Adalimumab Effective in Treating Stricturing Crohn Disease

At the time of the onset of Crohn disease (CD), most patients have inflammatory lesions that become stricturing or penetrating in the months or years after diagnosis. While medical therapy can treat inflammation, endoscopic treatment or surgery is often required to relieve small bowel obstructions resulting from stricturing lesions.

While anti—tumor necrosis factor (anti-TNF) therapies are effective in helping patients with CD gain remission, data on using anti-TNFs in patients with stricturing CD are conflicting; some reports suggest that anti-TNF agents increase the risk of intestinal obstruction. A new study, published in Gut, sought to estimate the efficacy of the anti-TNF agent adalimumab in patients with CD who had small bowel strictures and to identify factors predicting treatment success.

The prospective, multi-center, open-label, post-marketing observational study, conducted from January 2010 to December 2011, included patients (n = 97) aged 18 years or older who had a diagnosis of CD of a stricturing phenotype, a single or several strictures, obstructive symptoms within the last 8 weeks, failure of or contraindications with steroids or immunosuppressive agents and indications for anti-TNF treatments.

Adalimumab was administered subcutaneously at baseline at 160 mg, followed by 80 mg at week 2, then 40 mg every other week. Patients were assessed using the Crohn Disease Activity Index (CDA), complete blood cell count, and C-reactive protein serum level before inclusion and at weeks 8, 16, and 24. The primary endpoint of the study was success at week 24 (defined as no use of prohibited treatments, such as corticosteroids or other anti-TNF agents; no endoscopic dilation; no bowel surgery for resection of strictures; no severe adverse events leading to adalimumab withdrawal; no study withdrawal).

In total:

• 62 patients (64%) reached success at week 24
• 35 patients failed to achieve success and were switched to infliximab
• 8 patients underwent intestinal resection
• 2 patients had endoscopic dilation
• 10 patients had severe adverse effects that led to adalimumab discontinuation
• 2 patients interrupted adalimumab treatment
• 5 patients withdrew from the study
• 8 patients had treatment failure attributable to multiple causes
• 51 of the 97 patients (53%) were surgery-free after a median follow-up of approximately 4 years

Among the 62 patients who achieved success at week 24, 88% had a Crohn Disease Activity Index (CDAI) score of less than 150.

Factors associated with treatment success were combined treatment with adalimumab and immunosuppressive agents, recent and severe obstructive symptoms, a stricture length of less than 12 cm, and intermediate dilation of the small bowel proximal to the stricture, marked enhancement on delayed phase, and an absence of fistula. Notably, low C-reactive protein levels were associated with high success rates; “Therefore, what is true for luminal disease is probably false for stricturing disease, a result that needs to be confirmed,” say the authors.

The researchers concluded that a successful response to adalimumab was found in approximately two-thirds of the cohort, and that more than half of all the patients treated with adalimumab, regardless of treatment success, were surgery-free at approximately 4 years after treatment initiation.