ModifiedPremera BluecrossPolicy BCBSA Ref. Policy: 5.01.39

Site-of-service and medical necessity criteria for select autoimmune disorder therapies

Defines medical necessity, site-of-service review, and drug-specific coverage criteria for intravenous and injectable therapies used to treat a range of autoimmune conditions; applies to providers requesting coverage and site-of-service determination for affected drugs and members (with Alaska fully-insured exception for SOS criteria).

Policy Summary

PayerPremera Bluecross

PolicySite-of-service and medical necessity criteria for select autoimmune disorder therapies

Policy CodePolicy BCBSA Ref. Policy: 5.01.39

Change TypeMultiple additions and revisions (new drug criteria, SOS updates, formulary moves)

Effective DateJun. 1, 2026* May 12, 2026 Extracted from 5.01.550

Next Review Date

Key ActionObtain prior authorization demonstrating diagnosis, age eligibility, required prior therapy trials or intolerance, and specialist involvement before requesting coverage.

SourceLink

POLICY UPDATE CHANGES

This policy has been revised; site-of-service medical necessity criteria effective July 2, 2026.

Added criteria for Vyvgart for the treatment of generalized myasthenia gravis (gMG) in adult individuals who are anti-acetylcholine receptor (AChR) antibody positive.

Added criteria for Orencia for the prophylaxis of acute graft versus host disease (aGVHD).

Added criteria for Filspari for the treatment of proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression.

Added criteria for Vyvgart Hytrulo for the treatment of generalized myasthenia gravis (gMG) in adult individuals who are anti-AChR antibody positive.

Added coverage and formulary placement changes for multiple adalimumab and infliximab biosimilars and products, including designation of preferred and non-preferred products and effective dates for placement changes.

Added coverage criteria for Tarpeyo and updated Filspari and other IgAN drug criteria (including urine protein-to-creatinine threshold changes).

Removed Idacio (adalimumab-aacf) from the policy as it has been removed from the market.

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

listed drugs subject to site-of-service review

multipleautoimmune conditions covered

90 dayshospital outpatient initial-use

requiredspecialist prescriber required

13+ yrssite-of-service review applicability

2016-2026documented policy history years

Coverage Criteria and Drug-Specific Medical Necessity

Deficiency of Interleukin-1 Receptor Antagonist (DIRA), recurrent pericarditis, periodic fever syndromes, Still's disease, and related IL-1 blocker indications

Deficiency of Interleukin-1 Receptor Antagonist (DIRA), recurrent pericarditis (RP), periodic fever syndromes, Still's disease, and related IL-1 blocker indications — coverage criteria are below.

text":"Managed under pharmacy and medical benefit."},{"text":"DIRA: genetic testing has confirmed a mutation in the IL1RN gene; Kineret is prescribed by/with a rheumatologist, geneticist, or dermatologist."},{"text":"Cytokine release syndrome (treatment-induced grade 3 or 4 CRS): Kineret may be considered when temperature ≥38°C, hypotension requiring ≥1 vasopressor, and hypoxia requiring high-flow oxygen delivery or positive pressure; prescribed by appropriate specialist."},{"text":"Periodic fever syndromes / Still's disease: Kineret may be considered for CAPS (including NOMID when criteria met) and for SJIA/AOSD when prescribed by/with rheumatologist, geneticist, or dermatologist."}]},{"operator":"all","label":"Ilaris (canakinumab) — Interleukin-1β blocker","children":[{"text":"Managed under pharmacy and medical benefit; subject to site-of-service review when applicable."},{"text":"Indications covered: periodic fever syndromes (CAPS for ages ≥4 years; TRAPS, HIDS/MKD, FMF for ages ≥2 years as specified in prescribing information), and active Still's disease (AOSD, SJIA) in individuals aged ≥2 years when prescribed by/with rheumatologist, geneticist, or dermatologist."}]}]},{"text":"For all agents: documentation of prior therapies, objective diagnostic evidence, and rationale for agent selection must be provided as part of the authorization request."},{"text":"Concurrent use exclusions: IL-1 blockers should not be used concurrently with other agents where explicitly contraindicated by product labeling or other policy criteria; check specific medication criteria for prohibitions or concurrent-therapy restrictions."}]}

HCPCS / HCPCS Q / NDC and Related Codes

Drugs subject to site-of-service reviewmixed

Actemra (tocilizumab) IV	listed IV agent subject to SOS review
Avsola (infliximab-axxq) IV	listed IV agent subject to SOS review
Avtozma (tocilizumab-anoh) IV	listed IV agent subject to SOS review
Benlysta (belimumab) IV	listed IV agent subject to SOS review
Ilaris (canakinumab) SC	listed SC agent subject to SOS review
Inflectra (infliximab-dyyb) IV	listed IV agent subject to SOS review
Infliximab (Janssen - unbranded) IV	listed IV agent subject to SOS review
Remicade (infliximab) IV	listed IV agent subject to SOS review
Renflexis (infliximab-abda) IV	listed IV agent subject to SOS review
Saphnelo (anifrolumab-fnia) IV	listed IV agent subject to SOS review

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Referenced product identifiers and NDCsmixed

J-code/NDCs referenced

Multiple biologic product identifiers and NDC prefixes are listed (e.g., adalimumab-adbm NDCs starting with 82009; adalimumab NDCs starting with 72511; other NDC blocks noted in formulary updates)

Listed HCPCS/biologic codesHCPCS

C9305	Injection, nipocalimab-aahu (Imaavy), 3 mg
J0129	Injection, abatacept (Orencia), 10 mg
J0139	Injection, adalimumab (Humira), 1 mg
J0490	Injection, belimumab (Benlysta), 10 mg
J0491	Injection, anifrolumab-fnia (Saphnelo), 1 mg
J0638	Injection, canakinumab, (Ilaris), 1 mg
J1438	Injection, etanercept (Enbrel), 25mg
J1745	Injection, infliximab, excludes biosimilar (Remicade or Janssen unbranded), 10mg
J1823	Injection, inebilizumab-cdon, (Uplizna) 1 mg
J2793	Injection, rilonacept, (Arcalyst) 1 mg

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Sample HCPCS Q-codes for biosimilar injectablesHCPCS

Q5135	Injection, tocilizumab-aazg (Tyenne), biosimilar, 1 mg
Q5140	Injection, adalimumab-fkjp (Hulio), biosimilar, 1 mg
Q5141	Injection, adalimumab-aaty (Yuflyma), biosimilar, 1 mg
Q5142	Injection, adalimumab-ryvk (Simlandi), biosimilar, 1 mg
Q5143	Injection, adalimumab-adbm (Cyltezo), biosimilar, 1 mg
Q5144	Injection, adalimumab-aacf (Idacio), biosimilar, 1 mg
Q5145	Injection, adalimumab-afzb (Abrilada), biosimilar, 1 mg
Q5156	Injection, tocilizumab-anoh (Avtozma), biosimilar, 1 mg

Formulary NDC blocks and product identifiersNDC

NDCs starting with 72511	Amjevita (adalimumab-atto) non-preferred product reference
NDCs starting with 55513	Amjevita / alternate NDC block referenced in updates
NDCs starting with 83457	Hyrimoz (Cordavis) product NDC block referenced in updates
NDCs starting with 61314	Hyrimoz (Sandoz) / adalimumab-adaz NDC block referenced in formulary changes
NDCs starting with 00074	Humira (AbbVie) adalimumab NDC block referenced in formulary updates

Policy-related HCPCS/unspecified codesHCPCS

Q5102	HCPCS code (terminated 4/1/18)
Q5103	HCPCS code added effective 4/1/18
Q5104	HCPCS code added effective 4/1/18
Q5121	HCPCS code added (effective 2021)
J3590	Unclassified biologic HCPCS code used for multiple biologics
J0638	HCPCS code added for Ilaris (canakinumab)
J1823	HCPCS code added for Uplizna (inebilizumab-cdon)
J0135	HCPCS code referenced in history (adalimumab-related)
J9332	HCPCS code added (2022)
J9333	HCPCS code added (2024)

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HCPCS/J-code updatesHCPCS

C9305	HCPCS code added 10/01/25 (later replaced)
J3402	HCPCS code added 10/01/25
J9256	HCPCS code added to replace C9305 effective 01/01/26

inv-54: Hospital-based outpatient initial-use (first 90 days)

RuleHospital-based outpatient site is considered medically necessary for the initial course or re-initiation after ≥6 months for IV/SC infusion/injection therapy (first 90 days).

Applies toInitial course of infusion/injection OR re-initiation of therapy after ≥6 months (does not include standard dosing intervals ≥6 months).

Preferred sitesPhysician's office, infusion center, home infusion when criteria met; hospital outpatient limited to first 90 days under this rule.

inv-55: CRS severity for inpatient requirement

CRS grade definitionCRS grade 3 or 4 requires ALL: temperature ≥38°C; hypotension requiring ≥1 vasopressors; and hypoxia requiring high-flow oxygen delivery or positive pressure ventilation (CPAP/BiPAP/intubation/mechanical ventilation).

Prior Authorization, Documentation, and Step Therapy Requirements

Prior Authorization

Prior Authorization Required

Prior authorization (site-of-service review) is required for listed IV and SC biologics and related agents. Benefit routing (medical vs pharmacy) determines the authorization pathway — check member plan booklet/ID card for plan-specific applicability. Providers must confirm the medication is being used per FDA dosing/administration and supply required clinical documentation to support medical necessity.

Prior authorization required for listed IV/SC biologics (e.g., Actemra IV; Avsola IV; Benlysta IV; Ilaris SC; Inflectra IV; Remicade IV; Saphnelo IV; Tofidence IV; Tyenne IV; Uplizna IV; Vyvgart IV; Vyvgart Hytrulo SC).
Benefit routing: medications managed under pharmacy benefit vs medical benefit determine PA process (see policy lists). Verify member-specific benefit prior to submission.
Documentation must include office visit notes with diagnosis, relevant history, physical exam, medication history, and any condition-specific evidence (e.g., biopsy, UPCR, electrophysiologic testing, antibody status) supporting criteria.
Confirm FDA-approved age indications and dosing — site-of-service medical necessity applies only when criteria met; pediatric site-of-service review limited to age ≥13 (unless drug-specific pediatric criteria permit younger ages).
If site-of-service criteria are not met (including lack of approved outpatient infusion within 50 miles or lack of contracted home infusion agency when required), the requested site may be considered not medically necessary and denied.

Background and Policy Scope

Autoimmune disorders are characterized by immune activation directed at self‑tissues, resulting in chronic inflammation and organ‑specific manifestations. This policy defines medical necessity and site‑of‑service review rules for intravenous and injectable biologic and targeted therapies used across multiple autoimmune conditions (for example, systemic lupus erythematosus, hidradenitis suppurativa, pyoderma gangrenosum, IgG4‑related disease, and primary immunoglobulin A nephropathy). Coverage requires meeting the drug‑specific clinical criteria (age, documented diagnosis, prior therapy or intolerance, specialist involvement, and any specified laboratory or biopsy thresholds) and, for medical benefit members aged 13 years and older, evaluation under the site‑of‑service medical necessity criteria unless the member is an Alaska fully‑insured enrollee or otherwise exempt per plan rules.

Definitions and Clinical Terms

inv-103: Site of Service (SOS) definition

DefinitionSite of Service (SOS) = location where the drug is administered (e.g., hospital‑based outpatient, infusion center, physician's office, home).

SOS review applicabilitySite-of-service medical necessity review applies for individuals aged 13 and older (SOS criteria does NOT apply to Alaska fully‑insured members).

Preferred medically necessary sitesPhysician's office, infusion center, home infusion; hospital-based outpatient used per initial-use rule and other criteria.

inv-104: Hospital-based outpatient initial-use rule

Initial-use ruleHospital-based outpatient setting considered medically necessary for first 90 days for initial course or re-initiation after ≥6 months (does not include standard dosing intervals of ≥6 months).

Condition-based exceptions

Policy Change Log

06/01/26updated

Moved Fabhalta proteinuria coverage for C3G and IgAN to policy 5.01.571 and updated age and product availability (Cosentyx age lowered to 12 years; removed Yuflyma) and adjusted adalimumab product preferences and sequencing.

04/01/26updated

Clarified Filspari and Tarpeyo UPCR thresholds to at least 0.5 g/g or urine protein ≥0.5 g/day and updated related IgAN criteria.

03/01/26updated

Policy Summary

PayerPremera Bluecross

PolicySite-of-service and medical necessity criteria for select autoimmune disorder therapies

Policy CodePolicy BCBSA Ref. Policy: 5.01.39

Change TypeMultiple additions and revisions (new drug criteria, SOS updates, formulary moves)

Effective DateJun. 1, 2026* May 12, 2026 Extracted from 5.01.550

Next Review Date

Key ActionObtain prior authorization demonstrating diagnosis, age eligibility, required prior therapy trials or intolerance, and specialist involvement before requesting coverage.

SourceLink

On This Page

Setting implicationWhen CRS grade 3-4 is present, inpatient admission is required and hospital-based care is medically necessary for timely management.

Applies toTreatment-induced CRS (not limited to CAR-T products); tocilizumab IV and anakinra indicated per policy when criteria met.

inv-56: Minimum weight (Arcalyst/ DIRA)

Minimum weightIndividual must weigh at least 10 kg for Arcalyst (rilonacept) use in DIRA.

Genetic confirmationGenetic testing confirming IL1RN mutation required for DIRA (supporting Arcalyst/Kineret use).

PrescriberPrescribed by or in consultation with a rheumatologist, geneticist, or dermatologist.

inv-57: Minimum weight (Niktimvo chronic GVHD)

Minimum weightIndividual must weigh at least 40 kg for Niktimvo (axatilimab-csfr) use in chronic GVHD after failure of ≥2 prior systemic therapies.

Prior therapy requirementFailure of at least two systemic treatments (e.g., cyclosporine, ibrutinib, mycophenolate, ruxolitinib, sirolimus, tacrolimus) required.

PrescriberPrescribed by or in consultation with an oncologist, hematologist, or transplant-affiliated physician.

inv-58: EDSS score requirement for NMOSD Uplizna

EDSS cap for UpliznaExpanded Disability Status Scale (EDSS) score must be ≤7.5 for Uplizna (inebilizumab-cdon) eligibility in NMOSD.

Relapse historyHistory of ≥1 relapse in last 12 months or ≥2 relapses in last 24 months required as part of NMOSD criteria.

Diagnostic confirmationAt least one core clinical characteristic plus positive AQP4‑IgG antibody and exclusion of alternative diagnoses required.

inv-59: Urine protein-to-creatinine ratio (UPCR) thresholds

Filspari thresholdDocumented UPCR ≥0.5 g/g OR urine protein ≥0.5 g/day required for Filspari (sparsentan).

Voyxact thresholdDocumented UPCR ≥0.75 g/g OR urine protein ≥1.0 g/day required for Voyxact (sibeprenlimab).

Vanrafia thresholdDocumented UPCR ≥1.5 g/g required for Vanrafia (atrasentan).

inv-60: Trial entry thresholds (examples)

SELENA-SLEDAISELENA‑SLEDAI ≥6 used as an example trial entry threshold (pediatric Benlysta trial).

SLEDAI-2KSLEDAI‑2K ≥6 and clinical SLEDAI‑2K ≥4 used in anifrolumab (Saphnelo) trials as trial thresholds.

MG-ADL / QMGMyasthenia gravis trials used MG‑ADL ≥5 or ≥6 and QMG ≥11 as eligibility thresholds (Vyvgart/Uplizna studies).

inv-61: Proteinuria / UPCR trial thresholds used in trials

Tarpeyo / trial UPCRTarpeyo (budesonide) trial eligibility used UPCR ≥0.8 g/g or proteinuria ≥1 g/day and eGFR ≥35 mL/min/1.73 m2 (NefIgArd Part A).

Filspari trial proteinuriaPROTECT trial enrolled patients with persistent proteinuria >1.0 g/day despite maximized RAS inhibitor therapy (used in Filspari labeling).

Voyxact trial thresholdsVISIONARY required uPCR ≥0.75 g/g or proteinuria ≥1.0 g/day and eGFR ≥30 mL/min/1.73 m2 on stable ACEi/ARB ± SGLT2i.

inv-62: eGFR thresholds

Tarpeyo eGFRTarpeyo eligibility requires eGFR ≥35 mL/min/1.73 m2.

Voyxact / Vanrafia eGFRVoyxact and Vanrafia trial eligibility used eGFR ≥30 mL/min/1.73 m2.

ContexteGFR thresholds applied in trial-based prescribing information and policy criteria for IgAN agents.

inv-63: Tarpeyo urine protein-to-creatinine ratio (updated)

Updated Tarpeyo UPCRTarpeyo urine protein‑to‑creatinine ratio updated to ≥0.8 g/g (was ≥1.5 g/g); alternatively proteinuria ≥1.0 g/day accepted.

BasisChange reflected in 2025 update to align with NefIgArd Part A trial criteria and prescribing information.

Related eGFRTarpeyo criteria also reference eGFR threshold (≥35 mL/min/1.73 m2) per trial inclusion.

inv-64: Tarpeyo UPCR change historical note

Historical changeTarpeyo UPCR criterion changed from ≥1.5 g/g to ≥0.8 g/g or proteinuria ≥1 g/day per 2025 policy update and prescribing information.

Effective documentationPolicy history cites the change implemented in 2025 updates and reflected in prescribing/trial language.

ImplicationAllows Tarpeyo coverage for patients meeting the lower UPCR threshold used in the pivotal trial (NefIgArd Part A).

inv-65: UPCR / urine protein KDIGO-aligned threshold

KDIGO-aligned thresholdPolicy aligns UPCR/proteinuria threshold with 2025 KDIGO guidance: at least 0.5 g/g OR urine protein ≥0.5 g/day for certain indications (e.g., Filspari/Tarpeyo alignment noted).

Specific applicationFilspari criteria explicitly require UPCR ≥0.5 g/g or urine protein ≥0.5 g/day with ACEi/ARB trial or intolerance.

Policy noteHistory entry notes alignment with 2025 KDIGO guidance in updating UPCR thresholds across IgAN criteria.

Step Therapy

Step Therapy / Prior Treatment Documentation

Step therapy and sequencing requirements apply for multiple agents (e.g., adalimumab/infliximab products). For new starts, providers must document prior trials and inadequate response or intolerance to preferred agents as specified. Failure to provide required prior-therapy documentation may trigger denial.

Adalimumab and infliximab products: trial and failure with specified preferred alternatives required for many indications (see formulary sequencing and effective dates in History).
Brand/step therapy updates effective per history (providers should reference current preferred/non-preferred status when requesting non-preferred agents).
For certain indications (e.g., pyoderma gangrenosum, uveitis, sarcoidosis), documentation of trial and inadequate response to specified non-biologic and preferred biologic agents is required before authorization of second-line agents.

Documentation Required

Documentation Requirements and Denial Triggers

Provide condition-specific diagnostic and baseline clinical documentation with the PA request. Missing or inadequate documentation (e.g., biopsy for IgG4-RD, AQP4 antibody for NMOSD, UPCR for IgAN, electrophysiology for CIDP, MG-ADL/QMG scores for gMG, confirmation of CRS grade) may result in denial.

IgG4-RD (Uplizna): biopsy with immunostaining, imaging or elevated IgG4 with histopathologic features; documentation of organ involvement and prior glucocorticoid–responsive flare.
SLE/Saphnelo/Benlysta: diagnostic criteria (ACR or EULAR/ACR or SLICC), prior induction therapy documented, and absence of concurrent prohibited agents.
CIDP: diagnostic criteria including clinical course, hyporeflexia/areflexia ≥2 months, and electrophysiologic criteria per AAN.
IgAN (Filspari, Tarpeyo, Voyxact): biopsy-proven diagnosis and documented urine protein-to-creatinine ratio (UPCR) thresholds as specified.
gMG (Vyvgart, Vyvgart Hytrulo, Imaavy, Uplizna): antibody status, MG-ADL/QMG baseline scores, prior immunosuppressive therapy trials, and concurrent-use exclusions documented.

Denial Risk

Concurrent Therapy and Exclusions

Certain concurrent therapies are excluded; verify there is no prohibited concurrent use (e.g., Benlysta not used concurrently with Saphnelo or Gazyva for SLE; Vyvgart not used concurrently with listed agents). Also note trial protocols may have prohibited concomitant agents (e.g., SGLT2 inhibitors were prohibited in the PROTECT trial for sparsentan).

Confirm absence of concurrent-use exclusions for the requested agent (review policy-specific concurrent medication lists).
If member is receiving a prohibited concurrent medication, prior authorization should be denied unless evidence shows discontinuation or contraindication to the concurrent agent.
Note trial-context exclusions (e.g., SGLT2 inhibitor prohibition in sparsentan PROTECT study) are informational for evidence review but ensure clinical appropriateness in real-world use.

Billing Rule

Site-of-Service (SOS) Verification

Verify site-of-service medical necessity criteria before requesting hospital-based administration. Site-of-service review deems infusion in certain locations medically necessary only when specified access or clinical-risk conditions are met; failure to meet SOS criteria may result in denial.

Site-of-service medically necessary when no outpatient infusion center within 50 miles and no contracted home infusion agency willing to travel, or hospital is only place offering administration.
SOS allowed when individual has increased risk factors (e.g., significant cardiac/pulmonary disease, unstable renal function, difficult vascular access, severe prior reactions, acute cognitive impairment) or for grade 3–4 cytokine release syndrome.
Pediatric site-of-service review limited to individuals aged 13 and older unless drug-specific pediatric criteria state otherwise.
Providers should check member benefits (plan booklet/ID) — some members/plans (e.g., Alaska fully-insured per HB 226) have exceptions to SOS applicability.

Hospital outpatient also medically necessary when no outpatient infusion center within 50 miles or no contracted home infusion agency, or when clinical risk factors exist (e.g., cardiac/pulmonary instability, unstable renal function, difficult vascular access, severe prior reactions).

Age/SOS applicabilitySOS review applies for individuals aged ≥13; Alaska fully‑insured members exempt from SOS criteria per policy note.

inv-105: CIDP diagnostic criteria

Core diagnostic featuresProgressive or relapsing motor and/or sensory symptoms in >1 limb with hyporeflexia/areflexia ≥2 months plus electrophysiologic findings meeting 3 of 4 demyelinating criteria (partial conduction block, reduced conduction velocity, prolonged distal latency, prolonged/absent F waves).

Exclusions/supportive testsExclude alternative causes (Lyme, diphtheria, toxins, hereditary neuropathy, MMN, IgM gammopathy); supportive CSF or biopsy data if available strengthen diagnosis.

Specialist involvementDiagnosis and prescribing should involve a neurologist; electrophysiologic criteria are enumerated in policy.

inv-106: NMOSD diagnostic requirements

Core clinical requirementAt least one core clinical characteristic (optic neuritis, acute myelitis, area postrema syndrome, acute brainstem syndrome, diencephalic or cerebral syndromes) plus positive AQP4‑IgG antibody test and exclusion of alternative diagnoses for NMOSD diagnosis.

Relapse/history and EDSSHistory of ≥1 relapse in last 12 months or ≥2 relapses in last 24 months required; EDSS score must be ≤7.5 for Uplizna eligibility.

Specialist involvementPrescribed by or in consultation with a neurologist experienced in NMOSD; site-of-service review applies to some IV forms.

inv-107: Biopsy-proven primary IgA nephropathy (IgAN)

RequirementDiagnosis requires documented renal biopsy confirming primary IgA nephropathy for use of IgAN‑directed agents.

Associated criteriaPolicy pairs biopsy confirmation with UPCR/proteinuria thresholds, ACEi/ARB optimization, eGFR limits, and nephrologist involvement for coverage.

Applies toFilspari, Tarpeyo, Vanrafia, Voyxact and other IgAN therapies listed in policy.

inv-108: Generalized myasthenia gravis antibody positivity

Serologic positivityGeneralized myasthenia gravis coverage for listed agents requires serologic testing positive for anti‑AChR or anti‑MuSK antibodies (as specified).

Concomitant therapyPatients usually must be on acetylcholinesterase inhibitor (pyridostigmine) and stable immunosuppressive therapy; prior trials or intolerances documented per agent criteria.

Specialist involvementDiagnosis and prescribing should involve a neurologist experienced in MG management.

inv-109: IBMTR Severity Index (aGVHD)

IBMTR indexIBMTR Severity Index outlines organ‑based staging for aGVHD: skin, liver (total bilirubin), and GI (diarrhea volume) with stages A–D and corresponding severity thresholds.

UseIndex used to grade aGVHD severity to inform prophylaxis and treatment decisions in HSCT recipients.

ComponentsIncludes skin rash extent, bilirubin ranges, GI stool volume thresholds to categorize stages and overall severity.

inv-110: BlyS / BAFF definition

DefinitionBlyS (BAFF) = B‑lymphocyte stimulator (B‑cell activating factor), the molecular target of belimumab.

RoleBinding of belimumab to BlyS/BAFF inhibits BlyS biological activity affecting B‑cell survival and antibody formation.

Clinical relevanceBlyS/BAFF levels and B‑cell activity are central to SLE pathophysiology and guide belimumab use in SLE criteria.

inv-111: BICLA definition

BICLA responseBILAG‑Based Composite Lupus Assessment (BICLA) requires improvement in baseline BILAG scores without worsening elsewhere, no SLEDAI‑2K or PGA worsening, and limited use of restricted meds — used as trial endpoint in lupus studies.

Use caseBICLA employed as efficacy outcome in SLE/anifrolumab trials to define meaningful clinical response across organ domains.

ComponentsRelies on BILAG domain improvements, no new severe BILAG activity (A) or ≥2 new moderate (B) scores, and stable physician global assessment.

inv-112: SRI-4 definition

SRI‑4 definitionSLE Responder Index (SRI‑4) = ≥4‑point reduction in SELENA‑SLEDAI with no new BILAG A or ≥2 new B scores, no worsening in PGA, and no prohibited medication use; primary endpoint in belimumab trials.

Trial usageUsed as the primary efficacy endpoint at Week 52 in pediatric and adult belimumab trials (e.g., BLISS programs, Trial 4).

DocumentationPolicy expects baseline and follow‑up disease activity measures consistent with trial thresholds for coverage justification.

inv-113: MG-ADL responder definition

MG‑ADL responderAn MG‑ADL responder = ≥2‑point reduction in MG‑ADL sustained for ≥4 consecutive weeks with first reduction occurring no later than 1 week after last infusion of the cycle (per ADAPT/Vyvgart definitions).

Trial contextMG‑ADL responder definition used as primary efficacy measure in Vyvgart and other gMG trials; required for coverage documentation when aligning to trial outcomes.

Scoring rangeMG‑ADL total score ranges 0–24; higher scores indicate greater impairment; trials often set minimum baseline thresholds (eg ≥5) for eligibility.

inv-114: Acute graft-versus-host disease definition

DefinitionAcute graft‑versus‑host disease (aGVHD) = immune complication after allogeneic HSCT, typically presenting within 100 days and affecting skin, liver, GI tract; can be persistent or late‑onset beyond 100 days.

Clinical featuresManifests with rash, GI symptoms (nausea, vomiting, diarrhea), and liver dysfunction; severity graded using indices such as IBMTR or other staging systems.

ImplicationaGVHD grading informs prophylaxis and treatment eligibility (eg Orencia prophylaxis criteria and Ryoncil use for steroid‑refractory pediatric aGVHD).

inv-115: Primary immunoglobulin A nephropathy definition

DefinitionPrimary immunoglobulin A nephropathy (IgAN) = autoimmune kidney disease with IgA deposition in glomeruli causing hematuria, proteinuria and progressive renal damage potentially leading to ESRD.

Clinical featuresPresents with hematuria ± proteinuria; management emphasizes blood pressure control, proteinuria reduction via RAS inhibition, and selective immunosuppression.

Diagnostic requirementRenal biopsy confirmation required for policy coverage of disease‑directed therapies.

inv-116: Concurrent-use restriction summary

SummaryConcurrent‑use restrictions prohibit using listed therapies together (examples include Vyvgart, Vyvgart Hytrulo, Rystiggo, Soliris, Ultomiris, Zilbrysq, Imaavy, eculizumab products); such concurrent use may trigger denial.

MG/CIDP contextMyasthenia gravis and CIDP criteria explicitly state these agents should not be used concurrently with specified complement/IgG‑targeting therapies.

Prior authorization implicationPrior authorization must document absence of prohibited concurrent agents to satisfy medical necessity criteria.

inv-117: Site-of-Service criteria definition

DefinitionSite‑of‑Service criteria = medical necessity rules determining appropriate administration location for infusion/injectable therapies (physician office, infusion center, home, hospital outpatient per initial‑use rule and access/clinical exceptions).

Age applicabilitySOS review applies for individuals aged ≥13; policy notes Alaska fully‑insured exception where SOS criteria do not apply.

Operational notesHospital outpatient considered medically necessary for initial 90 days; exceptions for access within 50 miles or clinical risk factors defined in policy.

inv-118: Formulary preference definition (preferred vs non-preferred)

Preferred vs Non‑preferredFormulary preference designates products as preferred (first‑line) or non‑preferred (require prior trial/failure of preferred product) and influences step therapy and prior authorization requirements.

ImpactNew starts may be required to try preferred biosimilars/infliximab or adalimumab products before coverage of non‑preferred brands; effective dates and product lists specified in policy history.

ExceptionCertain custom Open/Preferred formulary plans may follow different criteria (see policy 5.01.647); providers must verify member plan.

inv-119: Concurrent-use restriction (therapies not used together)

Examples of prohibited combinationsMedications not to be used concurrently include Imaavy with eculizumab products, Rystiggo, Vyvgart, Vyvgart Hytrulo, Soliris, Ultomiris, and Zilbrysq per updated myasthenia gravis criteria.

ScopeConcurrent‑use exclusions apply across indications where multiple overlapping biologics/complement/IgG‑targeting agents exist (gMG, CIDP, others).

Denial riskRequests documenting concurrent use of prohibited agents may be denied; prior authorization must confirm absence of such concurrent therapies.

inv-120: UPCR threshold aligned with 2025 KDIGO guidance

2025 KDIGO alignmentPolicy states UPCR threshold alignment with 2025 KDIGO guidance: UPCR ≥0.5 g/g OR urine protein ≥0.5 g/day used for certain IgAN therapy eligibility.

Application examplesFilspari criteria use UPCR ≥0.5 g/g OR urine protein ≥0.5 g/day and require ACEi/ARB trial or intolerance; Tarpeyo and other IgAN criteria were updated accordingly.

Policy noteHistory entries reference alignment with KDIGO 2025 when updating UPCR/proteinuria thresholds across IgAN criteria.

Changed Benlysta SC/IV coverage age for active lupus nephritis from 18 to 5 years and added Otezla XR for Behcet's disease.

02/01/26added

Added coverage criteria for Voyxact and updated Uplizna for generalized myasthenia gravis; added concurrent-use additions to exclude Ultomiris for several MG agents.

01/01/26updated

Added HCPCS code J9256 to replace C9305 effective 01/01/26 and updated formulary placement and brand-step sequencing for multiple adalimumab/infliximab products.

02/01/25updated

Policy clarified that Site‑of‑Service medical necessity criteria does not apply to Alaska fully‑insured members and updated Filspari criteria and Tarpeyo UPCR threshold to ≥0.8 g/g or proteinuria ≥1 g/day (later refined).

09/01/23updated

Interim review effective 09/01/2023 added Humira biosimilars and moved Avsola to first‑line preferred with effective date 01/01/2024; Inflectra moved to second‑line non‑preferred for 01/01/2024.

01/01/24updated

Added new HCPCS codes (J9333, J9334) and updated adalimumab product preferred/non‑preferred designations and related step therapy sequencing.

11/01/23added

Added coverage criteria for Rystiggo (rozanolixizumab) for generalized myasthenia gravis and mapped Rystiggo to HCPCS J3590.

07/01/16added

New policy approved and site‑of‑service medical necessity review criteria for IV therapy were added to the Prescription Drug section.

2023 Updateadded

Added criteria for Filspari (sparsentan) for treatment of proteinuria in adults with primary IgA nephropathy at risk of rapid progression (PROTECT study evidence).

2022 Updateadded

Added criteria for Vyvgart for treatment of generalized myasthenia gravis in adult individuals who are AChR antibody positive and added Orencia for prophylaxis of acute GVHD.

2023 Updateadded

Added Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase‑qvfc) coverage criteria for gMG based on bridging and ADAPT study data.

2025 Updateadded

Tarpeyo approval basis documented: NefIgArd Part A supported use in biopsy‑verified IgAN with eGFR and proteinuria criteria (eGFR thresholds and UPCR/proteinuria entry criteria described).

02/01/26addedLatest

Added coverage criteria for Voyxact (sibeprenlimab) to reduce proteinuria in adults with biopsy‑confirmed IgAN (VISIONARY interim evidence cited).