Recent Developments in Crohn’s Disease

Derick Alison
Derick Alison
7 Min Read

New ground has been broken for treatments and general understanding about Crohn’s disease this year. Here’s a brief rundown.

FDA Clears First JAK Inhibitor for Crohn’s

Perhaps the biggest development in 2023 occurred in mid-May, when the FDA approved a Crohn’s disease indication for upadacitinib (Rinvoq). The drug thus became the first Janus-associated kinase (JAK) inhibitor — a class of oral drugs that have revolutionized therapy for rheumatoid arthritis, psoriasis, and other autoinflammatory disorders — to become officially available for the condition.

It’s not the first pill of any kind for Crohn’s, of course: oral products such as corticosteroids, azathioprine, and mycophenolate mofetil (MMF) have long been used and, indeed, remain the backbone of initial therapy even now. But these are blunderbuss immunosuppressants, whereas upadacitinib is a targeted agent with relatively few side effects. It’s not a first-line therapy, however: the FDA stipulated that it should be used only in patients “who have had an inadequate response or intolerance to one or more tumor necrosis factor [TNF] blockers.”

Shortly after the approval was announced, the New England Journal of Medicine published details on the pivotal trials underpinning the FDA’s decision, as well as an editorial commentary.

Entyvio May Deserve Broader Use

Also in May, researchers reported at Digestive Disease Week (DDW) that the adhesion molecule inhibitor vedolizumab (Entyvio) was effective in preventing recurrent Crohn’s disease after surgery. The product already carries an indication for treating active Crohn’s (and also ulcerative colitis), but not specifically for recurrence prevention.

The study was a randomized, placebo-controlled trial involving 80 patients who had undergone bowel resection for Crohn’s. Normally, some degree of recurrence would be expected and, in fact, all but one of the 37 assigned to placebo in the trial did develop new Crohn’s-like intestinal lesions within 6 months, as seen on colonoscopy. But in the vedolizumab group, 42% had no lesions at 6 months. Safety findings were as expected, based on previous experience with the drug as a treatment for active disease.

Devices May Flag Flares

Another DDW presentation indicated that subtle changes in patients’ sleep, breathing, and walking often precede full-blown disease flares in Crohn’s, and these can be detected by in-home sensors before patients themselves are aware of them.

In the 125-person study, those starting to have Crohn’s disease flares developed poorer sleep quality and more nighttime awakenings, higher respiration rate, and slowed walking speed. Radiofrequency sensors placed in patients’ homes assessed these parameters, and when combined with a proprietary algorithm, the system was 80% accurate (i.e., area under the receiver operating characteristic curve of 0.80) for predicting a clinical flare, as confirmed by calprotectin testing.

This study followed another reported in January in which a wearable sensor that measured C-reactive protein, TNF, and interleukin-6 in perspiration also was said to be reasonably accurate for predicting IBD flares.

‘Creeping Fat’ Drives Crohn’s Strictures

Crohn’s disease can lead to bowel strictures, one of the condition’s worst manifestations. At DDW, researchers reported that fatty tissues that surround the bowel — called “creeping fat” — may be indirectly responsible.

It’s not that the fat itself is choking the bowel. Rather, fatty acids secreted from these cells appear to stimulate hyperplasia in so-called muscularis propria smooth muscle, and that is what causes the stricturing.

The study reported at DDW involved lab and animal model experiments. When the signalling induced by free fatty acids was interrupted, smooth muscle proliferation and luminal narrowing did not occur.

Kids With Crohn’s Often Get Wrong Drugs

About one-quarter of pediatric Crohn’s disease patients treated at seven different U.S. clinics were given 5-aminosalicylate (5-ASA) agents, despite guidelines that recommend against them, researchers reported early in the year.

5-ASA drugs are first-line treatments for ulcerative colitis, but are considered largely ineffective against Crohn’s disease. In the study, which examined records of some 700 children with Crohn’s, 5-ASA agents were the initial therapy in 28% of cases.

Use of these drugs was “associated with a 4-month delay in starting biologic therapy,” the lead researcher told MedPage Today, when compared with otherwise similar children who did not receive 5-ASAs.

Eczema, IBD Linked

Individuals with atopic dermatitis, a.k.a. eczema — especially children — appear to be at significantly increased risk for developing Crohn’s disease as well as ulcerative colitis.

Appearing in JAMA Dermatology, a report indicated that kids with atopy were almost twice as likely as non-atopic children to be diagnosed later on with Crohn’s disease (HR 1.74, 95% CI 1.54-1.97). For adults with the skin condition, the hazard ratio for Crohn’s was lower but still significant at 1.36 (95% CI 1.26-1.47). Eczema severity was also a factor, with worse disease tied to increased risk for inflammatory bowel disease (IBD). The retrospective study examined records for some 2.2 million children and 3.3 million adults.

Insofar as upadacitinib is approved for atopic dermatitis as well as, now, Crohn’s disease, it wouldn’t be surprising that the two conditions’ pathologies might overlap. (Another JAK inhibitor, abrocitinib [Cibinqo], also has an atopic dermatitis indication.) Authors of the study recommended that dermatologists screen their eczema patients for possible IBD, as well as a team approach involving a gastroenterologist for patients with both conditions.

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    John Gever was Managing Editor from 2014 to 2021; he is now a regular contributor.

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