MIRIKIZUMAB-MRKZ INJ,SOLN
Clinical Criteria Summary
Document 581
Diagnosis & Indication
- Moderate to severe, active ulcerative colitis (UC) confirmed by endoscopy or imaging
- Prescribed and monitored by a VA / VA Community Care gastroenterologist / hepatologist or locally designated expert in UC
- Exclusion Criteria (Patient will NOT meet criteria if ANY are present)
- Uncontrolled, active, severe infection including evidence of C. difficile and undrained abscess (may start/restart once infection treatment is initiated)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- Liver cirrhosis unless potential benefits outweigh risks based on shared decision-making
- Mandatory Inclusion Criteria (ALL must be met)
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (at minimum, HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc] and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (may initiate while waiting for results)
- Obtained liver panel including bilirubin
- Additional Inclusion Criteria: Biologic/Small Molecule Failure (ONE of the following must be met)
- Tumor necrosis factor inhibitor (TNFI) is medically inadvisable and vedolizumab is medically inadvisable, not tolerated, or not adequate
- Primary nonresponse, inadequate partial response, or loss of response to TNFI therapy in the presence of adequate TNFI levels
- Loss of response (with active disease confirmed by endoscopy or imaging) to infliximab / biosimilar despite TDM-based optimized dosing to address pharmacokinetic failure
- Loss of response (with active disease confirmed by endoscopy or imaging) to one TNFI in the presence of adequate TNFI levels
- Additional Inclusion Criteria: Prior Therapy Failure (ALL must be met)
- Tofacitinib or upadacitinib is medically inadvisable, not tolerated or not adequate
- Etrasimod or ozanimod is medically inadvisable, not tolerated or not adequate
- Risankizumab-rzaa is medically inadvisable, not tolerated or not adequate
- Additional Inclusion Criteria: Special Populations & Safety (Select if appropriate)
- If HBsAg-negative but anti-HBc-positive: A GI / liver or infectious diseases expert has been consulted for advice on whether to start antiviral prophylaxis or to preemptively monitor for HBV reactivation
- For females who can become pregnant and patients with female partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception
Monitoring & Supplemental Considerations
- Routine retesting for TB, Hepatitis B, and Hepatitis C is not required for prescription renewals; retesting in high-risk patients should be considered
- Antiviral prophylaxis for HBV should utilize agents with a high genetic barrier to resistance (e.g., entecavir or tenofovir)
- Vaccinations should be updated before initiation when possible; recombinant zoster vaccine should be completed/initiated by the end of the first year, preferably when dosage is low, disease is stable, or a robust immune response is expected
- Medically inadvisable criteria for prior therapies include:
- Tofacitinib/upadacitinib: ≥1 cardiovascular risk factor; presence/history of thrombosis (PE, DVT, arterial); severe hepatic impairment; concurrent use with myelosuppressive agents; history of GI perforation; history of chronic/interstitial lung disease
- Etrasimod/ozanimod: recent MI, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, Class III/IV HF; Mobitz type II second- or third-degree AV block, sick sinus syndrome, sinoatrial block (except functioning pacemakers); infections, bradyarrhythmia, AV conduction delays, liver disease, macular edema, uncontrolled hypertension; severe untreated sleep apnea (ozanimod); concomitant MAOI (ozanimod)
- Ustekinumab: history of noninfectious pneumonia (interstitial, eosinophilic, cryptogenic organizing)
- TNFIs: heart failure, demyelinating disease, multiple sclerosis in first-degree relative, lupus, recurrent/serious infections
- Vedolizumab: liver disease and history of progressive multifocal leukoencephalopathy (PML)
- For HBsAg-negative but anti-HBc-positive patients, anti-HBs titers do not guarantee protection against HBV reactivation; management depends on the patient’s risk of HBV reactivation
Document 589
Indication & Patient Population
- Treatment of moderately to severely active ulcerative colitis (UC) in adults
- Patients with an inadequate response, intolerance, or medical inadvisability to conventional, biologic, or tofacitinib therapy
Pre-treatment Evaluations & Immunizations
- Evaluate for tuberculosis (TB) before initiating therapy
- Obtain baseline liver enzymes and bilirubin levels
- Administer all age-appropriate vaccinations according to current immunization guidelines
Dosage Regimen
- Induction Therapy: 300 mg by IV infusion at Weeks 0, 4, and 8
- Maintenance Therapy: 200 mg by SC injection (two consecutive injections of 100-mg each) at Week 12, then every 4 weeks thereafter
- No dosage modifications required due to patient factors (increases in body mass index or increases in clearance with increased body weight)
Contraindications & Safety Considerations
- Contraindicated: History of serious hypersensitivity reaction to mirikizumab-mrkz or excipients
- Warnings/Precautions: Infections, TB, hepatotoxicity
- Immunization precautions: Avoid live vaccines; no data on response to live or non-live vaccines
Place in Therapy & Formulary Criteria
- FDA-approved in 2023 with no prerequisite therapy required
- VA CFU Place in Therapy: TBD
- Projected VA Place in Therapy: Alternative mechanism of action for moderate to severe, active UC; place relative to other biologic and targeted synthetic immunomodulators is uncertain
Document 735
Exclusion Criteria
- Uncontrolled, active, severe infection (including evidence of C. difficile and undrained abscess) [may start/restart once infection is controlled]
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis [may initiate after starting antiviral prophylaxis]
- Untreated HIV infection [treated, well-controlled, asymptomatic HIV-positive patients may be treated]
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- Liver cirrhosis unless potential benefits outweigh risks based on shared decision-making
Core Inclusion Criteria
- Current or prior moderate to severe Crohn’s disease (CD) confirmed by endoscopy or imaging
- Prescribed and monitored by a VA / VA Community Care gastroenterologist or locally designated expert
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (at minimum, HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc] and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening [may initiate while waiting for test results]
- Obtained liver panel including bilirubin
- Vedolizumab or upadacitinib was tried (unless medically inadvisable) and not tolerated, not adequate, or lost response
- Risankizumab-rzaa was tried (unless medically inadvisable) and not tolerated, not adequate, or lost response
Therapy History & Sequencing Requirements
- ONE of the following must be met:
- Tumor necrosis factor inhibitor (TNFI) is medically inadvisable [Infliximab/biosimilar and adalimumab are preferred TNFIs in CD]
- Primary nonresponse, inadequate partial response, or loss of response after 12 weeks of one TNFI therapy in the presence of adequate TNFI levels (mechanistic failure)
- Loss of response to infliximab/biosimilar and another TNFI for CD despite therapeutic drug monitoring (TDM)-based optimized dosing to address pharmacokinetic failure
- Required sequencing: First-line (1L) must be infliximab or adalimumab; Second/Third-line (2L/3L) must include vedolizumab, upadacitinib, or risankizumab-rzaa (with one drug being risankizumab-rzaa); Fourth-line (4L) is mirikizumab-mrkz or ustekinumab
Special Populations & Consultation Requirements
- If HBsAg-negative but anti-HBc-positive: Consultation with a GI/liver or infectious diseases expert required for advice on antiviral prophylaxis vs. preemptive monitoring for HBV reactivation
- Females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception
Additional Clinical Considerations
- Routine retesting for TB or hepatitis C is not required for prescription renewals; retesting should be considered for high-risk patients
- Antiviral prophylaxis for HBV should utilize agents with a high genetic barrier to resistance (e.g., entecavir or tenofovir)
- Vaccinations should be updated prior to initiation; recombinant zoster vaccine should be completed or initiated by the end of the first year of treatment
- Criteria apply only to new starts; stable patients on maintenance therapy should not be switched for nonmedical reasons