SAFETY FOR ILARIS

The safety of ILARIS has been established in ≈500 patients1

Still’s disease (SJIA and AOSD) safety

Safety profile of ILARIS from pivotal SJIA clinical trials1

Pivotal Studies

SJIA Study 1

SJIA Study 2

Corticosteroid-tapering phase
ILARIS-withdrawal phase
ILARIS
(n=43)
Placebo
(n=41)
ILARIS
(n=177)
ILARIS
(n=50)
Placebo
(n=50)
All infections, %*
30
12
55
54
38
Exposure-adjusted incidence rate per 100 patient-days
1.26
1.37
0.91
0.59
0.63
Abdominal pain (upper), %
7
2
14
16
12
Exposure-adjusted incidence rate per 100 patient-days
0.25
0.23
0.16
0.15
0.08
Mild injection site reaction, %
0
7
11
12
4
Moderate injection site reaction, %
0
0
1
2
0

AOSD SAFETY

The safety profile of ILARIS in patients with AOSD in a randomized, double-blind, placebo-controlled study in 36 adults, 22 to 70 years old, was similar to what was observed in patients with SJIA.1

  • ILARIS has been associated with an increased risk of serious infections. Infections, predominantly of the upper respiratory tract, in some instances serious, have been reported with ILARIS1
  • Generally, the observed infections in ILARIS clinical trials responded to standard therapy. Isolated cases of unusual or opportunistic infections (eg, aspergillosis, atypical mycobacterial infections, cytomegalovirus, herpes zoster) were reported during ILARIS treatment. A causal relationship of ILARIS to these events cannot be excluded1
  • Serious infections (eg, 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 pivotal studies1

Additional safety for ILARIS throughout SJIA clinical trials1

  • No injection site reactions led to study discontinuation
  • No anaphylactic reactions attributable to treatment with canakinumab were reported
  • No neutralizing antibodies were detected
  • ILARIS did not appear to increase the incidence of MAS: Eleven cases of MAS were observed in 201 patients with SJIA treated with ILARIS in clinical trials. Based on the clinical trial experience, ILARIS does not appear to increase the incidence of MAS in Still's disease patients, but no definitive conclusions can be made1
    • MAS is a known, life-threatening disorder that may develop in patients with rheumatic conditions, in particular Still's disease, and should be aggressively treated
*The most commonly reported infections were nasopharyngitis and (viral) upper respiratory tract infection. Other infections included pneumonia, rhinitis, pharyngitis, tonsillitis, sinusitis, urinary tract infection, gastroenteritis, and viral infections.
Antibodies against ILARIS were observed in approximately 3.1% of the patients treated with ILARIS for SJIA. No apparent correlation of antibody development to clinical response or adverse events was observed.
FMF, HIDS/MKD, and TRAPS SAFETY

No new or unexpected safety findings emerged in the PFS clinical trial compared with the already approved indication for CAPS2

Safety profile of ILARIS from FMF, HIDS/MKD, and TRAPS clinical trials1

  • In Part 2, 90 patients were initially randomized to ILARIS 150 mg and 91 patients were randomized to placebo every 4 weeks
    • ILARIS group: 55.6% of patients remained on the initial dose through Week 16, with 6.7% receiving an additional ILARIS dose between Day 7 and Day 15
    • Placebo group: 9.9% of patients remained on placebo through Week 16, with 28.6% switching to ILARIS treatment by Day 15
  • Overall, there were 58 patients with FMF, 68 patients with HIDS/MKD, and 43 patients with TRAPS in the safety set with a cumulative exposure of 47.61 patient-years. The cumulative exposure in the placebo group was 8.03 patient-years

Most Common Adverse Drug Reactions (≥3%) in Patients Treated With ILARIS

Adverse reactions by preferred term in ≥3% of patients with FMF, HIDS/MKD, and TRAPS
ILARIS
%
Injection site reactions
10.1
Nasopharyngitis
10.7
Upper respiratory tract infection
7.1
Rhinitis
5.3
Gastroenteritis
3.0
Pharyngitis
3.0
  • The most common adverse reactions (≥10%) were injection-site reactions and nasopharyngitis
  • Serious infections (eg, conjunctivitis, pneumonia, pharyngitis, pharyngotonsillitis) were observed in approximately 2.4% (0.03 per 100 patient-days) of patients receiving ILARIS

Among all 3 patient cohorts in the ILARIS group2:

  • No deaths were reported
  • No anti-ILARIS antibodies were detected in any patient
  • No patients with FMF, 2 patients with HIDS/MKD, and 1 patient with TRAPS discontinued treatment due to AEs
CAPS SAFETY

Safety profile of ILARIS from CAPS clinical trials1

AEs by Preferred Term Occurring in >10% of Patients Throughout Entire Study

Preferred term
ILARIS
(N=35)
n (%)
Number of patients with AEs
35 (100)
Nasopharyngitis
12 (34)
Diarrhea
7 (20)
Influenza
6 (17)
Rhinitis
6 (17)
Nausea
5 (14)
Headache
5 (14)
Bronchitis
4 (11)
Gastroenteritis
4 (11)
Pharyngitis
4 (11)
Weight increased
4 (11)
Musculoskeletal pain
4 (11)
Vertigo
4 (11)
  • A total of 9 serious adverse reactions were reported with ILARIS in CAPS clinical trials, including infections and vertigo
    • 1 patient discontinued treatment due to potential infection
  • 9% of patients experienced injection site reactions in Part 1
    • Injection site reactions occurred in 1 patient in each arm (7%) of Part 2 and in 1 patient in Part 3
    • No severe injection site reactions were reported
  • Infections, predominantly of the upper respiratory tract, in some instances serious, were reported with ILARIS
    • Generally, the observed infections responded to standard therapy
    • Isolated cases of unusual or opportunistic infections (eg, aspergillosis, atypical mycobacterial infections, cytomegalovirus, herpes zoster) were reported during ILARIS treatment. A causal relationship of ILARIS to these events cannot be excluded
These data reflect exposure to ILARIS in 104 adult and pediatric patients with CAPS 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.1
AE=adverse event; AOSD=adult-onset Still’s disease; CAPS=cryopyrin-associated periodic syndromes; FMF=familial Mediterranean fever; HIDS=hyperimmunoglobulin D syndrome; MAS=macrophage activation syndrome; MKD=mevalonate kinase deficiency; PFS=periodic fever syndromes; SJIA=systemic juvenile idiopathic arthritis; TRAPS=tumor necrosis factor receptor–associated periodic syndrome.
References: 1. ILARIS [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2020. 2. Data on file. CACZ885N2301 FMF, HIDS/MKD, and TRAPS Clinical Study Report. Novartis Pharmaceuticals Corporation; 2016.
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IMPORTANT SAFETY INFORMATION

CONTRAINDICATION

ILARIS® (canakinumab) is contraindicated in patients with confirmed hypersensitivity to the active substance or to any of the excipients.

WARNINGS AND PRECAUTIONS

Serious Infections

ILARIS has been associated with an increased risk of serious infections. Physicians should exercise caution when administering ILARIS to patients with infections, a history of recurring infections or underlying conditions, which may predispose them to infections.

ILARIS should not be administered to patients during an active infection requiring medical intervention. Administration of ILARIS should be discontinued if a patient develops a serious infection.

Infections, predominantly of the upper respiratory tract, in some instances serious, have been reported with ILARIS. Generally, the observed infections responded to standard therapy. Isolated cases of unusual or opportunistic infections (eg, aspergillosis, atypical mycobacterial infections, cytomegalovirus, herpes zoster) were reported during ILARIS treatment. A causal relationship of ILARIS to these events cannot be excluded. In clinical trials, ILARIS has not been administered concomitantly with Tumor Necrosis Factor (TNF) inhibitors. An increased incidence of serious infections has been associated with administration of another interleukin-1 (IL-1) blocker in combination with TNF inhibitors. Coadministration of ILARIS with TNF inhibitors is not recommended because this may increase the risk of serious infections.

Drugs that affect the immune system by blocking TNF have been associated with an increased risk of new tuberculosis (TB) and reactivation of latent TB. It is possible that use of IL-1 inhibitors, such as ILARIS, increases the risk of reactivation of TB or of opportunistic infections.

Prior to initiating immunomodulatory therapies, including ILARIS, patients should be evaluated for active and latent TB infection. Appropriate screening tests should be performed in all patients. ILARIS has not been studied in patients with a positive TB screen, and the safety of ILARIS in individuals with latent TB infection is unknown. Patients testing positive in TB screening should be treated by standard medical practice prior to therapy with ILARIS. All patients should be instructed to seek medical advice if signs, symptoms, or high risk exposure suggestive of TB (eg, persistent cough, weight loss, subfebrile temperature) appear during or after ILARIS therapy.

Immunosuppression

The impact of treatment with anti-IL-1 therapy on the development of malignancies is not known. However, treatment with immunosuppressants, including ILARIS, may result in an increase in the risk of malignancies.

Hypersensitivity

Hypersensitivity reactions have been reported with ILARIS therapy. During clinical trials, no anaphylactic reactions attributable to treatment with canakinumab have been reported. It should be recognized that symptoms of the underlying disease being treated may be similar to symptoms of hypersensitivity. If a severe hypersensitivity reaction occurs, administration of ILARIS should be discontinued and appropriate therapy initiated.

Immunizations

Live vaccines should not be given concurrently with ILARIS. Prior to initiation of therapy with ILARIS, patients should receive all recommended vaccinations. In addition, because ILARIS may interfere with normal immune response to new antigens, vaccinations may not be effective in patients receiving ILARIS.

Canakinumab, like other monoclonal antibodies, is actively transported across the placenta mainly during the third trimester of pregnancy and may cause immunosuppression in the in utero exposed infant. The risks and benefits should be considered prior to administering live vaccines to infants who were exposed to ILARIS in utero for at least 4 to 12 months following the mother’s last dose of ILARIS.

Macrophage Activation Syndrome

Macrophage Activation Syndrome (MAS) is a known, life-threatening disorder that may develop in patients with rheumatic conditions, in particular Still’s disease, and should be aggressively treated. Physicians should be attentive to symptoms of infection or worsening of Still’s disease as these are known triggers for MAS. Eleven cases of MAS were observed in 201 SJIA patients treated with canakinumab in clinical trials. Based on the clinical trial experience, ILARIS does not appear to increase the incidence of MAS in Still’s disease patients, but no definitive conclusion can be made.

ADVERSE REACTIONS

Serious adverse reactions reported with ILARIS in the CAPS clinical trials included infections and vertigo. The most common adverse reactions greater than 10% associated with ILARIS treatment in CAPS patients were nasopharyngitis, diarrhea, influenza, rhinitis, headache, nausea, bronchitis, gastroenteritis, pharyngitis, weight increased, musculoskeletal pain, and vertigo.

The most common adverse reactions greater than or equal to 10% reported by patients with TRAPS, HIDS/MKD, and FMF treated with ILARIS were injection site reactions and nasopharyngitis.

The most common adverse drug reactions greater than 10% associated with ILARIS treatment in SJIA patients were infections (nasopharyngitis and upper respiratory tract infections), abdominal pain, and injection site reactions.

INDICATIONS

ILARIS® (canakinumab) is an interleukin-1β blocker indicated for the treatment of the following autoinflammatory Periodic Fever Syndromes:

  • Cryopyrin-Associated Periodic Syndromes (CAPS), in adults and children aged 4 years and older, including:
    • Familial Cold Autoinflammatory Syndrome (FCAS)
    • Muckle-Wells Syndrome (MWS)
  • Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS) in adults and pediatric patients
  • Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD) in adults and pediatric patients
  • Familial Mediterranean Fever (FMF) in adults and pediatric patients

ILARIS® (canakinumab) 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.

View more

IMPORTANT SAFETY INFORMATION

CONTRAINDICATION

ILARIS® (canakinumab) is contraindicated in patients with confirmed hypersensitivity to the active substance or to any of the excipients.

WARNINGS AND PRECAUTIONS

Serious Infections

ILARIS has been associated with an increased risk of serious infections. Physicians should exercise caution when administering ILARIS to patients with infections, a history of recurring infections or underlying conditions, which may predispose them to infections.

ILARIS should not be administered to patients during an active infection requiring medical intervention. Administration of ILARIS should be discontinued if a patient develops a serious infection.

Infections, predominantly of the upper respiratory tract, in some instances serious, have been reported with ILARIS. Generally, the observed infections responded to standard therapy. Isolated cases of unusual or opportunistic infections (eg, aspergillosis, atypical mycobacterial infections, cytomegalovirus, herpes zoster) were reported during ILARIS treatment. A causal relationship of ILARIS to these events cannot be excluded. In clinical trials, ILARIS has not been administered concomitantly with Tumor Necrosis Factor (TNF) inhibitors. An increased incidence of serious infections has been associated with administration of another interleukin-1 (IL-1) blocker in combination with TNF inhibitors. Coadministration of ILARIS with TNF inhibitors is not recommended because this may increase the risk of serious infections.

Drugs that affect the immune system by blocking TNF have been associated with an increased risk of new tuberculosis (TB) and reactivation of latent TB. It is possible that use of IL-1 inhibitors, such as ILARIS, increases the risk of reactivation of TB or of opportunistic infections.

Prior to initiating immunomodulatory therapies, including ILARIS, patients should be evaluated for active and latent TB infection. Appropriate screening tests should be performed in all patients. ILARIS has not been studied in patients with a positive TB screen, and the safety of ILARIS in individuals with latent TB infection is unknown. Patients testing positive in TB screening should be treated by standard medical practice prior to therapy with ILARIS. All patients should be instructed to seek medical advice if signs, symptoms, or high risk exposure suggestive of TB (eg, persistent cough, weight loss, subfebrile temperature) appear during or after ILARIS therapy.

Immunosuppression

The impact of treatment with anti-IL-1 therapy on the development of malignancies is not known. However, treatment with immunosuppressants, including ILARIS, may result in an increase in the risk of malignancies.

Hypersensitivity

Hypersensitivity reactions have been reported with ILARIS therapy. During clinical trials, no anaphylactic reactions attributable to treatment with canakinumab have been reported. It should be recognized that symptoms of the underlying disease being treated may be similar to symptoms of hypersensitivity. If a severe hypersensitivity reaction occurs, administration of ILARIS should be discontinued and appropriate therapy initiated.

Immunizations

Live vaccines should not be given concurrently with ILARIS. Prior to initiation of therapy with ILARIS, patients should receive all recommended vaccinations. In addition, because ILARIS may interfere with normal immune response to new antigens, vaccinations may not be effective in patients receiving ILARIS.

Canakinumab, like other monoclonal antibodies, is actively transported across the placenta mainly during the third trimester of pregnancy and may cause immunosuppression in the in utero exposed infant. The risks and benefits should be considered prior to administering live vaccines to infants who were exposed to ILARIS in utero for at least 4 to 12 months following the mother’s last dose of ILARIS.

Macrophage Activation Syndrome

Macrophage Activation Syndrome (MAS) is a known, life-threatening disorder that may develop in patients with rheumatic conditions, in particular Still’s disease, and should be aggressively treated. Physicians should be attentive to symptoms of infection or worsening of Still’s disease as these are known triggers for MAS. Eleven cases of MAS were observed in 201 SJIA patients treated with canakinumab in clinical trials. Based on the clinical trial experience, ILARIS does not appear to increase the incidence of MAS in Still’s disease patients, but no definitive conclusion can be made.

ADVERSE REACTIONS

Serious adverse reactions reported with ILARIS in the CAPS clinical trials included infections and vertigo. The most common adverse reactions greater than 10% associated with ILARIS treatment in CAPS patients were nasopharyngitis, diarrhea, influenza, rhinitis, headache, nausea, bronchitis, gastroenteritis, pharyngitis, weight increased, musculoskeletal pain, and vertigo.

The most common adverse reactions greater than or equal to 10% reported by patients with TRAPS, HIDS/MKD, and FMF treated with ILARIS were injection site reactions and nasopharyngitis.

The most common adverse drug reactions greater than 10% associated with ILARIS treatment in SJIA patients were infections (nasopharyngitis and upper respiratory tract infections), abdominal pain, and injection site reactions.

INDICATIONS

ILARIS® (canakinumab) is an interleukin-1β blocker indicated for the treatment of the following autoinflammatory Periodic Fever Syndromes:

  • Cryopyrin-Associated Periodic Syndromes (CAPS), in adults and children aged 4 years and older, including:
    • Familial Cold Autoinflammatory Syndrome (FCAS)
    • Muckle-Wells Syndrome (MWS)
  • Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS) in adults and pediatric patients
  • Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD) in adults and pediatric patients
  • Familial Mediterranean Fever (FMF) in adults and pediatric patients

ILARIS® (canakinumab) 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.