ModifiedCignaPolicy IP0646

Inflammatory Conditions - Zymfentra Prior Authorization Policy

Defines prior authorization requirements and medical necessity criteria for coverage of Zymfentra (infliximab‑dyyb SC) for adults with Crohn's disease or ulcerative colitis on Cigna-administered benefit plans.

Policy Summary

PayerCigna

PolicyInflammatory Conditions - Zymfentra Prior Authorization Policy

Policy CodePolicy IP0646

Change TypeNew policytitle and policy statement addedcoverage language clarified

Effective DateSep 1, 2025

Next Review Date

Key ActionObtain prior authorization for Zymfentra (bill using J1748) and document specialist involvement and induction with an infliximab IV product when requesting initial approval.

SourceLink

POLICY UPDATE CHANGES

New policy created for Zymfentra prior authorization.

Policy title updated to 'Inflammatory Conditions - Zymfentra Prior Authorization Policy' and 'Policy Statement' added.

Conditions Not Covered language clarified to explicitly disallow concurrent use with another biologic or targeted synthetic oral small molecule drug.

2FDA‑approved indications covered

J1748HCPCS code for Zymfentra

120 mg q2wrecommended SC dosing

6 mo / 1 yr

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Coverage Criteria for Zymfentra

FDA‑Approved Indications and Criteria

Covered when ONE of the following indication-specific pathways is met (Crohn's disease or Ulcerative colitis).

Indication: Patient has Crohn's disease OR Ulcerative colitis as an FDA‑approved indication for Zymfentra

See separate branches for Initial Therapy vs Currently Receiving an Infliximab Product.

Crohn's Disease - Initial Therapy: Approve for 6 months if ALL of the following are met

(i) Patient is ≥ 18 years of age; AND (ii) per prescriber, the patient is currently receiving infliximab IV maintenance therapy or will receive induction dosing with an infliximab IV product within 3 months of initiating Zymfentra; AND (iii) patient meets ONE of (a) tried or currently taking systemic corticosteroids, or corticosteroids are contraindicated; OR (b) tried one conventional systemic therapy for Crohn's disease (examples: azathioprine, 6‑mercaptopurine, methotrexate) — exception if patient has already tried at least one biologic other than the requested medication (a biosimilar of the requested biologic does not count); OR (c) enterocutaneous (perianal or abdominal) or rectovaginal fistulas; OR (d) prior ileocolonic resection; AND (iv) medication prescribed by or in consultation with a gastroenterologist.

Crohn's Disease - Currently Receiving an Infliximab Product: Approve for 1 year if BOTH are met

(i) Patient has been established on therapy for at least 6 months; AND (ii) patient meets at least one of: (a) experienced a beneficial clinical response from baseline by at least one objective measure (examples: fecal calprotectin, fecal lactoferrin, C-reactive protein, imaging [MRE/CTE], endoscopy, or reduced corticosteroid dose); OR (b) experienced improvement in at least one symptom (e.g., decreased pain, fatigue, stool frequency, and/or blood in stool).

Ulcerative Colitis - Initial Therapy: Approve for 6 months if ALL are met

Ulcerative Colitis - Currently Receiving an Infliximab Product: Approve for 1 year if BOTH are met

(i) Patient has been established on therapy for at least 6 months; AND (ii) patient experienced a beneficial clinical response from baseline by at least one objective measure (examples: fecal markers, serum markers, imaging, endoscopy, reduced corticosteroid dose) OR improvement in at least one symptom (e.g., decreased pain, fatigue, stool frequency, and/or rectal bleeding).

Zymfentra is not considered medically necessary for any indication other than the FDA‑approved uses specified in this policy. The policy explicitly states: “Zymfentra for any other use is considered not medically necessary.” Providers should refer to the approved indication pathways (Crohn's disease and Ulcerative colitis) when requesting coverage.

The policy prohibits concurrent administration of Zymfentra with other biologic agents or with targeted synthetic oral small molecule drugs for inflammatory conditions. As noted in the Conditions Not Covered section: “This medication should not be administered in combination with another biologic or with a targeted synthetic oral small molecule drug used for an inflammatory condition.”

The appendix provides an informational listing of agents, mechanisms, and indication abbreviations but is not an all‑inclusive list. It directs readers to the prescribing information for specific FDA‑approved indications and does not itself create explicit coverage exclusions beyond those stated in the main policy text.

Reiterating the policy position: concurrent use of Zymfentra with another biologic or with a targeted synthetic oral small molecule drug for inflammatory conditions is not covered. This restriction is intended to avoid combination regimens that lack controlled data demonstrating additive benefit and may increase adverse events (exceptions for conventional synthetic DMARDs are noted elsewhere).

The appendix does not include any separate not medically necessary determinations; it functions as a reference list of agents, mechanism abbreviations, and indication codes and instructs readers to consult each agent’s prescribing information for FDA‑approved uses.

Coding and Dosing Details

Considered Medically Necessary when criteria are metHCPCSCovered

J1748

Injection, infliximab-dyyb (Zymfentra), 10 mg (Code effective 07/01/2024)

Referenced agents and formulationsmixed

tildrakizumab-asmn	tildrakizumab-asmn SC injection (IL-23 inhibitor) - PsO
risankizumab-rzaa SC/IV	risankizumab-rzaa SC injection and IV infusion (IL-23 inhibitor) - CD, PSA, PsO, UC (SC); CD, UC (IV)
guselkumab SC/IV	guselkumab SC injection and IV infusion (IL-23 inhibitor) - PsA, PsO, UC (SC); UC (IV)
vedolizumab IV/SC	vedolizumab IV infusion and SC injection (integrin receptor antagonist) - CD, UC
apremilast (Otezla)	apremilast tablets (PDE4 inhibitor) - PsO, PsA
abrocitinib (Cibinqo)	abrocitinib tablets (JAK inhibitor) - Atopic dermatitis
baricitinib (Olumiant)	baricitinib tablets (JAK inhibitor) - RA, AA
ritlecitinib (Litfulo)	ritlecitinib capsules (JAK inhibitor) - AA
deuruxolitinib (Leqselvi)	deuruxolitinib tablets (JAK inhibitor) - AA
upadacitinib (Rinvoq) ER/ LQ	upadacitinib extended-release tablets and oral solution (JAK inhibitor) - AD, AS, nr-axSpA, RA, PsA, UC (ER); PsA, PJIA (LQ)

1–10 of 14

1/2

Zymfentra dosing frequency

Recommended maintenance dose120 mg subcutaneously once every 2 weeks

Route of administrationSubcutaneous (SC)

Dosing intervalOnce every 2 weeks (q2w)

Provider Actions, Prior Authorization, and Billing

Prior Authorization

Prior Authorization Required

Prior Authorization Required for Zymfentra (J1748). Prior authorization is required for Zymfentra. Initial approvals are typically 6 months for patients starting therapy and 1 year for patients established on an infliximab product. All approvals are provided for the duration noted in the policy; when expressed in months, 1 month = 30 days.

Zymfentra must be billed using HCPCS code J1748.
Initial approval duration (Initial Therapy): 6 months.
Continuation approval duration (Established on infliximab): 1 year.

Documentation Required

Prescriber Specialty / Documentation

Prescriber specialty and documentation expectations. Because of the specialized skills required for evaluation and monitoring, initial approval requires that Zymfentra be prescribed by or in consultation with a physician who specializes in the condition being treated (e.g., gastroenterologist for Crohn's disease or ulcerative colitis). Document the specialist prescribing or consulting on the request.

Background

Zymfentra is a subcutaneous formulation of infliximab, a tumor necrosis factor (TNF) inhibitor, indicated as maintenance therapy for adults with moderately to severely active Crohn's disease and Ulcerative colitis after induction with an infliximab intravenous product. The policy and overview describe Zymfentra as the SC maintenance option following the standard IV induction regimen (weeks 0, 2, and 6) for patients who have achieved clinical response or remission.

Definitions and Induction Regimen

Induction with infliximab IV

Induction regimen (infliximab IV)Intravenous infliximab administered at Weeks 0, 2, and 6 as the induction regimen prior to switching to Zymfentra subcutaneous maintenance

Timing for switch to SC maintenanceSwitch to Zymfentra may occur at Week 10 or at a scheduled infliximab IV infusion when clinical response/remission is achieved

Use contextInduction with infliximab IV is required for the FDA‑approved maintenance indication for Crohn's disease and ulcerative colitis

Abbreviations and definitions

SCSubcutaneous (SC)

IVIntravenous (IV)