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Treatment failure occurred in 10% of the intensive treatment group compared to 28% in the standard treatment group
Treatment can improve symptoms and disease scores in patients with Crohn's disease strictures.
A team, led by Julien D. Schulberg, Department of Gastroenterology, St Vincent's Hospital, examined whether strictures are responsive to drug treatment and whether intensive drug therapy is more effective than standard drug therapy.
Strictures remain the most common structural complication for patients with Crohn’s disease, with surgery and endoscopic balloon dilation considered the main treatment options. Drug therapy has also been considered contraindicated.
In the open-label, single-center, randomized, controlled trial, the investigators examined 123 adult patients with Crohn’s disease at 1 specialist IBD center in Australia between September 10, 2017 and September 6, 2019. Overall, 77 patients were included in the final analysis.
Each patient had a de novo or postoperative anastomotic intestinal stricture on MRI or ileocolonoscopic, symptoms consistent with chronic or subacute intestinal obstruction (postprandial abdominal pain in the presence of a confirmed stricture), and evidence of active intestinal inflammation.
Each participant was randomly assigned to receive either intensive high-dose adalimumab 160 mg once per week for 4 weeks followed by 40 mg every 2 weeks with an escalation dose at 4 months and 8 months if the assessment of disease activity indicated active inflammation with thiopurine—initial dose of azathioprine 2.5 mg/kg or mercaptopurine 1.5 mg/kg, with dose adjustment based on thiopurine metabolite testing (n = 52) or standard adalimumab monotherapy of 160 mg at week 0, 80 mg at week 2, and 40 mg every 2 weeks (n = 25).
The patients were randomized using stratified fixed block randomization, with factors including stricture dilation at study baseline colonoscopy and current biologic drug use.
The investigators sought primary endpoints of the improvement or decrease in the 14-day obstructive symptom score at 12 months by 1 or more points compared to baseline.
The results show there were improvements in obstructive symptoms scores in 79% (n = 41) of the intensive treatment group, besting the 64% (n = 16) in the standard treatment group (OR, 0.27; 95% CI, 0.73-6.01; P = 0.17).
Treatment failure occurred in 10% (n = 5) of the intensive treatment group compared to 28% (n = 7) in the standard treatment group (OR, 0.27; 95% CI, 0.08-0.97; P = 0.045). However, 4 patients in each group required additional stricture surgery (OR, 0.44; 95% CI, 0.10-1.92; P = 0.27).
Crohn's Disease Activity Index was less than 150 in 69% (n = 36) of patients in the intensive treatment group compared 60% (n = 15) in the standard treatment group (OR, 1.50; 95% CI, 0.56–4.05; P = 0.42), while MRI at 12 months showed improvement using the stricture MaRIA score (≥25%) in 61% (n = 31) in the high dose group compared to 28% (n = 7) (OR, 3.99; 95% CI, 1.41–11.26]; P = 0.0091) in the standard treatment group.
On the other hand, 20% (n = 10) of the intensive treatment group had MRI complete stricture resolution, compared to 16% (n = 4) of the standard treatment group (OR, 1.28; 95% CI, 0.36-4.57; P = 0.70).
The team also found intestinal ultrasound at 12 months showed improvement of more than 25% in bowel wall thickness in 51% (n = 22) in the intensive treatment group, compared to 33% (n = 21) of patients in the standard treatment group (OR, 2.10; 95% CI, 0.77-5.36; P = 0.15).
Fecal calprotectin normalized in 62% (n = 32) compared to 44% (n = 11) of patients (OR, 2.04; 95% CI, 0.77–5.36]; P = 0.15), while the normalization of CRP was seen in 62% (n = 32) compared to 44% (n = 11) of patients (OR, 2.04; 95% CI, 0.77–5.36]; P = 0.15).
For safety, there were 8 patients (15%) in the intensive treatment group and 4 patients (16%) in the standard treatment group reported serious adverse events.
“Crohn's disease strictures are responsive to drug treatment. Most patients had improved symptoms and stricture morphology,” the authors wrote. “Treat-to-target therapy intensification resulted in less treatment failure, a reduction in stricture-associated inflammation, and greater improvement in stricture morphology, although these differences were not significantly different from standard therapy.”
The study, “Intensive drug therapy versus standard drug therapy for symptomatic intestinal Crohn's disease strictures (STRIDENT): an open-label, single-center, randomized controlled trial,” was published online in The Lancet Gastroenterology & Hepatology.