Cigna Drug and Biologic Coverage Policy Subject Canakinumab Table of Contents Coverage Policy... 1 General Background... 3 Coding/Billing Information... 5 References... 5 Effective Date... 7/15/2017 Next Review Date... 7/15/2018 Coverage Policy Number... 1110 Hyperlink to Related Coverage Policies Abatacept Anakinra Anti Tumor Necrosis Factor Therapy Tocilizumab INSTRUCTIONS FOR USE The following Coverage Policy applies to health benefit plans administered by Cigna companies. Coverage Policies are intended to provide guidance in interpreting certain standard Cigna benefit plans. Please note, the terms of a customer s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ significantly from the standard benefit plans upon which these Coverage Policies are based. For example, a customer s benefit plan document may contain a specific exclusion related to a topic addressed in a Coverage Policy. In the event of a conflict, a customer s benefit plan document always supersedes the information in the Coverage Policies. In the absence of a controlling federal or state coverage mandate, benefits are ultimately determined by the terms of the applicable benefit plan document. Coverage determinations in each specific instance require consideration of 1) the terms of the applicable benefit plan document in effect on the date of service; 2) any applicable laws/regulations; 3) any relevant collateral source materials including Coverage Policies and; 4) the specific facts of the particular situation. Coverage Policies relate exclusively to the administration of health benefit plans. Coverage Policies are not recommendations for treatment and should never be used as treatment guidelines. In certain markets, delegated vendor guidelines may be used to support medical necessity and other coverage determinations. Proprietary information of Cigna. Copyright 2017 Cigna Coverage Policy Cigna covers canakinumab (Ilaris ) as medically necessary for ANY of the following: Cryopyrin-Associated Periodic Syndromes (CAPS) in adults and children 4 years of age and older including EITHER of the following: o Familial Cold Autoinflammatory Syndrome (FCAS) o Muckle-Wells Syndrome (MWS) Systemic Juvenile Idiopathic Arthritis (SJIA) in individuals 2 years of age and older Familial Mediterranean fever (FMF) meeting ALL of the following: o Individual is 2 years of age or older o Documented active disease defined as at least 1 flare per month despite colchicine therapy or documented intolerance to effective doses of colchicine o C-Reactive Protein (CRP) greater than 10 mg/l Hyperimmunoglobulin D (Hyper-IgD) syndrome (HIDS)/mevalonate kinase deficiency (MKD) meeting ALL of the following: o Individual is 2 years of age or older o Diagnosis confirmed according to known genetic MVK/enzymatic (MKD) finding o History of 3 or more febrile acute flares within a 6 month period o C-Reactive Protein (CRP) greater than 10 mg/l Tumor necrosis factor (TNF) receptor associated periodic syndrome (TRAPS) meeting ALL of the following: Page 1 of 6
o o o Individual is 2 years of age or older Chronic or recurrent disease defined as 6 or more flares per year C-Reactive Protein (CRP) greater than 10 mg/l Cigna does not cover the use of canakinumab (Ilaris) for any other indication including the following because it is considered experimental, investigational or unproven (this list may not be all-inclusive): Gout Gouty arthritis Neonatal Onset Multisystem Inflammatory Disorder (NOMID) Rheumatoid arthritis (RA) Type 1 and type 2 diabetes Concomitant use with any other biologic including all non-tumor necrosis factor (TNF) biologics and antitumor necrosis factor (TNF) biologics When coverage is available and medically necessary, the dosage, frequency, duration of therapy, and site of care should be reasonable, clinically appropriate, and supported by evidence-based literature and adjusted based upon severity, alternative available treatments, and previous response to canakinumab (Ilaris) therapy. Note: Receipt of sample product does not satisfy any criteria requirements for coverage FDA Approved Indications Periodic Fever Syndromes Ilaris (canakinumab) is an interleukin-1β (IL-1 β) blocker indicated for the treatment of the following autoinflammatory Periodic Fever Syndromes: Cryopyrin-Associated Periodic Syndromes (CAPS) Ilaris is indicated for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), in adults and children 4 years of age and older including: Familial Cold Autoinflammatory Syndrome (FCAS) Muckle-Wells Syndrome (MWS) Tumor Necrosis Factor Receptor (TNF) Associated Periodic Syndrome (TRAPS) Ilaris is indicated for the treatment of Tumor Necrosis Factor (TNF) receptor Associated Periodic Syndrome (TRAPS) in adult and pediatric patients. Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD) Ilaris is indicated for the treatment of Hyperimmunoglobulin D (Hyper-IgD) Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD) in adult and pediatric patients. Familial Mediterranean Fever (FMF) Ilaris is indicated for the treatment of Familial Mediterranean Fever (FMF) in adult and pediatric patients. Systemic Juvenile Idiopathic Arthritis (SJIA) Ilaris is indicated for the treatment of active Systemic Juvenile Idiopathic Arthritis (SJIA) in patients aged 2 years and older. FDA Recommended Dosing General Dosing Information Injection for subcutaneous use only Cryopyrin-Associated Periodic Syndromes (CAPS) Page 2 of 6
The recommended dose of Ilaris is 150 mg for CAPS patients with body weight greater than 40 kg. For CAPS patients with body weight greater than or equal to 15 kg and less than or equal to 40 kg, the recommended dose is 2 mg/kg. For children 15 to 40 kg with an inadequate response, the dose can be increased to 3 mg/kg. Ilaris is administered every eight weeks. Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS), Hyperimmunoglobulin D Syndrome/Mevalonate Kinase Deficiency (HIDS/MKD), and Familial Mediterranean Fever (FMF) The recommended dose of Ilaris for TRAPS, HIDS/MKD, and FMF patients is based on body weight. For patients with body weight less than or equal to 40 kg, the recommended dose is 2 mg/kg administered every 4 weeks. The dose can be increased to 4 mg/kg every 4 weeks if the clinical response is not adequate. For patients with body weight greater than 40 kg, the recommended dose is 150 mg administered every 4 weeks. The dose can be increased to 300 mg every 4 weeks if the clinical response is not adequate. Systemic Juvenile Idiopathic Arthritis (SJIA) The recommended dose of Ilaris for SJIA patients with a body weight greater than or equal to 7.5 kg is 4 mg/kg (with a maximum of 300 mg) administered every 4 weeks. Preparation and Administration of Ilaris Lyophilized Powder STEP 1: Using aseptic technique, reconstitute each vial of Ilaris lyophilized powder by slowly injecting 1 ml of Sterile Water for Injection with a 1-mL syringe and an 18-gauge x 2 needle. STEP 2: Swirl the vial slowly at an angle of about 45 for approximately 1 minute and allow to stand for 5 minutes. Do not shake. Then gently turn the vial upside down and back again ten times. Avoid touching the rubber stopper with your fingers. STEP 3: Allow to stand for about 15 minutes at room temperature. The reconstituted solution has a final concentration of 150 mg/ml. Do not shake. Do not use if particulate matter is present in the solution. Tap the side of the vial to remove any residual liquid from the stopper. The reconstituted solution should be clear to opalescent, colorless to a slightly brownish yellow tint, and essentially free from particulates. If the solution has a distinctly brown discoloration, do not use. Slight foaming of the product upon reconstitution is not unusual. After reconstitution, Ilaris should be kept from light, and can be kept at room temperature if used within 60 minutes of reconstitution. Otherwise, it should be refrigerated at 2 C to 8 C (36 F to 46 F) and used within 4 hours of reconstitution. STEP 4: Using a sterile 1-mL syringe and needle, carefully withdraw the required volume depending on the dose to be administered and subcutaneously inject using a 27-gauge x 0.5 needle. Injection into scar tissue should be avoided as this may result in insufficient exposure to Ilaris. Discard any unused product or waste material in accordance with local requirements. Administration of Ilaris Solution STEP 1: Ilaris solution has a concentration of 150 mg/ml. Do not shake. The solution should be essentially free from particulates, clear to opalescent, colorless to slightly brownish-yellow tint. If the solution has a distinctly brown discoloration, is highly opalescent or contains visible particles, do not use. STEP 2: Using a sterile 1-mL syringe and 18-gauge x 2 needle, carefully withdraw the required volume depending on the dose to be administered and subcutaneously inject using a 27-gauge x 0.5 needle. Injection into scar tissue should be avoided as this may result in insufficient exposure to Ilaris. Discard unused product or waste material in accordance with the local requirements. Drug Availability Each single-use vial of Ilaris contains 180 mg of canakinumab. Each vial is to be reconstituted with 1 ml of preservative-free Sterile Water for Injection resulting in a final concentration of 150 mg/ml. General Background Disease Overview Familial Mediterranean fever (FMF) FMF is characterized by sporadic and recurrent attacks of fever and serosal inflammation; which is manifested by abdominal and chest pain. The initial attack usually occurs prior to the ages of 10 years and 20 years. The Page 3 of 6
onset of fever and pain in FMF patients is usually abrupt and peaks soon after onset. Episodes typically have a duration of one to three days and then spontaneously resolve. Attack frequency is highly variable. The intervals in between the episodes are not regular and range from one week to several months or several years.(ben- Chetrit, 2015) Hyperimmunoglobulin (Hyper-IgD) syndrome (HIDS) Hyperimmunoglobulin D syndrome is a rare autosomal recessive genetic disorder. Hyper-IgD is characterized by recurrent febrile episodes that are typically associated with abdominal pain, lymphadenopathy, and elevated serum polyclonal immunoglobulin D level. Classic HIDS is caused from compound heterozygous or homozygous mutation in the mevalonate kinase gene (MVK). HIDS is one of the major periodic fever syndromes. Symptoms that characterize HIDS include continual fever lasting several days; in addition, the presence of lymphadenopathy, splenomegaly, arthralgia or arthritis, abdominal pain, and rash. (Padeh, 2016) Tumor Necrosis Factor (TNF) receptor associated periodic syndrome (TRAPS) The exact pathogenesis of human TRAPS remains unknown. The median age of presentation is 4.3 years with most presenting in their first decade of life. TRAPS is characterized by recurrent fevers over months or years that is absent of any bacterial or viral infection. Febrile episodes every five to six weeks are typical and fevers commonly last at least five days and usually continue for greater than a two week duration. Other symptoms may include: Focal myalgias and limb pain, sometimes migratory (incidence: 59%-85%), abdominal symptoms (36%-74%), conjunctivitis (18%-22%), rash (55%-63%), chest pain (14%-25%), monoarticular arthritis (13%), periorbital edema (9%-20%). (Nigrovic, 2017) Pharmacology Canakinumab is a human monoclonal anti-human IL-1β antibody of the IgG1/κ isotype. Canakinumab binds to human IL1β and neutralizes its activity by blocking its interaction with IL-1 receptors, but it does not bind IL-1α or IL-1 receptor antagonist (IL-1ra). CAPS refer to rare genetic syndromes generally caused by mutations in the NLRP-3 [nucleotide-binding domain, leucine rich family (NLR), pyrin domain containing 3] gene (also known as Cold-Induced Autoinflammatory Syndrome-1 [CIAS1]). CAPS disorders are inherited in an autosomal dominant pattern with male and female offspring equally affected. Features common to all disorders include fever, urticaria-like rash, arthralgia, myalgia, fatigue, and conjunctivitis. The NLRP-3 gene encodes the protein cryopyrin, an important component of the inflammasome. Cryopyrin regulates the protease caspase-1 and controls the activation of interleukin-1 beta (IL-1β). Mutations in NLRP-3 result in an overactive inflammasome resulting in excessive release of activated IL-1β that drives inflammation. Systemic juvenile idiopathic arthritis (SJIA) is a severe autoinflammatory disease, driven by innate immunity by means of pro-inflammatory cytokines such as interleukin 1β (IL-1β). Guidelines Cryopyrin-Associated Periodic Syndromes FCAS and MWS There are no published guidelines for the treatment of FCAS or MWS. Arcalyst and Ilaris are approved by the FDA for FCAS and MWS. Kineret is approved for the CAPS variant, neonatal onset multisystem inflammatory disorder (NOMID). Juvenile Idiopathic Arthritis: American College of Rheumatology (ACR) The 2013 ACR guidelines for juvenile idiopathic arthritis (JIA) were recently updated to specifically address treatment of systemic JIA (SJIA). Canakinumab is recommended as a therapeutic option for continued disease activity in patients with SJIA with active systemic features and varying degrees of synovitis after treatment with either glucocorticoid monotherapy, methotrexate or leflunomide, anakinra or tocilizumab regardless of the number of active joints (i.e., active joint count [AJC]) or the physician global assessment score (i.e., MD global [a 10 point numerical ranking scale]) or despite prior non-steroidal anti-inflammatory drug (NSAID) monotherapy for patients with an MD global score > 5 regardless of the AJC. For patients with SJIA without active systemic features and with varying degrees of active synovitis, canakinumab is a therapeutic option for continued disease activity if the AJC is > 4 and only after a trial of a disease-modifying antirheumatic drug (DMARD) plus anakinra or tocilizumab; a DMARD plus tumor necrosis factor alpha (TNF-α) inhibitor; or abatacept. For patients with SJIA with features concerning for macrophage activation syndrome (MAS), the ACR states that the use of Page 4 of 6
canakinumab is uncertain, except that it is not appropriate for patients with an MD global < 5 who had received no prior therapy, glucocorticoid monotherapy, or calcineurin monotherapy. (Ringold, 2013) Tumor Necrosis Factor Receptor (TNF) Associated Periodic Syndrome (TRAPS), Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD), There are no published guidelines for the treatment of Tumor Necrosis Factor Receptor (TNF) Associated Periodic Syndrome (TRAPS), Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD), or Familial Mediterranean Fever (FMF). Familial Mediterranean Fever (FMF): European League Against Rheumatism (EULAR) In FMF, EULAR recommends that colchicine should begin as soon as a diagnoses of FMF is made. Biologic treatment, for example anti-il 1 therapy, is indicated in patients that are not responding to maximum tolerated doses of colchicine. In addition, TNF inhibitors have been used to treat colchicine resistant patients. (Ozen et al, 2016). American College of Rheumatology (ACR): Gout The ACR guidelines for gout management state canakinumab is an option for severe attacks of acute gouty arthritis refractory to other agents based on randomized controlled trials and/or meta-analyses. However, due to an unclear risk/benefit ratio and lack of FDA approval, the guideline authors state that the role of IL-1 inhibitor therapy (e.g., canakinumab) for use in acute gout is uncertain. (Khanna, 2012) Experimental Investigational, Unproven Uses Ilaris has been evaluated for use in type 1 and type 2 diabetes, rheumatoid arthritis, gout, and gouty arthritis. At this time, however, there is insufficient published data in terms of safety and efficacy to support the use of Ilaris for these indications. (Hensen, 2013; Moran, 2013; Reike, 2011; Rissanen, 2012; Schlesinger, 2012) Coding/Billing Information Note: 1) This list of codes may not be all-inclusive. 2) Deleted codes and codes which are not effective at the time the service is rendered may not be eligible for reimbursement. Covered when medically necessary: HCPCS Codes J0638 Description Injection, canakinumab, 1 mg References 1. Ben-Chetrit, E. (2017, Feb 7). Clinical manifestations and diagnosis of familial Mediterranean fever. Retrieved from uptodate.com 2. Hensen J, Howard CP, Walter V, Thuren T. Impact of interleukin-1β antibody (canakinumab) on glycaemic indicators in patients with type 2 diabetes mellitus: Results of secondary endpoints from a randomized, placebo-controlled trial. Diabetes Metab 2013; 39: 524-31. 3. Hoffman HM, Rosengren S, Boyle DL, et al. Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonist. Lancet. Nov 13-19 2004; 364 (9447): 1779-1785. 4. Khanna D, Khanna PP, Fitzgerald JD, et al. 2012 American College of Rheumatology Guidelines for Management of Gout. Part 2: Therapy and Antiinflammatory Prophylaxis of Acute Gouty Arthritis. Arthritis Care Res 2012; 64 (10): 1447 61. Page 5 of 6
5. Maksimovic L, Stirnemann J, Caux F, et al. New CIAS1 mutation and anakinra efficacy in overlapping of Muckle-Wells and familial cold autoinflammatory syndromes. Rheumatology (Oxford, England). Mar 2008;47(3):309-310. 6. McEvoy GK, ed. AHFS 2016 Drug Information. Bethesda, MD: American Society of Health-Systems Pharmacists, Inc. 2016. 7. Moran A, Bundy B, Becker DJ, et al for the AIDA Study Group. Interleukin-1 antagonism in type 1 diabetes of recent onset: two multicentre, randomised, double-blind, placebo-controlled trials. Lancet 2013; 381: 1905-15. 8. Nigrovic, P. (2017, Jun 5). Tumor necrosis factor receptor-1 associated periodic syndrome (TRAPS). Retrieved from uptodate.com 9. Novartis Pharmaceuticals Corporation. Ilaris (canakinumab) injection for subcutaneous use [product information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation. October 2014. 10. Ozen S, Demirkaya E, Erer B, et al. EULAR recommendations for the management of familial Mediterranean fever. Ann Rheum Dis. 2016;75:644-51. 11. Padeh, Y. (2016, Jun 28). Hyperimmunoglobulin D syndrome: Clinical manifestations and diagnosis. Retrieved from www.uptodate.com 12. Rieke, A. et.al Efficacy and safety of the human anti-il-1beta monoclonal antibody canakinumab in rheumatoid arthritis: results of a 12-week, phase II, dose-finding study. BMC Musculoskelet Disord. 2011;12:153. 13. Ringold S, Weiss PF, Beukelman T, et al. 2013 Update of the 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: Recommendations for the medical therapy of children with systemic juvenile idiopathic arthritis and tuberculosis screening among children receiving biologic medications. Arthritis Rheum 2013; 65 (10): 2499-512. 14. Rissanen A, Howard CP, Botha J, Thuren T for the Global Investigators. Effect of anti-il-1β antibody (canakinumab) on insulin secretion rates in impaired glucose tolerance or type 2 diabetes: results of a randomized, placebo-controlled trial. Diabetes Obes Metab 2012; 14: 1088-96. 15. Schlesinger N, Alten RE, Bardin T, et al. Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions. Ann Rheum Dis 2012; 71(11):1839-48. The registered marks "Cigna" and the "Tree of Life" logo are owned by Cigna Intellectual Property, Inc., licensed for use by Cigna Corporation and its operating subsidiaries. All products and services are provided by or through such operating subsidiaries and not by Cigna Corporation. Such operating subsidiaries include Connecticut General Life Insurance Company, Cigna Health and Life Insurance Company, Cigna Behavioral Health, Inc., Cigna Health Management, Inc., and HMO or service company subsidiaries of Cigna Health Corporation. Page 6 of 6