Skyrizi (Risankizumab)
risankizumab-rzaa — selective anti-IL-23 p19 monoclonal antibody
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Moderate-to-severe plaque psoriasis | Adults candidates for systemic therapy or phototherapy | Monotherapy | FDA Approved |
| Active psoriatic arthritis | Adults | Monotherapy or with non-biologic DMARDs | FDA Approved |
| Moderately-to-severely active Crohn’s disease | Adults | IV induction then SC maintenance | FDA Approved |
| Moderately-to-severely active ulcerative colitis | Adults | IV induction then SC maintenance | FDA Approved |
Risankizumab is a selective IL-23 inhibitor that targets the p19 subunit, distinguishing it from ustekinumab which blocks the shared p40 subunit of both IL-12 and IL-23. This selectivity preserves IL-12-mediated Th1 responses involved in host defense while specifically suppressing Th17-driven inflammation. In dermatology, risankizumab has demonstrated very high rates of complete skin clearance (PASI 100) and is positioned as a first-line biologic for moderate-to-severe plaque psoriasis. In inflammatory bowel disease, it is approved for both Crohn’s disease and ulcerative colitis, using distinct IV induction dose levels for each condition.
Hidradenitis suppurativa: Phase 2 data and case series suggest benefit; phase 3 trials ongoing. Evidence quality: Low.
Ankylosing spondylitis / axial spondyloarthritis: Evaluated in clinical trials; mixed results. IL-23 inhibitors as a class have shown limited efficacy in axial disease. Evidence quality: Low.
Dosing
Adult Dosing by Clinical Scenario
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Plaque psoriasis — moderate-to-severe | 150 mg SC at Weeks 0 and 4 | 150 mg SC q12w | 150 mg q12w | Single injection with prefilled pen or syringe; no weight-based adjustment Self-injection after training is appropriate |
| Psoriatic arthritis — active disease | 150 mg SC at Weeks 0 and 4 | 150 mg SC q12w | 150 mg q12w | May use alone or with non-biologic DMARDs (e.g., methotrexate) Same dosing as psoriasis |
| Crohn’s disease — induction | 600 mg IV at Weeks 0, 4, and 8 | — | 600 mg per infusion | Infuse over at least 1 hour; single 600 mg vial per dose Check baseline LFTs and bilirubin before first dose |
| Crohn’s disease — maintenance | 180 mg or 360 mg SC at Week 12 | 180 mg or 360 mg SC q8w | 360 mg q8w | Use the lowest effective dose to maintain response; on-body injector or prefilled syringes available 360 mg: two 180 mg syringes or one 360 mg cartridge |
| Ulcerative colitis — induction | 1,200 mg IV at Weeks 0, 4, and 8 | — | 1,200 mg per infusion | Infuse over at least 2 hours; requires two 600 mg vials Double the CD induction dose; longer infusion time required |
| Ulcerative colitis — maintenance | 180 mg or 360 mg SC at Week 12 | 180 mg or 360 mg SC q8w | 360 mg q8w | Same maintenance options as Crohn’s disease Use lowest effective dosage needed to maintain response |
A key prescribing difference between risankizumab’s IBD indications is the induction dose: 600 mg IV for Crohn’s disease versus 1,200 mg IV for ulcerative colitis, with correspondingly different infusion durations (at least 1 hour vs at least 2 hours). Both indications then transition to the same SC maintenance options (180 mg or 360 mg q8w). This dose-escalation for UC reflects the higher drug exposure needed to achieve clinical response in colitis, as demonstrated in the INSPIRE and COMMAND trials. Clinicians should also obtain baseline liver enzymes and bilirubin before initiating IV induction for either IBD indication due to reports of hepatotoxicity.
Pharmacology
Mechanism of Action
Risankizumab is a humanized IgG1 monoclonal antibody that selectively binds to the p19 subunit of interleukin-23 (IL-23), blocking its interaction with the IL-23 receptor complex. Unlike agents targeting the shared p40 subunit (e.g., ustekinumab), risankizumab does not interfere with IL-12 signaling, preserving Th1-mediated immune surveillance including interferon-gamma production. IL-23 is a key driver of Th17 cell differentiation and maintenance, and its blockade reduces downstream production of IL-17A, IL-17F, IL-22, and other pro-inflammatory mediators central to psoriatic disease and intestinal inflammation. This targeted selectivity is hypothesized to contribute to the favorable safety profile observed in clinical trials, particularly the low rates of candidal infections compared with direct IL-17 blockade.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | SC bioavailability ~89% (psoriasis phase III); Tmax 3–14 days | High bioavailability allows reliable SC dosing; no food effect considerations |
| Distribution | Vss ~11.2 L (90 kg psoriasis patient); ~8.5 L (65 kg CD patient) | Confined to vascular and interstitial space; body weight affects Vd but no dose adjustment required |
| Metabolism | Degraded via catabolic pathways into peptides and amino acids; not CYP-mediated | No hepatic CYP interactions expected; no dose adjustment for renal or hepatic impairment anticipated |
| Elimination | Terminal t½ ~28 days (psoriasis); ~22–27 days (CD); CL ~0.31 L/day; steady state by Week 16 | Long half-life supports q12w (psoriasis/PsA) and q8w (IBD) maintenance intervals |
Side Effects
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Upper respiratory infections | 13.0% vs 9.7% placebo (PsO Wk 16) | Broad category including nasopharyngitis, sinusitis, pharyngitis, and viral URI; similar rates in CD induction (10.6%) |
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Headache | 3.5% vs 2.0% (PsO); 6.6% vs 5.6% (CD induction) | Usually mild; includes tension and sinus headache subtypes |
| Arthralgia | 5.0% vs 4.4% (CD induction); 9.2% vs 8.4% (CD maint 360 mg); 3% vs 1% (UC induction) | Most consistently reported adverse effect across all IBD trials; distinguish from underlying joint disease |
| Fatigue | 2.5% vs 1.0% (PsO) | Includes asthenia; dose-independent |
| Injection site reactions | 1.5% vs 1.0% (PsO); 5.6% vs 2.8% (CD maint 360 mg) | Includes erythema, pain, swelling, bruising; rotate injection sites |
| Tinea infections | 1.1% vs 0.3% (PsO) | Includes tinea pedis, cruris, and versicolor; treat with topical antifungals; does not require drug discontinuation |
| Abdominal pain | 8.5% vs 4.2% (CD maint 360 mg) | Higher with 360 mg dose; distinguish from underlying Crohn’s symptoms |
| Pyrexia | 4.9% vs 2.8% (CD maint 360 mg); 4.0–4.7% vs 3.5% (UC maint) | Low-grade; evaluate for infection if persistent |
| Anemia | 4.5–4.9% vs 4.2% (CD maintenance) | May reflect ongoing disease activity rather than direct drug effect |
| Back pain | 4.2% vs 2.1% (CD maint 360 mg) | More prominent at higher maintenance dose |
| Rash | 4.1% vs 1.7% (UC maint 180 mg) | Includes macular rash; also reported as postmarketing event |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Serious infections (cellulitis, osteomyelitis, sepsis, herpes zoster) | ≤0.4% (PsO controlled period); 2.6–5.6% (CD maint) | Any time during treatment | Hold risankizumab; initiate appropriate antimicrobial therapy; reassess before resuming |
| Anaphylaxis / serious hypersensitivity | Rare (1 case in phase 2 PsA trial) | Within hours of administration | Discontinue permanently; emergency treatment |
| Drug-induced liver injury (IBD induction) | Very rare (1 serious case reported in CD trials: ALT 54x ULN) | During IV induction phase (after 2 doses reported) | Monitor LFTs at baseline and during induction up to 12 weeks; interrupt if DILI suspected; corticosteroids may be needed |
| Lipid elevations (CD/UC) | Common (mean increase): total cholesterol +9.4 mg/dL, LDL-C +6.6 mg/dL by Wk 12 | First 4 weeks of induction; remains stable | Monitor fasting lipids; manage per cardiovascular risk guidelines; generally modest elevations |
A unique safety signal for risankizumab in IBD is drug-induced liver injury during IV induction. One patient with Crohn’s disease developed severe hepatotoxicity (ALT 54x ULN) after two induction doses, requiring hospitalization and corticosteroid treatment. The PI mandates baseline liver enzyme and bilirubin measurement before IV induction and monitoring at least through the first 12 weeks. Clinicians should consider alternative therapies in patients with pre-existing liver cirrhosis and promptly investigate any unexplained transaminase elevation.
Drug Interactions
Risankizumab is not metabolized by cytochrome P450 enzymes and is not expected to directly alter CYP activity. As an IgG1 monoclonal antibody, it undergoes catabolic degradation independently of hepatic metabolic pathways. No formal in vivo drug interaction studies have been conducted. Population pharmacokinetic analyses confirm that concomitant methotrexate, NSAIDs, and corticosteroids do not affect risankizumab clearance. However, as with other immunomodulatory biologics, resolution of chronic inflammation may theoretically normalize suppressed CYP450 enzyme activity, potentially affecting narrow-therapeutic-index substrates.
Monitoring
- TB ScreeningBaseline
RoutineTST or IGRA before first dose. Consider anti-TB therapy if latent TB is confirmed and adequate prior treatment cannot be documented. In psoriasis trials, no patients with latent TB on prophylaxis developed active TB. - Liver Enzymes (IBD)Baseline, then during induction up to 12 weeks
RoutineALT, AST, and total bilirubin before initiating IV induction for CD or UC. Monitor during induction; continue per routine patient management thereafter. Interrupt if drug-induced liver injury is suspected. - Infection SignsEvery visit
RoutineAssess for fever, cough, skin changes, urinary symptoms. Hold therapy for clinically significant infections. - Lipid Panel (IBD)Baseline, then at 12 weeks
RoutineTotal cholesterol and LDL-C increase modestly during induction (mean +9.4 mg/dL and +6.6 mg/dL respectively). Monitor and manage per cardiovascular risk profile. - Hepatic Events (PsA)Periodic
Trigger-basedALT/AST elevations were more common in PsA trials (5.4% vs 3.9% placebo). No serious hepatic events reported, but monitor if symptoms arise. - ImmunogenicityIf loss of response
Trigger-basedAnti-drug antibodies develop in ~24% (PsO), ~12% (PsA), ~3.4% (CD), and ~4–9% (UC). High-titer ADA (≥128) in ~1% of PsO patients associated with reduced drug levels and efficacy. Consider drug level measurement before switching.
Contraindications & Cautions
Absolute Contraindications
- History of serious hypersensitivity reaction to risankizumab-rzaa or any excipient (glacial acetic acid, polysorbate 20, sodium acetate, trehalose, succinic acid, sodium succinate, sorbitol)
Relative Contraindications (Specialist Input Recommended)
- Clinically important active infection — delay initiation until infection resolves or is adequately treated
- Active tuberculosis — do not administer; treat TB first
- Pre-existing liver cirrhosis (for IBD indications) — consider alternative treatment options given hepatotoxicity signal
- Chronic or recurrent infection history — careful risk-benefit assessment required
Use with Caution
- Pregnancy — insufficient human data; animal studies showed dose-dependent fetal/infant loss at 50 mg/kg (5x human exposure at maximum induction dose). Discuss contraception timing with prescriber given the drug’s long half-life (~28 days).
- Lactation — no human milk data; weigh breastfeeding benefits against potential infant exposure
- Patients scheduled for vaccination — complete all age-appropriate vaccines before treatment; avoid live vaccines during therapy
Drug-induced liver injury requiring hospitalization has been reported during IV induction with risankizumab in Crohn’s disease (ALT 54x ULN, AST 30x ULN, bilirubin 2.2x ULN after two 600 mg IV doses). The PI mandates liver enzyme and bilirubin monitoring at baseline and during induction for at least 12 weeks. This warning is specific to the IBD IV induction regimen and is not replicated in the psoriasis or PsA prescribing guidance.
Patient Counselling
Purpose of Therapy
Risankizumab works by selectively blocking IL-23, a single immune messenger that drives the inflammation underlying psoriasis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis. Because it targets only one pathway rather than broadly suppressing the immune system, it has a favorable safety profile. For psoriasis, treatment results in sustained skin clearance for many patients, with injections needed only every 12 weeks after the initial loading period. For bowel disease, the first three doses are given as an IV infusion in a clinic, followed by self-administered injections at home every 8 weeks.
How to Take
For psoriasis and psoriatic arthritis, the drug is self-injected using a prefilled pen or syringe at Weeks 0 and 4, then every 12 weeks. For Crohn’s disease and ulcerative colitis, the initial doses are infused intravenously in a healthcare setting, followed by subcutaneous injections (using a prefilled syringe or on-body injector) every 8 weeks starting at Week 12. Allow the pen or syringe to reach room temperature (15–90 minutes depending on formulation) before injection. Inject into the thigh or abdomen, rotating sites each time. Do not inject into skin that is tender, bruised, or affected by psoriasis.
Sources
- Skyrizi (risankizumab-rzaa) prescribing information. AbbVie Inc. Revised 3/2026. Full Prescribing InformationPrimary source for all dosing, indications, adverse reactions, warnings, PK data, and hepatotoxicity guidance in this monograph.
- Skyrizi (risankizumab) European Medicines Agency Summary of Product Characteristics. EMA SmPCEuropean regulatory perspective with supplementary safety and efficacy data.
- Gordon KB, Strober B, Lebwohl M, et al. Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials. Lancet. 2018;392(10148):650–661. DOIPivotal phase 3 trials demonstrating risankizumab superiority over ustekinumab and placebo in plaque psoriasis.
- Kristensen LE, Keiserman M, Engel K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 and KEEPsAKE 2 trials. Ann Rheum Dis. 2022;81(3):367–375. DOIPhase 3 trials establishing risankizumab efficacy in PsA, including biologic-experienced patients.
- D’Haens G, Panaccione R, Baert F, et al. Risankizumab as induction therapy for Crohn’s disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. Lancet. 2022;399(10340):2015–2030. DOICo-primary induction trials (ADVANCE, MOTIVATE) establishing IV induction efficacy in Crohn’s disease.
- Ferrante M, Panaccione R, Baert F, et al. Risankizumab as maintenance therapy for moderately to severely active Crohn’s disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. Lancet. 2022;399(10340):2031–2046. DOIFORTIFY maintenance trial establishing SC maintenance dosing (180 mg and 360 mg q8w) for Crohn’s disease.
- Louis E, Schreiber S, Panaccione R, et al; INSPIRE and COMMAND Study Group. Risankizumab for ulcerative colitis: two randomized clinical trials. JAMA. 2024;332(11):881–897. DOIPivotal phase 3 induction (INSPIRE) and maintenance (COMMAND) trials for the UC indication using 1,200 mg IV induction dose.
- Feuerstein JD, Ho EY, Shmidt E, et al. AGA clinical practice guidelines on the medical management of moderate to severe luminal and perianal fistulizing Crohn’s disease. Gastroenterology. 2021;160(7):2496–2508. DOIAGA guideline positioning IL-23 inhibitors in the Crohn’s disease treatment algorithm.
- Singh S, Loftus EV Jr, Limketkai BN, et al. AGA living clinical practice guideline on pharmacological management of moderate-to-severe ulcerative colitis. Gastroenterology. 2024;167(7):1307–1343. DOIUpdated AGA guideline recommending risankizumab as a higher-efficacy option for UC.
- Gaffen SL, Jain R, Garg AV, Cua DJ. The IL-23–IL-17 immune axis: from mechanisms to therapeutic testing. Nat Rev Immunol. 2014;14(9):585–600. DOIComprehensive review of IL-23/IL-17 biology underpinning the rationale for selective p19 blockade.
- Suleiman AA, Minocha M, Khatri A, Pang Y, Othman AA. Population pharmacokinetics of risankizumab in healthy volunteers and subjects with moderate to severe plaque psoriasis: integrated analyses of phase I–III clinical trials. Clin Pharmacokinet. 2019;58(10):1309–1321. DOIIntegrated PopPK analysis establishing Vss (11.2 L), CL (0.31 L/day), t½ (28 days), and SC bioavailability (89%) for risankizumab in psoriasis.
- Suleiman AA, Khatri A, Minocha M, Othman AA. Population pharmacokinetics of the interleukin-23 inhibitor risankizumab in subjects with psoriasis and Crohn’s disease: analyses of phase I and II trials. Clin Pharmacokinet. 2019;58(3):375–387. DOIPopPK model comparing risankizumab disposition in psoriasis (Vss 11.7 L, t½ 27 days) versus Crohn’s disease (Vss 8.45 L, t½ 22 days).
- Pang Y, Khatri A, Suleiman AA, Othman AA. Clinical pharmacokinetics and pharmacodynamics of risankizumab in psoriasis patients. Clin Pharmacokinet. 2020;59(3):311–326. DOIComprehensive PK/PD review confirming dose-exposure-response relationships supporting the 150 mg SC q12w regimen.