USTEKINUMAB INJ,SOLN
Clinical Criteria Summary
Document 719
Exclusion Criteria
- Untreated latent or active tuberculosis infection
- Uncontrolled, active, severe infection including evidence of C. difficile and undrained abscess (may start/restart once controlled)
- 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
- History or development of reversible posterior leukoencephalopathy syndrome (RPLS)
- Known or suspected noninfectious pneumonia (e.g., interstitial pneumonia, eosinophilic pneumonia, cryptogenic pneumonia)
- Administration of Bacillus Calmette-Guerin (BCG) vaccine including therapeutic intravesical BCG within 1 year prior to starting or for 1 year after discontinuation
- Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer (use with caution)
Core Inclusion Criteria
- Prescribed and monitored by a VA/VA Community Care gastroenterologist or locally-designated expert
- Current or prior moderate to severe Crohn’s disease (CD) confirmed by endoscopy or imaging
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (at minimum, HBsAg, total anti-HBc and anti-HBs)
- Current or past completion of hepatitis C screening (may initiate while waiting for results)
- Vedolizumab or upadacitinib was tried (unless medically inadvisable) and not tolerated or not adequate, or lost response
- Risankizumab-rzaa was tried (unless medically inadvisable) and not tolerated or not adequate, or lost response
Additional Inclusion Criteria (Mechanistic/Sequencing)
- 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
Additional Inclusion Criteria (Patient-Specific/Consultation)
- If HBsAg-negative but antibody-to-hepatitis-B-core-antigen (anti-HBc)-positive: Consultation with a GI/liver or infectious diseases expert for advice on antiviral prophylaxis vs. preemptive monitoring for HBV reactivation
- For women who can become pregnant: Counseling provided on potential risks vs benefits and use of effective contraception
Sequencing & Monitoring Guidance
- 1L: Infliximab or adalimumab
- 2L/3L: Vedolizumab, upadacitinib, or risankizumab-rzaa (one drug should be risankizumab-rzaa)
- 4L: Mirikizumab-mrkz or ustekinumab
- Routine retesting for TB and hepatitis C screening is not required for prescription renewals; retesting in high-risk patients should be considered
Document 720
Infection Screening & Management
- Exclusion: Untreated latent or active tuberculosis infection
- Exclusion: Uncontrolled, active, severe infection including evidence of C. difficile and undrained abscess (may start/restart once controlled)
- Exclusion: Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis)
- Exclusion: HBsAg-negative but antibody-to-hepatitis-B-core-antigen (anti-HBc)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis)
- Exclusion: Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients can be treated)
- Inclusion: Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Inclusion: Completed hepatitis B screening (at minimum, HBsAg, total anti-HBc and antibody to hepatitis B surface antigen [anti-HBs])
- Inclusion: Current or past completion of hepatitis C screening (may initiate while waiting for results)
Malignancy & Vaccination History
- Exclusion: Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer
- Exclusion: Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- Exclusion: Administration of Bacillus Calmette-Guerin (BCG) vaccine including therapeutic intravesical BCG within 1 year prior to starting ustekinumab
Disease Diagnosis & Clinical Status
- Inclusion: Diagnosis of chronic (at least 6 months) moderate to severe plaque psoriasis
- Exclusion: History or development of reversible posterior leukoencephalopathy syndrome (RPLS)
- Exclusion: Known or suspected noninfectious pneumonia (e.g., interstitial pneumonia, eosinophilic pneumonia, cryptogenic pneumonia)
Prior Therapy Requirements
- Inclusion: Methotrexate monotherapy is medically inadvisable, not tolerated or not adequate
- Inclusion: Phototherapy is medically inadvisable, not available, not feasible, not tolerated, or not adequate (i.e., NO treatment benefit after 12 treatments or inadequate partial response after 24 treatments)
- Inclusion: ONE tumor necrosis factor inhibitor (TNFi) is medically inadvisable, not tolerated or not adequate (i.e., NO or partial response after 12 weeks or loss of initial response)
- Inclusion: ONE IL-17Ai (ixekizumab preferred over secukinumab) is medically inadvisable, not tolerated, or not adequate (i.e., NO or partial response after 12 weeks or loss of initial response)
Provider Oversight
- Inclusion: Prescribed and monitored by a VA/VA Community Care dermatologist or locally-designated expert
Document 721
Exclusion Criteria
- Untreated latent or active tuberculosis infection
- Uncontrolled, active, severe infection including evidence of C. difficile and undrained abscess
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis
- HBsAg-negative but antibody-to-hepatitis-B-core-antigen (anti-HBc)-positive and not on antiviral prophylaxis
- Untreated HIV infection
- Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- History or development of reversible posterior leukoencephalopathy syndrome (RPLS)
- Known or suspected noninfectious pneumonia (e.g., interstitial pneumonia, eosinophilic pneumonia, cryptogenic pneumonia)
- Administration of Bacillus Calmette-Guerin (BCG) vaccine including therapeutic intravesical BCG within 1 year prior to starting or 1 year after therapy
Inclusion Criteria
- Prescribed and monitored by a VA/VA Community Care rheumatologist, dermatologist, or locally-designated expert
- Inflammatory articular disease (joint, spine, and/or entheseal) with a definite or provisional diagnosis of psoriatic arthritis
- Completed tuberculosis test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (at minimum, HBsAg, total anti-HBc and anti-HBs)
- Current or past completion of hepatitis C screening
- ONE TNFI therapy is medically inadvisable, not tolerated, or not adequate (i.e., NO or partial response after 12 weeks or loss of initial response)
- ONE IL-17AI (ixekizumab preferred) is medically inadvisable (e.g., severe or recurrent Candida infections), not tolerated, or not adequate (i.e., NO or partial response after 12 weeks or loss of initial response)
Clinical Precautions & Management Considerations
- Ustekinumab may be started/restarted once infections are controlled; initiation is permitted after starting antiviral prophylaxis for HBV
- Treated, well-controlled, asymptomatic HIV-positive patients are eligible for treatment
- Antiviral prophylaxis for HBV should utilize agents with a high genetic barrier to resistance (e.g., entecavir or tenofovir)
- Consultation with a hepatologist or infectious diseases expert is recommended to advise on initiating prophylactic antiviral therapy versus deferred prophylactic therapy with preemptive monitoring
- Anti-HBs titers ≥10 IU/L are generally considered protective and may identify patients requiring initial/booster vaccination or those with occult HBV from past infection
- TNFI may be medically inadvisable due to heart failure, demyelinating disease, multiple sclerosis in a first-degree relative, lupus, recurrent infections, or serious infections
- IL-17AI may be medically inadvisable due to inflammatory bowel disease (IBD), severe or recurrent Candida infections, or suicide ideation/behavior (specific to brodalumab)
Document 722
Exclusion Criteria
- Untreated latent or active tuberculosis infection
- Uncontrolled, active, severe infection including evidence of C. difficile and undrained abscess (may start/restart once controlled)
- 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
- History or development of reversible posterior leukoencephalopathy syndrome (RPLS)
- Known or suspected noninfectious pneumonia (e.g., interstitial pneumonia, eosinophilic pneumonia, cryptogenic pneumonia)
- Administration of Bacillus Calmette-Guerin (BCG) vaccine including therapeutic intravesical BCG within 1 year prior to starting or 1 year after therapy
- Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer (use with caution)
Inclusion Criteria (General Prerequisites)
- Prescribed and monitored by a VA/VA Community Care gastroenterologist or locally-designated expert
- Current or prior moderate to severe ulcerative colitis (UC) confirmed by endoscopy or imaging
- 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)
Additional Inclusion Criteria (Prior Therapy & Failure Types)
- One of vedolizumab, tofacitinib, upadacitinib, etrasimod, or ozanimod was tried (unless medically inadvisable) and not tolerated or not adequate, or lost response
- Risankizumab-rzaa was tried (unless medically inadvisable) and not tolerated or not adequate, or lost response
- ONE of the following must be selected:
- Tumor necrosis factor inhibitor (TNFI) is medically inadvisable (Infliximab/biosimilar is the preferred TNFI in UC)
- 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 a TNFI despite therapeutic drug monitoring (TDM)-based optimized dosing to address pharmacokinetic failure
Special Populations & Consultations
- If HBsAg-negative but anti-HBc-positive: GI/liver or infectious diseases expert consulted for advice on whether to start antiviral prophylaxis or preemptively monitor for HBV reactivation
- For women who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception
Monitoring, Sequencing, & Clinical Notes
- Routine retesting for TB, HBV, and HCV is not required for prescription renewals; retesting in high-risk patients should be considered
- Antiviral prophylaxis for HBV requires 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 end of first year, preferably at low dosage/stable disease
- Sequencing: 1L = Infliximab or adalimumab; 2L/3L = Vedolizumab, tofacitinib, upadacitinib, etrasimod, ozanimod, or risankizumab-rzaa (one drug must be risankizumab-rzaa); 4L = Mirikizumab-mrkz, guselkumab, or ustekinumab
- Infliximab/biosimilar is the preferred TNFI in UC; adalimumab is less preferred than vedolizumab and tofacitinib in TNFI-exposed UC patients