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

Non-invasive biomarkers are needed to improve the management of eosinophilic esophagitis (EoE). We investigated whether eosinophil and lymphocyte counts could be used to diagnose EoE among patients with dysphagia and assess histological, endoscopic, and clinical disease activity in patients with known EoE.

Aims & Methods

This was a prospective study conducted at four EoE referral centers (Pisa, Padova, Humanitas Research Hospital, Milano Policlinico San Donato). We enrolled consecutive patients undergoing esophagogastroduodenoscopy (EGD) for suspected or known EoE who had performed blood counts within one month before EGD. Histological remission and non-EoE-related dysphagia (NED) were defined according to current guidelines on EoE. Endoscopic characteristics were classified according to the EoE reference score (EREFS). Demographic, clinical and full blood count data were collected. After the EGD, all patients completed the Dysphagia Symptom Questionnaire over 14 days (DSQ). Kruskal-Wallis Rank Sum Test and Pearson’s Chi-squared were used for comparisons. ROC curve analysis was used to assess the diagnostic accuracy. Spearman’s test was used for correlations. Significance threshold was p<0.05.

Results

We included 210 consecutive patients. Of these, 123 had EoE (58.5% active; 41.5% in histological remission) while 87 had non-EoE dysphagia (NED). Characteristics in Table 1. Absolute eosinophil count (AEC) of active EoE was significantly higher than NED (335 vs 90/mm3; p<0.001), and so was eosinophil percentage (4.6% vs 1.1%; p<0.001), and median lymphocyte percentage (30 vs 27%; p<0.001). ROC curve analysis showed that a cut-off of 155 eosinophils/mm3 had an AUC of 0.85, with 71% specificity and 87% sensitivity for the identification of EoE among patients with dysphagia (Figure 1a). Other ROC analyses on the diagnosis of EoE reported in Table 2. With regards to disease monitoring, only eosinophil counts differed significantly between EoE and NED. Median AEC of active EoE was higher than EoE in remission (335 vs 200/mm3; p<0.01), and so was eosinophil percentage (4.6 vs 1.4%; p<0.001) (Table 3). Based on ROC analysis, a cut-off of 325 eosinophils/mm3 had and AUC of 0.70 for the identification of histological remission in EoE, with a specificity of 52.7%% and sensitivity of 82.3% (Figure 1b) (Table 3). There was modest positive correlation between AEC and the EREFS with Spearman’s Rho of 0.4 (p<0.0001), but there was no correlation between AEC and DSQ scores (Rho= -0.01; p=0.9).

Conclusion

Our results show that the AEC in peripheral blood has good accuracy for the diagnosis of EoE in patients with dysphagia and moderate accuracy for monitoring histological disease activity. In addition, AEC was modestly correlated with endoscopic disease activity (EREFS score) but not with symptoms.

Disclosure

Speaker or Consultancy for Apogee Therapeutics, Dr Falk Pharma, Malesci, JB Pharmaceuticals, Sanofi, Alfasigma

Introduction

Eosinophilic esophagitis (EoE) is a chronic, condition linked to a type 2 inflammatory response and frequently associated to other atopic conditions. EoE may presents either sporadically, or with aggregation of cases within a same family. Limited information has been provided on the differences in clinical characteristics and disease features between sporadic and familiar EoE, largely due to the lack of large patient cohorts.

Aims & Methods

To find differences in sporadic and familiar cases of EoE which may support distinct clinical management, a cross-sectional analysis of the multicenter EoE CONNECT registry was performed. Demographic and clinical from patients recruited at 42 hospitals in 4 European countries were extracted on March 28th, 2025. Information extracted included 1) age at diagnosis and diagnostic delay; 2) symptoms leading to diagnosis; 3) disease endoscopic and histologic features at diagnosis; and 4) atopic concomitances.

Results

	S-EoE	F-EoE
Age at diagnosis (n= 3,179) <18 years old	18.5%	30.6%
Inflammatory Score (n= 2,723)	1.62 ± 1.3	1.93 ± 1.32
Fibrosis Score (n=2,723)	1.04 ± 1.04	0.97 ± 1.08
Fibrosis (n=1,701)	58.6 %	62.8 %
EoE-Phenotype (n=3,017)
Inflammatory	75.9 %	79.6 %
Mixed	12.6 %	8.6 %
Stricturing	11.5 %	11.8 %

Overall, 4,053 patients (75.4 % males, mean age 33.3 ±15.2 years) were analyzed, including 3028 (74.7 %) sporadic (S-EoE), 714 (17.6%) without familiar data and 311 (7.7 %) familiar (F-EoE) cases including 89 families. Among the family forms, n= 76 families showed 2 affected members, n= 11 presented 3 members, and n= 2 with 4 members. In 85/89 families we identified the index case consisting in sons (13), parents (23), siblings (38), or other distant kinships.
The F-EoE forms were diagnosed at younger mean ± SD ages than S-EoE (29.8±15.6 vs. 33.7±15.1; p<0.001) and included a higher proportion of pediatric patients (considered as those below 18 at diagnosis; 30.6% vs. 18.5%; p<0.001)
Symptoms leading to EoE diagnosis were similar across study groups, with slightly higher presences of abdominal pain (as they included more pediatric cases; 7.7% vs. 4.5%; p=0.01) and chocking episodes (7.7% vs. 4.5%; p=0.01) among F-EoE.
Endoscopy presented more severe features according to EREFS among F-EoE (mean ± SD being 2.86 ± 1.66 vs. 2.64 ± 1.68; p=0.054) at the expense of both fibrotic and inflammatory features, despite only the later reach statistical significance (1.93 ± 1.32 vs. 1.62 ± 1.3; p<0.001). Esophageal biopsies exhibited higher mean ± SD peak eosinophil counts in F-EoE cases (57.11 ± 40.7 vs. 52.87 ± 37.97; p=0.04).
F-EoE were more allergic patients, as they presented a higher mean ± SD number of concomitant atopies (1.44 ± 1.25 vs. 1.25 ± 1.22; p=0.009) and all were more common among them, with conjunctivitis and hives reaching statistical significance (p=0.01 and p=0.002 respectively). Overall, a higher proportion of F-EoE had at least one atopy compared to S-EoE (69.4 % vs. 63.8%).

Conclusion

F-EoE seems to present more severely, with earlier onset, more inflammatory load in endoscopy and biopsies and higher concomitant allergic manifestations.

Introduction

Among the constellation of symptoms attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, dysphagia emerged as a rather rare manifestation. This post-COVID-19 dysphagia seems to arise from esophago-gastric junction (EGJ) disorders either triggered or fueled by SARS-CoV-2 infection. New-onset dysphagia is associated with EGJ-outflow obstruction (EGJ-oo) whereas post-COVID-19 aggravation of dysphagia is associated with Achalasia. Available evidence to guide treatment for patients with post-COVID-19 dysphagia are currently lacking.

Aims & Methods

To offer an evidence-based therapeutic approach for patients presenting with post-COVID-19 dysphagia. Patients presenting with post-COVID-19 dysphagia between January 2021-December 2022, underwent esophagogastroduodenoscopy, esophagram, computed tomography and two esophageal high-resolution manometry (HRM) studies 4-8 months apart. The Chicago classification 4.0 was used for HRM diagnosis. SARS-CoV-2 infection was documented through at least one positive reverse transcriptase polymerase chain reaction (RT-PCR) test. Demographics, history of anti-SARS-CoV-2 vaccination, Eckardt scores (ES) were also recorded. A step-up therapeutic approach was applied and evaluated. All patients received proton pump inhibitor (PPI-20mg rabeprazole od) therapy as a first step. If dysphagia and/or vomiting persisted or the patient experienced bolus impaction then pneumatic dilatation (PD) with a rigid 30mm balloon was applied. If dysphagia persisted despite PD then the patient underwent 35mm-PD or per-oral endoscopic myotomy (POEM), based on personal preference and anesthesia eligibility. In the occurrence of type III Achalasia, POEM was offered as second-line treatment. Informed consent was obtained from all patients.

Results

Thirty-two patients (23 females; mean age±SD: 61±8years) were included, eighteen with new-onset dysphagia (median ES:6) and fourteen with aggravation of pre-existing dysphagia (median ES:8 vs 3). All patients with new-onset dysphagia had EGJ-oo whereas those with pre-existing dysphagia exhibited either type II (N=13) or type III (N=1) Achalasia. A female predominance was evident in the EGJ-oo group (female:male ratio of 2.7:1). Achalasia patients exhibited higher median IRP values compared to the EGJ-oo group: 23.1(1.5) vs 17.4(1.7) (P<0.001). In patients with EGJ-oo, dysphagia resolved under PPI treatment over a median(IQR) of 4(2.2) months: IRP 13.4(1.2) vs 17.4(1.7) at baseline (P<0.05). PPI treatment was not effective in the group with pre-existing dysphagia (P=0.8) therefore PD at 30mm was applied in 13 patients and POEM in one patient with type III Achalasia. Interestingly, all patients within the PD-treated Achalasia group required further treatment escalation either PD at 35mm (N=6) or POEM (N=7) for resolution of symptoms. In the 35mm-PD group ES dropped from 8 to 3 (P<0.05) whereas in the POEM-treated group ES dropped from 8 to 1 (P<0.05). POEM was more effective in reducing symptoms compared to 35mm-PD (P=0.003).

Conclusion

Based on HRM, two post-COVID-19 dysphagia phenotypes can be identified each requiring different management. New-onset dysphagia is associated with EGJ-oo and seems to resolve under PPI over time. On the contrary, post-COVID-19 aggravation of dysphagia corresponds to type II or III Achalasia and requires aggressive endoscopic treatment either PD with a larger caliber balloon or POEM, with the latter yielding more favorable results.

References

1. Manolakis A, Trikola A, Chougias D, et al. An elusive manifestation of COVID-19: dysphagia due to esophago-gastric junction disorders. United European Gastroenterology Journal 2022; 10 (Supplement 8)
2. Webler K, Carpenter J, Hamilton V, et al. Dysphagia Characteristics of Patients Post SARS-CoV-2 During Inpatient Rehabilitation. Arch Phys Med Rehabil 2022;103:336-341
3. Lee MY, Oh BM, Seo HG. Prolonged Dysphagia After a COVID-19 Infection in a Patient With Parkinson Disease. Am J Phys Med Rehabil 2021;100:837-839

Disclosure

None