Efficacy

PROVEN EFFICACY
FOR
PATIENTS WITH
SJIA AND AOSD1

IT'S NOT LUCK. IT'S ILARIS.

Not an actual patient. Individual results will vary.

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

At Day 29, 81% (n/N=35/43) of patients receiving ILARIS compared with 10% (n/N=4/41) of patients receiving placebo achieved aACR30.3

POST
HOC
At Day 15, one-third (33%) of patients achieved inactive disease‡ (vs 0% of patients receiving placebo).2,3
  • Analysis is exploratory and has not been adjusted for multiple comparisons; no conclusions can be drawn
Study 1 Design
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. At baseline, 67% of patients taking ILARIS and 59% of patients receiving placebo were on methotrexate; 72% of patients taking ILARIS and 68% of patients receiving placebo were on prednisone therapy.1,3
*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
‡Inactive disease: Absence of active arthritis, fever, rheumatoid rash, serositis, splenomegaly, hepatomegaly, or generalized lymphadenopathy attributable to SJIA; normal ESR or CRP; physician’s global assessment of disease activity indicating no disease activity. P values were not determined for comparison regarding inactive disease.2,3
SJIA (STUDY 2)

ILARIS decreased steroid use and significantly reduced risk of flare1,3§

In Study 2 (Part 1):
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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)

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Significant reductions in the risk of flare

64% REDUCTION IN RELATIVE FLARE RISK

74% PROBABILITY OF REMAINING FLARE§ FREE VS 25% WITH PLACEBO

  • The study was ended after 37 flare events occurred. Median duration with ILARIS was 221.5 days vs 163.5 days with placebo. Hazard ratio was 0.36 (95% CI, 0.17-0.75)1,3,4
Study 2 Design (Part 1)
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. At baseline, 53% of patients taking ILARIS were on methotrexate; 72% of patients taking ILARIS were on prednisone therapy.1,3,4
  • The primary endpoint was corticosteroid tapering in at least 25% of patients being treated with corticosteroids (45% [57/128] were able to taper their doses of corticosteroids by the end of the steroid-tapering period in Study 2 [Part 1])1,3,4
Study 2 Design (Part 2)
A double-blind withdrawal trial in which patients from Study 2, Part 1 who achieved and sustained aACR30 or above in Part 1 and were not taking corticosteroids or who had undergone successful corticosteroid tapering were subsequently randomized to ILARIS 4 mg/kg (n=50) or placebo (n=50) every 4 weeks. At baseline, 56% of patients taking ILARIS and 52% of patients receiving placebo were on methotrexate; 64% of patients taking ILARIS and 60% of patients receiving placebo were on prednisone therapy.1,3,4
  • The primary endpoint was time to flare event with ILARIS vs placebo. This study continued until 37 flares had occurred1,3,4
§Flare: Worsening of ≥30% in at least 3 of the 6 core aACR response variables combined with improvement of ≥30% in no more than 1 of the 6 variables, or reappearance of fever not due to infections for at least 2 consecutive days.1
||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.4
SJIA (OTHER ENDPOINTS)
Additional Data

Many patients treated with ILARIS achieved aACR responses at the end of the study (≤8 months) and were fever free at Day 31,3,4

aACR Responses at the End of Study 2 (Part 1)

Bar graph depicting aACR Responses with ILARIS Treatment at the End of Study 2 (Part 1)
ILARIS
(N=175)
aACR30
77%
aACR50
73%
aACR70
65%
aACR90
51%
aACR100
34%
Study 2 (Part 1) lasted up to 8 months3,4
  • End of Study 2 (Part 1) results shown are based on patients’ last available assessments

After the initial dose, nearly all patients in the ILARIS group were fever free at Day 3 of each pivotal trial2,4

Only 3 Days After Their First Dose of ILARIS:

STUDY 1
100%
OF PATIENTS WERE FEVER FREE
(n/N=43/43) vs 87% with placebo (n/N=33/38)
STUDY 2 (Part 1)
99%
OF PATIENTS WERE FEVER FREE
(n/N=139/141)
Study 1 Design
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. At baseline, 67% of patients taking ILARIS and 59% of patients receiving placebo were on methotrexate; 72% of patients taking ILARIS and 68% of patients receiving placebo were on prednisone therapy.1,3
Study 2 Design (Part 1)
An open-label steroid-tapering phase in which 177 patients were treated with a subcutaneous dose of 4 mg/kg 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. At baseline, 53% of patients taking ILARIS were on methotrexate; 72% of patients taking ILARIS were on prednisone therapy.1,3,4
  • The primary endpoint was corticosteroid tapering in at least 25% of patients being treated with corticosteroids (45% [57/128] were able to taper their doses of corticosteroids by the end of the steroid-tapering period in Study 2 [Part 1])1,3,4
SJIA (ADDITIONAL DATA)
Additional Data

Once-monthly ILARIS provided systemic and arthritic improvements consistent with overall aACR response2,4

Median Reduction in Number of Active Arthritic Joints in Study 1 and Study 2 (Part 1)

Graph depicting median reduction in number of active arthritic joints in study 1 and study 2, part 1 (ILARIS vs placebo)
ILARIS
(N=43)
Placebo
(N=41)
Study 1: Day 15
–67%
0%
ILARIS
(N=38)
Placebo
(N=7)
Study 1: Day 29
–86%
–32%
ILARIS
(N=177)
End of Study 2 (Part 1)
88%

Median Reduction in Number of Joints With Limited Range of Motion in Study 1 and Study 2 (Part 1)

Graph depicting Median reduction in number of joints with limited range of motion in study 1 and study 2, part 1 (ILARIS vs placebo)
ILARIS
(N=43)
Placebo
(N=41)
Study 1: Day 15
–73%
0%
ILARIS
(N=38)
Placebo
(N=7)
Study 1: Day 29
–83%
–33%
ILARIS
(N=177)
End of Study 2 (Part 1)
–83%

Patients treated with ILARIS achieved a median reduction in CRP levels of approximately 90% in both pivotal trials.

  • In Study 1, patients receiving ILARIS (n=43) achieved a 91% median reduction from baseline in CRP level at Day 15 vs a 5% median increase in patients receiving placebo (n=25)2
  • In Study 2 (Part 1), patients receiving ILARIS (n=177) achieved an 87% median reduction from baseline in CRP level at the end of Study 2 (Part 1)4

The analysis of the aACR components have not been adjusted for multiple comparisons. No conclusions of statistical or clinical significance can be drawn.

AOSD

The only FDA-approved treatment for AOSD

The efficacy of ILARIS in adults with AOSD is based on the pharmacokinetic exposure and extrapolation of the established efficacy of ILARIS in patients with SJIA1

Efficacy of ILARIS was also assessed in a randomized, double-blind, placebo-controlled study that enrolled 36 patients (aged 22 to 70 years) diagnosed with AOSD

  • The efficacy data were generally consistent with the results of a pooled efficacy analysis of patients with SJIA1
ILARIS is approved for the treatment of active Still’s disease including AOSD and SJIA in patients ≥2 years old.
Mechanism of Action STILL'S DISEASE: Safety
aACR adapted JIA American College of Rheumatology; AOSD, adult-onset Still’s disease; CHAQ-DI, Child Health Assessment Questionnaire-Disability Index; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; SJIA, systemic juvenile idiopathic arthritis.
References: 1. Ilaris. Prescribing information. Novartis Pharmaceuticals Corp. 2. Data on file. CACZ885G2305 SJIA Study 1 Clinical Study Report. Novartis Pharmaceuticals Corp; 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. Data on file. CACZ885G2301 SJIA Study 2 Clinical Study Report. Novartis Pharmaceuticals Corp; 2012.
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IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

ILARIS is contraindicated in patients with confirmed hypersensitivity to canakinumab or to any of the excipients.

WARNINGS AND PRECAUTIONS

Serious Infections

ILARIS has been associated with an increased risk of serious infections. Exercise caution when administering ILARIS to patients with infections, a history of recurring infections or underlying conditions, which may predispose them to infections. Avoid administering ILARIS to patients during an active infection requiring medical intervention. Discontinue ILARIS 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, evaluate patients 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. Treat patients testing positive in TB screening according to standard medical practice prior to therapy with ILARIS. Instruct patients 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. Healthcare providers should follow current CDC guidelines both to evaluate for and to treat possible latent TB infections before initiating therapy with ILARIS.

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 Reactions

Hypersensitivity reactions have been reported with ILARIS. 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. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), characterized by serious skin eruptions, has been reported in patients with autoinflammatory conditions treated with ILARIS. If a severe hypersensitivity reaction occurs, immediately discontinue ILARIS; treat promptly and monitor until signs and symptoms resolve.

Immunizations

Avoid administration of live vaccines concurrently with ILARIS. Update all recommended vaccinations prior to initiation of therapy with ILARIS. 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.

The most common adverse reactions greater than 2% reported by adult patients with gout flares treated with ILARIS in clinical trials were nasopharyngitis, upper respiratory tract infections, urinary tract infections, hypertriglyceridemia, and back pain.

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

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 2 years of age and older.

ILARIS is indicated for the symptomatic treatment of adult patients with gout flares in whom nonsteroidal 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.

Please see full Prescribing Information, including Medication Guide, for ILARIS.

View more

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

ILARIS is contraindicated in patients with confirmed hypersensitivity to canakinumab or to any of the excipients.

WARNINGS AND PRECAUTIONS

Serious Infections

ILARIS has been associated with an increased risk of serious infections. Exercise caution when administering ILARIS to patients with infections, a history of recurring infections or underlying conditions, which may predispose them to infections. Avoid administering ILARIS to patients during an active infection requiring medical intervention. Discontinue ILARIS 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, evaluate patients 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. Treat patients testing positive in TB screening according to standard medical practice prior to therapy with ILARIS. Instruct patients 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. Healthcare providers should follow current CDC guidelines both to evaluate for and to treat possible latent TB infections before initiating therapy with ILARIS.

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 Reactions

Hypersensitivity reactions have been reported with ILARIS. 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. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), characterized by serious skin eruptions, has been reported in patients with autoinflammatory conditions treated with ILARIS. If a severe hypersensitivity reaction occurs, immediately discontinue ILARIS; treat promptly and monitor until signs and symptoms resolve.

Immunizations

Avoid administration of live vaccines concurrently with ILARIS. Update all recommended vaccinations prior to initiation of therapy with ILARIS. 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.

The most common adverse reactions greater than 2% reported by adult patients with gout flares treated with ILARIS in clinical trials were nasopharyngitis, upper respiratory tract infections, urinary tract infections, hypertriglyceridemia, and back pain.

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

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 2 years of age and older.

ILARIS is indicated for the symptomatic treatment of adult patients with gout flares in whom nonsteroidal 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.

Please see full Prescribing Information, including Medication Guide, for ILARIS.

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