ModifiedPremera BluecrossPolicy 5.01.39

Autoimmune disorders — infusion/injection drugs and site-of-service medical necessity

Medical necessity criteria for IV and injectable drugs used to treat a range of autoimmune disorders, including site-of-service review for individuals (13+) and specific drug therapy criteria for multiple conditions; applies to Premera members except Alaska fully-insured members for SOS criteria.

Policy Summary

PayerPremera Bluecross

PolicyAutoimmune disorders — infusion/injection drugs and site-of-service medical necessity

Policy CodePolicy 5.01.39

Change TypeMultiple additions and revisions (coverage criteria, step therapy, site-of-service and coding updates)

Effective DateApr. 1, 2026

Next Review DateN/A

Key ActionSubmit prior authorization with documentation of diagnosis, prior therapies and relevant severity measures (e.g., MG‑ADL, UPCR, SELENA‑SLEDAI) to support medical necessity.

SourceLink

POLICY UPDATE CHANGES

This policy has been revised (changes effective July 2, 2026 available via link).

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).

Updated Benlysta IV criteria for use in individuals aged 5 years and older.

Updated Ilaris (canakinumab) criteria to require prescribing by or in consultation with a rheumatologist, geneticist, or dermatologist.

Added Arcalyst (rilonacept) to policy for FDA-approved indications including CAPS, DIRA maintenance, and recurrent pericarditis.

Updated Ilaris (canakinumab) criteria to require prescribing by or in consultation with a rheumatologist, geneticist, or dermatologist.

Added criteria for Vyvgart for treatment of generalized myasthenia gravis in AChR antibody positive adults and for Orencia for aGVHD prophylaxis.

Added multiple biosimilar adalimumab and infliximab products with preferred/non-preferred designations and updated step therapy and line-of-therapy positions effective Jan 1, 2024 and later updates toward 2025.

Added coverage criteria for Cosentyx for moderate to severe hidradenitis suppurativa and removed adalimumab step therapy for that indication.

Added coverage criteria for multiple new agents including Filspari (IgAN), Tarpeyo (IgAN), Rezurock (cGVHD), Niktimvo, Fabhalta, Imaavy, Ryoncil, Bimzelx, Rinvoq, Vanrafia, and others across 2023–2025 updates.

Updated Vyvgart and Vyvgart Hytrulo criteria to prohibit concurrent use with specified other agents (e.g., Rystiggo, Soliris, Ultomiris, Zilbrysq) and added other concurrent-use clarifications with newer agents such as Imaavy and eculizumab products.

Clarified site-of-service review requirements and added exceptions for CRS treatment and Alaska fully-insured members per Alaska HB 226.

Updated urine protein-to-creatinine threshold for Tarpeyo from ≥1.5 g/g to ≥0.8 g/g (or proteinuria ≥1 g/day).

Added coverage criteria for Otezla XR for Behcet's disease and updated Benlysta SC age requirement for active lupus nephritis to 5 years and older.

Added an age requirement for sarcoidosis coverage criteria for multiple adalimumab/infliximab products and added an exception to site-of-service requirements for certain CRS treatments.

Added coverage criteria for Ryoncil (remestemcel-L-rknd).

Updated Humira (adalimumab) (AbbVie) [NDCs starting with 00074] from preferred to non-preferred.

Added coverage criteria for Bimzelx (bimekizumab-bkzx) for hidradenitis suppurativa and new HCPCS code J9038.

Clarified Site of Service Medical Necessity criteria can apply to injection drugs and added site of service review for additional drugs (Saphnelo, Vyvgart, Vyvgart Hytrulo).

Added coverage criteria for multiple products including Rinvoq (giant cell arteritis), Imaavy (generalized myasthenia gravis), Vanrafia (IgAN), and others; updated many step/age/concurrency requirements.

Added and updated HCPCS/Codes (e.g., C9305, J3402, Q5156, J9256) and removed others (J0135); multiple code replacements effective Jan 1, 2026.

Updated Avsola and Inflectra non-infectious intermediate/posterior/panuveitis criteria to require trial of 1 preferred adalimumab (rather than all preferred adalimumab products).

Updated Filspari and Tarpeyo criteria to clarify UPCR >=0.5 g/g OR urine protein >=0.5 g/day per 2025 KDIGO.

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~20+drugs listed for site-of-service review

manydistinct specialty agents listed

>20new/updated drug criteria added

50 mileshome infusion distance threshold

12 monthsmaximum approval period

Coverage Criteria and Clinical Eligibility

Site of Service Medical Necessity

Site of Service (SOS) medical necessity applies to medical benefit reviews for IV/injectable drugs and to site-of-service decisions for individuals aged 13 and older.

SOS scope: SOS criteria applies only to medical benefit reviews for IV and injectable drugs and does not apply to Alaska fully-insured members (see infusion/injection drug medical necessity criteria).

[chunks 3]

Medically necessary sites: Physician's office OR Infusion center OR Home infusion; hospital-based outpatient setting is considered medically necessary for the initial course (first 90 days) or for re-initiation after ≥6 months (except when standard dosing interval between administrations is ≥6 months).90 days

[chunk 5]

Home infusion necessity: Home infusion is medically necessary when there is no outpatient infusion center within 50 miles of the individual's home AND no contracted home infusion agency will travel, or when the hospital is the only place offering the infusion/injection for that drug, or when the individual's clinical condition increases infusion risk (conditions listed below).50 miles

[chunk 6]

Clinical indications requiring hospital-based care: Known cardiac or pulmonary condition (e.g., symptomatic arrhythmia, significant respiratory disease, FVC ≤40%), unstable renal function, difficult/unstable vascular access, acute mental status/cognitive impairment impacting safety, or prior severe adverse drug reactions/anaphylaxis to related drugs; OR cytokine release syndrome (CRS) grade 3–4 as defined below.

[chunk 6]

CRS grade 3–4 criteria: CRS grade 3 or 4 evidenced by ALL of: temperature ≥38 °C; hypotension requiring one or more vasopressors; hypoxia requiring high-flow oxygen delivery (high-flow nasal cannula, face mask, non-rebreather, Venturi) OR positive pressure support (CPAP, BiPAP, intubation, or mechanical ventilation).temperature ≥38 °C

[chunk 6]

Not medically necessary trigger: Hospital-based outpatient infusion site (or other sites) is considered not medically necessary for infusion/injectable therapy when the site-of-service criteria in this policy are not met; failure to meet SOS criteria may trigger denial of coverage at that site.

[chunk 6]

Age for SOS review: Site-of-service medical necessity review for administration location applies only to individuals aged 13 years or older.age ≥13 years

[chunk 3,57]

Condition-specific therapy criteria

Examples of condition- and agent-specific medical necessity criteria. Each listed therapy is covered when ALL of the conditions in its node are met.

Hidradenitis Suppurativa — First-line TNF-α (adalimumab): Individual aged ≥12 years AND tried at least one other therapy (e.g., intralesional/oral corticosteroids, systemic antibiotics) AND medication prescribed by or in consultation with a dermatologist.age ≥12

[chunk 7]

Hidradenitis Suppurativa — IL-17 or second-line options: For adults (e.g., Cosentyx or Bimzelx) individual aged ≥18 years AND tried at least one other therapy AND prescribed by or in consultation with a dermatologist; for some second-line adalimumab biosimilars, prior inadequate response/intolerance to specified agents is required.age ≥18

[chunks 7,10,112]

IgG4-Related Disease — Uplizna (inebilizumab): Individual aged ≥18 years AND biopsy-confirmed IgG4-RD with immunostaining plus organ involvement AND meets histopathologic criteria (≥2 features) AND history of disease in ≥2 organs AND IgG4-RD flare requiring glucocorticoid treatment in last 3 months AND prescribed by or in consultation with appropriate specialist.

Uveitis Agents - First and Second Line (adalimumab and infliximab biosimilars)

Covered when the specified age and prior therapy requirements are met

Age requirement: Individual is aged 2 years or older (for first-line adalimumab use in uveitis where indicated).age ≥2 years

[chunk 19]

Prior therapies tried: Has tried periocular, intraocular, or systemic corticosteroids OR immunosuppressive therapy prior to biologic therapy for uveitis.

[chunks 19,22]

Prior biologic/biosimilar trial requirement: For pharmacy-managed adalimumab products: has had inadequate response or intolerance to listed preferred adalimumab biosimilars per agent-level sequencing; for some infliximab products managed under medical benefit, inadequate response to one preferred adalimumab product and/or prior infliximab biosimilars is required (agent-specific differences apply).agent-specific

Giant Cell Arteritis / CIDP / Vyvgart Hytrulo criteria

Covered when listed diagnostic, age and prior therapy criteria are met

Giant Cell Arteritis (IL-6 antagonists / Rinvoq): Individual aged ≥18 years AND has tried and had inadequate response to a systemic corticosteroid OR is currently taking a systemic corticosteroid; medication prescribed by or in consultation with a rheumatologist per agent labeling.age ≥18

[chunk 25]

CIDP — Vyvgart Hytrulo: Individual aged ≥18 years AND diagnosis of CIDP based on progressive/relapsing motor and/or sensory symptoms in >1 limb plus hyporeflexia/areflexia present for ≥2 months AND other causes excluded AND supportive testing provided if available AND tried and failed IV or SC immune globulin; medication prescribed per specialist and subject to site-of-service review.age ≥18

[chunks 26,27]

Fabhalta (iptacopan) for C3G

Covered when ALL criteria are met

Age and diagnosis: Individual is aged 18 years or older AND has biopsy-proven complement 3 glomerulopathy (C3G).age ≥18

[chunk 27]

Proteinuria and renal function thresholds: Documented urine protein-to-creatinine ratio (UPCR) ≥1 g/g AND estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2.UPCR ≥1 g/g; eGFR ≥30 mL/min/1.73 m2

[chunk 27]

ACEi/ARB trial or intolerance: Has tried an ACE inhibitor or ARB with persistent UPCR ≥1 g/g OR has documented intolerance to ACEi/ARB.UPCR persistence ≥1 g/g

Cytokine Release Syndrome (CRS) agents (tocilizumab, anakinra)

Covered when severe treatment-induced CRS is documented

Age: Individual aged ≥2 years for specified tocilizumab formulations (agent-specific age labeling applies).age ≥2

[chunk 29]

CRS severity documented: Documented treatment-induced grade 3 or 4 CRS evidenced by ALL of: temperature ≥38 °C; hypotension requiring one or more vasopressors; hypoxia requiring high-flow oxygen delivery or positive pressure ventilation.temperature ≥38 °C

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Diagnosis documentation: Documentation confirming the CRS diagnosis must be provided when requesting tocilizumab (Actemra) for CRS; site-of-service review applies to IV formulations.

[chunks 29,111]

Interleukin-1 agents and periodic fever/Still's disease criteria

Covered when diagnostic and specialty prescribing criteria are met

CAPS and periodic fever syndromes — Ilaris / Arcalyst / Kineret: Medication (Ilaris or Arcalyst) prescribed by or in consultation with a rheumatologist, geneticist, or dermatologist AND indication-specific age thresholds met (e.g., Ilaris for CAPS in age ≥4; Arcalyst for CAPS ≥12 where applicable).agent- and age-specific

[chunks 33,34]

NOMID — Kineret (anakinra): Diagnosis of NOMID AND Kineret prescribed by or in consultation with a rheumatologist, geneticist, or dermatologist.

[chunk 34]

Graft-versus-host disease (GVHD) and related agents

Covered when prior lines tried and specialty prescribing requirements met

Chronic GVHD — Niktimvo, Rezurock, others: Has tried and had an inadequate response or intolerance to at least two prior lines of systemic therapy AND medication is prescribed by or in consultation with an oncologist, hematologist, or transplant center physician AND weight/dose limits per agent are respected (e.g., Niktimvo ≥40 kg and 35 mg q2w; Rezurock dose limit 200 mg daily).

[chunk 34]

Pediatric steroid-refractory aGvHD — Ryoncil: Pediatric individual aged 2 months to 17 years with grade C/D skin, liver, or GI aGvHD (or grade B liver/GI) AND inadequate response to systemic corticosteroids AND prescribed by transplant specialist AND dose limit 2×10^6 MSC/kg.

[chunks 35,36]

Orencia for GVHD prevention: Individual aged ≥2 years undergoing HSCT from matched unrelated or 1-allele-mismatched unrelated donor AND will receive calcineurin inhibitor and methotrexate AND prescribed by transplant specialist.age ≥2

NMOSD and Myasthenia Gravis agents

Covered when antibody status, relapse history, disability scores, and prior therapy requirements are met

Uplizna (inebilizumab) — NMOSD: Adult individual AQP4-IgG positive AND at least one core clinical characteristic for NMOSD AND exclusion of alternative diagnoses AND history of ≥1 relapse in last 12 months or ≥2 relapses in last 24 months AND EDSS ≤7.5 AND prescribed by appropriate specialist.EDSS ≤7.5

[chunk 31]

Enspryng (satralizumab) — NMOSD: Adult individual AQP4-IgG positive AND similar relapse history criteria AND EDSS ≤6.5 as specified for Enspryng trials AND prescribed by appropriate specialist.EDSS ≤6.5

[chunk 32]

Imaavy (nipocalimab) — generalized myasthenia gravis: Individual aged ≥12 years AND diagnosis of generalized myasthenia gravis with positive AChR or MuSK serology AND current use or trial of pyridostigmine (or intolerance/contraindication) AND current use of two or more immunosuppressive therapies (or prior inadequate response/intolerance to two ISTs) AND for AChR-positive disease has tried and had inadequate response or intolerance to at least one listed targeted biologic (e.g., eculizumab, ravulizumab, Vyvgart products) AND medication is not used concurrently with specified complement or other listed agents AND prescribed by specified specialist.

Myasthenia gravis agent criteria (partial)

Covered when ALL of the following are met for specified myasthenia gravis agents

Age: Minimum age requirement varies by agent (examples: ≥12 years for some agents; ≥18 years for others).agent-specific

[chunks 36,38,42]

Diagnosis of generalized myasthenia gravis with serologic confirmation (anti-AChR or anti-MuSK antibodies as applicable).positive serologic test

[chunks 36,38]

Acetylcholinesterase inhibitor trial: Current use of pyridostigmine OR trial with inadequate response/intolerance/contraindication to pyridostigmine documented.

[chunks 36,38,39]

IgA nephropathy agent criteria (partial)

Covered when ALL of the following are met for specified IgAN agents

Age: Individual is aged 18 years or older.≥18 years

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Diagnosis: Documented biopsy-proven primary immunoglobulin A nephropathy (IgAN).biopsy-proven

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Proteinuria threshold (agent-specific): Documented UPCR or urine protein meeting agent-specific thresholds: Fabhalta/Vanrafia ≥1.5 g/g (some historical criteria) OR Filspari/Tarpeyo ≥0.5 g/g (policy-aligned thresholds) OR Voyxact ≥0.75 g/g — apply agent-specific numeric criteria per product section.agent-specific UPCR

Sarcoidosis TNF-α antagonist criteria (partial)

Covered when ALL of the following are met for TNF-α antagonist therapy for sarcoidosis

Age: Individual is aged 18 years or older.≥18 years

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Prior corticosteroid trial: Has tried and had an inadequate response or intolerance to one corticosteroid.

[chunks 46-50]

Prior immunosuppressive trial: Has tried and had an inadequate response or intolerance to one immunosuppressive medication (examples: methotrexate, azathioprine, mycophenolate, cyclosporine, leflunomide, chlorambucil, cyclophosphamide, thalidomide, or chloroquine).

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Benefit assignment and site-of-service criteria

Coverage and benefit assignment when ALL of the following apply

Benefit assignment: Specific agents are assigned to the pharmacy, medical, or both benefits as listed (examples: Cosentyx, Fabhalta, Filspari, Lupkynis, Otezla, Rezurock, Rinvoq, Tarpeyo, Vanrafia managed through pharmacy; many TNF‑α, IL‑6, and myasthenia agents managed through medical benefit).

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Site-of-service age requirement: For site-of-service medical necessity review the individual must be aged 13 years or older.age ≥13 years

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Trial-based coverage candidate criteria

Trial-defined populations and endpoints that may inform coverage decisions (informational — presented in 'Covered when ALL of the following are met' style where applicable):

threshold":"SELENA‑SLEDAI ≥6 (pediatric)","note":"[chunks 72,75]","children":[]}

Anifrolumab (Saphnelo) trial-based elements: Adults 18–70 with SLEDAI‑2K ≥6 (excluding fever/headache), clinical SLEDAI‑2K ≥4, BILAG organ activity and PGA ≥1, stable on ≥1 SLE treatment; severe lupus nephritis and neuropsychiatric lupus were excluded in trials.SLEDAI‑2K ≥6; clinical SLEDAI‑2K ≥4

[chunks 78,79,81]

gMG biologics (trial-based elements): Trials required MGFA class II–IV, MG‑ADL thresholds (e.g., ≥5), QMG thresholds where specified, and stable background immunosuppression; primary endpoints used MG‑ADL responder definitions (e.g., ≥2‑point reduction sustained 4 weeks for Vyvgart).MG‑ADL ≥5; responder = ≥2‑point reduction sustained 4 weeks

[chunks 89,90,91]

Trial-based coverage considerations / indication-specific eligibility (informational)

Informational trial-based eligibility elements and endpoints for selected agents (policy criteria generally mirror these trial populations):

Vyvgart — ADAPT trial elements: Adults (≥18) with class II–IV gMG; baseline MG‑ADL ≥5 (>50% non‑ocular); on stable dose of ≥1 gMG treatment; primary efficacy in AChR‑Ab positive population with MG‑ADL responder = ≥2‑point reduction sustained ≥4 weeks.MG‑ADL ≥5; responder ≥2‑point reduction

[chunks 90,91]

Vyvgart Hytrulo — bridging study: SC formulation compared to IV Vyvgart with weekly dosing for 4 weeks; primary endpoint mean IgG reduction (~66.6% SC vs ~62.2% IV); SC associated with higher injection site reactions.mean IgG reduction ~66%

[chunk 92]

Rystiggo — MycarinG trial elements: Adults anti‑AChR or anti‑MuSK Ab+; dosing SC weekly for 6 weeks; primary efficacy MG‑ADL reduction at Day 43 (−3.4 vs −0.8); safety profile includes headache, infections, diarrhea, pyrexia, hypersensitivity, nausea.

Selected Updated Coverage Criteria

Selected updated coverage criteria added or revised for multiple agents — highlights below (apply agent-specific criteria in product sections).

Arcalyst (rilonacept) added indications: Arcalyst added for FDA‑approved indications including CAPS, maintenance of remission of DIRA, and recurrent pericarditis; prescribing specialist requirements apply.

[chunk 108,33]

Ilaris prescriber requirement: Ilaris (canakinumab) criteria revised to require prescribing by or in consultation with a rheumatologist, geneticist, or dermatologist for CAPS management.

[chunk 108,33]

Vyvgart concurrency prohibition: Vyvgart and Vyvgart Hytrulo criteria updated to prohibit concurrent use with each other and with specified complement inhibitors or other listed agents (e.g., Rystiggo, Soliris, Ultomiris, Zilbrysq), with later updates also prohibiting concurrent use with Imaavy and eculizumab products.

[chunks 112,116,142]

Selected drug coverage updates

Selected coverage updates and additions reflected in policy history (high‑level):

Filspari added for IgAN: Coverage criteria were added for Filspari (sparsentan) for adults with primary IgAN at risk of rapid progression; criteria reference maximized RAS inhibitor therapy and UPCR thresholds per product labeling and PROTECT trial context.per prescribing information

[chunk 137,101]

Tarpeyo UPCR change in history: History records update of Tarpeyo UPCR requirement to ≥0.8 g/g or proteinuria ≥1 g/day for coverage eligibility.UPCR ≥0.8 g/g or proteinuria ≥1 g/day

[chunk 142,103]

Vyvgart concurrency and CIDP updates: History documents updated Vyvgart and Vyvgart Hytrulo criteria to prohibit concurrent use with certain complement inhibitors and other agents; Hytrulo also updated for CIDP in selected individuals.

Amended coverage criteria highlights

Selected amended coverage criteria highlights reflected in policy history:

Sarcoidosis age requirement amendment: An age requirement was added to sarcoidosis coverage criteria for multiple adalimumab and infliximab products (policy history notes reflect addition of age-based limits).age requirement per product

[chunk 144]

Uveitis infliximab/adalimumab sequencing change: For uveitis treatment with certain infliximab products (Avsola, Inflectra, Remicade, Renflexis, Janssen infliximab), new starts must have tried one preferred adalimumab product (policy changed from requiring trial of all preferred adalimumab products to trial of one preferred product).trial of 1 preferred adalimumab

[chunk 150]

Filspari/Tarpeyo proteinuria KDIGO alignment: Policy history documents alignment of Filspari and Tarpeyo proteinuria thresholds to UPCR ≥0.5 g/g OR urine protein ≥0.5 g/day per 2025 KDIGO guidance in certain updates (see product sections for final numeric thresholds used in criteria).

Site-of-Service (SOS) Medical Necessity criteria applies only to medical-benefit reviews of IV and injectable agents and does NOT apply to Alaska fully‑insured members; those members follow the infusion/injection drug Medical Necessity criteria per Alaska HB 226. For individuals aged 13 years and older the policy also requires review of the site where a drug is administered (hospital‑based outpatient, infusion center, physician office, or home). When the SOS criteria in this policy are not met, hospital‑based outpatient infusion sites are considered not medically necessary for the service and may trigger a denial of coverage for that site.

Fabhalta (iptacopan) coverage for biopsy‑proven complement 3 glomerulopathy (C3G) excludes individuals with rapidly progressive crescentic glomerulonephritis. Rapidly progressive crescentic GN is defined in the policy as a ≥50% decline in eGFR within 3 months with crescents present in ≥50% of glomeruli, or a renal biopsy showing >50% interstitial fibrosis/tubular atrophy; such findings preclude Fabhalta eligibility.

Imaavy (nipocalimab) and certain other myasthenia gravis biologics include concurrency restrictions. The policy specifies that these agents must not be used concurrently with listed complement inhibitors or other named agents (examples include eculizumab, ravulizumab/Ultomiris, efgartigimod products, rozanolixizumab/Rystiggo, inebilizumab/Uplizna, and zilucoplan); updates in the history also add Ultomiris to the concurrency list.

Use of agents in combinations or for conditions not described in this policy (or in the referenced policies) is considered investigational. The policy explicitly states that when the named agents are used together or for indications outside those outlined here, those uses are investigational and may be denied.

Site‑of‑service review for medical necessity is limited to individuals aged 13 years and older. The policy explains that pediatric patients under 13 are excluded from SOS review because of unique physiologic and care needs that require specialty pediatric infusion resources; requests for SOS determinations for children under 13 may therefore be limited or denied under this policy.

The randomized trials that support belimumab did not evaluate individuals with severe renal or severe central nervous system (neuropsychiatric) lupus; the policy notes these populations were excluded from key trials. As a result, severe lupus nephritis and neuropsychiatric lupus were not evaluated and may not be supported by the trial evidence cited for belimumab.

In the PROTECT study of sparsentan (Filspari) use of SGLT2 inhibitors was prohibited during trial conduct; therefore the trial population excluded patients receiving SGLT2 inhibitors. The policy highlights this restriction when interpreting trial results and concomitant‑therapy considerations.

The policy’s adalimumab medical‑necessity language was updated to require prior trial and failure with preferred adalimumab products for some new starts; however, those criteria do not apply to members in one Open formulary (Formulary ID: 6062; Rx Plan F1) and one Incentive formulary (Formulary ID: 6064; Rx Plan G3) — members with those plans follow policy 5.01.647. The history notes also describe movement of adalimumab products between preferred and non‑preferred tiers and associated step therapy changes.

A previously referenced Preferred formulary entry (Formulary ID: 6064; Rx Plan G3) was removed from the policy because it is no longer available; the history documents that reference removal.

Per the policy history and Alaska statutory guidance, the Site‑of‑Service Medical Necessity criteria does not apply to Alaska fully‑insured members in accordance with Alaska HB 226; those members follow the infusion/injection drug Medical Necessity criteria instead.

The Avsola and Inflectra uveitis criteria include an exception for one Open formulary plan (Formulary ID: 6062; Rx Plan F1) — the policy explicitly states that the non‑infectious intermediate/posterior/panuveitis criteria for these agents do not apply to that custom Open formulary, and members with that plan follow criteria in policy 5.01.647.

Hospital‑based outpatient infusion is considered medically necessary for an initial course (or re‑initiation after an interval) when the policy’s site‑of‑service criteria are met; specifically, hospital‑based outpatient settings may be medically necessary for the initial 90 days of therapy or for re‑initiation after ≥6 months, consistent with the policy’s site‑of‑service rules.

Belimumab subgroup analyses showed variable efficacy across populations; the pivotal Phase III trials demonstrated more consistent benefit in some demographic groups and limited or no demonstrated efficacy in certain subgroups (for example, reduced efficacy signals in African American participants in some analyses). These subgroup observations are noted as limitations when applying trial evidence to individual cases.

Anifrolumab (Saphnelo) produced mixed trial results: the TULIP‑1 trial did not meet the primary SRI‑4 endpoint (no significant benefit at 52 weeks for the primary SRI‑4 outcome), while other analyses (for example TULIP‑2 BICLA endpoint) showed benefit. The policy highlights that TULIP‑1 failure to meet SRI‑4 limits interpretation of primary endpoint efficacy for that study.

Filspari (sparsentan) is subject to a REMS program for safety monitoring; the policy notes REMS restrictions and indicates that dosing or use outside labeled populations or REMS requirements is not supported by the policy language.

For some infliximab products, new‑start coverage requires documentation of prior inadequate response or intolerance to preferred products or specified infliximab biosimilars. The policy updates and history clarify these prior‑response requirements as part of step therapy for certain infliximab formulations.

The content of these coverage criteria sections is primarily administrative and coding‑focused; the policy does not add explicit blanket 'not medically necessary' statements beyond site‑of‑service triggers and trial‑based exclusions, and many updates relate to coding and product placement rather than categorical non‑coverage language.

Administrative notes in the history document multiple interim updates to coverage criteria, HCPCS code additions and replacements, and formulary status changes; these entries are administrative in nature and do not themselves state additional not‑medically‑necessary determinations beyond the policy’s existing exclusions and site‑of‑service rules.

Billing Codes, Thresholds, and Key Clinical Metrics

Drugs subject to site-of-service reviewmixed

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

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Listed specialty agentsmixed

Hadlima (adalimumab-bwwd)	Hadlima subcutaneous adalimumab biosimilar
Hulio (adalimumab-fkjp)	Hulio subcutaneous adalimumab biosimilar
Humira (adalimumab)	Humira subcutaneous adalimumab
Hyrimoz (adalimumab-adaz)	Hyrimoz subcutaneous adalimumab biosimilar
Yusimry (adalimumab-aqvh)	Yusimry subcutaneous adalimumab biosimilar
Avsola (infliximab-axxq)	Avsola intravenous infliximab
Inflectra (infliximab-dyyb)	Inflectra intravenous infliximab biosimilar
Renflexis (infliximab-abda)	Renflexis intravenous infliximab biosimilar
Actemra (tocilizumab)	Tocilizumab IV/SC IL‑6 antagonist
Avtozma (tocilizumab-anoh)	Tocilizumab IV/SC biosimilar

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Covered HCPCS/J codes listed in this segmentHCPCSCovered

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), 25 mg
J1745	Injection, infliximab, excludes biosimilar, 10 mg
J1823	Injection, inebilizumab-cdon (Uplizna), 1 mg
J2793	Injection, rilonacept (Arcalyst), 1 mg

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Medical Benefit HCPCS/J Codes (selected)HCPCS

C9305	Injection, nipocalimab-aahu (Imaavy), 3 mg (code termed 01/01/26)
J0129	Injection, abatacept (Orencia), 10 mg (use when physician-administered)
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), 25 mg
J1745	Injection, infliximab (excludes biosimilar Remicade), 10 mg
J1823	Injection, inebilizumab-cdon (Uplizna), 1 mg
J2793	Injection, rilonacept (Arcalyst), 1 mg

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Biosimilar and additional HCPCS/Q CodesHCPCS | Q-codes

J9038	Injection, axatilimab-csfr (Niktimvo), 0.1 mg
J9256	Injection, nipocalimab-aahu, 3 mg (new code effective 01/01/26)
J9332	Injection, efgartigimod alfa-fcab (Vyvgart), 2 mg
J9333	Injection, rozanolixizumab-noli (Rystiggo), 1 mg
J9334	Injection, efgartigimod alfa and hyaluronidase (Vyvgart Hytrulo), 2 mg
Q5103	Injection, infliximab-dyyb (Inflectra), 10 mg
Q5104	Injection, infliximab-abda (Renflexis), 10 mg
Q5121	Injection, infliximab-axxq (Avsola), 10 mg
Q5133	Injection, tocilizumab-bavi (Tofidence), 1 mg
Q5135	Injection, tocilizumab-aazg (Tyenne), 1 mg

1–10 of 17

1/2

HCPCS/Coding updates and unclassified codesHCPCS

Q5102	HCPCS code noted as terminated 4/1/18 (historical)
Q5103	HCPCS code added effective 4/1/18 (historical)
Q5104	HCPCS code added effective 4/1/18 (historical)
Q5109	HCPCS code added effective 1/1/19 (historical)
Q5121	HCPCS code added (historical)
J3590	Unclassified HCPCS code used for multiple drug names/biosimilars
J0638	HCPCS code added (historical)
J1823	HCPCS code added (historical)
Q5135	HCPCS code added effective 10/1/2024
J9334	Coding update referenced

1–10 of 19

1/2

HCPCS updates and additionsHCPCS

C9305	new HCPCS code added (temporary/replaced later)
J3402	new HCPCS code added
Q5156	HCPCS code added
J9256	HCPCS code added to replace C9305 effective Jan 1, 2026
J9038	new HCPCS code added for Bimzelx
J0135	deleted HCPCS code removed from policy

Home infusion distance threshold — when home infusion considered (miles)

Home infusion distance thresholdHome infusion is considered medically necessary when there is no outpatient infusion center within 50 miles of the member's home and no contracted home infusion agency will travel

Alternate conditions when home infusion consideredWhen a hospital is the only place that offers the infusion or injection of the drug

Documentation contextApplies to site-of-service determinations for individuals aged 13 and older under SOS Medical Necessity

Hospital-based outpatient medically necessary period for initial course — 90 days

Provider Action Items, Prior Authorization, and Documentation

Step Therapy

Provider action: Prior therapy trials required

Prior therapy trials are required for many agents listed in this policy. Document prior use, dates, and reason for discontinuation (inadequate response or intolerance). Common step/ prior-therapy requirements include trials of corticosteroids, immunosuppressants (e.g., azathioprine, mycophenolate, methotrexate, cyclosporine), ACE inhibitor/ARB optimization for IgAN/IgAN-related agents, and specified preferred adalimumab/infliximab products before non-preferred options. For gMG and SLE biologics, document stability of background therapy and prior biologic or complement inhibitor trials as specified in the drug-specific criteria.

Include trial dates and outcomes (response, intolerance)
For sparsentan (Filspari) and Fabhalta, document maximal tolerated ACE inhibitor or ARB trial per criteria
For adalimumab/infliximab: new starts require trial and inadequate response or intolerance to preferred adalimumab products; infliximab products often require trial of preferred infliximab biosimilars before non-preferred products

Clinical Background and Trial Evidence

Autoimmune disorders encompass conditions in which the immune system targets host tissues, producing chronic inflammation and organ‑specific injury. This policy addresses medical‑necessity criteria for IV and injectable biologic and specialty agents across a range of autoimmune diseases (for example, hidradenitis suppurativa, systemic lupus erythematosus, IgA nephropathy, uveitis, myasthenia gravis, and graft‑versus‑host disease), and includes site‑of‑service review for individuals aged 13 years and older. The policy summarises agent‑specific eligibility, prior‑therapy and diagnostic documentation requirements, site‑of‑service rules, and related coding and benefit assignment details applicable to Premera members (excluding the Alaska fully‑insured statutory exception for SOS criteria).

Definitions and Diagnostic Criteria

Site of service definition — location where drug administered

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

Age applicabilitySite-of-service review applies to individuals aged 13 years and older

Benefit scopeSOS Medical Necessity criteria applies only to medical benefit reviews (not to Alaska fully-insured members)

CRS grade 3-4 clinical features — temperature, hypotension, hypoxia thresholds

CRS grade 3–4 clinical featuresTemperature ≥ 38 °C; hypotension requiring one or more vasopressors; hypoxia requiring high‑flow oxygen or positive pressure ventilation

CRS coverage context

Policy Revision History and Effective Dates

2023-08-01addition

Added coverage criteria for Filspari (sparsentan) for proteinuria in adults with primary IgA nephropathy and added Vyvgart Hytrulo for gMG; multiple adalimumab biosimilars added with coverage designations.

2024-01-03coding/coverage_movement

Avsola moved to preferred (1st line) and Inflectra moved to second-line with product sequencing changes effective Jan 1, 2024; multiple adalimumab product status updates implemented.

2025-01-03policy_clarification

Site-of-Service Medical Necessity criteria clarified to not apply to Alaska fully-insured members per Alaska HB 226; Tarpeyo UPCR threshold changed to ≥0.8 g/g and other CRS/site-of-service clarifications made.

Policy Summary

PayerPremera Bluecross

PolicyAutoimmune disorders — infusion/injection drugs and site-of-service medical necessity

Policy CodePolicy 5.01.39

Change TypeMultiple additions and revisions (coverage criteria, step therapy, site-of-service and coding updates)

Effective DateApr. 1, 2026

Next Review DateN/A

Key ActionSubmit prior authorization with documentation of diagnosis, prior therapies and relevant severity measures (e.g., MG‑ADL, UPCR, SELENA‑SLEDAI) to support medical necessity.

SourceLink

On This Page

Systemic Lupus Erythematosus — Benlysta: Individual aged ≥5 years AND diagnosis of SLE by ACR/EULAR or SLICC criteria AND used as add-on therapy following standard induction therapy (e.g., mycophenolate, cyclophosphamide, azathioprine or other immunosuppressant plus corticosteroid) AND not used concurrently with specified agents (e.g., anifrolumab, obinutuzumab) AND prescribed by appropriate specialist.age ≥5

[chunk 12]

Saphnelo (anifrolumab) — SLE: Individual aged ≥18 years AND diagnosis of moderate to severe SLE by ACR/EULAR or SLICC criteria AND used as add-on therapy following standard induction AND does not have severe active CNS lupus or severe active lupus nephritis AND not used concurrently with excluded agents.age ≥18

[chunk 14]

Pyoderma Gangrenosum — TNF-α agents: Individual aged ≥18 years AND failed one standard non-biologic therapy AND medication prescribed by or in consultation with a dermatologist; certain infliximab/infliximab-biosimilar sequencing and prior trial requirements apply for specific products.age ≥18

[chunks 15,16]

Prescribing specialist: Medication is prescribed by or in consultation with an ophthalmologist (or other specified specialist per agent and indication).

[chunk 19]

Exclusions: Does NOT have rapidly progressive crescentic glomerulonephritis (defined as ≥50% eGFR decline in 3 months with crescents in ≥50% glomeruli) AND renal biopsy does not show IF/TA >50%.

[chunk 27]

Prescriber specialty: Medication prescribed by or in consultation with a nephrologist.

[chunks 27,44]

Immunosuppressive therapy trials: Current use of two or more immunosuppressive therapies OR prior inadequate response/intolerance to two ISTs OR contraindications to two ISTs documented.

[chunks 36,38,39,41]

Prior targeted biologic trial (AChR-positive): Has tried and had inadequate response or intolerance to at least one listed targeted biologic for AChR-positive disease (e.g., eculizumab, ravulizumab, efgartigimod products, rozanolixizumab).

[chunks 36-39]

No concurrent prohibited therapies: Medication is not being used concurrently with listed complement inhibitors or other named agents (e.g., eculizumab products, ravulizumab, efgartigimod products, rozanolixizumab, inebilizumab, zilucoplan) per product-specific concurrency restrictions.

[chunks 37,39,41]

Prescriber: Prescribed by or in consultation with the specified specialist(s) per agent criteria (e.g., neurologist, neuromuscular specialist).

[chunk 36]

[chunks 43-46,44,45]

ACEi/ARB trial: Has tried a maximally tolerated ACE inhibitor or ARB with persistent UPCR above the agent-specific threshold OR has documented intolerance to ACEi/ARB.agent-specific UPCR persistence

[chunks 44,116,146]

Prior agent sequencing: Has tried and had inadequate response or intolerance to other listed IgAN agents when specified (e.g., Fabhalta requires prior Filspari or Tarpeyo trial per product-specific sequencing).

[chunk 43,44]

Prescriber: Medication prescribed by or in consultation with a nephrologist.

[chunks 44-46]

Dose_limit_Fabhalta: Fabhalta dose limited to 400 mg per day.400 mg/day

[chunk 44]

Dose_limit_Tarpeyo: Tarpeyo dose limited to 16 mg daily.16 mg/day

[chunk 45]

Duration_limit_Vanrafia: Total duration of Vanrafia therapy limited to 9 months.9 months

[chunk 45]

Additional prior biologic requirements (second-line):

For some second-line approvals, member must have had inadequate response/intolerance to specified adalimumab products (agent-specific sequencing applies).

Prescriber: Medication prescribed by or in consultation with a pulmonologist, ophthalmologist, or dermatologist as specified by presentation and agent.

[chunks 47-50]

Site-of-service review: Certain infliximab and infliximab-biosimilar agents are subject to site-of-service review per medical benefit assignment and SOS criteria.

[chunks 47,50]

6‑week treatment period

Orencia — aGVHD prophylaxis trial elements: Used with calcineurin inhibitor and methotrexate in HSCT recipients; dosing schema per trials and populations ≥6 years in GVHD‑1; demonstrated improvements in aGVHD‑free survival and overall survival in trial cohorts.trial dosing schema

[chunk 95]

Filspari (sparsentan) — PROTECT trial elements: Adults with persistent proteinuria >1.0 g/day despite maximized RAS inhibitor; primary endpoint UPCR change at 36 weeks; trial prohibited SGLT2 inhibitors and showed 49.8% mean proteinuria reduction with sparsentan vs 15.1% with irbesartan.UPCR >1.0 g/day

[chunk 101]

Tarpeyo (budesonide) — NefIgArd elements: Adults with biopsy‑verified IgAN, eGFR ≥35, proteinuria ≥1 g/day or UPCR ≥0.8 on stable maximally tolerated RAS inhibitor; primary endpoint % reduction in UPCR at 9 months (34% Tarpeyo vs 5% placebo in Part A).eGFR ≥35; UPCR ≥0.8 or proteinuria ≥1 g/day

[chunk 103]

Vanrafia (atrasentan) — ALIGN trial elements: Adults with biopsy‑proven IgAN, eGFR ≥30, urine protein ≥1 g/day on stable RASi; interim analysis showed significant UPCR reduction vs placebo; class effects include fluid retention and hepatotoxicity risk.eGFR ≥30; urine protein ≥1 g/day

[chunk 104]

Voyxact (sibeprenlimab) — VISIONARY interim elements: Biopsy‑confirmed IgAN, uPCR ≥0.75 g/g or urine protein ≥1.0 g/day, eGFR ≥30, stable supportive therapy (ACEi/ARB ± SGLT2) ≥3 months; interim 9‑month proteinuria reduction ~51% vs placebo.uPCR ≥0.75 g/g or urine protein ≥1.0 g/day; eGFR ≥30

[chunk 105]

Tarpeyo UPCR update: Tarpeyo eligibility updated: urine protein‑to‑creatinine ratio requirement changed to ≥0.8 g/g OR proteinuria ≥1 g/day for adults with primary IgAN on stable RAS inhibitor therapy.UPCR ≥0.8 g/g or proteinuria ≥1 g/day

Cosentyx HS coverage: Added coverage for Cosentyx (secukinumab) for adults with moderate to severe hidradenitis suppurativa and removed prior adalimumab step therapy requirement for that indication.

[chunks 7,112]

Benlysta age update: Benlysta SC age requirement for active lupus nephritis updated from 18 years to 5 years and older per 2026 update.age ≥5

[chunks 12,122]

[chunks 137,142,146]

UPCR ≥0.5 g/g OR urine protein ≥0.5 g/day

Product concurrency restrictions amended: Multiple therapies (e.g., Imaavy, Rystiggo, Vyvgart products) updated to prohibit concurrent use with specified complement inhibitors or other listed products; see individual product criteria for exact concurrency exclusions.concurrency restrictions per product

[chunks 146,150]

Hospital-based outpatient medically necessary period

Hospital-based outpatient setting is considered medically necessary for the initial course of infusion/injection for the first 90 days

Re-initiation ruleAlso medically necessary for re-initiation of an agent after 6 months or longer following discontinuation (unless standard dosing interval ≥6 months)

Applicable sitesIncludes outpatient hospital IV infusion department and hospital-based outpatient clinical level of care

UPCR threshold (example)

UPCR example threshold (C3G/Fabhalta)>= 1 g/g (Fabhalta for biopsy-proven C3G)

UPCR example threshold (Filspari)>= 0.5 g/g OR urine protein >= 0.5 g/day (Filspari eligibility per KDIGO alignment)

UPCR example threshold (Tarpeyo initial)>= 0.75 g/g or >=1.0 g/day for some IgAN agents (policy varies by agent)

eGFR threshold (example)

eGFR threshold (C3G)>= 30 mL/min/1.73 m2 (Fabhalta C3G requirement)

eGFR threshold (IgAN - Vanrafia)>= 30 mL/min/1.73 m2 for some IgAN agents (Vanrafia trials/criteria)

eGFR threshold (Tarpeyo)>= 35 mL/min/1.73 m2 noted in Tarpeyo trial context (policy references)

CRS temperature threshold

CRS temperature thresholdTemperature at least 38 °C is required as part of grade 3–4 CRS criteria

CRS physiologic criteriaGrade 3–4 CRS also requires hypotension needing vasopressors and hypoxia requiring high‑flow oxygen or positive pressure ventilation

Age applicability for tocilizumabTocilizumab formulations may be considered for individuals aged 2 years or older for CRS

EDSS threshold for NMOSD (Enspryng)

EDSS threshold for Enspryng (NMOSD)Enspryng eligibility includes Expanded Disability Status Scale (EDSS) score ≤ 6.5

PopulationApplies to adult individuals who are AQP4-IgG positive with qualifying core clinical characteristics and relapse history

Prescriber noteRequires exclusion of alternative diagnoses and specialist management

EDSS threshold for Uplizna

EDSS threshold for Uplizna (NMOSD)Uplizna eligibility includes Expanded Disability Status Scale (EDSS) score ≤ 7.5

PopulationApplies to adult individuals who are AQP4-IgG positive with qualifying core clinical characteristics and relapse history

Relapse requirementHistory of ≥1 relapse in last 12 months or 2 relapses in last 24 months required

Urine protein-to-creatinine ratio (agent-specific thresholds)

Agent-specific UPCR thresholds (selected)Fabhalta/Vanrafia: ≥1.5 g/g (Fabhalta for IgAN per some criteria); Filspari/Tarpeyo: ≥0.5 g/g OR urine protein ≥0.5 g/day (KDIGO alignment); Voyxact/other agents: ≥0.75 g/g or urine protein ≥1.0 g/day depending on agent

Tarpeyo updated thresholdTarpeyo criteria updated to ≥0.8 g/g or proteinuria ≥1 g/day (policy history)

Agent prescriber requirementAll IgAN agents require biopsy-proven diagnosis and nephrologist prescribing/consultation

IBMTR Severity Index components (GVHD staging table reference)

IBMTR Severity Index — skin stagingStage definitions for skin involvement range from <25% rash (Stage A/1) to bullae (Stage D/4)

IBMTR Severity Index — liver (bilirubin)Liver involvement staging uses total bilirubin ranges (e.g., <34 µmol/L for Stage A/0 up to >255 µmol/L for Stage D/4)

IBMTR Severity Index — GI/diarrhea volumeGI involvement staged by diarrhea volume (e.g., <500 mL/day for Stage A/0; >1500 mL/day for Stage C/3)

Disease activity score thresholds (SELENA-SLEDAI, SLEDAI-2K, MG-ADL etc.)

SELENA‑SLEDAI threshold (pediatric Benlysta)SELENA‑SLEDAI ≥6 required for pediatric Benlysta Trial 4 enrollment

SLEDAI‑2K threshold (anifrolumab)SLEDAI‑2K ≥6 (excluding fever/headache) and clinical SLEDAI‑2K ≥4 required in anifrolumab trials

MG‑ADL thresholds (gMG trials)MG‑ADL ≥5 at baseline used in Vyvgart ADAPT; Uplizna trials used MG‑ADL 6–10 or ≥11 depending on criteria

Tarpeyo UPCR updated threshold

Tarpeyo UPCR updated thresholdTarpeyo urine protein-to-creatinine ratio requirement updated to ≥ 0.8 g/g or proteinuria ≥ 1 g/day

Context of changeChange documented in 2025 update and policy history reflecting revised Tarpeyo criteria

Documentation requirementAuthorization documentation must reflect UPCR ≥0.8 g/g or proteinuria ≥1 g/day for Tarpeyo

Tarpeyo UPCR change note (from previous threshold)

Tarpeyo UPCR change noteTarpeyo UPCR requirement changed from ≥1.5 g/g to ≥0.8 g/g or proteinuria ≥1 g/day per 2025 update and policy history

Reason/referenceChange noted in 2025 Update and History entries aligning with updated evidence and KDIGO guidance

ImplicationAuthorizations after the change require documentation meeting the new lower UPCR threshold

Proteinuria threshold (KDIGO alignment)

Proteinuria threshold aligned to KDIGOUPCR >= 0.5 g/g OR urine protein >= 0.5 g/day specified for Filspari and Tarpeyo per 2025 KDIGO alignment

Policy applicationApplies when assessing eligibility for Filspari and Tarpeyo in adults with IgAN

Documentation noteAuthorization requests should document UPCR or 24‑hour urine protein consistent with the threshold

Billing Rule

Provider action: Code-based benefit assignment and authorization

Many biologic and infusion agents are assigned to medical benefit and require prior authorization with the correct HCPCS/J‑codes or J‑codes. Verify benefit assignment (medical vs pharmacy) before submission and include the appropriate code on the prior authorization request to avoid processing delays.

Refer to policy coding list when submitting: J0129, J0139, J0490, J0491, J0638, J1438, J1745, J1823, J2793, J3262, J3402, J3590, J9038, J9256, J9332–J9334, Q5103–Q5156, C9305 (replaced by J9256) (see Coding section)
Confirm whether the vial/prefilled syringe is managed under medical or pharmacy benefit (policy lists products per benefit)

Prior Authorization

Provider action: Benlysta (pediatric) authorization criteria

For pediatric Benlysta (belimumab) IV use, include documentation demonstrating active SLE with SELENA‑SLEDAI ≥6, positive autoantibodies, and that the patient is on a stable standard-of-care SLE regimen. Provide baseline disease activity details and prior/concomitant steroid dosing.

Record SELENA‑SLEDAI score and antibody status at screening
Document stability of background SLE therapy and any steroid-sparing effect observed

Prior Authorization

Provider action: Anifrolumab (Saphnelo) authorization criteria

For anifrolumab (Saphnelo), include baseline SLEDAI‑2K (≥6 excluding fever/headache/organic brain syndrome), BILAG organ activity (≥1 A or ≥2 B items) documentation, and confirmation the individual is on stable SLE therapy. Note exclusions (severe lupus nephritis, neuropsychiatric lupus) per trial populations.

Provide SLEDAI‑2K score with component detail and BILAG organ domain scores
State concurrent SLE medications and stability period

Prior Authorization

Provider action: gMG biologics authorization criteria

Authorization for generalized myasthenia gravis (gMG) biologics requires objective baseline disease severity and prior therapy documentation. For AChR‑positive patients, report MG‑ADL, QMG, and MGFA class as applicable, confirm prior use and response to pyridostigmine and multiple immunosuppressive therapies, and document stability of background therapy.

Include MG‑ADL and QMG scores, MGFA classification, and dates/response to pyridostigmine and ISTs
For Vyvgart: document MG‑ADL responder definition and cycle dosing schedule (10 mg/kg IV: 4 weekly infusions per cycle; repeat as needed no sooner than 8 weeks)
State any concurrent biologic/complement therapy exclusions (e.g., eculizumab products, Imaavy) per agent-specific rules

Prior Authorization

Provider action: Prior authorization and site-of-service review requirements

Site‑of‑service (SOS) medical necessity review applies to many IV/injectable medical‑benefit drugs for individuals aged 13 and older. Prior authorization must include justification for the requested administration site per SOS criteria. SOS does not apply to Alaska fully‑insured members (Alaska HB 226).

For SOS review (age ≥13): document lack of outpatient infusion center within 50 miles or lack of contracted home infusion, or clinical condition increasing infusion risk (e.g., significant cardiac/pulmonary disease, unstable renal function, difficult vascular access, severe prior anaphylaxis)
Exception: individuals under 13 — SOS review is limited (pediatric exclusion)
Alaska fully‑insured members: SOS criteria do not apply; follow infusion drug medical necessity criteria only

Denial Risk

Provider action: SOS denial trigger

If SOS criteria are not met, the requested hospital‑based outpatient or infusion site may be considered not medically necessary and could lead to denial. Include clear documentation supporting the clinical need for the requested site to mitigate denial risk.

Attach objective evidence: distance to nearest infusion center, attempts to arrange home infusion, and specific clinical risk factors supporting higher‑acuity site
For CRS cases meeting the exception, document grade 3–4 CRS and planned inpatient admission as required

Note

Provider action: Age-based site-of-service restriction

The policy limits site‑of‑service review to individuals aged 13 years and older. For pediatric patients younger than 13, SOS medical necessity review is not applied; however, ensure pediatric safety and specialty infusion training are documented when seeking higher‑acuity administration.

For pediatric infusions, document clinician specialty, infusion nurse expertise, and rationale if seeking non‑standard site

Denial Risk

Provider action: Trial exclusions may limit covered indications

Trial exclusions and clinical trial population differences may limit coverage for certain indications (e.g., severe lupus nephritis, neuropsychiatric lupus were excluded in Saphnelo trials). Off‑label requests may be considered only with substantial supporting evidence and rationale.

Provide literature rationale and individual risk/benefit when requesting investigational or off‑label use
Note that combinations or uses not outlined in this policy are considered investigational and may be denied

Note

Provider action: Use of SGLT2 inhibitors was prohibited

In the PROTECT trial for sparsentan (Filspari) the use of SGLT2 inhibitors was prohibited during the study. When documenting prior therapy and trial context for sparsentan, note trial design differences (e.g., prohibited concomitant agents) that may affect interpretation of evidence.

Document prior RAS inhibitor (ACEi/ARB) optimization and UPCR baseline per current KDIGO‑aligned thresholds
State if SGLT2 inhibitors are being used in the patient's regimen and rationale for sparsentan use

Documentation Required

Provider action: IgG4-RD diagnostic documentation

For IgG4‑related disease (IgG4‑RD) requests (e.g., Uplizna), provide biopsy‑proven diagnosis with immunostaining and histopathologic criteria: confirm IgG‑positive cells, IgG4+/IgG+ plasma cell ratio >40% and >10 IgG4+ plasma cells per HPF, typical storiform fibrosis or obliterative phlebitis, imaging, and history of multi‑organ involvement and recent glucocorticoid‑requiring flare.

Attach pathology reports with immunostaining results and high‑power field counts
Include imaging and documentation of at least two organs affected historically and glucocorticoid‑responsive flare within past 3 months

Documentation Required

Provider action: Medical record documentation

Submit complete medical record documentation with all prior authorization requests. Include office visit notes with diagnosis, relevant history, physical examination, medication history, baseline disease severity measures, prior therapy trial dates and outcomes, and the plan of care demonstrating medical necessity.

Include chart notes that demonstrate positive clinical response for reauthorization requests (approvals up to 12 months)
Provide objective scoring data where required (MG‑ADL, QMG, SLEDAI, BILAG, UPCR, eGFR)

Billing Rule

Provider action: Billing code usage

When submitting claims or prior authorization requests, use the HCPCS and J‑codes listed in the policy and map biosimilars to the appropriate Q‑codes as applicable. Incorrect coding or failure to indicate benefit assignment (medical vs pharmacy) can delay processing.

Common codes: J0490 (belimumab), J0491 (anifrolumab), J3262 (tocilizumab), J1745 (infliximab), J9332 (Vyvgart), J9334 (Vyvgart Hytrulo), J9256 (nipocalimab), J3402 (Ryoncil), Q5103–Q5156 for infliximab/adalimumab biosimilars
Use J3590 (unclassified biologics) when appropriate per coding guidance and include brand/specimen details

Documentation Required

Provider action: Document baseline disease severity and prior therapies

Document baseline disease severity and all prior therapies thoroughly: include scores (MG‑ADL, QMG, SLEDAI, BILAG), UPCR/proteinuria values, eGFR, dates of prior trials, dose/duration, and reasons for discontinuation to support medical necessity or reauthorization.

For renal agents, report UPCR and eGFR and ACEi/ARB optimization status
For gMG and SLE biologics, include baseline scoring and steroid dosing history

Documentation Required

Provider action: Ryoncil dosing/response

For Ryoncil (remestemcel‑L‑rknd) requests in pediatric steroid‑refractory acute GVHD, include dosing and response documentation: standard dosing is 2 × 10^6 MSCs/kg IV twice weekly for 4 weeks; report Day‑28 overall response rate and subsequent responses if therapy continued beyond 4 weeks.

Provide weight-based dosing calculations and dates of each infusion
Report Day‑28 response status (CR, PR, NR) and any continued therapy rationale

Documentation Required

Provider action: Actemra CRS diagnosis documentation

For Actemra (tocilizumab) requests for cytokine release syndrome (CRS), include documentation confirming the diagnosis and severity (grade 3–4): temperature ≥38°C plus hypotension requiring vasopressor(s) and hypoxia requiring high‑flow oxygen or positive pressure ventilation, and plan for inpatient admission if required.

Attach vitals, vasopressor usage, oxygen support details, and the treating team's CRS grade assessment
State whether CRS is treatment‑induced and the causative therapy (e.g., CAR‑T or other)

Documentation Required

Provider action: Document that medications are being used

Document that medications are being used per the product's FDA‑approved dosing and administration or per the policy's specified criteria. For non‑formulary or off‑label requests, include a clear rationale and supporting evidence. Reauthorization requires documentation of ongoing positive clinical response.

State current dosing regimen, administration dates, and any quantity limits applied
Non‑formulary exceptions may be approved up to 12 months with supporting documentation

Step Therapy

Provider action: Step therapy prior to TNF‑α or infliximab use

For uveitis and related indications, step therapy requires prior trials of corticosteroids or immunosuppressives before initiating TNF‑α or infliximab products. Additionally, updated product sequencing requires trial of preferred adalimumab products (one preferred adalimumab for certain uveitis indications) before non‑preferred infliximab products.

Document prior periocular, intraocular, or systemic corticosteroid and immunosuppressive use and outcomes
For new starts on infliximab or non‑preferred adalimumab, include documented failure/intolerance to preferred adalimumab products and preferred infliximab biosimilars as required

Note

Provider action: Off-label/step considerations

Off‑label requests may be considered when significant supporting evidence and clinical rationale are provided. However, many off‑label or combination uses not specifically outlined in this policy are considered investigational and may be denied; provide peer‑reviewed literature or guidelines to support coverage.

Include literature citations, clinical rationale, and why standard options are unsuitable for the member
Note: combinations of policy‑listed agents without explicit coverage language are typically investigational

Note

Provider action: In the PROTECT trial sparsentan was comp

For sparsentan (Filspari) context from the PROTECT trial, note that sparsentan demonstrated substantial proteinuria reduction versus irbesartan and the trial prohibited SGLT2 inhibitor use; when requesting coverage, document baseline UPCR, prior RAS inhibitor maximization, and any concurrent SGLT2 use to aid clinical assessment.

Provide UPCR and eGFR baseline values and statement of RAS inhibitor maximization
Explain any deviations from trial concomitant‑therapy restrictions (e.g., SGLT2 usage)

Step Therapy

Provider action: Adalimumab/infliximab step therapy and product sequencing

Adalimumab and infliximab product sequencing and step therapy have been updated: new starts of non‑preferred adalimumab require trial and inadequate response to all preferred adalimumab products; preferred infliximab products should be tried prior to non‑preferred infliximab agents per the policy update timeline. Document trials, NDCs where applicable, and reasons for switching.

When requesting non‑preferred adalimumab or infliximab, include documentation of trials of preferred branded/biosimilar products and dates
Refer to policy history for effective dates of product tier changes and for plan‑specific formulary exceptions

Treatment-induced grade 3–4 CRS meets criteria for hospital-based care and specialized treatment such as tocilizumab or anakinra

Age noteTocilizumab formulations and anakinra coverage include pediatric ages (e.g., ≥2 years for some formulations)

NMOSD AQP4-IgG positive definition

NMOSD AQP4‑IgG positive definitionAdult NMOSD requires core clinical characteristics (e.g., optic neuritis, acute myelitis, area postrema syndrome) plus positive AQP4‑IgG antibody testing and exclusion of alternative diagnoses

Relapse/history requirementAlso requires history of ≥1 relapse in last 12 months or ≥2 relapses in 24 months for some agents

Specialist involvementDiagnosis and treatment typically require neurologist/neuroimmunology specialist involvement

C3G biopsy-proven definition and thresholds

C3G biopsy‑proven definitionComplement 3 glomerulopathy confirmed by renal biopsy with documented UPCR ≥ 1 g/g and eGFR ≥ 30 mL/min/1.73 m2 after ACEi/ARB trial or documented intolerance

Exclusion (rapidly progressive)Excludes rapidly progressive crescentic GN defined as 50% decline in eGFR within 3 months with crescents in ≥50% glomeruli

Prescriber requirementPrescribed by or in consultation with a nephrologist

generalized myasthenia gravis serology definition (AChR/MuSK)

Generalized MG serology definitionDiagnosis of generalized myasthenia gravis requires serologic testing positive for anti‑AChR or anti‑MuSK antibodies

Concomitant therapy requirementCandidates typically should be on pyridostigmine and two or more immunosuppressive therapies or have tried/failed them

Concurrent-use exclusionsCertain agents are not used concurrently with specified complement inhibitors or other listed biologics (see agent criteria)

primary IgA nephropathy definition (biopsy-proven with UPCR thresholds)

Primary IgA nephropathy definitionBiopsy‑proven primary IgA nephropathy with documented UPCR meeting agent‑specific thresholds

Agent-specific UPCR examplesExamples: Fabhalta ≥1.5 g/g; Filspari/Tarpeyo ≥0.5 g/g (or KDIGO‑aligned thresholds); Voyxact ≥0.75 g/g or urine protein ≥1.0 g/day depending on agent

Management prerequisitesRequires trial of maximally tolerated ACE inhibitor or ARB unless intolerant; nephrologist prescribing/consultation required

HiSCR definition (hidradenitis suppurativa clinical response)

HiSCR definitionHidradenitis Suppurativa Clinical Response (HiSCR) used in HS trials (e.g., HiSCR rates reported at 12 weeks)

HiSCR trial contextExample: HS Study I HiSCR with Humira 40 mg weekly = 42% vs placebo 26% at Week 12

Use in coverage criteriaHiSCR is a validated endpoint referenced when assessing clinical response for HS therapies

BLyS definition (belimumab target)

BLyS definitionBLyS (B‑lymphocyte stimulator, also known as BAFF) is a protein involved in B‑cell survival and differentiation and is targeted by belimumab

Clinical roleBLyS inhibition reduces B‑cell activity, autoantibody production, and mediates clinical effects in SLE trials

Relevance to BenlystaBenlysta binds soluble BLyS and was studied in Phase III BLISS trials showing SRI‑4 benefit

Anifrolumab (Saphnelo) mechanism summary

Anifrolumab (Saphnelo) mechanism summaryHuman IgG1κ monoclonal antibody that binds IFNAR1 to inhibit type I interferon signaling and reduce IFN‑responsive gene expression

Clinical contextStudied in adult SLE (TULIP trials) for moderate to severe disease; mechanism reduces plasma cell differentiation and downstream inflammation

Implication for coverageUsed as add‑on therapy in adults meeting trial disease activity thresholds (SLEDAI‑2K) and without severe renal/CNS lupus

SRI-4 definition

SRI‑4 definitionSLE Responder Index (SRI‑4) requires ≥4‑point reduction in SLEDAI‑2K, no new severe/worsening BILAG items, no worsening in PGA, and no prohibited medication changes

Use in trialsPrimary endpoint in BLISS and pediatric Benlysta trials at Week 52

InterpretationUsed to define clinical response for belimumab efficacy assessments

MG-ADL responder definition (Vyvgart ADAPT trial)

MG‑ADL responder (Vyvgart ADAPT) — trial definitionMG‑ADL responder = ≥2‑point reduction in total MG‑ADL score from treatment cycle baseline sustained for at least 4 consecutive weeks, with first reduction no later than 1 week after last infusion of the cycle

Vyvgart dosing contextVyvgart administered 10 mg/kg IV as four weekly infusions per cycle; primary endpoint assessed during first cycle in AChR‑Ab positive population

Clinical interpretationUsed as the efficacy metric for gMG biologic authorizations and reauthorization evidence

MG-ADL responder definition (general)

MG‑ADL responder (general)An MG‑ADL responder is an individual with a ≥2‑point reduction in MG‑ADL total score compared to treatment cycle baseline for at least 4 consecutive weeks

Score rangeMG‑ADL total score ranges 0–24; higher scores indicate greater impairment

Use in authorizationResponder definition used to document clinical benefit for gMG biologic reauthorization

aGVHD definition

aGVHD definitionAcute graft‑versus‑host disease (aGVHD) is an immune‑mediated complication after allogeneic HSCT, classically presenting within 100 days and affecting skin, liver, and GI tract with severity graded clinically

Clinical featuresManifests as rash, persistent nausea/vomiting, abdominal cramping, diarrhea; severity grading informs therapy decisions

Relevance to policyOrencia and Ryoncil criteria reference IBMTR severity staging and grade C/D involvement for pediatric aGVHD eligibility

CAPS definition (IL-1 pathway agents)

CAPS definitionCryopyrin‑associated periodic syndromes (CAPS) are inherited autoinflammatory syndromes treated with IL‑1 pathway agents (e.g., Kineret, Ilaris, Arcalyst)

Therapeutic implicationPolicy added Arcalyst and aligned Ilaris prescribing requirements with rheumatologist/geneticist/dermatologist consultation

Age/indication notesSpecific age and indication criteria apply per individual agent prescribing information

IgAN definition and proteinuria threshold usage

IgAN definition and proteinuria threshold usagePrimary IgAN requires biopsy‑proven diagnosis and agent‑specific UPCR or urine protein thresholds to determine eligibility for therapy

Examples of thresholdsPolicy references UPCR thresholds ranging by agent (e.g., 0.5, 0.75, 1.0, 1.5 g/g) and aligns some agents to KDIGO recommendations

Prescriber requirementNephrologist prescribing or consultation required for IgAN agents

KDIGO IgAN guideline reference

KDIGO IgAN guideline referencePolicy references KDIGO 2025 Clinical Practice Guideline for the Management of IgA Nephropathy

Alignment purposeUsed to align UPCR/urine protein thresholds (e.g., 0.5 g/g or 0.5 g/day) for agent eligibility and documentation

Reference citationKDIGO 2025 guideline cited in policy references

UPCR term definition

UPCR term definitionUrine protein‑to‑creatinine ratio (UPCR) — a laboratory measure used to quantify proteinuria and applied as eligibility thresholds across IgAN and C3G criteria

Alternate measureUrine protein (g/day) is an acceptable equivalent for threshold comparisons (policy uses both UPCR and g/day)

Documentation requirementAuthorization requests should include UPCR or 24‑hour urine protein values to support eligibility

2026-04-01revisionLatest

Policy reviewed (effective Apr. 1, 2026) with multiple updates including Benlysta SC age change for active lupus nephritis and addition of Otezla XR for Behcet's disease.

2025-05-06addition

Effective May 6, 2025 (after 90-day provider notification) site-of-service review added for Tyenne (tocilizumab-aazg) IV and age requirements for sarcoidosis criteria were added for multiple adalimumab/infliximab products.

2025-07-01addition

Effective July 1, 2025 (after provider notification) added coverage criteria for Ryoncil (remestemcel-L-rknd) and updated Humira (AbbVie) NDC group status for new starts/step positioning.

2025-10-03clarification

Effective October 3, 2025 (after 90-day provider notification) clarified that Site of Service Medical Necessity can apply to injection drugs and added site-of-service review for Saphnelo and Vyvgart products.

2025-09-01interim_review

Interim review approved Aug 12, 2025 (effective 09/01/25) added coverage for Rinvoq (upadacitinib) in giant cell arteritis and expanded concurrency/exclusion rules among myasthenia gravis agents.

2025-03-01interim_review

Interim review approved Feb 11, 2025 (effective 03/01/25) added coverage criteria for Ryoncil (remestemcel-L-rknd).

2026-02-01update

History entry notes series of interim reviews between 09/01/25 and 03/01/26 updating indications, step therapy, and concurrency restrictions for multiple products including Imaavy, Vanrafia, and Rinvoq.

2026-03-10review_dateLatest

Policy last reviewed on Mar. 10, 2026 as reflected in policy metadata prior to the April 1, 2026 effective revision.