Introduction

The revised Finnish guidelines for coeliac disease in 2018 enabled for the first time to establish a no-biopsy diagnosis in adults with serum transglutaminase antibodies >10x upper limit of normal and positive endomysial antibodies. We investigated the implementation of the new guidelines and significance of the diagnostic process on the treatment success and patients´ experiences.

Aims & Methods

Altogether 194 adult members of the Finnish Coeliac Society diagnosed after 2018 answered to a comprehensive study questionnaire concerning socio‐demographic and health-related characteristics and quality of life and various coeliac disease-related issues. The results were compared between patients diagnosed with and without duodenal biopsy.

Results

Sixty-nine (36%) patients were diagnosed without a biopsy. They were younger (median age 44 vs. 52 years, p=0.029), diagnosed less often in hospital settings (11% vs. 35%, p=0.001), suffered less often from oesophageal symptoms (17% vs. 30%, p=0.047) and osteoporosis (1% vs. 10%, p=0.035) and experienced the diagnostic process more often easier (49% vs. 30%, p=0.032) than those diagnosed by biopsy (n=125). The no-biopsy group had also been informed on their diagnosis more often by other healthcare professional than a physician (14% vs. 4%, p=0.046) and reported more persistent symptoms (36% vs. 21%, p=0.026) and stress due to the gluten-free diet (68% vs. 47%, p=0.042). The groups did not differ in gender, socio-economic characteristics, general health, quality of life, other than oesophageal symptoms, diagnostic delay, presence of follow-up or experiences of a gluten-free diet or dietary adherence. After adjusting the groups with age, the difference in osteoporosis was no longer significant.

Conclusion

Up to one-third of adult coeliac disease patients were diagnosed without gastrointestinal endoscopy, which may provide less burdensome diagnostic process and significant healthcare savings. However, increased risk for persistent symptoms and dietary stress in these patients remind that adequate guidance at diagnosis regardless of the diagnostic process and healthcare unit should be provided.

Introduction

Recent years have seen a significant increase in randomized controlled trials (RCT) published on the efficacy of probiotics on irritable bowel syndrome (IBS), which several reviews have tried to comprehensively review. Two recent trials, Yang et al. 2024¹ and Chen et al. 2023² report the safety and efficacy of probiotics for IBS, which seems to reflect prevailing favorable view of this therapeutic option by most reviews conducted. Yet, despite efforts in this field, major organizations have not changed their stance in this and make no assertive recommendation for probiotics in afflicted patients^3,4. While further investigations are required, two challenges are faced: (1) repeated reviews have been undertaken in this field, resulting in a "multiplicity problem", (2) traditional meta-analytic techniques may also fail to provide a conclusive answer on the sufficiency of evidence, particularly when the data are sparse, and the risk of type I and type II errors is significant. This indicates a need for.

Aims & Methods

This study aims to evaluate the efficacy of probiotics in alleviating symptoms of IBS and improve quality of life through a timely implemented trial sequential analysis (TSA) and rigorously evaluate the evidence for recommendations on future studies. Medline, Embase, Web of Science, and Cochrane were screened for randomized controlled trials (RCTs) comparing probiotics to placebo in adult patients with IBS. Primary outcomes included IBS Symptom Severity Score (IBS-SSS) and IBS Quality of Life (IBS-QOL) scores comparing probiotics and placebo groups. Traditional pairwise meta-analysis conducted in restricted maximum likelihood was conducted, with subsequent TSA . Study quality was graded according to risk-of-bias 2 (ROB-2) and certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE).

Results

42 studies were included. Overall, probiotics demonstrated non-significant improvements in IBS-SSS (MD: -27.64; 95% CI: -56.90 to 1.63; p=0.06) and IBS-QOL (MD: 1.33; 95% CI: -3.65 to 6.30; p=0.59). TSA was conducted on IBS-SSS demonstrated current evidence has not reached the required information size. The representative cumulative Z-curve demonstrated neither futility, benefit nor detrimental effect, indicating the need for further trials. Assessment with ROB-2 indicates high quality amongst most trials included in this study. GRADE evaluation of the evidence demonstrated low certainty of existing evidence.

Table 1: GRADE Evaluation

No. of studies	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Probiotics	Placebo	Relative (95% CI)	Absolute (95% CI)	Certainty
Probiotics effectively reduces a patient's IBS-SSS score
24	randomised trials	not seriousa	very seriousb	not serious	very seriousc	publication bias strongly suspectedd	2237	1599	-	MD 27.64 lower (56.9 lower to 1.63 higher)	⨁◯◯◯ Very lowa,b,c,d
Probiotics effectively reduces a patient's IBS-QOL score
24	randomised trials	not seriousa	very seriousb	not serious	not seriouse	publication bias strongly suspectedd	2292	1712	-	MD 1.33 higher (3.65 lower to 6.3 higher)	⨁◯◯◯ Very lowa,b,d,e

CI: confidence interval; MD: mean difference

Two contributing factors to the low certainty of current evidence include: (1) Inconsistency of existing trials – there exists high level of heterogeneity as detected by statistical analysis through I² and Cochran Q amongst studies; (2) Suspected publication bias through inspection of a funnel plot, though Egger’s regression did not demonstrate statistical significance.

Conclusion

Existing evidence is insufficient to make conclusive recommendations regarding the role probiotics should play in the management of IBS in symptoms and QOL. Given the persistent heterogeneity and potential publication bias, future research should focus on standardizing probiotic interventions and clarifying their clinical utility to truly advance the field.

References

1. Yang R, Jiang J, Ouyang J, Zhao Y, Xi B. Efficacy and safety of probiotics in irritable bowel syndrome: a systematic review and meta-analysis. Clinical Nutrition ESPEN. 2024;
2. Chen M, Yuan L, Xie C-R, et al. Probiotics for the management of irritable bowel syndrome: a systematic review and three-level meta-analysis. International Journal of Surgery. 2023;109(11):3631-3647.
3. Su GL, Ko CW, Bercik P, et al. AGA Clinical Practice Guidelines on the Role of Probiotics in the Management of Gastrointestinal Disorders. Gastroenterology. 2020;159(2):697-705. doi:10.1053/j.gastro.2020.05.059
4. McKenzie Y, Thompson J, Gulia P, Lomer M. British Dietetic Association systematic review of systematic reviews and evidence‐based practice guidelines for the use of probiotics in the management of irritable bowel syndrome in adults (2016 update). Journal of Human Nutrition and Dietetics. 2016;29(5):576-592.
5. Lacy BE, Pimentel M, Brenner DM, et al. ACG clinical guideline: management of irritable bowel syndrome. Official journal of the American College of Gastroenterology| ACG. 2021;116(1):17-44.

Disclosure

All authors of the manuscript do not have a conflict of interest to declare.

Introduction

Many irritable bowel syndrome (IBS) patients report gastrointestinal (GI) symptoms due to various foods, resulting in food avoidance. However, a detailed description of trigger foods and related GI symptoms and avoidance behaviour is lacking. Therefore, we evaluated the extent and nature of food intolerance and avoidance in IBS patients, and its relation to GI symptoms and psychological comorbidities.

Aims & Methods

Food intolerance and avoidance behaviour were evaluated in 124 IBS patients and 113 healthy controls (HC) using a questionnaire with 257 food products of 13 food groups. Per product, participants were asked if they experience symptoms (i.e. nausea, constipation, diarrhoea, bloating, abdominal pain) after consumption, and if they consumed this product despite these symptoms. Furthermore, IBS symptom severity and psychological factors were assessed.

Results

IBS patients reported a higher number of food products with perceived intolerance than HC (median of 18.0 (25^th-75^th percentile 10.0-33.5) vs 1.0 (0.0-8.0), p<0.001). A wide variety of trigger foods was reported, with gas-producing foods and fatty/cream-based dairy products most frequently reported by both groups. Predominant symptoms were abdominal pain and bloating. The number of avoided foods was higher in IBS (15.0 (8.0-27.0) vs 1.0 (0.0-7.0), p<0.001). Food avoidance was not significantly related to symptom type, but was associated with an IBS diagnosis, female sex, and higher screening scores for somatisation and Avoidant/Restrictive Food Intake Disorder.

Conclusion

Self-reported food intolerance and avoidance is higher in IBS than HC, with a wide variety of trigger foods. Food avoidance was significantly related to psychological factors, but not to symptom type. This warrants individual dietary guidance, as well as attention for psychological factors.

Disclosure

D Keszthelyi: DK reports receiving research funding from ZonMw, MLDS, UEG, Rome Foundation, Horizon Europe, Horizon 2020, Grunenthal, Allergan and speaker’s fee from Dr Falk (paid to host institute).
DMAE Jonkers: DMAEJ reports receiving a public–private partnership grant of TKI Well on Wheat? and TKI grants from Agri & Food and Health Holland, the Carbokinetics programme as part of the Netherlands Organisation for Scientific Research–Carbohydrate Competence Center partnership, Organic A2BV/Mothersfinest, and Horizon 2020.

Introduction

Individuals with coeliac disease (CeD) commonly complain of persistent symptoms despite adhering to a gluten free diet (GFD). We analysed baseline data from the prospective pseudonymized German CeD Registry to identify factors associated with ongoing complaints.

Aims & Methods

​​​​​​After written informed consent, participants self-reported demographic, clinical and healthcare related information at baseline and yearly thereafter. Symptoms before diagnosis and during the four weeks prior to completing the baseline questionnaire were retrospectively assessed. Factors associated with symptoms after at least one year of gluten-free diet (GFD) were evaluated by multivariate logistic regression.

Results

From 11/2019 to 10/2021, 2164 participants provided baseline data: 78% were female, median age 36 years (range 1.1 to 93.2), median time since diagnosis 6.3 years (0 to 58.7), and median diagnostic delay (time from first symptom to diagnosis) 2.2 years (0 to 64.8). Most common symptoms before diagnosis included abdominal pain (83%), bloating (82%), fatigue (78%), and diarrhoea (71%). Individuals diagnosed in adulthood were more symptomatic compared to paediatric patients. Although 93.4% of participants reported improvement after diagnosis, a substantial proportion of those keeping a GFD >1year (n=1861, 86% of cohort) had ongoing symptoms. Factors associated with regularly experiencing above symptoms included female gender, having the same symptom before diagnosis, feeling insufficiently informed by their physician about CeD and implications for their daily life, and age at diagnosis (per decade), but not time since diagnosis (table).

Variable	Abdominal pain		Bloating		Diarrhoea		Fatigue
	OR [95%-CI]	p-value	OR [95%-CI]	p-value	OR [95%-CI]	p-value	OR [95%-CI]	p-value
Gender female	1.79 [1.34; 2.40]	<0.001	1.30 [0.99; 1.70]	0.062	1.60 [1.13; 2.32]	<0.001	1.32 [1.00; 1.75]	0.049
Abdominal pain (bloating, diarrhoea or fatigue) present before diagnosis	3.45 [2.45; 4.96]	<0.001	3.06 [2.23; 4.27]	<0.001	3.19 [2.21; 4.73]	<0.001	2.18 [1.64; 2.92]	<0.001
Insufficient information given after diagnosis	1.25 [1.00; 1.57]	0.046	1.23 [0.98; 1.53]	0.069	1.29 [0.98; 1.69]	0.067	1.38 [1.11; 1.73]	0.005
Age at diagnosis per decade	1.11 [1.04; 1.18]	<0.001	1.15 [1.08; 1.22]	<0.001	1.07 [1.00; 1.16]	0.066	1.16 [1.09; 1.24]	<0.001
Time since diagnosis per decade	0.90 [0.79; 1.01]	0.089	1.11 [0.98; 1.25]	0.093	1.01 [0.88; 1.16]	0.866	1.11 [0.98; 1.26]	0.098

Table: Factors associated with persistence of symptoms (abdominal pain, bloating, diarrhoea or fatigue) after at least one year keeping a gluten free diet

Conclusion

Our findings revealed deficits in awareness, the diagnostic process, and post-diagnostic care. In this large cohort of patients with CeD we identified factors associated with persistence of symptoms despite keeping a GFD for at least one years. Early diagnosis, providing comprehensive education after confirmed diagnosis, and ensuring strict dietary adherence are pivotal for symptom resolution. A population-based mass-screening for CeD in childhood should be further explored. Implementing a multifaceted approach will enhance care for individuals with CeD and ultimately improve long-term health and well-being.

Introduction

CT-P13 subcutaneous (SC) infliximab formulation demonstrated superiority over placebo in maintenance therapy in Crohn's disease (CD)¹ and Ulcerative Colitis (UC)² patients in two parallel 54 weeks studies (LIBERTY-CD and LIBERTY-UC). We performed a post-hoc subgroup analysis comparing patients treated with CT-P13 SC with and without combination immunosuppressants (IS) at baseline in CD and UC.

Aims & Methods

Patients with moderately to severely active CD and UC who responded at W10 to CT-P13 intravenous infliximab 5mg/kg (Weeks 0, 2 and 6) were randomized (2:1) to receive CT-P13 SC 120 mg (CT-P13 SC) or placebo every 2 weeks until W54 as maintenance therapy. IS (azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate [MTX]) were allowed if patients maintained stable doses at least 8 weeks prior to W0, and stable doses were maintained up to W54.

Results

231 CD and 294 UC patients were randomized to receive CT-P13 SC maintenance therapy. Among them, 71 (30.7%) and 65 (22.1%) patients received CT-P13 SC with IS in CD and UC, respectively (In CD; 63, 4 and 4 patients of AZA, 6-MP, MTX, respectively, In UC; 63, 2 and 0 patients of AZA, 6-MP, MTX, respectively). There were no statistically significant differences in all of the efficacy outcomes between monotherapy and combination therapy groups at W54 in both studies (Table 1). A trend is seen for higher rates of corticosteroid-free remission with combination therapy in both CD and UC patients.
No statistically significant differences were seen between monotherapy and combination therapy groups in the maintenance period in incidences of treatment-emergent adverse event (TEAE), systemic injection reactions (SIR) in combined analysis of CD and UC patients (TEAE 68.0% vs 74.3% [p=0.1989], SIR 3.3% vs 1.4% [p=0.3743], respectively).
A significantly lower incidence of infection was seen with monotherapy during the maintenance period in combined analysis of both studies (26.9 % monotherapy vs 36.4% combination therapy [p=0.0400]). In the combined analysis of both studies, the serious infections were reported for 10 (2.5%) patients in the monotherapy and 3 (2.1%) patients in the combination therapy.
In combined analysis of CD and UC patients, rate of anti-drug antibody [ADA] positive conversion up to W54 was statistically lower in combination therapy group (70.2% monotherapy vs 47.8% combination therapy [p<0.0001]).

Table 1. Proportion of patients achieving efficacy outcomes at W54

CT-P13 SC 120mg in LIBERTY-CD				CT-P13 SC 120mg in LIBERTY-UC
n (%)	Monotherapy (N=160)	Combination therapy (N=71)	P-valuea	n (%)	Monotherapy (N=229)	Combination therapy (N=65)	P-valuea
Clinical remissionb	97 (60.6)	47 (66.2)	0.7194	Clinical remissionh	95 (41.5)	32 (49.2)	0.4119
Endoscopic responsec	81 (50.6)	37 (52.1)	0.9492	Endoscopic-histologic mucosal improvementi	78 (34.1)	27 (41.5)	0.4763
Clinical responsed	103 (64.4)	49 (69.0)	0.7686	Clinical responsej	124 (54.1)	34 (52.3)	0.5760
Corticosteroid-free remissione	27/76 (35.5)	13/23 (56.5)	0.4875	Corticosteroid-free remissionk	32/94 (34.0)	12/26 (46.2)	0.1966
Clinical remission (alternative definition)f	89 (55.6)	42 (59.2)	0.5647	-	-	-	-
Endoscopic remissiong	55 (34.4)	25 (35.2)	0.8439	-	-	-	-
a The nominal p-value was obtained from Cochran-Mantel-Haenszel test b Clinical remission at Week 54, defined as an absolute Crohn’s disease activity index (CDAI) score of <150 points c Endoscopic response at Week 54, defined as a 50% decrease in Simplified endoscopic activity score for Crohn’s disease (SES-CD) score from the baseline value d Clinical response at Week 54, defined as a decrease in CDAI score of 100 points or more from the baseline value e Corticosteroid-free remission at Week 54, defined as being in clinical remission (by an absolute CDAI score of <150) in addition to not receiving any corticosteroids for at least 8 weeks prior to Week 54, among the patients who used oral corticosteroids at baseline f Clinical remission at Week 54, defined as Stool frequency subscore of 0 or 1 point, rectal bleeding subscore 0 point, and endoscopic subscore 0 or 1 point g Endoscopic remission at Week 54, defined as an absolute SES-CD score of ≤4 and at least 2-point reduction from the baseline value with no sub-score of >1 h Clinical remission at Week 54, defined as modified Mayo score with stool frequency subscore of 0 or 1 point, rectal bleeding subscore 0 point, and endoscopic subscore 0 or 1 point i Endoscopic-histologic mucosal improvement at Week 54, defined as absolute endoscopic subscore of 0 or 1 point from modified Mayo score and an absolute Robarts Histopathology Index (RHI) score of 3 points or less with an accompanying lamina propria neutrophils and neutrophils in epithelium subscore of 0 point j Clinical response at Week 54, defined as decrease in modified Mayo score from baseline of at least 2 points and at least 30%, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1 point k Corticosteroid-free remission at Week 54, defined as being in clinical remission (by modified Mayo score) in addition to not requiring any treatment with corticosteroid for at least 8 weeks at Week 54, among the patients who used oral corticosteroids at baseline

Conclusion

No statistical differences in efficacy outcomes at W54 were observed between monotherapy and combination therapy in CD and UC patients. Concomitant IS use was associated with less ADA formation, whereas more infections are seen for combination therapy during maintenance period in CD and UC patients. The overall safety profile during maintenance period was otherwise comparable between monotherapy and combination therapy in CD and UC patients. This post-hoc analysis suggests limited benefit of concomitant IS with CT-P13 SC but a higher infection risk. Notably, patients were not randomized according to IS use nor were the studies ‘powered’ to demonstrate differences.

References

1 Colombel JF et al. DOP86 Subcutaneous infliximab (CT-P13 SC) as maintenance therapy for Crohn’s disease: A phase 3, randomised, placebo-controlled study (LIBERTY-CD). Journal of Crohn’s and Colitis. 2023;17(Supplement_1):i161-i162
2 Sands BE et al. P492 subcutaneous infliximab (CT-P13 SC) as maintenance therapy for ulcerative colitis: A phase 3, randomized, placebo-controlled study: Results of the Liberty-UC Study. Journal of Crohn's and Colitis. 2023;17(Supplement_1):i623–i624.

Disclosure

- S. Schreiber: Consultancy and personal fees from AbbVie, Arena, BMS, Biogen, Celltrion, Celgene, Falk, Ferring, Fresenius, Gilead, HIKMA, IMAB, Janssen, MSD, Mylan, Pfizer, Protagonist, Provention Bio, Sandoz, Takeda, and Theravance.
- J.F. Colombel: Receiving research grants from AbbVie, Janssen Pharmaceuticals and Takeda. Receiving payment for lectures from AbbVie, Amgen, Allergan, Inc. Ferring Pharmaceuticals, Shire, and Takeda. Receiving consulting fees from AbbVie, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, BMS, Celgene Corporation, Eli Lilly, Ferring Pharmaceuticals, Galmed Research, Genentech, Glaxo Smith Kline, Janssen Pharmaceuticals, Kaleido Biosciences, Imedex, Immunic, Iterative Scopes, Merck, Microbia, Novartis, PBM Capital, Pfizer, Protagonist Therapeutics, Sanofi,Takeda, TiGenix, Vifor. Hold stock options in Intestinal Biotech Development.
- S.B. Hanauer: Consultancy from AbbVie, Allergan, Amgen, Arena, Astra Zeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cosmos, Catalys Pacific, Covance, Genentech, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Progenity, Prometheus, Receptos, Salix, Samsung Bioepis, Seres Therapeutics, Sorriso, Takeda, TLL, UCB, Vhsquared. Clinical Research for AbbVie, Allergan, Amgen, Celgene, Genentech, GSK, Janssen, Lilly, Novartis, Pfizer, Prometheus, Receptos, Takeda, UCB. Speaker for AbbVie, Bristol Myers Squibb, Janssen, Pfizer, Takeda. Independent Data Monitoring Conference for Arena, Boehringer Ingelheim, Bristol Myers Squibb, Gossamer, Prometheus, Protagonist.
- W.J. Sandborn: Consulting fees from Abbvie, Abivax, Alfasigma, Alimentiv, Beigene, Biora (Progenity), Celltrion, Forbion, Genentech, Gossamer Biosciences, Index Pharmaceuticals, Prometheus Biosciences, Protagonist Therapeutics, Shoreline Biosciences, Vedanta Biosciences, Ventyx Biosciences, Zealand Pharma. Stock or stock options from BeiGene, Gossamer Bio, Biora (Progenity), Prometheus Biosciences, Prometheus Laboratories, Shoreline Biosciences, Ventyx Biosciences, Vimalan Biosciences, Vivreon Gastrosciences. Employee at Shoreline Biosciences and Ventyx Biosciences.
- B.E. Sands: Consultant/ Speaker’s fees from AbbVie, Abivax, Adiso Therapeutics, Alimentiv, Amgen, Arena Pharmaceuticals, Artizan Biosciences, Artugen Therapeutics, AstraZeneca, Bacainn Therapeutics, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Calibr, Celltrion Healthcare, ClostraBio, Connect Biopharm, Cytoki Pharma, Eli Lilly and Company, Entera, Evommune, Ferring, Fresenius Kabi, Galapagos, Gilead, Genentech, Glaxo SmithKline, Gossamer Bio, HMP Acquisition, Imhotex, Immunic, InDex Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Ironwood Pharmaceuticals, Janssen, Johnson & Johnson, Kaleido, Kalyope, Merck, MiroBio, Morphic Therapeutic, MRM Health, OSE Immunotherapeutics, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, RedHill Biopharma, Sun Pharma Global, Surrozen, Synlogic Operating Company, Takeda, Target RWE, Theravance Biopharma R&D, TLL Pharmaceutical, USWM Enterprises, Ventyx Biosciences, Viela Bio. Stock options from Ventyx Biosciences.
- S. Danese: Consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial, Vifor. Reports lecture fees from Abbvie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer, Takeda.
- S.J. Lee, S.H Kim, Y. Bae, S. Lee, S.G. Lee, J.H. Lee, J.M. Kim, S. Yang, J. Lee, G. Park, J. Lee: Employee of Celltrion, Inc.

Introduction

Anti-tissue transglutaminase IgA antibodies (tTG) are used in the follow-up of celiac disease (CD) to assess adherence to a gluten-free diet (GFD). Persistent positivity may indicate the need for histological reassessment. There is limited information about the rate of complete normalization of tTG and associated factors. Our objective was to evaluate the percentage, kinetics, and factors related to tTG normalization.

Aims & Methods

This was a retrospective observational study including patients with tTG testing at diagnosis and follow-up monitoring of these antibodies from 1991 to 2023 in a specialized unit dedicated to patients with CD. Inclusion criteria were: patients over 16 years of age at diagnosis, initially elevated tTG titres, and at least one serological follow-up after starting a GFD. Time to tTG normalization was estimated using the Kaplan-Meier method. Comparisons between groups were performed using the log-rank test. The association between demographic and clinicopathological characteristics at diagnosis and time to tTG normalization was assessed using Cox regression analysis.

Results

A total of 179 patients were included (75% female, mean age 40 ± 16 years). Duodenal atrophy was present in 81%, and 79% had symptoms. 83% strictly adhered to a GFD. Median follow-up was 3 years. The incidence rate of tTG normalization was 35% per patient-year. The cumulative tTG normalization rate was 38% (95% CI: 30-45) at 1 year, 61% (53-69) at 2 years, 70% (63-77) at 3 years, 80% (73-87) at 4 years, 81% (74-89) at 5 years, and 95% (88-100) at 10 years. The median time to tTG normalization was 24 months (95% CI: 20–28). Table 1 shows Kaplan–Meier estimates expressed as percentages of tTG normalization by adherece to GFD and baseline tTG. In the multivariable analysis, two factors were found to be significantly associated with the normalization of tTG: lower baseline tTG and good adherence to a GFD. Regarding baseline tTG level, patients with titres ≤ 286 U/ml (median) had 2.46 times higher likelihood of antibody normalization compared to those with higher titres (HR: 2.46; 95% CI: 1.69–3.56; p < 0.001). Regarding adherence to a GFD, patients who followed a strict GFD had 5.38 times higher likelihood of tTG normalization (HR: 5.38; 95% CI: 2.79–10.36; p < 0.001).

Table 1. Kaplan–Meier estimates expressed as percentages of normalization (with 95% CIs) after CD diagnosis, by adherece to GFD and baseline tGA titres.

Months		12	24	36	48	60
GFD	Yes	43 (35-51)	69 (60-76)	79 (70-85)	89 (83-94)	91 (84-95)
	No	11 (0.2-22)	26 (10-42)	31 (13-49)	37 (15-59)	-
Baseline tTG titres	≤ 286*	56 (45-66)	80 (71-89)	83 (75-92)	85 (77-94)	-
	> 286*	19 (11-27)	42 (31-53)	56 (44-68)	75 (63-86)	77 (66-88)

​
​
​
​CD: celiac disease; GFD: gluten-free diet; tTG: anti-tissue transglutaminase IgA antibodies; CI: confidence interval; *median​

Conclusion

1. The incidence rate of tTG normalization in CD patients after initiating a GFD was 35% per patient-year of follow-up.
2. In the long-term (10 years), 95% of CD patients achieved tTG normalization.
3. Lower tTG titres at diagnosis and good adherence to the GFD were predictive factors for tTG normalization.
4. Understanding the kinetics of tTG normalization according to various factors is essential before considering histological reassessment for suspected poor disease progression.