Endoscopic and histologic remission are recommended as treatment targets in Crohn’s disease due to their association with reduced hospitalization and surgery rates. The goal of the present study was to evaluate the efficacy of vedolizumab in achieving these endpoints after 26 to 52 weeks of treatment. This is a prospective, 22-site, European, open-label study of adult patients with Crohn’s disease and confirmed ulcerations at baseline endoscopy who received induction vedolizumab (VDZ) 300 mg at 0, 2, and 6 weeks followed by maintenance 300 mg VDZ every 8 weeks. Endoscopies were performed at weeks 0, 26, and 52 and scored using the SES-CD by central readers; biopsies were taken at weeks 0 and 26 with histologic activity scored using the Geboes and Robarts histopathology systems. Vedolizumab serum trough levels and antibodies were obtained prior to each infusion.
Of 110 patients enrolled, 76 completed week 26 and 63 completed week 52. At week 26, clinical remission was observed in 29% and endoscopic remission in 33%; histologic remission was observed in 64% to 66%. At week 52, clinical remission was observed in 31% and endoscopic remission in 36%. VDZ trough levels >10 mg/L at week 22 were associated with higher endoscopic 26-week remission rates. In assessing VDZ trough quartiles, endoscopic remission rates at week 26 were 32%, 56%, 58%, and 75% among quartiles 1 through 4 (p=0.08).
Endoscopic remission rates with VDZ are similar to what has been previously reported with anti-TNF monotherapy at 26 weeks: adalimumab (EXTEND), 27%; infliximab (SONIC), 30%. Despite their clinical benefits, their efficacy in achieving endoscopic remission is disappointingly low. Similar to what has been seen with anti-TNF agents, higher VDZ levels were associated with higher endoscopic and histologic remission. Further study is needed, however, before therapeutic VDZ drug monitoring can be recommended. The clinical relevance of the high histologic remission seen in this trial is uncertain.
Lowenberg M, Vermeire S, Mostafavi N, et al. Vedolizumab induces endoscopic and histologic remission in patients with Crohn’s disease. Gastroenterology
2019 June 5. (Epub ahead of print) (https://doi.org/10.1053/j.gastro.2019.05.067