EFFICACY OF ILARIS

ILARIS is proven efficacious in 7 autoinflammatory diseases across Still’s disease and a range of PFS1

Approved Autoinflammatory Disease Indications

Still’s disease
  • SJIA
  • AOSD
Periodic fever syndromes
  • FMF
  • TRAPS
  • HIDS/MKD
  • CAPS (FCAS and MWS)
SJIA EFFICACY
In Study 1:

Significant improvements in aACR responses were seen with ILARIS at Day 151-3

aACR Responses* After the First Dose of ILARIS vs Placebo at Day 151-3

aACR Responses After the First Dose of ILARIS vs Placebo at Day 15.

aACR Responses* After the First Dose of ILARIS vs Placebo at Day 151-3

ILARIS
(n=43)
Placebo
(n=41)
aACR30
84%
10%
PRIMARY ENDPOINT
aACR50
67%
5%
aACR70
60%
2%
aACR90
42%
0%
aACR100
33%
0%
(P<.001).

SJIA Study 1 Design1,3

A randomized, double-blind, placebo-controlled study in 84 patients with SJIA assessed the efficacy of a single subcutaneous dose of ILARIS (4 mg/kg) vs placebo over 29 days. The primary endpoint was aACR30 at Day 15.

In Study 2 (Part 1):

ILARIS decreased use of steroids within 5 months of treatment1,3

Of the 92 patients who attempted to taper their corticosteroids,

62% SUCCESSFULLY TAPERED their steroid dose (n/N=57/92)

ALMOST HALF (46%) were steroid free (n/N=42/92)

SJIA Study 2 Design (Part 1)1-3

An open-label steroid-tapering phase in which 177 patients were treated with a 4-mg/kg subcutaneous dose of ILARIS every 4 weeks for 12 to 32 weeks. Patients receiving concomitant corticosteroids at the beginning of the study were allowed to taper corticosteroid use from Week 9 through Week 28 if they achieved minimum aACR50.

  • The primary endpoint was corticosteroid tapering in at least 25% of patients being treated with corticosteroids (45% [57/128] were able to taper their dose of corticosteroids by the end of the steroid-tapering period in Study 2 [Part 1])

AOSD EFFICACY

The efficacy of ILARIS in adults with AOSD is based on the established efficacy of ILARIS patients with SJIA.

*aACR response: Percentage improvement (at least 30%, 50%, 70%, 90%, 100%) from baseline in at least 3 of the 6 pediatric ACR core outcome components along with the absence of fever (≤38 °C in the preceding 7 days) and worsening of >30% in no more than 1 of the remaining components. The disease activity components include CRP level, number of joints with active arthritis, number of joints with limited range of motion, physician’s global assessment of disease activity, parent’s or patient’s global assessment of patient’s overall well-being, and functional ability (CHAQ-DI).2,3
Successful corticosteroid tapering: Oral prednisone (or equivalent) dose reduction from >0.8 to ≤0.5 mg/kg/day, or from ≥0.5 and ≤0.8 mg/kg/day by at least 0.3 mg/kg/day, or from any initial dose to ≤0.2 mg/kg/day, while maintaining a minimum aACR30 response.2
§The efficacy of ILARIS in adults with AOSD is based on the pharmacokinetic exposure and extrapolation of the established efficacy of ILARIS in SJIA patients. Efficacy of ILARIS was also assessed in a randomized, double-blind, placebo-controlled study that enrolled 36 patients (22 to 70 years old) diagnosed with AOSD. The efficacy data were generally consistent with the results of a pooled efficacy analysis of SJIA patients.1
FMF, HIDS/MKD, and TRAPS Efficacy

Rapid resolution of index flare at Day 15—with no new flares through Week 16—was achieved by significantly more patients receiving ILARIS1

Percent of Patients Achieving Complete Response vs Placebo at Week 161

Percent of Patient Achieving Complete Responses vs Placebo at Week 16.

Percent of Patients Achieving Complete Response vs Placebo at Week 161

ILARIS 150 mg or 2 mg/kg
Placebo
FMF
61%
(n=31)
6%
(n=32)
(P<.0001)
(OR [95% CI]; 23.75 [4.38, 227.53])
HIDS/MKD
35%
(n=37)
6%
(n=35)
(P=.002)
(OR [95% CI]; 8.94 [1.72, 86.41])
TRAPS
46%
(n=22)
8%
(n=24)
(P=.005)
(OR [95% CI]; 9.17 [1.51, 94.61])

FMF, HIDS/MKD, and TRAPS Study Design1

The efficacy of ILARIS was assessed in patients with PFS across 3 disease cohorts: FMF, HIDS/MKD, and TRAPS. In the 16-week, double-blind, placebo-controlled treatment period, patients were randomized to receive ILARIS 150 mg (2 mg/kg for a body weight ≤40 kg) or placebo every 4 weeks for 16 weeks and were allowed uptitration to ILARIS 300 mg (or 4 mg/kg) every 4 weeks for patients whose disease flare did not resolve or who had persistent disease, or active treatment.

The primary endpoint of the 16-week treatment period was the proportion of patients achieving a complete response without any dose adjustments.

Complete response defined as resolution of index flare (PGA <2 and CRP ≤10 mg/L or a ≥70% reduction from baseline) at Day 15 and no new flare (PGA ≥2 and CRP ≥30 mg/L) throughout the 16-week treatment period.
A 5-point PGA scale was used by physicians to assess overall disease severity, where 0=no disease-associated signs and symptoms, 1=minimal, 2=mild, 3=moderate, and 4=severe. The key signs and symptoms assessed in the PGA for each condition were the following: FMF: abdominal pain, skin rash, chest pain, arthralgia/arthritis; HIDS/MKD: abdominal pain, lymphadenopathy, aphthous ulcers; TRAPS: abdominal pain, skin rash, musculoskeletal pain, eye manifestations.
CAPS Efficacy
In Part 2,

After 3 doses of ILARIS, 100% of patients remained flare free through 24 weeks1,4#

Percent of Patients Who Were Flare Free vs Placebo at Week 32

Percent of CAPS Patients who were flare free at week 32.
ILARIS
Placebo
100%
(n/N=15/15)
19%
(n/N=3/16)

CAPS Study Design1,4

Patients with CAPS (MWS) treated with a subcutaneous dose of ILARIS 150 mg (in patients weighing >40 kg) or ILARIS 2 mg/kg (in patients weighing ≥15 kg and ≤40 kg) every 8 weeks.

PART 1

An 8-week open-label treatment period in which 35 patients were treated with a single injection of ILARIS 150 mg.

PART 2

A double-blind, randomized withdrawal phase in which patients who achieved a complete clinical response and did not relapse by Week 8 in Part 1 were randomized to ILARIS 150 mg or 2 mg/kg in patients weighing ≥15 kg and ≤40 kg (n=15) or placebo (n=16) every 8 weeks for 24 weeks. During Part 2, patients continued with blinded treatment unless a relapse occurred.**

The primary endpoint was the proportion of patients experiencing disease flare or relapse in Part 2.††

For patients with CAPS, ILARIS is dosed once every 8 weeks.
#Ten patients in the placebo group met the criteria for clinical relapse, and 3 patients discontinued Part 2 due to unsatisfactory therapeutic effect.5
**Complete clinical response was defined as meeting all of the following criteria1,4:
  • Physician’s assessment of disease activity ≤ minimal (rated on a 5-point scale consisting of absent, minimal, mild, moderate, and severe)
  • Assessment of skin disease ≤ minimal (rated on a 5-point scale consisting of absent, minimal, mild, moderate, and severe)
  • Normal serum values of CRP and SAA (<10 mg/L)
Assessment of disease activity included a composite of the following symptoms: urticarial skin rash, headache/migraine, fatigue/malaise, conjunctivitis, arthralgia, myalgia, and other symptoms related or unrelated to CAPS.
††Defined as CRP and/or SAA value >30 mg/L and either a score of mild or worse for physician’s assessment of disease activity, or a score of minimal or worse for physician’s assessment of disease activity and assessment of skin disease.1
aACR=adapted JIA American College of Rheumatology; AOSD=adult-onset Still’s disease; CAPS=cryopyrin-associated periodic syndromes; CHAQ-DI=Child Health Assessment Questionnaire-Disability Index; CRP=C-reactive protein; ESR=erythrocyte sedimentation rate; FCAS=familial cold autoinflammatory syndrome; FMF=familial Mediterranean fever; HIDS=hyperimmunoglobulin D syndrome; MKD=mevalonate kinase deficiency; MWS=Muckle-Wells syndrome; 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. CACZ885G2305 SJIA Study 1 Clinical Study Report. Novartis Pharmaceuticals Corporation; 2011. 3. Ruperto N, Brunner HI, Quartier P, et al; PRINTO; PRCSG. Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012;367(25):2396-2406. doi:10.1056/NEJMoa1205099 4. Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, et al; Canakinumab in CAPS Study Group. Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med. 2009;360(23):2416-2425. doi:10.1056/NEJMoa0810787 5. Data on file. CACZ885D2304 CAPS Clinical Study Report. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2009.
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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.