Studies support vedolizumab benefit for IBD

Data presented at the Crohn’s & Colitis Congress (CCC) 2023 reflect the benefit of vedolizumab for inflammatory bowel disease (IBD; Crohn’s disease and ulcerative colitis), be it alone or in a combination regimen. In one study however, extraintestinal manifestations were observed following vedolizumab use.

As monotherapy

In a pooled analysis of retrospective studies evaluating patients with steroid-refractory microscopic colitis (n=164), clinical remission rate was higher with vedolizumab (64 percent; p=0.08) as opposed to tumour necrosis factor alpha (TNF-α) inhibitors such as infliximab (58 percent; p=0.75) and adalimumab (39 percent; p=0.02). [CCC 2023, abstract P050]

The rate of maintenance of remission remained higher with vedolizumab (60 percent; p=0.03) than with infliximab (45 percent; p=0.36) or adalimumab (32 percent; p=0.14).

Conversely, treatment cessation rate owing to biologic-related adverse events (AEs) was lower with vedolizumab than the other two agents (12 percent vs 33 percent and 23 percent).

“[However,] given the nature of included studies, superiority of either therapy could not be elucidated,” the researchers noted. They called for further investigation comparing vedolizumab against TNF-α inhibitors and to evaluate treatment effects on patients’ quality of life.

Dual therapy

Twenty-one patients (mean age 36.4 years, 52 percent female) with treatment-resistant ulcerative colitis were started on vedolizumab and tofacitinib dual therapy. All patients had advanced disease, with nearly two-thirds (62 percent) having extensive colitis. The rest had left-sided colitis. About 90 percent of participants have previously received at least two biologics. [CCC 2023, abstract P039]

At 6 months, mean partial Mayo score dropped to 0.5 from a baseline score of 5.6 (p=0.0020). Other parameters that improved between these two timepoints were faecal calprotectin (from 1,829 to 225 μg/g; p=0.0068), mean C-reactive protein (from 11.4 to 5.4 mg/L; p=ns), and average endoscopic Mayo score (from 2.8 to 1.4; p=0.0005).

The baseline endoscopic Mayo score of 2.8 represents mostly severe disease activity, the investigators noted. By month 6, disease activity in half of the cohort was mild to none (ie, endoscopic Mayo score 0–1).

A third of participants had to discontinue the regimen, mostly due to treatment failure (n=4). The other three either refused to continue, stopped for reimbursement reasons, or had an AE.

Some patients with ulcerative colitis do not respond to biologic agents. Others who do respond initially may eventually experience secondary loss of response. Combining two different targeted molecules may be feasible in these cases, said the researchers.

The study, albeit small, reflects the efficacy of combining vedolizumab with tofacitinib, with half of participants achieving mucosal healing at 6 months. The combination regimen also did not raise significant safety signals, the researchers noted.

Rheumatologic manifestations

In a systematic review and meta-analysis, of the 1,822 participants receiving vedolizumab for moderate-to-severe IBD, 232 developed arthritis or arthralgia of any kind. The corresponding rate in the placebo arm was lower (66 out of 644 participants). A comparison between arms yielded an odds ratio of 0.95 (p_{heterogeneity}=0.23). [CCC 2023, abstract P053]

Although statistical significance was not achieved, the extraintestinal manifestations may have been due to the drug, the researchers postulated. “The new onset of worsening arthritis and arthralgia may be associated with the course of the disease itself, the body’s response to drugs or the exclusion of corticosteroids or anti-TNF-α from concomitant treatment with vedolizumab.”

Larger studies are warranted to further evaluate the incidence of joint manifestations and other rheumatologic issues in IBD patients, and to ascertain whether these events are indeed triggered by vedolizumab, they added.