JAMA Guideline on the Management of Crohn Disease Save

JAMA has published a current Clinical Guidelines Synopsis on the Management of Crohn Disease (CD) in Adults.

Key Takeaways

• Fecal calprotectin (>50–100 μg/g) is the recommended non-invasive screening and monitoring tool for CD — potentially useful in rheumatology patients on biologics who develop new GI symptoms.
• The 2025 ACG guideline adds IL-23 inhibitors (risankizumab, guselkumab, mirikizumab) and upadacitinib as strongly recommended options for moderate-to-severe CD.
• Oral mesalamine has no role in CD. Budesonide is effective short-term for mild ileocecal disease but must not be used as maintenance beyond 3 months.
• Early biologic therapy (PROFILE trial) achieves 79% steroid-free, surgery-free remission at 1 year vs 15% with step-up; reinforcing early aggressive and treat-to-target principles in rheumatology.
• IL-17 inhibitors and etanercept are contraindicated in active CD. When axSpA and CD coexist, monoclonal anti-TNF agents or risankizumab are the preferred options; co-management with gastroenterology is essential.
• The JAKi upadacitinib (for CD) carries the same FDA black box warning (VTE, MACE, malignancy). Cardiovascular risk screening should be used.

Crohn disease (CD) shares mechanism and therapies with many rheumatologic conditions. Up to 25% of axial spondyloarthritis (axSpA) patients carry a concurrent IBD diagnosis, and CD can be the presenting condition before arthritis is recognized. Conversely, biologic therapy chosen for joint disease can induce or worsen CD — possibly notably TNF receptor fusion proteins (etanercept) and IL-17 inhibitors, which are contraindicated in active IBD. 

CD diagnosis requires requisite evidence: symptoms, endoscopic and radiologic findings, and histologic confirmation of chronic mucosal inflammation. Key monitoring tools endorsed by the updated 2025 ACG guideline include:

• Fecal calprotectin (FC): A cutoff of >50–100 μg/g differentiates inflammatory from functional bowel disease with 88% sensitivity and 72% specificity (strong recommendation, moderate evidence). FC also tracks disease activity longitudinally and identifies early flares — relevant when patients on shared biologics develop GI symptoms.
• CRC surveillance: Patients with Crohn colitis involving ≥30% of the colon require surveillance colonoscopy every 2–3 years starting 8 years after diagnosis. Those with concurrent primary sclerosing cholangitis need annual colonoscopy.

The 2025 ACG guideline meaningfully expands first-line options for moderate-to-severe CD beyond the 2018 framework of anti-TNF, vedolizumab, and ustekinumab:

• New IL-23 inhibitors — risankizumab, guselkumab, and mirikizumab — carry strong recommendations for induction and maintenance, with a more favorable infection profile than anti-TNF agents.
• Upadacitinib (JAK1 inhibitor), an oral tsDMARD already used in rheumatology for RA and axSpA, now has a strong recommendation for moderate-to-severe CD. Rheumatologists prescribing it for joint disease must be alert to its CD indication — and its FDA black box warning (VTE, MACE, serious infections, malignancy), though the cardiovascular safety data originate from older RA populations and may not fully apply to younger IBD patients.
• Oral mesalamine is explicitly not recommended for CD induction or maintenance — a practice gap still encountered in primary care.
• Ileal-release budesonide (9 mg/d) remains the preferred induction agent for mild-to-moderate ileocecal CD; it should not be continued beyond ~3 months.

The PROFILE trial (386 patients, newly diagnosed moderate-to-severe CD) demonstrated that upfront biologic therapy with infliximab plus an immunomodulator achieved steroid-free, surgery-free remission at 1 year in 79% of patients, versus 15% with a conventional step-up approach (P < .001). This strongly endorses early top-down therapy for moderate-to-severe disease — a paradigm already familiar in rheumatology from RA treat-to-target strategies.