Effective Date

Date of Origin 

07-01-2024            

Arcalyst^®

(rilonacept)

Subcutaneous injection

Treatment of Cryopyrin Associated Periodic Syndrome (CAPS), including Familial Cold Auto-Inflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in adults and children 12 years and older 

Maintenance of remission of deficiency of interleukin-1 receptor antagonist (DIRA) in adults and pediatric patients weighing at least 10 kg

Treatment of recurrent pericarditis (RP) and reduction in risk of recurrence in adults and pediatric patients 12 years and older

1

Cryopyrin-Associated Periodic Syndromes (CAPS)

Cryopyrin-associated periodic syndrome (CAPS) is a rare autosomal dominant hereditary autoimmune disorder associated with a defect in the cryopyrin protein. CAPS syndrome is caused by a gain of function mutation in the NLRP3 gene leading to over secretion of fever causing cytokine IL-1B. The CAPS spectrum includes mild, moderate, and severe phenotypes. The mild phenotype is called familial cold autoinflammatory syndrome (FCAS), the moderate phenotype is also known as Muckle-Wells syndrome (MWS), the neonatal-onset multisystem inflammatory disease (NOMID)/chronic infantile neurologic cutaneous articular syndrome (CINCA) describes the severe phenotype. CAPS is diagnosed clinically and genetically. There are more than 240 sequence variants of the NLRP3 gene and  mutations in this gene are not inclusive of a CAPS diagnosis. The diagnostic criteria of CAPS recognize that all but a few patients with CAPS have detectable systemic inflammation and use unique CPS-specific clinical features along the whole disease spectrum to achieve reasonable specificity and sensitivity to aid clinicians in making the CAPS diagnosis. These diagnostic criteria do not include genetic confirmation, and therefore can be applied in places where genetic testing is not available. The diagnostic criteria for CAPS are as follows:(6)

• Raised inflammatory markers (CRP/SAA)
• The presence of at least two of the following signs/symptoms:
  • Urticaria-like rash
  • Cold/stress triggered episodes
  • Sensorineural hearing loss
  • Musculoskeletal symptoms of arthralgia/arthritis/myalgia
  • Chronic aseptic meningitis
  • Skeletal abnormalities of epiphyseal overgrowth/frontal bossing

FCAS is characterized by episodes of rash, fever. and joint pain following generalized exposure to cold. Attacks usually occur 1-2 hours after exposure and last less than 24.(2) Patients experience urticaria, arthralgia, fever with chills, severe thirst, red-eyes, and headache after a general cold exposure, including air conditioning. In MWS, inflammation can occur spontaneously as well as from triggers, such as stress, cold, or exercise, with episodes lasting from one to three days. MWS shares the same characteristics as FCAS, but is also characterized by renal amyloidosis, sensorineural hearing loss, and conjunctivitis. Hearing loss, partial or complete, often develop by teenage years.(3)  

NOMID is a rare chronic inflammatory disease. NOMID is characterized by fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss, and intellectual disability. An urticaria-like rash develops within the first six weeks of life, and a characteristic bony overgrowth predominantly involving the knees develops in most affected children. Therapies are aimed at suppressing inflammation and have included high-dose corticosteroids, disease-modifying antirheumatic drugs, and biologic agent targeting tumor necrosis factor (TNF). Selective blockade of interleukin-1B is effective in the pathophysiology and organ-specific manifestations of NMOSD, in particular the CNS manifestations of the disease.(5)

Treatment aims are to suppress systemic inflammation, to improve functionality, to prevent organ damage, and to increase patients' quality of life. To achieve these aims, cytokine targeting drugs are important and evidence-based treatment. Since IL-1 plays a central role in CAPS pathogenesis, the anti-IL1 treatments (anakinra, canakinumab, and rilonacept) are recommended for the whole CAPS spectrum.(6)

Deficiency of the IL-1 Receptor Antagonist (DIRA)

Systemic autoinflammatory diseases (SAIDs) are a group of multisystem immunodysregulatory disorders caused primarily by the dysfunction of the innate immune system. Currently, SAIDs are comprised of a wide range of disorders with systemic and organ-specific inflammation in the absence of infections or autoimmunity. In a subset of genetically defined SAIDs, the pathogenesis is driven by increased release or signaling of the pro-inflammatory cytokine IL-1.(7)  

Patients with DIRA present with early-onset pustular rashes that can be triggered by mechanical stress (pathergy), with sterile osteomyelitis, and nail changes (onychomadesis). Although inflammatory markers are typically highly elevated, fever may be absent. Vertebral involvement can include odontoid osteomyelitis resulting in destruction and neck instability, vertebral block formation and gibbus-like spinal changes that need to be screened for by MRI or CT. The differential diagnosis for DIRA includes chronic recurrent multifocal osteomyelitis (CRMO), synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome and pustular psoriasis. Genetic testing for monogenic defects with overlapping clinical features should include LPIN2, FGR, FBLIM1 for CRMO, CARD14 for CARD14-Mediated Psoriasis (CAMPS), IL36RN for Deficiency of IL-36 Receptor Antagonist (DITRA), AP1S3 for other pustular psoriasis and MEFV for Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis (PAAND).(7)

Aims of therapy are early control of disease activity, prevention of disease and treatment related damage, and optimal health-related quality of life. The ultimate goal of a treat-to-target approach is complete remission. In absence of a consensus definition of remission or minimal disease activity for these diseases, remission has been defined for clinical studies and clinical monitoring as an absence of clinical symptoms and normal inflammatory markers. Anakinra and rilonacept both block IL-1α and IL-1β and should be used for DIRA patients.(7) 

Recurrent Pericarditis

Pericarditis is inflammation of the pericardial layers around the heart and is the most common form of pericardial disease. Pericarditis may be caused infections, post-cardiac injury syndrome, or pericarditis may be idiopathic. Pericarditis is categorized into four types, acute, incessant, recurrent, and chronic. These categories are based on the length of time of the attack and the presentation. Acute pericarditis is an event lasting 4 weeks or less, incessant is an event lasting more than 4 weeks without a remission, recurrent pericarditis is new signs and symptoms of pericarditis after a symptom-free interval of 4 to 6 weeks, and chronic is an event lasting more than 3 months. Roughly 20% to 30% of patients that develop acute pericarditis will have recurrences, and 50% of patients that have a recurrence will experience more recurrences.(9) 

The treatment algorithm for therapeutic management of patients with recurrent pericarditis is as follows:(10)

• First line therapy: Aspirin or other nonsteroidal anti-inflammatory drug (NSAID) for 1-2 weeks plus colchicine for 6-12 months and exercise restrictions 
• Second line therapy: Low dose corticosteroids for 1 week plus colchicine
• Third line: Aspirin or other NSAID plus colchicine plus corticosteroids triple therapy
• Fourth line: IL-1 inhibitors (anakinra, rilonacept) for inflammatory phenotype and azathioprine, IVIG for non-inflammatory phenotype
• Fifth line: Pericardiectomy

The American College of Cardiology note that mycophenolate mofetil and methotrexate  have also been shown to be effective in the treatment of recurrent pericarditis that are not responsive to corticosteroids, corticosteroid dependent, or intolerant to corticosteroids.(9) 

Safety

Arcalyst does not have any FDA labeled contraindications.(1)

1

Arcalyst prescribing information. Kiniksa Pharmaceuticals (UK), Ltd. May 2021.

2

Hoffman HM, Wanderer AA, Broide DH. Familial cold autoinflammatory syndrome: phenotype and genotype of an autosomal dominant periodic fever. J Allergy Clin Immunol. 2001 Oct;108(4):615-20. doi: 10.1067/mai.2001.118790. PMID: 11590390; PMCID: PMC4321996.

3

Yu, J. R., & Leslie, K. S. (2010). Cryopyrin-associated periodic syndrome: an update on diagnosis and treatment response. Current allergy and asthma reports, 11(1), 12-20.

4

Reference no longer used. 

5

Goldbach-Mansky R, Dailey NJ, Canna SW, Gelabert A, Jones J, Rubin BI, Kim HJ, Brewer C, Zalewski C, Wiggs E, Hill S, Turner ML, Karp BI, Aksentijevich I, Pucino F, Penzak SR, Haverkamp MH, Stein L, Adams BS, Moore TL, Fuhlbrigge RC, Shaham B, Jarvis JN, O'Neil K, Vehe RK, Beitz LO, Gardner G, Hannan WP, Warren RW, Horn W, Cole JL, Paul SM, Hawkins PN, Pham TH, Snyder C, Wesley RA, Hoffmann SC, Holland SM, Butman JA, Kastner DL. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. N Engl J Med. 2006 Aug 10;355(6):581-92. doi: 10.1056/NEJMoa055137. PMID: 16899778; PMCID: PMC4178954.

6

Welzel T, Kuemmerle-Deschner JB. Diagnosis and Management of the Cryopyrin-Associated Periodic Syndromes (CAPS): What Do We Know Today? J Clin Med. 2021 Jan 1;10(1):128. doi: 10.3390/jcm10010128. PMID: 33401496; PMCID: PMC7794776.

7

Romano M, Arici ZS, Piskin D, Alehashemi S, Aletaha D, Barron K, Benseler S, Berard RA, Broderick L, Dedeoglu F, Diebold M, Durrant K, Ferguson P, Foell D, Hausmann JS, Jones OY, Kastner D, Lachmann HJ, Laxer RM, Rivera D, Ruperto N, Simon A, Twilt M, Frenkel J, Hoffman HM, de Jesus AA, Kuemmerle-Deschner JB, Ozen S, Gattorno M, Goldbach-Mansky R, Demirkaya E. The 2021 EULAR/American College of Rheumatology Points to Consider for Diagnosis, Management and Monitoring of the Interleukin-1 Mediated Autoinflammatory Diseases: Cryopyrin-Associated Periodic Syndromes, Tumour Necrosis Factor Receptor-Associated Periodic Syndrome, Mevalonate Kinase Deficiency, and Deficiency of the Interleukin-1 Receptor Antagonist. Arthritis Rheumatol. 2022 Jul;74(7):1102-1121. doi: 10.1002/art.42139. Epub 2022 May 27. PMID: 35621220; PMCID: PMC9531906.

8

Reference no longer used

9

Chiabrando JG, Bonaventura A, Vecchié A, et al. Management of Acute and Recurrent Pericarditis: JACC State-of-the-Art Review. J Am Coll Cardiol 2020; 75:76.

10

Andreis A, Imazio M, Casula M, Avondo S, Brucato A. Recurrent pericarditis: an update on diagnosis and management. Intern Emerg Med. 2021 Apr;16(3):551-558. doi: 10.1007/s11739-021-02639-6. Epub 2021 Feb 28. PMID: 33641044; PMCID: PMC7914388.

Arcalyst

Rilonacept For Inj 220 MG

220 MG

M ; N ; O ; Y

N

Arcalyst

Rilonacept For Inj 220 MG

220 MG

8

Vials

28

DAYS

Arcalyst

Rilonacept For Inj 220 MG

220 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Arcalyst

Rilonacept For Inj 220 MG

220 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. ONE of the following:
   1. The requested agent is eligible for continuation of therapy AND ONE of the following:

1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR
2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed OR
3. BOTH of the following:
   1. ONE of the following
      1. BOTH of the following:
         1. The patient has ONE of the following indications:
            1. Cryopyrin Associated Periodic Syndrome (CAPS) OR
            2. Familial Cold Auto-Inflammatory Syndrome (FCAS) OR
            3. Muckle-Wells Syndrome (MWS) AND
         2. BOTH of the following:
            1. The patient has elevated pretreatment serum inflammatory markers (C-reactive protein/serum amyloid A) AND
            2. The patient has at least TWO symptoms typical for CAPS (i.e., urticaria-like rash, cold/stress triggered episodes, sensorineural hearing loss, musculoskeletal symptoms of arthralgia/arthritis/myalgia, chronic aseptic meningitis, skeletal abnormalities of epiphyseal overgrowth/frontal bossing) OR
      2. BOTH of the following:
         1. The patient has a diagnosis of deficiency of interleukin-1 receptor antagonist AND
         2. The requested agent is being used for maintenance of remission OR
      3. The patient has a diagnosis of recurrent pericarditis AND ONE of the following
         1. BOTH of the following:
            1. The patient has tried and had an inadequate response to at least a 6-month trial of colchicine AND
            2. ONE of the following:
               1. Colchicine was used concomitantly with at least a 1 week trial of a non-steroidal anti-inflammatory drug (NSAID) AND a corticosteroid OR
               2. The patient has an intolerance or hypersensitivity to BOTH an NSAID AND a corticosteroid OR
               3. The patient has an FDA labeled contraindication to ALL NSAIDs AND ALL corticosteroids OR
         2. The patient has an intolerance or hypersensitivity to colchicine OR
         3. The patient has an FDA labeled contraindication to colchicine OR
         4. The patient has tried and had an inadequate response to an oral immunosuppressant (i.e., azathioprine, methotrexate, mycophenolate) used in the treatment of recurrent pericarditis OR
         5. The patient has an intolerance or hypersensitivity to oral immunosuppressants used in the treatment of recurrent pericarditis OR
         6. The patient has an FDA labeled contraindication to oral immunosuppressants used in the treatment of recurrent pericarditis OR
      4. The patient has another FDA approved indication for the requested agent AND
   2. If the patient has an FDA approved indication, then ONE of the following:
      1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
      2. There is support for using the requested agent for the patient’s age for the requested indication OR
4. The patient has another indication that is supported in compendia for the requested agent AND
5. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., allergist, immunologist, pediatrician, cardiologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
6. ONE of the following (Please refer to “Agents NOT to be used Concomitantly” table): 
   1. The patient will NOT be using the requested agent in combination with another immunomodulatory agent (e.g., TNF inhibitors, JAK inhibitors, IL-4 inhibitors) OR
   2. The patient will be using the requested agent in combination with another immunomodulatory agent AND BOTH of the following:
      1. The prescribing information for the requested agent does NOT limit the use with another immunomodulatory agent AND
      2. There is support for the use of combination therapy (copy of support required, e.g., clinical trials, phase III studies, guidelines) AND
7. The patient does NOT have any FDA labeled contraindications to the requested agent

Compendia Allowed: AHFS or DrugDex 1 or 2a level of evidence

Length of Approval:  12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has been previously approved for the requested agent through plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND
2. The patient has had clinical benefit with the requested agent AND
3. The prescriber is a specialist in area of the patient’s diagnosis (e.g., allergist, immunologist, pediatrician, cardiologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
4. ONE of the following (Please refer to “Agents NOT to be used Concomitantly” table): 
   1. The patient will NOT be using the requested agent in combination with another immunomodulatory agent (e.g., TNF inhibitors, JAK inhibitors, IL-4 inhibitors) OR
   2. The patient will be using the requested agent in combination with another immunomodulatory agent AND BOTH of the following:
      1. The prescribing information for the requested agent does NOT limit the use with another immunomodulatory agent AND
      2. There is support for use of combination therapy (copy of support required, e.g., clinical trials, phase III studies, guidelines) AND
5. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met:

1. The requested quantity (dose) does NOT exceed the program quantity limit OR
2. ALL of the following:
   1. The requested quantity (dose) exceeds the program quantity limit AND
   2. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
   3. The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does not exceed the program quantity limit OR
3. ALL of the following:
   1. The requested quantity (dose) exceeds the program quantity limit AND
   2. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
   3. There is support for therapy with a higher dose for the requested indication

Length of Approval: up to 12 months

Agents NOT to be used Concomitantly

Abrilada (adalimumab-afzb)

Actemra (tocilizumab)

Adalimumab

Adbry (tralokinumab-ldrm)

Amjevita (adalimumab-atto)

Arcalyst (rilonacept)

Avsola (infliximab-axxq)

Benlysta (belimumab)

Bimzelx (bimekizumab-bkzx)

Cibinqo (abrocitinib)

Cimzia (certolizumab)

Cinqair (reslizumab)

Cosentyx (secukinumab)

Cyltezo (adalimumab-adbm)

Dupixent (dupilumab)

Enbrel (etanercept)

Entyvio (vedolizumab)

Fasenra (benralizumab)

Hadlima (adalimumab-bwwd)

Hulio (adalimumab-fkjp)

Humira (adalimumab)

Hyrimoz (adalimumab-adaz)

Idacio (adalimumab-aacf)

Ilaris (canakinumab)

Ilumya (tildrakizumab-asmn)

Inflectra (infliximab-dyyb)

Infliximab

Kevzara (sarilumab)

Kineret (anakinra)

Litfulo (ritlecitinib)

Nucala (mepolizumab)

Olumiant (baricitinib)

Omvoh (mirikizumab-mrkz)

Opzelura (ruxolitinib)

Orencia (abatacept)

Otezla (apremilast)

Remicade (infliximab)

Renflexis (infliximab-abda)

Riabni (rituximab-arrx)

Rinvoq (upadacitinib)

Rituxan (rituximab)

Rituxan Hycela (rituximab/hyaluronidase human)

Ruxience (rituximab-pvvr)

Siliq (brodalumab)

Simponi (golimumab)

Simponi ARIA (golimumab)

Skyrizi (risankizumab-rzaa)

Sotyktu (deucravacitinib) 

Stelara (ustekinumab)

Taltz (ixekizumab)

Tezspire (tezepelumab-ekko)

Tremfya (guselkumab)

Truxima (rituximab-abbs)

Tysabri (natalizumab)

Velsipity (etrasimod)

Wezlana (ustekinumab-auub)

Xeljanz (tofacitinib)

Xeljanz XR (tofacitinib extended release)

Xolair (omalizumab)

Yuflyma (adalimumab-aaty)

Yusimry (adalimumab-aqvh)

Zeposia (ozanimod)

Zymfentra (infliximab-dyyb)