HELP TAKE THE
FIRE OUT OF
AUTOINFLAMMATORY
DISEASE

ILARIS is the only biologic indicated to treat
7 autoinflammatory diseases across Still’s disease
and a range of Periodic Fever Syndromes (PFS)

  • Still’s disease: SJIA and AOSD
  • PFS: FMF, HIDS/MKD, TRAPS, CAPS (FCAS and MWS)

ILARIS is the only biologic indicated to treat
7 autoinflammatory diseases across Still’s disease
and a range of Periodic Fever Syndromes (PFS)

  • Still’s disease: SJIA and AOSD
  • PFS: FMF, HIDS/MKD, TRAPS, CAPS (FCAS and MWS)

ILARIS is dosed once monthly in Still’s disease, FMF, HIDS/MKD, and TRAPS and once every 2 months in CAPS (FCAS and MWS)1

ILARIS selectively targets IL-1β—a critical driver of autoinflammatory disease to block inflammatory signaling1-5

ILARIS offers dedicated and dependable support for patients throughout their ILARIS treatment journey

Interleukin 1 beta (or IL-1β) is a critical driver of autoinflammatory diseases such as Still’s disease (systemic idiopathic juvenile arthritis and adult-onset Still’s disease) and periodic fever syndromes (eg, familial Mediterranean fever, hyperimmunoglobulin D syndrome/mevalonate kinase deficiency, tumor necrosis factor receptor–associated periodic syndrome, cryopyrin-associated periodic syndromes). IL-6, IL-18, and TNF also play a role in autoinflammatory diseases. IFN-γ and IL-17 are key drivers of autoimmune diseases.2-8 Interleukin 1 beta (or IL-1β) is primarily induced and actively produced by immune cells under disease conditions.9,10 In certain autoinflammatory diseases, there is an excessive release of activated interleukin 1 beta (or IL-1β).3,5,11 This overabundance can cause an inflammatory cascade in Still’s disease and periodic fever syndromes, driving fever and systemic inflammation.5,9,11-17 Interleukin 1 beta (or IL-1β) is one of the master mediators of autoinflammatory disease. The ILARIS (canakinumab) mechanism of action involves selective targeting of interleukin 1 beta (or IL-1β) to block inflammatory signaling.1

ILARIS (canakinumab) is a recombinant, human anti-human–IL-1β monoclonal antibody and the only IL-1β–specific inhibitor.1 ILARIS (canakinumab) is proven efficacious in 7 autoinflammatory diseases across Still’s disease and a range of periodic fever syndromes.1 Additionally, ILARIS (canakinumab) dosing is once monthly in Still’s disease, familial Mediterranean fever, hyperimmunoglobulin D syndrome/mevalonate kinase deficiency, and tumor necrosis factor receptor–associated periodic syndrome. ILARIS (canakinumab) is administered once every 2 months in cryopyrin-associated periodic syndromes, including familial cold autoinflammatory syndrome and Muckle-Wells syndrome.1 The ILARIS support program—also known as ILARIS Companion—offers dedicated and dependable savings and support throughout the treatment journey for patients prescribed ILARIS.

AOSD=adult-onset Still’s disease; CAPS=cryopyrin-associated periodic syndromes; FCAS=familial cold autoinflammatory syndrome; FMF=familial Mediterranean fever; HIDS=hyperimmunoglobulin D syndrome; IL=interleukin; MOA=mechanism of action; MOD=mechanism of disease; 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. Jesus AA, Oliveira JB, Hilário MO, et al. Pediatric hereditary autoinflammatory syndromes. J Pediatr (Rio J). 2010;86(5):353-366. doi:10.2223/JPED.2015 3. Church LD, Cook GP, McDermott MF. Primer: inflammasomes and interleukin 1β in inflammatory disorders. Nat Clin Pract Rheumatol. 2008;4(1):34-42. doi:10.1038/ncprheum0681 4. Lin Y-T, Wang C-T, Gershwin ME, Chiang B-L. The pathogenesis of oligoarticular/polyarticular vs systemic juvenile idiopathic arthritis. Autoimmun Rev. 2011;10(8):482-489. doi:10.1016/j.autrev.2011.02.001 5. Lachmann HJ, Quartier P, So A, Hawkins PN. The emerging role of interleukin-1β in autoinflammatory diseases. Arthritis Rheum. 2011;63(2):314-324. doi:10.1002/art.30105 6. Mellins ED, Macaubas C, Grom AA. Pathogenesis of systemic juvenile idiopathic arthritis: some answers, more questions. Nat Rev Rheumatol. 2011;7(7):416-426. doi:10.1038/nrrheum.2011.68 7. Warrington R, Watson W, Kim HL, Antonetti FR. An introduction to immunology and immunopathology. Allergy Asthma Clin Immunol. 2011;7(suppl 1):S1. doi:10.1186/1710-1492-7-S1-S1 8. Rossi-Semerano L, Koné-Paut I. Is Still’s disease an autoinflammatory syndrome? Int J Inflam. 2012;2012:480373. doi:10.1155/2012/480373 9. Dinarello CA, Simon A, van der Meer JWM. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov. 2012;11(8):633-652. doi:10.1038/nrd3800 10. Dinarello CA. Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol Rev. 2018;281(1):8-27. doi:10.1111/imr.12621 11. Jesus AA, Goldbach-Mansky R. IL-1 blockade in autoinflammatory syndromes. Annu Rev Med. 2014;65:223-244. doi:10.1146/annurev-med-061512-150641 12. McGeough MD, Pena CA, Mueller JL, et al. Cutting edge: IL-6 is a marker of inflammation with no direct role in inflammasome-mediated mouse models. J Immunol. 2012;189(6):2707-2711. doi:10.4049/jimmunol.1101737 13. Ostrov BE. Immunotherapeutic biologic agents to treat autoinflammatory diseases. In: Metodiev K, ed. Immunotherapy - Myths, Reality, Ideas, Future. InTech; 2017:chap 12. Accessed March 2, 2020. doi:10.5772/66547 14. Lopez-Castejon G, Brough D. Understanding the mechanism of IL-1β secretion. Cytokine Growth Factor Rev. 2011;22(4):189-195. doi:10.1016/j.cytogfr.2011.10.001 15. Lopalco G, Cantarini L, Vitale A, et al. Interleukin-1 as a common denominator from autoinflammatory to autoimmune disorders: premises, perils, and perspectives. Mediators Inflamm. 2015;2015:194864. doi:10.1155/2015/194864 16. Jamilloux Y, Gerfaud-Valentin M, Martinon F, Belot A, Henry T, Sève P. Pathogenesis of adult-onset Still’s disease: new insights from the juvenile counterpart. Immunol Res. 2015;61(1-2):53-62. doi:10.1007/s12026-014-8561-9 17. Gurion R, Lehman TJA, Moorthy LN. Systemic arthritis in children: a review of clinical presentation and treatment. Int J Inflam. 2012;2012:271569. doi:10.1155/2012/271569
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.

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.