Skyrizi, known by its generic name risankizumab, is a biologic medication that has become an important treatment option for adults with moderate to severe Crohn's disease. It works by targeting and blocking the interleukin-23 (IL-23) protein, which is a key driver of the inflammatory response in inflammatory bowel disease (IBD). By disrupting this inflammatory pathway, Skyrizi helps to reduce intestinal inflammation, leading to symptom relief, remission, and mucosal healing.
Clinical Trial Success Rates
Clinical trial results provide a clear picture of Skyrizi's efficacy during both the initial induction phase and the subsequent maintenance phase. Data from the pivotal ADVANCE, MOTIVATE, and FORTIFY Phase 3 studies demonstrated significant results compared to placebo, both for patients with and without prior biologic therapy failure.
Induction Phase (12 Weeks)
During the induction phase, patients receive intravenous doses to quickly reduce active inflammation. The initial success rates were notably high:
- Clinical Remission: In the ADVANCE and MOTIVATE trials, approximately 42–45% of patients achieved clinical remission (defined by a significant reduction in the Crohn's Disease Activity Index or CDAI) at Week 12. This was a substantial improvement compared to the placebo group, where remission rates were between 20–25%.
- Endoscopic Response: Visible improvement of the intestinal lining, or endoscopic response, was also a key metric. About 29–40% of patients on Skyrizi achieved this at 12 weeks, versus only 12% on placebo.
Maintenance Phase (52 Weeks)
For patients who respond to induction, the goal shifts to maintaining remission with subcutaneous injections. The FORTIFY maintenance trial demonstrated impressive durability over one year.
- Clinical Remission: In the FORTIFY trial, patients who had responded to induction were randomized to continue Skyrizi or switch to placebo. A significantly higher percentage of those who continued Skyrizi (at either 180 mg or 360 mg) maintained clinical remission compared to the placebo group (e.g., 55% with 180 mg vs. 41% with placebo).
- Endoscopic Response: Similarly, lasting endoscopic response was observed, with rates of 47% for both the 180 mg and 360 mg maintenance doses after one year.
Long-Term Efficacy and Real-World Data
Beyond the initial one-year clinical trials, extended studies have shown that the benefits of Skyrizi are sustainable over multiple years. An analysis tracking outcomes up to Week 152 (nearly three years) found that a significant portion of patients maintained their response. For example, CDAI clinical remission was sustained in 47.2% of patients in a pooled population. Real-world data from observational studies further support these findings, showing that long-term treatment with risankizumab is both effective and safe for many patients with Crohn's disease.
Comparison to Other Biologics
A head-to-head clinical trial, known as the SEQUENCE study, directly compared the effectiveness of Skyrizi to another common biologic, Stelara (ustekinumab), in patients who had failed previous anti-TNF therapy. The results provided valuable context on Skyrizi's place in the treatment paradigm.
- Clinical Remission: At Week 24, Skyrizi demonstrated non-inferiority to Stelara for clinical remission, with 59% of Skyrizi patients achieving remission compared to 40% of Stelara patients.
- Endoscopic Remission: By Week 48, Skyrizi proved superior to Stelara for endoscopic remission, with rates of 32% versus 16%.
Skyrizi vs. Stelara in the SEQUENCE Study
| Endpoint | Skyrizi (Risankizumab) | Stelara (Ustekinumab) | Comparative Result |
|---|---|---|---|
| Clinical Remission at Week 24 | 59% | 40% | Non-inferiority demonstrated |
| Endoscopic Remission at Week 48 | 32% | 16% | Superiority demonstrated (p<0.0001) |
| Steroid-Free Endoscopic Remission at Week 48 | 31% | 15% | Superiority demonstrated |
| Endoscopic Response at Week 48 | 45% | 22% | Superiority demonstrated |
Factors Influencing Treatment Success
Individual patient outcomes with Skyrizi can be influenced by several factors:
- Disease Duration: Studies have shown that starting treatment with Skyrizi earlier in the disease course is associated with higher rates of clinical and endoscopic success. Patients with shorter disease duration (<2 years) tend to have better outcomes than those with longer-standing disease (>10 years).
- Prior Biologic Exposure: While Skyrizi is effective for patients who have failed prior biologic therapies, evidence suggests that biologic-naive patients may achieve numerically higher response rates. The head-to-head SEQUENCE trial, however, showed superiority over Stelara even in patients with prior anti-TNF failure.
- Disease Phenotype: Certain types of Crohn's disease, such as penetrating disease, have been identified as potential risk factors for treatment failure or the need for treatment escalation. Similarly, perianal fistulizing disease has been associated with a higher likelihood of treatment escalation.
- Adherence to Treatment: Consistent adherence to the prescribed dosing schedule is crucial for maintaining remission and preventing a loss of response over time.
Important Safety Information
Like all medications, Skyrizi has potential side effects. The most common side effects observed in clinical trials for Crohn's disease include upper respiratory infections, headache, joint pain, abdominal pain, and injection site reactions.
More serious side effects can occur, and patients should be aware of the following:
- Increased Infection Risk: Skyrizi can lower the immune system's ability to fight infections. Before starting treatment, doctors will screen for tuberculosis (TB). Patients should report any signs of infection, such as fever or persistent cough, to their doctor.
- Allergic Reactions: Serious allergic reactions are possible, though rare. Signs like swelling of the face, lips, or tongue, or difficulty breathing, require immediate emergency medical attention.
- Liver Problems: During intravenous induction, liver problems have been reported. Regular blood tests are necessary to monitor liver function.
Conclusion
Skyrizi has demonstrated significant success rates for inducing and maintaining clinical remission and endoscopic response in adults with moderate to severe Crohn's disease. Clinical trial data, supported by real-world evidence, indicates durable long-term effectiveness and a favorable safety profile. Its performance in head-to-head studies against other biologics further solidifies its position as a valuable treatment option, particularly for patients with previous biologic failure. However, treatment success can vary based on individual factors like disease duration and prior therapy exposure. Open communication with a healthcare provider is essential to determine if Skyrizi is the right choice and to manage expectations based on a patient's specific health profile. For those seeking additional information on managing their condition, the Crohn's & Colitis Foundation offers comprehensive resources and support.
