Commercial

Medical Policy

Notification

Ustekinumab for Intravenous Infusion

Notification Issue Date:

This version of the policy will become effective 01/06/2020.

This policy was updated to communicate the coverage criteria for the new FDA approval of ustekinumab (Stelara®) for the treatment of ulcerative colitis, including dosing and frequency requirements. Prior medications used in Crohn's disease have also been updated.

Title:

Ustekinumab for Intravenous Infusion

Policy #:

08.00.82r

Policy

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

MEDICALLY NECESSARY

COMPANY-DESIGNATED PREFERRED AND NONPREFERRED PRODUCTS

Although there are many ustekinumab products on the market, there is no reliable evidence of the superiority of any one ustekinumab product compared with other ustekinumab products. The preferred product, ustekinumab-kfce (Yesintek), is less costly and at least as likely to produce equivalent therapeutic results as the nonpreferred* ustekinumab products.

PREFERRED USTEKINUMAB PRODUCT	NONPREFERRED USTEKINUMAB PRODUCTS*
ustekinumab-kfce (Yesintek)	ustekinumab (Stelara)
	ustekinumab-aauz (Otulfi)
	ustekinumab-aekn (Selarsdi)
	ustekinumab-auub (Wezlana)
	ustekinumab-hmny (Starjemza)
	ustekinumab-srlf (Imuldosa)
	ustekinumab-stba (Steqeyma)
	ustekinumab-ttwe (Pyzchiva)
	other nonpreferred ustekinumab biosimilars

According to the US Food and Drug Administration (FDA), “a biosimilar is a biological product that has no clinically meaningful differences from the existing FDA-approved reference product. All biosimilar products meet the FDA’s rigorous standards for approval for the indications described in the product labeling. Once a biosimilar has been approved by the FDA, the safety and effectiveness of these products have been established, just as they have been for the reference product.” Coverage of a biosimilar product as an alternate to a reference product is not considered a form of step therapy by the Company.

*Use of a nonpreferred ustekinumab product to treat the specified indication is eligible for coverage when the individual has documentation of a contraindication(s) or intolerance(s) (e.g., as documented per the FDA labeling), or inadequate response to the preferred product, ustekinumab-kfce (Yesintek), for a period sufficient to determine clinical response as outlined in the clinical trial for the indication requested.

INITIAL THERAPY WITH USTEKINUMAB PRODUCTS FOR INTRAVENOUS USE

CROHN DISEASE AND ULCERATIVE COLITIS
Ustekinumab products for intravenous infusion are considered medically necessary and, therefore, covered for the treatment of individuals with moderate-to-severe active Crohn disease or moderate-to-severe active ulcerative colitis when both of the following criteria and the Dosing and Frequency Requirements listed below are met:

The individual is at least 18 years of age for ulcerative colitis
The individual is at least 2 years of age for Crohn disease

IMMUNE-CHECKPOINT INHIBITOR–RELATED TOXICITY MANAGEMENT

Ustekinumab products for intravenous infusion are considered medically necessary and, therefore, covered for the management of the following autoimmune-like toxicities (also known as immune-related adverse events), when other etiologies have been ruled out and any of the following criteria and the Dosing and Frequency Requirements listed below are met:

Infliximab- and/or vedolizumab-refractory mild (Grade 1) diarrhea or colitis if persistent or progressive symptoms and positive lactoferrin/calprotectin

Infliximab- and/or vedolizumab-refractory moderate (Grade 2) or severe (Grade 3-4) diarrhea or colitis

DOSING AND FREQUENCY OF ADMINISTRATION

The following dosage and frequency information was taken from the Prescribing Information for this product at the time the policy was being developed:

CROHN DISEASE, ULCERATIVE COLITIS, AND IMMUNE-CHECKPOINT INHIBITOR–RELATED TOXICITY MANAGEMENT (DIARRHEA, COLITIS)

For initial intravenous infusion in adults:
- For persons whose weight is up to 55 kg, the recommended dose is 260 mg (two vials).
- For persons whose weight is more than 55 kg to 85 kg, the recommended dose is 390 mg (three vials).
- For persons whose weight is more than 85 kg, the recommended dose is 520 mg (four vials).
For initial intravenous infusion in pediatric ( 2 years and older) Crohn disease ONLY:

For persons whose weight is 10 kg to 25 kg, the recommended dose is 10 mg/kg.
For persons whose weight is more than 25 kg, follow the above adult dosing.

Note: Maintenance treatment is administered by subcutaneous formulation.

NOT MEDICALLY NECESSARY

Use of a nonpreferred* ustekinumab product is considered not medically necessary and, therefore, not covered because it is more costly than the preferred product that is at least as likely to produce equivalent therapeutic results for that individual's illness.

EXPERIMENTAL/INVESTIGATIONAL

Use of ustekinumab products in the pediatric population for the treatment of Crohn disease, ulcerative colitis, or immune-checkpoint inhibitor–related toxicities is considered experimental/investigational and, therefore, not covered because the safety and/or effectiveness of this biologic cannot be established by review of the available published peer-reviewed literature.

All other uses of ustekinumab products are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the medical policy on off-label coverage for prescription drugs and biologics.

DOSING AND FREQUENCY REQUIREMENTS

The Company reserves the right to modify the Dosing and Frequency Requirements listed in this policy to ensure consistency with the most recently published recommendations for the use of ustekinumab products. Changes to these guidelines are based on a consensus of information obtained from resources such as, but not limited to, the FDA; Company-recognized authoritative pharmacology compendia; or published peer-reviewed clinical research. The professional provider must supply supporting documentation (i.e., published peer-reviewed literature) in order to request coverage for an amount of ustekinumab products outside of the Dosing and Frequency Requirements listed in this policy. For a list of Company-recognized pharmacology compendia, view our policy on off-label coverage for prescription drugs and biologics.

Accurate member information is necessary for the Company to approve the requested dose and frequency of this drug. If the member’s dose, frequency, or regimen changes (based on factors such as changes in member weight or incomplete therapeutic response), the provider must submit those changes to the Company for a new approval based on those changes as part of the precertification process. The Company reserves the right to conduct postpayment review and audit procedures for any claims submitted for ustekinumab products.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

When coverage of ustekinumab products are requested outside of the Dosing and Frequency Requirements listed in this policy, the prescribing professional provider must supply documentation (i.e., published peer-reviewed literature) to the Company that supports this request.

BILLING REQUIREMENTS

For drugs that have more than one method of administration, the appropriate modifier must be appended to indicate the route of administration.

To report the intravenous route of administration, append the following modifier: JA Administered Intravenously

Inclusion of a code in this policy does not imply reimbursement. Eligibility, benefits, limitations, exclusions, utilization management/referral requirements, provider contracts, and Company policies apply.

Guidelines

Individuals should not be receiving concurrent therapy with any other biologic disease–modifying antirheumatic drug (DMARD) (i.e., anti–tumor necrosis factor agents) while receiving ustekinumab products.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, ustekinumab products are covered under the medical benefits of the Company’s products when the medical necessity criteria and Dosing and Frequency Requirements listed in this medical policy are met. Ustekinumab products for subcutaneous injection may be available for coverage under any applicable pharmacy benefit. Individual benefits must be verified.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Ustekinumab (Stelara) received FDA approval on September 25, 2009, for the treatment of adults (18 years or older) with moderate-to-severe plaque psoriasis who are candidates for phototherapy or systemic therapy. Supplemental approvals for ustekinumab (Stelara) have since been issued by the FDA for the treatment of psoriatic arthritis, Crohn disease, and ulcerative colitis. The FDA has issued subsequent approvals for biosimilar products.

PEDIATRIC USE

The safety and effectiveness of ustekinumab products in pediatric individuals for the treatment of ulcerative colitis have not been evaluated.

Description

CROHN DISEASE AND ULCERATIVE COLITIS

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract of unknown etiology. IBD has two major categories: ulcerative colitis (UC) and Crohn disease (CD). The most common symptoms in UC and CD are diarrhea, rectal bleeding, urgency to have bowel movements, abdominal cramps, pain, fever, and weight loss. Although UC and CD have similar clinical presentations, they differ in the body areas affected. UC primarily causes inflammation of the mucosal lining and is generally limited to the colon and rectum, whereas CD affects the entire digestive system and can produce ulcers that extend deep into the intestinal wall.

The treatment of CD and UC is focused on stopping the inflammation and preventing flare-ups. The type of treatment depends on the type and severity of symptoms. Mild symptoms may respond to an antidiarrheal medicine such as loperamide (e.g., Imodium). Treatment for individuals who may be having mild-to-moderate symptoms include aminosalicylates (and antibiotics for CD), whereas individuals with severe symptoms may be treated with corticosteroids, immunomodulators, or biologics.

US FOOD AND DRUG ADMINISTRATION (FDA) APPROVAL OF USTEKINUMAB (STELARA)

Ustekinumab (Stelara) for subcutaneous injection received FDA approval on September 25, 2009, for the treatment of adult individuals (18 years or older) with moderate-to-severe plaque psoriasis and who are candidates for phototherapy or systemic therapy. This indication was later expanded to include pediatric individuals 6 to 17 years of age with moderate-to-severe plaque psoriasis and who are candidates for phototherapy or systemic therapy. In September 2013, the FDA approved ustekinumab (Stelara) for subcutaneous injection for the treatment of adult individuals (18 years or older) with active plaque psoriasis, to be used alone or in combination with methotrexate; this indication was expanded in July 2022 to include pediatric individuals 6 to 17 years of age with active plaque psoriasis. In September 2016, the FDA approved ustekinumab (Stelara) for intravenous infusion for the treatment of moderately to severely active CD in adult individuals (18 years or older) who have failed or were intolerant to treatment with immunomodulators or corticosteroids but never failed treatment with a tumor necrosis factor (TNF) blocker, or who failed or were intolerant to treatment with one or more TNF blockers. Subsequent maintenance therapy for CD is by subcutaneous injection. In October 2019, the FDA approved ustekinumab (Stelara) for intravenous infusion and subsequent and subcutaneous injection for the treatment of adult individuals (18 years or older) with moderately to severely active UC who have failed or were intolerant to treatment with a biologic, corticosteroids, or immunomodulators.

Ustekinumab (Stelara) is a human immunoglobulin G1 kappa (IgG1қ) monoclonal antibody (a human interleukin [IL]-12 and -23 antagonist) that binds with high affinity and specificity to the p40 protein subunit used by both the interleukin IL-12 and IL-23 cytokines. IL-12 and IL-23 are naturally occurring cytokines that are involved in inflammatory and immune responses. In in vitro models, ustekinumab (Stelara) was shown to disrupt IL-12– and IL-23–mediated signaling and cytokine cascades.

PEER-REVIEWED LITERATURE - ADULTS

SUMMARY FOR CROHN DISEASE

The FDA approval was based on three randomized, double-blind, placebo-controlled clinical studies in adult individuals with moderately to severely active CD (Crohn’s Disease Activity Index [CDAI] score of 220–450). There were two 8-week intravenous induction studies (CD-1 and CD-2) followed by a 44-week subcutaneous randomized withdrawal maintenance study (CD-3) representing 52 weeks of therapy.

In studies CD-1 and CD-2, 1409 individuals were randomly assigned, of whom 1368 (CD-1, n=741; CD-2, n=627) were included in the final efficacy analysis. Induction of clinical response (defined as a reduction in CDAI score of ≥100 points or CDAI score of <150) at week 6 and clinical remission (defined as a CDAI score of <150) at week 8 were evaluated. In both studies, individuals were randomly assigned to receive a single intravenous administration of ustekinumab (Stelara) at either approximately 6 mg/kg, placebo, or 130 mg (a lower dose than recommended).

In Study CD-1, individuals had failed or were intolerant to prior treatment with a TNF blocker: 29% of individuals had an inadequate initial response (primary nonresponders), 69% responded but subsequently lost response (secondary nonresponders) and 36% were intolerant to a TNF blocker. Of these individuals, 48% failed or were intolerant to one TNF blocker and 52% had failed two or three prior TNF blockers. At baseline and throughout the study, approximately 46% of the individuals were receiving corticosteroids and 31% of the individuals were receiving immunomodulators (azathioprine, 6-mercaptopurine, methotrexate). The median baseline CDAI score was 319 in the ustekinumab (Stelara) approximately 6 mg/kg group and 313 in the placebo group.

In Study CD-2, individuals had failed or were intolerant to prior treatment with corticosteroids (81% of individuals), at least one immunomodulator (6-mercaptopurine, azathioprine, methotrexate; 68% of individuals) or both (49% of individuals). Additionally, 69% never received a TNF blocker and 31% previously received but had not failed a TNF blocker. At baseline, and throughout the study, approximately 39% of the individuals were receiving corticosteroids and 35% of the individuals were receiving immunomodulators (azathioprine, 6-mercaptopurine, methotrexate). The median baseline CDAI score was 286 in the ustekinumab (Stelara) and 290 in the placebo group. In these induction studies, a greater proportion of individuals treated with ustekinumab (Stelara) achieved clinical response at week 6 and clinical remission at week 8 compared to placebo. Clinical response and remission were significant as early as week 3 in ustekinumab (Stelara)-treated individuals and continued to improve through week 8.

The maintenance study (CD-3) evaluated 388 individuals who achieved clinical response (≥100 point reduction in CDAI score) at week 8 of induction with ustekinumab (Stelara) in studies CD-1 or CD-2. Individuals were randomly assigned to receive a subcutaneous maintenance regimen of either 90 mg ustekinumab (Stelara) every 8 weeks or placebo for 44 weeks. At Week 44, 47% of individuals who received ustekinumab (Stelara) were corticosteroid-free and in clinical remission, compared to 30% of individuals in the placebo group. At week 0 of Study CD-3, 34 of 56 (61%) ustekinumab (Stelara)-treated individuals who previously failed or were intolerant to TNF-blocker therapies were in clinical remission and 23 of 56 (41%) of these individuals were in clinical remission at Week 44. In the placebo arm, 27 of 61 (44%) individuals were in clinical remission at week 0 while 16 of 61 (26%) of these individuals were in remission at week 44. At week 0 of Study CD-3, 46 of 72 (64%) ustekinumab (Stelara)-treated individuals who had previously failed immunomodulator therapy or corticosteroids (but not TNF blockers) were in clinical remission, and 45 of 72 (63%) of these individuals were in clinical remission at week 44. In the placebo arm, 50 of 70 (71%) of these individuals were in clinical remission at week 0 while 31 of 70 (44%) were in remission at week 44. In the subset of these individuals who were also naïve to TNF blockers, 34 of 52 (65%) of ustekinumab (Stelara)-treated individuals were in clinical remission at week 44 as compared to 25 of 51 (49%) in the placebo arm. Individuals who were not in clinical response 8 weeks after ustekinumab (Stelara) induction were not included in the primary efficacy analyses for study CD-3; however, these individuals were eligible to receive a 90-mg subcutaneous injection of ustekinumab (Stelara) upon entry into study CD-3. Of these individuals, 102 of 219 (47%) achieved clinical response 8 weeks later and were followed up for the duration of the study.

A Phase 3, open-label UNITI Jr trial, which evaluated the efficacy, safety, and pharmacokinetics of Stelara in 101 pediatric individuals from 2 to 17 years of age with moderate-to-severe active CD through Week 52 (8 weeks of induction and 44 weeks of maintenance treatment) was conducted. Individuals enrolled in the trial had an inadequate response and/or intolerance to conventional therapies and/or biologic therapy (TNF antagonists or vedolizumab). The primary endpoint was clinical remission, defined as a Pediatric Crohn’s Disease Activity Index (PDCAI) score of 10 or less at Week 8. At Week 8, 46% of patients achieved clinical remission. Of the 81 individuals who achieved clinical response or remission at Week 8, 39 individuals received subcutaneous maintenance therapy. At Week 52, 51% (20/39) achieved clinical remission.

SUMMARY FOR ULCERATIVE COLITIS
The FDA approval was based on two randomized, double-blind, placebo-controlled clinical studies in 961 adult individuals with moderate to severe UC who had an inadequate response to or failed to tolerate a biologic (i.e., TNF blocker and/or vedolizumab), corticosteroids, or immunomodulators (e.g., 6-mercaptopurine or azathioprine therapy). Participants received an intravenous induction dose of ustekinumab (Stelara), either 130 mg (N=320) or a weight-range–based dose that approximated 6 mg/kg of body weight (N=322) or placebo (N=319), and were reassessed at week 8. Those who responded were randomly assigned again to receive subcutaneous maintenance injections of 90 mg of ustekinumab either every 12 weeks (N=172) or every 8 weeks (N=176) or placebo (N=175).

The primary end point in the induction trial (week 8) and the maintenance trial (week 44) was clinical remission (defined as a total score of ≤2 on the Mayo scale [range, 0–12, with higher scores indicating more severe disease] and no subscore greater than 1 [range, 0–3] on any of the four Mayo scale components). Week 8 results showed those who received ustekinumab (Stelara) (either 130 mg or 6 mg/kg dose) had higher rates of clinical remission compared to placebo (15.6%, 15.5%, vs 5.3%, respectively) (P<0.001 for both). Week 44 results showed those who received ustekinumab (Stelara) (either every 12 weeks or every 8 weeks) had higher rates of clinical remission compared to placebo (38.4%, 43.8%, vs. 24%, respectively) (P=0.002 and P<0.001, respectively). The rates of serious adverse events in those who received ustekinumab (Stelara) compared with placebo were similar.

PEER-REVIEWED LITERATURE: PEDIATRICS

SUMMARY FOR ULCERATIVE COLITIS

As previously mentioned, the first-line therapies for CD or UC may include aminosalicylates, corticosteroids, and immunomodulators. Once an individual has failed or is intolerant to these therapies, a biologic such as infliximab is initiated in the pediatric population. Over time, some individuals lose response to this initial biologic and need another biologic option. (Ruemmele et al., 2014; van Rheenen et al., 2020; Turner et al., 2018). Clinical remission for CD or UC may be reported using several scoring systems^†, including abbreviated Paediatric Crohn's Disease Activity Index [aPCDAI], partial Mayo Score (PMS), and the Harvey-Bradshaw Index (HBI).

The safety and effectiveness of ustekinumab (Stelara) for the treatment of pediatric individuals with UC are still being established. The evidence is mainly based on case series, retrospective reviews, and small cohort studies with a heterogenous mix of individuals with and without IBD. The limitations of the literature consist of small sample sizes, retrospective designs, heterogeneous population (e.g., dosing not standardized, previous medication exposures). While low-quality studies with small data sets, with typically incomplete follow-ups, report clinical remission at a measurable level (40%–60% at 1 year) (Chavannes et al., 2019; Cohen et al., 2020; Dayan et al., 2019), there is a lack of endoscopic data, fecal calprotectin (FC) data, and histologic data to determine the extent of bowel improvement in this subset of individuals. There are no extensive analyses completed in these investigations to demonstrate which attributes an individual possesses to forecast if they will respond to therapy. The limited data in the pediatric population showed a relatively good safety profile (no/few adverse events).

While the objective clinical outcome needed to establish effectiveness, namely clinical remission, had been investigated, those data are primarily from studies that lack appropriate controls and were not prospectively conducted.

^†Abbreviated Paediatric Crohn's Disease Activity Index [aPCDAI] is a clinical index containing three history items (abdominal pain, number, and consistency of stools and individuals functioning) and three physical examinations (weight change, abdominal mass or tenderness, and perirectal disease). The aPCDAI has been found to demonstrate sufficient correlation with the full PCDAI. Scores range from 0 (clinical remission) to 70 (severe, active disease), with the suggested cutoff points being less than 10 (remission), 10 to 15 (mild disease), 16 to 25 (moderate disease), and greater than 25 (severe disease).

Partial Mayo score [pMS]: The partial Mayo Score (PMS) uses the three noninvasive components of the full Mayo Score (stool frequency, rectal bleeding, and PGA). Each is ranked at a score of 0 to 3; the maximum score is 9.

Harvey-Bradshaw Index (HBI): Five variables are recorded on one occasion: general well-being, abdominal pain, number of liquid stools daily, abdominal mass, extraintestinal complications.

Remission: <5
Mild Disease: 5 to 7
Moderate Disease: 8 to 16
Severe Disease: >16

OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

References

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Rosh JR, Turner D, Griffiths A, et al. Ustekinumab in Paediatric Patients with Moderately to Severely Active Crohn's Disease: Pharmacokinetics, Safety, and Efficacy Results from UniStar, a Phase 1 Study. J Crohns Colitis. 2021;15(11):1931-1942.

Ruemmele FM, Veres G, Kolho KL, et al.; European Crohn's and Colitis Organisation; European Society of Pediatric Gastroenterology, Hepatology and Nutrition. Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn's disease. J Crohns Colitis. 2014;8(10):1179-1207.

Sands BE, Sandborn WJ, Panaccione R; UNIFI Study Group, et al. Ustekinumab as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med. 2019;381(13):1201-1214.

Sandborn WJ, Rebuck R, Wang Y, et al. Five-year efficacy and safety of ustekinumab treatment in Crohn's disease: the IM-UNITI Trial. Clin Gastroenterol Hepatol. 2022;20(3):578-590.

Sipponen T, Savilahti E, Kolho KL, et al. Crohn's disease activity assessed by fecal calprotectin and lactoferrin: correlation with Crohn's disease activity index and endoscopic findings. Inflamm Bowel Dis. 2008;14(1):40-46.

Thomas AS, Ma W, Wang Y. Ustekinumab for Refractory Colitis Associated with Immune Checkpoint Inhibitors. N Engl J Med. 2021;384(6):581-583.

Torres J, Bonovas S, Doherty G, et al. ECCO Guidelines on Therapeutics in Crohn's Disease: Medical Treatment. J Crohns Colitis. 2020:1;14(1):4-22.

Turner D, Rosh JR, Cohen SA, et al; UniStar Study Group. Ustekinumab in paediatric patients with moderately to severely active Crohn's disease: UniStar study long-term extension results. J Pediatr Gastroenterol Nutr. 2024;79(2):315-324.

Turner D, Ruemmele FM, Orlanski-Meyer E, et al. Management of Pediatric Ulcerative Colitis, Part 1: Ambulatory Care-An Evidence-based Guideline From European Crohn's and Colitis Organization and European Society of Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2018;67(2):257-291.

Turner D, Ruemmele FM, Orlanski-Meyer E, et al. Management of Pediatric Ulcerative Colitis, Part 2: Ambulatory Care-An Evidence-based Guideline From European Crohn's and Colitis Organization and European Society of Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2018;67(2):292-310.

US Food and Drug Administration (FDA). Ustekinumab (Stelara®) [prescribing information]. [FDA Web site]. Original 09/25/09. Updated 06/2025. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed July 7, 2026.

US Food and Drug Administration (FDA). ustekinumab-auub (Wezlana) [prescribing information]. [FDA Web site]. Original 10/31/2023. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed July 7, 2026.

US Food and Drug Administration (FDA). ustekinumab-aekn (Selarsdi) [prescribing information]. [FDA Web site]. Original 10/18/2024. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed July 7, 2026.

US Food and Drug Administration (FDA). ustekinumab-aauz (Otulfi) [prescribing information]. [FDA Web site]. Original 09/27/2024. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed July 7, 2026.

US Food and Drug Administration (FDA). ustekinumab-hmny (Starjemza) [prescribing information]. [FDA Web site]. Original 05/22/2025. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed July 7, 2026.

US Food and Drug Administration (FDA). ustekinumab-ttwe (Pyzchiva) [prescribing information]. [FDA Web site]. Original 06/28/2024. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed July 7, 2026.

US Food and Drug Administration (FDA). ustekinumab-srlf (Imuldosa) [prescribing information]. [FDA Web site]. Original 10/10/2024. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed July 7, 2026.

US Food and Drug Administration (FDA). ustekinumab-kfce (Yesintek) [prescribing information]. [FDA Web site]. Original 11/19/2024. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed July 7, 2026.

US Food and Drug Administration (FDA). ustekinumab-stba (Steqeyma) [prescribing information]. [FDA Web site]. Original 12/17/2024. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed July 7, 2026.

Ustekinumab (Stelara®). [prescribing information] Horsham, PA: Janssen Biotech, Inc.; updated 03/2024. Available at: https://www.stelarainfo.com/. Accessed July 7, 2026.

van Rheenen PF, Aloi M, Assa A, et al. The Medical Management of Paediatric Crohn's Disease: an ECCO-ESPGHAN Guideline Update. J Crohns Colitis. 2020 Oct 7:jjaa161.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

See Attachment A.

HCPCS Level II Code Number(s)

J3358 Ustekinumab, for intravenous injection, 1 mg

Q5098 Injection, ustekinumab-srlf (imuldosa), biosimilar, 1 mg

Q5099 Injection, ustekinumab-stba (steqeyma), biosimilar, 1 mg

Q5100 Injection, ustekinumab-kfce (yesintek), biosimilar, 1 mg

Q5138 Injection, ustekinumab-auub (Wezlana), biosimilar, IV, 1 mg

Q5164 Injection, ustekinumab-hmny (starjemza), biosimilar, 1 mg

Q9997 Injection, ustekinumab-ttwe (Pyzchiva), intravenous, 1 mg

Q9998 Injection, ustekinumab-aekn (selarsdi), biosimilar, 1 mg

Q9999 Injection, ustekinumab-aauz (otulfi), biosimilar, 1 mg

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub
Modifiers

JA Administered Intravenously

Coding and Billing Requirements

For drugs that have more than one method of administration, the appropriate modifier must be appended to indicate the route of administration.

To report the intravenous route of administration, append the following modifier: JA Administered Intravenously

Cross Reference

Policy History

Revisions From 08.00.82r:

09/21/2026

This version of the policy will become effective 09/21/2026.

This policy was updated to include coverage criteria for pediatric individuals 2 years of age and older with Crohn disease, in alignment with the US Food and Drug administration (FDA) labeling. Pediatric intravenous induction dosing for Crohn disease was added. The biologic step therapy requirement for initial intravenous induction therapy was removed.

The following HCPCS codes have been added to this policy as Medically Necessary:

K50.00, K50.011, K50.012, K50.013, K50.014, K50.018, K50.019, K50.10, K50.111, K50.112, K50.113, K50.114, K50.118, K50.119, K50.80, K50.811, K50.812, K50.813, K50.814, K50.818, K50.819, K50.90, K50.911, K50.912, K50.913, K50.914, K50.918, K50.919, K51.00, K51.011, K51.012, K51.013, K51.014, K51.018, K51.019, K51.20, K51.211, K51.212, K51.213, K51.214, K51.218, K51.219, K51.30, K51.311, K51.312, K51.313, K51.314, K51.318, K51.319, K51.40, K51.411, K51.412, K51.413, K51.414, K51.418, K51.419, K51.50, K51.511, K51.512, K51.513, K51.514, K51.518, K51.519, K51.80, K51.811, K51.812, K51.813, K51.814, K51.818, K51.819, K51.90, K51.911, K51.912, K51.913, K51.914, K51.918, K51.919, K52.1

Revisions From 08.00.82q:

07/01/2026

This version of the policy will become effective 07/01/2026.

The following NOC code has been removed from this policy, which is used to represent Starjemza (ustekinumab-hmny) and is replaced by the following HCPCS code:

REMOVED:

C9399 Unclassified drugs or biologics
J3590 Unclassified biologics

REPLACED WITH: Q5164 Injection, ustekinumab-hmny (starjemza), biosimilar, 1 mg

Revisions From 08.00.82p:

01/01/2026

This version of the policy will become effective 01/01/2026.

This policy was updated to communicate a change in coverage. The subcutaneous formulations and the associated indications for plaque psoriasis and psoriatic arthritis are no longer covered under the Medical Benefit.

Billing requirements were added regarding the JA Administered Intravenously modifier.

All of the ICD-10 CM codes have been removed from this policy, since they are informational (they were in Attachment A that has been archived). Report the most appropriate diagnosis code in support of medically necessary criteria as listed in the policy.

The following HCPCS codes have been removed from this policy, since they are SC formulations:

J3357 Ustekinumab, for subcutaneous injection, 1 mg

Q5137 Injection, ustekinumab-auub (Wezlana), biosimilar, SC, 1 mg

Q9996 Injection, ustekinumab-ttwe (Pyzchiva), subcutaneous, 1 mg

The following modifier language was added:

THE FOLLOWING MODIFIER IS USED WHEN REPORTING INTRAVENOUS USE

JA Intravenous administration

Revisions From 08.00.82o:

07/01/2025

This version of the policy will become effective 07/01/2025.

This policy was updated to communicate the coverage position for the newly added biosimilar agents. The Company has designated the biosimilar, ustekinumab-kfce (Yesintek) as its preferred product.

Additionally, the route of administration for the following conditions were clarified: Crohn disease, ulcerative colitis, and immune-checkpoint inhibitor-related toxicities.
The management of immunotherapy-related toxicities was updated for infliximab- and/or vedolizumab-refractory mild (Grade 1) symptoms, in alignment with the National Comprehensive Cancer Network (NCCN) compendium.
The experimental/investigational position was added for the use in the pediatric population in those with Crohn disease, ulcerative colitis, or immune-checkpoint inhibitor–related toxicities.
Continuation therapy was clarified for use of ustekinumab, with timeframes based on the clinical trials.

The following HCPCS codes have been added to this policy as Medically Necessary: