CurrentBlue Cross Blue Shield - MassachusettsPolicy 123

Rituximab Medical Necessity Criteria

Defines medical necessity criteria, prior authorization requirements, preferred status of rituximab products, covered indications (selected FDA and off-label autoimmune, hematologic, vasculitic, transplant-related conditions) and investigational exclusions for non-oncologic uses for BCBSMA commercial members. Applies to outpatient medical and pharmacy benefits per formulary/prior authorization table.

Policy Summary

PayerBlue Cross Blue Shield - Massachusetts

PolicyRituximab Medical Necessity Criteria

Policy CodePolicy 123

Change TypeMultiple updates (removals, formulary preference changes, dose/frequency alignment)

Effective DateNov 1, 2020

Next Review Date

Key ActionPrior authorization is required for rituximab per the formulary table; physicians should call Pharmacy Operations or submit the prior authorization/formulary exception form.

SourceLink

POLICY UPDATE CHANGES

Removed rituximab from the Cotivity program.

Updated to require dose and frequency for the policy to coincide with the Medical claim edits.

Updated policy to make Truxima preferred and Riabni non-preferred.

Reformatted policy.

Updated policy to make Riabni preferred and Truxima non-preferred.

BCBSA National medical policy review; no changes to policy statements, new references added.

New medical policy describing medically necessary and investigational indications.

3Primary covered indications listed

15Off-label indications considered medically necessary (selected)

Coverage Summary

This policy defines medical necessity criteria and prior authorization requirements for nononcologic uses of rituximab for BCBSMA commercial members and applies to outpatient medical and pharmacy benefits per the formulary/prior authorization table. It specifies covered FDA and selected off-label autoimmune, hematologic, vasculitic, and transplant-related indications and lists investigational exclusions for other nononcologic uses. Coverage and prior authorization follow the formulary table (preferred and non-preferred products) and physicians may call or fax Pharmacy Operations or submit the standard prior authorization/formulary exception form. For any oncology diagnosis, refer to the Quality Care Cancer Program Oncology Policy 099 (oncology requests routed to Carelon).

Policy metadata

Policy number123

Policy titleRituximab Medical Necessity Criteria

PayerBlue Cross Blue Shield - Massachusetts

Effective date2020-11-01

Last review2026-01-15

StatusCURRENT

Scope summaryDefines medical necessity criteria, prior authorization requirements, preferred status of rituximab products, covered indications (selected FDA and off-label autoimmune, hematologic, vasculitic, transplant-related conditions) and investigational exclusions for non-oncologic uses for BCBSMA commercial members. Applies to outpatient medical and pharmacy benefits per formulary/prior authorization table.

Medically Necessary Criteria

Medically Necessary Indications (nononcologic)

Rituximab may be considered MEDICALLY NECESSARY when ONE of the following primary indications is met and formulary/prior authorization rules followed:

ALL of the following

Primary indications (any)
- Rheumatoid Arthritis
- Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA)
- Pemphigus Vulgaris (PV)
Biosimilar policy notes

Investigational / Not Medically Necessary

Investigational / Not Medically Necessary Indications

Rituximab is INVESTIGATIONAL for all other nononcologic uses including (but not limited to):

Investigational / Not Medically Necessary (examples)

Idiopathic thrombocytopenic purpura in patients who do not respond to first-line treatments
Paroxysmal cold hemoglobinuria
Mixed connective tissue disease
Multiple sclerosis
Treatment of myasthenia gravis

Coding & Formulary Status

Informational procedure/diagnosis codes (listed as included when medical necessity met)mixed

No codes listed

Drug products and formulary status (from drug table)NDC|HCPCS|mixed

Rituxan	rituximab (originator) - Non-preferred with Prior Authorization; special biosimilar rules and exception for PV
Riabni	rituximab-arrx - Non-preferred with Prior Authorization; approvals require two preferred biosimilars except where noted
Ruxience	rituximab-pvvr - Preferred with Prior Authorization
Truxima	rituximab-abbs - Preferred with Prior Authorization

All formulary-covered rituximab products require prior authorization (medical and/or pharmacy benefits) per the formulary table. The drug table identifies preferred (Ruxience, Truxima) and non-preferred (Rituxan, Riabni) products with prior authorization requirements and includes special biosimilar rules: approvals for Rituxan or Riabni generally require use of two preferred biosimilars except where noted, and Rituxan for Pemphigus Vulgaris is exempt from the biosimilar requirement because biosimilars were not FDA approved prior to allowing the originator product. Per the 3/2024 update, requests must include the dose and frequency to align with Medical claim edits.

Provider Actions

Prior Authorization

Prior authorization required

Prior authorization is required for rituximab (medical and/or pharmacy benefits) per the formulary table. Physicians may call BCBSMA Pharmacy Operations at 1-800-366-7778 or fax 1-800-583-6289. Submit the prior authorization/formulary exception form when requesting coverage.

Documentation Required

Dose/frequency alignment

Requests should include dose and frequency details. The policy was updated in 3/2024 to require dose and frequency to coincide with Medical claim edits; include dose and frequency information when submitting requests.

Background & Evidence

Rituximab is an intravenous chimeric anti-CD20 monoclonal antibody that depletes pre-B and mature B lymphocytes by complement-dependent and antibody-dependent cell-mediated cytotoxicity, reducing pathogenic B-cell activity in autoimmune diseases. It is infused intravenously for approved and selected nononcologic indications.

Rituximab carries boxed warnings for fatal infusion reactions within 24 hours (most with first infusion), severe mucocutaneous reactions, hepatitis B virus reactivation (including fulminant hepatitis and hepatic failure), and progressive multifocal leukoencephalopathy (PML). Additional labeled warnings include tumor lysis syndrome (in hematologic malignancies), infections, cardiac arrhythmias/angina, bowel obstruction/perforation, withholding live vaccines, and cytopenias.

This policy covers nononcologic uses of rituximab; for any oncology diagnosis, refer to the separate oncology policy 099 and submit oncology requests to Carelon.

Label	Summary
Warm AIHA RCTs	Two randomized controlled trials found overall response rates were better with rituximab than control at 1 year; serious adverse events were higher with rituximab versus corticosteroids in one RCT but lower than placebo in the other. Evidence judged sufficient to improve net health outcome.
ITP evidence	A randomized trial of rituximab as second‑line therapy in adults failed to demonstrate improved outcomes; observational studies exist but evidence is insufficient to determine effects on health outcomes.
TTP evidence	Phase 2 and cohort studies (nonrandomized) and case series report consistent evidence of improved outcomes, including substantially lower relapse rates versus historical controls; evidence considered sufficient to improve net health outcome.
HCV-associated cryoglobulinemic vasculitis	Two randomized controlled trials plus a phase 2 nonrandomized trial and observational studies report response rates consistent with improved health outcomes; evidence sufficient to determine meaningful improvement.
Range of literature cited	References include randomized trials, systematic reviews, cohort studies, consensus guidelines and specialty society recommendations (references numbered 74 through 172 and other cited references).

Individual Consideration: A process to submit requests that do not meet the policy's clinical criteria, with supporting clinical information, for case-by-case review by BCBSMA Pharmacy Operations. Physicians may send relevant clinical information by mail, phone, or fax to Pharmacy Operations for review.

Cotivity program: Referenced internal program from which rituximab was removed (action dated 1/15/2026); no further detail on the program is provided in this policy.

Revision History

2026-01-15removedLatest

Removed rituximab from the Cotivity program. (Policy history entry: 1/15/2026)

2024-03revised

Policy updated to require dose and frequency details to align with Medical claim edits (requests should include dose and frequency). (3/2024)

2024-01revised

Policy updated to make Truxima preferred and Riabni non-preferred. (1/2024)

Medically Necessary — Off-Label Indications (selected)

Rituximab may be considered MEDICALLY NECESSARY for the following off-label indications (including any additional criteria in sub-bullets):

Off-label indications (selected)

Autoimmune hemolytic anemias (AIHA): warm AIHA in glucocorticoid-refractory or glucocorticoid-dependent patients
Cold agglutinin syndrome
Thrombotic thrombocytopenic purpura (TTP) in patients with refractory disease or relapse (lack of response to plasma exchange therapy and glucocorticoids)
Churg-Strauss syndrome (eosinophilic granulomatosis with polyangiitis): first-line with glucocorticoids for severe organ-threatening disease OR add-on for treatment-refractory disease
Factor inhibitors in patients with hemophilia refractory to conventional first-line treatments, preferably as add-on therapy
Add-on therapy for hepatitis C virus-associated cryoglobulinemic vasculitis when active disease resistant to antivirals or severe/life-threatening
Multicentric Castleman disease (first- or second-line therapy)
Primary Sjögren syndrome refractory to glucocorticoids and other immunosuppressives
Add-on therapy for systemic lupus erythematosus refractory to standard first-line treatment
Add-on therapy for lupus nephritis refractory to standard first-line regimens
Systemic sclerosis (scleroderma) refractory to first-line treatment
Neuromyelitis optica for relapse prevention
Idiopathic membranous nephropathy
Glucocorticoid-refractory chronic graft-versus-host disease
Desensitization of HLA-sensitized renal transplant candidates before transplantation