Studies suggest vedolizumab as maintenance treatment in ulcerative colitis

Two meta-analyses presented at AIBD 2019 suggest that vedolizumab, be it in intravenous (IV) or subcutaneous (SC) form, may be effective as maintenance treatment of ulcerative colitis (UC).

The first meta-analysis used data from the GEMINI 1, VISIBLE 1, ULTRA-2, and VARSITY* studies, where researchers compared the maintenance treatment strategies of SC adalimumab (40 mg Q2W) or IV vedolizumab (300 mg Q4W or 300 mg Q8W) with SC vedolizumab (108 mg Q2W). Patients in GEMINI 1 and VISIBLE 1 who responded to treatment were re-randomized at the end of the induction period, while ULTRA-2 and VARSITY were treat-through** trials.

Maintenance of response at 52/54 weeks was lower among patients who received adalimumab compared with those who received SC vedolizumab (odds ratio [OR], 0.60, 95 percent credible interval [CrI], 0.33–1.08), as was maintenance of remission (OR, 0.59, 95 percent CrI, 0.33–1.09), though these did not reach statistical significance. [AIBD 2019, abstract P038]

At 52 weeks, overall adverse event (AE) incidence was significantly higher among adalimumab than SC vedolizumab recipients (OR, 2.02). However, infections and serious infections occurred at a comparable rate between adalimumab and SC vedolizumab recipients (OR, 1.86 and 0.39, respectively), as did serious AEs (OR, 1.41). AEs leading to treatment discontinuation also occurred in a similar proportion of adalimumab and SC vedolizumab recipients (OR, 2.58).

The maintenance of response and remission, and AE profile were similar between patients who received the SC and IV formulations of vedolizumab.

Previously, the VARSITY trial showed that clinical remission in patients with moderate-to-severe UC was greater with IV vedolizumab than with SC adalimumab. [N Engl J Med 2019;381:1215-1226] However, there was no data on the effects of the new SC formulation of vedolizumab vs adalimumab.

“Results from this indirect treatment comparison suggest that SC vedolizumab may achieve higher rates of maintenance response and remission among responders at start of maintenance than adalimumab and is associated with a lower risk of overall AEs,” said the authors led by Dr Vipul Jairath from Western University and London Health Sciences Centre, London, Ontario, Canada.  

“In the absence of a head-to-head trial between SC vedolizumab and SC adalimumab, these findings support a favourable benefit-risk profile of SC vedolizumab in UC,” they said.

In the second meta-analysis, researchers identified 16 randomized clinical trials (RCTs) assessing the safety and efficacy of different dose strategies of vedolizumab (IV and SC), adalimumab, infliximab, golimumab, ustekinumab, and tofacitinib.

Maintenance of response at 52/54 weeks was significantly lower with adalimumab 40 mg (OR, 0.62, 95 percent CrI, 0.45–0.86), golimumab 50 mg (OR, 0.54, 95 percent CrI, 0.31–0.94), and ustekinumab 90 mg Q12W (OR, 0.58, 95 percent CrI, 0.34–0.98) compared with vedolizumab 300 mg Q8W, with similar findings noted with regard to maintenance of remission (OR, 0.62, 0.54, and 0.58, respectively). The other treatments analysed had comparable efficacy to the vedolizumab 300 mg Q8W regimen. 

AE incidence was significantly higher among golimumab 100 mg (OR, 2.17) and 50 mg (OR, 1.90) recipients compared with vedolizumab 300 mg Q8W recipients, with AE leading to discontinuation significantly elevated among golimumab 100 mg recipients (OR, 3.43). Infection rates were significantly higher among golimumab 100 mg (OR, 1.84) and tofacitinib 10 mg (OR, 2.03) recipients, and lower among ustekinumab 90 mg Q12W recipients (OR, 0.58) compared with vedolizumab 300 mg Q8W recipients. Safety outcomes for adalimumab 40 mg and infliximab 5 mg/kg or 10 mg/kg were comparable with that of vedolizumab 300 mg Q8W.

“Results from this [network meta-analysis] based on RCTs indicate a favourable benefit-risk profile for vedolizumab 300 mg Q8W compared with other advanced therapeutic options available for UC,” said Jairath and co-authors.