FMF, HIDS/MKD, AND TRAPS

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

Percentage of Patients Achieving Complete Response* vs Placebo at Week 161

Bar graph depicting percent of patients with either FMF, HIDS/MKD, and TRAPS achieving complete response at Week 16 with ILARIS.
ILARIS
150 mg
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])
  • At Day 15, the majority of patients with FMF (81%, n/N=25/31), HIDS/MKD (65%, n/N=24/37), and TRAPS (64%, n/N=14/22) who received ILARIS achieved resolution of index disease flare vs placebo: FMF (31%, n/N=10/32), HIDS/MKD (37%, n/N=13/35), and TRAPS (21%, n/N=5/24)
*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.
CAPS

In Study Part 1:
The majority of patients achieved complete clinical response at Weeks 1 and 8 after the first dose of ILARIS1,3

Percentage of Patients Achieving Complete Clinical Response With ILARIS

WEEK 1
71%
(n/N=25/35)
WEEK 8
97%
(n/N=34/35)
Complete clinical response was defined as meeting all of the following criteria3:
  • 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.

In Study Part 2:
After 3 doses of ILARIS, 100% of patients remained flare free through 24 weeks1,3‡

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

Bar graph depicting percentage of patients with CAPS who were flare free with Ilaris vs placebo at week 32
ILARIS
Placebo
100%
(n/N=15/15)
19%
(n/N=3/16)
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.4
§Disease relapse: 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
||Includes all 15 patients randomized to ILARIS in Part 2 and 15 of 16 patients randomized to placebo in Part 2. Disease relapse was 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.1,4
CAPS, cryopyrin-associated periodic syndromes; CRP, C-reactive protein; FMF, familial Mediterranean fever; HIDS, hyperimmunoglobulin D syndrome; MKD, mevalonate kinase deficiency; MWS, Muckle-Wells syndrome; OR, odds ratio; PFS, periodic fever syndromes; PGA, Physician’s Global Assessment; SAA,serum amyloid A; TRAPS, tumor necrosis factor receptor-associated periodic syndrome.
References: 1.Ilaris. Prescribing information. Novartis Pharmaceuticals Corp. 2. Data on file. CACZ885N2301 FMF, HIDS/MKD, and TRAPS Clinical Study Report. Novartis Pharmaceuticals Corp; 2016. 3. Lachmann HJ, Koné‑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 4. Data on file. CACZ885D2304 CAPS Clinical Study Report. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2009.
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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

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

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.

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

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

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.