Extended treatment with Skyrizi ‘may ultimately benefit’ refractory Crohn’s disease
Key takeaways:
- Most patients with moderate to severe CD who did not initially respond to risankizumab achieved clinical response after extension.
- Delayed responders also demonstrated clinical and endoscopic benefits.
Patients with moderate to severe Crohn’s disease who did not achieve clinical response to IV induction with Skyrizi benefitted from an additional 12 weeks of treatment, according to study results in Clinical Gastroenterology and Hepatology.
“The findings of the extended induction study confirmed what we suspected for many years — that some patients don’t need more drug, per se, but more time,” Remo Panaccione, MD, FRCPC, professor of medicine and director of the Inflammatory Bowel Disease Unit at the University of Calgary in Canada, told Healio.
According to results of the ADVANCE and MOTIVATE phase 3 induction studies, Skyrizi (risankizumab, AbbVie), an anti-interleukin-23 75 p19 monoclonal antibody, outperformed placebo in clinical remission and endoscopic response in patients with moderate to severe CD; those who achieved response in these trials continued on with treatment in the maintenance FORTIFY trial.
However, because some patients did not respond or inadequately responded to risankizumab during the initial induction period, the researchers sought to investigate the efficacy and safety of an additional 12 weeks of treatment for this group of patients.
They re-randomly assigned initial nonresponders 1:1:1 to receive extended blinded treatment, which consisted of a higher dose of IV risankizumab (1,200 mg at weeks 12, 16 and 20); the initiation of subcutaneous risankizumab (180 mg or 360 mg at weeks 12 and 20), which was the dose used for maintenance therapy in the FORTIFY trial; or placebo. Patients who achieved a response at week 24, deemed “delayed responders,” were then eligible to continue maintenance therapy in FORTIFY.
The endpoints of the studies included stool frequency and abdominal pain score (SF/APS) clinical response and remission, Crohn’s disease activity index (CDAI) response and remission, and endoscopic response and remission.
Overall, 70.4% of patients achieved SF/APS clinical response after 12 weeks of IV risankizumab. Of the 313 who did not achieve a response, 252 were re-randomly assigned to receive 1,200 mg IV risankizumab (n = 77; mean age, 40.4 years) or 180 mg (n = 84; mean age, 37.8 years) or 360 mg subcutaneous risankizumab (n = 91; mean age, 40.6 years).
After extended treatment, the researchers found that most initial nonresponders achieved SF/APS clinical response at week 24, with clinical response rates greater than weeks 16 and 20 in all groups (IV 1,200 mg: 62.3%; 95% CI, 51.5%-73.2%; subcutaneous 180 mg: 76.2%; 95% CI, 67%-85.3%; subcutaneous 360 mg: 63.7%; 95% CI, 53.9%-73.6%). Researchers noted a similar trend at week 24 for SF/APS clinical remission, CDAI clinical response and remission, and endoscopic response and remission, with no significant differences in advantage between subcutaneous and IV dosing.
Including the initial and extended treatment periods, the researchers found that the absolute SF/APS clinical response rate was 89.1%. Further, 76.2% of patients achieved CDAI clinical response, 51.1% of patients achieved SF/APS clinical remission, 46.2% achieved endoscopic response and 28.4% achieved endoscopic remission.
Patients in the FORTIFY trial with a delayed SF/APS clinical response to subcutaneous risankizumab continued to demonstrate clinical response, with a greater response observed at week 52 for 360 mg (69.7%) vs. 180 mg (56.7%) and similar trends observed across endpoints. Overall, the 360 mg subcutaneous group showed higher efficacy rates compared with the 180 mg subcutaneous group at weeks 0 and 52.
Finally, the researchers found that extended treatment with risankizumab was well-tolerated, with no new safety risks identified.
The authors noted some limitations to this study, including that patients were aware that they were receiving risankizumab due to the study design.
“Going forward, incorporating an extended treatment period for patients who do not respond after a predefined induction period is critical to understand the proportion of patients who may ultimately benefit from a therapy,” Panaccione told Healio.
For more information:
Remo Panaccione, MD, FRCPC, can be reached at rpanacci@ucalgary.ca.
Collapse
Read more about