What Is Skyrizi (Risankizumab)?
Skyrizi is the brand name for risankizumab, an IL-23 inhibitor biologic developed by AbbVie and Boehringer Ingelheim. It belongs to the newest generation of targeted biologic therapies for immune-mediated inflammatory diseases and has demonstrated skin clearance rates in plaque psoriasis that surpass many older biologics. Since its initial approval for psoriasis in 2019, Skyrizi has expanded to treat psoriatic arthritis, Crohn's disease, and ulcerative colitis — all driven by the shared role of the IL-23 inflammatory pathway in these conditions.
Mechanism: Selectively Blocking IL-23
The interleukin-23 (IL-23) cytokine is a master regulator of several downstream inflammatory pathways. It is produced by dendritic cells and macrophages and drives the differentiation and survival of Th17 cells — the T helper cell subset responsible for producing the inflammatory cytokines (particularly IL-17) that mediate chronic plaque psoriasis, inflammatory bowel disease, and psoriatic arthritis.
IL-23 is a heterodimeric protein made of two subunits: p19 and p40. The p40 subunit is shared with IL-12, while the p19 subunit is unique to IL-23. Risankizumab is a highly specific monoclonal antibody that targets only the p19 subunit of IL-23. This selectivity for IL-23 p19 (rather than both IL-12 and IL-23 via p40, as older agents like ustekinumab do) is a key mechanistic distinction — blocking only IL-23 while leaving IL-12 signaling intact may preserve some beneficial immune functions that IL-12 mediates.
How IL-23 Inhibitors Compare to Earlier Biologics
| Drug Class | Target | Examples | Psoriasis Efficacy |
|---|---|---|---|
| TNF-alpha inhibitors | TNF-α | Humira (adalimumab), Enbrel (etanercept) | Moderate (PASI 75 ~50–60%) |
| IL-12/23 inhibitors | IL-12 + IL-23 (p40) | Stelara (ustekinumab) | Good (PASI 75 ~70%) |
| IL-17 inhibitors | IL-17A or IL-17 receptor | Cosentyx (secukinumab), Taltz (ixekizumab) | High (PASI 90 ~50–60%) |
| IL-23 inhibitors (p19) | IL-23 (p19 only) | Skyrizi (risankizumab), Tremfya (guselkumab), Ilumya (tildrakizumab) | Very high (PASI 90 ~70–75%) |
Clinical Trial Clearance Rates in Plaque Psoriasis
In the UltIMMa-1 and UltIMMa-2 pivotal trials for plaque psoriasis, risankizumab achieved PASI 90 response (90% improvement in psoriasis severity) in approximately 75% of patients at week 16, and PASI 100 (complete skin clearance) in approximately 36% — compared to about 42% PASI 90 and 12% PASI 100 for ustekinumab. In the IMMvent trial comparing risankizumab to adalimumab (Humira), risankizumab significantly outperformed adalimumab across all psoriasis severity endpoints. These data established risankizumab as among the most effective biologic therapies available for plaque psoriasis.
Dosing Schedule
For plaque psoriasis, Skyrizi is given as two subcutaneous injections at week 0 (initial dose), then a single injection at week 4, followed by every 12-week maintenance injections. This quarterly maintenance schedule — one injection every three months — is among the most convenient in the biologic landscape and is a meaningful practical advantage for patients who have difficulty with more frequent administration.
For Crohn's disease and ulcerative colitis, Skyrizi uses a different route of administration for induction — intravenous infusions — followed by subcutaneous maintenance injections.
FDA-Approved Indications
- Moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy (2019)
- Active psoriatic arthritis in adults (2022)
- Moderate-to-severely active Crohn's disease in adults (2022)
- Moderately to severely active ulcerative colitis in adults (2023)
Side Effects
Upper respiratory infections
Upper respiratory tract infections (nasopharyngitis, sinusitis) are among the most commonly reported side effects in Skyrizi trials, reflecting the mild immunosuppressive effects of the drug. Most are mild and manageable.
Injection site reactions
Injection site pain, redness, and swelling are common with subcutaneous administration. Allowing the pen to reach room temperature before use and rotating injection sites helps minimize discomfort.
SERIOUS INFECTIONS: Risankizumab may increase susceptibility to serious bacterial, fungal, and viral infections. Do not use Skyrizi during active serious infections. Patients should report signs of infection (fever, chills, persistent cough, skin wounds that are not healing, painful urination) to their provider.
TUBERCULOSIS SCREENING REQUIRED: Patients must be evaluated and tested for latent tuberculosis before starting Skyrizi. Latent TB must be treated before initiating risankizumab therapy. Patients should also be screened for fungal infections in endemic areas before starting treatment.
Hypersensitivity reactions
Serious hypersensitivity reactions including anaphylaxis have been reported. Patients should seek immediate medical attention if they develop signs of a severe allergic reaction after injection.
Want to compare Skyrizi to Humira, Dupixent, or other biologics?
Compare MedicationsFrequently Asked Questions
For plaque psoriasis specifically, head-to-head clinical trial data (IMMvent trial) have demonstrated that risankizumab (Skyrizi) produces significantly greater skin clearance rates than adalimumab (Humira) across all measured endpoints — PASI 90, PASI 100, and IGA scores. For psoriasis, IL-23 inhibitors as a class have largely surpassed TNF inhibitors like Humira in terms of skin clearance efficacy. However, Humira has a much broader approval profile covering rheumatoid arthritis, inflammatory bowel disease, and other conditions where Skyrizi is not yet approved or where the two have not been head-to-head compared. The choice between them depends on which condition is being treated and individual patient factors.
Skyrizi (risankizumab) is FDA-approved for moderate-to-severe plaque psoriasis in adults, active psoriatic arthritis, moderately to severely active Crohn's disease, and moderately to severely active ulcerative colitis. All of these conditions involve pathological overactivation of the IL-23/Th17 inflammatory axis, which risankizumab suppresses by blocking the p19 subunit of IL-23. Its use in psoriasis and inflammatory bowel disease represents a significant advance over older biologic therapies in terms of both efficacy and dosing convenience.
In plaque psoriasis clinical trials, meaningful skin improvement is typically seen within the first 4–8 weeks. PASI 90 response rates peak around weeks 16–24 and are sustained with ongoing maintenance therapy. Some patients experience near-complete or complete skin clearance within the first few months. For Crohn's disease and ulcerative colitis, clinical response during the intravenous induction phase may be assessed at week 12. Individual response timelines vary, and full assessment of response typically occurs at 3–6 months of therapy. Patients who do not respond adequately may require evaluation for alternative treatment options.