Introduction

Tofacitinib, filgotinib, and upadacitinib, are Janus kinase inhibitors (iJAKs) approved for inflammatory bowel disease (IBD) treatment. Although no direct comparative studies exist, potential differences in efficacy and safety are attributed to in vitro-demonstrated affinity of each molecule for different JAK isoforms. JAK1 plays a crucial role in modulating cytokine-mediated immune responses, such as IL-6 and interferon, which are involved in inflammation and skin homeostasis. Its inhibition can promote conditions that may trigger acne.
Acne may be increased in iJAK-treated patients, meaning a clinical challenge for gastroenterologists.

Aims & Methods

A retrospective study was conducted at ten referral centers in Spain, including all IBD patients who had received iJAK therapy and had at least 3 months of follow-up. Demographic data, disease-related variables, and acne characteristics when appropriate, were collected. Univariate and multivariate logistic regressions were used to identify risk factors for acne; model discrimination was assessed by AUC.

Results

A total of 549 patients included: 258 (47%) were women; 354 (64%) had ulcerative colitis, 191 (35%) had Crohn’s disease and 1% had indeterminate colitis. Mean age was 41 years (IQR 30-52). 219 patients (40%) were treated with tofacitinib, 281 (51%) with upadacitinib, and 49 (9%) with filgotinib.
Ninety patients (16%) developed acne during iJAK treatment: 69% were mild, with only 4 severe cases (4%). Acne occurred early (median onset 42 days, IQR 7-122), predominantly on the face (56%), trunk (13%) or both (31%). Acne morphology included comedones (60%), papules (59%), pustules (39%), nodular-cystic (12%), scarring (9%); 48% showed more than one morphology.
Thirty-six patients received specific acne treatment: 89% topical (antiseptics, benzoyl peroxide, retinoids), 69% systemic (antibiotics, retinoids, antiandrogens), and 44% combined treatment. 83% of those patients responded to acne specific treatment, and only 8 patients (9% of those with acne; 1.5% overall) had to discontinue iJAK treatment, with acne resolving in all cases.
Acne developed in 26%, 6% and 6% of upadacitinib, tofacitinib and filgotinib treated patients respectively (p=0.001). Multivariate analysis showed that acne development was associated with upadacitinib (OR 10.28;IC95%=4,7–22,6; p<0,001) and history of acne (OR 3.52; IC95%=1,5–8,3; p=0,004), while older age (>35 years, OR 0.31; IC95% 0,11–0,83; p=0,02) and Crohn’s disease (OR 0.47; IC95% 0,25–0,90; p=0,02) showed to be protective. This model was reliable in predicting acne development (AUC 0.79). Additionally, univariate analysis showed high dose of iJAK was also associated with acne development, which could not be confirmed in multivariate analysis.

Conclusion

Acne occurred in a relevant proportion of iJAK-treated patients, was generally mild and manageable with dermatological care, and rarely required treatment discontinuation. Risk factors for iJAK-associated acne included use of upadacitinib (probably reflecting a greater affinity for JAK1) and history of acne, while older age and Crohn’s disease were protective.
Gastroenterologists should be aware of both likelihood and management of this specific adverse event when considering iJAK therapy.

Disclosure

Y G-L, MC, GB, ER, IB, DC, M B-dA, LM, I M-J, DG, IV have provided scientific advisory / participated in educational activities / received unrestricted research grants / received payments for lecturing from Johnson & Johnson, ​Takeda, Pfizer, Amgen, AbbVie, Lilly, AlfaSigma, Ferring, Gilead.

Introduction

Eosinophilic oesophagitis (EoE) is a chronic, immune-mediated oesophageal disease affecting approximately 34.2 per 100,000 people1, and has prompted shifts in both clinical recognition and therapeutic strategies. Over time, treatment has progressed from proton pump inhibitors (PPIs) to topical corticosteroids, with newer approaches exploring the role of biologics. Budesonide remains a widely used corticosteroid, while dupilumab, a monoclonal antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13) signalling2, has emerged as a promising alternative. However, comparative evidence between these two agents remains limited, reinforcing the need for an updated synthesis of trial data to guide therapeutic decision-making.

Aims & Methods

This systematic review and meta-analysis aimed to evaluate and indirectly compare the effectiveness of budesonide and dupilumab, each against placebo, in achieving histological remission in patients with EoE. A comprehensive literature search of PubMed, Scopus, and the Cochrane Library identified 3,949 records, screened in accordance with PRISMA guidelines. Screening was assisted by Rayyan.AI and eligible studies were included based on randomised controlled trials (RCTs) in human subjects, populations in the last 10 years. The primary outcome was histological remission, as defined by each study. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model in R (version 4.5.0) via RStudio, utilising the meta and metafor packages. Forest plots were used to visualize study-level effects and overall estimates, and funnel plots were generated to assess potential publication bias.

Results

Our results found nine RCTs evaluating budesonide (n = 945) producing a pooled RR of 31.41 [95% CI: 16.13–61.15]. This demonstrates a substantial benefit over placebo with no observed heterogeneity (I² = 0%). Forest plots illustrated strong, consistent effects across studies. Egger’s test for funnel plot asymmetry showed no evidence of small-study effects or publication bias (p = 0.22), and visual inspection revealed no significant asymmetry. These findings suggest a low risk of publication bias in the budesonide literature. Three RCTs assessed dupilumab (n = 199), yielding a pooled RR of 16.31 [95% CI: 5.77–46.09]. Dupilumab demonstrated strong efficacy with minimal heterogeneity (I² = 0%). A funnel plot was generated, though interpretation was limited by the small number of included studies, reinforcing the need for further research.

Conclusion

Both budesonide and dupilumab significantly outperform placebo in achieving histological remission in EoE. Budesonide remains a well-established treatment, while dupilumab presents a valuable alternative for patients with steroid-refractory or intolerant disease. Despite limited comparative evidence between the two therapies, this review offers a novel and quantitative synthesis using forest plot and meta-analytical techniques in R. These findings provide a solid foundation for clinical decision-making and future comparative research in EoE. The strength and consistency of evidence across trials reinforce budesonide’s role as a reliable and effective therapy in EoE. Dupilumab also demonstrates considerable promise, and further research is encouraged to better define its long-term role in clinical practice. As the treatment landscape for EoE continues to expand, this analysis offers a timely contribution that may inform current clinical strategies and inspire future innovation.

References

1. Baldovich K. Increasing Incidence Rates of Eosinophilic Esophagitis in Active Component Service Members, U.S. Armed Forces, 2009–2021 [Internet]. Military Health System. Health.mil; 2023 [cited 2025 Apr 23]. Available from: https://www.health.mil/News/Articles/2023/05/01/Eosinophilic-Esophagitis
2. D’Ippolito D, Pisano M. Dupilumab (Dupixent): An Interleukin-4 Receptor Antagonist for Atopic Dermatitis. Pharmacy and Therapeutics [Internet]. 2018 Sep;43(9):532. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC6110636/

Introduction

Sexually transmitted infections (STIs) are increasingly recognized as causes of proctitis, particularly among men who have sex with men (MSM). These infections frequently mimic inflammatory bowel diseases (IBD) in clinical, endoscopic, and histological presentations, leading to potential misdiagnosis and inappropriate treatments. Accurate recognition requires detailed sexual history and targeted diagnostic tests.

Aims & Methods

Patients were identified from IBD outpatient visits (2021–2023) and retrospectively selected for suspected infectious proctitis mimicking IBD. Diagnosis was confirmed via clinical evaluation, targeted tests (rectal swabs, PCR, serology), and histology. Follow-up continued for six months post-treatment.

Results

1. A 42-year-old MSM with secondary syphilis treated with benzathine penicillin presented with bloody diarrhea, tenesmus, anorectal pain, and 10-kg weight loss. Mild anemia (Hb 12 g/dL) and elevated CRP were noted. Rectosigmoidoscopy (RSCS) revealed fibrinous ulcers causing luminal narrowing. Rectal swabs confirmed Chlamydia trachomatis. Treatment with doxycycline led to clinical and endoscopic resolution at six months.
2. A 33-year-old MSM with unprotected intercourse reported mucorrhea and tenesmus for one month. Calprotectin levels were elevated (861 µg/g). Colonoscopy revealed mild proctitis with mucosal hyperemia, and histology showed mild-to-moderate inflammation with crypt abscesses. Swabs confirmed Neisseria gonorrhoeae. Ceftriaxone resolved symptoms and normalized calprotectin (40 µg/g).
3. A 34-year-old male with primary sclerosing cholangitis (PSC) presented with two weeks of tenesmus, anal bleeding, and pruritus. Colonoscopy appeared macroscopically normal, but histology revealed human papillomavirus (HPV) infection. Anal canal condylomas were identified and successfully treated with cryotherapy, resulting in significant relief.

Conclusion

The rising prevalence of STI-related proctitis highlights the need for awareness among clinicians, as these infections often mimic IBD. Misdiagnosis can lead to inappropriate treatments, including steroids or biologics, causing adverse effects and delays in proper management. Detailed sexual history and targeted diagnostics, such as PCR and rectal swabs, are critical for accurate identification and effective treatment. These cases emphasize the critical role of integrating sexual history into clinical evaluation for proctitis. Awareness and timely recognition of STI-related proctitis are crucial to avoid misdiagnosis as IBD, ensure effective and targeted treatment, improve patient outcomes, and prevent inappropriate and prolonged follow-up.

References

-Infectious Proctitis: When to Suspect It Is Not InflammatoryBowel DiseaseFrank Hoentjen • David T. Rubin (Dig Dis Sci (2012) 57:269–273) -Proctitis: a glance beyond inflammatory bowel diseasesStefano Rizza et all Minerva Gastroenterol Dietol. 2020 Sep;66(3):252-266
-Proctitis in Men Who Have Sex with Men. Julia M. Steed et all

Introduction

Gastroparesis (GP) is a chronic motility disorder characterized by recurrent upper gastrointestinal (GI) symptoms, namely early satiety, nausea and vomiting, in the absence of a mechanical obstruction. Functional Lumen Imaging Probe (FLIP) is a potential game-changer in anatomical sphincter assessment. Recently, wide prospective trials[1] and a randomized sham-controlled study[2] implemented FLIP to predict response of pyloric-targeted treatments. This has prompted the need for a comprehensive analysis of available FLIP data in GP.

Aims & Methods

The aim of this systematic review was to investigate FLIP role in GP. Meta analysis of normative values and treatment comparative outcomes was also performed. A systematic search was performed until May 2024 on 4 major databases (Pubmed-MEDLINE, Embase, Web of Science, Cochrane). Studies on post-oncological/bariatric surgery gastroparesis were excluded. Pooled baseline mean of FLIP metrics and mean differences (MDs) pre vs post-treatment were calculated. In addition to estimate clinically meaningful normative values for GP, upper-limit reference ranges were estimated by pooled standard deviations (SDs) implementing the formula pooled mean ± 1.96 × pooled SD. Random effects meta-analysis with Knapp-Hartung correction for 95% confidence intervals (CIs) adjustment and I² statistics with subgroup analysis to address heterogeneity were performed.

Results

Twenty studies (N= 805 patients) were included. The majority focused on treatment response, particularly pyloromyotomy. The most assessed FLIP metrics were distensibility index (DI) and cross-sectional area (CSA). Three studies (on 7 total) reported a positive correlation between DI and CSA with specific symptoms (dyspepsia spectrum and nausea/vomiting) and their severity at baseline. Ten studies (on 15 total) studies showed an association between FLIP parameters with clinical response. Pooled mean DI ranged from 7.5 to 8.9 mm²/mmHg and CSA from 85.5 to 195.6 mm² at baseline. Minimum diameter (Dmin) ranged between 10.6 and 16.5 mm while Pressure (P) between 14.8 and 34.5 mmHg (table 1.). Upper-limit normative values for GP ranged from 173-317 mm² for CSA, 17-27 mm for Dmin, 32-64 mmHg for P (between 30-50 mL of fill volumes), while for DI at 50mL the reference limit attested at 21.5 mm²/mmHg. Comparing pre-and post-treatment response, MD of 2.5 mm²/mmHg (I² 24%) for DI at 50 mL, 46.7 mm² (I² 47%) and 68.8 mm² (I² 0%) for CSA at 40 and 50 mL respectively, were statistically significant.

Table 1. FLIP metrics pooled mean values at different fill volumes at baseline in gastroparesis patients

Conclusion

This is the first systematic effort in gathering evidence on FLIP in gastroparesis. CSA and DI significantly changed after pylorus-targeted treatments. Normative values displayed substantial heterogeneity and wide CIs. The cut-off of 10 mm²/mmHg for DI seems feasible to categorize patients to be addressed to pylorus-targeted treatments. Further studies to calculate prediction ability of this cut-off are warranted.

References

1. Jacques J, Pagnon L, Hure F, Legros R, Crepin S, Fauchais A-L, et al. Peroral endoscopic pyloromyotomy is efficacious and safe for refractory gastroparesis: prospective trial with assessment of pyloric function. Endoscopy. 2019;51(1):40-9.
2. Martinek J, Hustak R, Mares J, Vackova Z, Spicak J, Kieslichova E, et al. Endoscopic pyloromyotomy for the treatment of severe and refractory gastroparesis: a pilot, randomised, sham-controlled trial. Gut. 2022;71(11):2170-8.

Disclosure

E.V. received speaker and/or consulting fees from Sanofi/Regeneron, Falk Pharma, Apollo Therapeutics, and Aurora Biofarma. AJB received research funding from BMS, Sanofi/Regeneron, SST, and Dr. Falk Pharma and received speaker and/or consulting fees from Uniquity, Laborie, Medtronic, BMS, Dr. Falk Pharma, Calypso Biotech, Eupraxia, Aqilion, Alimentiv, Sanofi/Regeneron, Uniquity, Reckitt, AlfaSigma and AstraZeneca. All other authors did not have any disclosures.