Both ustekinumab and vedolizumab demonstrated high efficacy as third-line biologics in the treatment of patients with highly refractory Crohn disease (CD), according to study findings published in Digestive and Liver Disease.
Researchers conducted a multicenter, real-world evaluation at 16 centers licensed to prescribe biologics, obtaining data up until December 2021. Researchers compared the efficacies of ustekinumab and vedolizumab to determine which medication was superior as a third-line biologic for 143 patients with highly refractory CD. Of these 143 patients, 113 received ustekinumab and 30 received vedolizumab.
These patients failed to improve after taking at least 1 tumor necrosis factor-alpha inhibitor (TNFα-i) in addition to failure with either ustekinumab or vedolizumab. Treatment with the third line using ustekinumab involved induction and maintenance therapy periods, while treatment with vedolizumab was fixed at 300 mg at baseline, weeks 2, 6, and every 8 weeks afterward.
At baseline, significant differences between the ustekinumab and vedolizumab groups existed, with the ustekinumab group being older in age compared with the vedolizumab group (average age of 51 vs 38.7 years; P =.009). Patients in the ustekinumab group also demonstrated higher rates of previous resections (69% vs 46.7%; P=.040) and structuring disease (64.6% vs 36.7%; P =.009) than the vedolizumab group.
Measures used to determine clinical response, clinical remission, and steroid-free clinical remission included the Harvey-Bradshaw index (HBI) score reduction and use of steroids.
After 16 weeks of induction therapy, 70 of the 113 patients (61.9%) in the ustekinumab group achieved a clinical response, 55 (48.7%) achieved clinical remission while still taking steroids, and 43 (38.1%) achieved steroid-free clinical remission. Furthermore, 14 of 54 patients (25.9%) with abnormal levels of C-reactive protein at baseline reached normal levels of C-reactive protein after 16 weeks.
Independent predictors of achieving steroid-free clinical remission in the ustekinumab group included non-smoking status, need for steroids at baseline, and baseline HBI scores.
In comparison, after 14 weeks, 18 out of 30 patients (60%) in the vedolizumab group achieved a clinical response, 16 (53.3%) achieved clinical remission, and 13 (43.3%) achieved steroid-free clinical remission. Of the 14 patients with abnormal baseline C-reactive protein levels, 3 (21.4%) reached normal levels after 14 weeks.
No independent factors predicted steroid-free clinical remission in the vedolizumab group.
After 52 weeks of maintenance therapy, clinical response and steroid-free clinical remission rates totaled 65.9% and 51.8% in the ustekinumab group, and 71.4% and 57.1% in the vedolizumab group, respectively.
“Our real-world multicenter study demonstrated the effectiveness of both UST [ustekinumab] and VDZ [vedolizumab] as third-line biologic therapy in patients with CD, showing high rates of CR [clinical response] and SFCR [steroid-free clinical remission] at both induction and maintenance,” the study authors wrote. “Obviously, further research is required to identify the proper drug positioning in CD, and to further understand which patients would benefit from additional lines of medical therapy and which ones who would benefit from surgery.”
Study limitations include the retrospective design, the difference in group sizes and characteristics, potential bias in response assessment, lack of endoscopic and fecal calprotectin data, lack of assessment as to why patients were taking steroids (possible extraintestinal use), and assessment of clinical outcomes at predetermined points in time.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Macaluso FS, Grova M, Saladino M, et al. The effectiveness of ustekinumab and vedolizumab as third-line biologic therapy in patients with Crohn’s disease. Dig Liver Dis. Published online September 17, 2022. doi:10.1016/j.dld.2022.08.028