ModifiedUnitedHealthcarePolicy IEXD0003.15

Rituximab (non-oncology indications)

Defines UnitedHealthcare medical benefit coverage, preferred products, and diagnosis-specific medical necessity criteria for rituximab injections for intravenous infusion in non-oncology indications for applicable individual exchange plans.

Policy Summary

PayerUnitedHealthcare

PolicyRituximab (non-oncology indications)

Policy CodePolicy IEXD0003.15

Change TypePreferred product designation and multiple coverage clarifications

Effective DateJan 1, 2026

Next Review DateN/A

Key ActionObtain prior authorization and document that patient meets the Diagnosis-Specific Criteria and preferred-product requirements (use preferred products Riabni, Ruxience, or Truxima unless documented intolerance/contraindication).

SourceLink

POLICY UPDATE CHANGES

Added language to indicate Riabni (rituximab-arrx) is a preferred rituximab product and coverage will be provided contingent on the coverage criteria in the Diagnosis-Specific Criteria section.

Removed language requiring members already on Riabni to change therapy to Ruxience or Truxima unless they meet the criteria in the Preferred Product section.

Replaced language expanding which rituximab products qualify when patient has intolerance/contraindication/serious adverse event to preferred products; now specifies treatment with Rituxan or other rituximab products is medically necessary when history of intolerance/contraindication/serious adverse event to Riabni, Ruxience, or Truxima.

Revised coverage criteria for Immune Thrombocytopenic Purpura (ITP) replacing an allowance related to prior TPO-RA failure/contraindication/intolerance with a modified statement (text truncated in this excerpt).

Updated rheumatoid arthritis section: added Cimzia and Simponi to TNF inhibitor examples and removed Remicade; updated list of targeted immunomodulators not to be used in combination with rituximab — added Olumiant, Orencia, Rinvoq and removed adalimumab.

Updated References section to reflect current information and archived previous policy version IEXD0003.14.

3Preferred products

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IntoleranceNon-preferred exception

12 moInitial auth max

MostApplicable states

Diagnosis-Specific Coverage Criteria

Neuromyelitis Optica Spectrum Disorder (NMO/NMOSD)

Neuromyelitis Optica Spectrum Disorder (NMOSD) — Initial and Continuation Therapy

Initial Therapy

ALL of the following
- Serologic testing for anti-aquaporin-4 immunoglobulin G (AQP4-IgG)/NMO-IgG antibodies has been performed.
- - Optic neuritis
  - Acute myelitis
  - Area postrema syndrome: episode of otherwise unexplained hiccups or nausea and vomiting
  - Acute brainstem syndrome
  - Symptomatic narcolepsy or acute diencephalic clinical syndrome with NMOSD-typical diencephalic MRI lesions
  - Symptomatic cerebral syndrome with NMOSD-typical brain lesions
Diagnosis of multiple sclerosis or other diagnoses have been ruled out.
Prescribed by or in consultation with a neurologist.
- Disease-modifying therapies for multiple sclerosis (e.g., fingolimod, dimethyl fumarate, ocrelizumab, etc.)
- Anti-IL6 therapy (e.g., tocilizumab, sarilumab).
- Complement inhibitors (e.g., eculizumab, ravulizumab).
Initial authorization will be for no more than 12 months.

Continuation Therapy

- Disease-modifying therapies for multiple sclerosis (e.g., fingolimod, dimethyl fumarate, ocrelizumab, etc.).
- Anti-IL6 therapy (e.g., tocilizumab, sarilumab).
- Complement inhibitors (e.g., eculizumab, ravulizumab).
Reauthorization will be for no more than 12 months.
Documentation of clinical response or appropriate monitoring as documented by the treating neurologist (e.g., relapse frequency, disability measures, MRI findings, or B-cell monitoring if used by the treating clinician).
Clinical practice supports individualized retreatment; some specialists use B-cell (CD27+ memory B-cell) monitoring to guide maintenance dosing and retreatment intervals.

Dosing and Monitoring Considerations

Induction regimens commonly referenced include either two 1 g infusions separated by 2 weeks or four weekly infusions of 375 mg/m2.
Maintenance dosing strategies vary; repeated treatment every 6 months is often used given typical B-cell depletion duration; individualized schedules guided by CD27+ memory B-cell reemergence have been reported (e.g., retreat when CD27+ memory B cells >0.05% in first 2 years and >0.1% thereafter).
Evidence from open-label and retrospective series supports substantial reductions in annualized relapse rate and improved relapse-free survival with rituximab in NMOSD, and reduction in AQP4-IgG titers has been observed after treatment.

Authorization, Documentation, and Prescriber Responsibilities

Prior Authorization

Authorization duration and requirement

Prior authorization is required for all rituximab products. Initial authorizations and reauthorizations will be limited to no more than 12 months unless otherwise specified in the Diagnosis-Specific Criteria. Coverage decisions are contingent on meeting the applicable Diagnosis-Specific Criteria and the member's benefit plan document; consult the Certificate of Coverage and any state mandates which may supersede this policy.

Authorization duration: Initial and reauthorization periods are generally limited to ≤ 12 months (see diagnosis-specific exceptions).
Member benefit governs: confirm member-specific benefit plan and state mandates prior to approval.

Prior Authorization

Prior authorization requirements for rituximab

Prior authorization is required and will be approved only when diagnosis-specific medical necessity criteria are met. For non-preferred rituximab products (e.g., Rituxan or other non-preferred rituximab products), coverage requires documentation of intolerance, contraindication, or serious adverse event to preferred products (Riabni, Ruxience, or Truxima) and physician attestation that the same issue would not be expected with the non-preferred product. Members already on non-preferred products may be required to switch to a preferred product unless they meet these criteria.

Applicable Procedure and Diagnosis Codes

Applicable HCPCS/J-codesHCPCS

J9311	Injection, rituximab 10 mg and hyaluronidase
J9312	Injection, rituximab, 10 mg
Q5115	Injection, rituximab-abbs, biosimilar, (Truxima), 10 mg
Q5119	Injection, rituximab-pvvr, biosimilar, (Ruxience), 10 mg
Q5123	Injection, rituximab-arrx, biosimilar, (Riabni), 10 mg

Applicable ICD-10-CM Codes (selected excerpt)ICD-10

D89.84	IgG4-related disease
G35.B0	Primary progressive multiple sclerosis, unspecified
G35.B1	Active primary progressive multiple sclerosis
G35.B2	Non-active primary progressive multiple sclerosis
G35.C0	Secondary progressive multiple sclerosis, unspecified
G35.C1	Active secondary progressive multiple sclerosis
G35.C2	Non-active secondary progressive multiple sclerosis
G35.A	Relapsing-remitting multiple sclerosis
G35.D	Multiple sclerosis, unspecified
G36.0	Neuromyelitis optica

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Applicable ICD-10 Diagnosis CodesICD-10

M05.80	Other rheumatoid arthritis with rheumatoid factor of unspecified site
M05.811	Other rheumatoid arthritis with rheumatoid factor of right shoulder
M05.812	Other rheumatoid arthritis with rheumatoid factor of left shoulder
M05.819	Other rheumatoid arthritis with rheumatoid factor of unspecified shoulder
M05.821	Other rheumatoid arthritis with rheumatoid factor of right elbow
M05.822	Other rheumatoid arthritis with rheumatoid factor of left elbow
M05.829	Other rheumatoid arthritis with rheumatoid factor of unspecified elbow
M05.831	Other rheumatoid arthritis with rheumatoid factor of right wrist
M05.832	Other rheumatoid arthritis with rheumatoid factor of left wrist
M05.839	Other rheumatoid arthritis with rheumatoid factor of unspecified wrist

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inv-39: ITP platelet count eligibility thresholds

ITP trial enrollment platelet criteriaEligible trial patients had platelet counts ≤25 x10^9/L or ≤50 x10^9/L with bleeding symptoms.

Policy ITP initial therapy threshold (brief)Policy initial therapy node references platelet count < 30 x10^9/L as threshold for coverage consideration.

Reauthorization interval for ITPReauthorization limited to no more than 12 months with documented positive clinical response per General Requirements.

inv-40: CD27+ memory B cell threshold for maintenance dosing in NMO (Kim et al.)

CD27+ memory B-cell redosing thresholds (Kim et al.)Redose if CD27+ memory B cells > 0.05% during the first 2 years, and > 0.1% thereafter.

Policy Background, Definitions, and Clinical Context

Rituximab is a chimeric anti‑CD20 monoclonal antibody used intravenously for multiple autoimmune and hematologic non‑oncology indications addressed in this policy. The document distinguishes rituximab formulations without hyaluronidase (collectively referred to as rituximab) from Rituxan Hycela (rituximab with hyaluronidase), which is considered unproven for non‑oncology uses. Clinical applications in this policy include immune thrombocytopenic purpura, pemphigus vulgaris, autoimmune hemolytic anemia, neuromyelitis optica spectrum disorder, multiple sclerosis forms, IgG4‑related disease, thrombotic thrombocytopenic purpura, PTLD, and rheumatoid arthritis, with indication‑specific medical necessity criteria and documentation requirements.

inv-70: Rituximab / Rituxan Hycela definition and status

Definition'Rituximab' refers to all rituximab products without hyaluronidase (intravenous formulations).

Rituxan Hycela statusRituxan Hycela (rituximab and hyaluronidase) is considered unproven and not medically necessary for non-oncology indications.

Policy scope notePolicy applies to rituximab injections for intravenous infusion for non-oncology conditions and lists named products (Riabni, Rituxan, Rituxan Hycela, Ruxience, Truxima).

Clinical Evidence Summaries and Guidelines

Administration and Billing Notes

At the administration and safety level, the policy highlights FDA‑labeled indications across products and reiterates the FDA boxed warning regarding HBV reactivation risk. Clinicians are instructed to document indication alignment with FDA labeling and to perform recommended HBV screening and monitoring for patients with prior HBV infection prior to and during therapy.

Policy updates effective 01/01/2026 designate Riabni (rituximab‑arrx) as a preferred rituximab product and clarify preferred‑product handling. The revision also reiterates that Rituxan Hycela remains unproven for non‑oncology indications. These changes affect preferred product language and how non‑preferred product exceptions are applied.

Policy Updates and Change Log

2026-01-01preferred_product_updateLatest

Added language designating Riabni (rituximab-arrx) as a preferred rituximab product; coverage contingent on meeting the Diagnosis-Specific Criteria section.

2026-01-01preferred_product_update

Removed prior language requiring members already on Riabni to change therapy to Ruxience or Truxima for continued coverage.

2026-01-01product_exception_revision

Policy Summary

PayerUnitedHealthcare

PolicyRituximab (non-oncology indications)

Policy CodePolicy IEXD0003.15

Change TypePreferred product designation and multiple coverage clarifications

Effective DateJan 1, 2026

Next Review DateN/A

SourceLink

On This Page

Preferred products: Riabni (rituximab-arrx), Ruxience (rituximab-pvvr), Truxima (rituximab-abbs).
Non-preferred exception: history of intolerance/contraindication/serious adverse event to a preferred product + prescriber attestation.

Documentation Required

Applicable diagnosis codes for authorization

Applicable ICD-10 diagnosis codes must be submitted with the authorization request to support the requested indication. Use the member's specific diagnosis code(s) that correspond to the Diagnosis-Specific Criteria.

Examples include ICD-10 codes for rheumatoid arthritis, polyarteritis nodosa, thrombotic microangiopathy, Wegener's granulomatosis, microscopic polyangiitis, ITP, PTLD, NMOSD, IgG4-RD, and related codes as listed in the Applicable Codes section of the policy.
Include Z92.22 (personal history of monoclonal drug therapy) or relevant T-codes when applicable to document prior treatment adverse events.

Documentation Required

PA for FDA-indicated uses (documentation to support labeled uses)

FDA-approved indications for rituximab products should be documented when relevant. FDA approval by itself does not guarantee coverage; the indication must also meet the medical necessity criteria and member benefit provisions.

Document the specific FDA-labeled indication being requested (e.g., NHL, CLL, RA with methotrexate, GPA/MPA, PV where applicable to the product).
If requesting coverage for an FDA-indicated use, provide documentation that the patient's condition aligns with the labeled indication and any product-specific age or combination-therapy requirements.

Documentation Required

Use indications and documentation to support prior authorization

When requesting authorization, clearly state the clinical indication and provide supporting evidence that the request meets the Diagnosis-Specific Criteria. For indications without an FDA dosing guideline, prescriber must attest to published clinical evidence supporting the dosing.

Provide diagnosis, relevant laboratory/radiology results (e.g., AQP4-IgG for NMOSD), prior treatment history, and dates of prior therapies or procedures.
For continuation requests include documentation of positive clinical response.
For initial therapy, prescriber must attest dosing is per FDA labeling or supported by published evidence.

Prior Authorization

Prior authorization contingent on diagnosis-specific criteria

Prior authorization approvals are contingent on meeting the Diagnosis-Specific Criteria in this policy (see the Diagnosis-Specific Criteria section for detailed requirements for each indication).

Do not approve requests that fail to meet ALL relevant diagnosis-specific criteria.
Reauthorization requires continued documentation consistent with the continuation criteria for the specific diagnosis.

Denial Risk

Prohibited concomitant therapies

Rituximab must not be used concomitantly with certain other immunomodulatory or targeted therapies as specified in the Diagnosis-Specific Criteria; authorization may be denied if requested in combination with prohibited agents.

Prohibited combinations include, but are not limited to: other B-cell targeted therapies (e.g., ocrelizumab, ofatumumab), disease-modifying therapies for MS (e.g., fingolimod, dimethyl fumarate, natalizumab, interferons, cladribine, siponimod, teriflunomide), targeted immunomodulators for RA (e.g., abatacept, tofacitinib, baricitinib, upadacitinib), anti-IL6 agents (tocilizumab, sarilumab), complement inhibitors (eculizumab, ravulizumab), and disease-modifying therapies for IgG4-RD (e.g., inebilizumab).
Requests showing concomitant use with these agents should include justification and will be reviewed for medical necessity; absence of justification may result in denial.

Note

Benefit coverage conditional on member plan

Benefit coverage is subject to the member's specific benefit plan and applicable state/federal mandates. Always verify coverage with the member's Certificate of Coverage prior to authorization.

Some Certificates of Coverage or state mandates may allow coverage for off-label or investigational uses under defined circumstances; those mandates supersede this policy.
When benefit language conflicts with this policy, the member-specific benefit plan governs.

Documentation Required

Dosing and response documentation requirement

Prescribers must document dosing, clinical response, and relevant diagnostic testing to support the request. For initial therapy attest dosing aligns with FDA labeling or published evidence; for continuation provide objective evidence of response.

Dosing documentation: treatment regimen, dose, schedule, total planned doses.
Response documentation: clinical notes, lab values (e.g., platelet counts for ITP), imaging, or specialist assessments.
For ITP: platelet counts and prior use/failure/intolerance to listed therapies (anti-D, corticosteroids, IVIg, TPO-RA, splenectomy).

Documentation Required

Required diagnostic and treatment history documentation

Some diagnoses require specific diagnostic testing and treatment history to be documented with the authorization request. Provide the tests and prior therapy details as specified for the diagnosis.

NMOSD: neurologist confirmation, AQP4-IgG (NMO-IgG) serologic testing result, clinical history meeting required attack phenotype criteria, and documentation ruling out MS or other diagnoses.
IgG4-RD: positive assessment per ACR/EULAR classification criteria with documentation of organ involvement, exclusion criteria, and inclusion criteria elements; specialist involvement required.
PTLD: diagnosis documentation and sequencing of therapy per PTLD guidance (rituximab monotherapy recommended first-line for monomorphic or polymorphic PTLD where applicable).

Documentation Required

FDA indications and safety documentation (including HBV screening)

Clinicians should document FDA indications and safety considerations when applicable, including screening for hepatitis B virus (HBV) infection prior to initiating therapy per FDA boxed warning and alert.

Document that the indication aligns with FDA-labeled uses when applicable and include product-specific combination or age restrictions.
HBV screening: document baseline HBV serology and monitoring plan; note that HBV reactivation has been reported and can be fatal.
Failure to screen/monitor for HBV may increase patient risk and will be considered during medical necessity review.

Billing Rule

Therapeutic interchange to preferred products

Therapeutic interchange to preferred products may be required. Coverage will be provided for Riabni, Ruxience, or Truxima contingent on meeting the Diagnosis-Specific Criteria. Members on other rituximab products may be required to transition to a preferred product unless they meet the non-preferred exception criteria.

If requesting continuation of a non-preferred rituximab product, include documentation supporting a medical exception (intolerance/contraindication/serious adverse event to preferred product plus prescriber attestation).
Pharmacy/medical administration scheduling and infusion site should reflect the selected product (preferred or approved non-preferred).

Step Therapy

RA step therapy requirements and treatment sequencing (ITP, PTLD)

Rheumatoid arthritis and other immune-mediated diagnoses have step therapy and sequencing requirements that must be satisfied prior to approval.

RA: moderate to severe disease activity plus concurrent methotrexate use or documented contraindication/intolerance to methotrexate, and history of failure/contraindication/intolerance to at least one TNF inhibitor.
ITP and PTLD: follow diagnosis-specific sequencing — e.g., rituximab is a guideline-recommended second-line option for ITP and is recommended as first-line monotherapy for many PTLD presentations; include prior therapy details in the request.

NEMOS typical redosing intervalBecause most patients remain B-cell deficient for ~6 months after treatment, redosing about every 6 months is considered adequate when not using individualized monitoring.

Clinical outcomes with CD27+-guided retreatmentKim et al. reported marked ARR reduction (mean pretreatment vs posttreatment ARR 2.4 vs 0.3) with sustained responses and no serious discontinuation events over median 60 months.

inv-71: NMOSD diagnostic requirements (definition)

Diagnostic responsibilityDiagnosis of NMOSD must be made by a neurologist who confirms required elements.

Serologic testing requirementSerologic testing for anti-aquaporin-4 immunoglobulin G (AQP4-IgG/NMO-IgG) must be performed.

Clinical syndrome requirementIf AQP4-IgG positive: one listed clinical feature (e.g., optic neuritis, acute myelitis, area postrema syndrome) required; if AQP4-IgG negative: two listed clinical features required.

inv-72: IgG4-RD confirmation definition (ACR/EULAR criteria)

Primary confirmation methodConfirmation of IgG4-related disease requires positive assessment using the ACR/EULAR classification criteria.

Organ involvement requirementInvolvement of ≥1 organ consistent with IgG4-RD must be present and evaluated per criteria.

Specialist involvementPrescribed by or in consultation with a specialist experienced in IgG4-RD for initial and continuation therapy per policy.

inv-73: MS covered forms definition (PPMS, relapsing forms)

Covered MS formsPrimary progressive multiple sclerosis (PPMS)

Covered MS forms (relapsing)Relapsing forms of MS (e.g., relapsing‑remitting MS, secondary‑progressive MS with relapses, progressive‑relapsing MS with relapses)

Combination therapy prohibitionPatient must not be receiving rituximab in combination with MS disease‑modifying therapies, other B‑cell targeted therapy, or lymphocyte trafficking blockers for coverage.

inv-74: Rituximab mechanism of action definition

Mechanism overviewRituximab is a chimeric murine/human monoclonal antibody directed against the CD20 antigen on B‑lymphocytes.

Functional effectThe Fab domain binds CD20; the Fc domain recruits immune effector functions to mediate B‑cell lysis in vitro.

CD20 propertiesCD20 is not shed from the cell surface and does not internalize upon antibody binding; it regulates early activation steps in B‑cell cycle initiation and differentiation.

inv-75: Individualized B-cell-guided retreatment definition

DefinitionIndividualized B‑cell‑guided retreatment: maintenance dosing where redosing is determined by monitoring reemerging CD27+ memory B cells in peripheral blood and administering rituximab when thresholds are exceeded.

Example thresholdsExample thresholds reported: redose if CD27+ >0.05% in first 2 years, and >0.1% thereafter (Kim et al.).

Clinical rationaleThis approach aims to prevent relapse by responding to B‑cell repopulation rather than fixed‑interval redosing; studies report sustained clinical responses with acceptable tolerability.

inv-76: Rituximab products (Rituxan and biosimilars) — definition

Included productsNamed rituximab products: Riabni (rituximab‑arrx), Rituxan (rituximab), Rituxan Hycela (rituximab+hyaluronidase), Ruxience (rituximab‑pvvr), Truxima (rituximab‑abbs).

Biosimilars and preferred statusRiabni, Ruxience, and Truxima are identified as preferred rituximab products in the policy; other FDA‑approved rituximab biosimilars not listed by name are considered non‑preferred until reviewed.

Non‑oncology Hycela statusRituxan Hycela is considered unproven and not medically necessary for non‑oncology indications; refer to oncology policy for Hycela oncology use.

inv-77: Boxed Warning - Hepatitis B reactivation

Boxed warning summaryFDA boxed warning: risk of hepatitis B virus (HBV) reactivation with rituximab (and ofatumumab); screening and monitoring of patients with prior HBV infection is recommended.

Regulatory actionFDA issued an alert (Sept 25, 2013) highlighting additional boxed warning information and recommending thorough patient screening and monitoring before and during therapy.

Clinical implicationInadequate screening/monitoring for prior HBV infection may lead to HBV reactivation events including deaths; document HBV screening when seeking authorization.

Revised non-preferred/exception language to specify that treatment with Rituxan or other rituximab products is medically necessary when patient has documented intolerance, contraindication, or serious adverse event to Riabni, Ruxience, or Truxima (replacing prior wording listing Truxima or Ruxience only).

2026-01-01criteria_clarification

Revised Immune Thrombocytopenic Purpura (ITP) coverage criteria, modifying the statement related to prior thrombopoietin receptor agonist (TPO-RA) failure/contraindication/intolerance.

2026-01-01clinical_criteria_update

Updated rheumatoid arthritis section: added Cimzia and Simponi to TNF inhibitor examples and updated the list of targeted immunomodulators not to be coadministered with rituximab (added Olumiant, Orencia, Rinvoq; removed adalimumab and Remicade from examples).

2026-01-01references_update

Updated References section and archived previous policy version IEXD0003.14.

The revision history documents multiple substantive updates: addition of Riabni to the preferred product list and associated coverage contingency; removal of language requiring members already on Riabni to switch therapies; replacement of the product‑substitution hierarchy so that Rituxan and other rituximab products are medically necessary only when patients have intolerance/contraindication/serious adverse events to the preferred products (Riabni, Ruxience, Truxima); and updates to rheumatoid arthritis language and contraindicated combination therapy lists. References were also updated.