RISANKIZUMAB-RZAA INJ,SOLN
Clinical Criteria Summary
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Exclusion Criteria
- Uncontrolled, active, severe infection including evidence of C. difficile and undrained abscess (risankizumab-rzaa may be started/restarted once infection treatment 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 can 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 the prescriber documents that potential benefits outweigh risks
Inclusion Criteria (General & Screening)
- Prescribed and monitored by a VA/VA Community Care gastroenterologist or locally designated expert
- Current or prior moderate to severe Crohn’s disease confirmed by endoscopy or imaging
- Completed tuberculosis 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 pretreatment liver enzymes and bilirubin levels
Additional Inclusion Criteria (Therapeutic History & Sequencing)
- ONE of the following must be met:
- Tumor necrosis factor inhibitor (TNFI) is medically inadvisable (Infliximab/biosimilar and adalimumab are preferred TNFIs in Crohn’s disease)
- Primary nonresponse, inadequate partial response, or loss of response after 12 weeks of TNFI therapy in the presence of adequate TNFI levels (mechanistic failure)
- Loss of response to infliximab/biosimilar and another TNFI for Crohn’s disease despite therapeutic drug monitoring-based optimized dosing to address pharmacokinetic failure
- Drug Sequencing: First-line is Infliximab or adalimumab; Second/Third-line includes vedolizumab, upadacitinib, or risankizumab-rzaa (one drug should be risankizumab-rzaa as 2L or 3L drug); Fourth-line is mirikizumab-mrkz or ustekinumab
Special Populations & Expert Consultation
- 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 hepatitis B virus reactivation
- For women who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception during therapy and for 5 months after stopping treatment
Monitoring & Re-testing Guidelines
- Routine retesting for tuberculosis, hepatitis B, and hepatitis C screening is not required for prescription renewals; retesting in high-risk patients should be considered
- Anti-HBs titers ≥10 IU/L are generally considered protective and may help identify need for initial/booster vaccination or occult hepatitis B virus
- Infliximab may be medically inadvisable due to heart failure, demyelinating disease, multiple sclerosis in a first-degree relative, lupus, recurrent infections, or serious infections
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Exclusion Criteria
- Active, serious, systemic or localized infection, including undrained abscess (may start/restart once controlled)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis)
- HBsAg-negative but antibody-to-hepatitis-B-core-antigen (anti-HBc)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis)
- Untreated HIV infection or at high risk for 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
Inclusion Criteria
- Prescribed and monitored by a VA / VA Community Care rheumatologist, dermatologist, or locally designated psoriasis expert
- Prescribed at the FDA-approved dose for psoriatic arthritis
- Inflammatory articular disease (joint, spine, and/or entheseal) with a definite or provisional diagnosis of psoriatic arthritis
- 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 antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (may initiate while waiting for results)
- 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)
- ONE interleukin-17A inhibitor (IL-17AI; i.e., ixekizumab [preferred] or secukinumab) is medically inadvisable, not tolerated or not adequate (i.e., NO response after 12 weeks, inadequate partial response after 24 weeks, or loss of initial response)
Additional Inclusion Criteria
- For patients 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
Supplemental Clinical Considerations
- Anti-HBs does not guarantee protection against HBV reactivation in HBsAg-negative/anti-HBc-positive patients; consult hepatologist or infectious diseases expert for prophylaxis vs preemptive monitoring
- TNFI may be medically inadvisable due to heart failure, demyelinating disease, multiple sclerosis in first-degree relative, lupus, recurrent infections, serious infections, etc.
- IL-17A inhibitors (ixekizumab/secukinumab) may be medically inadvisable due to Crohn’s disease, ulcerative colitis, or recurrent/severe Candida infections
- Ustekinumab may be medically inadvisable due to history of noninfectious pneumonia (interstitial, eosinophilic, cryptogenic organizing) and severe plaque psoriasis (risankizumab-rzaa preferred)
- Ustekinumab 45 mg is preferred for PsA with concomitant psoriasis in patients weighing ≤ 100 kg and for PsA without psoriasis; cost-benefit lost with 90 mg
- Ustekinumab and IL-23 inhibitors (guselkumab, risankizumab-rzaa) are ineffective for axial psoriatic arthritis
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Infection Screening & Testing
- Completed tuberculosis (TB) testing using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (at minimum: HBsAg, total anti-HBc, and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (initiation permitted while awaiting results)
HIV Status
- Untreated HIV infection or high risk for HIV infection is an exclusion criterion
- Treated, well-controlled, asymptomatic HIV-positive patients are eligible
Vaccination Status
- Concomitant live or live-attenuated vaccines, or administration of inactivated, live, or live-attenuated vaccines within 2 weeks prior to initiation, are exclusion criteria
Disease Severity & Diagnosis
- Chronic (≥ 6 months) moderate to severe plaque psoriasis (including nail-only involvement)
- Prescribed at the FDA-approved dose for plaque psoriasis
Prior Systemic and Topical Therapy Exclusions
- Methotrexate monotherapy must be medically inadvisable, not tolerated, or not adequate (defined as no treatment benefit after 3 months with at least 2 months at standard target dose [15–25 mg once weekly], or inadequate partial response after 6 months)
- Phototherapy must be medically inadvisable (e.g., confirmed skin cancer/melanoma history or strong likelihood per Fitzpatrick skin type I/II), inadequate (no benefit after 12 treatments or inadequate partial response after 24 treatments), not available, or not feasible
- Tumor necrosis factor inhibitor (TNFI) must be medically inadvisable (e.g., heart failure, demyelinating disease, multiple sclerosis in first-degree relative, lupus, recurrent/serious infections), not tolerated, or not adequate
- Interleukin-17A inhibitor (ixekizumab preferred, secukinumab) must be medically inadvisable (e.g., Crohn’s disease, ulcerative colitis, recurrent/severe Candida infections), not tolerated, or not adequate (defined as no response after 12 weeks, inadequate partial response after 24 weeks, or loss of initial response)
- Ustekinumab is no longer a prerequisite
Hepatitis B Management & Consultation
- HBsAg-positive status without antiviral prophylaxis is an exclusion; initiation permitted after starting prophylaxis
- If HBsAg-negative but anti-HBc-positive, consultation with a GI/liver or infectious diseases expert is required to advise on initiating antiviral prophylaxis versus preemptive monitoring for HBV reactivation
Special Populations & Counseling
- For patients who can become pregnant and partners who can become pregnant: counseling on potential risks vs benefits and use of effective contraception is required
Prescribing & Monitoring Requirements
- Must be prescribed and monitored by a VA/VA Community Care dermatologist or locally designated psoriasis expert
- Active, serious, systemic, or localized infection (including undrained abscess) is an exclusion; initiation/restart permitted once infection is controlled
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Indication & Patient Population
- • Treatment of active psoriatic arthritis (PsA) in adults
- • Active PsA defined as symptom onset ≥ 6 months, meeting classification criteria for PsA, TJC ≥ 5 of 68, SJC ≥ 5 of 66, ≥ 1 erosion in hands and/or feet or hsCRP ≥ 3.0 mg/L, and active PsO (≥ 1 plaque ≥ 2 cm diameter or nail psoriasis)
Prior Therapy Requirements & Place in Therapy
- • FDA-approved indication does not require trials of any prior therapies
- • May be used as an alternative to (at the same level as) ustekinumab and guselkumab for patients with active nonaxial, nonerosive PsA who have had an inadequate response to at least one TNFI and at least one IL-17AI, unless medically inadvisable
- • Ixekizumab is preferred in new starts within the IL-17AI class
- • Supported for patients with active PsA who have had an inadequate response to conventional immunomodulators and/or biologics, or for whom these therapies are medically inadvisable
Efficacy Considerations & Disease Features
- • Effective for: achievement of ACR20 response, minimal disease activity (MDA), improvement in joint/entheseal/dactylitis/nail manifestations, function, and quality of life
- • IL-23 inhibitors may be preferred over ustekinumab for severe PsA-associated plaque psoriasis
- • Ineffective or low certainty for: short-term (24-week) improvement in dactylitis, preventing radiographic progression of peripheral erosive disease, and symptomatic MRI-verified axial PsA
Safety Considerations
- • Safety considerations include infections and TB
- • Safety profile generally consistent with that in plaque psoriasis
Dosing & Administration
- • 150 mg subcutaneously at Weeks 0 and 4, then every 12 weeks
- • May be administered alone or in combination with nonbiologic immunomodulators
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Indication
- Treatment of moderately to severely active Crohn’s disease (CD) in adults.
Patient Selection & Place in Therapy
- May be less preferred than TNFIs (infliximab-abda or adalimumab) as first-line treatment to induce clinical remission in patients with moderate to severe, active luminal CD who have an inadequate response to conventional therapies.
- May be preferred over vedolizumab for second-line induction therapy in biologic-exposed patients.
- May be effective for skin and joint comorbidities of CD based on FDA approvals for plaque psoriasis and psoriatic arthritis.
Dosing & Administration
- Induction: 600 mg IV infusion over at least 1 hour at Weeks 0, 4, and 8.
- Maintenance: 180 mg or 360 mg SC at Week 12 then every 8 weeks thereafter; use the lowest effective dosage to maintain therapeutic response.
- On-Body Injector (wearable injector) adheres to the skin and administers each dose over up to 5 minutes; must be kept at least 12 inches away from electronic devices during administration and should not be exposed to magnetic resonance imaging.
- Duration of an adequate therapeutic trial is 12 weeks; onset of effects occurs at 4 weeks.
Monitoring & Pre-treatment Requirements
- Before initiating treatment: obtain liver enzymes and bilirubin levels, evaluate for tuberculosis (TB) infection, and complete all guideline-recommended vaccinations.
- Monitor liver enzymes and bilirubin during induction for up to at least 12 weeks of therapy, then per routine patient management.
Safety, Contraindications & Warnings
- Contraindicated in patients with a history of serious hypersensitivity reaction to risankizumab-rzaa or any excipients.
- Hepatotoxicity: Drug-induced liver injury has occurred during induction therapy; consider other treatment alternatives in patients with evidence of liver cirrhosis.
- Warnings/Precautions include hypersensitivity reactions, infections (including TB), and avoiding use of live vaccines.
Limitations & Evidence Gaps
- Efficacy and safety not reported in patients with fistulizing CD; not evaluated in patients with stricturing CD.
- Comparative efficacy and safety of combination therapy with conventional immunomodulators relative to risankizumab-rzaa monotherapy is unknown.
- On-Body Injector may not be suitable for patients who are blind without sighted assistance or have impaired dexterity.
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Exclusion Criteria
- Uncontrolled, active, severe infection (including evidence of C. difficile and undrained abscess); may start/restart once infection treatment has been initiated
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis
- Untreated HIV infection
- Concomitant live or live-attenuated vaccines, or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- Liver cirrhosis unless the prescriber deems that the potential benefits outweigh the risks
Inclusion Criteria
- Current or prior moderate to severe ulcerative colitis (UC) confirmed by endoscopy or imaging
- Prescribed and monitored by a VA/VA Community Care gastroenterologist/hepatologist 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
- Obtained liver panel including bilirubin
Additional Inclusion Criteria (Therapy History & Sequencing)
- Must meet ONE of the following:
- 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 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
- Sequencing: Risankizumab-rzaa is designated as a second-line or third-line agent. First-line therapy is infliximab (preferred) or adalimumab. Fourth-line options include mirikizumab-mrkz, guselkumab, or ustekinumab.
Special Considerations & Consultations
- HBsAg-negative but anti-HBc-positive: GI/hepatology or infectious diseases expert consultation required to advise on starting antiviral prophylaxis versus preemptively monitoring for HBV reactivation
- Women who can become pregnant: Counseling must be provided on potential risks vs benefits of treatment and the use of effective contraception
- Vaccinations: Update before initiation when possible; recombinant zoster (SHINGRIX) vaccine should be completed or initiated by the end of the first year, preferably when dosage is low, disease is stable, or a robust immune response can be expected
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Indication
- Treatment of moderately to severely active ulcerative colitis (UC)
Patient Population & Clinical Criteria
- Patients with inadequate response (IR) or intolerance (INT) to oral aminosalicylates, glucocorticoids (GCs), conventional immunomodulators (cIMMs) alone; ≥ 1 biologic, Janus kinase inhibitor (JAKi), and/or sphingosine-1-phosphate receptor modulator (S1PRM); or combination of conventional and advanced therapies
- No prior exposure to ustekinumab (p40) or IL-23 (p19) inhibitors
- Disease severity: modified Mayo score (mMS) of 5–9 and endoscopy subscore (ES) of 2–3
VHA PBM Guidance & Place in Therapy
- No prerequisite therapy specified for UC
- May be used for patients with medical inadvisability to, or mechanistic failure of, a TNFi, or pharmacokinetic failure of infliximab/biosimilar (the preferred TNFi in UC)
- Evidence supports efficacy in inducing and maintaining clinical remission and endoscopic remission; place in therapy remains uncertain due to lack of head-to-head trials
Pretreatment & Monitoring Requirements
- Obtain liver enzymes and bilirubin levels prior to treatment
- Evaluate for tuberculosis (TB) infection prior to treatment
- Administer guideline-recommended vaccinations prior to treatment
- Monitor liver enzymes and bilirubin levels during induction (up to ≥ 12 weeks)
- Monitor liver enzymes and bilirubin levels during subsequent treatment per routine patient management
Dosage Regimen
- Induction: 1200 mg IV infusion over at least 2 hours at Weeks 0, 4, and 8
- Maintenance: 180 mg or 360 mg SC at Week 12 then every 8 weeks thereafter; use the lowest effective dosage needed to maintain therapeutic response
Safety Considerations & Contraindications
- Contraindicated in patients with a history of serious hypersensitivity reaction to risankizumab-rzaa or excipients
- Warnings include hypersensitivity reactions, infections, TB, hepatotoxicity during induction, and avoidance of live vaccines
- Most common adverse events (≥3%): Arthralgia (induction); arthralgia, pyrexia, injection site reactions, rash (maintenance)
- Geriatric use: Limited data available; 103 UC patients were aged ≥ 65 years in clinical trials
- Drug interactions: No clinically significant changes observed for CYP450 substrates (caffeine, warfarin, omeprazole, metoprolol, midazolam)