Effective Date

Date of Origin 

07-01-2025            

Arcalyst^®

(rilonacept)

Subcutaneous injection

Treatment of Cryopyrin Associated Periodic Syndrome (CAPS), including Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in adults and pediatric patients 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 is caused by a gain-of-function mutation in the NLRP3 gene, the gene encoding cryopyrin, leading to over secretion of fever causing cytokine interleukin (IL)-1B. The CAPS spectrum includes mild, moderate, and severe phenotypes. The mild phenotype is familial cold autoinflammatory syndrome (FCAS), the moderate phenotype is Muckle-Wells syndrome (MWS), and 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 recognizes that all but a few patients with CAPS have detectable systemic inflammation and use unique CAPS-specific clinical features along the whole disease spectrum to achieve reasonable specificity and sensitivity to aid clinicians in making the CAPS diagnosis.(6) The diagnostic criteria does not include genetic confirmation and can be applied to all CAPS subtypes regardless of NLRP3 mutation. The diagnostic criteria for CAPS are as follows:(2)

• Raised inflammatory markers (C-reactive protein [CRP]/serum amyloid A [SAA]), AND
• 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

Goals of treatment include suppressing systemic inflammation, improving functionality, preventing organ damage, and  improving quality of life.(6) IL-1 blocking therapy is the preferred treatment for CAPS and is the recommended standard of care. IL-1 blocking therapies control inflammation in the absence of corticosteroids. Current IL-1 blocking therapies include anakinra, canakinumab, and rilonacept. Each of these drugs blocks the effect of IL-1B on the IL-1 receptor and downstream signaling.(7)

Deficiency of Interleukin-1 Receptor Antagonist (DIRA)

Deficiency of interleukin (IL)-1 receptor antagonist (DIRA) is a very rare, autosomal recessive inflammatory disease caused by biallelic deleterious loss-of-function mutations in the IL1RN gene, which encodes the IL-1 receptor antagonist (IL-1Ra). These mutations lead to the absence of IL-1Ra, which allows unopposed action of IL-1 and an increased response to proinflammatory cytokines IL-1α and IL-1β stimulation. This results in life-threatening systemic inflammation and marked skin and bone involvement.(3)  

DIRA presents in early childhood, sometimes at birth, with pustular rashes, osteomyelitis, and/or nail changes (onychomadesis). Which features a patient may present with is dependent on the domain affected by the mutation, with some patients presenting primarily with skin involvement and minimal bone involvement, or vice versa. Although inflammatory markers are typically highly elevated, patients rarely present with flare-associated fever unless an infection is present. The diagnosis of DIRA is typically suspected based on clinical features and confirmed on subsequent genetic testing. DIRA can only be diagnosed by genetic analysis and detection of mutations in the IL1RN gene. If untreated, DIRA can result in multiorgan failure and death in early childhood.(3) 

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, with remission defined as an absence of clinical symptoms and normal inflammatory markers. In patients with DIRA, treatment with agents that block both IL-1α and IL-1β is recommended and includes anakinra and rilonacept. Both drugs have shown benefit in controlling disease flares and in preventing long-term complications. Anakinra is typically used initially in all patients with DIRA to achieve disease control, while rilonacept is used to maintain remission.(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 or post-cardiac injury syndrome, or it 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)

Recurrent pericarditis is diagnosed after a patient has an initial documented attack of acute pericarditis, a symptom-free interval of 4 to 6 weeks (or longer), and then a recurrence of subsequent pericarditis. Typically the recurrence is seen within 18 to 24 months, but there is currently no established upper limit of time.(8) Patients with recurrent pericarditis may present with an inflammatory phenotype (e.g., fever and elevated C-reactive protein [CRP] levels) or non-inflammatory phenotype, which is used to guide treatment.(10)

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

• First line therapy: Aspirin or nonsteroidal anti-inflammatory drug (NSAID) for 1-2 weeks plus colchicine for 6-12 months
• Second line therapy: Corticosteroids for 1 week plus colchicine
• Third line therapy: Aspirin or NSAID plus colchicine plus corticosteroids triple therapy
• Fourth line therapy:
  • IL-1 inhibitor (rilonacept) for inflammatory phenotype
  • Azathioprine or IVIG for non-inflammatory phenotype
• Fifth line therapy: Pericardiectomy

Safety

Arcalyst has no FDA labeled contraindication for use.(1)

1

Arcalyst prescribing information. Kiniksa Pharmaceuticals (UK), Ltd. November 2024.

2

Kuemmerle-Deschner JB, Ozen S, Tyrrell PN, et al. Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS). Annals of the Rheumatic Diseases. 2016;76(6):942-947. doi:10.1136/annrheumdis-2016-209686

3

Rivera-Sepulveda A, Colón-Fontánez F, López M, Puig-Ramos G. Deficiency of interleukin-1 receptor Antagonist: new genetic autoinflammatory disease as a diagnostic challenge for pediatricians. Journal of Pediatric Genetics. 2021;12(03):227-232. doi:10.1055/s-0041-1724113

4

Reference no longer used. 

5

Reference no longer used.

6

Welzel T, Kuemmerle-Deschner JB. Diagnosis and Management of the Cryopyrin-Associated Periodic Syndromes (CAPS): What Do We Know Today? Journal of Clinical Medicine. 2021;10(1):128. doi:10.3390/jcm10010128.

7

Romano M, Arici ZS, Piskin D, et al. 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 & Rheumatology. 2022;74(7):1102-1121. doi:10.1002/art.42139

8

Adler Y, Charron P, Imazio M, et al. 2015 ESC Guidelines for the diagnosis and management of pericardial diseases. European Heart Journal. 2015;36(42):2921-2964. doi:10.1093/eurheartj/ehv318

9

Chiabrando JG, Bonaventura A, Vecchié A, et al. Management of acute and recurrent pericarditis. Journal of the American College of Cardiology. 2020;75(1):76-92. doi:10.1016/j.jacc.2019.11.021

10

Andreis A, Imazio M, Casula M, Avondo S, Brucato A. Recurrent pericarditis: an update on diagnosis and management. Internal and Emergency Medicine. 2021;16(3):551-558. doi:10.1007/s11739-021-02639-6

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. 1. 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
   2. BOTH of the following:
      1. ONE of the following
         1. The patient has a diagnosis of Cryopyrin-Associated Periodic Syndrome (CAPS) AND BOTH of the following:
            1. The patient has ONE of the following disorders (phenotypes):
               1. Familial Cold Autoinflammatory Syndrome (FCAS) OR
               2. Muckle-Wells Syndrome (MWS) AND
            2. BOTH of the following:
               1. The patient has a history of elevated pretreatment serum inflammatory markers (C-reactive protein/serum amyloid A) AND
               2. The patient has a history of 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. The patient has a diagnosis of deficiency of interleukin-1 receptor antagonist (DIRA) AND BOTH of the following:
            1. The patient's diagnosis was confirmed via genetic testing for mutations in the IL1RN gene AND
            2. The requested agent is being used for maintenance of remission OR
         3. The patient has a diagnosis of recurrent pericarditis AND BOTH of the following
            1. The patient has pericarditis that recurs after a symptom-free interval of 4 weeks or longer after an (initial) acute pericarditis episode AND
            2. ONE of the following:
               1. ALL of the following:
                  1. The patient has tried and had an inadequate response to colchicine after at least a 6-month duration of therapy AND
                  2. ONE of the following:
                     1. Colchicine was used concomitantly with a non-steroidal anti-inflammatory drug (NSAID) for at least a 1-week duration of therapy OR
                     2. Colchicine was used concomitantly with aspirin for at least a 1-week duration of therapy OR
                     3. The patient has an intolerance or hypersensitivity to ONE NSAID or aspirin OR
                     4. The patient has an FDA labeled contraindication to ALL NSAIDs AND aspirin AND
                  3. ONE of the following:
                     1. Colchicine was used concomitantly with a corticosteroid for at least a 1-week duration of therapy OR
                     2. The patient has an intolerance or hypersensitivity to ONE corticosteroid OR
                     3. The patient has an FDA labeled contraindication to ALL corticosteroids OR
            3. The patient has an intolerance or hypersensitivity to colchicine OR
            4. The patient has an FDA labeled contraindication to colchicine OR
         4. The patient has another FDA labeled indication for the requested agent and route of administration AND
      2. If the patient has an FDA labeled 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
   3. The patient has another indication that is supported in compendia for the requested agent and route of administration AND
2. If the requested agent is Arcalyst for a diagnosis of DIRA, then the patient weighs greater than or equal to 10 kg AND
3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., allergist, cardiologist, immunologist, pediatrician, rheumatologist) 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 the use of combination therapy (submitted copy of clinical trials, phase III studies, or guidelines required) AND
5. 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 the area of the patient’s diagnosis (e.g., allergist, cardiologist, immunologist, pediatrician, rheumatologist) 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 the use of combination therapy (submitted copy of clinical trials, phase III studies, or guidelines required) 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. The requested quantity (dose) exceeds the program quantity limit AND ONE of the following:
   1. BOTH of the following:
      1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication OR
   2. BOTH of the following:
      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
      2. There is support for why 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. BOTH of the following:
      1. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
      2. There is support of 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)
Ebglyss (lebrikizumab-lbkz)
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)
Imuldosa (ustekinumab-srlf)
Inflectra (infliximab-dyyb)
Infliximab
Kevzara (sarilumab)
Kineret (anakinra)
Leqselvi (deuruxolitinib)
Litfulo (ritlecitinib)
Nemluvio (nemolizumab-ilto)
Nucala (mepolizumab)
Olumiant (baricitinib)
Omvoh (mirikizumab-mrkz)
Opzelura (ruxolitinib)
Orencia (abatacept)
Otezla (apremilast)
Otulfi (ustekinumab-aauz)
Pyzchiva (ustekinumab-ttwe)
Remicade (infliximab)
Renflexis (infliximab-abda)
Riabni (rituximab-arrx)
Rinvoq (upadacitinib)
Rituxan (rituximab)
Rituxan Hycela (rituximab/hyaluronidase human)
Ruxience (rituximab-pvvr)
Saphnelo (anifrolumab-fnia)
Selarsdi (ustekinumab-aekn)
Siliq (brodalumab)
Simlandi (adalimumab-ryvk)
Simponi (golimumab)
Simponi ARIA (golimumab)
Skyrizi (risankizumab-rzaa)
Sotyktu (deucravacitinib) 
Spevigo (spesolimab-sbzo) subcutaneous injection
Stelara (ustekinumab)
Steqeyma (ustekinumab-stba)
Taltz (ixekizumab)
Tezspire (tezepelumab-ekko)
Tofidence (tocilizumab-bavi)
Tremfya (guselkumab)
Truxima (rituximab-abbs)
Tyenne (tocilizumab-aazg)
Tysabri (natalizumab)
Ustekinumab
Velsipity (etrasimod)
Wezlana (ustekinumab-auub)
Xeljanz (tofacitinib)
Xeljanz XR (tofacitinib extended release)
Xolair (omalizumab)
Yesintek (ustekinumab-kfce)
Yuflyma (adalimumab-aaty)
Yusimry (adalimumab-aqvh)
Zeposia (ozanimod)
Zymfentra (infliximab-dyyb)