ModifiedPremera BluecrossPolicy 5.01.24

Rituximab products (Rituxan, Ruxience, Truxima, Riabni) site-of-service and medical necessity

Medical necessity and site-of-service criteria for IV and injectable rituximab products and listed biosimilars for non-oncologic indications; governs Premera Bluecross reviews for covered members (with an Alaska fully-insured exception for SOS rules).

Policy Summary

PayerPremera Bluecross

PolicyRituximab products (Rituxan, Ruxience, Truxima, Riabni) site-of-service and medical necessity

Policy CodePolicy 5.01.24

Change TypeFormulary/step-therapy and site-of-service updates (material)

Effective DateOct 3, 2025

Next Review DateN/A

Key ActionSubmit prior authorization with documentation of prior therapies and trials of preferred biosimilars (Ruxience or Truxima) when requesting non-preferred rituximab products.

SourceLink

POLICY UPDATE CHANGES

The policy consolidates site-of-service medical necessity criteria and lists Ruxience and Truxima as first-line products with Riabni as a second-line product.

Changed Ruxience (rituximab-pvvr) to a preferred product and updated preferred/non-preferred status for other rituximab products and adalimumab products effective January 3, 2025.

Updated coverage criteria for Riabni (rituximab-arrx), Rituxan, and Rituxan Hycela to require an adequate trial and failure with Ruxience or Truxima.

Added an exception to the site-of-service requirements for certain individuals receiving treatment for cytokine release syndrome (CRS).

Clarified that non-formulary exception review authorizations for all drugs listed in this policy may be approved up to 12 months.

~14indications discussed

12 monthsapproval length

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SOS exception: CRSCRS exception added

2024-2025recent updates

Medical Necessity and Indication-Specific Criteria

Covered indications and indication-specific criteria

Ruxience or Truxima may be considered medically necessary when specific, indication-dependent criteria are met:

Rheumatoid arthritis: Moderately to severely active rheumatoid arthritis AND administered in combination with methotrexate AND inadequate response to one or more standard agents (e.g., TNF inhibitors, methotrexate or other conventional synthetic DMARD) or contraindication to those agents; use consistent with FDA label and guideline-based sequencing.

Evidence includes RCTs and observational studies supporting meaningful improvement in net health outcome.

ANCA-associated vasculitis (GPA/MPA): Diagnosis of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) AND initial therapy with azathioprine, methotrexate and/or mycophenolate has been tried and failed or is contraindicated AND medication used in combination with glucocorticoids.

Trials demonstrated noninferiority/superiority to cyclophosphamide regimens.

Eosinophilic granulomatosis with polyangiitis (EGPA): Used as first-line treatment in combination with glucocorticoids for individuals with severe (organ-threatening) disease OR used as add-on therapy for treatment-refractory disease.

Policy allows first-line use for severe organ-threatening EGPA or add-on for refractory disease.

HCV-associated cryoglobulinemic vasculitis: Used as add-on therapy for individuals with active disease resistant to antiviral therapy OR for severe or life-threatening cryoglobulinemic vasculitis.

Supported by randomized trials and considered sufficient for meaningful improvement.

Idiopathic membranous nephropathy: Used after failure of other immunosuppressive regimens (e.g., cyclophosphamide plus glucocorticoids, chlorambucil plus glucocorticoids, cyclosporine, tacrolimus) or in patients with moderate risk who have not previously received immunosuppressive therapy per guideline considerations.

RCT and observational data suggest moderate benefit.

Neuromyelitis optica spectrum disorder (NMOSD): Documented NMOSD diagnosis with at least one core clinical characteristic (e.g., optic neuritis, acute myelitis, area postrema syndrome, acute brainstem syndrome, symptomatic narcolepsy/diencephalic syndrome, symptomatic cerebral syndrome) AND additional diagnostic confirmation as required by NMOSD criteria; used for relapse prevention per guideline recommendations.

Consensus guidance recommends rituximab as a first-line or second-line option.

Second-line products

Second-line agents (Riabni, Rituxan, Rituxan Hycela) coverage:

Second-line requirement: Member must meet the medical necessity criteria for the requested indication AND have had an inadequate response to or intolerance of preferred first-line biosimilars Ruxience (rituximab-pvvr) or Truxima (rituximab-abbs). Exception: Rituxan Hycela may be approved with documentation of difficult venous access.

Policy update effective Jan 3, 2025 requires trial and failure of preferred biosimilars before these second-line products unless exception documented.

Investigational indications

Not covered / investigational

Investigational uses: Rituximab is investigational for all other non-oncologic uses not outlined in this policy, including but not limited to: induction immunosuppression for kidney transplantation, induction immunosuppression for heart transplantation, mixed connective tissue disease, multiple sclerosis, paroxysmal cold hemoglobinuria, prophylaxis for graft-versus-host disease, treatment of antibody-mediated rejection in solid organ transplant recipients (including after pancreatic islet transplantation), minimal change disease, myasthenia gravis, and other uses not specified as covered in this policy.

Investigational status per policy statement.

Rheumatoid arthritis (FDA label)

Rheumatoid arthritis — covered when ALL of the following are met

RA initial therapy criteria: Moderately to severely active rheumatoid arthritis AND inadequate response to one or more standard agents (e.g., TNF inhibitors, methotrexate or other conventional synthetic DMARD) AND rituximab administered in combination with methotrexate per FDA label and dosing guidance.

Evidence includes 4 RCTs and observational studies demonstrating meaningful improvement in net health outcome; reassess response per guidelines (~6 months).

ANCA-associated vasculitides

ANCA-associated vasculitides — covered when ALL of the following are met

GPA/MPA induction or maintenance criteria: Diagnosis of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) AND rituximab used in combination with glucocorticoids for induction or used for maintenance therapy as appropriate AND prior standard therapies (e.g., cyclophosphamide) are contraindicated, have exceeded cumulative dose, or have failed per guideline criteria.

RCTs demonstrated noninferiority or superiority to cyclophosphamide-based regimens; NICE and ACR/NVasculitis guidance support use.

Pemphigoid and pemphigus diseases

Pemphigus and selected pemphigoid diseases — covered when ALL of the following are met

Pemphigus/pemphigoid refractory criteria: Diagnosis of pemphigus or a pemphigoid disease AND standard initial therapy (including at least two of: glucocorticoids, azathioprine, mycophenolate, dapsone) has been tried and failed OR, for pemphigus, rituximab may be considered as first-line with short-term corticosteroids per FDA label for newly diagnosed pemphigus disease; rituximab given in combination with corticosteroids as described in the literature.

RCT evidence in pemphigus shows improved complete response and reduced steroid exposure; pemphigoid evidence is more limited but supports use in refractory patients.

Autoimmune hemolytic anemia (AIHA)

Autoimmune hemolytic anemia — covered when ALL of the following are met

Warm AIHA criteria: Diagnosis of warm autoimmune hemolytic anemia AND inadequate response to first-line corticosteroids or corticosteroid-dependent disease AND use of rituximab consistent with FDA-labeled hematologic indications.

RCTs and observational studies show improved overall response rates with rituximab at 1 year; rituximab is not considered a treatment option for paroxysmal cold hemoglobinuria.

ITP (relapsed/refractory)

Idiopathic thrombocytopenic purpura (ITP) — stance

ITP criteria: For relapsed or refractory ITP in adults, available RCT evidence does not demonstrate clear benefit of rituximab as second-line therapy; policy considers evidence insufficient to establish rituximab as standard second-line therapy in adults. For chronic (>=3 months) corticosteroid-dependent or corticosteroid-refractory ITP, rituximab may be an option per ASH conditional recommendations and guideline-aligned justification is required for authorization.duration >=3 months

Documentation should include prior therapies and justification per ASH guidance.

TTP (relapsed/refractory)

Thrombotic thrombocytopenic purpura (TTP) — covered when ALL of the following are met

Refractory TTP criteria: Diagnosis of relapsed or refractory TTP (progression during plasma exchange or relapsing disease) AND rituximab used in conjunction with plasma exchange and corticosteroids as clinically indicated.

Nonrandomized studies and guideline recommendations (BCSH, ISTH) support use; rituximab lowers relapse rates and may be considered for relapse prevention.

Factor inhibitors in hemophilia

Factor inhibitors in hemophilia — covered when ALL of the following are met

Hemophilia with inhibitors refractory to first-line therapy: Congenital or acquired hemophilia A with inhibitory antibodies refractory to first-line immune tolerance induction (ITI) or recommended immunosuppressive therapy AND rituximab used as second-line therapy (often as add-on to other immunosuppressive agents).

Evidence includes phase 2 and cohort studies with response rates 25%–50%; considered a meaningful improvement when first-line ITI fails or is contraindicated.

Mixed connective tissue disease (MCTD)

Mixed connective tissue disease (MCTD) — stance

MCTD criteria: Evidence for rituximab in MCTD is limited to case series; benefits on clinical outcomes and pulmonary function are not established and evidence is insufficient to determine effects on health outcomes.

Policy classifies MCTD indication as insufficient evidence/not established.

Multicentric Castleman disease

Multicentric Castleman disease — covered when ALL of the following are met

Multicentric Castleman disease criteria: Diagnosis of multicentric Castleman disease AND rituximab used as therapy in patients (HIV-negative or as alternative in HIV-infected patients) based on cohort data demonstrating improved overall survival and reduced progression to non-Hodgkin lymphoma.

Evidence from prospective and retrospective cohort studies considered sufficient for meaningful improvement in net health outcome.

Multicentric Castleman disease