ModifiedPremera BluecrossPolicy 5.01.556

5.01.556 Rituximab: Non-oncologic and Miscellaneous Uses

Defines medical necessity criteria, site-of-service review rules, covered non-oncologic indications, investigational indications, length of approval, documentation and coding requirements for rituximab products (Riabni, Ruxience, Truxima, Rituxan and Rituxan Hycela) for commercial plan members (with a note about Alaska fully-insured members). Applies to IV/injectable administration and site-of-service for ages ≥13.

Policy Summary

PayerPremera Bluecross

Policy5.01.556 Rituximab: Non-oncologic and Miscellaneous Uses

Policy CodePolicy 5.01.556

Change TypeMODIFIED — multiple formulary/product-preference and site-of-service updates (2019–2026)

Effective DateJun 1, 2026

Next Review Date

Key ActionRequests for rituximab products will be reviewed for medical necessity; approval requires documentation that all indication-specific criteria are met (see policy), and site-of-service restrictions apply for ages ≥13 when applicable.

SourceLink

POLICY UPDATE CHANGES

Policy revised and replaced prior policies including 5.01.550 and others; lists related policies and notes about site-of-service applicability for Alaska fully-insured members.

2020: Added Ruxience to site-of-service review; updated RA criteria to add Rinvoq as first-line option and updated pregnancy information and ASH ITP guideline references.

2021: Added biosimilar Riabni as second-line agent for all covered indications; updated guideline links and references.

2023: Reviewed prescribing information; moved Ruxience to second line (non-preferred); adjusted preferred adalimumab biosimilars list and product preferences; various formulary updates effective Jan 1, 2024.

2024: Clarified preferred Humira product for RA; added Simlandi as preferred; noted FDA dosing applies; added note about specific formularies exempted from preferred adalimumab list; announced changes effective Jan 3, 2025 to preferred status of rituximab products and requirement of trial/failure with Ruxience or Truxima for Rituxan/Ritabni/Rituxan Hycela.

2025: Added Alaska fully-insured exemption to site-of-service criteria; clarified non-formulary exception approvals up to 12 months; updated preferred product lists and step therapy exceptions; updated several rituximab and adalimumab product preferences.

2026: Updated RA criteria to include adalimumab-aaty, adalimumab-adaz, adalimumab-adbm as preferred alternatives; literature review through Aug 26, 2025.

Updated preferred rituximab and adalimumab product lists and product preference status multiple times between 2019 and 2026.

Added and removed HCPCS/J codes and Q-codes across revisions.

Clarified that site-of-service medical necessity criteria is applicable only to certain ages or membership types at various times.

Added biosimilars and biosimilar-specific coverage language over time.

Policy language standardized from 'patient' to 'individual' throughout.

20+Listed non-oncologic indications covered/conditional

6 moInitial authorization duration

12 moRe-authorization duration (with response)

13+Age threshold for site-of-service review

7Conditions supported as sufficient evidence in this part

13Conditions judged insufficient evidence in this part

Coverage summary and scope

This policy defines medical necessity criteria for IV/injectable rituximab (Rituxan) and biosimilars for multiple non-oncologic autoimmune, hematologic, and related conditions and includes site-of-service review rules for administration. Rituximab is a monoclonal anti-CD20 antibody used to deplete B cells in B-cell–mediated diseases such as rheumatoid arthritis, lupus, and vasculitides (background).

Rituximab carries prominent safety warnings including black box warnings for fatal infusion reactions (most often with the first infusion), severe mucocutaneous reactions, hepatitis B reactivation, and progressive multifocal leukoencephalopathy (PML), and label precautions for infections, cytopenias, cardiac and renal events, and embryo‑fetal toxicity; the drug must be administered where appropriate medical support is available to manage severe infusion reactions.

The policy applies to IV/injectable medical benefit administration and includes site-of-service medical necessity review for members aged 13 years and older (site-of-service review does not apply to Alaska fully‑insured members per the policy note).

Headline thresholds & authorization durations

Initial authorizationUp to 6 months

Re-authorizationUp to 12 months (with continued positive clinical response)

Age threshold for site-of-service review13+ years

Distance threshold for hospital site50 miles (no outpatient infusion center within 50 miles)

Conditions supported as sufficient evidence (count)7

Conditions judged insufficient evidence (count)13

Medicare NCDNo national coverage determination

Medical-necessity criteria

General Site-of-Service Medical Necessity

Site-of-Service Medical Necessity (general).

ALL of the following

Prior authorization is required for IV or injectable rituximab products for members age ≥13 when site-of-service review applies.
Site-of-service decisions will prioritize the most appropriate, safe, and cost-effective location (physician office, infusion center, home infusion, or hospital-based outpatient setting).
Hospital-based outpatient setting is medically necessary when ANY of the following apply:
- Initial course of infusion of a pharmacologic or biologic agent (first 90 days).

Evidence summary and indication-level coverage stance

Evidence synthesis and covered vs insufficient-evidence indications.

The policy's evidence review draws on randomized controlled trials, systematic reviews, cohort studies, and guideline statements. It identifies indications with sufficient evidence to support coverage (examples include: factor inhibitors in hemophilia refractory to first-line therapy; multicentric Castleman disease; HCV-associated cryoglobulinemic vasculitis; glucocorticoid‑refractory chronic GVHD; pretransplant HLA desensitization for renal transplant candidates; idiopathic membranous nephropathy; and neuromyelitis optica for relapse prevention).

The policy also lists conditions judged to have insufficient evidence (examples: mixed connective tissue disease, primary Sjögren syndrome, systemic lupus erythematosus overall, lupus nephritis in some trials, systemic sclerosis, EGPA/Churg‑Strauss mixed results, multiple sclerosis across phenotypes, myasthenia gravis, minimal change disease in adults, antibody‑mediated rejection in solid organ transplant, and ABMR after islet transplantation).

Guideline-based recommendations (summary):

Major society guidance is summarized and informs the policy. KDIGO (2021 and 2024 updates) recommends rituximab as an induction option or for specific membranous nephropathy and ANCA‑associated vasculitis scenarios and supports rituximab for maintenance in many AAV cases (with specific populations preferred for rituximab).

ISHLT (heart and lung transplant) recommends rituximab for HLA desensitization and in combination regimens for antibody‑mediated rejection (class 2a/2b, level C) and for isohemagglutinin titer management >1:32 in certain settings.

ISTH (2020) conditionally recommends adding rituximab to corticosteroids and TPE for acute iTTP and for relapse, and for prophylaxis in remission with low ADAMTS13 activity (conditional, very low–certainty evidence).

HCPCS / J-codes and related coding

HCPCS codes for rituximab productsHCPCS

J3590	Unclassified biologics (use to report: Amjevita, Cyltezo, Hyrimoz HCF, Sandoz and Simlandi)
J9311	Injection, rituximab 10 mg and hyaluronidase (Rituxan Hycela)
J9312	Injection, rituximab (Rituxan), 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
Q5156	Injection, tocilizumab-anoh (Avtozma), biosimilar, 1 mg (new code effective 10/01/25)

HCPCS / J-codes and Q-codes mentioned in historyHCPCS|mixed

J9311	HCPCS code added 01/01/19 (new codes effective 1/1/19)
J9312	HCPCS code added 01/01/19 (new codes effective 1/1/19)
Q5115	HCPCS code added 08/01/19 to support Truxima (rituximab-abbs)
J3590	Unlisted code referenced/added/removed in various history entries (added 01/01/20, removed 07/01/21)
Q5119	HCPCS code referenced in history (added, date unspecified)
Q5123	HCPCS code added 07/01/21 then effective date deleted 07/01/22
J9310	HCPCS code terminated 1/1/19 (removed)
Q5156	HCPCS code added (new code effective 10/01/25) referenced 11/01/25

Providers must report the specific HCPCS code corresponding to the administered rituximab product (for example, Q‑codes for biosimilars such as Q5115/Q5119/Q5123, J9312 for Rituxan, and J9311 for Rituxan Hycela) and include clinical documentation supporting medical necessity.

Per policy notes, the unlisted biologics code J3590 may be used for unclassified biologics as referenced in the coding table, and product‑specific Q/J codes should be used when available; submission of diagnosis, history/physical, prior treatments, and site‑of‑service justification (when requesting hospital outpatient infusion) is required.

Provider actions and billing impact

Prior Authorization

Prior Authorization Required

Prior authorization is required for rituximab and rituximab biosimilars for non-oncologic indications. Providers must submit indication-specific documentation supporting medical necessity at the time of the authorization request.

Affected HCPCS/Codes: J9312, J9311, Q5115, Q5119, Q5123, J3590
Indication-specific documentation required (see documentation callout)

Documentation Required

Medical Record Documentation Required

Medical record documentation must accompany prior authorization requests and must include: the specific diagnosis, objective details of disease severity (e.g., joint counts, laboratory markers, organ involvement), prior therapies tried and the reason for discontinuation (lack of efficacy, intolerance, contraindication), dates of prior treatments, and rationale for administering the drug in a hospital outpatient setting when requested (see Site-of-Service criteria).

Definitions, thresholds, and clinical parameters

Key terms and numeric thresholds used in criteria are summarized here and are used throughout the policy to define eligibility, thresholds, and site‑of‑service rules.

Definitions

Site of service (SOS)Location where the drug is administered (hospital outpatient, infusion center, physician's office, or at home)

CRS grade 3 or 4Fever plus hypotension requiring vasopressors and severe hypoxia requiring high-flow oxygen or positive pressure ventilation

Refractory to first-line therapyFailure to respond to standard first-line treatments (e.g., corticosteroids, cyclophosphamide, MMF) or disease relapse despite initial therapy

TPETherapeutic plasma exchange

ITPImmune thrombocytopenia

Evidence sources and guideline citations

Literature review cutoff and evidence types: the policy's literature review includes evidence through August 26, 2025 and cites randomized controlled trials, systematic reviews and meta‑analyses, observational cohort studies, and recommendations from professional guideline bodies.

Evidence item	Summary/notes
Rheumatoid arthritis evidence	4 RCTs and observational studies show improved disease-related outcomes vs methotrexate alone; used with methotrexate for moderately–severely active RA (evidence supports net health benefit).
ANCA-associated vasculitides evidence	Three RCTs and observational studies demonstrating noninferiority/superiority versus cyclophosphamide for induction; maintenance benefit vs azathioprine with uncertainty. KDIGO 2024 recommends glucocorticoids + rituximab or cyclophosphamide for induction and rituximab for maintenance in many scenarios.
Pemphigus RCT	One RCT found rituximab plus short-term corticosteroids superior to long-term corticosteroids (better complete response, lower cumulative steroid dose, fewer severe AEs).
TTP evidence	Phase 2 trial and cohort data show lower relapse rates and improved outcomes versus historical controls; guideline (BCSH/ISTH) recommend rituximab in acute/refractory iTTP and for prophylaxis in low ADAMTS13.
MENTOR trial outcome (idiopathic membranous nephropathy)	MENTOR trial: rituximab noninferior and superior to cyclosporine for 24-month complete or partial remission; other RCTs (STARMEN, RI-CYCLO) provide comparative context. KDIGO 2021 recommends rituximab for MN with risk factors.
Neuromyelitis optica systematic review	Systematic reviews, RCT and observational data show significant reductions in relapse rate and improved EDSS with rituximab; NEMOS recommends rituximab as first-line. Evidence supports net benefit for relapse prevention refractory to first-line therapy.
HCV-associated cryoglobulinemic vasculitis evidence	Systematic reviews and 2 RCTs show improved outcomes with rituximab as add-on when antivirals fail or disease is severe/life-threatening.
Factor inhibitors in hemophilia	Systematic reviews, phase 2 trial, cohort studies report response rates ~25%-50% depending on mono- vs combination therapy; evidence shows improved net health outcome for refractory inhibitors.
Autoimmune hemolytic anemia evidence	Two RCTs and observational studies found higher overall response rates with rituximab in warm AIHA; evidence sufficient for improvement in net health outcome.
Multicentric Castleman disease evidence	Systematic reviews and cohort studies indicate rituximab improved overall survival and reduced incidence of NHL in multicentric Castleman disease.
ITP evidence	Systematic reviews and trials show mixed results; adult RCT failed to show benefit for second-line rituximab—evidence insufficient for routine coverage; ASH provides conditional recommendations favoring alternative sequencing.
Minimal change disease evidence	Pediatric RCTs and observational studies show benefit in children with frequently relapsing/steroid-dependent disease; adult evidence limited—KDIGO recommends rituximab as glucocorticoid-sparing in select pediatric cases.
Glucocorticoid-refractory chronic GVHD evidence	Multiple cohort studies demonstrate response with sustained improvements and steroid-sparing effects; evidence considered sufficient for meaningful net benefit.
KDIGO membranous nephropathy recommendation	KDIGO (2021) recommends rituximab or cyclophosphamide + alternate-month glucocorticoids for MN with risk factors; KDIGO AAV (2024) recommends rituximab for induction and maintenance in many patients.
Guideline—ISHLT (transplant) recommendations	ISHLT recommends rituximab for desensitization in HLA-sensitized heart transplant candidates and as part of combination treatment for ABMR (class 2a/2b, level C); routine induction not recommended. Evidence supports use in desensitization protocols.
BCSH/ISTH TTP guidance	BCSH recommends considering rituximab on admission with plasma exchange and corticosteroids for acute idiopathic TTP with neurologic or cardiac pathology and for refractory/relapsing disease; ISTH suggests adding rituximab to TPE and steroids (conditional).
ATS 2023 systemic sclerosis-ILD guidance	ATS conditionally recommends rituximab for SSc-ILD based on very low-quality evidence; timing and patient selection remain uncertain.
AAN / MS evidence	AAN (2018) found rituximab likely more effective than placebo for RRMS for some outcomes (moderate confidence) but insufficient for progressive MS; overall evidence for MS mixed and guideline inclusion variable.
Neuromyelitis Optica Study Group recommendation	NEMOS (2014) recommended rituximab as first-line (along with azathioprine) and second-line after azathioprine failure for NMO/NMOSD.
Key prescribing information / biosimilars updates	Prescribing information for Truxima, Ruxience, Riabni revised June 2025; policy incorporates biosimilar product positioning and step/second-line requirements.
Systematic reviews and meta-analyses cited	Multiple systematic reviews and meta-analyses across indications (e.g., NMO, AIHA, cryoglobulinemia, membranous nephropathy) underpin coverage determinations. Literature review through Aug 26, 2025.

Prescribing information updates and formulary history: the prescribing information for biosimilars Truxima, Ruxience, and Riabni was revised in June 2025, and the policy history documents multiple formulary and product‑preference changes between 2019 and 2026 (including changes to preferred vs non‑preferred status and step‑therapy/trial‑and‑failure requirements over 2019–2026).

Medicare determinations

Medicare national coverage determination: No national coverage determination exists for rituximab per the policy.

Revision history (chronological)

2015-01-13policy_created

New policy created with literature review through May 5, 2014; outlines non-oncologic labeled and off-label indications for which rituximab is considered medically necessary.

2016-11-01clarified

Clarified that site-of-service review is applicable only to those age 13 and older; drug criteria review applies to all ages.

2019-01-01coding_update

Added HCPCS codes J9311 and J9312 (effective 01/01/19) and updated policy with literature through August 2018; idiopathic membranous nephropathy added to medically necessary statement.

Policy metadata

Document metadata

PayerPremera Blue Cross

Policy number5.01.556

Policy titleRituximab: Non-oncologic and Miscellaneous Uses

Effective date2026-06-01

Last review2026-05-12

StatusMODIFIED

Scope summaryDefines medical necessity criteria, site-of-service review rules, covered non-oncologic indications, investigational indications, length of approval, documentation and coding requirements for rituximab products for commercial plan members (note: Alaska fully-insured members exempt from SOS review). Applies to IV/injectable administration and SOS for ages ≥13.

Policy Summary

PayerPremera Bluecross

Policy5.01.556 Rituximab: Non-oncologic and Miscellaneous Uses

Policy CodePolicy 5.01.556

Change TypeMODIFIED — multiple formulary/product-preference and site-of-service updates (2019–2026)

Effective DateJun 1, 2026

Next Review Date

SourceLink

On This Page

Re-initiation of an agent after ≥6 months off therapy (does not include standard dosing intervals of ≥6 months).

No outpatient infusion center within 50 miles and no contracted home infusion agency available to travel, or hospital is the only place offering the drug.

Individual has a clinical condition that increases risk of infusion complications (e.g., symptomatic cardiac arrhythmia, significant respiratory disease, %FVC ≤40%, unstable renal function, difficult/unstable vascular access, acute cognitive impairment affecting safety, or history of severe drug reactions/anaphylaxis to related agents).

Individual has grade 3–4 cytokine release syndrome (CRS) requiring vasopressors and high-flow oxygen/positive pressure support and will be admitted to inpatient setting.

Hospital-based outpatient setting is NOT medically necessary when site-of-service criteria in this policy are not met.

Medically necessary sites of service

Medically necessary sites of service for IV infusion when criteria are met.

ALL of the following

Preferred medically necessary sites: physician's office, infusion center, or home infusion when available and appropriate.
Hospital-based outpatient is medically necessary for the first 90 days for initial courses, and per criteria in the Site-of-Service group when risk factors apply.
Home infusion is medically necessary when a contracted home infusion agency will provide services and the patient meets safety criteria for home administration.

Riabni / Ruxience / Truxima medical necessity by indication (biosimilars first-line)

Riabni / Ruxience / Truxima — biosimilars considered first-line for non-oncologic indications when criteria below are met. Guideline-based recommendations summarized across indications.

ALL of the following

Rheumatoid arthritis (RA)
- Riabni, Ruxience, or Truxima may be considered medically necessary for moderately to severely active RA when used in combination with methotrexate.
- Used as second-line therapy after failure of at least one first-line biologic or targeted synthetic DMARD (examples: preferred adalimumab products, etanercept, preferred infliximab products, tocilizumab products, tofacitinib/Xeljanz, upadacitinib/Rinvoq), OR in patients with inadequate response to methotrexate or other conventional synthetic DMARD and who are not suitable candidates for TNF inhibitors (e.g., recent history of lymphoma/malignancy within 5 years, latent TB with contraindication to prophylaxis, prior demyelinating disease).
ANCA-associated vasculitis (granulomatosis with polyangiitis, microscopic polyangiitis)
- Riabni, Ruxience, or Truxima may be considered medically necessary when initial therapy with azathioprine, methotrexate, and/or mycophenolate has failed or is contraindicated, and used in combination with glucocorticoids.
Eosinophilic granulomatosis with polyangiitis (EGPA)
- May be used as first-line in combination with glucocorticoids for individuals with severe (organ‑threatening) disease.
- May be used as add-on therapy for treatment‑refractory disease.
Cryoglobulinemic vasculitis associated with HCV
- Use consistent with guideline-based management of HCV‑associated cryoglobulinemic vasculitis (consider in refractory or organ‑threatening disease; coordinate with antiviral therapy).
Idiopathic membranous nephropathy
- May be considered when guideline-based immunosuppressive therapy is ineffective or contraindicated; follow renal‑specific guidance for use of rituximab.
Lupus nephritis / Systemic lupus erythematosus (SLE)
- May be considered in select cases refractory to standard therapy per guideline recommendations (e.g., persistent nephritis despite conventional immunosuppression); use per specialist guidance.
Neuromyelitis optica spectrum disorders (NMOSD)
- May be considered according to guideline-directed therapy when approved/standard therapies are ineffective, not tolerated, or contraindicated; coordinate with neurologist and disease‑specific agents.
Primary Sjögren syndrome
- May be considered for severe systemic manifestations or glandular dysfunction refractory to standard therapies based on specialist recommendation.
Systemic sclerosis (scleroderma)
- May be considered for selected severe or refractory manifestations per specialty guideline recommendations.
Dermatologic autoimmune diseases (pemphigus, pemphigoid)
- Riabni, Ruxience, or Truxima may be considered for pemphigus and pemphigoid diseases when standard therapies have failed or for severe disease, consistent with dermatology guidelines.
Autoimmune hemolytic anemia (AIHA)
- May be considered for warm AIHA refractory to first‑line treatments (e.g., corticosteroids) per hematology guidance.
Chronic graft-versus-host disease (chronic GVHD)
- May be considered for steroid‑refractory or steroid‑dependent disease per transplant/hematology guidelines.
HLA desensitization
- May be considered as part of desensitization protocols in transplant candidates per transplant center guidance.
Hemophilia with factor inhibitors
- May be considered for eradication of inhibitors in coordination with hemophilia treatment center per specialty recommendations.
Immune thrombocytopenia (ITP)
- May be considered for adults with ITP refractory to first‑line therapies or with relapsed disease per hematology guidelines.
Thrombotic thrombocytopenic purpura (TTP)
- May be considered as adjunctive therapy in acquired TTP per hematology guidelines.
Multicentric Castleman disease
- May be considered in selected cases per specialty guidance when other therapies are ineffective or contraindicated.

Rituxan and Rituxan Hycela — second-line products

Rituxan and Rituxan Hycela — second‑line (non-preferred) products. Step/failure requirements and exceptions.

ALL of the following

Rituxan or Rituxan Hycela are considered second‑line products and require documentation of failure, intolerance, or contraindication to Riabni, Ruxience, or Truxima unless a medical exception is granted.
Documentation must include reason for using Rituxan (e.g., prior adverse reaction to a biosimilar, formulary restriction, or clinical rationale) and prior trial evidence of biosimilar failure or unsuitability.
Exception: members with difficult venous access may be approved for Rituxan Hycela when subcutaneous administration is clinically indicated and supported by documentation of vascular access issues.

Investigational / Not covered uses

Investigational / Not covered uses.

ALL of the following

All indications not specifically listed as medically necessary in this policy are considered investigational and not covered.
Use of rituximab products for indications without guideline support or insufficient evidence is considered investigational (examples to be reviewed in Evidence Review).
Prior authorization may be denied for investigational uses; appeals should include robust clinical rationale and supporting literature.

Length of Approval

Length of approval for initial and re-authorization.

ALL of the following

Initial authorization duration: up to 12 months unless indication‑specific shorter duration is clinically indicated.
Re-authorization: up to 12 months; renewal requires documentation of clinical response, ongoing need, and absence of unacceptable toxicity. For some indications (e.g., ANCA vasculitis, NMOSD, nephrology indications), specialty-specific renewal intervals and monitoring may apply per guideline recommendations.

ASH (2019) provides conditional recommendations in immune thrombocytopenia (suggesting corticosteroids first-line, and rituximab as an option vs splenectomy or TPORAs in specific situations).

ATS (2023) gives a conditional recommendation for rituximab in systemic sclerosis‑associated ILD based on very low‑quality evidence. AAN (2018) judged rituximab likely more effective than placebo for RRMS relapse outcomes but insufficient for progressive MS, and the Myasthenia Gravis Foundation (2020) recommends considering rituximab early for MuSK‑Ab+ MG and as an option in refractory AChR‑Ab+ MG.

Many recommendations are conditional or based on lower‑quality evidence (level C/very low), and the policy notes these distinctions when aligning coverage criteria with guideline statements.

Required: diagnosis, disease severity measures, prior treatments with dates and outcomes
Required: documentation of trial and failure or contraindication to guideline-preferred therapies when applicable
If requesting hospital outpatient site-of-service, provide clinical justification per SOS criteria (e.g., high-risk cardiac/pulmonary status, difficult vascular access, recent severe infusion reaction, CRS grade 3–4)

Billing Rule

Use Applicable HCPCS Codes

Use applicable HCPCS codes when billing. Map product to the appropriate code per payer guidance; miscoding may delay payment or prior authorization processing.

Q-codes for biosimilars (e.g., Q5115, Q5119, Q5123) when applicable
J9312 — Rituxan (rituximab) single-source product
J9311 — Rituxan Hycela (rituximab/hyaluronidase) when clinically indicated
J3590 — Unclassified biologic (use only when no specific code applies and per billing rules)

Denial Risk

Denial Risk for Hospital Outpatient Site-of-Service

Hospital outpatient infusion services may be denied if the Site-of-Service (SOS) medical necessity criteria are not met. Authorization and documentation must demonstrate that outpatient infusion center, physician office, or home infusion are not appropriate or that one of the medical exceptions applies.

Denials may occur when SOS criteria (distance, lack of contracted home infusion, clinical risk factors, CRS severity thresholds, or initial-course requirements) are not satisfied
Provide explicit clinical justification when requesting hospital outpatient administration beyond the preferred sites

Billing Rule

Formulary Preference and Step Therapy

Formulary preference and step-therapy expectations apply. Where the formulary or step edits require trial of preferred biosimilars (for example Ruxience or Truxima) prior to coverage of Rituxan or Rituxan Hycela, providers should document trials/failures of preferred products or provide rationale for medical necessity of bypassing step requirements. Follow current formulary and product-preference rules when submitting prior authorization requests.

Product-preference/step edits: trial of preferred biosimilars (e.g., Ruxience, Truxima) may be required before Rituxan or Rituxan Hycela
Providers must document trial duration, response, and reason for failure/intolerance when a step is claimed to be failed
Follow the payer's current formulary and step-therapy rules in effect at the time of service

Billing Rule

Site-of-Service Exception for Alaska Fully-Insured Members

The Site-of-Service (SOS) medical necessity criteria within this policy DO NOT apply to Alaska fully-insured members. For Alaska fully-insured members, follow the infusion drug Medical Necessity criteria only and applicable Alaska-specific statutes (e.g., HB 226) or state-mandated exceptions.

Alaska fully-insured members: SOS criteria do not apply — follow infusion drug medical necessity criteria
Document membership/plan type if requesting an SOS exception based on Alaska fully-insured status

Prior Authorization

Prior Authorization and Documentation Expectations for Covered Indications

For all covered indications, prior authorization and supporting documentation must demonstrate that the requested use is consistent with guideline-recommended indications and that the member has had refractory or failed prior therapies when those are required by the criteria. Provide clear clinical rationale when requesting rituximab for covered indications, including why alternatives were not appropriate.

Document guideline-specified indication and the reason rituximab is indicated for this patient
Document prior therapies tried, objective response, and reasons for discontinuation
When applicable, document why other guideline-recommended options are unsuitable or contraindicated

Documentation Required

Non-Formulary Exception Duration

Non-formulary exceptions may be granted for up to 12 months in accordance with prior policy history and exception processes. Providers should request non-formulary exceptions through the standard prior authorization pathway and provide documentation supporting the time-limited need.

Non-formulary exception duration: may be approved up to 12 months when supported by clinical documentation
Follow current non-formulary exception submission requirements and include rationale for the requested duration

Immune-mediated thrombotic thrombocytopenic purpura

Policy thresholds

Rheumatoid arthritis joint countsAt least 8 swollen and at least 8 tender joints

ITP platelet thresholdPlatelet counts at or ≤ 30,000

Distance for outpatient infusion center availability50 miles (no outpatient infusion center within 50 miles of patient's home)

Pulmonary function (%FVC)%FVC ≤ 40%

CRS temperature≥ 38 °C

Isohemagglutinin titer (pre-op)>1:32 (per ISHLT guideline for preoperative consideration)

ADAMTS13 activity<5% (consider elective rituximab in remission per BCSH)

2020-07-01revised

Added Ruxience (rituximab-pvvr) to site-of-service review and updated RA criteria to add Rinvoq (upadacitinib) as a first-line treatment option (changes effective Oct 2, 2020).

2021-02-01revised

Added biosimilar Riabni (rituximab-arrx) to policy as a second-line agent and updated coding (J3590 added then replaced; Q5123 added later).

2023-09-01revised

Reviewed prescribing information; moved Ruxience to second line (non-preferred) and standardized wording from 'patient' to 'individual'; updated preferred adalimumab biosimilars and product preferences effective Jan 1, 2024.

2024-01-03material_change

Effective Jan 3, 2025 (noted in 2024 update): changed product preferences — Ruxience moved to preferred; Rituxan and Rituxan Hycela changed to non-preferred and coverage updated to require trials/failure with Ruxience or Truxima prior to Rituxan/Rituxan Hycela.

2025-02-01material_change

Policy updated to indicate Site of Service Medical Necessity criteria does not apply to Alaska fully-insured members (per Alaska HB 226); clarified non-formulary exception review authorizations may be approved up to 12 months and added exception for cytokine release syndrome (CRS).

2025-10-01revised

Effective Jan 2, 2026: updated product preference statuses and required trials with preferred rituximab products; updated various preferred/non-preferred adalimumab and rituximab product listings and formulary specifics across 2023–2026.

2026-05-12revisedLatest

Policy last revised May 12, 2026 with effective date Jun 1, 2026; updated RA criteria to include adalimumab-aaty, adalimumab-adaz, and adalimumab-adbm as preferred alternatives and literature review through Aug 26, 2025.