Badr Al-Bawardy

Background and Aims: Inflammatory bowel disease (IBD) is increasing in the Middle East and North Africa (MENA), yet region-specific evidence on phenotype and treatment patterns remains limited. We aimed to characterize IBD epidemiology, clinical phenotypes, and therapy use across MENA centers. Methods: This was a multicenter cross-sectional study across 13 centers in seven MENA countries. Adults with ulcerative colitis (UC), Crohn’s disease (CD), or IBD-unclassified (IBD-U) were included. Demographics, Montreal phenotype/behavior, smoking status, disease duration, perianal disease, and therapies were collected. Descriptive statistics and between-group comparisons were performed. Results: We analyzed 10 340 patients (52% UC, 45% CD, 3% IBD-U). Mean age was 39.79 ± 14.4 years in UC and 34.57 ± 12.9 years in CD (P < .0001). UC patients were slightly more often female (51.6%), while CD patients were male-predominant (59.0%). Current smoking was more common in CD than in UC (12.0% vs 5.6%). Mean disease duration was 9.73 ± 7.5 years, longest in Jordan (14.1 years) and shortest in Qatar (2.45 years; P < .001). Biologic exposure differed by subtype (P < .001), with the highest rate in CD (57.9%). In UC, extensive colitis (E3) was the most common phenotype. In CD, ileocolonic involvement (L3) predominated with mainly non-stricturing, non-penetrating behavior (B1). Perianal disease affected approximately 13% overall, with rates varying by country, highest in UAE and lowest in Egypt and Qatar. Conclusion: This multi-country hospital-based registry study helps define contemporary IBD patterns in MENA: slight UC predominance, high rates of extensive UC and ileocolonic B1 CD, and heterogeneous biologic use. Our data provide insights into regional IBD epidemiological trends and treatment adoption.

Tumor necrosis factor-like ligand 1A (TL1A), encoded by TNFSF15, signals through death receptor 3 on effector T cells, innate lymphoid cells, and intestinal myofibroblasts, driving both chronic intestinal inflammation and tissue fibrosis. In this narrative review, we provide a contemporary appraisal of TL1A-directed therapeutics in inflammatory bowel disease based on electronic searches through May 2026. Three anti-TL1A monoclonal antibodies (tulisokibart, afimkibart, and duvakitug) have advanced to phase 3 trials across multiple global programs, with phase 2 clinical remission rates of 26%-48% in ulcerative colitis (placebo-adjusted differences 15-26 percentage points) and endoscopic response rates of 26%-48% in Crohn’s disease, alongside favorable safety profiles. Mucosal transcriptomic and serum proteomic analyses from phase 2 trials, including DDW 2026 readouts from ARTEMIS-UC and TUSCANY-2, provide the first human-tissue confirmation of class antifibrotic activity through the suppression of Th17, myeloid, and extracellular matrix pathways. TNFSF15 risk-variant companion diagnostics are advancing, although their incremental utility remains modest and will be definitively tested in phase 3. The pipeline has expanded to at least 19 development programs, including extended half-life antibodies (XmAb942, SPY002, and BCD-261), bispecifics combining TL1A with IL-23 or α4β7 (RO7837195, XmAb412, LQ080, and ALX001), a first-in-class oral anti-TL1A nanobody, and a first-in-class DR3 receptor antagonist (SL-325). We discuss therapeutic positioning and timing, the opportunity in acute severe UC, and the unusual standing of IBD as the lead indication for this mechanism class. Phase 3 results anticipated in 2026-2027 will be particularly informative for fibrostenotic phenotypes and biologic-refractory patients.

Background: Off-label high-dose upadacitinib (UPA) may be necessary for select inflammatory bowel disease (IBD) patients. Objectives: To evaluate the rates, patient characteristics, and outcomes of extended induction and high-dose UPA maintenance in IBD. Design: We conducted a two-center, retrospective cohort study of IBD patients treated with UPA from January 1, 2022, to March 1, 2025. Methods: Extended induction was defined as receiving UPA 45 mg for 16 weeks in ulcerative colitis (UC) and 24 weeks in Crohn’s disease (CD). High-dose maintenance was defined as continuing UPA 45 mg after induction/extended induction. Primary outcomes included rates and characteristics of high-dose maintenance. Secondary outcomes included clinical response (CR), steroid-free clinical remission (SFCR), endoscopic remission (ER), and adverse events, comparing standard and high-dose UPA groups. Results: Among 128 patients (46.9% CD, 48.4% UC, 4.7% IBD-unclassified), 51.6% ( n = 66) received extended induction and 34.4% ( n = 44) continued high-dose UPA maintenance. On multivariate analysis, UPA high-dose maintenance patients were more likely to have a higher number of prior biologic exposures (odds ratio (OR) 1.84, 95% confidence interval (CI) 1.05–3.19, p = 0.022) and concomitant biologic use (OR 6.18, 95% CI 1.15–33.18, p = 0.034). In the high-dose maintenance group, rates of CR were 73.7%, SFCR 65.8%, and ER 36.7%. Adverse event rates were similar between high- and standard-dose maintenance groups (25% vs 26.8%), with no cases of herpes zoster, venous thromboembolism, or major adverse cardiovascular events. Conclusion: One-third of patients remained on high-dose UPA maintenance, reflecting more refractory disease and modest response rates. Treatment was generally well tolerated. Larger, long-term studies are needed to validate safety.

Background: Inborn errors of immunity (IEI) are increasingly recognized to present with gastrointestinal (GI) manifestations, including immune-mediated colitis and inflammatory bowel disease (IBD)-like phenotypes. However, systematic data integrating immunologic classification with endoscopic and histopathologic findings in unselected IEI cohorts remain scarce.Methods: We conducted a retrospective observational cohort study of IEI patients followed at a tertiary referral center. Immunologic diagnoses were standardized according to established criteria. Clinical, endoscopic, histopathologic, treatment, and outcome data were analyzed for patients who underwent colonoscopic evaluation, with final GI phenotypes adjudicated using integrated clinical, endoscopic, and pathology findings.Results: Among 392 IEI patients, syndromic and monogenic disorders constituted the largest group (52.6%), followed by combined immunodeficiency (22.8%) and common variable immunodeficiency (CVID; 20.8%). Forty-eight patients with documented gastrointestinal inflammation were analyzed in detail (median age 26.5 years, IQR 21.0–34.3). CVID was the predominant diagnosis (45.8%). Chronic diarrhea was the most frequent symptom (25.0%), although 43.8% presented with other GI complaints. All patients underwent colonoscopy, with macroscopic colitis identified in 29.2%. Among abnormal biopsies, autoimmune colitis was most common (16.7%), followed by active or nonspecific colitis (12.5%). Classical IBD was uncommon, with Crohn’s disease in two patients (4.2%) and ulcerative colitis in one (2.1%). Infectious complications occurred frequently, including bacterial enteric infections (6.2%) and CMV colitis (2.1%). Responses to conventional IBD therapies were often limited or complicated by adverse outcomes.Conclusions: GI disease in IEI is heterogeneous, with a high prevalence of normal histology despite symptoms, underscoring the need for comprehensive diagnostic evaluation. Immune-mediated colitis—particularly in CVID—represents the dominant inflammatory phenotype, whereas classical IBD is rare. A high burden of infectious complications complicates management, highlighting the need for multidisciplinary management involving gastroenterology, immunology, and infectious disease specialists.

Background: Janus kinase (JAK) inhibitors are effective oral therapies for inflammatory bowel disease (IBD). While acne is a known adverse event in dermatological cohorts, its incidence and risk factors in the IBD population are not well-defined. We aimed to determine the pooled incidence of acne in IBD patients treated with JAK inhibitors and to explore this risk across key clinical subgroups. Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines. MEDLINE, EMBASE, and CENTRAL were searched from inception to September 2025 for randomized controlled trials (RCTs) and observational studies reporting acne incidence in IBD patients on JAK inhibitors. Data were pooled using a random-effects generalized linear mixed-effects model. Pre-specified subgroup analyses were performed. Results: A total of 50 studies (5 RCTs, 45 observational) involving 9902 IBD patients were included. The overall pooled incidence of acne was 8.6% (95% CI: 6.4%-11.6%). Acne rates were significantly higher (P < .0001) with the upadacitinib (12.2%), compared to tofacitinib (2.6%) and filgotinib (2.3%). A numerically higher incidence was observed during induction (8.6%) versus maintenance (4.2%) therapy, though this difference was not statistically significant (P = .07). The incidence was significantly higher in the pediatric population (12.2%) compared to adults (7.4%) (P = .03). In RCTs, JAK inhibitors were associated with significantly increased odds of acne compared to placebo (OR 2.43, 95% CI: 1.33-4.43, P = .019). No statistically significant difference was observed by IBD subtype. Conclusion: Acne is a common adverse event in IBD patients treated with JAK inhibitors. The reported incidence of acne was significantly higher with upadacitinib, in the pediatric population, and numerically higher during the induction phase of treatment.

Background and Aims: Up to 70%-80% of patients with primary sclerosing cholangitis (PSC) will have concomitant inflammatory bowel disease (IBD). Scarce data are available regarding outcomes of advanced therapies to treat IBD-PSC. We performed a systematic review and meta-analysis to assess the effectiveness and safety of advanced therapies in IBD-PSC. Methods: A systematic search was conducted in Cochrane Library, Embase, Google Scholar, Ovid Medline, PubMed, Scopus, and Web of Science from database inception to January 29, 2025. We included studies that reported on IBD clinical response with advanced therapies. Meta-analysis was performed using the random effects model. Subgroup analyses were conducted to further investigate proportion differences between covariates. Results: Nineteen studies (n = 864) were included in the final analysis. Among IBD-PSC patients treated with advanced therapies, clinical response was observed in 52% (95% CI, 40%-65%; I2 = 85%), clinical remission in 43% (95% CI, 25%-62%; I2 = 91%), and endoscopic remission in 26% (95% CI, 13%-42%; I2 = 75%). Infections occurred in 22% of patients (95% CI, 8%-40%; I2 = 82%) and acute cholangitis was observed in 14% of patients (95% CI, 2%-33%; I2 = 80%). The endoscopic remission rate with anti-tumor necrosis factor (anti-TNF) agents was 29% (95% CI, 10%-52%; I2 = 28%) vs. 15% (95% CI, 4%-29%; I2 = 70%) in those who received non-anti-TNF biologics. The rates of overall infections were similar in patients who received anti-TNF vs. non-anti-TNF biologics. Conclusions: Advanced therapies show efficacy and comparable safety in IBD-PSC. The study findings are limited by significant heterogeneity and further prospective studies with standardized endpoints are needed.

Background: Intra-abdominal abscess (IAA) is a serious complication of Crohn’s disease (CD). Management strategies include medical therapy, percutaneous drainage (PD), and initial surgery, but the optimal approach is debated. We performed a systematic review and meta-analysis to compare these strategies. Methods: A systematic search of 4 electronic databases was conducted. The primary outcome was the need for surgical intervention (resection or reoperation). Secondary outcomes included recurrence and complications. Data were pooled using random-effects models. Results: Twenty-three studies were included. Compared with initial surgery, both PD (odds ratio [OR], 5.28; 95% confidence interval [CI], 1.65-16.91) and medical management (antibiotics alone ± corticosteroids) (OR, 4.40; 95% CI, 1.25-15.45) were associated with significantly higher odds of requiring surgical intervention, relative to the reoperation rate in the surgery group. PD was associated with significantly lower odds of overall postintervention complications compared with initial surgery (OR, 0.48; 95% CI, 0.23 to 0.96), with no significant difference in length of stay. Adjunctive exclusive enteral nutrition was associated with a significant reduction in the need for subsequent surgery (OR, 0.26; 95% CI, 0.10 to 0.67). Pooled proportions for requiring subsequent surgery were 48% for medical management, 47% for PD, and 21% for the reoperation rate in the initial surgical group. Conclusion: Initial surgical management is the most definitive treatment for CD-related IAA, with the lowest reoperation rates. PD serves as a less invasive bridge to surgery that reduces postintervention complications. Medical management alone is less effective and should be reserved for select patients.

Background: Inflammatory bowel disease (IBD) can lead to zinc deficiency, which plays a critical role in immune function and tissue repair. This study aims to determine the prevalence, clinical characteristics, and impact of zinc deficiency in IBD patients. Methods: This is a retrospective study of patients aged ≥14 years with confirmed IBD and available zinc level measurement. Zinc deficiency was defined as a level p < 0.001) levels, and were more likely to be on corticosteroids (p = 0.04). Zinc deficiency was associated with higher rates of IBD-related hospitalizations (48.0% vs. 17.7%), surgeries (19.6% vs. 5.8%), complications (30.4% vs. 12.4%), and emergency room visits (40.2% vs. 17.3%) (all p < 0.001). Upon multivariate analysis, predictors of IBD-related hospitalization were zinc deficiency (OR 2.42, 95% CI 1.07–5.48, p = 0.03) and low albumin (OR 9.03, 95% CI 3.38–24.15, p < 0.001). Zinc deficiency was associated with IBD-related surgeries (OR 5.23, 95% CI 1.27–21.45, p = 0.02) and complications (OR 3.98, 95% CI 1.52–10.41, p = 0.005). Conclusions: Zinc deficiency is prevalent in patients with IBD, associated with a high inflammatory burden, and was linked to worse clinical outcomes after controlling for markers of inflammation.