CurrentEmblemHealthPolicy N/A

Rituximab Intravenous Products Utilization Management — Medical Policy

Medicare Advantage medical utilization policy governing prior authorization, coverage criteria, dosing, and approval durations for rituximab intravenous products (including biosimilars) for covered indications in applicable Medicare Advantage lines of business.

Policy Summary

PayerEmblemHealth

PolicyRituximab Intravenous Products Utilization Management — Medical Policy

Policy CodePolicy N/A

Change TypeNo material clinical or coverage changes

Effective DateN/A

Next Review DateSep 10, 2025

Key ActionObtain prior authorization and submit documentation of indication, regimen, dosing, and prior therapies or responses as required by the indication-specific criteria.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

26distinct indications listed

1 yroncologic/hematologic approval duration

1 moinitial non‑oncology approval

375 mg/m2 or 1,000 mgcommon dosing options

Recommended Authorization Criteria by Indication

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inv-01: ANCA-associated vasculitis (induction and follow-up) — Covered when ALL of the following are met

Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis - Covered when ALL of the following are met

ANCA-associated vasculitis initial/maintenance: Patient has an ANCA-associated vasculitis (examples include granulomatosis with polyangiitis); AND the requested agent is being administered in combination with glucocorticoids; AND for follow-up treatment after induction, the patient achieved disease control with induction and at least 16 weeks elapse between courses when retreatment is considered a subsequent course.

Dosing options include 375 mg/m2 IV weekly x4 (doses separated by >=7 days) OR up to two 1,000-mg IV doses separated by >=2 weeks; follow-up dosing and alternative regimens listed in policy.

inv-02: Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma — eviCore-managed criteria

Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma - eviCore-managed criteria

CLL/SLL: Patient meets eviCore criteria for chronic lymphocytic leukemia or small lymphocytic lymphoma requiring rituximab.

Approve for 1 year. Dosing: approve up to 500 mg administered IV on the specified day of each cycle as listed in the policy.

inv-03: B-cell lymphomas — eviCore-managed criteria

B-cell lymphomas - eviCore-managed criteria

B-cell lymphoma: Patient meets eviCore criteria for a B-cell lymphoma indication (examples include follicular, diffuse large B-cell lymphoma, high-grade B-cell lymphoma, Burkitt, marginal zone/MALT, mantle cell, primary mediastinal, primary cutaneous, pediatric aggressive mature B-cell, post-transplant lymphoproliferative disorders, and gray zone lymphoma).

Approve for 1 year. Dosing options include 375 mg/m2 IV with doses separated by >=7 days or 375 mg/m2 on two days of each cycle as specified.

inv-04: Pemphigus vulgaris — Covered when ONE of the following is met

Pemphigus vulgaris - Covered when ONE of the following is met

Pemphigus vulgaris: A) Initial treatment: one course consisting of up to two 1,000-mg IV doses administered separated by at least 2 weeks; OR B) Maintenance: subsequent infusions administered no sooner than 16 weeks following the previous rituximab infusion.

Initial approval: 1 month; maintenance/longer-term dosing per timing in policy (maintenance dose example up to 500 mg IV per dose).

inv-05: Rheumatoid arthritis (initial and subsequent courses) — Covered when ALL of the following are met

Rheumatoid arthritis (RA) - Covered when ALL of the following are met

RA initial therapy: Initial therapy: patient has tried at least one conventional synthetic DMARD for >=3 months (examples: methotrexate, leflunomide, hydroxychloroquine, sulfasalazine) unless an exception applies (e.g., prior biologic).

Approve for 1 month to administer one course (up to two 1,000-mg IV doses separated by >=2 weeks). A biosimilar of the requested biologic does not count as a separate biologic for step requirements.

RA repeat courses: If the patient has already received two or more courses, subsequent courses require >=16 weeks between courses AND evidence of beneficial clinical response by at least one objective measure or improvement in symptoms (examples: CDAI, DAS28-ESR/CRP, PAS-II, RAPID-3, SDAI).

Dosing: one course consists of up to two 1,000-mg IV doses separated by >=2 weeks.

inv-06: Acute lymphoblastic leukemia (CD20-positive) — eviCore-managed criteria

Acute lymphoblastic leukemia (CD20-positive) - eviCore-managed criteria

ALL: Patient has CD20-positive acute lymphoblastic leukemia and meets eviCore criteria for therapy with rituximab.

Approve for 1 year. Dosing: approve up to 375 mg/m2 IV with doses separated by at least 7 days as specified.

inv-07: Graft-versus-host disease — Covered when ONE of the following is met

Graft-versus-host disease (GVHD) - Covered when ONE of the following is met

GVHD initial or prior-treatment: A) Initial therapy: patient has tried at least one conventional systemic treatment for GVHD (examples include systemic corticosteroids, cyclosporine, tacrolimus, mycophenolate); OR B) Patient previously treated with rituximab who demonstrates clinical improvement on objective measures or symptoms compared with baseline.

Initial approval: 1 month; prior-treated approvals may be for 1 year. Dosing: approve up to 375 mg/m2 IV with doses separated by >=7 days.

inv-08: Hairy cell leukemia — eviCore-managed criteria

Hairy cell leukemia - eviCore-managed criteria

Hairy cell leukemia: Patient meets eviCore criteria for hairy cell leukemia requiring rituximab therapy.

Approve for 1 year. Dosing: approve up to 375 mg/m2 IV with doses separated by at least 7 days.

inv-09: Nodular lymphocyte-predominant disease — eviCore-managed criteria

Nodular lymphocyte-predominant disease - eviCore-managed criteria

Nodular lymphocyte-predominant disease: Patient has nodular lymphocyte-predominant disease and meets eviCore criteria for rituximab therapy.

Approve for 1 year. Dosing: approve up to 375 mg/m2 IV with doses separated by at least 7 days.

inv-10: Hairy Cell Leukemia — Covered when ALL of the following are met

Covered when ALL of the following are met

HCL approval: Patient has hairy cell leukemia requiring therapy with rituximab and meets eviCore criteria.

Approve for 1 year. Dosing: up to 375 mg/m2 IV with doses separated by at least 7 days.

inv-11: Nodular lymphocyte-predominant disease — Covered when ALL of the following are met

Covered when ALL of the following are met

NLP disease approval: Patient has nodular lymphocyte-predominant disease and meets eviCore criteria for rituximab therapy.

Approve for 1 year. Dosing: up to 375 mg/m2 IV with doses separated by at least 7 days.

inv-12: Immune Thrombocytopenia (ITP) — Approve if the patient meets ONE of the following (A or B)

Approve if the patient meets ONE of the following (A or B)

Initial Therapy: Initial therapy: Approve for 1 month if the patient has tried at least one other therapy for ITP (examples: IVIG, anti-D, corticosteroids, splenectomy).

At least 6 months must elapse between treatment courses when retreating; dosing: up to 375 mg/m2 IV with doses separated by >=7 days.

Retreatment after prior rituximab: Patient has already received a course of a rituximab product for ITP: Approve for 1 month if the patient responded to therapy and the prescriber determines the patient has relapsed.

Response examples include platelet count increase; relapse defined as recurrence of thrombocytopenia after remission.

inv-13: Immunotherapy-Related Toxicities (checkpoint inhibitors) — Approve when both criteria A and B are met

Immunotherapy-Related Toxicities (checkpoint inhibitors) - Approve when both criteria A and B are met

Initial refractory toxicity: Initial therapy: Approve for 1 month if the patient is symptomatic despite a trial of at least one systemic corticosteroid and meets severity criteria.

Dosing options include up to 500 mg IV for 2 doses separated by >=14 days OR up to 375 mg/m2 IV for 4 doses separated by >=7 days.

inv-14: Multiple Sclerosis — Approve for 1 year if the patient meets ONE of the following (A or B)

Multiple Sclerosis - Approve for 1 year if the patient meets ONE of the following (A or B)

Initial Therapy: Initial therapy: Approve if the patient has experienced inadequate efficacy or significant intolerance to at least one other disease-modifying agent for MS, and at least 6 months will elapse between treatment courses when retreatment is considered.

Each course is up to 2,000 mg total (administered as two infusions over one month).

Currently receiving rituximab: Patient currently receiving rituximab: Approve for 1 year if timing criteria are met (e.g., >=6 months between courses) OR if the patient demonstrates objective clinical benefit on measures such as MRI, EDSS, NEDA, MSFC, 6-minute walk, or FSIQ-RMS.

Dosing: each course up to 2,000 mg total as two infusions over one month.

inv-15: Neuromyelitis Optica Spectrum Disorder (NMO) — Covered when criteria met

Neuromyelitis Optica Spectrum Disorder (NMO) - Covered when criteria met

NMO dosing: Approve for 1 month with one of the following dosing options: up to two 1,000-mg IV doses separated by >=2 weeks OR up to 375 mg/m2 IV for 4 doses separated by >=7 days.

Dosing selection per prescriber and clinical scenario.

inv-16: Primary Central Nervous System Lymphoma — Covered when ALL of the following are met

Primary Central Nervous System Lymphoma - Covered when ALL of the following are met

PCNSL approval: Patient has primary central nervous system lymphoma and requires rituximab per eviCore/labeled indications.

Approve for 1 year. Dosing: up to 375 mg/m2 IV with doses separated by at least 7 days.

inv-17: Systemic Lupus Erythematosus (SLE) — Approve for the duration noted if patient meets ONE of the following (A or B)

Systemic Lupus Erythematosus (SLE) - Approve for the duration noted if patient meets ONE of the following (A or B)

Initial Therapy: Initial therapy: Approve for 1 month if the patient has tried at least one standard immunomodulating or immunosuppressant agent (examples: hydroxychloroquine, corticosteroids, methotrexate, azathioprine, mycophenolate, cyclophosphamide).

If retreatment, at least 6 months must elapse between courses; dosing: approve the requested dose per prescriber.

Retreatment: Approve for 1 month if >=6 months will elapse between treatment courses (e.g., nephrotic syndrome in SLE).

inv-18: Waldenström Macroglobulinemia / Lymphoplasmacytic Lymphoma — Covered when ALL of the following are met

Waldenström Macroglobulinemia / Lymphoplasmacytic Lymphoma - Covered when ALL of the following are met

WM approval: Patient has Waldenström macroglobulinemia/lymphoplasmacytic lymphoma and meets eviCore/labeled criteria for rituximab therapy.

Approve for 1 year. Dosing: up to 375 mg/m2 IV with doses separated by at least 7 days.

inv-19: Antibody-Mediated Rejection (AMR) — Transplant — Approve for the duration noted if ONE of the following (A or B) is met

Antibody-Mediated Rejection (AMR) — Transplant - Approve for the duration noted if ONE of the following (A or B) is met

Second-line or combination for AMR: Requested medication is used as second-line treatment or as part of combination therapy for AMR in kidney, lung, or cardiac transplant patients.

Dosing: up to two 1,000-mg IV doses separated by >=2 weeks OR up to 375 mg/m2 IV with doses separated by >=7 days.

Desensitization protocol: Initial therapy: approve for 1 month if used as part of a desensitization protocol in a highly sensitized patient awaiting donor transplant.

inv-20: Immune-mediated Myopathy / Idiopathic Inflammatory Myopathy — Approve for duration noted if ONE of the following (A or B) is met

Immune-mediated Myopathy / Idiopathic Inflammatory Myopathy - Approve for duration noted if ONE of the following (A or B) is met

Initial refractory disease: Initial therapy: Approve for 1 month if the patient has refractory disease and has failed all first-line therapies.

Dosing options: up to two 1,000-mg IV doses separated by >=2 weeks OR up to 375 mg/m2 IV for 4 doses separated by >=7 days.

Retreatment after prior response: Approve for 1 month if the patient had a positive response to a previous course of a rituximab product for immune-mediated myopathy/idiopathic inflammatory myopathy.

inv-21: Acquired Hemophilia — Approve for duration noted if ONE of the following is met

Acquired Hemophilia - Approve for duration noted if ONE of the following is met

First-line combination use: Approve if patient has acquired or refractory hemophilia and rituximab is used as first-line therapy in combination with corticosteroids.

Initial therapy: approve for 1 month if criteria met; retreatment allowed after prior response. Dosing administered IV with doses separated by at least 7 days.

Refractory disease: Approve for 1 month if patient has refractory disease and the requested medication is used as a second-line agent.

inv-22: Acquired Thrombotic Thrombocytopenic Purpura (TTP) — Approve for the duration noted if ONE of the following (A or B) is met

Acquired Thrombotic Thrombocytopenic Purpura (TTP) - Approve for the duration noted if ONE of the following (A or B) is met

Severe/relapsed/refractory TTP: Patient has severe, relapsed, or refractory TTP and has failed first-line therapy (plasma exchange and glucocorticoids).

Initial therapy: approve for 1 month; dosing options include up to 375 mg/m2 IV with doses separated by >=7 days OR 100 mg IV with doses separated by >=5 days. Retreatment allowed after prior response.

Retreatment after prior response: Approve for 1 month if patient had positive response to prior rituximab course.

inv-23: Immunoglobulin G4-Related Disease (IgG4-RD) — Approve for the duration noted if ONE of the following (A or B) is met

Immunoglobulin G4-Related Disease (IgG4-RD) - Approve for the duration noted if ONE of the following (A or B) is met

Second-line for refractory disease: Medication used as second-line therapy after failure of all first-line therapies or for refractory/relapsed IgG4-RD.

Initial therapy: approve for 1 month if contraindication to glucocorticoids or other criteria met; dosing: up to two 1,000-mg IV doses separated by 2 weeks OR up to 375 mg/m2 IV with doses separated by >=7 days.

Retreatment after prior response: Approve for 1 month if patient had a positive response to a previous course of a rituximab product for IgG4-RD.

inv-24: Minimal Change Disease (MCD) — Approve for the duration noted if ONE of the following (A or B) is met

Minimal Change Disease (MCD) - Approve for the duration noted if ONE of the following (A or B) is met

Adult steroid-dependent/steroid-sensitive nephrotic syndrome: Initial therapy: Approve for 1 month if patient is >=18 years with steroid-dependent or steroid-sensitive nephrotic syndrome and frequent relapses despite optimal prednisone and steroid-sparing agents; alternatively if failed durable remission with cyclophosphamide or calcineurin inhibitors.

Dosing options: two 1,000-mg IV doses separated by 2 weeks OR up to 375 mg/m2 IV with doses separated by >=7 days.

Retreatment after prior response: Approve for 1 month if patient had positive response to previous rituximab course for MCD.

inv-25: Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) — Approve for the duration noted if ONE of the following (A or B) is met

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) - Approve for the duration noted if ONE of the following (A or B) is met

Initial Therapy failure: Initial therapy: Approve for 1 month if the patient has failed IVIG, glucocorticoids, and plasma exchange.

Alternate: approve for 1 month if prior positive response to rituximab. Dosing: up to 375 mg/m2 IV with doses separated by >=7 days.

Dosing: up to 375 mg/m2 IV with doses separated by at least 7 days.

inv-26: Sjögren's Syndrome — Approve for the duration noted if ONE of the following (A or B) is met

Sjögren's Syndrome - Approve for the duration noted if ONE of the following (A or B) is met

Initial Therapy: Initial therapy: Approve for 1 month if the patient tried corticosteroids and other immunosuppressive agents and these were ineffective.

Or approve for 1 month if prior positive response to rituximab. Dosing: up to two 1,000-mg IV doses separated by at least 2 weeks.

Dosing: up to two 1,000-mg IV doses separated by at least 2 weeks.

inv-27: Systemic Sclerosis — Approve for the duration noted if ONE of the following (A or B) is met

Systemic Sclerosis - Approve for the duration noted if ONE of the following (A or B) is met

Initial Therapy: Initial therapy: Approve for 1 month if the patient tried corticosteroids and other immunosuppressive agents and these were ineffective.

Or approve for 1 month if prior positive response to rituximab; dosing: up to two 1,000-mg IV doses separated by 2 weeks.

inv-28: Susac Syndrome — Approve for the duration noted if ONE of the following (A or B) is met

Susac Syndrome - Approve for the duration noted if ONE of the following (A or B) is met

Initial severe disease: Initial therapy: Approve for 1 month if the patient has severe or extremely severe disease and initial treatments (examples: corticosteroids, IVIG) are inadequate.

Dosing options: 250 mg once then repeated in 2 weeks followed by 500 mg every 6 months OR single 500 mg dose repeated in 6 months. Retreatment: approve for 1 month if prior positive response to rituximab.

inv-29: Systemic Sclerosis — Systemic Sclerosis — Approve when ONE of the following is met

Systemic Sclerosis — Approve when ONE of the following is met

Systemic Sclerosis approval options: A) Initial therapy: approve for 1 month if the patient has tried corticosteroids and other immunosuppressive agents and these were ineffective; OR B) Approve for 1 month if the patient had a positive response to a previous course of a rituximab product for systemic sclerosis.

Dosing: up to two 1,000-mg IV doses separated by at least 2 weeks.

inv-30: Susac Syndrome — Susac Syndrome — Approve when ONE of the following is met

Susac Syndrome — Approve when ONE of the following is met

Susac Syndrome approval options: A) Initial therapy: approve for 1 month if initial treatments are inadequate and the patient has severe or extremely severe disease; OR B) Approve for 1 month if the patient had a positive response to a previous course of a rituximab product for Susac Syndrome.

Dosing: either single 500 mg repeated in 6 months, or 250 mg once then repeated in 2 weeks followed by 500 mg every 6 months.

Riabni, Ruxience, and Truxima are approved as biosimilars to Rituxan intravenous and have demonstrated no clinically meaningful differences in safety or effectiveness relative to the reference product; however, they are not designated as interchangeable and interchangeability is not claimed in this policy.

Some coverage criteria require documentation of prior therapies or prior clinical response before rituximab will be approved. Requests that do not include supporting documentation showing the required prior treatment trials or evidence of response (for example, prior use of IVIG, corticosteroids, splenectomy for ITP, or prior disease-modifying therapy for MS) may effectively be excluded from approval under the stated criteria.

Coverage is limited to the indications and situations explicitly listed in the Recommended Authorization Criteria. Situations not described in those criteria are not recommended for coverage; the criteria will be updated as new published evidence becomes available.

When the policy specifies step-therapy or prior-trial requirements, use of rituximab without meeting those conditions is considered not medically necessary. Examples include initiating rituximab for ITP without first trying at least one other appropriate therapy, for MS without documented inadequate efficacy or intolerance to another disease-modifying agent, or for CIDP without prior failure of IVIG, glucocorticoids, and plasma exchange.

Regimens and Dosing Schemas

Regimen	Indication / Context	Coverage Status
Rituximab combined with CHOP (cyclophosphamide, doxorubicin/epirubicin, vincristine, prednisone)
Used for previously untreated diffuse large B-cell CD20-positive disease in combination with anthracycline-based chemotherapy per labeled indications and NCCN guidelines

Rituximab combined with CVP (cyclophosphamide, vincristine, prednisone)
Used for non-progressing low‑grade or follicular CD20-positive B‑cell disease as single-agent maintenance after first‑line CVP chemotherapy or combined per guideline recommendations

Rituximab combined with fludarabine + cyclophosphamide (FC)
Used for treatment of chronic lymphocytic leukemia (CLL), in combination with fludarabine and cyclophosphamide for CD20-positive disease per labeled indication

Dosing Option	Typical Use / Notes	Coverage Status
375 mg/m2 IV, once weekly for 4 doses (q7d x4)
Commonly used for lymphoma indications and some neurologic/autoimmune regimens; doses separated by at least 7 days as specified

1,000 mg IV, two doses separated by ≥2 weeks (e.g., day 0 and day 14)
Frequently used for indications such as pemphigus vulgaris, NMO, AMR, IgG4‑RD, systemic sclerosis, and others; interval between the two 1,000‑mg doses is typically ≥2 weeks

Up to 500 mg IV regimens (single 500 mg or 2 × 500 mg schedules; e.g., two 500 mg doses separated by 6 months or 500 mg ×1 repeated at 6 months)
Referenced for indications such as checkpoint inhibitor–related toxicities and Susac Syndrome (alternative regimens include 250 mg then 500 mg maintenance); exact schedule varies by indication

250 mg IV once then repeat in 2 weeks followed by 500 mg every 6 months (Susac Syndrome alternative)
Specific alternative maintenance regimen cited for Susac Syndrome; initial small dose then repeat at 2 weeks with 6‑month maintenance

100 mg IV doses separated by ≥5 days
Option referenced for TTP dosing in specific situations as an alternative lower‑dose schedule

Billing, Codes, and Dosing References

Referenced LCD/LCA codesmixed

L39297	Local Coverage Determination or related article referenced
A59101	Local Coverage Determination or related article referenced

(no additional groups)mixed

No codes listed

Referenced dosing optionsmixed

375 mg/m2	Dose option: up to 375 mg/m2 IV with doses separated by at least 7 days (or as specified)
1,000 mg	Dose option: one or two 1,000-mg IV doses separated by at least 2 weeks
500 mg	Dose option referenced for some indications (e.g., immunotherapy-related toxicity: up to 500 mg IV for 2 doses separated by 14 days; or single 500 mg dose repeated in 6 months for Susac Syndrome)
250 mg	Dose option for Susac Syndrome regimen (250 mg once then repeated in 2 weeks followed by 500 mg every 6 months)
100 mg	Dose option referenced for TTP (100 mg IV with doses separated by at least 5 days)

inv-37: Minimum interval between courses

Maintenance/follow-up intervalAt least 16 weeks must elapse between prior course and subsequent maintenance or follow-up dosing when specified by the indication (e.g., ANCA-associated vasculitis, pemphigus vulgaris, rheumatoid arthritis).

Initial two 1,000 mg dosesWhen using the two‑1,000 mg dosing schema for initial therapy (indications that allow this regimen), the two 1,000 mg IV doses must be separated by at least 2 weeks.

375 mg/m2 dosing intervalDosing schedules using 375 mg/m2 require doses separated by at least 7 days (e.g., weekly x4 or as specified per regimen).

Alternative short-interval dosesSome indications reference shorter minimum spacing for specific low-dose regimens (see indication-specific dosing).

inv-38: Course separation interval

General course separation requirementWhere retreatment is considered a subsequent course (examples: ITP, MS, SLE), at least 6 months must elapse between the first dose of the prior course and the first dose of the requested course.

ITP-specific timingFor ITP, policy explicitly notes a minimum of 6 months separating the first dose of the previous course and the first dose of the requested course when retreating.

MS timing and conditionsFor multiple sclerosis, at least 6 months must elapse between courses; continuation or reauthorization also requires meeting objective response or timing criteria described in the MS section.

What Providers Must Do

Prior Authorization

Prior Authorization Recommended

Prior authorization is recommended for medical-benefit coverage of rituximab IV products. Providers must submit documentation supporting the requested indication, regimen, dosing, prior treatments (where required by criteria), and objective response data where applicable. Lack of prior authorization may result in non-coverage; the presence or absence of specific HCPCS/ICD-10 codes alone is not sufficient to determine coverage.

Submit indication, regimen, and dosing
Provide documentation of prior therapies when required by indication
Include objective measures of response when applicable (e.g., MRI changes, EDSS, platelet counts, liver function tests)
Reference companion billing/coding articles for HCPCS and ICD‑10 lists (codes are for reference only)

Documentation Required

Document Prior Therapies and Objective Response for MS

For multiple sclerosis (MS) requests, document prior disease‑modifying therapy failure or intolerance and objective measures of response or stabilization (examples: MRI showing absence or decrease in gadolinium‑enhancing lesions or new/enlarging T2 lesions; change in EDSS; NEDA status; relapse frequency; validated gait/walk or fatigue scales).

List prior DMTs tried and reasons for discontinuation (inefficacy or intolerance)
Attach objective data: MRI reports, EDSS scores, relapse history, MSFC or 6‑minute walk results, NEDA documentation

Step Therapy

Step / Failed‑Therapy Requirements

Step/failed‑therapy requirements apply for multiple indications. Requests may be denied if required prior therapies were not tried. Examples: ITP requires a trial of at least one other therapy before initial rituximab; RA requires trial of at least one conventional synthetic DMARD for ≥3 months (exceptions noted for prior biologic use); Graft‑versus‑host disease and several autoimmune indications require prior systemic therapy trials.

ITP: trial of at least one other therapy (e.g., IVIG, corticosteroids, anti‑D) required for initial approval
RA: trial of one conventional synthetic DMARD for ≥3 months required for initial approval (biologic history may alter requirement)
Many autoimmune indications: document failure, intolerance, or contraindication to first‑line agents

Documentation Required

Prior Therapy Required for Certain Indications

For some indications (for example, rheumatoid arthritis and graft‑versus‑host disease), the prescriber must document that the patient has tried at least one conventional systemic therapy prior to initiation of rituximab, or provide documentation of why such therapy was not appropriate or tolerated.

RA: one conventional synthetic DMARD trial (examples: methotrexate, leflunomide, hydroxychloroquine, sulfasalazine) for ≥3 months unless exception applies
Graft‑versus‑host disease: trial of at least one conventional systemic treatment (e.g., corticosteroids, calcineurin inhibitors, mycophenolate) for initial approval

Note

Drug List Only — Appendices Are Informational

Appendices list medications and modes of administration for reference only. These appendix drug lists do not by themselves state specific prior authorization rules or denial criteria in the provided excerpt.

Appendix A/B: drug names, mechanisms, and modes of administration are informational
Do not rely on appendix listings alone to determine coverage; follow indication‑specific criteria and companion billing/coding articles

Denial Risk

No Denial Criteria in Appendices — Documentation Still Required to Avoid Denial

No denial criteria are specified in the appendix excerpts. However, requests may be denied when the patient does not meet the Recommended Authorization Criteria (including step therapy, prior-treatment, or objective response requirements). Providers should ensure documentation addresses all applicable criteria to avoid denials.

Absence of explicit appendix denial language does not preclude denials for unmet clinical criteria
Verify indication‑specific requirements before submission to reduce denial risk

Definitions, Background, and Notes

Rituximab products are CD20-directed cytolytic antibodies with regulatory approvals across a broad range of hematologic, rheumatologic, dermatologic, neurologic, and transplant-related indications. Multiple rituximab intravenous products and biosimilars share the same mechanism of action, route, dosage form, and strength; biosimilars have demonstrated biosimilarity but are not currently interchangeable with the reference product.

inv-56: Biosimilar

DefinitionA biosimilar is a product approved as biosimilar to Rituxan IV indicating no clinically meaningful differences in safety and effectiveness compared with the reference product; biosimilars share mechanism, route, dosage form, and strength but may differ in inactive components.

Interchangeability statusBiosimilars listed (Riabni, Ruxience, Truxima) have demonstrated biosimilarity but have not been designated interchangeable in the policy/excerpt.

Regulatory implicationBiosimilarity does not equal interchangeability; the policy treats biosimilars as equivalent in indication coverage but does not claim automatic interchangeability.

inv-57: IC-ISGP / IC-L / IC-COMP / IC-EC

IC-L / IC-COMP / IC-ISGP / IC-EC meaningsInternal coverage notations: IC-L = criteria supported by labeled indication; IC-COMP = criteria supported by CMS‑approved compendia; IC-ISGP = internal criteria to interpret or supplement general provisions of applicable NCDs/LCDs; IC-EC = internal criteria to expand coverage beyond NCDs/LCDs.

Usage in policyThese notations are applied throughout the policy to denote the evidentiary or regulatory basis for indication-specific criteria and any internal modifications.

Reference guidanceDetails and rationale for internal coverage criteria are available in the Sources of Information and are used where indicated in individual indication sections.

inv-58: Course separation

Six-month separation ruleWhen retreatment is considered a subsequent course (examples include ITP, MS, SLE), at least 6 months must elapse between the first dose of the prior course and the first dose of the requested course.

Example — ITPITP section explicitly states a minimum 6‑month separation between courses when retreatment is requested following a prior rituximab course.

MS and SLE referencesMultiple sclerosis and systemic lupus erythematosus sections reference the same >=6‑month interval between courses as a timing condition for reauthorization or continuation.

inv-59: Objective measures of MS response

MRI-based measuresObjective MRI measures include absence or decrease in gadolinium enhancing lesions and decrease in number of new or enlarging T2 lesions.

Clinical scales and compositesExamples of objective clinical measures include the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), NEDA‑3/NEDA‑4 criteria, and FSIQ‑RMS.

Functional testsFunctional assessments cited include the six‑minute walk test and 12‑Item Multiple Sclerosis Walking Scale; improvement or stabilization on these may support continued therapy.

inv-60: Initial Therapy

Approval basis for initial therapyInitial Therapy status is granted when the patient meets the indication-specific entry criteria (for example, prior trial of specified agents or severe disease presentation) and is typically approved for an initial course duration as specified per indication (commonly 1 month for many non-oncology initial uses).

Examples of entry criteriaExamples include trial and inadequate response to conventional synthetic DMARDs for rheumatoid arthritis or failure of first-line therapies for CIDP and other autoimmune conditions.

Dosing with initial approvalsInitial therapy dosing follows the indication-specific regimens (e.g., up to two 1,000 mg doses separated by >=2 weeks or 375 mg/m2 weekly x4) as listed in each indication section.

inv-61: Previous course with positive response

Reauthorization after prior positive responseIf the patient had a previous course of a rituximab product with documented clinical improvement, reauthorization may be approved for 1 month for the requested retreatment when criteria are met.

Documentation requiredPrescriber must document prior positive response (examples vary by indication, e.g., platelet count increase in ITP) to support reauthorization requests based on prior benefit.

Applies across indicationsThis provision for 1‑month reauthorization after prior positive response appears in multiple indication sections (e.g., TTP, IgG4‑RD, systemic sclerosis, Susac Syndrome).

inv-62: Mechanism of Action entries in Appendix A

Purpose of Appendix A entriesAppendix A lists medications with a Mechanism of Action entry that specifies the biological target class (e.g., inhibition of IL‑17A, IL‑23, JAK pathways, integrin receptor antagonist).

Example entriesAppendix A entries include specific biologics and their mechanism descriptors (examples: Cosentyx — inhibition of IL‑17A; Skyrizi — inhibition of IL‑23).

Use in policy contextMechanism of Action entries are provided for reference and classification of agents in Appendix A; they do not by themselves establish prior authorization rules in this excerpt.

inv-63: Appendix B entries specify how a medication is administered

Purpose of Appendix B entriesAppendix B specifies the Mode of Administration for listed medications (examples: oral, injection self‑administered, intravenous infusion).

Examples from Appendix BEntries include numerous agents with modes such as Oral (Aubagio), Injection self‑administered (Betaseron), and Intravenous infusion (Lemtrada, Ocrevus).

Reference utilityMode of Administration entries are included as a reference for clinicians and reviewers when assessing administration route for a requested medication.

Therapy Line Designations

inv-64: first-line | maintenance — 1 top-level node

first-line | maintenance

Induction vs maintenance: Rituximab may be used as induction in combination with chemotherapy and as maintenance single-agent therapy for certain B-cell lymphomas and after induction for ANCA-associated vasculitis per criteria.

Specific dosing and timing depend on indication (see coverage criteria).

inv-65: salvage — 1 top-level node

salvage

Oncology indications: Approve for 1 year when diagnosis matches listed hematologic malignancy and dosing criteria are met.

No explicit line-of-therapy sequencing (first-line vs later-line) specified in these chunks; eviCore-managed oncology indications apply.

Biomarker and Test Requirements

inv-66: CD20

Biomarker requirementCD20 expression is required for coverage in indications where specified (e.g., acute lymphoblastic leukemia and other B‑cell malignancies noted to require CD20‑positive disease).

Applicable indicationsCD20 requirement is explicitly cited for acute lymphoblastic leukemia and is relevant to other B‑cell malignancies referenced in the policy.

Documentation expectationPrescribers must document CD20‑positive disease where indicated to meet the coverage criteria for those malignancies.

Policy Revision Timeline

07/11/2018policy_created

Policy created as a new Medicare Advantage Medical Policy for rituximab intravenous products.

08/28/2019policy_revision

Policy revised and reviewed in accordance with Local Coverage Article A52452 and the Rituximab Intravenous Products Utilization Review Policy.

12/11/2019policy_revision

Non-clinical update added clarifying incorporation of Medicare coverage guidance (NCDs, LCDs) and use of HCPCS/ICD-10 lists for reference purposes only.

01/12/2021policy_revision

Riabni (new biosimilar) added to the policy; ANCA-associated vasculitis dosing and multiple condition-specific dosing and indication updates made without changing criteria applicability across rituximab products.

07/21/2021policy_revision

Multiple clinical updates including alternative induction dosing for ANCA-associated vasculitis, additions to B-cell lymphoma examples, and clarifications to rheumatoid arthritis and multiple sclerosis response/authorization criteria.

08/04/2022policy_revision

Removed several indications (e.g., pre-transplant high PRA suppression, dermatomyositis/polymyositis, Graves' ophthalmopathy) and added multiple indications (AMR, immune-mediated myopathy, acquired hemophilia, acquired TTP, IgG4-RD, MCD, CIDP, Sjögren's syndrome, systemic sclerosis).

03/01/2023policy_revision

Dosing updates specified for ANCA-associated vasculitis and other conditions; Immunotherapy-related toxicities condition added; Neuromyelitis Optica dosing specified; other administrative updates.

09/26/2023policy_revision

Policy revisions reflecting dosing specification updates (e.g., total number of initial doses for ANCA-associated vasculitis) and addition of certain conditions per guideline updates.

09/04/2024policy_review

Policy review performed; no criteria changes identified.

01/07/2025policy_review

Policy review performed with no clinical criteria changes; formatting and notation updates applied.

03/12/2025policy_revision

Policy updated based on NCD surveillance review to add Susac syndrome as an approvable indication per LCD L39297 update.

09/10/2025policy_revisionLatest

Policy revision with updates to applicable dates and references (finalized revision effective 09/10/2025).

Policy Summary

PayerEmblemHealth

PolicyRituximab Intravenous Products Utilization Management — Medical Policy

Policy CodePolicy N/A

Change TypeNo material clinical or coverage changes

Effective DateN/A

Next Review DateSep 10, 2025

Key ActionObtain prior authorization and submit documentation of indication, regimen, dosing, and prior therapies or responses as required by the indication-specific criteria.

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