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Crohn’s strictures may respond to immunosuppressive drug therapy

Lancet Gastroenterology & Hepatology
Reuters Health - 31/12/2021 - Symptomatic strictures related to Crohn's disease (CD) may respond to immunosuppressive drug therapy, with improvements in symptoms and stricture morphology, according to results of a study from Australia.

"This study shows that Crohn's disease-associated bowel wall damage, characteristic of inflammatory strictures, is potentially reversible with drug treatment," the study team reports in The Lancet Gastroenterology & Hepatology.

"Combination immune suppression with treat-to-target treatment escalation based on objective measures of persistent inflammation provided better outcomes than did standard drug therapy," they add.

Strictures are the most common structural complication of CD, and surgery and endoscopic balloon dilation are the chief treatment options. Drug therapy has been considered contraindicated, note Dr. Julian Schulberg of St. Vincent's Hospital, in Melbourne, and colleagues.

The STRIDENT study is believed to be the first randomized controlled trial of drug treatment in patients with CD strictures.

The study included 77 adults with CD and a de novo or postoperative anastomotic intestinal stricture, symptoms consistent with chronic or subacute intestinal obstruction and evidence of active intestinal inflammation.

Fifty-two were randomly allocated to intensive treatment consisting of high-dose adalimumab (160 mg once weekly for four weeks followed by 40 mg every two weeks, with escalation of dose at four months and eight months if assessment of disease activity indicated active inflammation) plus thiopurine (azathioprine 2.5 mg/kg or mercaptopurine 1.5 mg/kg to start, with dose adjustment based on thiopurine metabolite testing).

The remaining 25 patients were randomly allocated to standard adalimumab monotherapy (160 mg at baseline, 80 mg at two weeks and 40 mg every two weeks thereafter). Patient characteristics were similar in the two groups at baseline.

Among the key findings:

- At 12 months, 79% of patients in the intensive-treatment group had improvement in obstructive symptoms compared with 64% in the standard-treatment group (odds ratio, 2.10; P=0.17).

- Treatment failure was more common with standard than intensive treatment (28% vs. 10%; OR, 0.27; P=0.045), although four patients in each group required stricture surgery.

- Crohn's Disease Activity Index (CDAI) fell below 150 (indicating remission) in 69% of patients in the intensive-treatment group compared with 60% in the standard treatment group, from a baseline index score of 167 and 179, respectively (OR, 1.50; P=0.42).

- MRI at 12 months showed improvement (based on stricture MaRIA score of 25% or greater) in 61% of the intensive treatment group versus 28% of the standard treatment group (OR, 3.99; P=0.009). Complete stricture resolution on MRI was seen in 20% and 16%, respectively.

- Intestinal ultrasound at 12 months showed improvement of more than 25% in bowel wall thickness in 51% of patients in the intensive-treatment group compared with 33% in the standard-treatment group (OR, 2.10; P=0.15).

- Fecal calprotectin normalized in 62% of patients on intensive therapy compared with 44% of patients on standard therapy (OR, 2.04; P=0.15), while normalization of C-reactive protein was seen in 62% and 44%, respectively (OR, 2.04; P=0.15).

- There were no deaths during the study. Eight patients (15%) in the intensive-treatment group and four (16%) in the standard group reported serious adverse events.

"Compared with the widespread belief that strictures are predominantly fibrotic, with irreversible structural changes, this study has established that there are reversible components," the authors say.

"This study provides a clear strategy for treating and assessing patients with strictures, the most common and disabling Crohn's disease complication. Strictures are responsive to drug therapy, and intensive therapy together with tight control of inflammation leads to the best outcomes," they add.

In their view, "Drug therapy should be considered for the treatment of Crohn's disease strictures, with objective measures used to adjust therapy."

AbbVie, which makes adalimumab, helped fund the study.

SOURCE: https://bit.ly/3yMpneC Lancet Gastroenterology & Hepatology, online December 7, 2021.

By Reuters Staff

© 2023 The Author(s). Published by Medicom Medical Publishers.
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