MIRIKIZUMAB-MRKZ INJ,SOLN NEW
Clinical Criteria Summary
Document 581: Mirikizumab OMVOH in Ulcerative Colitis Criteria
Indication & Clinical Monitoring
- 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 ulcerative colitis
Screening & Laboratory Requirements
- 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
- Obtained liver panel including bilirubin
Exclusion Criteria
- Active infection (may start/restart once treatment for the infection has been initiated)
- 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
Prior Therapy Requirements
- Medical inadvisability, primary nonresponse, inadequate partial response, or loss of response after 8 weeks (single IV induction dose) or 16 weeks (if using second IV induction dose) of ustekinumab
- ONE of the following must be met:
- Tumor necrosis factor inhibitor (TNFI) is medically inadvisable (Infliximab is the preferred TNFI in UC)
- 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 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
- ALL of the following must be met:
- Vedolizumab is medically inadvisable, not tolerated or not adequate
- Tofacitinib or upadacitinib is medically inadvisable, not tolerated or not adequate
- Guselkumab or risankizumab-rzaa is medically inadvisable, not tolerated or not adequate
- Etrasimod or ozanimod is medically inadvisable, not tolerated, or not adequate
Special Populations & Counseling
- If HBsAg-negative but anti-HBc-positive: GI / liver or infectious diseases expert consulted for advice on whether to start antiviral prophylaxis or to preemptively monitor for HBV reactivation
- Females who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception
- Females who are breastfeeding/providing breastmilk to an infant: Counseling provided on potential risks vs benefits of treatment
Treatment Sequencing & Additional Notes
- Applies to new starts only; stable patients should not be switched to a criteria-required prior treatment for nonmedical reasons
- Routine rescreening is not required for prescription renewals; retesting in high-risk patients should be considered
- UC Treatment Sequencing: 1L includes Infliximab (preferred), adalimumab, or ustekinumab; Vedolizumab may be used 1L for “moderate” UC, absence of extraintestinal manifestations, or pouchitis. 2L includes TNFI or ustekinumab if not previously used. 3L includes Mirikizumab along with other specified agents.
- Certain patients with severe UC may require earlier escalation to 3L therapies after initial TNFI failure to reduce risk of disease-related complications or colectomy; decisions should be made collaboratively by the IBD prescriber and pharmacy.
Document 589: MON Mirikizumab mrkz OMVOH in Ulcerative Colitis Monograph Mar 2024
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: Mirikizumab OMVOH in Crohns Disease Criteria
Exclusion Criteria
- Active infection (may start/restart once treatment for the infection is initiated)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive status 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/live-attenuated vaccines less than 2 weeks before initiation
- Liver cirrhosis unless potential benefits outweigh risks based on shared decision-making
Mandatory 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
- Medical inadvisability, primary nonresponse, inadequate partial response, or loss of response to vedolizumab, upadacitinib, guselkumab, or risankizumab
- Primary nonresponse, inadequate partial response, or loss of response after 8 weeks of ustekinumab
Additional Inclusion Criteria (One Required)
- 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
Conditional/Additional Inclusion Criteria
- For HBsAg-negative but anti-HBc-positive patients: Consultation with a GI/liver or infectious diseases expert regarding antiviral prophylaxis or preemptive monitoring for HBV reactivation
- For patients who can become pregnant: Counseling on potential risks vs benefits of treatment and use of effective contraception
Treatment Sequencing & Management
- First-line (1L): Infliximab, adalimumab, or ustekinumab; vedolizumab may be used 1L for “moderate” CD, absence of extraintestinal manifestations, or pouchitis
- Second-line (2L): TNFI (if not previously used) or ustekinumab (if not previously used)
- Third-line (3L): Vedolizumab, upadacitinib (after TNFi or alternative systemic therapy if TNFi is medically inadvisable), guselkumab, or risankizumab
- Fourth-line (4L): Mirikizumab
- Severe CD may require earlier escalation to 3L therapies after initial TNFI failure to reduce risk of disease-related complications or colectomy