CurrentUnitedHealthcarePolicy N/A

Rituxan Rituximab La Cs

This section provides clinical background, trial evidence, and FDA indications for rituximab and biosimilars across multiple autoimmune, hematologic, neurologic, and transplant-related conditions; includes lists of applicable ICD-10 diagnosis codes. It is part 2 of a longer UnitedHealthcare policy document describing clinical rationale and evidence for coverage.

Policy Summary

PayerUnitedHealthcare

PolicyRituxan Rituximab La Cs

Policy CodePolicy N/A

Change TypeMultiple (added indication, updated exclusions, retired LA plan)

Effective DateDec 1, 2025

Next Review Date

Key ActionProviders should reference the FDA-approved indications for rituximab/approved biosimilars and clinical trial evidence summarized in the policy when requesting coverage for specified diagnoses.

SourceLink

POLICY UPDATE CHANGES

Added IgG4-Related Disease (IgG4-RD) as a proven indication and defined medical necessity criteria including ACR/EULAR classification confirmation and specialist involvement.

Updated rheumatoid arthritis examples of TNF inhibitors to include Cimzia (certolizumab) and Simponi (golimumab).

Updated neuromyelitis optica list of drugs not to be combined with rituximab to include Kevzara (sarilumab) and Ultomiris (ravulizumab).

Policy retired for Louisiana plan membership effective April 1, 2026.

Added ICD-10 diagnosis code D89.84 to applicable codes.

Updated Clinical Evidence and References sections to reflect the most current information.

1New Indication Added (IgG4-RD)

1ICD-10 Codes Added

12Authorization Months Limit

multipleIndications discussed

dozensICD-10 codes listed

Coverage Summary & Scope

This document is an informational Medical Benefit Drug Policy (Part 2 of 3) summarizing clinical evidence and coverage rationale for rituximab across multiple non‑oncology indications including autoimmune, hematologic, neurologic, and transplant‑related conditions. The policy lists proven indications such as immune thrombocytopenic purpura (ITP), pemphigus vulgaris, autoimmune hemolytic anemia (including chronic cold agglutinin disease), post‑transplant B‑lymphoproliferative disorder (PTLD), neuromyelitis optica (NMO), thrombotic thrombocytopenic purpura (TTP), multiple sclerosis (MS), and newly added Immunoglobulin G4‑Related Disease (IgG4‑RD) with defined medical necessity criteria and specialist involvement. The policy also covers rheumatoid arthritis and other immune‑mediated conditions where criteria apply.

The policy specifies administrative limits and updates: initial and reauthorization durations are limited to 12 months for listed indications, IgG4‑RD was added as a proven indication with requirement for confirmation by the ACR/EULAR classification criteria and specialist prescribing, and the policy was retired for Louisiana plan membership effective April 1, 2026.

Key policy facts

Effective dateDecember 1, 2025

StatusRetired for Louisiana effective April 1, 2026 (policy retired) / CURRENT as of 12/01/2025

New indication addedImmunoglobulin G4‑Related Disease (IgG4‑RD) — added as a proven, medically necessary indication with ACR/EULAR confirmation and specialist involvement

Authorization months limitInitial and reauthorization limited to no more than 12 months

Plans retiredLouisiana plan membership disenrolled April 1, 2026

IgG4-Related Disease (IgG4-RD) — Initial Therapy Criteria

IgG4-Related Disease — Authorization Length

Immunoglobulin G4-Related Disease (IgG4-RD) - Authorization Length

Initial and reauthorization limits

Authorization: Initial authorization will be for no more than 12 months

IgG4-Related Disease — Continuation / Reauthorization Criteria

Concomitant Therapy Exclusions (By Indication)

Rheumatoid Arthritis - Concomitant Therapy Exclusions (updated examples)

Patients must not be receiving certain targeted immunomodulators in combination with rituximab:

Not in combination with

Olumiant (baricitinib)
Orencia (abatacept)
Rinvoq (upadacitinib)

Examples of TNF inhibitors to which patient has history of failure, contraindication, or intolerance (updated list)

Cimzia (certolizumab)

Applicable Codes

Applicable ICD-10 diagnosis codes (rheumatologic / vasculitic / adverse effect / history codes listed in this part)ICD-10

M06.329	Rheumatoid nodule, unspecified elbow.
M06.331	Rheumatoid nodule, right wrist.
M06.332	Rheumatoid nodule, left wrist.
M06.339	Rheumatoid nodule, unspecified wrist.
M06.341	Rheumatoid nodule, right hand.
M06.342	Rheumatoid nodule, left hand.
M06.349	Rheumatoid nodule, unspecified hand.
M06.351	Rheumatoid nodule, right hip.
M06.352	Rheumatoid nodule, left hip.
M06.359	Rheumatoid nodule, unspecified hip.

1–10 of 57

1/6

Added ICD-10 Diagnosis CodesICD-10Covered

D89.84

Immunoglobulin G4-related disease (added to applicable codes)

Policy references to product prescribing information (biosimilars/examples)mixed

Ruxience (Pfizer, Oct 2023)	Prescribing information referenced
Truxima (Teva, Feb 2022)	Prescribing information referenced
Riabni (Amgen, Feb 2023)	Prescribing information referenced

Provider Actions & Prior Authorization Requirements

Prior Authorization

Specialist prescription and documentation required for IgG4-RD

Specialist prescription and documentation required for IgG4-related disease (IgG4-RD). Prior authorization requests must include documentation confirming diagnosis per ACR/EULAR criteria, description of involved organs and objective evidence of organ dysfunction or disease activity, and a specialist consultation (rheumatologist, immunologist, or other appropriate specialist) that justifies rituximab therapy.

Documentation of ACR/EULAR confirmation or equivalent diagnostic criteria for IgG4-RD
List and objective evidence of organ involvement (e.g., imaging, biopsy, laboratory markers, functional impairment)
Specialist consult note (rheumatology, immunology, or relevant subspecialist) supporting rituximab use

Prior Authorization

Clinical Evidence Summary

58%ITP sustained response (rituximab + dex) vs 37% at 6 months

89%Pemphigus complete remission rate at final follow‑up (median time to relapse 15 mo)

54%Chronic cold agglutinin disease overall response rate; median duration ~11 months

93-97%IgG4‑RD response rates reported (93.5% and 97% in studies); maintenance prolongs relapse‑free survival

The clinical evidence summarized in the policy includes positive randomized or observational trial results supporting rituximab for multiple indications: ITP (improved sustained response with rituximab + dexamethasone), pemphigus (high complete remission rates and durable remissions), autoimmune hemolytic anemia and cold agglutinin disease (high overall response rates and meaningful relapse‑free survival), neuromyelitis optica (large reductions in annualized relapse rate and high relapse‑free proportions), TTP (shorter time to durable remission and reduced relapses), multiple sclerosis (phase 2 reduction in gadolinium‑enhancing lesions and relapses), IgG4‑RD (high response rates 93–97% and benefit of maintenance retreatment), rheumatoid arthritis (benefit of rituximab + MTX over MTX alone), and others.

By contrast, systemic lupus erythematosus trials failed to meet primary endpoints (LUNAR and EXPLORER showed no superiority over control in primary outcomes). Safety considerations highlighted include the FDA boxed warning for risk of hepatitis B reactivation requiring screening and monitoring, and the policy references a broad evidence base (numerous references numbered approximately 10–119) supporting indications and safety guidance.

Background & Definitions

Rituximab is a chimeric anti‑CD20 monoclonal antibody that binds the CD20 antigen on B lymphocytes, recruiting immune effector functions to deplete B cells. The policy notes its mechanism in depleting CD20+ B cells and describes its use across hematologic malignancies and a wide range of immune‑mediated diseases, with prescribing information and guideline data informing non‑oncology coverage criteria.

Term	Definition
CR	Complete response as defined per study (disease-specific definitions provided in trials). Example: in CAD trials, CR defined as absence of anemia, no signs of hemolysis, no clinical symptoms of CAD, no detectable monoclonal serum protein, and no signs of clonal lymphoproliferation.
PR	Partial response as defined per study (disease-specific definitions provided in trials). Example: in CAD trials, PR included a stable increase in hemoglobin of ≥2 g/dL or to normal range, ≥50% reduction in serum IgM or to normal range, clinical improvement, and transfusion independence.
ARR	Annualized relapse rate; used in neurologic studies (e.g., NMO and MS) to quantify relapses per year and measure treatment effect—rituximab reduced ARR significantly in multiple series (eg, up to ~88% reduction in NMO studies).
IgG4-RD	Immunoglobulin G4-related disease; diagnosis to be confirmed by a positive assessment using the ACR/EULAR classification criteria as specified in the policy (involvement of ≥1 organ consistent with IgG4-RD; negative exclusion criteria; positive inclusion criteria); rituximab shown to have high response rates (93–97%) in published series.

Revision History

12/01/2025material_change

Added Immunoglobulin G4-Related Disease (IgG4-RD) as a proven indication and defined medical necessity criteria including confirmation by ACR/EULAR classification criteria and specialist involvement.

12/01/2025material_change

Initial and reauthorization authorization durations for multiple indications (including IgG4-RD and other diagnosis-specific criteria) limited to no more than 12 months.

12/01/2025material_change

Added ICD-10 diagnosis code D89.84 (Immunoglobulin G4-related disease) to the list of applicable diagnosis codes.

Policy Summary

PayerUnitedHealthcare

PolicyRituxan Rituximab La Cs

Policy CodePolicy N/A

Change TypeMultiple (added indication, updated exclusions, retired LA plan)

Effective DateDec 1, 2025

Next Review Date

SourceLink

On This Page

Neuromyelitis Optica - Concomitant Therapy Exclusions (updated examples)

Patients must not be receiving certain drugs in combination with rituximab:

Not in combination with: Kevzara (sarilumab)

Not in combination with: Ultomiris (ravulizumab)

Authorization duration limit

Authorization duration limit. Initial authorizations and reauthorizations for rituximab will be granted for no more than 12 months. Requests for treatment beyond 12 months must include justification and supporting documentation of ongoing medical necessity.

Initial authorization: ≤ 12 months
Reauthorization: ≤ 12 months; include documentation of ongoing benefit

Documentation Required

Monitor for Hepatitis B reactivation

Monitor for Hepatitis B reactivation — providers must screen and document Hepatitis B virus (HBV) screening and monitoring per rituximab boxed warning and institutional protocols. Include baseline HBsAg and anti-HBc testing and documented monitoring plan during and after therapy.

Document baseline HBsAg and anti-HBc results
Provide a monitoring plan for HBV reactivation during and after therapy (labs and schedule)
Document any antiviral prophylaxis if indicated

Documentation Required

Use FDA indications and clinical evidence to support coverage requests

Use FDA indications and clinical evidence to support coverage requests. Providers should reference FDA‑approved indications, labeling, and relevant peer‑reviewed clinical evidence or guideline recommendations when submitting prior authorization requests. Requests for biosimilars should reference product identity and any supporting evidence when seeking non-preferred product coverage.

Reference to the specific FDA‑approved rituximab product and indication
Attach supporting clinical evidence or guideline statements for off‑label or non‑FDA dosing where applicable
For biosimilars, specify product name and provide rationale if requesting non-preferred product

Denial Risk

Concomitant therapy exclusion

Concomitant therapy exclusion — claims may be denied if rituximab is used concomitantly with specified therapies. Verify and document that rituximab is not being prescribed in combination with excluded targeted immunomodulators, disease‑modifying MS therapies, anti‑IL6 agents, complement inhibitors, or other listed agents unless policy allows. Examples include TNF inhibitors, abatacept, tofacitinib, baricitinib, upadacitinib, fingolimod, dimethyl fumarate, ocrelizumab, tocilizumab, eculizumab, and ravulizumab.

Do not combine rituximab with targeted immunomodulators (e.g., adalimumab, etanercept, certolizumab, golimumab) for rheumatoid arthritis coverage
Avoid concurrent use with MS disease-modifying therapies (e.g., fingolimod, dimethyl fumarate, ocrelizumab)
Avoid concurrent use with anti‑IL6 agents (e.g., tocilizumab) or complement inhibitors (e.g., eculizumab, ravulizumab)

04/01/2026material_changeLatest

Policy retired for Louisiana plan membership effective April 1, 2026.

12/01/2025non_material_update

Updated concomitant therapy examples and references: expanded lists of targeted immunomodulators and TNF inhibitors not to be combined with rituximab (examples added include Olumiant, Orencia, Rinvoq, Cimzia, Simponi) and updated NMO concomitant drug examples (Kevzara, Ultomiris); Clinical Evidence and References sections updated and prior policy version archived.