Introduction

Curcumin longa Linn has been used in Asia as an herbal remedy for gastrointestinal disorder. However, the benefit of curcumin on GERD treatment is still not well evaluated.

Aims & Methods

The aim of this study was to compare efficacy of curcumin and omeprazole on GERD symptom relief over the course of 4 weeks and duration of symptoms relief after treatment. From July 2021 to December 2022, subjects diagnosed with GERD according to ROME IV criteria were enrolled. Subjects were randomized into curcumin, or omeprazole groups. The Gastroesophageal Reflux Disease Symptom Assessment Scale (GSAS) was used to evaluate clinical effectiveness after 4 weeks.

Results

A total of 62 subjects were randomized. Thirty and 32 subjects in the curcumin and omeprazole groups, respectively. At 4 weeks, no significant difference of the mean GSAS score was observed between curcumin and omeprazole groups ( -2.53 ± 0.59 vs -2.37 ± 0.46; P = 0.83). Omeprazole group had greater improvement of number of subjects who had severe symptom than curcumin group (50% to 3.1% vs 16.6% to 10%). Mean duration of symptom improvement was 14 days in curcumin and 10 days in omeprazole groups. No report of adverse reaction or worsening of GERD symptoms in both groups.

Table 1 Comparison of mean GSAS (gastroesophageal reflux disease symptom assessment scale) at entry and after 4 weeks of treatment

Conclusion

Curcuma longa Linn can improve GERD symptoms equivalent to omeprazole in treatment of GERD without worsening of symptoms. However, the effect of omeprazole was faster symptom improvement in our cohort.

References

Gupta SC, Patchva S, Aggarwal BB. Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials. AAPS J. 2013 Jan;15(1):195–218.

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

Hepatocellular carcinoma (HCC) is an end stage liver disease with increasing morbidity and mortality worldwide. Development of the disease is dependent on various genetic, dietary and environmental factors. While alcohol-related liver disease (ALD/MetALD) remains a major contributor, metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming increasingly relevant in clinical practice. There is increasing evidence for the role of bacteria, for instance, such as Bifidobacterium and Blautia, which were considered protective, while Streptococcus has been associated with disease progression. However, little is known about the alteration of microRNAs (miRNAs) in liver diseases and its interrelationship with microbial environment in view of etiological factors.

Aims & Methods

This study aimed to elucidate gastrointestinal miRNA alterations and explore their relationship with microbiome composition in patients with different stages of liver disease in terms of disease etiology. Multi-omics analyses were performed in a subset of well characterized patients (n=59) with liver disease and healthy controls. Systematic characterization included clinical, laboratory, demographic and imaging characterization and dietary preferences. Patients subclassification included fibrosis stage (no fibrosis, fibrosis, liver cirrhosis(LC)) and etiology (MetALD/ALD vs. MASLD). Fecal miRNAs were extracted using the Qiagen miRNeasy Kit and profiled via Agilent miRNA microarray. Microbiome analyses were performed amplifying the V1-V2 region of the 16S rRNA gene following Illumina sequencing.

Results

For miRNA analysis stringent criteria were applied to identify high quality miRNA targets. From approximately 4,000 candidates filtering resulted in selection of 202 high-quality miRNAs with reliably measurable concentrations. 28 of these miRNAs showed significantly positive alterations in concentration in patients with liver disease and 7 miRNAs significant negative alterations. Specifically, miR-642a-3p, miR-5006, miR-6781, and miR-6849 were elevated in feces in patients with LC. In contrast, miR-6869, miR-4467, and miR-5001 were present in lower concentration in LC patients. Notably, miR-4467 also showed strong negative associations with liver-specific laboratory markers, including gamma-glutamyl transferase (GGT) (r=-0.34; p=0.026) and M65, a marker of apoptosis (r=-0.42; p=0.005). Cross-sectional comparison of miRNA and microbiome data revealed miRNA alterations associated with specific microbial signatures. MiR-6795-5p, which was associated with liver stiffness (r = 0.39, p = 0.01), also correlated positively with the abundance of Streptococcus, a genus linked to disease progression (r=0.29; p=0.047). Conversely, miR-6869, miR-4467, and miR-5001 showed positive correlations with the potentially protective genera Blautia and Bifidobacterium (miR-6869: r_{Bifidobacterium}=0.35; p_{Bifidobacterium}=0.012; r_Blautia=0.37; p_Blautia=0.008; miR-4467: r_Blautia=0.41; p_Blautia=0.002; miR-5001: r_Blautia=0.38; p_Blautia=0.006).

Conclusion

Multi-omics analysis reveals distinct alterations in fecal miRNAs and gut microbiota across different stages of liver disease. Changes in microbial composition were associated with shifts in miRNA profiles, suggesting a functional link in maintaining intestinal homeostasis. These findings highlight the potential of integrated microbiome–miRNA signatures as novel diagnostic and therapeutic targets. Further studies are warranted to validate these associations and explore their clinical applications.

Introduction

Azathioprine and mercaptopurine are commonly used to treat Inflammatory Bowel Disease (IBD), with around 6 in 10 patients being prescribed them at some point. Adherence to treatment is important to maintain disease control, prevent flare ups, reduce the need for steroids and improve wellbeing. A good response to treatment may delay or negate the need to escalate treatment to Biologic medications or surgery. Despite this, treatment non-adherence is a common problem among patients with chronic diseases, averaging at around 50%. In IBD specifically, the data varies widely, but non-adherence to oral therapy has been reported to be as high as 72%.

Aims & Methods

The aim of this study was to determine the adherence to azathioprine and mercaptopurine in IBD patients across the Bristol, North Somerset, South Gloucestershire Integrated Care Board (BNSSG ICB). Primary care records were searched to identify all patients with IBD prescribed azathioprine or mercaptopurine. Demographic data as well as data on disease type, length of treatment and co-prescription with a Biologic treatment was collected. Medication adherence was determined by GP records of pharmacy refill data.

Results

A total of 1313 patients were identified as having IBD and a current prescription for azathioprine or mercaptopurine, from 78 GP surgeries (98% of surgeries within the BNSSG ICB). 154 patients were excluded as they had been on azathioprine for less than 1 year. 59% of the 1159 included patients had Crohn’s disease. 360 patients (31%) were on combination therapy with a Biologic medication. 324 patients (28%) were found to be non-adherent with their medication based on prescription refill data suggesting that they do not have an adequate supply of medication.

Conclusion

Our data suggests that adherence to the immunosuppressant medications azathioprine and mercaptopurine in patients with IBD is comparable or slightly better than in other chronic diseases. However, pharmacy refill data is an indirect measure of medication adherence so adherence may have been overestimated. There remains a substantial proportion of patients who are not adhering to treatment, which is likely to be associated with poorer outcomes.

References

Chan W, Chen A, Tiao D, et al. Medication adherence in inflammatory bowel disease. Intest Res. 2017 Oct;15(4):434-445

Disclosure

No conflicts of interest to declare.

Introduction

Thiopurines (TP) (azathioprine AZA, and 6 mercaptopurine 6MP) are immunosuppressive drugs (IS) used in the treatment of chronic inflammatory bowel diseases (IBD), particularly Crohn's disease (CD). The aim of our work is to see if they still have an indication in monotherapy, in the era of biotherapies and small molecules.

Aims & Methods

This is a retrospective analytical study conducted at the Hepato-Gastroenterology and Proctology Department "Medicine B" from January 2012 to July 2022. 740 patients were followed for CD during this period. 407 patients were put on TP. Age, sex, different characteristics of CD, indication for and type of TP treatment, and course of treatment were collected from all patients. SPSS 20.0 software was used for statistical analysis. The khi-2 test was used to compare categorical variables. The binary logistic regression model was used for multivariate analysis.

Results

There were 375 patients followed up for CD on TP monotherapy (92.13%) and 32 on combination therapy (7.86%). The sex ratio was F/H=1.5. The average age was 39.8 years (15-72). The location was ileal in 69 patients (16.95%), colonic in 78 patients (19.16%), ileocolic in 257 patients (63.14%), 6 patients (1.47%) had upper gastrointestinal tract involvement of CD and 3 patients (0.73%) had anal CD. 99 patients (24.32%) had ano-perineal lesions (APL). The phenotype was stenosing in 47 cases (11.54%), fistulizing in 159 cases (39%), stenosing and fistulizing in 60 cases (14.74%) and inflammatory in 141 cases (34.64%). The type of TP used was AZA in 299 patients (73.46%) and 6MP in 108 patients (26.53%). TP was indicated as maintenance treatment in 270 cases (66.33%), as monotherapy in the absence of biotherapy (which was not available before 2016) in fistulizing forms in 105 cases (25.8%), and in case of cortico-dependency in 32 cases (7.86%).
Clinical remission was obtained with monotherapy in 326 cases (86.93%) and with combotherapy in 24 cases (75%), this difference is statistically non-significant p=0.08. Mucosal healing was noted with monotherapy in 124 cases (33%) in patients who performed a control endoscopy, and with combotherapy in 15 cases (46.87%), this difference is statistically not significant p=0.07.
CRP was negatived in monotherapy in 149 patients (39.73%) and in combination therapy in 27 patients (84.37%), this difference is statistically significant p<0.001. Fecal calprotectin was not always available. Among the patients who had it performed (65: 15.97%), it was negative in 18 cases (41.86%) in monotherapy and 3 cases (13.63%) in combination therapy. This difference is statistically significant p=0.015. Metabolite dosing was also rarely available. In cases where this was done (43 cases: 10.56%), 6-TGN was in the therapeutic range only in 14 cases (32.55%) and in 36 cases (83.72%) for 6-MMP, requiring therapeutic adjustment.
In multivariate analysis and adjusting for the different confounding parameters, it was found that only the combination therapy was a predictive factor for mucosal healing [OR=1.8; [0.8 - 3.9]; p=0.01].

Conclusion

The results of this study show that TPs still have a place in the therapeutic arsenal of CD, but that their combination with biotherapy allows more clinical and biological remission and especially mucosal healing.

Introduction

Janus Kinase (JAK) inhibitors are licensed for the treatment of ulcerative colitis with the benefits of a fast onset of action and a short half-life.[i] This makes them a potential treatment option for patients hospitalised with UC, including those previously treated with, or unsuitable for, infliximab or cyclosporine. There is currently limited published evidence in this setting, drawn from small case series.

Aims & Methods

We performed a retrospective analysis of data collected at 14 sites in the United Kingdom, including both tertiary IBD centres (n=10) and general hospitals (n=4) between January 2019 to January 2024. We included patients who were hospitalised due to active UC and commenced a JAK inhibitor for that indication during the same admission. Baseline data included disease duration and extent, prior exposure to advanced therapies, clinical and endoscopic assessments of disease activity and laboratory parameters. We reviewed treatments administered during the same admission, including corticosteroids and advanced therapies.
Coprimary endpoints were colectomy rate at 30 days and 12 months. 12 week, 6 month and 12month persistence data was collected. Adverse outcomes and treatment persistence at the same time points were also recorded.

Results

80 patients (filgotinib (n=15), tofacitinib (n=25) and Upadacitinib (n=40) were included, with a minimum of 12 weeks follow-up. 43/80 (54%) were male, mean age was 37±14, mean admission albumin 35 and CRP 52. Extent of disease was E1 1/80 (1%), E2 31/80 (39%) and E3 48/80 (60%).
63/80 (79%) of patients had prior anti-TNF exposure (infliximab 47/80 (59%), including 13/80 (16%) of whom had received it as a previous rescue therapy). 31/80 (39%) were on prednisolone at admission.
50/80 (63%) had a baseline endoscopic assessment within 72 hours of admission, of which 34/50 (68%) had severe (Mayo 3) endoscopic activity.
During admission, prior to JAK inhibitor administration, treatments given included IV hydrocortisone (93%), methylprednisolone (5%), infliximab (4%) and cyclosporine (1%).
Colectomy rates were 8% and 14% at day 30 and week 12 respectively. In patients for whom 12-month follow-up data were available, 5/34 (15%) had undergone a colectomy at that timepoint.
There was one recorded herpes zoster infection and no recorded thromboses or major adverse cardiovascular events.

Table 1. JAK Inhibitor & Treatment Persistence

Conclusion

JAK inhibitors appear to offer a valuable treatment option for patients hospitalised with active UC. This appears to be the case even in patients with prior anti-TNF exposure. 86% of patients avoided colectomy at 12 weeks, with a similar proportion colectomy-free at 12-months. The risk of adverse events was small. Our study is, to our knowledge, the largest dataset examining the initiation of JAK inhibitors for those hospitalised with UC.

References

[i] Agrawal M, Kim ES, Colombel J-F. JAK inhibitors safety in ulcerative colitis: practical implications. Journal of Crohn's and Colitis. 2020;14(Supplement_2):S755-S60.

Introduction

Orodispersible budesonide (ODB) is an effective treatment for eosinophilic oesophagitis (EoE), with clinical trials reporting clinical remission rates of 75% at 48 weeks. Real-world data is lacking, particularly for longer term ODB maintenance treatment. We have conducted the first UK multicentre review of real-world outcomes on adults with EoE taking ODB from 5 tertiary hospitals.

Aims & Methods

Databases at 5 UK centres were screened to identify adults taking ODB. Audit approval was obtained by each centre. Electronic results and documentation were reviewed. Patients were telephoned and validated surveys completed to assess symptoms – Reflux Disease Questionnaire (RDQ), Hospital Odynophagia Dysphagia Questionnaire (HODQ) and Adult EoE Quality of Life Survey (EoE-QoLS). A numeric rating scale was used for pts to gauge their response to ODB.

Results

104pts aged 24-86y (med 41y), 27F:77M, taking ODB for 3-60months (med8.5m, mean14.2m) were included.
97pts completed questionnaires – 98% reported ODB had improved their symptoms. Scores on ODB were low, suggesting clinical remission: RDQ 0-52 (med0), HODQ 0-29 (med2), and EoE-QoLS 37-120 (med60).
71% received PPI first line prior to ODB, of which 81% reported inadequate improvement in dysphagia and 94% did not achieve histological remission (HR, <15eos/hpf) on PPI prior to ODB. 21pts continued PPI in addition to ODB - 1/21 was not in HR.
82pts underwent OGD on ODB – 77% were in HR. 74% pts had fibrotic findings (stricture, trachealisation) which had improved or resolved for 49% on ODB. 78% pts had inflammatory findings (oedema, exudate, furrows) which had improved or resolved for 67% on ODB.
14% experienced oro-oesophageal candidiasis on ODB. ODB was not discontinued.
Following ≥8week induction with 1mg BD ODB, 51pts had tried a reduced maintenance dose of 1mg OD ODB – 77% reported no deterioration in their symptoms on 1mg OD vs BD. 10pts had undergone OGD on 1mg OD – 7/10 were in HR.

Conclusion

Symptomatic and histopathological remission rates on ODB in this multicentre UK study are comparable to clinical trial outcomes yet resolution of endoscopic signs was lower. 1mg OD ODB kept a majority with symptomatic control but this was not always accompanied by histological/endoscopic remission. QoL scores were not proportionately as low as symptom scores on ODB, suggesting a persisting psychological burden despite treatment and warrants further study.

References

Lucendo et al, Gastroenterology (2019)
Miehlke et al, UEG Journal (2022)
Straumann et al, Gastroenterology (2020)
Dhar et al, Gut (2022)