Skyrizi (risankizumab) is a biologic drug classified as a monoclonal antibody. More specifically, it’s an interleukin-23 (IL-23) antagonist, meaning it works by blocking a specific protein in the immune system that drives inflammation. First approved by the FDA in April 2019, Skyrizi is used to treat several chronic inflammatory conditions, including plaque psoriasis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis.
How Skyrizi Works
Your immune system uses signaling proteins called interleukins to coordinate its inflammatory response. One of these, IL-23, plays a key role in triggering the kind of chronic, overactive inflammation seen in autoimmune conditions. In people with psoriasis or inflammatory bowel disease, IL-23 is essentially stuck in overdrive, telling immune cells to keep attacking healthy tissue.
Skyrizi is a lab-engineered antibody designed to latch onto a specific part of IL-23 called the p19 subunit. By binding to this subunit, the drug physically prevents IL-23 from connecting with its receptor on immune cells. Without that connection, the downstream chain reaction that produces inflammatory molecules is shut down. This is a targeted approach: rather than suppressing the entire immune system, Skyrizi blocks one narrow pathway responsible for the excess inflammation.
What Makes It a Biologic
Skyrizi is not a traditional pill-based medication. It’s a biologic, which means it’s a large, complex protein made from living cells. Specifically, it’s produced using genetically engineered hamster ovary cells through recombinant DNA technology. The resulting molecule is a humanized immunoglobulin G1 (IgG1) monoclonal antibody with a molecular weight of roughly 149 kilodaltons, far larger and more complex than a typical small-molecule drug like ibuprofen or methotrexate.
Because biologics are proteins, they would be destroyed by stomach acid if swallowed. That’s why Skyrizi is given either as an injection under the skin or, for certain conditions, as an intravenous infusion at a clinic.
Conditions Skyrizi Treats
Skyrizi has FDA approval for four conditions, each tied to the same underlying problem of IL-23-driven inflammation.
- Moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. This was the original approval in April 2019. In a long-term study, all 21 patients achieved 90% skin clearance by week 104, and 17 of 21 reached complete clearance.
- Psoriatic arthritis in adults, approved in January 2022.
- Crohn’s disease in adults with moderately to severely active disease.
- Ulcerative colitis in adults with moderately to severely active disease.
How It’s Given
The way you receive Skyrizi depends on what condition is being treated. For plaque psoriasis and psoriatic arthritis, it’s a subcutaneous injection (a shot under the skin, similar to an insulin injection) given at the start, again four weeks later, and then once every 12 weeks. Many people learn to give themselves these injections at home.
For Crohn’s disease and ulcerative colitis, treatment starts with a higher-dose induction phase delivered through an IV at a clinic. For Crohn’s, this involves three infusions over the first eight weeks. For ulcerative colitis, the induction dose is double that of Crohn’s, also given as three infusions. After the induction phase, both conditions switch to subcutaneous injections every eight weeks for ongoing maintenance.
Screening Before Starting Treatment
Because Skyrizi suppresses part of the immune system’s inflammatory response, certain infections need to be ruled out or managed before you begin. You’ll be tested for tuberculosis using either a skin test or a blood test. You’ll also be screened for hepatitis B and hepatitis C. If you carry hepatitis B, antiviral treatment needs to be started before Skyrizi can be prescribed.
Vaccination timing matters too. Live vaccines (like the shingles vaccine Zostavax or the MMR vaccine) cannot be given while you’re on Skyrizi, and any vaccines, including inactivated ones, should be completed at least two weeks before your first dose. This is a practical detail worth planning for if you’re about to start treatment.
How Skyrizi Compares to Other Biologics
Skyrizi belongs to a newer generation of biologics that target IL-23 specifically. Older biologics in the same general family, like ustekinumab, block both IL-12 and IL-23 because they target a protein subunit shared by both. Skyrizi’s advantage is its precision: by targeting only the p19 subunit unique to IL-23, it leaves IL-12 signaling intact. IL-12 plays a role in fighting infections and certain cancers, so preserving that pathway is considered a benefit.
Structural studies have shown that Skyrizi binds to a larger surface area on IL-23 compared to ustekinumab, with more water-attracting contact points. This tighter, more extensive grip on the target may contribute to its strong and durable clinical effects, including the ability to maintain skin clearance on a dosing schedule of just once every 12 weeks for psoriasis.