← Issue №12/ week of Sep 20, 2026/IBD

Leucine-rich alpha-2 glycoprotein as a predictor of primary non-response to anti-TNF-α therapy in biologic-naïve Egyptian IBD patients.

From GI Signals issue №12: what this paper found, what it changes, and where it sits against the current standard of care, reviewed by Simon Mathews, MD.

IBD prospective cohort · n=100 · Sep 18, 2026 · BMC Gastro · IF 2.5

Leucine-rich alpha-2 glycoprotein as a predictor of primary non-response to anti-TNF-α therapy in biologic-naïve Egyptian IBD patients.

Diagnosticbiologicsanti-TNFbiomarkerCrohn's disease
Clinical takeawayConsider measuring baseline serum LRG in biologic-naïve Egyptian IBD patients to estimate moderate-risk (not definitive) of primary non-response to anti-TNF-α therapy. Patients with LRG >29 µg/mL may benefit from alternative therapeutic strategies.
What it foundBaseline serum LRG >29 µg/mL predicted primary non-response to anti-TNF-α therapy (adalimumab or infliximab) vs response, with sensitivities of 74.2% (UC) and 80.0% (CD) and specificities of 69.57% (UC) and 65.71% (CD) in biologic-naïve Egyptian IBD patients.
ContextThis study introduces LRG as a predictive biomarker with moderate discriminatory ability for anti-TNF-α response in Egyptian patients, addressing a gap in current practice where primary non-response remains a significant challenge.
Refinessuggested applicable standard· ACG Clinical Guideline Update: Ulcerative Colitis in Adults, Am J Gastroenterol 2025;120(6):1187-1224; AGA Living Guideline on Pharmacological Management of Moderate-to-Severe UC, Gastroenterology 2024 (panel review March 2026, no changes)

Decision at stakepredicting primary non-response to anti-TNF therapy in ulcerative colitis

Confirm ulcerative colitis with endoscopy showing continuous colonic inflammation from the rectum plus histology, after excluding infection with two-step CDI testing. Do not cycle within the anti-TNF class after primary non-response; switch mechanism.

From our summary of this standard, unedited — the part the paper bears on. marks omitted text. Our wording, not the guideline's; read the source for its own text.

Our full summary of this standard

Confirm ulcerative colitis with endoscopy showing continuous colonic inflammation from the rectum plus histology, after excluding infection with two-step CDI testing. Treat mild-moderate disease with 5-ASA by route and extent (suppository for proctitis, enema for left-sided, oral plus rectal for extensive); if 5-ASA fails, treat as moderate-to-severe rather than stepping up gradually. Position advanced therapy by EFFICACY TIER, not by an anti-TNF-first rule. Advanced-therapy-naive, higher efficacy: infliximab, vedolizumab, ozanimod, etrasimod, upadacitinib, risankizumab, guselkumab; intermediate: golimumab, ustekinumab, tofacitinib, filgotinib, mirikizumab; lower: adalimumab. PREVIOUSLY TNF-EXPOSED, higher efficacy: tofacitinib, upadacitinib, ustekinumab; lower: adalimumab, vedolizumab, ozanimod, etrasimod - S1P modulators are weakest in exactly this group. Do not cycle within the anti-TNF class after primary non-response; switch mechanism. Apply treat-to-target (STRIDE-II) to endoscopic improvement (MES 0-1). Screen for acute severe UC by Truelove-Witts and admit for IV steroids. Begin CRC surveillance 8-10 years after DIAGNOSIS for extensive or left-sided disease; isolated proctitis follows average-risk screening.

ACG Clinical Guideline Update: Ulcerative Colitis in Adults, Am J Gastroenterol 2025;120(6):1187-1224; AGA Living Guideline on Pharmacological Management of Moderate-to-Severe UC, Gastroenterology 2024 (panel review March 2026, no changes) ↗
Amer I … El Sharawy S · BMC Gastroenterology · IF 2.5 · PubMed ↗Permalink
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