Florian Rieder, MD: Positioning Biologics Effectively in the Treatment of IBD

Antitumor necrosis factor (TNF) and anti-integrin therapies were found to be more effective when used early in the disease course among patients with Crohn disease (CD), Florian Rieder, MD, noted during his presentation at the Advances in Inflammatory Bowel Disease virtual meeting held on April 20-April 21. No such association was found with the biologic agents in the disease duration among patients with ulcerative colitis (UC).

Dr Rieder is vice-chair and codirector of the inflammatory bowel disease (IBD) section, and director of the Advanced IBD Fellowship program at the Cleveland Clinic in Cleveland, Ohio. His clinical focus is patients with IBD with a special emphasis on pathogenesis, prediction, and therapy of intestinal fibrosis. He received the Sherman Emerging Leader Prize in 2019.

“Vedolizumab was effective in CD, but less so than anti-TNF and particularly lower in anti-TNF failures,” Dr Rieder said during his presentation on biologic agents in the treatment of intestinal inflammation.

Dr Rieder touched upon all the major anti-TNF biologics in play—infliximab, certolizumab pegol, adalimumab, and golimumab—that are approved for moderate to severe UC. Among anti-integrin biologics, he focused primarily on vedolizumab, which is approved for moderate to severe UC and CD. Natalizumab is also approved for CD; however, it is rarely used, Dr Rieder said.

The GEMINI 1 trial studied vedolizumab in induction and maintenance of UC. The randomized, double-blind, placebo-controlled trial, which included 895 participants, found vedolizumab to be more effective than placebo as induction and maintenance therapy.

The EVOLVE study compared the outcomes of first-line anti-TNF vs second-line anti-TNF following vedolizumab in a multicenter retrospective setting with 579 patients with CD and UC. At 3 and 6months, results suggested that first-line vedolizumab did not have an impact on the effectiveness of subsequent anti-TNF therapy in real-world clinical practice, Dr Rieder summarized.

Dr Rieder referenced the VARSITY trial, which compared vedolizumab to adalimumab in terms of clinical remission and endoscopic improvement among patients with active UC; 383 participants randomly received vedolizumab and 386 were given adalimumab.

At week 52, clinical remission was reported in 31.3% of the vedolizumab group vs 22.5% of the adalimumab group. Endoscopic improvement was higher in the vedolizumab group (39.7%) than in the adalimumab group (27.7%) The trial demonstrated the superiority of vedolizumab over adalimumab in achieving higher clinical remission rates and endoscopic improvement.

“This trial, however, had certain limitations such as no dose escalation, or no drug levels,” Dr Rieder commented.

Shifting gears to optimal positioning of biologics among patients with CD, Dr Rieder said the phase 3B trial of VERSIFY found that at 26 and 52 weeks of treatment with vedolizumab, patients with moderate to severe CD showed better endoscopic, radiologic, and histologic healing. The dose was 300 mg at weeks 0,2, and 6, and then every 8 weeks thereafter.

The systematic review and network meta-analysis including 2931 biologic-naive patients and 2479 patients with previous biologic exposure explored the comparative efficacy and safety of biologic therapies after previous exposure. The findings revealed that infliximab monotherapy; infliximab combined with azathioprine; adalimumab monotherapy; and ustekinumab were all associated with significantly higher odds of inducing remission, compared to certolizumab pegol. Infliximab-azathioprine combination therapy was also associated with significantly higher odds of inducing remission than vedolizumab.

These results suggest that “either infliximab with azathioprine or adalimumab as a first-line therapy, and adalimumab (after infliximab loss of response) or risankizumab as a second-line therapy, are appropriate for induction of clinical remission,” Dr Rieder said.

Dr Rieder emphasized the importance of accurate and timely identification of biomarkers— whether RNA or genetic, serological, stool, or mucosal—that can predict responses to anti-TNFs in IBD. Identifying several biomarkers can help reduce costs, reduce unnecessary medication, and find alternate treatment strategies.

“The ideal predictive biomarker must be easy to obtain, show high accuracy, and have quick feedback in clinical practice,” Dr Rieder noted.

—Priyam Vora

Reference:
Rieder F. The role of anti-TNF and anti-integrin in IBD. Presented at: Advances in Inflammatory Bowel Disease virtual meeting. April 20-21, 2023.