CENTENE Corporation

Clinical Policy: Guselkumab (Tremfya)
Reference Number: CP.PHAR.364
Effective Date: 08.29.17
Last Review Date: 05.26
Line of Business: Medicaid                                 Revision Log

See Important Reminder at the end of this policy for important regulatory and legal
information.

Description
Guselkumab (Tremfya®) is an interleukin-23 (IL-23) blocker.

FDA Approved Indication(s)
Tremfya is indicated for the treatment of:
*   Adults and pediatric patients 6 years of age and older who also weigh at least 40 kg with
    moderate-to-severe plaque psoriasis (PsO) and who are candidates for systemic therapy or
    phototherapy
*   Adults and pediatric patients 6 years of age and older who also weigh at least 40 kg with
    active psoriatic arthritis (PsA)
*   Adults with moderately to severely active ulcerative colitis (UC)
*   Adults with moderately to severely active Crohn’s disease (CD)


    9.  Dose does not exceed 100 mg at weeks 0 and 4, followed by maintenance dose of 100
        mg every 8 weeks.

Approval duration: 12 months



Approval duration: 12 months


    8.  Dose does not exceed both of the following (a and b):
        a.  Induction (i or ii):
            i.  IV: 200 mg at Weeks 0, 4, and 8;
            ii. SC: 400 mg at Weeks 0, 4, and 8;
        b.  Maintenance (i or ii):
            i.  SC: 100 mg at Week 16 and every 8 weeks thereafter;
            ii. SC: 200 mg at Week 12 and every 4 weeks thereafter.

Approval duration: 12 months


    8.  Dose does not exceed both of the following (a and b):
        a.  Induction (i or ii):
            i.  IV: 200 mg at Weeks 0, 4, and 8;
            ii. SC: 400 mg at Weeks 0, 4, and 8;
        b.  Maintenance (i or ii):
            i.  SC: 100 mg at Week 16 and every 8 weeks thereafter;
            ii. SC: 200 mg at Week 12 and every 4 weeks thereafter.

Approval duration: 12 months

E. Other diagnoses/indications (must meet 1 or 2):
    1.  If this drug has recently (within the last 6 months) undergone a label change (e.g.,
        newly approved indication, age expansion, new dosing regimen) that is not yet
        reflected in this policy, refer to one of the following policies (a or b):
        a.  For drugs on the formulary (commercial, health insurance marketplace) or PDL
            (Medicaid), the no coverage criteria policy for the relevant line of business:
            CP.PMN.255 for Medicaid; or
        b.  For drugs NOT on the formulary (commercial, health insurance marketplace) or
            PDL (Medicaid), the non-formulary policy for the relevant line of business:
            CP.PMN.16 for Medicaid; or
    2.  If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed
        under section III (Diagnoses/Indications for which coverage is NOT authorized) AND
        criterion 1 above does not apply, refer to the off-label use policy for the relevant
        line of business: CP.PMN.53 for Medicaid.


    4.  If request is for a dose increase, new dose does not exceed one of the following (a or
        b):
        a.  For PsO, PsA: 100 mg every 8 weeks;
        b.  For CD, UC: 200 mg every 4 weeks.

Approval duration: 12 months

B. Other diagnoses/indications (must meet 1 or 2):
    1.  If this drug has recently (within the last 6 months) undergone a label change (e.g.,
        newly approved indication, age expansion, new dosing regimen) that is not yet
        reflected in this policy, refer to one of the following policies (a or b):
        a.  For drugs on the formulary (commercial, health insurance marketplace) or PDL
            (Medicaid), the no coverage criteria policy for the relevant line of business:
            CP.PMN.255 for Medicaid; or
        b.  For drugs NOT on the formulary (commercial, health insurance marketplace) or
            PDL (Medicaid), the non-formulary policy for the relevant line of business:
            CP.PMN.16 for Medicaid; or
    2.  If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed
        under section III (Diagnoses/Indications for which coverage is NOT authorized) AND
        criterion 1 above does not apply, refer to the off-label use policy for the relevant
        line of business: CP.PMN.53 for Medicaid.

III. Diagnoses/Indications for which coverage is NOT authorized:
A. Non-FDA approved indications, which are not addressed in this policy, unless there is
    sufficient documentation of efficacy and safety according to the off label use policy –
    CP.PMN.53 for Medicaid or evidence of coverage documents.
B. Combination use with biological disease-modifying antirheumatic drugs (bDMARDs) or
    potent immunosuppressants, including but not limited to any tumor necrosis factor (TNF)
    antagonists [e.g., Cimzia®, Enbrel®, Humira® and its biosimilars, Remicade® and its
    biosimilars, Simponi®], interleukin agents [e.g., Actemra® (IL-6RA) and its biosimilars,
    Arcalyst® (IL-1 blocker), Bimzelx® (IL-17A and F antagonist), Cosentyx® (IL-17A
    inhibitor), Ilaris® (IL-1 blocker), Ilumya® (IL-23 inhibitor), Kevzara® (IL-6RA),
    Kineret® (IL-1RA), Omvoh™ (IL-23 antagonist), Siliq™ (IL-17RA), Skyrizi™ (IL-23
    inhibitor), Spevigo® (IL-36 antagonist), Stelara® (IL-12/23 inhibitor) and its biosimilars,
    Taltz® (IL-17A inhibitor), Tremfya® (IL-23 inhibitor)], Janus kinase inhibitors (JAKi)
    [e.g., Cibinqo™, Olumiant™, Rinvoq™, Xeljanz®/Xeljanz XR], anti-CD20 monoclonal
    antibodies [Rituxan® and its biosimilars], selective co-stimulation modulators [Orencia®],
    integrin receptor antagonists [Entyvio®], tyrosine kinase 2 inhibitors [Sotyktu®], and
    sphingosine 1-phosphate receptor modulator [Velsipity™] because of the additive
    immunosuppression, increased risk of neutropenia, as well as increased risk of serious
    infections.

IV. Appendices/General Information
Appendix A: Abbreviation/Acronym Key
CD: Crohn’s disease
FDA: Food and Drug Administration
IL-23: interleukin-23
JAKi: Janus kinase inhibitors
MTX: methotrexate
PsA: psoriatic arthritis
PsO: plaque psoriasis
UC: ulcerative colitis

Appendix B: Therapeutic Alternatives
This table provides a listing of preferred alternative therapy recommended in the approval
criteria. The drugs listed here may not be a formulary agent and may require prior
authorization.

| Drug Name | Dosing Regimen | Dose Limit/Maximum Dose |
|-----------|---------------|------------------------|
| acitretin (Soriatane®) | PsO<br>25 or 50 mg PO daily | 50 mg/day |
| azathioprine (Azasan®, Imuran®) | CD*<br>1.5 – 2.5 mg/kg/day PO | 2.5 mg/kg/day |
| corticosteroids | UC<br>Prednisone 40 mg – 60 mg PO QD, then taper dose by 5 to 10 mg/week<br>Budesonide (Uceris®) 9 mg PO QAM for up to 8 weeks | Various |
| cyclosporine (Sandimmune®, Neoral®) | PsO<br>2.5 – 4 mg/kg/day PO divided BID | 4 mg/kg/day |
| 6-mercaptopurine (Purixan®) | CD*<br>50 mg PO QD or 0.75 – 1.5 mg/kg/day | 1.5 mg/kg/day |
| methotrexate (Trexall®, Otrexup™, Rasuvo®, RediTrex®, Rheumatrex®, Jylamvo®) | CD<br>15 – 25 mg/week IM or SC<br>PsO<br>10 to 25 mg/week IM, SC or PO or 2.5 mg PO Q12 hr for 3 doses/week | 30 mg/week |
| Hadlima (adalimumab-bwwd), Simlandi | CD, UC<br>Initial dose: 160 mg SC on Day 1, then 80 mg SC on Day 15 | 40 mg every other week |
| (adalimumab-ryvk), Yusimry (adalimumab-aqvh), adalimumab-aaty (Yuflyma®), adalimumab-adaz (Hyrimoz®), adalimumab-fkjp (Hulio®), adalimumab-adbm (Cyltezo®) | Maintenance dose: 40 mg SC every other week starting on Day 29<br>PsA<br>40 mg SC every other week<br>PsO<br>Initial dose:<br>80 mg SC<br>Maintenance dose:<br>40 mg SC every other week starting one week after initial dose |  |
| Otezla®, Otezla XR™ (apremilast) | PsA<br>Initial dose: Otezla only:<br>Day 1: 10 mg PO QAM<br>Day 2: 10 mg PO QAM and 10 mg PO QPM<br>Day 3: 10 mg PO QAM and 20 mg PO QPM<br>Day 4: 20 mg PO QAM and 20 mg PO QPM<br>Day 5: 20 mg PO QAM and 30 mg PO QPM<br>Maintenance dose:<br>Day 6 and thereafter:<br>• Otezla: 30 mg PO BID<br>• Otezla XR: 75 mg PO QD<br><br>Pediatric: Otezla only:<br>Weight ≥ 50 kg:<br>Initial dose:<br>Day 1: 10 mg PO QAM<br>Day 2: 10 mg PO QAM and 10 mg PO QPM<br>Day 3: 10 mg PO QAM and 20 mg PO QPM<br>Day 4: 20 mg PO QAM and 20 mg PO QPM<br>Day 5: 20 mg PO QAM and 30 mg PO QPM<br>Maintenance dose:<br>Day 6 and thereafter:<br>• Otezla: 30 mg PO BID<br>• Otezla XR: 75 mg PO QD<br><br>Weight 20 kg to < 50 kg:<br>Initial dose:<br>Day 1: 10 mg PO QAM | Adults:<br>• Otezla: 60 mg/day<br>• Otezla XR: 75 mg/day<br><br>Pediatric:<br>Weight ≥ 50 kg:<br>• Otezla: 60 mg/day<br>• Otezla XR: 75 mg/day<br><br>Weight 20 kg to < 50 kg:<br>40 mg/day |
|  | Day 2: 10 mg PO QAM and 10 mg PO QPM<br>Day 3: 10 mg PO QAM and 20 mg PO QPM<br>Day 4: 20 mg PO QAM and 20 mg PO QPM<br>Day 5: 20 mg PO QAM and 20 mg PO QPM<br>Maintenance dose:<br>Day 6 and thereafter, Otezla only:<br>20 mg PO BID |  |
| Otlufi® (ustekinumab-aauz), Pyzchiva® (ustekinumab-ttwe), Selarsdi™ (ustekinumab-aekn), Steqeyma® (ustekinumab-stba), Yesintek™ (ustekinumab-kfce) | CD, UC<br>Weight based dosing IV at initial dose:<br>Weight ≤ 55 kg: 260 mg<br>Weight > 55 kg to 85 kg: 390 mg<br>Weight > 85 kg: 520 mg<br>Maintenance dose:<br>90 mg SC every 8 weeks<br><br>PsO<br>Weight based dosing SC at weeks 0 and 4, followed by maintenance dose every 12 weeks<br><br>Adult:<br>Weight ≤ 100 kg: 45 mg<br>Weight > 100 kg: 90 mg<br><br>Pediatrics (age 6 years to 17 years):<br>Otlufi, Pyzchiva, Yesintek:<br>Weight < 60 kg: 0.75 mg/kg<br><br>Otlufi, Pyzchiva, Selarsdi, Steqeyma, Yesintek:<br>Weight 60 to 100 kg: 45 mg<br>Weight > 100 kg: 90 mg<br><br>PsA<br>Weight based dosing SC at weeks 0 and 4, followed by maintenance dose every 12 weeks<br><br>Adult:<br>45 mg SC at weeks 0 and 4, followed by 45 mg every 12 weeks<br><br>Pediatrics (age 6 years to 17 years):<br>Weight based dosing SC at weeks 0 and 4, then every 12 weeks thereafter | CD, UC:<br>90 mg every 8 weeks<br><br>PsO:<br>90 every 12 weeks<br><br>PsA:<br>45 mg every 12 weeks |
|  | Otlufi, Pyzchiva, Yesintek:<br>Weight < 60 kg: 0.75 mg/kg<br><br>Otlufi, Pyzchiva, Selarsdi, Steqeyma, Yesintek:<br>Weight ≥ 60 kg: 45 mg |  |
| Taltz® (ixekizumab) | PsO<br>Initial dose:<br>160 mg (two 80 mg injections) SC at week 0,<br>then 80 mg SC at weeks 2, 4, 6, 8, 10, and 12<br>Maintenance dose:<br>80 mg SC every 4 weeks<br><br>PsA<br>Initial dose: 160 mg (two 80 mg injections) SC at week 0<br>Maintenance dose:<br>80 mg SC every 4 weeks | 80 mg every 4 weeks |
| Xeljanz® (tofacitinib) | PsA<br>5 mg PO BID | 10 mg/day |
| Xeljanz XR® (tofacitinib extended-release) | PsA<br>11 mg PO QD | 11 mg/day |

Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only
and generic (Brand name®) when the drug is available by both brand and generic.

Appendix C: Contraindications/Boxed Warnings
*   Contraindication(s): history of serious hypersensitivity reaction to guselkumab or any of
    the excipients
*   Boxed warning(s): none reported

Appendix D: General Information
*   Definition of failure of MTX or DMARDs
    *   Child-bearing age is not considered a contraindication for use of MTX. Each drug has
        risks in pregnancy. An educated patient and family planning would allow use of MTX
        in patients who have no intention of immediate pregnancy.
    *   Social use of alcohol is not considered a contraindication for use of MTX. MTX may
        only be contraindicated if patients choose to drink over 14 units of alcohol per week.
        However, excessive alcohol drinking can lead to worsening of the condition, so
        patients who are serious about clinical response to therapy should refrain from
        excessive alcohol consumption.
*   TNF blockers:
    *   Etanercept (Enbrel®), adalimumab (Humira®) and its biosimilars, infliximab
        (Remicade®) and its biosimilars (Avsola™, Renflexis®, Inflectra®), certolizumab
        pegol (Cimzia®), and golimumab (Simponi®, Simponi Aria®).

Appendix E: Mayo Score, Modified Mayo Score, or Mayo Endoscopic Score
*   Mayo Score: evaluates ulcerative colitis stage, based on four parameters: stool frequency,
    rectal bleeding, endoscopic evaluation, and Physician’s global assessment. Each
    parameter of the score ranges from zero (normal or inactive disease) to 3 (severe activity)
    with an overall score of 12.

| Score | Decoding |
|-------|----------|
| 0 – 2 | Remission |
| 3 – 5 | Mild activity |
| 6 – 10 | Moderate activity |
| >10 | Severe activity |

*   Modified Mayo Score: developed from the full Mayo score and evaluates ulcerative
    colitis stage, based on three parameters: stool frequency, rectal bleeding, and endoscopic
    evaluation. The modified Mayo Score gives a maximum overall score of 9. The FDA
    currently accepts the modified Mayo Score for the assessment of disease activity in
    pivotal UC clinical trials.
*   Mayo Endoscopic Score: tool used to assess severity based on endoscopic findings during
    a colonoscopy and ranges from 0 to 3. A score of 2 or higher means there is moderate-to-
    severe inflammation.

| Score | Decoding |
|-------|----------|
| 0 | Normal or inactive disease |
| 1 | Mild disease (erythema, decreased vascular pattern, mild friability) |
| 2 | Moderate disease (marked erythema, absent vascular pattern, moderate friability, erosions) |
| 3 | Severe disease (spontaneous bleeding, ulcerations) |

Appendix F: Immunomodulator Medical Justification
*   The following may be considered for medical justification supporting inability to use an
    immunomodulator for CD:
    *   Inability to induce short-term symptomatic remission with a 3-month trial of systemic
        glucocorticoids
    *   High-risk factors for intestinal complications may include:
        *   Initial extensive ileal, ileocolonic, or proximal GI involvement
        *   Initial extensive perianal/severe rectal disease
        *   Fistulizing disease (e.g., perianal, enterocutaneous, and rectovaginal fistulas)
        *   Deep ulcerations
        *   Penetrating, stricturing or stenosis disease and/or phenotype
        *   Intestinal obstruction or abscess
    *   For TNF-inhibitors, high risk factors for postoperative recurrence may include:
        *   Less than 10 years duration between time of diagnosis and surgery
        *   Disease location in the ileum and colon

CLINICAL POLICY

Guselkumab

• Perianal fistula
• Prior history of surgical resection
• Use of corticosteroids prior to surgery

V. Dosage and Administration

VI. Product Availability

• Subcutaneous injection
  
  • Single-dose prefilled syringe: 100 mg/mL, 200 mg/2 mL
  • Single-dose One Press patient-controlled injector: 100 mg/mL
  • Single-dose prefilled pen (Tremfya Pen): 100 mg/mL, 200 mg/2 mL
• Intravenous infusion
  
  • Single-dose vial: 200 mg/20 mL

Coding Implications

Codes referenced in this clinical policy are for informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage. Providers should reference the most up-to-date sources of professional coding guidance prior to the submission of claims for reimbursement of covered services.

Reviews, Revisions, and Approvals

Important Reminder

This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health professional organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information. The Health Plan makes no representations or accepts no liability with respect to the content of any external information used or relied upon in developing this clinical policy. This clinical policy is consistent with standards of medical practice current at the time that this clinical policy was approved. “Health Plan” means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan’s affiliates, as applicable.

The purpose of this clinical policy is to provide a guide to medical necessity, which is a component of the guidelines used to assist in making coverage decisions and administering benefits. It does not constitute a contract or guarantee regarding payment or results. Coverage decisions and the administration of benefits are subject to all terms, conditions, exclusions, and limitations of the coverage documents (e.g., evidence of coverage, certificate of coverage, policy, contract of insurance, etc.), as well as to state and federal requirements and applicable Health Plan-level administrative policies and procedures.

This clinical policy is effective as of the date determined by the Health Plan. The date of posting may not be the effective date of this clinical policy. This clinical policy may be subject to applicable legal and regulatory requirements relating to provider notification. If there is a discrepancy between the effective date of this clinical policy and any applicable legal or regulatory requirement, the requirements of law and regulation shall govern. The Health Plan retains the right to change, amend or withdraw this clinical policy, and additional clinical policies may be developed and adopted as needed, at any time.

This clinical policy does not constitute medical advice, medical treatment, or medical care. It is not intended to dictate to providers how to practice medicine. Providers are expected to exercise professional medical judgment in providing the most appropriate care, and are solely responsible for the medical advice and treatment of members. This clinical policy is not intended to

CLINICAL POLICY

Guselkumab

recommend treatment for members. Members should consult with their treating physician in connection with diagnosis and treatment decisions.

Providers referred to in this clinical policy are independent contractors who exercise independent judgment and over whom the Health Plan has no control or right of control. Providers are not agents or employees of the Health Plan.

This clinical policy is the property of the Health Plan. Unauthorized copying, use, and distribution of this clinical policy or any information contained herein are strictly prohibited. Providers, members, and their representatives are bound to the terms and conditions expressed herein through the terms of their contracts. Where no such contract exists, providers, members and their representatives agree to be bound by such terms and conditions by providing services to members and/or submitting claims for payment for such services.

Note: For Medicaid members, when state Medicaid coverage provisions conflict with the coverage provisions in this clinical policy, state Medicaid coverage provisions take precedence. Please refer to the state Medicaid manual for any coverage provisions pertaining to this clinical policy.

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