Coverage Policy Manual
Policy #: 2020026
Category: Pharmacy
Initiated: February 2021
Last Review: August 2023
  Canakinumab (e.g., Ilaris™)
Description:
Canakinumab is a recombinant, human anti-human-IL-1β monoclonal antibody that belongs to the IgG1/κ isotype subclass. Canakinumab binds to human IL-1β 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). (Ilaris, 2020)
 
Regulatory Status
 
Canakinumab (e.g., Ilaris™) is approved by the U.S. Food and Drug Administration (FDA) for the following indications:
    1. Periodic Fever Syndrome
a. Cryopyrin-Associated Periodic Syndromes (CAPS)
b. Familial Mediterranean Fever (FMF)
c. Hyperimmunoglobulin D Syndrome/ Mevalonate Kinase Deficiency (HIDS/MKD)
d. Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS)
2. Still’s Disease
a. Adult-Onset Still’s Disease (AOSD)
b. Systemic Juvenile Idiopathic Arthritis (SJIA)  
 
Coding
 
See CPT/HCPCS Code section below.
 
Policy/
Coverage:
Effective February 25, 2021 Prior Approval is required for Canakinumab (e.g., Ilaris™).
 
The initial use of this drug requires documentation of direct physician involvement and signature in the ordering and evaluation as documented in the medical records submitted for prior approval. Concurrent review will require continued evidence of appropriate physician involvement.  
 
The Step Therapy Medication Act is applicable to fully-insured (Arkansas Blue Cross, Health Advantage, and Exchange) and specified governmental (ASE/PSE and ASP) health plans. The law is not applicable to FEP or self-insured ERISA groups (including but not limited to Walmart, Tyson or other Blue Advantage groups). Initial approval for exigent request is 28 days. Otherwise, initial approval for standard review is up to 1 year.
 
Effective August 23, 2023
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
 
The use of Canakinumab meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when the following criteria are met based on diagnosis:
 
Cryopyrin-Associated Periodic Syndromes
Individual 4 years of age or older has diagnosis of either of the following CAPS:
    1. Familial cold auto inflammatory syndrome (FDA, 2020) OR
    2. Muckle-Wells syndrome (FDA, 2020) AND
    3. Documentation submitted confirming NLRP3 mutation (Lachmann, 2009) AND 
    4. Individual will not be using in combination with TNF antagonists or other IL-1 antagonist AND
    5. Individual does not have Tuberculosis, other active serious infections, or a history of recurrent infections, AND
    6. Individual has not had a tuberculin skin test (TST) or a Centers for Disease Control (CDC-) and Prevention -recommended equivalent to evaluate for latent tuberculosis prior to initiating Canakinumab AND
    7. Must be dosed in accordance with the FDA label.
 
Familial Mediterranean Fever
Individual 2 years of age or older has a diagnosis of FMF AND
    1. Individual has had active flares within the last 6 months defined as:
a.  Physician’s Global Assessment score greater than or equal to 2 (Benedetti, 2018) OR
b.  C-reactive protein (CRP) greater than 10 mg/L (Benedetti, 2018) AND
2.  Individual has had an inadequate response to, is intolerance of, or has a contraindication to colchicine (Benedetti, 2018) AND
3.  Documentation submitted confirming at least one known MEFV gene exon 10 mutation (Benedetti, 2018) AND
4. Individual will not be using in combination with TNF antagonists or other IL-1 antagonist AND
5. Individual does not have Tuberculosis, other active serious infections, or a history of recurrent infections, AND
6. Individual has not had a tuberculin skin test (TST) or a Centers for Disease Control (CDC-) and Prevention -recommended equivalent to evaluate for latent tuberculosis prior to initiating Canakinumab AND
7. Must be dosed in accordance with the FDA label.
 
Hyperimmunoglobulin D Syndrome/ Mevalonate Kinase Deficiency
Individual 2 years of age or older has a diagnosis of HIDS/MKD AND
    1. Individual has had active flares within the last 6 months defined as:
a.  Physician’s Global Assessment score greater than or equal to 2 (Benedetti, 2018) OR
b.  C-reactive protein (CRP) greater than 10 mg/L (Benedetti, 2018) AND  
2.  Documentation submitted confirming genetic or enzymatic diagnosis of mevalonate kinase deficiency (Benedetti, 2018) AND
3. Individual will not be using in combination with TNF antagonists or other IL-1 antagonist AND
4. Individual does not have Tuberculosis, other active serious infections, or a history of recurrent infections, AND
5. Individual has not had a tuberculin skin test (TST) or a Centers for Disease Control (CDC-) and Prevention -recommended equivalent to evaluate for latent tuberculosis prior to initiating Canakinumab AND  
6. Must be dosed in accordance with the FDA label.
 
Tumor Necrosis Factor Receptor Associated Periodic Syndrome
Individual 2 years of age or older has a diagnosis of TRAPS AND
    1. Individual has had active flares within the last 6 months defined as:
a.  Physician’s Global Assessment score greater than or equal to 2 (Benedetti, 2018) OR
b.  C-reactive protein (CRP) greater than 10 mg/L (Benedetti, 2018) AND
2.  Documentation submitted confirming TNFRSF1A mutation (Benedetti, 2018) AND
3. Individual will not be using in combination with TNF antagonists or other IL-1 antagonist AND
4. Individual does not have Tuberculosis, other active serious infections, or a history of recurrent infections, AND
5. Individual has not had a tuberculin skin test (TST) or a Centers for Disease Control (CDC-) and Prevention -recommended equivalent to evaluate for latent tuberculosis prior to initiating Canakinumab AND
6. Must be dosed in accordance with the FDA label.
 
Adult-Onset Still’s Disease & Systemic Juvenile Idiopathic Arthritis
Individual 2 years of age or older has a diagnosis of SJIA or AOSD AND
    1. Individual has had an inadequate response to at least a two-week trial, is intolerant of, or has a contraindication to oral or intravenous corticosteroids (ACR, 2013) OR
    2. Individual has had an inadequate response to at least a one-month trial, is intolerant of, or has a contraindication to NSAIDs (ACR, 2013) OR
    3. Individual has had an inadequate response to at least a three-month trial, is intolerant of, or has a contraindication to methotrexate or leflunomide (ACR, 2013) AND 
    4. Individual will not be using in combination with TNF antagonists or other IL-1 antagonist AND
    5. Individual does not have Tuberculosis, other active serious infections, or a history of recurrent infections, AND
    6. Individual has not had a tuberculin skin test (TST) or a Centers for Disease Control (CDC-) and Prevention -recommended equivalent to evaluate for latent tuberculosis prior to initiating Canakinumab AND 
    7. Must be dosed in accordance with the FDA label.
 
Continuation for 12 months:
 
Authorization for continuation may be granted for all individuals who achieve or maintain positive clinical response as evidence by low disease activity or improvement in signs and symptoms.
 
Physician Global Assessment of disease activity, taking into account fever and clinical signs and symptoms associated with each disease (as listed below) with the use of a 5-point scale with scores of 0 (none), 1 (minimal), 2 (mild), 3 (moderate) and 4 (severe).
 
FMF                                     HIDS/MKD                              TRAPS
Chest pain                            Lymphadenopathy                    Skin rash
Abdominal pain                     Aphthous ulcers                         Musculoskeletal pain
Arthralgia/arthritis                  Abdominal pain                        Abdominal pain
Skin rash                                                                            Eye manifestations
 
Dosage and Administration
Dosing per FDA Guidelines
 
The recommended dose of Canakinumab is based on indication:
 
CAPS- 150 mg for individuals with body weight greater than 40 kg and 2 mg/kg for individuals with body weight greater than or equal to 15 kg and less than or equal to 40 kg. For children 15 to 40 kg with an inadequate response, the dose can be increased to 3 mg/kg. Administer subcutaneously every 8 weeks.
 
FMF, HIDS/MKD, and TRAPS- 150mg for patients with body weight greater than 40 kg and can be increased to 300mg if the clinical response is not adequate. 2mg/kg for patients with body weight less than or equal to 40 kg and can be increased to 4mg/kg if the clinical response is not adequate. Administer subcutaneously every 4 weeks.
 
AOSD and SJIA- 4 mg/kg (with a maximum of 300 mg) for individuals with a body weight greater than or equal to 7.5 kg. Administer subcutaneously every 4 weeks.
 
Canakinumab is administered by subcutaneous injection by a healthcare provider.
 
Canakinumab is available as 150mg lyophilized powder in single dose vials and 150mg solution in single dose vials.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of canakinumab for any indication or circumstance other than those described above does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For individuals with contracts without primary coverage criteria, the use of Canakinumab for any indication or circumstance not described above is considered investigational.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective December 1, 2021 to August 22, 2023
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
The use of Canakinumab meets primary coverage criteria when dosed in accordance with FDA approved labeling AND when the following criteria are met based on diagnosis:
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
 
Cryopyrin-Associated Periodic Syndromes
Individual 4 years of age or older has diagnosis of either of the following CAPS:
    1. Familial cold auto inflammatory syndrome (FDA, 2020) OR
    2. Muckle-Wells syndrome (FDA, 2020) AND
    3. Documentation submitted confirming NLRP3 mutation (Lachmann, 2009)
    4. Must be dosed in accordance with the FDA label unless otherwise specified.
 
Familial Mediterranean Fever
Individual 2 years of age or older has a diagnosis of FMF AND
    1. Member has had active flares within the last 6 months defined as:
a.  Physician’s Global Assessment score greater than or equal to 2 (Benedetti, 2018) OR
b.  C-reactive protein (CRP) greater than 10 mg/L (Benedetti, 2018) AND
2.  Individual has had an inadequate response to, is intolerance of, or has a contraindication to colchicine (Benedetti, 2018) AND
3.  Documentation submitted confirming at least one known MEFV gene exon 10 mutation (Benedetti, 2018)
4.  Must be dosed in accordance with the FDA label unless otherwise specified.
 
Hyperimmunoglobulin D Syndrome/ Mevalonate Kinase Deficiency
Individual 2 years of age or older has a diagnosis of HIDS/MKD AND
    1. Individual has had active flares within the last 6 months defined as:
a.  Physician’s Global Assessment score greater than or equal to 2 (Benedetti, 2018) OR
b.  C-reactive protein (CRP) greater than 10 mg/L (Benedetti, 2018) AND  
2.  Documentation submitted confirming genetic or enzymatic diagnosis of mevalonate kinase deficiency (Benedetti, 2018)
3.  Must be dosed in accordance with the FDA label unless otherwise specified.
 
Tumor Necrosis Factor Receptor Associated Periodic Syndrome
Individual 2 years of age or older has a diagnosis of TRAPS AND
    1. Individual has had active flares within the last 6 months defined as:
a.  Physician’s Global Assessment score greater than or equal to 2 (Benedetti, 2018) OR
b.  C-reactive protein (CRP) greater than 10 mg/L (Benedetti, 2018) AND
2.  Documentation submitted confirming TNFRSF1A mutation (Benedetti, 2018)
3.  Must be dosed in accordance with the FDA label unless otherwise specified.
 
Adult-Onset Still’s Disease & Systemic Juvenile Idiopathic Arthritis
Individual 2 years of age or older has a diagnosis of SJIA or AOSD AND
    1. Individual has had an inadequate response to at least a two-week trial, is intolerant of, or has a contraindication to oral or intravenous corticosteroids (ACR, 2013) OR
    2. Individual has had an inadequate response to at least a one-month trial, is intolerant of, or has a contraindication to NSAIDs (ACR, 2013) OR
    3. Individual has had an inadequate response to at least a three-month trial, is intolerant of, or has a contraindication to methotrexate or leflunomide (ACR, 2013)
    4. Must be dosed in accordance with the FDA label unless otherwise specified.
 
Continuation for 12 months:
Authorization for continuation may be granted for all members who achieve or maintain positive clinical response as evidence by low disease activity or improvement in signs and symptoms.
 
Physician Global Assessment of disease activity, taking into account fever and clinical signs and symptoms associated with each disease (as listed below) with the use of a 5-point scale with scores of 0 (none), 1 (minimal), 2 (mild), 3 (moderate) and 4 (severe).
 
FMF                                     HIDS/MKD                              TRAPS
Chest pain                            Lymphadenopathy                    Skin rash
Abdominal pain                     Aphtous ulcers                         Musculoskeletal pain
Arthralgia/arthritis                  Abdominal pain                        Abdominal pain
Skin rash                                                                            Eye manifestations
 
Dosage and Administration
 
The recommended dose of Canakinumab is based on indication:
    1. CAPS- 150 mg for patients with body weight greater than 40 kg and 2 mg/kg for patients with body weight greater than or equal to 15 kg and less than or equal to 40 kg. For children 15 to 40 kg with an inadequate response, the dose can be increased to 3 mg/kg. Administer subcutaneously every 8 weeks.
    2. FMF, HIDS/MKD, and TRAPS- 150mg for patients with body weight greater than 40 kg and can be increased to 300mg if the clinical response is not adequate. 2mg/kg for patients with body weight less than or equal to 40 kg and can be increased to 4mg/kg if the clinical response is not adequate. Administer subcutaneously every 4 weeks.
    3. AOSD and SJIA- 4 mg/kg (with a maximum of 300 mg) for patients with a body weight greater than or equal to 7.5 kg. Administer subcutaneously every 4 weeks.
 
Canakinumab is administered by subcutaneous injection by a healthcare provider. Canakinumab is available as 150mg lyophilized powder in single dose vials and 150mg solution in single dose vials.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of canakinumab does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes including the following:
    1. In combination with TNF antagonists or other IL-1 antagonist OR  
    2. Tuberculosis, other active serious infections, or a history of recurrent infections; OR  
    3. Individual has not had a tuberculin skin test (TST) or a Centers for Disease Control (CDC-) and Prevention -recommended equivalent to evaluate for latent tuberculosis prior to initiating Canakinumab
 
For individuals with contracts without primary coverage criteria, the use of Canakinumab for any indication or circumstance not described above is considered investigational including the following:
    1. In combination with TNF antagonists or other IL-1 antagonist OR  
    2. Tuberculosis, other active serious infections, or a history of recurrent infections; OR  
    3. Individual has not had a tuberculin skin test (TST) or a Centers for Disease Control (CDC-) and Prevention -recommended equivalent to evaluate for latent tuberculosis prior to initiating Canakinumab
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective 2/18/2021 to11/30/2021
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
The use of Canakinumab meets primary coverage criteria when dosed in accordance with FDA approved labeling AND when the following criteria are met based on diagnosis:
 
Initial approval for 12 months:
 
Cryopyrin-Associated Periodic Syndromes
Member 4 years of age or older has diagnosis of either of the following CAPS:
  1. Familial cold auto inflammatory syndrome OR
  2. Muckle-Wells syndrome AND
  3. Documentation submitted confirming NLRP3 mutation
 
Familial Mediterranean Fever
Member 2 years of age or older has a diagnosis of FMF AND
  1. Member has had active flares within the last 6 months defined as:
a.  Physician’s Global Assessment score greater than or equal to 2 (Benedetti, 2018) OR
b.  C-reactive protein (CRP) greater than 10 mg/L (Benedetti, 2018) AND
2.  Member has had an inadequate response to, is intolerance of, or has a contraindication to colchicine AND
3.  Documentation submitted confirming at least one known MEFV gene exon 10 mutation (Benedetti, 2018)
 
Hyperimmunoglobulin D Syndrome/ Mevalonate Kinase Deficiency
Member 2 years of age or older has a diagnosis of HIDS/MKD AND
  1. Member has had active flares within the last 6 months defined as:
a.  Physician’s Global Assessment score greater than or equal to 2 (Benedetti, 2018) OR
b.  C-reactive protein (CRP) greater than 10 mg/L (Benedetti, 2018) AND
2.  Documentation submitted confirming elevated serum IgD based on member age OR
3.  Documentation submitted confirming genetic mutation in the MVK gene (Benedetti, 2018)
 
Tumor Necrosis Factor Receptor Associated Periodic Syndrome
Member 2 years of age or older has a diagnosis of TRAPS AND
  1. Member has had active flares within the last 6 months defined as:
a.  Physician’s Global Assessment score greater than or equal to 2 (Benedetti, 2018) OR
b.  C-reactive protein (CRP) greater than 10 mg/L (Benedetti, 2018) AND
2.  Documentation submitted confirming TNFRSF1A mutation (Benedetti, 2018)
 
Adult-Onset Still’s Disease & Systemic Juvenile Idiopathic Arthritis
Member 2 years of age or older has a diagnosis of SJIA or AOSD AND
  1. Member has had an inadequate response to at least a two-week trial, is intolerant of, or has a contraindication to oral or intravenous corticosteroids OR
  2. Member has had an inadequate response to at least a one-month trial, is intolerant of, or has a contraindication to NSAIDs OR
  3. Member has had an inadequate response to at least a three-month trial, is intolerant of, or has a contraindication to methotrexate or leflunomide
 
Continuation for 12 months:
Authorization for continuation may be granted for all members who achieve or maintain positive clinical response as evidence by low disease activity or improvement in signs and symptoms.
 
Physician Global Assessment of disease activity, taking into account fever and clinical signs and symptoms associated with each disease (as listed below) with the use of a 5-point scale with scores of 0 (none), 1 (minimal), 2 (mild), 3 (moderate) and 4 (severe).
 
FMF                                     HIDS/MKD                              TRAPS
Chest pain                            Lymphadenopathy                    Skin rash
Abdominal pain                     Aphtous ulcers                          Musculoskeletal pain
Arthralgia/arthritis                  Abdominal pain                         Abdominal pain
Skin rash                                                                             Eye manifestations
 
Requests for Canakinumab do not meet primary coverage criteria for the following:
  • In combination with TNF antagonists or other IL-1 antagonist OR  
  • Tuberculosis, other active serious infections, or a history of recurrent infections; OR  
  • Individual has not had a tuberculin skin test (TST) or a Centers for Disease Control (CDC-) and Prevention -recommended equivalent to evaluate for latent tuberculosis prior to initiating Canakinumab.
 
Dosage and Administration
The recommended dose of Canakinumab is based on indication:
  1. CAPS- 150 mg for patients with body weight greater than 40 kg and 2 mg/kg for patients with body weight greater than or equal to 15 kg and less than or equal to 40 kg. For children 15 to 40 kg with an inadequate response, the dose can be increased to 3 mg/kg. Administer subcutaneously every 8 weeks.
  2. FMF, HIDS/MKD, and TRAPS- 150mg for patients with body weight greater than 40 kg and can be increased to 300mg if the clinical response is not adequate. 2mg/kg for patients with body weight less than or equal to 40 kg and can be increased to 4mg/kg if the clinical response is not adequate. Administer subcutaneously every 4 weeks.
  3. AOSD and SJIA- 4 mg/kg (with a maximum of 300 mg) for patients with a body weight greater than or equal to 7.5 kg. Administer subcutaneously every 4 weeks.
 
Canakinumab is administered by subcutaneous injection by a healthcare provider. Canakinumab is available as 150mg lyophilized powder in single dose vials and 150mg solution in single dose vials.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of canakinumab does not meet member benefit certificate primary coverage criteria for any other indication.
 
For members with contracts without primary coverage criteria, the use of Canakinumab in any other condition than listed above is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Rationale:
The efficacy and safety of Canakinumab for the treatment of CAPS was demonstrated in a three-part, 48-week, double-blind, placebo-controlled, randomized, withdrawal study. Patients who had CAPS associated with a NLRP3 mutation and who required treatment were eligible for enrollment. 35 patients received 150mg of Canakinumab (2mk/kg for patients weighing 15 to 40kg) subcutaneously in Part 1. At Week 8, 34 of the 35 patients (97%) had complete response to Canakinumab and entered into Part 2. These patients were randomly assigned to receive either 150mg of Canakinumab or placebo every 8 weeks for up to 24 weeks. After 24 weeks or at the time of relapse, whichever occurred first, patients entered into Part 3. These patients received at least two more doses of Canakinumab once every 8 weeks in an open-label active treatment phase.   81% of the patients randomized to placebo in Part 2 flared as compared to non (0%) of the patients randomized to Canakinumab. 28/30 (90%) of patients who completed part 3 were in remission.
 
The efficacy and safety of Canakinumab for the treatment of TRAPS, HIDS/MKD, and FMF was demonstrated in a 4-part study consisting of three separate disease cohorts. Eligible patients was 2 years of age or older. Inclusion criteria for patients with FMF were fulfillment of Tel-Hasomer diagnostic criteria, at least one known MEFV exon 10 mutation, and historical data documenting at least one fever episode per month despite standard dose of colchicine. Patients were allowed to continue colchicine dose. Inclusion criteria for patients with HIDS/MKD was a genetic or enzymatic diagnosis of mevalonate kinase deficiency and historical data documenting at least three fever episodes in a 6-month period. Inclusion criteria for patients with TRAPS was TNFRSF1A mutation and chronic or recurrent disease (recurrent disease was defined as >6 fever episodes per year).
 
The primary outcome was the proportion of patients who had a complete response, defined as resolution of baseline flare at Day 15 and no new flare until Week 16. Resolution of the disease flare was defined as a Physician’s Global Assessment (PGA) Disease Activity score less than 2 and CRP within normal range or reduction greater than or equal to 70% from baseline. A new flare was defined as a PGA score greater than or equal to 2 and CRP greater to or equal than 30mg/L.
185 patients were enrolled in the study. Patients in each cohort entered a 12-week screening period during which they were evaluated for the onset of disease flare. Patients were randomized at flare onset into a 12-week double-blind, placebo-controlled treatment period where they received either 150 Canakinumab (2mk/kg for patients weighing less than or equal to 40kg) or placebo once every four weeks. Patients treated with Canakinumab were given an additional dose of 150mg Canakinumab (2mg/kg for patients weighing less than or equal to 40kg) if their disease flare did not resolve, or they had persistent disease activity from Day 8 to Day 14. Patients treated with Canakinumab also received an additional dose of 150mg Canakinumab or 2mg/kg for patients weighing less than or equal to 40kg if their disease flare did not resolve, or who has persistent disease activity from Day 15 to Day 28.
 
46 patients were randomized in the TRAPS cohort. 22 patients were randomized to receive 150mg Canakinumab every 4 weeks and 11/22 (50%) of these patients received up-titration to 300mg every 4 weeks during the 16-week treatment period. 21/24 (87.5%) patients randomized to placebo crossed over to Canakinumab. At Week 16 10/22 (45.5%) of the Canakinumab patients and 2/24 (8.3%) of the placebo patients achieved complete response. 72 patients were randomized in the NID/MKD cohort. 37 patients were randomized to receive 150mg Canakinumab every 4 weeks and 19/37 (51.4%) of these patients received up-titration to 300mg every 4 weeks during the 16-week treatment period. 31/35 (88.6%) patients randomized to placebo crossed over to Canakinumab. At Week 16, 13/37 (35.1%) of the Canakinumab patients and 2/35 (5.7%) of the placebo patients achieved complete response. 63 patients were randomized in the FMF cohort. 31 patients were randomized to receive 150mg Canakinumab every 4 weeks and 10/31 (32.3%) of these patients received up-titration every 4 weeks during the 16-week treatment period. 27/32 (84.4%) patients randomized to placebo crossed over to Canakinumab. At Week 16, 19/31 (61.3%) of the Canakinumab patients and 2/32 (6.3%) of the placebo patients achieved complete response.
 
The efficacy of Canakinumab for the treatment of active SJIA was evaluated in two phase 3, randomized, double-blind, placebo-controlled studies. Patients aged 2 to 19 years of age with SJIA were eligible. Inclusion criteria was active disease, defined as at least 2 joints with active arthritis, documented spiking, intermittent fever, and CRP > 30mg/L. Patients were allowed to continue methotrexate, corticosteroids, and/or NSAIDs without change, except for tapering of the corticosteroid dose as per study design in Study 2.  
 
Study 1 was a single-dose 4-week study assessing the short-term efficacy of Canakinumab in 84 patients randomized to receive a single subcutaneous dose of 4mg/kg Canakinumab or placebo. The primary objective was the portion of patients who achieved at least 30% improvement in an adapted pediatric American College of Rheumatology (ACR) response criterion which included both the pediatric ACR core set and absence of fever at Day 15.
 
At Day 15, 36 patients (84%) in the Canakinumab group had an adapted ACR 30 response compared to 4 patients (10%) in the placebo group. At Day 29, 81% of patients in the Canakinumab group had an adapted ACR 30 response compared to 10% in the placebo group.
 
Study 2 was a withdrawal study of flare prevention by Canakinumab in patients with active SJIA. Flare was defined by worsening of greater than or equal to 30% in at least 3 of the 6 core pediatric ACR response variables combined with improvement of greater than or equal to 30% in no more than 1 of the 6 variables, or reappearance of fever not due to infection for at least 2 consecutive days. Part 1 enrolled 177 patients who received 4mg/kg Canakinumab subcutaneously once every 4 weeks. 100 of these patients continued into Part 2 to receive either 4mg/kg Canakinumab or placebo subcutaneously every 4 weeks. Of the total 128 patients taking corticosteroids who entered the open-label portion of Study 2, 92 attempted corticosteroid tapering. 62% of patients who attempted tapering were able to successfully taper their corticosteroid dose and 46% discontinued corticosteroids altogether.  
 
Part 2, randomized withdrawal design, demonstrated that the time to flare was longer with Canakinumab than with placebo. There was a 64% relative reduction in the risk of flare for patients in the Canakinumab group compared to those in the placebo group.  
 
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. (Ilaris, 2020)
 
2022 Update
The CLUSTER trial evaluated the effect of canakinumab on health-related quality of life (HRQoL), work/school and social life of patients with autoinflammatory recurrent fever syndromes, including colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency, and tumor necrosis factor receptor-associated periodic syndrome.
 
HRQoL of patients who received canakinumab 150 mg or 300 mg every four weeks in the CLUSTER trial (n=173) was assessed at baseline and Weeks 17 and 41. For children we used the Child Health Questionnaire - Parent Form 50 (CHQ-PF50), including psychosocial (PsS) and physical (PhS) component summary scores. For adults, the Short-Form-12 (SF-12) Health Survey was used, including physical (PFS) and mental (PCS) component summary scores. The Sheehan Disability Scale (SDS) was used to determine the impact of treatment on work/school, social and family life.
 
The results obtained were remarkably consistent in both pediatric and adult patients across the three disease cohorts. At baseline, median scores for physical components were relatively low (26-29 for PhS and 34-38 for PFS); they improved to values similar to those expected in the general population by Week 17, and this improvement was sustained at Week 41, when median PhS scores were 47-50 and PFS 44-54. Psychosocial and mental scores also improved from baseline to Week 17 and 41, with scores comparable to the general population. Notable improvements were also observed in the SDS scale.
 
Patients with three inherited autoinflammatory syndromes experienced sustained improvements on their HRQoL, work/school, and social life on treatment with canakinumab. (Lachmann HJ, Lauwerys B, Miettunen P, 2021)
 
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through August 2023. No new literature was identified that would prompt a change in the coverage statement.
CPT/HCPCS:
J0638Injection, canakinumab, 1 mg
References: De Benedetti F, Gattorno M, Anton J, et al;(2018) Canakinumab for the Treatment of Autoinflammatory Recurrent Fever Syndrome. New England Journal of Medicine. 2018; 378(20): 1908-1919.

Ilaris [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; June 2020.

Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, et al;(2009) Canakinumab in CAPS Study Group. Use of canakinumab in the cryopyrin-associated periodic syndrome. New England Journal of Medicine. 2009;360(23):2416-2425.

Lachmann HJ, Lauwerys B, Miettunen P, Kallinich T, Jansson A, Rosner I, Manna R, Murias S, Savic S, Smeets S, De Benedetti F, Simon A.(2021) Canakinumab improves patient-reported outcomes in children and adults with autoinflammatory recurrent fever syndromes: results from the CLUSTER trial. Clin Exp Rheumatol. 2021 Sep-Oct;39 Suppl 132(5):51-58. doi: 10.55563/clinexprheumatol/e92f7o. Epub 2021 Oct 6. PMID: 34622762.

Nirmala N, Brachat A, Feist E, et al.(2015) Gene-expression analysis of adult-onset Still’s disease and systemic juvenile idiopathic arthritis is consistent with a continuum of a single disease entity. Pediatric Rheumatology. 2015

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 Arthritis & Rheumatism. 2013:65:2499-2512

Rupert N, Brunner H, Quartier P, et al.(2012) Two Randomized Trials of Canakinumab in Systemic Juvenile Idiopathic Arthritis. New England Journal of Medicine. 2012:367(25):2396-2406
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