This policy version was replaced May 2, 2022. To find the newest version, go to https://www.bluecrossmn.com/providers/medical-policy-and-utilization-management, read and accept the Blue Cross Medical Policy Statement, then select “Blue Cross and Blue Shield of Minnesota Medical Policies.” This will bring up the Medical Policy search screen. Enter the policy number without the version number (last 3 digits).

Reslizumab is a recombinant, humanized monoclonal antibody specific to interleukin-5 (IL-5), the major cytokine responsible for growth, differentiation, recruitment, activation, and survival of eosinophils. Reslizumab binds to IL-5 and inhibits its interaction with the alpha subunit of the IL-5 receptor (IL-5R-alpha) on the surface of eosinophils, thereby reducing the production and survival of these cells. Reslizumab is administered by intravenous infusion.

The U.S. Food and Drug Administration (FDA) has approved reslizumab (Cinqair®) for add-on maintenance treatment of patients with severe asthma aged 18 years and older, and with an eosinophilic phenotype. According to the prescribing information, reslizumab is not indicated for treatment of other eosinophilic conditions, or for relief of acute bronchospasm or status asthmaticus.

Serious adverse reactions have occurred in patients receiving reslizumab, including anaphylaxis and malignancy. Due to these safety concerns, the FDA requires the prescribing information for reslizumab to include a black box warning.

I.   Initial Review for Reslizumab (Cinqair®)

Reslizumab may be considered MEDICALLY NECESSARY AND APPROPRIATE when ALL of the following criteria are met:

• Age 18 years or older; AND
• Diagnosis of severe eosinophilic asthma; AND
• Blood eosinophil level ≥400 cells/µL within the previous 12 months; AND
• Used as add-on therapy for patients currently receiving regular maintenance treatment with BOTH of the following:
  • Maximally tolerated inhaled corticosteroid OR documented intolerance, FDA labeled contraindication, or hypersensitivity to inhaled corticosteroids; and
  • An additional asthma controller medication (long-acting beta-2 agonist, leukotriene receptor antagonist, long-acting muscarinic antagonist, or theophylline) OR documented intolerance, FDA labeled contraindication, or hypersensitivity to controller medications; AND
• ONE of the following:
  • History of 1 or more asthma exacerbations requiring systemic corticosteroid treatment within the previous 12 months; or
  • Serious asthma exacerbation requiring hospitalization, mechanical ventilation, or visit to the emergency room or urgent care within the previous 12 months; or
  • Controlled asthma that worsens when the doses of inhaled or systemic corticosteroids are tapered; or  
  • Pretreatment forced expiratory volume in 1 second (FEV¹) <80% predicted;
• AND
• Prescribed by or in consultation with a pulmonologist, allergist, or immunologist; AND
• Not used in combination with mepolizumab (Nucala®), benralizumab (Fasenra®), omalizumab (Xolair®), or dupilumab (Dupixent®); AND
  
• No FDA labeled contraindications to reslizumab (see table 1 below); AND
• The dose is within the FDA labeled dose for the indication (see table 2 below); AND
• For commercial health plan members only, reslizumab is administered in accordance with site of service criteria (see policy XI-06); AND
  
• For commercial health plan members only, step therapy supplement criteria may apply for select conditions (see policy II-242: Step Therapy Supplement).
  

II.  Renewal Review for Reslizumab (Cinqair®)

Reslizumab may be considered MEDICALLY NECESSARY AND APPROPRIATE when ALL of the following criteria are met:

• Previously approved for reslizumab through the initial review process; AND
• Demonstrated positive clinical response to reslizumab therapy (e.g., decreased use of rescue medications, decreased frequency of exacerbations, increase in percent predicted FEV₁, reduction in asthma-related symptoms); AND
• Used as add-on therapy for patients currently receiving regular maintenance treatment with a maximally tolerated inhaled corticosteroid AND an additional asthma controller medication (long-acting beta-2 agonist, leukotriene receptor antagonist, long-acting muscarinic antagonist, or theophylline) OR documented intolerance, FDA labeled contraindication, or hypersensitivity to inhaled corticosteroids and controller medications; AND
• Prescribed by or in consultation with a pulmonologist, allergist, or immunologist; AND
• Not used in combination with mepolizumab (Nucala®), benralizumab (Fasenra®), omalizumab (Xolair®), or dupilumab (Dupixent®); AND
  
• No FDA labeled contraindications to reslizumab (see table 1 below); AND
• The dose is within the FDA labeled dose for the indication (see table 2 below); AND
• For commercial health plan members only, reslizumab is administered in accordance with site of service criteria (see policy XI-06).
  

III. Experimental/Investigative Uses

All other uses of reslizumab are considered EXPERIMENTAL/INVESTIGATIVE due to the lack of clinical evidence demonstrating an impact on improved health outcomes.

Table 1. FDA Labeled Contraindications

Table 2. Dosing

Documentation Submission:

Documentation supporting the medical necessity criteria described in the policy must be included in the prior authorization. In addition, the following documentation must also be submitted:

Initial Review 

1. Clinical notes describing the diagnosis and clinical features of the diagnosis.
2. Clinical notes describing current and past medications for the diagnosis, including response to the medications.
3. Laboratory documentation of blood eosinophil level.
4. The dose being requested, including the patient’s weight if the diagnosis requires weight-based dosing. If the requested dose is higher or more frequent than the dosing guidelines provided in the table above, a clear explanation for the medical necessity of the requested dose MUST be submitted, including prior dosing (strength and frequency) associated with inadequate response.
5. For commercial health plan members only, the site of service for reslizumab administration is specified, including CMS place of service code (see policy XI-06). If reslizumab is administered in a hospital outpatient facility, a clear explanation for the medical necessity of the site of service MUST be submitted, including documentation for one or more of the site of service criteria provided in policy XI-06.
6. For commercial health plan members only, when step therapy requirements apply for the requested indication, documentation for one or more of the step therapy supplement criteria MUST be provided (see policy II-242).

Renewal Review  

1. Documentation of prior approval for reslizumab through the initial review process.
2. Documentation supporting positive clinical response.
3. Clinical notes describing current and past medications for the diagnosis, including response to the medications.
4. The dose being requested, including the patient’s weight if the diagnosis requires weight-based dosing. If the requested dose is higher or more frequent than the dosing guidelines provided in the table above, a clearexplanation for the medical necessity of the requested dose MUST be submitted, including prior dosing (strength and frequency) associated with inadequate response.
5. For commercial health plan members only, the site of service for reslizumab administration is specified, including CMS place of service code (see policy XI-06). If reslizumab is administered in a hospital outpatient facility, a clear explanation for the medical necessity of the site of service MUST be submitted, including documentation for one or more of the site of service criteria provided in policy XI-06.