Rituximab Non-Oncology

POLICY NUMBER

L.5.01.518

Riabni (rituximab-arrx)Rituxan (rituximab)Ruxience (rituximab-pvvr)Truxima (rituximab-abbs)

Please perform a formulary drug search on your patient’s member ID to ensure the prescription drug is covered under their benefit plan. The medication(s) in this medical policy may not be covered under a specific member’s benefit plan.

DESCRIPTION

Rituximab is a monoclonal antibody that works with the body’s own immune system to fight certain diseases by attaching to and killing B cells. While rituximab is often used to treat certain cancers, it is also approved for moderate to severe rheumatoid arthritis, granulomatosis with polyangiitis, and moderate to severe pemphigus vulgaris.

Related medical policies - 

POLICY

Prior authorization is required.

The use of samples by an individual will not be considered current or stable therapy to satisfy of Medical Policy requirements.

Initial Evaluation:

Ruxience (rituximab-pvvr) and Truxima (rituximab-abbs) may be considered medically necessary for non-oncologic indications when ALL of the following are met:

1. The individual is 18 years of age or older (unless otherwise specified below);

2. ONE of the following:

   1. There is documentation that the individual is currently being treated with the product requested;

   2. The individual has a diagnosis of moderate to severe rheumatoid arthritis (RA) and ALL of the following:

      1. ONE of the following:

         1. The individual has failed ONE conventional agent prerequisite (i.e., azathioprine, methotrexate, leflunomide, sulfasalazine, hydroxychloroquine);

         2. The individual has a documented intolerance, FDA labeled contraindication, or hypersensitivity to ALL conventional agents;

      2. ONE of the following:

         1. Medication history indicates failure of TWO preferred biologic immunomodulatory agents indicated for RA (see  Anti-Rheumatic Biologicals medical policy);

         2. The individual has a documented intolerance, FDA labeled contraindication, or hypersensitivity to TWO preferred biologic immunomodulatory agents indicated for RA (see  Anti-Rheumatic Biologicals medical policy);

   3. The individual has a diagnosis of granulomatosis with polyangitis (GPA) [Wegener’s granulomatosis] and microscopic polyangitis (MPA) and BOTH of the following:

      1. The individual is 2 years of age or older;

      2. ONE of the following:

         1. The individual will receive corticosteroids in combination with rituximab;

         2. The individual has a documented intolerance, FDA labeled contraindication, or hypersensitivity to at least ONE corticosteroid;

   4. The individual has a diagnosis of moderate to severe pemphigus vulgaris (PV) and ALL of the following:

      1. ONE of the following:

         1. The individual had an inadequate response to corticosteroids;

         2. The individual has a documented intolerance, FDA labeled contraindication, or hypersensitivity to at least ONE corticosteroid;

      2. ONE of the following:

         1. Medication history indicates failure of ONE oral immunosuppressant therapy (i.e., MMF, azathioprine, cyclosporine, MTX, etc.);

         2. The individual has a documented intolerance, FDA labeled contraindication, or hypersensitivity to ALL oral immunosuppressants;

      3. Other causes of blistering or erosive skin and mucous membrane diseases have been ruled out;

   5. The individual has a diagnosis of autoimmune hemolytic anemia and ONE of the following:

      1. Medication history indicates failure of systemic corticosteroids;

      2. The individual is corticosteroid-dependent (e.g., high doses of corticosteroids to maintain response or maintenance corticosteroids for >3 months);

   6. The individual has a diagnosis of chronic graft versus host disease and ALL of the following:

      1. The individual is 8 years of age or older;

      2. ONE of the following:

         1. The individual had an inadequate response to corticosteroids;

         2. The individual has a documented intolerance, FDA labeled contraindication, or hypersensitivity to at least ONE corticosteroid;

      3. ONE of the following:

         1. Medication history indicates failure of ONE oral immunosuppressant (i.e., cyclosporine, sirolimus, tacrolimus, etc.);

         2. The individual has a documented intolerance, FDA labeled contraindication, or hypersensitivity to ALL oral immunosuppressants;

   7. The individual has a diagnosis of acute or chronic immune thrombocytopenia (ITP) and BOTH of the following:

      1. The individual's platelet count is <30,000µL;

      2. ONE of the following:

         1. The individual had an inadequate response to corticosteroids AND immunoglobulin therapy (i.e., failure to achieve and maintain a platelet count ≥30,000/µL for 3-6 months following completion of treatment) with or without a splenectomy;

         2. The individual has a documented intolerance, FDA labeled contraindication, or hypersensitivity to one corticosteroid AND immunoglobulin therapy;

   8. The individual has a diagnosis of neuromyelitis optica and ONE of the following:

      1. Medication history indicates failure to at least ONE first-line therapy (i.e., azathioprine, MMF, MTX, mitoxantrone, glucocorticoids);

      2. The individual has a documented intolerance, FDA labeled contraindication, or hypersensitivity to ALL conventional agents;

   9. The individual has a diagnosis of active systemic lupus erythematosus and ONE of the following:

      1. Medication history indicates failure of TWO immunosuppressants (i.e., hydroxychloroquine, MMF, cyclophosphomide, azathioprine, etc.);

      2. The individual has a documented intolerance, FDA labeled contraindication, or hypersensitivity to ALL oral immunosuppressants;

   10. The individual has a diagnosis of thrombotic thrombocytopenic purpura (TTP) that is refractory to plasma exchange and corticosteroids;

   11. The individual has a diagnosis of primary progressive or relapsing forms of multiple sclerosis (MS) and BOTH of the following:

       1. The individual is not currently being treated with ANY of the following:

          1. Disease modifying therapy (e.g., interferon beta preparations, dimethyl fumarate, glatiramer, natalizumab, fingolimod, cladribine, siponimod, or teriflunomide);

          2. B cell targeted therapy (e.g., ocrelizumab, belimumab, ofatumumab);

          3. Lymphocyte trafficking blockers (e.g., alemtuzumab, mitoxantrone);

       2. Prescriber is a neurologist;

3. The individual is not currently being treated with another biologic immunomodulatory agent (i.e., TNF-inhibitor, IL-inhibitor, anti IgE antibody, etc.), Xeljanz/Xeljanz XR, or Otezla;

4. BOTH of the following:

   1. The individual has been screened for hepatitis B infection measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc);

   2. If positive, the individual has begun hepatitis B therapy;

5. The individual does not have any FDA-labeled contraindication(s) to therapy with the requested agent;

6. The prescribed dosage is within the program quantity limits based on FDA approved labeled dosage.

Length of Approval: 12 months  

Renewal Evaluation:

Ruxience (rituximab-pvvr) and Truxima (rituximab-abbs) may be approved for RENEWAL when ALL of the following are met:

1. The individual has been previously approved for the requested agent through the BCBSMS PA process;

2. The individual has documented clinical response/improvement (i.e., slowing of disease progression, stabilization of disease, decrease in symptom severity and/or frequency, etc.);

3. The individual is not currently being treated with another biologic immunomodulatory agent (i.e., TNF-inhibitor, IL-inhibitor, anti IgE antibody, etc.), Xeljanz/Xeljanz XR, or Otezla;

4. The individual does not have any FDA-labeled contraindication(s) to therapy with the requested agent;

5. The prescribed dosage is within the program quantity limits based on FDA approved labeled dosage.

Length of Approval: Up to 12 months

 Rituxan Hycela is considered investigational when used for treatment of non-oncologic diagnoses.

Riabni (rituximab-arrx) and Rituxan (rituximab) are considered not medically necessary on all Blue Cross & Blue Shield of Mississippi formularies as there are other formulary alternatives available.

POLICY EXCEPTIONS

State Health Plan (State and School Employees) Participants

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D;

A. consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B. appropriate with regard to standards of good medical practice; and

C. not solely for the convenience of the Member, his or her Provider; and

D. the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary. 

BCBSMS may request medical records for determination of medical necessity. When medical records are requested, letters of support and/or explanation are often useful, but are not sufficient documentation unless all specific information needed to make a medical necessity determination is included.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.

Medication Failure

Medication failure is defined as disease progression at generally accepted doses (≥3 months use) as appropriate for the disease state being treated. Dosages below the recommended dose for the specific condition being treated and/or experience of common side effects of medication will not be considered medication failure or lack of response for the purpose of this review.

BCBSMS determines patient medication trial and adherence by a review of pharmacy claims data over the preceding twelve months. Additional information may be requested on a case-by-case basis to allow for proper review. If individual is new to BCBSMS and pharmacy records are needed to confirm medication trials and adherence, it is the responsibility of the individual and/or requesting provider to obtain said records and to submit them to BCBSMS upon request. Medical records from the provider that list previously prescribed medications will not be sufficient to show medication trials or adherence.

POLICY HISTORY

04/01/2018: New policy added.

12/20/2018: Code Reference section updated to add new HCPCS code J9312, effective 01/01/2019.

08/08/2019: Policy Exceptions updated to add that for State Health Plan members, Rituxan (rituximab) does not require prior authorization. However, the drug will be reviewed for medical necessity based on medical policy guidelines. Effective 04/01/2019.

10/01/2019: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Policy statement updated to add neuromyelitis optica (relapse prevention), refractory to first-line therapy (azathioprine, MMF, MTX, mitoxantrone, glucocorticoids) as a medically necessary indication. Sources updated. Code Reference section updated to add ICD-10 diagnosis code G36.0.

05/18/2020: Added Ruxience (rituximab-pvvr) and Truxima (rituximab-abbs) to the policy. Policy description updated to add moderate to severe pemphigus vulgaris as a condition approved for treatment with rituximab. Policy section updated to add: When available, the biosimilar product must be tried for at least 3 maintenance doses, not including induction doses, before consideration of coverage of the reference product. Medically necessary criteria updated to add: 1) examples of biologic immunomodulatory agents 2) reference to Policy Guidelines for definition of failure 3) links to Anti-Rheumatic Biologicals policy 4) medically necessary criteria regarding moderate to severe pemphigus vulgaris, autoimmune hemolytic anemia, chronic graft versus host disease, idiopathic or immune thrombocytopenic purpura, active systemic lupus erythematosus, and thrombotic thrombocytopenic purpura. Added the following as medically necessary: 1) If request is for Rituxan (rituximab), the Member has tried biosimilar as outlined above; and 2) The patient is not currently being treated with another biologic immunomodulatory agent. Removed list of biologic agents contraindicated as concomitant therapy. Policy Guidelines updated regarding medication failure. Code Reference section updated to remove deleted HCPCS code J9310.

06/29/2020: Code Reference section updated to add new HCPCS code Q5119, effective 07/01/2020.

09/29/2020: Code Reference section updated to add new ICD-10 diagnosis code M06.0A, effective 10/01/2020.

05/15/2021: Policy title changed from "Rituxan (rituximab) Non-Oncology" to "Rituximab Non-Oncology." Added drug name to the top of the policy. Policy description updated. Policy section updated to state that the use of samples by a Member will not be considered current or stable therapy for purposes of Medical Policy review. Medically necessary policy statement updated to remove Truxima (rituximab-abbs), add Riabni (rituximab-arrx), and revise criteria. Revised criteria for renewal evaluation. Added the following statements: 1) Rituxan Hycela is considered investigational when used for treatment of non-oncologic diagnoses. 2) Truxima (rituximab-abbs) is considered not medically necessary as both the reference product and biosimilars are covered by the Plan. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders" and "Medically Necessary" to "medical necessity." Added information regarding BCBSMS request for medical records and defined medication failure. Sources updated. Code Reference section updated to add HCPCS codes C9399 and Q5115.

07/01/2021: Code Reference section updated to add new HCPCS code Q5123, effective 07/01/2021.

02/01/2023: Policy Exceptions updated to add the following: State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

02/28/2023: Policy section updated to state that Riabni (rituximab-arrx), Rituxan (rituximab), and Truxima (rituximab-abbs) are considered not medically necessary on all Blue Cross & Blue Shield of Mississippi formularies as there are other formulary alternatives available. Code Reference section updated to move J9312 and Q5123 to the Not Medically Necessary Codes table. Added link to Biosimilar Medications medical policy. Effective 04/01/2023.

07/01/2023: Policy Exceptions updated regarding State Health Plan (State and School Employees) Participants.

10/01/2024: Policy reviewed and approved by the Pharmacy & Therapeutics (P&T) Committee. Policy language updated to change "member" to "individual." Policy statement criteria updated with minor changes. Sources updated.

03/21/2025: Policy section updated to move Truxima (rituximab-abbs) from not medically necessary to medically necessary when the listed indications are met. Code Reference section updated to move HCPCS code Q5115 from the Not Medically Necessary Codes table to the Medically Necessary Codes table.

09/09/2025: Policy reviewed by Pharmacy & Therapeutics (P&T) Committee; no changes to policy statement. Sources updated.

SOURCE(S)

1. Blue Cross & Blue Shield Association Policy 5.01.24 Nononcologic Uses of Rituximab.

2. Riabni prescribing information. Amgen, Inc. June 2025. Last accessed July 2025.

3. Rituxan prescribing information. Genentech, Inc. January 2025. Last accessed July 2025.

4. Ruxience prescribing information. Pfizer Laboratories Div. Pfizer, Inc. June 2025. Last accessed July 2025.

5. Truxima prescribing information. Cephalon, Inc. June 2025. Last accessed July 2025.

6. Murrell DF, Peña S, Joly P, et al. Diagnosis and management of pemphigus: Recommendations of an international panel of experts. J Am Acad Dermatol. 2020;82(3):575-585.e1. doi:10.1016/j.jaad.2018.02.021

7. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 clinical practice guideline for the management of glomerular diseases. Kidney Int. 2021;100(4S):S1-S276

8. Jarius, S, Aktas, O, Ayzenberg, I, et al. Update on the diagnosis and treatment of neuromyelits optica spectrum disorders (NMOSD) – revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part I: Diagnosis and differential diagnosis. J Neurol 270, 3341–3368 (2023). https://doi.org/10.1007/s00415-023-11634-0

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Medically Necessary Codes

Not Medically Necessary Codes

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