Anthem Blue Cross California Stelara (ustekinumab) Form

Overview Clinical criteria Overview Coding Document history References This document addresses the use of Ustekinumab agents (Stelara and Wezlana), monoclonal antibodies which binds to the p40 protein subunit used by both the interleukin-12 and interleukin-23 (IL-12/23) cytokines disrupting their interaction with receptors and thereby inhibiting the release of proinflammatory cytokines and chemokines. Stelara and Wezlana are approved for the treatment of plaque psoriasis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis. Wezlana is designated as an interchangeable biosimilar to the reference product Stelara. Plaque Psoriasis (otherwise known as psoriasis vulgaris): The American Academy of Dermatology (AAD) and National Psoriasis Foundation (NPF) published joint guidelines on the management and treatment of psoriasis with biologics. The guidelines do not include a treatment algorithm or compare biologics to each other or conventional therapy. The guideline notes that patients with mild- moderate disease may be adequately controlled with topical therapy and/or phototherapy while moderate to severe disease may necessitate treatment with a biologic. Biologics approved for psoriasis were studied in a population with 10% or greater BSA involvement. Moderate to severe disease is defined as involvement in > 3% of body surface area (BSA) or involvement in sensitive areas that significantly impact daily function (such as palms, soles of feet, head/neck, or genitalia). Tumor necrosis factor inhibitor (TNFi) biologics, ustekinumab, IL17 inhibitors, and IL23 inhibitors are all recommended as monotherapy treatment options for adult patients with moderate to severe plaque psoriasis. Combination use of TNFi biologics (etanercept, infliximab, adalimumab) and ustekinumab with apremilast is poorly studied and the AAD has given this practice a grade C recommendation based on limited-quality evidence. Psoriatic Arthritis: The American College of Rheumatology (ACR) guidelines recommend that initial treatment of patients with active severe PsA or concomitant psoriasis should include a TNFi biologic over an oral small molecule (OSM; including methotrexate, sulfasalazine, cyclosporine, leflunomide, and apremilast). For initial therapy, OSMs are preferred over IL-17 and ustekinumab; and may be considered over TNFi biologics in mild to moderate disease without comorbid conditions or in those who prefer oral therapy. Recommendations involving biologics over OSMs as first line therapy are conditional and based on low quality evidence. Evidence cited includes indirect comparisons of placebo-controlled trials, studies with open-label design, and extrapolation from studies in plaque psoriasis. Furthermore, most pivotal trials for TNFi biologics included a study population that were DMARD experienced. Overall, there is a lack of definitive evidence for the safety and efficacy of biologic drugs over conventional therapy for the initial treatment of most patients with psoriatic arthritis. The ACR guidelines also include recommendations for patients whose disease remains active despite treatment with an OSM. Here, TNFi biologics are recommended over other therapies including IL-17 inhibitors, ustekinumab, tofacitinib, and abatacept. When TNFi biologics are not used, IL-17 inhibitors are preferred over ustekinumab; both of which are preferred over tofacitinib and abatacept. For disease that remains active despite TNFi monotherapy, switching to a different TNFi is recommended over other therapies. Crohn’s Disease: According to the American Gastrointestinal Association clinical practice guidelines, evidence supports the use of methotrexate, corticosteroids, TNFi +/- immunomodulator, ustekinumab, or vedolizumab for induction of remission. Among the biologics, infliximab, adalimumab, ustekinumab, or vedolizumab are recommended or suggested over certolizumab for induction of remission. Evidence supports biologic agents, thiopurines, and methotrexate for maintenance of remission. Ustekinumab and vedolizumab are options for individuals with primary nonresponse to initial treatment with TNFi. Adalimumab, ustekinumab, or vedolizumab may be used in cases where an individual previously responded to infliximab and then lost response (secondary nonresponse). Ulcerative Colitis: The American Gastroenterological Association (AGA) guidelines define moderate to severe UC as those who are dependent on or refractory to corticosteroids, have severe endoscopic disease activity, or are at high risk of colectomy. AGA strongly recommends biologics (TNFi, vedolizumab, or ustekinumab) or tofacitinib over no treatment in induction and maintenance of remission (moderate quality of evidence). For biologic-naïve individuals, Infliximab or vedolizumab are conditionally recommended over adalimumab for induction of remission (moderate quality evidence). 1 Biosimilar and Interchangeable Agents: Biosimilar products must be highly similar to the reference product and there must be no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product. Biosimilars must utilize the same mechanism of action (MOA), route of administration, dosage form and strength as the reference product; and the indications proposed must have been previously approved for the reference product. The potential exists for a biosimilar product to be approved for one or more indications for which the reference product is licensed based on extrapolation of data intended to demonstrate biosimilarity in one indication. Sufficient scientific justification for extrapolating data is necessary for FDA approval. Factors and issues that should be considered for extrapolation include the MOA for each indication, the pharmacokinetics, bio-distribution, and immunogenicity of the product in different patient populations, and differences in expected toxicities in each indication and patient population. As biosimilar agents must demonstrate similarity to the reference product in FDA indications, it is reasonable that biosimilarity can be extrapolated to off-label indications as well. In contrast to biosimilar status, an interchangeable biologic must meet the biosimilar standards, but also must be expected to product the same clinical result as the reference product in any given patient; and if administered more than once to a patient, the risk in terms of safety or diminished efficacy from altering or switching between use of the reference or interchangeable product is not greater than that from use of the reference product without such alteration or switch. Wezlana is the only FDA approved biosimilar to the reference product Stelara; and it is designated as an interchangeable biosimilar. Supportive data for interchangeability includes a multi-switch randomized phase 3 study in subjects with moderate to severe plaque psoriasis (NCT04761627). Clinical Criteria When a drug is being reviewed for coverage under a member’s medical benefit plan or is otherwise subject to clinical review (including prior authorization), the following criteria will be used to determine whether the drug meets any applicable medical necessity requirements for the intended/prescribed purpose. Ustekinumab Agents (Stelara, Wezlana) Initial requests for Stelara (ustekinumab) or Wezlana (ustekinumab-auub) may be approved for the following: I. Crohn’s disease (CD) when the following criteria are met: A. For individuals requesting intravenous induction dose: 1. 2. 3. Individual is 18 years of age or older with moderate to severe CD; AND Individual has had an inadequate response to or is intolerant of conventional therapy (such as systemic corticosteroids or immunosuppressants [such as thiopurines or methotrexate]); OR Individual has a contraindication to systemic corticosteroids or thiopurines or methotrexate; OR B. For individuals requesting subcutaneous maintenance therapy: 1. Individual is 18 years of age or older with moderate to severe CD; AND 2. Individual has completed the intravenous induction dose with Stelara/Wezlana and will be using subcutaneous Stelara/Wezlana for maintenance therapy; OR II. OR III. OR IV. Psoriatic arthritis (PsA) when the following criteria are met: A. B. Individual is 6 years of age or older with moderate to severe PsA; AND Individual has had an inadequate response to or is intolerant of conventional therapy [nonbiologic DMARDs (such as methotrexate, sulfasalazine, cyclosporine or leflunomide)]; OR Individual has a contraindication to methotrexate, sulfasalazine, cyclosporine or leflunomide; C. Plaque psoriasis (Ps) when the following criteria are met: A. Individual is 6 years of age or older with chronic moderate to severe (that is, extensive or disabling) plaque Ps with either of the following (AAD 2019): 1. Plaque Ps involving greater than three percent (3%) body surface area (BSA); OR 2. Plaque Ps involving less than or equal to three percent (3%) BSA involving sensitive areas or areas that significantly impact daily function (such as palms, soles of feet, head/neck, or genitalia); AND B. C. Individual has had an inadequate response to, is intolerant of phototherapy or other systemic therapy (such as acitretin, cyclosporine, or methotrexate); OR Individual has a contraindication to phototherapy, acitretin, cyclosporine, and methotrexate; Ulcerative colitis (UC) when the following criteria are met: A. For individuals requesting intravenous induction dose: 1. 2. 3. Individual is 18 years of age or older with moderate to severe UC; AND Individual has had an inadequate response to or is intolerant of conventional therapy (such as 5-Aminosalicylic acid products, systemic corticosteroids, or immunosuppressants [such as thiopurines]); OR Individual has a contraindication to 5-ASA products or systemic corticosteroids or thiopurines; 2 OR B. For individuals requesting subcutaneous maintenance therapy: 1. 2. Individual is 18 years of age or older with moderate to severe UC; AND Individual has completed the intravenous induction dose with Stelara/Wezlana and will be using subcutaneous Stelara/Wezlana for maintenance therapy; OR V. Immunotherapy-related toxicities when each of the following criteria are met (NCCN 2A): A. B. C. Symptoms persist despite treatment with steroids and biologics (infliximab and/or vedolizumab). Individual is undergoing immune checkpoint inhibitor therapy for a cancer diagnosis; AND Individual is experiencing moderate to severe diarrhea or colitis as a result of immune checkpoint inhibitor treatment; AND Continuation requests for Stelara (ustekinumab) or Wezlana (ustekinumab-auub) may be approved if the following criteria are met: I. II. Individual has been receiving and is maintained on a stable dose of Stelara/Wezlana; AND There is confirmation of clinically significant improvement or stabilization in clinical signs and symptoms of the disease. Requests for Stelara (ustekinumab) or Wezlana (ustekinumab-auub) may not be approved for the following: I. II. III. IV. V. In combination with phototherapy; OR In combination with oral or topical JAK inhibitors, apremilast, ozanimod, etrasimod, deucravacitinib, or any of the following biologic immunomodulators: Other TNF antagonists, IL-23 inhibitors, IL-17 inhibitors, IL-6 inhibitors, IL-1 inhibitors, vedolizumab, abatacept, rituximab, or natalizumab; OR History of posterior reversible encephalopathy syndrome; OR Tuberculosis, other active serious infections, or a history of recurrent infections [repeat TB testing not required for ongoing therapy]; OR If initiating therapy, individual has not had a tuberculin skin test (TST) or a Centers for Disease Control (CDC-) and Prevention -recommended equivalent to evaluate for latent tuberculosis (unless switching therapy from another targeted immune modulator and no new risk factors); OR VI. When the above criteria are not met and for all other indications. Quantity Limits Ustekinumab Agents Quantity Limits Stelara 130 mg/26 mL (5 mg/mL) vial Drug Stelara 45 mg/0.5 mL vial*^ Stelara 45 mg/0.5 mL single-use prefilled syringe*†^ Stelara 90 mg/1 mL single-use prefilled syringe#^ Wezlana 130 mg/26 mL (5 mg/mL) vial Wezlana 45 mg/0.5 mL vial*^ Wezlana 45 mg/0.5 mL single-use prefilled syringe*†^ Wezlana 90 mg/1 mL single-use prefilled syringe#^ Limit Body weight 55 kg or less: 2 vials (8 week supply, one time fill) Body weight more than 55kg to 85 kg: 3 vials (8 week supply, one time fill) Body weight more than 85 kg [max limit]: 4 vials (8 week supply, one time fill) 1 vial per 84 days (12 weeks) 1 syringe per 84 days (12 weeks) 1 syringe per 84 days (12 weeks) Body weight 55 kg or less: 2 vials (8 week supply, one time fill) Body weight more than 55kg to 85 kg: 3 vials (8 week supply, one time fill) Body weight more than 85 kg [max limit]: 4 vials (8 week supply, one time fill) 1 vial per 84 days (12 weeks) 1 syringe per 84 days (12 weeks) 1 syringe per 84 days (12 weeks) *Initiation of therapy for Plaque Psoriasis (Ps) or Psoriatic Arthritis (PsA) in individuals less than or equal to 100 kg (220 lbs.): May approve 1 (one) additional syringe or vial (45 mg/0.5 mL) in the first 84 days (12 weeks) of treatment. Override Criteria †Initiation of therapy for PsA in individuals greater than 100 kg (220 lbs.): May approve 1 (one) additional syringe (45 mg/0.5 mL) in the first 84 days (12 weeks) of treatment. #Initiation of therapy for Ps or concomitant PsA and moderate to severe Ps in individuals greater than 100 kg (220 lbs.): May approve 1 (one) additional syringe (90 mg/1 mL) in the first 84 days (12 weeks) of treatment. 3 ^Maintenance therapy for adult Crohn’s Disease (CD) and Ulcerative Colitis (UC): May approve 1 (one) 90 mg syringe or 2 (two) 45 mg vials/syringes every 8 weeks (56 days). ^For CD or UC, may also approve increased dosing, up to 1 (one) 90 mg syringe or 2 (two) 45 mg vials/syringes every 4 weeks if the following criteria are met: I. II. III. IV. V. VI. Individual has been treated with standard maintenance dosing (i.e. every 8 weeks) for at least 2 doses or 16 weeks; AND The increased dosing is being prescribed by or in consultation with a gastroenterologist; AND Individual initially achieved an adequate response to standard maintenance dosing but has subsequently lost response, as determined by the prescriber; OR Individual partially responded but had an inadequate response to standard maintenance dosing as determined by the prescriber; AND Symptoms, if present, are not due to active infections or any other gastrointestinal disorder other than the primary disease; AND Requested dosing does not exceed up to 1 (one) 90 mg syringe or 2 (two) 45 mg vials/syringes every 4 weeks. Initial approval duration for increased dosing for CD or UC: 16 weeks ^Requests for continued escalated dosing for CD and UC may be approved if the following criteria are met: I. II. III. IV. Requested dosing does not exceed up to 1 (one) 90 mg syringe or 2 (two) 45 mg vials/syringes every 4 weeks; AND Individual has subsequently regained response or achieved adequate response following increased dosing, as shown by improvement in signs and symptoms of the disease (including but not limited to reduction in stool frequency/bloody stools, improvement abdominal pain, or endoscopic response); AND Individual is not experiencing unacceptable adverse effects from increased dosing; AND Individual will be assessed regularly for dose de-escalation. Continued approval duration for increased dosing CD or UC: 6 months ^For CD or UC, Increased dosing may not be approved for the following: I. II. Individual has had no response to ustekinumab at standard maintenance dosing (i.e. every 8 weeks); OR Individual is requesting dose escalation in absence of signs and symptoms of the disease (for example, requesting based on results of therapeutic drug level or anti-drug antibody testing alone). Coding The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member. HCPCS J3357 J3358 Ustekinumab, for subcutaneous injection, 1 mg [Stelara subcutaneous] Ustekinumab, for intravenous injection, 1 mg [Stelara IV] ICD-10 Diagnosis K50.00-K50.919 Crohn's disease [regional enteritis] K51.00-K51.919 Ulcerative colitis L40.0 L40.1 L40.2 L40.3 L40.4 Psoriasis vulgaris Generalized pustular psoriasis Acrodermatitis continua Pustulosis palmaris et plantaris Guttate psoriasis L40.50-L40.59 Arthropathic psoriasis L40.8 L40.9 Other psoriasis Psoriasis, unspecified Document History 4 Revised: 11/17/2023