Rilonacept (Arcalyst) coverage
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Defines Aetna's medical necessity, prescriber requirements, dosing, and coding for rilonacept (Arcalyst) for CAPS, DIRA maintenance, and recurrent pericarditis, and lists experimental/investigational uses. Applies to Aetna coverage determinations.
No material clinical or coverage changes in this revision.
Coverage Criteria and Evidence
Initial Therapy — CAPS
Covered when ALL of the following are met
Prescriber specialty and TB screening per policy.
Initial Therapy — DIRA
Covered when ALL of the following are met
Based on FDA approval and open-label maintenance study dosing and population.
Initial Therapy — Recurrent Pericarditis
Covered when ALL of the following are met
Prescriber specialty, prior therapy failure and TB screening per policy; clinical response measures for continuation are listed separately.
Continuation Therapy
Covered when ANY of the following improvement measures are met for ongoing therapy
Includes new members already on therapy; mirrors continuation criteria in policy.
Experimental and Investigational / Not Covered Indications
Not covered (considered experimental/investigational) for the following uses
See Experimental and Investigational section of policy; concomitant biologic use explicitly considered experimental.
Covered Indications and trial-derived entry criteria
Coverage aligned to indications supported by regulatory approval and trial evidence:
Based on phase III CAPS trial and FDA approval.
Based on 2-year open-label maintenance study (n=6) and FDA approval.
Based on RHAPSODY trial criteria and regulatory review.
Evidence summaries by indication
Indication-specific evidence summary and implications for coverage decisions:
See Terkeltaub 2013 trial.
See PRESURGE-2 and related phase 3 data.
See Yin et al. Cochrane update.
See Krause et al. open-label study.
See Carroll et al. trial.
Other (off‑label/investigational) indications — evidence summaries
Evidence summaries for off‑label or investigational uses (study-level findings):
Small uncontrolled study suggests potential efficacy.
Rilonacept inferior to standard corticosteroid in this trial.
Investigational in SSc.
Negative for preserving beta-cell function.
Requests for concomitant use of rilonacept with any other biologic drug or targeted synthetic drug are considered experimental and investigational because effectiveness of combined biologic/targeted approaches has not been established. Examples listed in the policy include tumor necrosis factor inhibitors and IL-1 agents (e.g., adalimumab, anakinra, etanercept, infliximab, tocilizumab) and targeted synthetics (e.g., tofacitinib).
Although rilonacept is FDA-approved for CAPS (FCAS and Muckle-Wells syndrome), the policy states that rilonacept has not been studied in NOMID
Randomized controlled trial evidence does not support use of rilonacept for treatment of acute gout flares. In a trial comparing rilonacept plus indomethacin versus indomethacin alone, addition of rilonacept did not produce a statistically significant incremental pain reduction over indomethacin, and rilonacept monotherapy provided less pain reduction than indomethacin over the 72-hour assessment. Based on these RCT results, rilonacept is not supported for routine treatment of acute gout flares.
Systematic reviews and current UpToDate summaries for systemic sclerosis do not list rilonacept as a therapeutic option. Although phase I/II studies have evaluated many targeted therapies (rilonacept among them), UpToDate topic reviews of SSc management do not mention rilonacept, indicating it is not an accepted management choice in those reviews.
The policy considers rilonacept experimental and investigational for numerous off‑label indications where effectiveness is unestablished. Examples explicitly listed include adult-onset Still’s disease, COVID-19, gout (outside trial contexts), Schnitzler syndrome, subacromial bursitis, systemic sclerosis, familial Mediterranean fever, juvenile idiopathic arthritis, cardiovascular indications, and others. Small uncontrolled or early-phase studies exist for some conditions, but the policy deems these uses investigational pending stronger evidence.
A randomized 12-week trial in patients with stage 3–4 CKD found no meaningful changes in markers of CKD‑MBD or in most measures of physical or cognitive function with rilonacept versus placebo. Because the trial did not demonstrate improvement in biochemical markers or functional endpoints, use of rilonacept for CKD‑MBD or to improve physical/cognitive function in stage 3–4 CKD is unsupported by the available trial evidence.
Given randomized evidence showing at best no additional benefit or inferior pain reduction compared with standard NSAID therapy for acute gout flares, the policy concludes that rilonacept is not medically necessary as monotherapy or adjunctive therapy for routine management of acute gout flares.
A phase I trial of rilonacept in recent-onset type 1 diabetes (n=13, 26 weeks) was well tolerated but showed declines in C‑peptide and no convincing preservation of beta‑cell function. The study authors concluded rilonacept is unlikely to be effective as a single agent for preserving beta-cell function in recent-onset T1DM.
Billing and Coding
| 96372 | Therapeutic, prophylactic, or diagnostic injection; subcutaneous or intramuscular. |
| J2793 | Injection, Rilonacept, 1 mg |
| M04.2 | Cryopyrin-associated periodic syndromes [age 12 and older] |
| M04.8 | Other autoinflammatory syndromes [Deficiency of interleukin-1 receptor antagonist (DIRA)] |
| I30.0 - I30.9 | Acute pericarditis |
| I31.0 | Chronic adhesive pericarditis |
| I31.1 | Chronic constrictive pericarditis |
| I01.0 | Acute rheumatic pericarditis |
| D47.2 | Monoclonal gammopathy [Schnitzler syndrome] |
| M06.1 | Adult-onset Still's disease |
| U07.1 | COVID-19 |
| No codes listed |
Provider Requirements and Prior Authorization
Prior Authorization Required
Prior authorization is required for HCPCS J2793 (Injection, rilonacept, 1 mg). Coverage is contingent on meeting the policy's clinical criteria and submitting the required documentation below.
- Prior authorization required: HCPCS J2793 (injection, rilonacept, 1 mg).
- Coverage contingent on meeting indication-specific and dosing-specific clinical criteria in the policy.
Indication-Specific Prior Authorization
Requests must state the specific indication for rilonacept (CAPS subtype: FCAS or MWS; DIRA; or recurrent pericarditis) and include supporting diagnostic documentation as described in the medical necessity criteria.
- Indication must be specified: CAPS (FCAS or MWS), DIRA, or recurrent pericarditis.
- Include diagnostic/supporting documentation (e.g., clinical features for FCAS/MWS, genetic confirmation of IL1RN mutation for DIRA, records documenting ≥2 pericarditis episodes for recurrent pericarditis).
Indication- and Dosing-Specific Prior Authorization
Some indications require dosing- or context-specific justification (for example, prophylaxis during initiation of urate-lowering therapy for gout). Include indication- and dosing-specific rationale when applicable.
- For gout flare prevention during initiation of urate-lowering therapy, document prior initiation of urate-lowering therapy and history of ≥2 gout flares in the past 12 months; specify dose regimen requested (e.g., 80 mg or 160 mg weekly).
- For DIRA maintenance, include prior use of anakinra and rationale for transition to rilonacept and any dose escalation history.
Prior Authorization Not Specified in Excerpt
The excerpt does not list any additional administrative prior authorization codes or separate requirements beyond standard prior authorization for the drug code (J2793) and the clinical documentation requirements noted elsewhere.
- No other prior authorization codes or administrative steps specified in this excerpt.
TB Screening Requirement
A documented negative TB screening test (tuberculin skin test [PPD], interferon-gamma release assay [IGRA], or chest x-ray) within 6 months prior to initiating therapy is required for members naïve to biologic or targeted synthetic agents associated with increased TB risk. Positive screens require further evaluation and treatment before therapy.
- Negative TB test (PPD, IGRA, or chest x-ray) within 6 months prior to initiation for biologic/targeted-synthetic–naïve patients.
- If TB screening is positive, further testing to rule out active disease is required; do not administer rilonacept for active TB. If latent TB is identified, start TB treatment before initiating rilonacept.
Lack of Clinical Response as a Barrier to Continuation
Continuation of therapy requires documentation of a positive clinical response. Lack of clinical response is a basis for denying continued therapy.
- For CAPS and DIRA: evidence of low disease activity or improvement in signs/symptoms.
- For recurrent pericarditis: improvement in pericarditic chest pain, pericardial rubs, ECG, pericardial effusion, or CRP.
- Patients who do not meet run-in or response criteria (e.g., as in RHAPSODY/run-in) would not qualify for continued therapy.
Acute Gout Flare — Limited Benefit
RCT evidence shows limited or no meaningful benefit of rilonacept as monotherapy for acute gout flares compared with standard acute therapies; rilonacept is not supported as a replacement for standard acute gout treatments.
- Rilonacept showed no statistically significant improvement over indomethacin for acute gout pain in the pivotal trial; therefore it is not recommended as a substitute for standard acute gout therapies (NSAIDs, colchicine, corticosteroids).
Gout Flare Prevention — Context-Specific
Rilonacept has demonstrated efficacy for prevention of gout flares when used during initiation of urate-lowering therapy in patients with a history of multiple flares; its use is context-specific and requires documentation of the clinical context.
- Indicated context for gout: prophylaxis during initiation of urate-lowering therapy (e.g., allopurinol) in patients with ≥2 gout flares in the prior 12 months.
- Provide documentation of initiation of urate-lowering therapy and prior gout flare history when requesting rilonacept for prophylaxis.
None Specified in This Excerpt
No additional provider actions are specified in this excerpt beyond the clinical and documentation requirements already listed.
- No other provider actions specified in this excerpt.
Required Clinical Documentation
Submit required clinical documentation with the prior authorization request to support medical necessity.
- Diagnosis documentation (e.g., clinical notes supporting FCAS or MWS for CAPS; genetic testing confirming IL1RN mutation for DIRA; records showing ≥2 pericarditis episodes for recurrent pericarditis).
- Clinical course and prior treatments, baseline and follow-up inflammatory markers (e.g., CRP), and objective findings (ECG, imaging) as applicable.
Diagnosis and Response Documentation
Provide documentation of the diagnosis and clinical response when applicable to demonstrate both initial eligibility and continued benefit.
- For DIRA: IL1RN mutation documentation and prior anakinra response/transition notes.
- For recurrent pericarditis: documentation of clinical response during run-in or treatment (e.g., pain resolution, CRP normalization) and details of prior recurrences.
Gout Prevention Documentation
When seeking approval for gout prophylaxis during urate-lowering therapy initiation, include documentation specific to gout prevention criteria.
- Document initiation date of urate-lowering therapy (e.g., allopurinol) and that the patient has had ≥2 gout flares in the past 12 months.
- Specify the rilonacept dose requested (e.g., 80 mg or 160 mg weekly) and duration of prophylaxis.
Prior Standard Therapies Expected
Prior therapies expected before rilonacept for recurrent pericarditis include standard agents; documentation of failure or intolerance is required.
- For recurrent pericarditis, member must have failed at least two agents of standard therapy (examples: colchicine, NSAIDs, corticosteroids).
- Provide records showing prior use and inadequate response or intolerance to these agents.
Step Therapy for Acute Gout
For gout indications, step therapy through standard first-line acute treatments is expected prior to considering IL-1 inhibitor therapy for an acute flare.
- Step through NSAIDs, colchicine, or corticosteroids for acute gout management before considering rilonacept for acute flares.
- Rilonacept may be considered for prophylaxis during ULT initiation in patients with recurrent flares, not as first-line acute therapy.
Background, Definitions and Indications
Rilonacept (Arcalyst) is an interleukin‑1 blocker that acts as a soluble decoy receptor for IL‑1α and IL‑1β. It is FDA‑approved for treatment of cryopyrin‑associated periodic syndromes (CAPS: familial cold autoinflammatory syndrome and Muckle‑Wells syndrome) in adults and children aged ≥12 years, for maintenance therapy in deficiency of interleukin‑1 receptor antagonist (DIRA) for patients meeting weight criteria, and for reduction in recurrence of recurrent pericarditis. Common adverse reactions reported include injection‑site reactions and upper respiratory tract infections.
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