Site of Service and Medical Necessity for IV/Injectable Autoimmune Therapies
Governs medical benefit review and site-of-service medical necessity for specified intravenous and injectable drugs used to treat a range of autoimmune conditions; affects providers seeking coverage for infusion/injection administration (and drug preapproval) for applicable Premera members.
Policy Summary
PayerPremera Bluecross
PolicySite of Service and Medical Necessity for IV/Injectable Autoimmune Therapies
Policy CodePolicy N/A
Change TypeMultiple additions and revisions (drug criteria, biosimilars, UPCR thresholds)
Effective DateJul. 2, 2026* May 12, 2026
Next Review DateN/A
Key ActionObtain prior authorization and submit diagnostic documentation (e.g., UPCR/eGFR or biopsy confirmation) per the drug-specific criteria before drug administration.
Added criteria for Orencia for the prophylaxis of acute graft versus host disease (aGVHD).
Added coverage criteria for Filspari (sparsentan) for proteinuria in adults with primary IgA nephropathy at risk of rapid progression.
Added coverage criteria for Tarpeyo (budesonide) for adults with primary IgA nephropathy.
Added coverage criteria for Rezurock (belumosudil) for chronic graft versus host disease.
Updated Vyvgart and Vyvgart Hytrulo criteria to prohibit concurrent use with certain other agents (Rystiggo, Soliris, Ultomiris, Zilbrysq).
Added coverage for multiple adalimumab and infliximab biosimilars and changed preferred/non-preferred designations and step requirements.
Added coverage for Voyxact (sibeprenlimab) with Phase 3 interim results showing 51% placebo-adjusted reduction in proteinuria at nine months in IgAN.
Added coverage criteria for Cosentyx (secukinumab) for adults with moderate to severe hidradenitis suppurativa and removed adalimumab step therapy requirement for that indication.
Updated Lupkynis (voclosporin) criteria to clarify combination therapy requirements.
Updated Benlysta (belimumab) SC coverage to include pediatric individuals 5 years and older.
Updated Vyvgart (efgartigimod alfa-fcab) criteria to require it not be used concurrently with Vyvgart Hytrulo, Rystiggo, Soliris, Ultomiris, or Zilbrysq.
Added coverage criteria for Tarpeyo (budesonide) for adults with primary IgA nephropathy and adjusted urine protein-to-creatinine ratio threshold.
Updated Vyvgart Hytrulo coverage to include treatment of certain individuals with CIDP and added related non-concurrent medication requirements.
Added coverage criteria for multiple new products (e.g., Niktimvo, Fabhalta, Ryoncil, Bimzelx, Imaavy, Otezla XR, Vanrafia, Rinvoq, Avtozma) and expanded indications.
Removed Idacio (adalimumab-aacf) from policy as it has been removed from the market.
Updated Tarpeyo (budesonide) urine protein-to-creatinine ratio/urine protein thresholds and Filspari (sparsentan) UPCR thresholds to align with 2025 KDIGO guidelines (e.g., UPCR >= 0.5 g/g or urine protein >= 0.5 g/day).
Updated numerous product coverage statuses, preferred/non-preferred adalimumab and infliximab biosimilar designations and step/age requirements for indications such as pyoderma gangrenosum and sarcoidosis.
Added coverage criteria for multiple recently approved drugs (e.g., Niktimvo, Fabhalta, Voyxact, Ryoncil, Bimzelx, Avtozma, Imaavy) and new HCPCS codes through 2026.
Added coverage criteria for Avtozma (tocilizumab-anoh) IV/SC and HCPC code Q5156.
Added coverage criteria for Voyxact (sibeprenlimab-szsi) for IgA nephropathy and Uplizna (inebilizumab-cdon) for generalized myasthenia gravis; updated multiple neonatal/adult biologic entries.
Clarified UPCR criteria for Filspari and Tarpeyo as at least 0.5 g/g OR urine protein ≥0.5 g/day to align with KDIGO.
Updated criteria for Voyxact (sibeprenlimab-szsi) to change UPCR threshold to ≥0.5 g/g or urine protein ≥0.5 g/day and added eGFR and prior therapy requirements.
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.
~20+listed drugs subject to site-of-service review (IV/SC)
~20+ agentsbiologic/targeted therapies listed
UPCR >= 0.5proteinuria threshold for IgAN therapies
90 dayshospital outpatient first 90 days
50 mileshome infusion distance threshold
Coverage and Medical Necessity Criteria
Site-of-Service Medical Necessity
Covered when ALL of the following are met (site-of-service determinations for IV/SC therapies):
Site-of-Service Review Applies: Site-of-service review applies to specified IV and injectable drugs for all ages; for individuals aged 13 and older the site of service will be reviewed
See drug list for included agents
Medically Necessary Sites: Preferred medically necessary sites: physician's office, infusion center, home infusion (if criteria met)
Hospital-based outpatient setting is medically necessary for the initial 90 days or re-initiation after ≥6 months or when clinical risk factors are present
Hospital-based outpatient necessity: Hospital-based outpatient setting is medically necessary for the first 90 days for the initial course OR re-initiation after ≥6 months following discontinuation, except when standard dosing interval is ≥6 months90 days
Also medically necessary when patient has high-risk clinical conditions
Home infusion necessity: Home infusion is medically necessary when no outpatient infusion center exists within 50 miles and no contracted home infusion agency will travel, or hospital is the only place offering the infusion50 miles
High-risk clinical conditions for hospital-based care: Known cardiac or pulmonary condition increasing risk (e.g., symptomatic arrhythmia, significant respiratory disease, %FVC ≤40%), unstable renal function, difficult vascular access, acute mental status changes, or prior severe adverse drug reactions/anaphylaxis
CRS Criteria: For cytokine release syndrome (CRS) hospital-based care is medically necessary when CRS is grade 3 or 4 evidenced by temperature ≥38°C, hypotension requiring ≥1 vasopressors, and hypoxia requiring high‑flow oxygen or positive pressure ventilation; individual will be admitted inpatient as soon as possible
Benlysta (belimumab) — SLE and Lupus Nephritis
Benlysta (belimumab) coverage when ALL of the following are met:
Benlysta for SLE: Individual aged ≥5; diagnosis of SLE confirmed by ACR/EULAR-ACR or SLICC criteria; benlysta is being used as add-on therapy following standard induction therapy (mycophenolate, cyclophosphamide, azathioprine, or immunosuppressant plus corticosteroid); benlysta is not used concurrently with anifrolumab (Saphnelo) or obinutuzumab (Gazyva)
Applies to IV and SC formulations; prescribed by or in consultation with appropriate specialist as indicated
Benlysta for Lupus Nephritis: Individual aged ≥5; diagnosis of SLE confirmed by ACR/EULAR-ACR or SLICC criteria; receiving standard therapy with mycophenolate, cyclophosphamide, azathioprine, or immunosuppressant plus corticosteroid; has class III, IV, and/or V lupus nephritis; no dialysis in prior 12 months; benlysta is not used concurrently with Lupkynis (voclosporin) or obinutuzumab; prescribed by or in consultation with a nephrologist or rheumatologist
Lupkynis (voclosporin) — Lupus Nephritis
Lupkynis may be considered medically necessary when ALL are met:
Lupkynis Criteria: Individual aged ≥18; diagnosis of SLE confirmed by ACR/EULAR-ACR or SLICC criteria; Lupkynis is used in combination with mycophenolate, cyclophosphamide, azathioprine, or an immunosuppressant AND a corticosteroid; has class III, IV, and/or V lupus nephritis; no dialysis in past 12 months; not used concurrently with Benlysta (belimumab) or obinutuzumab; dose limited to 47.4 mg per day (three 7.9 mg capsules twice daily); prescribed by or in consultation with a nephrologist or rheumatologist47.4 mg/day
Managed under pharmacy benefit
Saphnelo (anifrolumab) — SLE
Saphnelo may be considered medically necessary when ALL are met:
Saphnelo Criteria: Individual aged ≥18; diagnosis of SLE confirmed by ACR/EULAR-ACR or SLICC criteria; Saphnelo is used as add-on therapy following standard induction therapy (e.g., mycophenolate, azathioprine, or other immunosuppressant plus corticosteroid); does not have severe active central nervous system lupus or severe active lupus nephritis (excluded populations in pivotal trials)
Subject to site-of-service review
Pyoderma Gangrenosum — Biologic Agent Criteria
Biologic therapy for pyoderma gangrenosum when ALL are met:
First-line biologics (pyoderma gangrenosum): Individual aged ≥18; has not responded to one standard non-biologic therapy (e.g., oral corticosteroids, systemic cyclosporine, topical tacrolimus, etc.); medication is prescribed by or in consultation with a dermatologist (examples: certain adalimumab products, secukinumab)
Some agents managed under pharmacy benefit; specific product/NDC requirements may apply
Infliximab-class (medical benefit): Avsola and Inflectra may be considered medically necessary for pyoderma gangrenosum when individual is aged ≥18, failed one standard non-biologic therapy, and medication is prescribed by or in consultation with a dermatologist; other infliximab products (Remicade, Janssen unbranded, Renflexis) require prior inadequate response or intolerance to Avsola and Inflectra (applies to individuals not previously treated with requested therapy)
Site-of-service review applies
Uplizna (inebilizumab) — IgG4-Related Disease
Uplizna may be considered medically necessary when ALL are met:
Uplizna for IgG4-RD: Individual aged ≥18; documented diagnosis of IgG4-related disease confirmed by biopsy with immunostaining, imaging, or elevated IgG4 with histopathologic features; one or more listed organs involved (e.g., lung, orbits, pachymeninges, pancreas, retroperitoneum, salivary gland, thyroid gland, aorta, bile ducts); meets at least two histopathologic criteria (dense lymphoplasmacytic infiltrate with fibrosis; IgG4+/IgG+ plasma cell ratio >40% and >10 IgG4+ cells/HPF; typical storiform fibrosis or obliterative phlebitis); history of IgG4-RD affecting ≥2 organs at any time; has experienced IgG4-RD flare requiring glucocorticoid treatment within last 3 months; prescribed by or in consultation with an appropriate specialist
Managed under medical benefit; subject to site-of-service review
Pyoderma gangrenosum — infliximab
Infliximab agents for pyoderma gangrenosum — Managed under medical benefit
Prior therapy – non-biologic: Has not responded to 1 standard non-biologic therapy (e.g., oral corticosteroids, systemic cyclosporine, topical tacrolimus, etc.)
Prior biologic/biosimilar: Has had an inadequate response or intolerance to Avsola (infliximab-axxq) AND Inflectra (infliximab-dyyb) (note: applies only to individuals not previously treated with requested therapy)
Prescriber: Medication is prescribed by or in consultation with a dermatologist
Adalimumab agents — pyoderma gangrenosum and uveitis
Adalimumab agents for pyoderma gangrenosum and uveitis — Managed under pharmacy benefit
Adalimumab (pharmacy-managed) for pyoderma gangrenosum
Age: Individual is aged 18 years or older
Prior non-biologic therapy: Has not responded to 1 standard non-biologic therapy (e.g., oral corticosteroids, systemic cyclosporine, topical tacrolimus, etc.)
Prior adalimumab agents: Has had an inadequate response or intolerance to ALL the following agents: adalimumab-aaty, adalimumab-adaz, adalimumab-adbm [NDCs starting with 00597]
Prescriber: Medication is prescribed by or in consultation with a dermatologist
Giant cell arteritis — IL-6 antagonists and JAK inhibitor
Tocilizumab and upadacitinib for giant cell arteritis — Managed under pharmacy and/or medical benefit
IL-6 antagonists for giant cell arteritis: Individual is aged 18 years or older; has tried and had an inadequate response to a systemic corticosteroid OR is currently taking a systemic corticosteroid; medication is prescribed by or in consultation with a rheumatologist
Applies to tocilizumab products (IV/SC) subject to site-of-service review
Rinvoq (upadacitinib) for GCA: Individual is aged 18 years or older; has tried and had an inadequate response to a systemic corticosteroid OR is currently taking a systemic corticosteroid; medication is prescribed by or in consultation with a rheumatologist
Managed under pharmacy benefit
CIDP — Vyvgart Hytrulo
Vyvgart Hytrulo and CIDP criteria — Managed under medical and pharmacy benefit
Vyvgart Hytrulo for CIDP: Individual is aged 18 years or older; diagnosed with CIDP based on progressive or relapsing motor and/or sensory symptoms in >1 limb with hyporeflexia/areflexia for ≥2 months AND electrophysiologic findings meeting 3 of 4 AAN demyelination criteria AND exclusion of other causes; has tried and had an inadequate response or intolerance to IV or SC immune globulin; prescribed by or in consultation with a neurologist
Cytokine release syndrome — IL-6 and IL-1 agents
Tocilizumab and anakinra for cytokine release syndrome (CRS)
CRS — IL-6 antagonists (tocilizumab products): Individual is aged ≥2 years; has documented treatment-induced grade 3 or 4 CRS as evidenced by temperature ≥38°C AND hypotension requiring ≥1 vasopressors AND hypoxia requiring high-flow oxygen or positive pressure ventilation; medication is prescribed per acute care guidance
Hospital admission and inpatient care required as soon as possible
CRS — Anakinra (Kineret): Documented treatment-induced grade 3 or 4 CRS with same physiologic criteria (fever ≥38°C, hypotension requiring vasopressors, hypoxia requiring high‑flow oxygen or positive pressure ventilation)
Managed under pharmacy and medical benefit
NMOSD — B-cell and IL-6 targeted therapies
Uplizna and Enspryng for NMOSD — Managed under medical and pharmacy benefit
Uplizna (inebilizumab) for NMOSD (AQP4-IgG positive): Individual is aged ≥18; documented NMOSD with at least one core clinical characteristic (optic neuritis, acute myelitis, area postrema syndrome, brainstem/diencephalic/cerebral syndrome) AND positive AQP4-IgG antibody test AND exclusion of alternative diagnoses; history of ≥1 relapse in last 12 months or ≥2 relapses in last 24 months AND EDSS ≤7.5; prescribed by or in consultation with a neurologist
Enspryng (satralizumab) for NMOSD (AQP4-IgG positive): Mirrors Uplizna criteria: aged ≥18; documented core clinical characteristic(s) AND positive AQP4-IgG AND exclusion of other diagnoses; relapse history and EDSS thresholds applied
Managed under pharmacy and medical benefit
Autoinflammatory syndromes and recurrent pericarditis
Arcalyst, Kineret, and Ilaris for autoinflammatory syndromes, recurrent pericarditis, and periodic fever syndromes
Arcalyst (rilonacept) for DIRA: Genetic testing confirming IL1RN mutation AND individual weighs at least 10 kg AND prescribed by or in consultation with a rheumatologist, geneticist, or dermatologist
Arcalyst for Recurrent Pericarditis: Individual aged ≥12 with prior acute pericarditis episode, typical pleuritic chest pain AND at least one clinical sign (fever, pericardial rub, ECG changes, new/worsening effusion, elevated inflammatory markers) OR imaging evidence of pericardial inflammation after ≥4-week symptom-free interval; prior treatment with NSAID or corticosteroid unless contraindicated; prescribed by/with a cardiologist
Ilaris and Kineret for periodic fever syndromes and Still's disease: Covered when listed diagnostic and age criteria are met for CAPS, TRAPS, HIDS/MKD, FMF, and Still's disease and prescribed by/with rheumatologist/geneticist/dermatologist
GVHD — multiple agents and indications
Agents for graft-versus-host disease (GVHD) and related transplant indications
Niktimvo (axatilimab) for chronic GVHD: Individual weighs at least 40 kg; has tried and had inadequate response or intolerance to at least two systemic treatments (examples: cyclosporine, ibrutinib, mycophenolate, ruxolitinib, sirolimus, tacrolimus); prescribed by or in consultation with an oncologist, hematologist, or transplant physician
Managed under medical benefit
Orencia (abatacept) for prevention of acute GVHD: Individual is aged ≥2 years; will receive standard therapy with a calcineurin inhibitor and methotrexate; will undergo HSCT from a matched unrelated donor or 1-allele mismatched unrelated donor; prescribed by or in consultation with transplant-affiliated physician
Rezurock (belumosudil) for chronic GVHD: Individual is aged ≥12; has tried and had inadequate response or intolerance to at least two systemic treatments; prescribed by or in consultation with an oncologist, hematologist, or transplant physician
Generalized myasthenia gravis — Imaavy
Imaavy (nipocalimab) for generalized myasthenia gravis — Managed under medical benefit
Imaavy for generalized myasthenia gravis: Individual is aged ≥12; diagnosis of generalized MG with serologic testing for anti‑AChR or anti‑MuSK antibodies; currently using pyridostigmine or tried and had inadequate response/intolerance or contraindication; currently using two or more immunosuppressive therapies or tried and had inadequate response/intolerance to two ISTs or contraindications; for AChR+ MG has tried and had inadequate response or intolerance to at least one of: eculizumab, ravulizumab, Vyvgart, Vyvgart Hytrulo; medication is not used concurrently with eculizumab products, Rystiggo, Ultomiris, Uplizna, Vyvgart, Vyvgart Hytrulo, or Zilbrysq
Dose limits and specialty prescriber requirements apply
Imaavy (nipocalimab) — Myasthenia Gravis
Imaavy (nipocalimab-aahu) may be considered medically necessary for generalized myasthenia gravis when ALL of the following are met:
Imaavy MG criteria
Age: Individual is aged 12 years or older>=12 years
Diagnosis of generalized myasthenia gravis with serologic test for anti-AChR or anti-MuSK antibodies
Acetylcholinesterase inhibitor trial: Currently using pyridostigmine, or tried and had an inadequate response/intolerance, or contraindication
Immunosuppressive therapy trials: Currently using two or more ISTs, or tried and had an inadequate response/intolerance to two ISTs, or contraindications to two ISTs
Other MG biologics (Rystiggo, Uplizna, Vyvgart)
These agents may be considered medically necessary for generalized myasthenia gravis when ALL of the following are met:
Generalized MG biologic criteria
Age: Individual is aged 18 years or older (agent-specific exceptions may allow age 12+)>=18 years
Diagnosis of generalized myasthenia gravis with serologic test for anti‑AChR or anti‑MuSK antibodies
Pyridostigmine trial: Currently using pyridostigmine or tried and had an inadequate response/intolerance, or contraindication
Immunosuppressive therapy trials: Currently using two or more ISTs or tried and had an inadequate response/intolerance to two ISTs or have contraindications
Filspari (sparsentan) — Initial therapy
Filspari (sparsentan) may be considered medically necessary to slow kidney function decline in adults with primary IgAN at risk for progression when ALL of the following are met:
Filspari (sparsentan) criteria: Individual is aged ≥18; documented biopsy-proven primary IgA nephropathy; documented UPCR ≥0.5 g/g OR urine protein ≥0.5 g/day; either tried ACE inhibitor or ARB with persistent UPCR ≥0.5 g/g OR has intolerance to ACEi/ARB; not used concurrently with other ACE inhibitors, ARBs, endothelin receptor antagonists, or aliskiren; prescribed by or in consultation with a nephrologistUPCR >=0.5 g/g
Managed under pharmacy benefit
Tarpeyo (budesonide) — Initial therapy
Tarpeyo (budesonide) may be considered medically necessary to reduce loss of kidney function in adults with primary IgAN when ALL of the following are met:
Tarpeyo criteria: Individual is aged ≥18; documented biopsy-proven primary IgA nephropathy; documented UPCR ≥0.5 g/g OR urine protein ≥0.5 g/day; used in combination with an ACE inhibitor or ARB; prescribed by or in consultation with a nephrologist; dose limited to 16 mg dailyUPCR >=0.5 g/g
Vanrafia and Voyxact may be considered medically necessary to reduce proteinuria in adults with primary IgAN at risk of progression when ALL of the following are met:
Vanrafia/Voyxact criteria: Individual is aged ≥18; documented biopsy-proven primary IgA nephropathy; documented UPCR ≥0.5 g/g OR urine protein ≥0.5 g/day; for Voyxact eGFR ≥30 mL/min/1.73 m2 and not on dialysis or post‑transplant; either tried ACEi/ARB with persistent UPCR ≥0.5 g/g OR has intolerance to ACEi/ARB; prescribed by or in consultation with a nephrologist; dose limits: Vanrafia 0.75 mg daily; Voyxact 0.75 mg dailyUPCR >=0.5 g/g; eGFR >=30 mL/min/1.73 m2 (Voyxact)
For Voyxact prior inadequate response or intolerance to Filspari or Tarpeyo is required
Sarcoidosis — TNF-α antagonists
TNF-α antagonists may be considered medically necessary for treatment of sarcoidosis when ALL of the following are met:
Sarcoidosis TNF-alpha criteria: Individual is aged ≥18; tried and had an inadequate response or intolerance to one corticosteroid; tried and had an inadequate response or intolerance to one immunosuppressive medication (examples listed); medication is prescribed by or in consultation with pulmonologist, ophthalmologist, or dermatologist
For second-line biosimilars, prior inadequate response/intolerance to first-line specified adalimumab products is required; for some infliximab products prior inadequate response to specified biosimilars may be required
Trial-aligned coverage criteria (informational)
Clinical eligibility/coverage considerations based on pivotal trials (apply when ALL of the following are met unless otherwise specified):
SLE (anifrolumab) trial-aligned criteria: Age 18-70; meets ACR criteria for SLE; moderate to severe active disease defined by SLEDAI-2K ≥6 (excluding fever/HA/organic brain syndrome) and clinical SLEDAI-2K ≥4; BILAG organ involvement (≥1 A or ≥2 B items) and PGA ≥1; stable on ≥1 SLE treatment; exclude severe lupus nephritis or neuropsychiatric lupusas stated
Derived from TULIP-1 and TULIP-2 inclusion/exclusion
gMG (FcRn/B-cell therapies) trial-aligned criteria: MGFA class II-IV; MG-ADL score thresholds per trial (e.g., ≥5 or higher depending on study); stable dose of steroids and/or immunosuppressants prior to enrollment; antibody-positive subgroups (AChR or MuSK) were primary efficacy populations for several agentsas stated
Derived from Vyvgart, Imaavy, Uplizna, Rystiggo trials
GVHD (abatacept) trial-aligned criteria:
Trial-based coverage/indication summaries
Coverage described or supported by trial populations and indications; coverage often contingent on meeting trial-like eligibility and prior therapy requirements.
Orencia for aGVHD prophylaxis (supporting evidence): Orencia was studied for prophylaxis in HSCT recipients ≥6 years in combination with calcineurin inhibitor and methotrexate with improved grade II-IV and overall survival outcomes in trials; dosing and donor types per trialsage >=6 years; donor types per trial
Efficacy endpoints included grade II-IV aGVHD-free survival and Day 180 overall survival
Rezurock for chronic GVHD: Rezurock demonstrated 75% overall response rate at 200 mg QD in patients ≥12 years with cGVHD after 2-5 prior systemic therapies>=12 years; 2-5 prior systemic therapies
Supported by ROCKstar Phase 2 randomized trial
Ryoncil for steroid-refractory aGVHD in pediatrics:
Summary of updated coverage criteria and new indications
Coverage changes and new indication statements (summarized):
Cosentyx for hidradenitis suppurativa: Added coverage criteria for adults with moderate to severe hidradenitis suppurativa; adalimumab step therapy requirement removed
Concurrent-use prohibitions updated: Vyvgart, Vyvgart Hytrulo, Rystiggo and related agents updated to prohibit concurrent use with specified complement or Fc-targeting therapies (e.g., Soliris, Ultomiris, Zilbrysq, Imaavy) depending on agent
Tarpeyo for IgAN — prior thresholds: Tarpeyo urine protein-to-creatinine ratio threshold previously updated to >=0.8 g/g or proteinuria >=1 g/day in 2025 updates>=0.8 g/g or >=1 g/day
Subsequently aligned to lower UPCR thresholds in 2026 updates
Benlysta SC age expansion:
Selected Updated Coverage Rules
Selected coverage criteria updates and requirements (summarized from history entries):
KDIGO-aligned IgAN protein thresholds: UPCR >=0.5 g/g OR urine protein >=0.5 g/day required for certain IgAN therapies (Filspari, Tarpeyo, Voyxact) where specifiedUPCR >=0.5 g/g OR urine protein >=0.5 g/day
Aligned to KDIGO 2025 guidance
Formulary/product-preference trials for adalimumab/infliximab: Many infliximab and adalimumab products require trial and inadequate response or intolerance to preferred products or specified biosimilars prior to coverage of non-preferred agentstrial and failure with preferred product(s)
See product-specific history entries for details
CRS coverage for tocilizumab-class agents: Coverage for tocilizumab IV products for cytokine release syndrome is medically necessary when CRS is treatment-induced and grade 3-4; documentation confirming diagnosis required
Summarized updated medical necessity criteria
Recent coverage criteria changes and requirements (summarized):
Voyxact (sibeprenlimab) updated criteria: Requires UPCR >=0.5 g/g OR urine protein >=0.5 g/day; eGFR >=30 mL/min/1.73 m2; not on dialysis or post‑transplant; prior inadequate response or intolerance to Filspari (sparsentan) or Tarpeyo (budesonide)as stated
UPCR threshold lowered from prior higher values; effective dates per history
Filspari and Tarpeyo proteinuria criteria: UPCR >=0.5 g/g OR urine protein >=0.5 g/day per KDIGO alignmentas stated
clarified measurement equivalence
Benlysta (belimumab) SC for active lupus nephritis: Age requirement updated to 5 years and olderage >=5 years
Per state-specific guidance, Site-of-Service (SOS) medical necessity criteria do NOT apply to Alaska fully‑insured members. For those members the policy’s SOS review is exempt under Alaska HB 226; however, standard medical necessity criteria for the infused or injected drug itself (for example, indication, prior therapy, age, and dosing requirements) continue to apply and will be reviewed as part of benefit determination. Providers should verify member plan type (member ID card or plan booklet) to confirm whether the Alaska fully‑insured exception applies before submitting a site‑of‑service review request.
A limited formulary exception is in effect for one Custom Open formulary: Formulary ID: 6062; Rx Plan F1. For members enrolled in that plan, specific policy criteria (including some infliximab/adalimumab step and site‑of‑service requirements) do not apply; instead, clinicians should follow the medical necessity criteria in policy 5.01.647 (Medical Necessity Criteria for Custom Open Formulary). Verify plan and formulary status using the member ID or plan booklet prior to prior authorization submission to ensure the correct criteria set is applied.
Uses of the listed agents that fall outside the indications, dosing, administration, or combination restrictions described in this policy are considered investigational and not medically necessary. This includes off‑label combinations of the named biologics with one another or use for conditions not specifically outlined in this policy or referenced companion policies. Requests lacking documentation that the drug will be used per FDA‑approved dosing/administration and the policy’s medical necessity criteria may be denied.
Codes, Dose Limits, and Thresholds
Drugs Listed for Review / Managementmixed
Actemra (tocilizumab) IV
Drug subject to site-of-service review
Avsola (infliximab-axxq) IV
Drug subject to site-of-service review
Avtozma (tocilizumab-anoh) IV
Drug subject to site-of-service review
Benlysta (belimumab) IV
Drug subject to site-of-service review
Ilaris (canakinumab) SC
Drug subject to site-of-service review
Inflectra (infliximab-dyyb) IV
Drug subject to site-of-service review
Infliximab (Janssen - unbranded) IV
Drug subject to site-of-service review
Remicade (infliximab) IV
Drug subject to site-of-service review
Renflexis (infliximab-abda) IV
Drug subject to site-of-service review
Rystiggo (rozanolixizumab-noli)
Drug subject to site-of-service review
1–10 of 19
1/2
Agent list (brand/generic) as presentedmixed
JXXXX
Placeholder — specific HCPCS/J-codes not listed in this excerpt
Injection, infliximab, excludes biosimilar (Remicade or Janssen unbranded), 10mg
J1823
Injection, inebilizumab-cdon, (Uplizna) 1 mg
J2793
Injection, rilonacept, (Arcalyst) 1 mg
1–10 of 30
1/3
Historical coding updatesHCPCS
Q5102
HCPCS code added historically (site-of-service/infusion related) per history.
HCPCS/Unclassified Codes and additionsHCPCS
J3590
Unclassified biologic drug code (multiple drug names added under J3590)
Q5103
HCPCS code added (noted in 2018 history)
Q5121
HCPCS code added (noted in 2020 history)
J9332
HCPCS code added 07/01/22
J9333
HCPCS code added 01/01/24
J9334
HCPCS code added 01/01/24
Q5133
HCPCS code added for Tofidence
J9038
HCPCS code added 04/01/25
J9256
HCPCS code replacing C9305 effective January 1, 2026
Q5156
HCPCS code added in 11/01/25 history
Added HCPCS CodesHCPCS
Q5156
HCPCS code added
Replaced HCPCS CodesHCPCS
J9256
HCPCS code added to replace C9305 effective January 1, 2026
inv-50: Hospital outpatient first-course window — first 90 days considered medically necessary in some situations
Policy ruleHospital-based outpatient administration is considered medically necessary for the initial course or for re-initiation after ≥6 months for the first 90 days
Applies toSpecified IV and injectable drugs subject to site-of-service review for individuals aged 13 and older
Purpose of 90-day windowCovers initial course of infusion/injection or re-initiation of therapy when clinical risk factors or monitoring needs may require hospital-level outpatient care
inv-51: Home infusion distance threshold — home infusion medically necessary if no outpatient infusion center within 50 miles
Prior Authorization, Documentation, and Step Therapy
Prior Authorization
Preapproval and Site‑of‑Service Review Requirement
Prior Authorization Required and Site‑of‑Service Review — Many IV and injectable biologic agents listed in this policy require preapproval (prior authorization) and, for medical‑benefit‑administered products, a site‑of‑service medical necessity review for individuals aged 13 and older. Site‑of‑service medical necessity applies only to medical benefit reviews and does NOT apply to Alaska fully‑insured members. Requests for infusion/injection at sites that do not meet site‑of‑service medical necessity criteria may be denied as not medically necessary.
Applies to listed IV/SC agents managed under the medical benefit (see Medical Benefit list).
Site‑of‑service review defines acceptable locations (hospital outpatient infusion department, hospital‑based outpatient clinical level of care, contracted home infusion when criteria met).
Exception: certain CRS (cytokine release syndrome) patients may be eligible for inpatient or alternative site‑of‑service per CRS criteria.
Prior Authorization
Benefit‑Specific Prior Authorization and Benefit Assignment Documentation
Benefit Assignment and Prior Authorization — Several products are managed under pharmacy, medical, or both benefits. Providers must identify the benefit under which the drug will be billed and obtain the appropriate benefit‑specific prior authorization. Benefit assignment affects whether site‑of‑service review is performed.
Clinical and Policy Background
Autoimmune disorders are characterized by immune activation against self‑tissues resulting in chronic inflammation and organ dysfunction. This policy governs preapproval and medical‑benefit review for specified intravenous and injectable immunomodulatory and biologic therapies across multiple autoimmune conditions (for example, SLE/lupus nephritis, myasthenia gravis, IgA nephropathy, pyoderma gangrenosum, NMOSD, CIDP, sarcoidosis, and graft‑versus‑host disease). In addition to indication‑specific medical necessity criteria, the policy defines site‑of‑service rules that determine when administration in a physician’s office, infusion center, home infusion, or hospital‑based outpatient setting is medically necessary; these site rules apply primarily to medical‑benefit administration and include exceptions for certain populations and plans.
Key Definitions and Diagnostic Criteria
inv-103: Site of service definition — physical location where drug administered
DefinitionSite of service: the physical location where a drug is administered (e.g., hospital-based outpatient, infusion center, physician's office, or home)
Review applicabilitySite-of-service medical necessity criteria applies to medical benefit reviews and is reviewed for individuals aged 13 and older
Alaska exceptionDoes not apply to Alaska fully‑insured members per policy note; refer to infusion/injection drug medical necessity criteria only
inv-104: Medical necessity for hospital-based outpatient — first 90 days rule and clinical reasons
Hospital outpatient first 90 daysHospital-based outpatient setting considered medically necessary for the first 90 days for the initial course or re-initiation after ≥6 months
Clinical reasons
Policy Updates and Change Log
2025-10-14interim_review
Added coverage criteria for Avtozma (tocilizumab-anoh) IV/SC; updated infliximab products to include treatment of certain uveitis indications and added HCPCS Q5156; replaced C9305 with J9256 effective 01/01/2026.
2026-01-13interim_review
Added coverage criteria for Voyxact (sibeprenlimab-szsi) for IgA nephropathy and Uplizna (inebilizumab-cdon) for generalized myasthenia gravis; updated multiple MG and FcRn-related product criteria.
2026-02-10annual_review
Policy Summary
PayerPremera Bluecross
PolicySite of Service and Medical Necessity for IV/Injectable Autoimmune Therapies
Policy CodePolicy N/A
Change TypeMultiple additions and revisions (drug criteria, biosimilars, UPCR thresholds)
Effective DateJul. 2, 2026* May 12, 2026
Next Review DateN/A
Key ActionObtain prior authorization and submit diagnostic documentation (e.g., UPCR/eGFR or biopsy confirmation) per the drug-specific criteria before drug administration.
Renflexis second-line: Renflexis (infliximab-abda) may be considered medically necessary when aged ≥18, failed one standard non-biologic therapy, and had inadequate response or intolerance to Avsola and Inflectra
Ryoncil (remestemcel-L) for pediatric steroid-refractory aGVHD: Individual aged 2 months to 17 years; diagnosed with Grade C or D aGVHD involving skin, liver, or GI tract OR Grade B aGVHD involving liver or GI tract; tried and had inadequate response or intolerance to systemic corticosteroid therapy; prescribed by or in consultation with an oncologist/hematologist/transplant physician
Dose limits and quantity limits per product labeling
Prior biologic/comparator trial for AChR+ MG: For AChR antibody positive MG, tried and had inadequate response/intolerance to at least one of: eculizumab, ravulizumab, efgartigimod (Vyvgart), Vyvgart Hytrulo
Concomitant therapy restriction: Medication is not used concurrently with eculizumab product, Rystiggo (rozanolixizumab), Ultomiris, Uplizna, Vyvgart, Vyvgart Hytrulo, or Zilbrysq
Concomitant exclusions: Medication is not used concurrently with eculizumab products, Rystiggo, Ultomiris, Uplizna, Vyvgart, Vyvgart Hytrulo, or Zilbrysq
Prior complement/targeted therapies: For AChR+ MG, tried/inadequate response/intolerance to at least one complement inhibitor or efgartigimod (list varies by agent)
Concomitant therapy restriction: Not used concurrently with listed competing biologic agents (eculizumab products, nipocalimab, rozanolixizumab, ravulizumab, inebilizumab, efgartigimod products, zilucoplan)
Agent-specific prescriber requirement: Medication prescribed by or in consultation with neurology specialists experienced in MG management
HSCT recipients per trial schedules (e.g., matched unrelated donor), receiving abatacept with calcineurin inhibitor and methotrexate for prophylaxis; endpoints included grade II-IV and III-IV aGVHD-free survival and overall survival
as stated
Derived from GVHD-1 and GVHD-2 studies
Ryoncil supported by Phase 3 single-arm trial in pediatric patients 2 months-17 years with steroid-refractory aGVHD showing ORR 70% at Day 28 and Day 100 survival outcomes
age 2 months-17 years; steroid-refractory grade B-D aGVHD
Dose per label: 2x10^6 MSCs/kg IV twice weekly x4 weeks
Filspari (sparsentan) for primary IgAN: Sparsentan reduced proteinuria vs irbesartan at week 36 in adults with persistent proteinuria >1.0 g/day despite maximized RAS inhibitor; accelerated approval based on proteinuria reductionadults with persistent proteinuria >1.0 g/day on maximized RASi
PROTECT trial excluded SGLT2i during trial
Tarpeyo (budesonide) for primary IgAN: Tarpeyo showed reduction in UPCR in adults with biopsy-verified IgAN on stable maximally tolerated RAS inhibitor and eGFR thresholds per trial; dosing 16 mg dailyeGFR >=35 mL/min/1.73m2; UP >=1 g/day or UPCR >=0.8
NefIgArd Part A results
Vanrafia (atrasentan) interim efficacy for IgAN: Vanrafia showed significant UPCR reduction at week 36 in interim analysis in adults with biopsy-proven IgAN and eGFR >=30; safety consistent with ERA classeGFR >=30 mL/min/1.73m2; urine protein >=1 g/day
ALIGN interim analysis
Voyxact (sibeprenlimab) for IgAN: Voyxact interim Phase 3 results show 51% placebo-adjusted reduction in proteinuria at 9 months in adults with biopsy-confirmed IgAN on stable supportive therapy; trial population required uPCR >=0.75 g/g or urine protein >=1.0 g/day and eGFR >=30uPCR >=0.75 g/g or urine protein >=1.0 g/day; eGFR >=30
VISIONARY Phase 3 interim analysis
Benlysta SC coverage criteria updated to include pediatric individuals 5 years and older for SLE and active lupus nephritis
age >=5 years
Infliximab/adalimumab biosimilar updates: Multiple infliximab and adalimumab branded and biosimilar products had preferred/non-preferred status and line-of-therapy/step requirements updated; new-starts may require trial and failure of preferred products or specific listed agents
CRS grade 3-4 and treatment-induced
Prior authorization duration: Non-formulary exception authorizations for drugs in this policy may be approved up to 12 monthsup to 12 months
replaced prior age 18+ requirement for this indication
Uveitis infliximab/adalimumab step therapy: Updated requirement: trial of 1 preferred adalimumab product is required prior to Avsola/Inflectra/Remicade/Renflexis for uveitis treatment (preferred adalimumab alternatives updated)1 preferred adalimumab trial
See history for product-specific effective dates
Distance threshold
Home infusion is considered medically necessary when there is no outpatient infusion center within 50 miles and no contracted home infusion agency will travel
Additional conditionHome infusion also considered when hospital is the only place offering the infusion
Clinical risk exceptionHospital-based outpatient may be required when the individual has clinical conditions that increase infusion risk (e.g., unstable cardiac/pulmonary disease, difficult vascular access)
inv-52: Lupkynis dosing limit — dosing limit example
Daily dosing limit47.4 mg per day (taken as three 7.9 mg capsules twice daily)
Indication contextDose limit applies when Lupkynis (voclosporin) is used in combination with mycophenolate/cyclophosphamide/azathioprine or other immunosuppressant plus corticosteroid for lupus nephritis
Age restrictionIndicated for adults aged 18 years or older per policy criteria
inv-53: Weight or age thresholds — examples of age/weight thresholds for certain agents
Common adult age thresholdMost agent criteria specify age ≥18 years for adults
Pediatric example — ArcalystArcalyst weight requirement: at least 10 kg for DIRA indication
Weight example — NiktimvoNiktimvo criteria reference weight threshold (used in GVHD criteria) — typically ≥40 kg for some agents
Proteinuria rangesTrials frequently required urine protein ≥0.75–1.0 g/day or UPCR/uPCR thresholds (e.g., ≥0.8 or ≥1.0 g/day in some studies)
Age thresholdsAge eligibility examples: ≥18 years for many adult trials; some pediatric indications used lower age limits (e.g., ≥12 years for Rezurock)
inv-60: Tarpeyo urine protein-to-creatinine ratio (prior threshold) — >= 0.8 g/g or proteinuria >= 1 g/day
Prior Tarpeyo UPCR thresholdPreviously cited Tarpeyo urine protein-to-creatinine ratio threshold: ≥0.8 g/g or proteinuria ≥1 g/day
Study contextNefIgArd Part A enrolled adults with UPCR ≥0.8 g/g or ≥1 g/day and eGFR ≥35 mL/min/1.73 m2 on stable RASi therapy
Dosing in trialTarpeyo 16 mg once daily for 9 months (then taper) used in efficacy trial
inv-61: UPCR / urine protein (updated) — >= 0.5 g/g OR urine protein >= 0.5 g/day
Updated UPCR thresholdUPCR ≥ 0.5 g/g OR urine protein ≥ 0.5 g/day (policy updated to align with KDIGO 2025 guidance)
Applies toFilspari, Tarpeyo, Voyxact and other specified IgAN therapies per updated criteria
Effective timingClarified in history entries and effective with interim updates through 2026 (see policy history)
inv-62: UPCR / urine protein (duplicate) — UPCR >= 0.5 g/g OR urine protein >= 0.5 g/day
Policy UPCR requirementUPCR ≥ 0.5 g/g OR urine protein ≥ 0.5 g/day required for eligibility for specified IgAN therapies
Covered agentsFilspari (sparsentan), Tarpeyo (budesonide), Voyxact (sibeprenlimab) among others referenced in policy updates
DocumentationLaboratory documentation of UPCR or 24‑hour urine protein should be submitted to support authorization
Medical benefit examples: Avsola, Inflectra, Remicade, Renflexis, Uplizna, Vyvgart (vials).
Managed under both examples: Actemra, certain adalimumab and tocilizumab products; check product list for billing pathway.
Documentation Required
Confirm Diagnosis and Disease Severity
Confirm Diagnosis and Disease Severity — Prior authorization requires documentation confirming the indicated diagnosis and disease severity using the diagnostic criteria or disease activity measures specified for the condition (e.g., biopsy‑confirmed IgAN, SLEDAI‑2K, MG‑ADL, QMG, HiSCR, BICLA/SRI definitions where applicable).
IgAN agents (Filspari, Tarpeyo, Voyxact, Voyxact): require biopsy‑confirmed diagnosis, UPCR/uPCR thresholds and eGFR thresholds as specified.
SLE agents (Saphnelo): require SLEDAI‑2K and BILAG criteria per trial definitions.
gMG agents (Uplizna, Vyvgart): require MG‑ADL, QMG thresholds and antibody status as applicable.
Step Therapy
Prior Authorization and Prior Therapy / Step Therapy Requirements
Prior Therapy, Step Therapy, and Brand‑to‑Brand Sequencing — Many biologics require trials and documented inadequate response or intolerance to specified prior therapies, including trials of preferred biosimilars or preferred brand products prior to non‑preferred/brand agents. Updated biosimilar sequencing and adalimumab/infliximab step requirements must be followed for new starts.
Adalimumab: new Humira starts require trial and failure of a preferred adalimumab product; non‑preferred adalimumab products require prior trial of all preferred adalimumab products.
Infliximab: many indications require trial and inadequate response or intolerance to preferred infliximab products (Inflectra, Avsola, etc.) before non‑preferred infliximab products (Janssen unbranded, Remicade, Renflexis) are approved.
Rystiggo and other agents: brand‑step requirements updated (see product‑specific criteria).
Biosimilar step/failure: failure to try preferred biosimilars per updated sequencing may risk denial.
Step Therapy
Therapy Sequencing / Prior Failures Required
Required Prior Therapy Trials and Evidence‑Informed Sequencing — Coverage requires documentation of prior conventional therapies where specified (e.g., topical/systemic immunosuppressives before biologics in dermatologic indications) and aligns trial requirements with available trial evidence where provided.
Hidradenitis Suppurativa: require trial of at least one other therapy (intralesional/oral corticosteroids, systemic antibiotics) before adalimumab or secukinumab.
Pyoderma Gangrenosum and Sarcoidosis: require failure of standard non‑biologic therapy and specified prior biologic trials per agent lists.
Myasthenia gravis and CIDP: require trials of specified immunosuppressives/evidence per diagnostic criteria.
Documentation Required
Documentation and Ongoing Response Required
Documentation and Ongoing Response — Authorization decisions require submission of medical records that document meeting coverage criteria at initial request and continued clinical benefit at reauthorization. Approvals are generally for up to 12 months and reauthorization requires documentation of ongoing response.
Initial and reauthorization approvals may be up to 12 months.
Records must include clinic visit notes, relevant labs, and medication history demonstrating clinical improvement.
Lack of documentation of response or missing records may result in denial.
Documentation Required
Required Clinical Documentation Examples / Medical Record Elements
Required Clinical Documentation Examples and Medical Record Elements — Submit office visit notes with diagnosis, relevant history, physical exam, prior medication trials, dates/doses, and supporting diagnostic tests or labs. For certain conditions, include disease‑specific measures and baseline labs (e.g., UPCR/uPCR, eGFR, antibody testing, electrophysiology for CIDP).
General: office visit notes with diagnosis, history, physical, medication history, and prescriber specialty.
IgAN/Voyxact/Filspari/Tarpeyo: biopsy report, UPCR/uPCR, eGFR, documentation of ACEi/ARB trial or intolerance.
CIDP: electrophysiologic criteria and supportive CSF/other testing where available.
gMG: antibody status (AChR or MuSK), MG‑ADL/QMG scores, prior ISTs and response.
Documentation Required
Diagnostic and Baseline Lab Documentation
Diagnostic and Baseline Laboratory Documentation — For agents treating renal or autoimmune conditions, include baseline and follow‑up lab values required by the product criteria (e.g., UPCR/uPCR, urine protein/day, eGFR) and biopsy proof when specified.
Voyxact/Filspari/Tarpeyo: UPCR/uPCR thresholds (policy updated to ≥0.5 g/g or ≥0.5 g/day for some agents) and eGFR minimums (e.g., eGFR ≥30 mL/min/1.73 m2 where specified).
Biopsy‑proven IgAN required for renal agents.
Document prior maximally tolerated ACEi/ARB trial or documented intolerance.
Documentation Required
CRS Diagnosis Documentation and Site‑of‑Service Exception
CRS (Cytokine Release Syndrome) — Agents used for CRS (e.g., Actemra/tocilizumab IV) require documentation confirming CRS diagnosis and that CRS meets grade 3–4 severity criteria per the policy (temperature ≥38 °C, vasopressor‑dependent hypotension, and hypoxia requiring high‑flow oxygen or positive pressure ventilation). Site‑of‑service exceptions may apply for CRS treatment.
Actemra IV and other tocilizumab IV products require CRS diagnosis documentation.
CRS criteria and site‑of‑service exception noted — document grade and supportive signs.
Approval contingent on documentation and inpatient admission plan when indicated.
Voyxact Specific Documentation — For Voyxact (sibeprenlimab‑szsi) requests include biopsy‑confirmed IgAN, UPCR/uPCR meeting policy thresholds, eGFR (≥30 mL/min/1.73 m2), not on dialysis or post‑transplant, and documentation of prior trial and inadequate response or intolerance to Filspari or Tarpeyo as required by updated criteria.
UPCR/uPCR: policy thresholds updated to ≥0.5 g/g OR ≥0.5 g/day for effective date July 2, 2026.
eGFR >= 30 mL/min/1.73 m2 and not on dialysis or post‑transplant required.
Document prior trial/failure or intolerance to Filspari (sparsentan) or Tarpeyo (budesonide).
Billing Rule
HCPCS Code Changes and Billing Rule
HCPCS and Coding Updates — New and replacement HCPCS codes have been added over time and may be required on PA submissions. Recent additions/replacements include codes such as C9305 (replaced), J9256 (replacement effective 01/01/2026), Q5156, J9332, J9333, J9334, J3402, and others noted in history. Include the correct HCPCS/NDC on submissions.
Providers should reference the policy history for additional HCPCS additions (J9332, J9333, J9334, J3402, etc.).
Include product name and appropriate HCPCS/NDC on PA forms to avoid processing delays.
Denial Risk
Age‑Based Site‑of‑Service Denial Risk
Age‑Based Site‑of‑Service Denial Risk — Site‑of‑service medical necessity reviews are applied only to individuals aged 13 years and older. Requests for site‑of‑service review or non‑standard sites for pediatric individuals under age 13 may be limited or denied unless specific pediatric criteria and specialty infusion capabilities are documented.
Pediatric considerations: pediatric physiology and infusion needs justify limiting site‑of‑service review to ≥13 years.
Document specialty pediatric infusion capabilities if requesting non‑standard sites for under‑13 individuals.
Denial Risk
Product No Longer Marketed — Denial/Non‑actionable Risk
Product Market Status and Non‑Actionable Requests — Products removed from market (e.g., Idacio adalimumab‑aacf) have been removed from the policy; PA requests for discontinued products may be non‑actionable. Check current product availability before submission.
Idacio (adalimumab‑aacf) removed from market; requests involving removed products are non‑actionable.
Providers should verify market status and NDCs; policy history documents removals and effective dates.
Note
Formulary‑Specific Applicability and State Exceptions
Formulary‑Specific Applicability and Exceptions — Certain coverage criteria and step‑therapy rules do NOT apply to specific custom formularies (e.g., Open formulary Formulary ID: 6062; Rx Plan F1 and other plan‑specific exceptions). Always verify member’s plan/formulary and consult policy 5.01.647 for custom formulary exceptions.
Note: Some adalimumab and infliximab criteria do not apply to one custom Open formulary (Formulary ID: 6062; Rx Plan F1).
Check member ID card/plan booklet to determine applicability; use policy 5.01.647 for custom plan criteria.
Also medically necessary when patient has high-risk conditions (e.g., symptomatic arrhythmia, significant respiratory disease, unstable renal function, difficult vascular access, acute mental status changes, prior severe adverse reactions/anaphylaxis)
CRS exceptionFor treatment-induced grade 3–4 cytokine release syndrome (fever ≥38°C, hypotension requiring vasopressors, hypoxia requiring high-flow oxygen or positive pressure), hospital-based care and inpatient admission required
inv-105: CIDP diagnostic criteria — electrophysiologic and clinical features required
CIDP diagnostic requirementsProgressive or relapsing motor and/or sensory symptoms in >1 limb with hyporeflexia/areflexia for ≥2 months plus electrophysiologic findings meeting 3 of 4 demyelination criteria and exclusion of alternative causes
Supportive testingIf available, CSF, nerve imaging, or biopsy results to support diagnosis should be provided
PrescriberPrescribed by or in consultation with a neurologist per policy criteria
NMOSD diagnostic requirementsAt least one core clinical characteristic (e.g., optic neuritis, acute myelitis, area postrema syndrome, acute brainstem, diencephalic, or cerebral syndromes) plus positive AQP4-IgG test and exclusion of alternative diagnoses
Relapse historyHistory of ≥1 relapse in last 12 months or ≥2 relapses in last 24 months and EDSS ≤7.5 required per policy for NMOSD therapies
AgeMost NMOSD biologic criteria specify age ≥18 years
inv-107: Generalized myasthenia gravis criteria — serology, age thresholds, clinical features
Generalized MG criteria — ageTypically requires age 18 years or older (agent-specific exceptions may allow ≥12 years)
Serology and therapiesDiagnosis with serologic testing for anti‑AChR or anti‑MuSK antibodies; trial of pyridostigmine unless contraindicated; trial of two or more immunosuppressive therapies or documented intolerance/contraindication
Prior targeted therapyFor AChR+ disease, prior inadequate response/intolerance to at least one complement inhibitor or efgartigimod may be required depending on agent
inv-108: IgA nephropathy criteria — biopsy-proven primary IgAN with UPCR >= 0.5 g/g and prior ACEi/ARB trial
IgAN core criteriaBiopsy-proven primary IgA nephropathy with UPCR ≥0.5 g/g (or urine protein ≥0.5 g/day), age ≥18 years, and prior trial of ACE inhibitor or ARB (or documented intolerance)
Specialist involvementPrescribed by or in consultation with a nephrologist
Concomitant therapyMany IgAN agents require continued ACEi/ARB unless intolerant; some require prior trial of specific IgAN therapies (e.g., Filspari or Tarpeyo) before Voyxact
HiSCR definitionHidradenitis Suppurativa Clinical Response (HiSCR): ≥50% reduction in abscess and inflammatory nodule count with no increase in abscess count and no increase in draining fistula count
UseUsed as primary efficacy outcome in HS trials (e.g., Humira and Cosentyx trials) and informs coverage decisions
BlyS (BAFF) targetB‑lymphocyte stimulator (BAFF), a protein promoting B‑cell survival and differentiation targeted by belimumab
Clinical relevanceInhibition of BAFF reduces autoantibody production in SLE and is the mechanism of Benlysta
Drug exampleBenlysta (belimumab) is FDA‑approved and included in policy criteria
inv-111: Type I interferon signature — definition and relevance to anifrolumab
Type I interferon signatureElevated expression of type I interferon‑inducible genes seen in ~60–80% of adults with active SLE; relevant to anifrolumab response
Drug mechanismAnifrolumab (Saphnelo) blocks IFNAR1 to inhibit type I IFN signaling
Clinical trialsTULIP trials evaluated anifrolumab in SLE but excluded severe lupus nephritis and neuropsychiatric lupus
inv-112: Anifrolumab (Saphnelo) — drug mechanism summary
MechanismAnifrolumab (Saphnelo) is a human IgG1κ monoclonal antibody that binds IFNAR1 to inhibit type I IFN signaling
Indication contextUsed as add‑on therapy for SLE per policy criteria; not indicated for severe active lupus nephritis per trial exclusions
Site-of-service reviewSaphnelo is subject to site‑of‑service review for administration location
DefinitionAcute graft‑versus‑host disease (aGVHD): immune‑mediated damage typically presenting within 100 days after allogeneic HSCT affecting skin, liver, and GI tract
Incidence and outcomesaGVHD occurs in ~20–80% of HSCT recipients; overall 5‑year survival improved to ~72% with modern care
Prophylaxis relevanceaGVHD prophylaxis (e.g., abatacept) criteria added to policy for eligible HSCT recipients
IgAN definitionImmunoglobulin A nephropathy (IgAN) is autoimmune kidney disease with IgA deposition in glomerular mesangium causing hematuria and proteinuria potentially progressing to ESRD
Management principlesIncludes supportive care, BP control, RAS inhibition to reduce proteinuria, and immunomodulatory therapies when indicated
Policy linkageMultiple new IgAN‑specific therapies (Filspari, Tarpeyo, Vanrafia, Voyxact) have coverage criteria in policy
CRS definitionCytokine release syndrome (CRS): systemic inflammatory response that can be treatment‑induced and meet grade 3–4 physiologic criteria (fever ≥38°C, hypotension requiring vasopressors, hypoxia requiring high‑flow oxygen or positive pressure)
Treatment implicationCRS grade 3–4 is a trigger for hospital‑based care and tocilizumab/anakinra coverage per policy
DocumentationCoverage requires documentation confirming CRS diagnosis and severity per policy criteria
inv-118: IgAN (alternate reference) — indication for Filspari and Fabhalta per KDIGO
KDIGO alignmentPolicy UPCR thresholds for IgAN therapies updated to align with KDIGO 2025: UPCR ≥0.5 g/g OR urine protein ≥0.5 g/day
Affected agentsFilspari, Tarpeyo, Voyxact and related IgAN criteria updated accordingly
Policy historyClarification documented in policy history entries effective with 2026 interim updates
inv-119: UPCR threshold — UPCR updated to >= 0.5 g/g OR urine protein >= 0.5 g/day per KDIGO
UPCR/KDIGO updateUPCR threshold updated to ≥0.5 g/g OR urine protein ≥0.5 g/day per KDIGO 2025 guidance and policy revisions
Policy applicationApplied to Filspari, Tarpeyo, Voyxact and other IgAN therapies where specified
Documentation noteProviders should submit UPCR or 24‑hour urine protein and eGFR to support authorization
inv-120: Updated proteinuria threshold — UPCR ≥0.5 g/g OR urine protein ≥0.5 g/day
Updated numeric thresholdUpdated proteinuria threshold: UPCR ≥0.5 g/g OR urine protein ≥0.5 g/day
ScopeUsed consistently across policy entries for IgAN therapies after 2025–2026 updates
Effective date noteChanges reflected in history with effective implementation dates noted in policy history entries
inv-121: Pediatric age requirement — Benlysta SC age changed to 5 years and older for active lupus nephritis
Benlysta SC pediatric age changeBenlysta (belimumab) SC age requirement updated to 5 years and older for active lupus nephritis and SLE per policy history
Prior agePreviously the SC formulation age requirement for active lupus nephritis was 18 years and older
Prescribing contextApplies when Benlysta is prescribed by or in consultation with a nephrologist or rheumatologist per policy criteria
Added Otezla XR (apremilast extended-release) for Behcet's disease and updated Benlysta (belimumab) SC age requirement for active lupus nephritis from 18 to 5 years and older.
2026-03-01interim_review_effective_notice
Policy changes clarifying UPCR thresholds for Filspari and Tarpeyo to at least 0.5 g/g OR urine protein ≥0.5 g/day to align with KDIGO 2025; these changes effective July 2, 2026 following 90-day provider notification.
2026-06-01interim_reviewLatest
Updated Voyxact criteria: lowered UPCR threshold to ≥0.5 g/g (or urine protein ≥0.5 g/day), added eGFR ≥30 mL/min/1.73 m2 and prior therapy requirements; added site-of-service review for Rystiggo; additional product/formulary and biosimilar preference updates through May 12, 2026.
Selected recent updates and effective dates: policy history reflects multiple interim and annual reviews adding new product criteria and aligning numeric thresholds with KDIGO guidance. Notable changes include: addition of coverage criteria for agents such as Orencia for aGVHD prophylaxis, Filspari (sparsentan), Tarpeyo (budesonide), Rezurock (belumosudil), Voyxact (sibeprenlimab), and Avtozma (tocilizumab‑anoh); updated urine protein/UPCR thresholds for IgA nephropathy therapies to UPCR ≥ 0.5 g/g OR urine protein ≥ 0.5 g/day to align with KDIGO 2025 guidance; replacement of HCPCS code C9305 with J9256 effective 01/01/2026; and multiple adalimumab/infliximab biosimilar preference and step‑therapy updates. Several changes were effective following 90‑day provider notification, with documented interim review approval dates spanning 2024–2026 and effective dates including January 3, 2025, January 1, 2026, and policywide updates effective July 2, 2026 where noted.