17 years who received Ilaris. Overall, there were no clinically meaningful differences in the efficacy, safety and tolerability profile of Ilaris in pediatric patients compared to the overall TRAPS, HIDS/MKD, and FMF populations (comprised of adult and pediatric patients, N=169). The majority of pediatric patients achieved improvement in clinical symptoms and objective markers of inflammation.

      Geriatric Use

Clinical studies of Ilaris did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently from younger subjects.

      Patients with Renal Impairment 

No formal studies have been conducted to examine the pharmacokinetics of Ilaris administered subcutaneously in patients with renal impairment.

      Patients with Hepatic Impairment

No formal studies have been conducted to examine the pharmacokinetics of Ilaris administered subcutaneously in patients with hepatic impairment.

Before you start treatment with Ilaris, your doctor may perform tests to make sure you do not have tuberculosis or other infections.

Ilaris is injected under the skin. A healthcare provider will give you this injection.

Ilaris is usually given once every 4 to 8 weeks depending on the condition being treated. Follow your doctor's instructions.

Tell your doctor if you have any changes in weight. Canakinumab doses are based on weight (especially in children and teenagers), and any changes may affect the dose.

Ilaris can weaken your immune system. Your blood may need to be tested often.