State and School Employees' Health Insurance Plan - Rituximab Non-Oncology

POLICY NUMBER

S.5.01.518

Riabni (rituximab-arrx)

Rituxan (rituximab)

Ruxience (rituximab-pvvr)

Truxima (rituximab-abbs)

Please perform a search of the State Health Plan Medical Drug Formulary for drugs administered and billed through the medical setting.

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, microscopic polyangiitis, and moderate to severe pemphigus vulgaris. 

Related medical policies - 

• State and School Employees' Health Insurance Plan - Biosimilar Medications

• Plasma Exchange

• State and School Employees' Health Insurance Plan - Immune Thrombocytopenia

• State and School Employees' Health Insurance Plan - Immunoglobulin Therapy

• State and School Employees' Health Insurance Plan - Anti-Rheumatic Biologicals

• State and School Employees' Health Insurance Plan - Systemic Lupus Erythematosus (SLE) & Lupus Nephritis (LN)

• State and School Employees' Health Insurance Plan - Multiple Sclerosis

POLICY

The use of samples by an individual will not be considered current or stable therapy to satisfy 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. 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. Individual has a diagnosis of moderate to severely active rheumatoid arthritis (RA) and ONE of the following:

      1. Individual has tried and had an inadequate response to ONE conventional agent prerequisite (i.e., azathioprine, methotrexate, leflunomide, sulfasalazine, hydroxychloroquine) after at least a 3-month duration of therapy (see definition of Medication Failure in The Policy Guidelines section);

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

      3. The individual’s medication history indicates use of another biologic immunomodulator agent used for the treatment of RA;

   3. Individual has a diagnosis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (i.e., granulomatosis with polyangiitis (GPA) [Wegener’s granulomatosis], microscopic polyangiitis (MPA), Churg-Strauss syndrome, or pauci-immune glomerulonephritis) and BOTH of the following:

      1. Individual is 2 years of age or older; AND

      2. ONE of the following:

         1. Individual will receive a corticosteroid in combination with rituximab; OR

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

   4. Individual has a diagnosis of pemphigus vulgaris or other refractory autoimmune blistering disease (i.e., pemphigus foliaceus, paraneoplastic pemphigus, bullous pemphigoid, epidermolysis bullosa acquisita) and ONE of the following:

      1. The individual has moderate to severe pemphigus vulgaris (PV) and ONE of the following:

         1. The individual will receive a corticosteroid in combination with rituximab; OR

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

      2. The individual has treatment-refractory pemphigoid disease and has had an inadequate response to corticosteroids AND oral immunosuppressant therapy (i.e., mycophenolate, azathioprine, cyclosporine, methotrexate);

   5. Individual has a diagnosis of autoimmune hemolytic anemia (AIHA) and ONE of the following:

      1. The individual has warm AIHA and is glucocorticoid-refractory or glucocorticoid-dependent; OR

      2. The individual has cold agglutinin disease (CAD);

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

      1. Individual is 8 years of age or older;

      2. ONE of the following:

         1. Individual has tried and had an inadequate response to corticosteroid therapy; OR

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

      3. ONE of the following:

         1. The individual has tried and had an inadequate response to at least ONE oral immunosuppressant (i.e., cyclosporine, sirolimus, tacrolimus, etc.); OR

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

   7. Individual has a diagnosis of immune thrombocytopenia (ITP) and ALL of the following:

      1. ONE of the following:

         1. Acute ITP evidenced by ONE of the following:

            1. Platelet count <30 X 10⁹/L;

            2. Platelet count <50 X 10⁹/L with significant bleeding symptoms (e.g., mucosal bleeding) or high risk for bleeding (e.g., peptic ulcer disease, liver disease, >60 years of age, concurrent anticoagulation/anti-platelet therapy); OR

            3. Platelet count <100 X 10⁹/L with increased platelet count required prior to invasive surgical procedures, such as splenectomy; OR

         2. Chronic/persistent ITP (≥3 months since diagnosis) with increased bleeding risk evidenced by ONE of the following:

            1. Platelet count <30 x 10⁹/L; OR

            2. Platelet count <50 x 10⁹/L with significant bleeding symptoms (e.g., mucosal bleeding) or documented high risk for bleeding (e.g., peptic ulcer disease, liver disease, >60 years of age, concurrent anticoagulation/anti-platelet therapy); AND

      2. ONE of the following:

         1. The individual has a documented inadequate response (defined as platelet count <30 x 10⁹/L, or platelet count >30 x 10⁹/L but with bleeding symptoms) or dependence (i.e., unable to taper) to corticosteroids after a 4-6 week duration of therapy AND an adequate trial of IVIG, with or without a splenectomy; OR

         2. The individual has a documented intolerance, FDA labeled contraindication, or hypersensitivity to corticosteroid AND IVIG therapies;

   8. Individual has a diagnosis of neuromyelitis optica spectrum disorder and ALL of the following:

      1. Serologic testing for anti-aquaporin-4 immunoglobulin G (AQP4-IgG) antibodies has been performed;

      2. Past medical history of (at least ONE of the following if AQP4-IgG positive or at least TWO of the following if AQP4-IgG negative):

         1. Optic neuritis;

         2. Acute myelitis;

         3. Area postrema syndrome (episode of otherwise unexplained hiccups or nausea and vomiting);

         4. Acute brainstem syndrome;

         5. Symptomatic narcolepsy or acute diencephalic clinical syndrome with NMOSD-typical diencephalic MRI lesions; OR

         6. Symptomatic cerebral syndrome with NMOSD-typical brain lesions;

      3. The individual has had at least 1 discrete clinical attack of CNS symptoms; AND

      4. Alternative diagnoses (e.g., multiple sclerosis, ischemic optic neuropathy) have been ruled out;

   9. Individual has a diagnosis of active systemic lupus erythematosus with or without lupus nephritis and ONE of the following:

      1. The individual has tried and had an inadequate response to at least TWO immunosuppressants (i.e., hydroxychloroquine, mycophenolate, cyclophosphamide, azathioprine, etc.); OR

      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) and BOTH of the following:

       1. The requested agent will be used in combination with plasma exchange therapy; AND

       2. The individual is receiving concurrent corticosteroid therapy unless there is a documented failure, contraindication, or intolerance to corticosteroids;

   11. Individual has a diagnosis of primary progressive or relapsing forms of multiple sclerosis (MS) and the requested agent will not be used in combination 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); OR

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

   12. The individual has a diagnosis of membranous nephropathy/membranous glomerular nephropathy and is at moderate to high risk of progressive loss of kidney function as evidenced by at least ONE of the following:

       1. eGFR < 60 ml/min/1.73m²;

       2. Proteinuria >8 g/day for >6 months;

       3. Proteinuria >3.5 g/day and no decrease >50% after 6 months of conservative therapy with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB); OR

       4. Individual has experienced serious complications of nephrotic syndrome (e.g., acute kidney injury, infection, thromboembolic events, etc.); OR

   13. The individual has a diagnosis of refractory myasthenia gravis and ONE of the following:

       1. The individual has tried and had an inadequate response to at least one conventional therapy (i.e., corticosteroids, azathioprine, cyclosporine, mycophenolate, etc.); OR

       2. The individual has a documented intolerance, FDA labeled contraindication, or hypersensitivity to ALL conventional therapies used in the treatment of myasthenia gravis (i.e., corticosteroids, azathioprine, cyclosporine, mycophenolate, etc.);

3. Individual is not currently being treated with another immunomodulatory agent (i.e., TNF-inhibitor, JAK inhibitor, IL-inhibitor, anti IgE antibody, Otezla, etc.);

4. BOTH of the following:

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

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

5. The prescriber is or has consulted with a specialist in the area of the individual’s diagnosis;

6. Individual does not have any FDA-labeled contraindication(s) to therapy with the requested agent; AND

7. The prescribed dosage is within the program quantity limits based on FDA approved labeled dosage or compendia-supported dosing for the requested agent.

Length of Approval: Up to 12 months

Renewal Evaluation:

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

1. Individual has been previously approved for the requested agent through the BCBSMS review process;

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

3. Individual is not currently being treated with another immunomodulatory agent (i.e., TNF-inhibitor, JAK inhibitor, IL-inhibitor, anti IgE antibody, Otezla etc.);

4. Individual does not have any FDA-labeled contraindications to therapy with the requested agent; AND

5. The prescribed dosage is within the program quantity limits based on FDA approved labeled dosage or compendia-supported dosing for the requested agent.

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.

Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary.

POLICY EXCEPTIONS

None

POLICY GUIDELINES

Medical Policy Manual coverage guidelines should not be used in lieu of the Participant's specific benefit plan language outlined in the Mississippi's State and School Employees’ Life and Health Insurance Plan.

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 Participant'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 Participant'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 Participant, his or her Provider; and

D. the most appropriate supply or level of care which can safely be provided to the Participant. When applied to the care of an Inpatient, it further means that services for the Participant's medical symptoms or conditions require that the services cannot be safely provided to the Participant 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 member is new to BCBSMS and pharmacy records are needed to confirm medication trials and adherence, it is the responsibility of the member 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

07/01/2023: New policy added.

10/01/2024: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Policy statement criteria updated with minor changes for clarity purposes. 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.

06/15/2026: Policy description updated regarding indications for rituximab. Policy section updated to revise criteria for the listed conditions. Added prescriber and dosage requirement.

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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