Skyrizi (risankizumab) works by blocking a specific immune signal called interleukin-23 (IL-23) that drives the chronic gut inflammation behind Crohn’s disease. It’s a targeted antibody, approved for moderately to severely active Crohn’s, that latches onto one part of IL-23 and prevents it from triggering the inflammatory chain reaction that damages the intestinal lining. In clinical trials, roughly 42 to 45 percent of patients reached clinical remission within 12 weeks of starting treatment, compared to 20 to 25 percent on placebo.
The Immune Signal Behind Crohn’s Inflammation
In a healthy gut, the immune system uses signaling molecules called interleukins to coordinate its response to bacteria and other threats. IL-23 is one of those signals, and in Crohn’s disease, it’s overactive. It tells several types of immune cells in the gut wall to produce inflammatory compounds (IL-17A, IL-17F, and IL-22) that, when produced in excess, cause the chronic inflammation and tissue damage characteristic of Crohn’s.
Skyrizi is a high-affinity antibody that binds to the p19 subunit of IL-23, which is unique to IL-23 alone. This is an important distinction: an older, related molecule called IL-12 shares a different subunit (p40) with IL-23, and some treatments block both. By targeting only p19, Skyrizi shuts down IL-23 signaling without interfering with IL-12, which plays a separate role in immune defense. The result is a more precise intervention. Once Skyrizi binds to IL-23, the molecule can no longer dock with its receptor on immune cells, and the downstream inflammatory cascade slows down.
What the Clinical Trials Showed
Skyrizi’s approval for Crohn’s disease was based on three major Phase 3 trials: ADVANCE and MOTIVATE (both 12-week induction studies) and FORTIFY (a 52-week maintenance study).
In ADVANCE, 45 percent of patients receiving Skyrizi achieved clinical remission at 12 weeks, versus 25 percent on placebo. Pain and stool frequency scores followed a similar pattern: 43 percent of treated patients saw those symptoms resolve, compared to 22 percent on placebo. Perhaps more striking, 40 percent of patients showed visible healing of intestinal damage on endoscopy, versus just 12 percent on placebo.
MOTIVATE enrolled patients who had already failed at least one prior biologic therapy, a harder-to-treat group. Even so, 42 percent reached clinical remission with Skyrizi, compared to 20 percent on placebo. Endoscopic response rates were 29 to 34 percent versus 11 percent on placebo. Symptom improvement began appearing as early as week 4 in both trials.
Long-Term Results at One Year
The FORTIFY trial followed patients who had responded to Skyrizi during induction and asked whether the drug could maintain those gains over a full year. Patients were randomly assigned to continue Skyrizi or switch to placebo (effectively withdrawing the drug). At 52 weeks, 52 percent of patients continuing Skyrizi remained in clinical remission, compared to 41 percent of those switched to placebo. The gap was even wider for endoscopic response: 47 percent on Skyrizi versus 22 percent on placebo still showed intestinal healing.
These numbers tell two stories. First, many patients who respond to induction need ongoing treatment to keep their disease controlled. Second, nearly half of patients on maintenance Skyrizi showed measurable healing of the gut lining at one year, not just symptom relief.
How Treatment Is Given
Skyrizi for Crohn’s disease uses a two-phase dosing schedule. During the induction phase, you receive three intravenous (IV) infusions of 600 mg, each lasting at least one hour, given at weeks 0, 4, and 8. These are administered at an infusion center or clinic.
Starting at week 12, treatment shifts to self-administered injections under the skin (subcutaneous), given every 8 weeks at either 180 mg or 360 mg. This is a meaningful practical difference: after the first three months of clinic visits, ongoing treatment happens at home with a prefilled device, similar to other biologic injections.
Side Effects and Safety
The most common side effects in clinical trials were mild: upper respiratory infections (nasopharyngitis), stomach bugs (gastroenteritis), and fatigue. Because Skyrizi dials down part of the immune system, infections are the primary concern. In a long-term safety study, about 9 percent of patients experienced a serious infection, including things like abscesses or viral gastroenteritis severe enough to require medical attention. Opportunistic infections (the kind that take advantage of a weakened immune system) were uncommon, occurring in under 5 percent of patients, and were mostly fungal infections of the mouth or esophagus.
Liver enzyme elevations showed up in about 9 percent of patients but were consistently mild, never serious, and returned to normal without stopping the drug. No cases met the threshold for significant liver injury.
How Skyrizi Compares to Similar Treatments
The closest comparison is ustekinumab (Stelara), another antibody that blocks IL-23 but does so by binding the shared p40 subunit, meaning it also blocks IL-12. In the head-to-head SEQUENCE trial involving patients who had previously tried anti-TNF therapy, Skyrizi matched ustekinumab’s clinical remission rates at 24 weeks and was superior in endoscopic remission (visible gut healing) at 48 weeks.
Real-world data from biologic-naive patients, those who had never taken a biologic before, tells a slightly different story. A multicenter retrospective study presented at DDW 2025 found no significant differences between the two drugs in clinical remission, hospitalizations, surgeries, emergency visits, steroid use, or markers of disease progression at either one or two years. This held true even when ustekinumab was given at an optimized, more frequent dosing schedule. For patients new to biologic therapy, the two treatments appear to perform similarly in practice, though Skyrizi’s edge in endoscopic healing from the SEQUENCE trial may matter for long-term outcomes.
What to Expect as a Patient
If you’re starting Skyrizi for Crohn’s, the first three infusions over eight weeks are the most time-intensive part. Some patients notice symptom improvement within the first four weeks. By 12 weeks, your doctor will assess whether you’ve responded well enough to continue on maintenance injections. Roughly 4 in 10 patients see meaningful symptom relief and gut healing during this induction window. Among those who do respond, about half maintain remission through at least one year of continued treatment.
The shift to home injections every eight weeks is a relatively low maintenance schedule compared to some other biologics. Routine blood work to monitor liver enzymes and signs of infection is typical during treatment, and your gastroenterologist will likely schedule periodic endoscopies to track how well the intestinal lining is actually healing, not just whether symptoms have improved.