Introduction

The role of early immunomodulator or biologic agent treatment on clinical outcomes in inflammatory bowel disease (IBD) has emerged in the era of precision medicine. We aimed to analyze the impact of early use of immunomodulator or biologic treatment on clinical outcomes of intestinal Behçet’s disease (BD).

Aims & Methods

Of 780 patients with intestinal BD, 342 patients received immunomodulator and 114 patients received biologic treatments between 1997 and 2021 at Severance Hospital, Seoul, South Korea. We compared the cumulative rates of intestinal-BD related hospitalization, emergency room visit, biologics use, and surgery between early treatment group and late treatment group.

Results

179 patients (22.9%) received late immunomodulator therapy after 1 year from diagnosis, and 163 patients (20.9%) received early immunomodulator therapy within 1 year. Age, disease activity index for intestinal BD (DAIBD) score, systemic BD rate, C-reactive protein (CRP) at diagnosis were significantly higher in the early immunomodulatory group than in the late immunomodulatory group. In a Cox regression multivariate analysis, the early immunomodulator group was positively associated with future hospitalization (HR: 2.029, 95% CI: 1.518-2.712, p value<0.001), emergency room visit (HR: 2.018, 95% CI 1.435-2.838, p value<0.001), biologics use (HR: 1.891, 95% CI: 1.182-3.027, p value=0.008), but was negatively associated with future surgery (HR: 0.614, 95% CI: 0.416-0.904, p value=0.014). 81 patients (10.4%) received late biologic agent therapy after 1 year from diagnosis, and 33 patients (4.2%) received early biologic agent therapy within 1 year. Systemic BD rate at diagnosis was significantly higher in the early biologics group than in the late biologics group. In a Cox regression multivariate analysis, the early biologics group was positively associated with future hospitalization (HR: 2.923, 95% CI: 1.754-4.870, p value<0.001), emergency room visit (HR: 2.878, 95% CI: 1.674-4.948, p value<0.001), but early biologic agent therapy was not associated with future surgery (HR: 0.775, 95% CI: 0.383-1.568, p value=0.479).

		Immunomodulator use		Biologics use
		Late use (N=179)	Early use (N=163)	Late use (N=81)	Early use (N=33)
Hospitalization	Event	125 (69.8%)	109 (66.9%)	67 (82.7%)	25 (75.8%)
	Multivariable-adjusted HR (95% CI)a	Referent	2.029 (1.528-2.712)**	Referent	2.923 (1.754-4.870)**
Emergency room visit	Event	93 (52.0%)	84 (51.5%)	56 (69.1%)	22 (66.7%)
	Multivariable-adjusted HR (95% CI)a	Referent	2.018 (1.435-2.838)**	Referent	2.878 (1.674-4.948)**
Intestinal BD-related surgery	Event	88 (49.2%)	41 (25.2%)	48 (59.3%)	10 (30.3%)
	Multivariable-adjusted HR (95% CI)a	Referent	0.614 (0.416-0.904)**	Referent	0.775 (0.383-1.568)
Biologics use	Event	44 (24.6%)	49 (30.2%)
	Multivariable-adjusted HR (95% CI)a	Referent	1.891 (1.182-3.027)**

^a Multivariable model adjusted for the age at diagnosis, sex, health insurance, smoking, appendectomy history, family history of IBD, marriage status, DAIBD score at diagnosis, systemic BD, number of ulcers, shape of ulcers, size of ulcer, depth of ulcers, type of ulcers, and laboratory findings at diagnosis
^*p < 0.10, ^**p < 0.05
HR, hazard ratio; CI, confidence interval; BD, Behçet’s disease; IBD, inflammatory bowel disease; DAIBD, disease activity index for intestinal Behçet’s disease

Conclusion

Intestinal BD patients who took immunomodulator or biological agents at an earlier time had severe disease activity at diagnosis, but were less likely to undergo future surgery, the most important prognostic index of this disease, than those who took later.

Introduction

Intestinal ultrasound (IUS) is a non-invasive modality for monitoring disease activity in inflammatory bowel disease (IBD). While widely used for long-term assessment, its utility in early response evaluation following biologic therapy initiation or modification remains underexplored.

Aims & Methods

This prospective study aimed to assess early ultrasonographic response at week 6 in ulcerative colitis (UC) and Crohn’s disease (CD) patients undergoing induction, dose escalation, or switching of biologic therapy. A total of 24 patients (mean age: 40.1 ± 12.8 years; 54.2% female) were included. Fourteen patients (58.3%) were initiating biologic treatment, 4 (16.7%) underwent dose escalation, and 6 (25%) were switched to another biologic agent. Biologic therapies included infliximab (70.8%), adalimumab (16.7%), and others (12.5%). IUS examination was performed at baseline and at week 6. The following parameters were assessed: bowel wall thickness (BWT), wall stratification, color doppler signal activity and mesenteric fat inflammation. IUS remission was defined as bowel wall thickness less than 3 mm and no color doppler signal. IUS improvement was defined as more than 25% decrease in bowel wall thickness without increase in color doppler signal. IUS activity assesment was performed at the same segment of the bowel at the 6th weeks.

Results

A total of 24 patients were included in the study, with a mean age of 40.1 ± 12.8 years; 13 (54.2%) were female. Seven patients (29.2%) had ulcerative colitis (UC), and 17 (70.8%) had Crohn’s disease (CD). Fourteen patients (58.3%) had newly initiated biologic therapy, 4 (16.7%) underwent dose escalation, and 6 (25%) were switched to a different biologic agent. Anti-TNF agents were used in 21 patients (87.5%), including infliximab in 17 (70.8%) and adalimumab in 4 (16.7%). The remaining 3 patients (12.5%) were treated with other biologic agents. At baseline, the most active intestinal segment on IUS was the terminal ileum in CD patients (9 patients, 52.9%) and the sigmoid colon in UC patients (4 patients, 57.1%) (p = 0.021). At week 6, 11 patients (45.8%) showed ultrasonographic improvement, 9 patients (37.5%) had no change, and 4 patients (16.7%) showed worsening. The baseline mean bowel wall thickness (BWT) of the most active segment was 5.5 ± 1.3 mm, which decreased to 4.4 ± 1.7 mm at week 6. A reduction in BWT was observed in 18 patients (75%), while an increase was seen in 6 patients (25%) (p = 0.002). In multivariate regression analysis, higher baseline bowel wall thickness was identified as an independent predictor of ultrasonographic improvement at week 6 (OR: 3.137; 95% CI: 1.005–9.790; p = 0.04). In patients who showed improvement, bowel wall thickness significantly decreased from baseline 6.2 ± 1.5 mm to 3.7 ± 1.6 mm at week 6 (to; p = 0.003), whereas in patients who worsened, an increase in wall thickness was observed (5.3 ± 1.0 mm to 6.7 ± 1.7 mm; p = 0.068). By disease group, 5 of the UC patients (71.4%) showed ultrasonographic improvement, 1 (14.3%) remained unchanged, and 1 (14.3%) worsened. Among CD patients, 6 (35.3%) showed improvement, 8 (47.1%) had no change, and 3 (17.6%) worsened. However, there was no statistically significant difference in response patterns between the UC and CD groups (p = 0.244).

Conclusion

Intestinal ultrasound at week 6 effectively detected early treatment response, with baseline bowel wall thickness emerging as a predictor of improvement. These results support its use in routine early monitoring of IBD patients on biologic therapy.

References

1. Calabrese E, Rispo A, Zorzi F, De Cristofaro E, Testa A, Costantino G, Viola A, Bezzio C, Ricci C, Prencipe S, Racchini C, Stefanelli G, Allocca M, Scotto di Santolo S, D'Auria MV, Balestrieri P, Ricchiuti A, Cappello M, Cavallaro F, Guarino AD, Maconi G, Spagnoli A, Monteleone G, Castiglione F. Ultrasonography Tight Control and Monitoring in Crohn's Disease During Different Biological Therapies: A Multicenter Study. Clin Gastroenterol Hepatol. 2022 Apr;20(4):e711-e722.
2. Paredes JM, Moreno N, Latorre P, Ripollés T, Martinez MJ, Vizuete J, Moreno-Osset E. Clinical Impact of Sonographic Transmural Healing After Anti-TNF Antibody Treatment in Patients with Crohn's Disease. Dig Dis Sci. 2019 Sep;64(9):2600-2606.

Introduction

The impact of underweight and obesity on clinical outcomes for intestinal Behçet’s disease (BD) is unknown. We aimed to identify the association between body mass index (BMI) and clinical outcomes in patients with intestinal BD.

Aims & Methods

We categorized 760 patients with intestinal BD according to the BMI at diagnosis into four groups (underweight, normal, overweight, obese) at Severance Hospital, Seoul, Korea between 1997 and 2021.We performed a Cox proportional hazard analysis to investigate the predictive capability of BMI for clinical outcomes such as biologics use, surgery, hospitalization and emergency room visit.

Results

Of the 760 patients, 130 patients were classified into underweight group (BMI<18.5), 384 patients into normal group (BMI 18.5~22.9), 152 patients into overweight group (BMI 23~24.9), and 94 patients into obese group (BMI≥25). Patients with a higher BMI group showed significantly lower cumulative rates of biologics use (p trend = 0.001), surgery (p trend = 0.008), hospitalization (p trend = 0.002), and emergency room visits (p trend = 0.003) than those with a lower BMI group. In a multivariate analysis, normal BMI group (HR: 0.667, 95% CI 0.483-0.992, p =0.014), overweight group (HR: 0.589, 95% CI 0.394-0.879, p=0.010), and obese group (HR: 0.515, 95% CI 0.321-0.828, p=0.006) were negatively associated with future hospitalization compared to underweight group. Overweight group (HR: 0.490, 95% CI 0.241-0.996, p =0.049) and obese group (HR: 0.312, 95% CI 0.116-0.840, p =0.021) were negatively associated with future biologics use compared to the underweight group. Normal BMI group (HR: 0.706, 95% CI 0.484-1.029, p=0.070) and obese group (HR : 0.556, 95% CI 0.303-1.020, p=0.058) were negatively associated with future surgery compared to the underweight group. Normal BMI group (HR: 0.711, 95% CI 0.513-0.985, p=0.041) and obese group (HR: 0.602, 95% CI 0.376-0.963, p=0.034) were negatively associated with future emergency room visit compared to the underweight group.

Variables		BMI
		<18.5 (n=130) Underweight	18.5~22.9 (n=384) Normal	23~24.9 (n=152) Overweight	≥25 (n=94) Obese	p value for trend
Biologics use	Event	34 (26.2%)	50 (13.1%)	21 (13.8%)	9 (9.6%)	0.001
	Multivariable-adjusteda	Reference	0.619 (0.366-1.047)*	0.490 (0.241-0.966)**	0.312 (0.116-0.840)**
Surgery	Event	45 (34.6%)	87 (22.7%)	35 (23%)	15 (16%)	0.008
	Multivariable-adjusteda	Reference	0.706 (0.484-1.029)*	0.669 (0.411-1.088)	0.556 (0.303-1.020)*
Hospitalization	Event	87 (66.9%)	194 (50.8%)	69 (45.4%)	46 (48.9%)	0.002
	Multivariable-adjusteda	Reference	0.667 (0.483-0.922)**	0.589 (0.394-0.879)**	0.515 (0.321-0.828)**
Emergency room visit	Event	71 (55%)	144 (37.6%)	61 (40.1%)	32 (34%)	0.003
	Multivariable-adjusteda	Reference	0.711 (0.513-0.985)**	0.775 (0.523-1.149)	0.602 (0.376-0.963)**

*p <0.10
**p <0.05
^aMultivariate Cox proportional hazard analysis, including the confounders such as, age, gender, medical aid, smoking, appendectomy history, family history of BD, marriage status, DAIBD score, extraintestinal manifestation, systemic BD, number of ulcers, shape of ulcers, depth of ulcers, type of ulcers, laboratory findings.

Conclusion

Underweight could affect poor outcomes in intestinal Behçet’s disease. Physicians should pay attention to the patients with underweight and make an effort to improve nutritional status.

Introduction

Biologic therapies such as anti-TNF-alpha agents (infliximab, adalimumab), interleukin modulators, and gut-selective integrin antagonists like vedolizumab have significantly improved outcomes in inflammatory bowel disease (IBD), leading to enduring remission, better quality of life, and reduced surgical intervention and hospitalizations. However, many patients may eventually lose response, often due to factors like the formation of anti-drug antibodies, altered drug metabolism, or individual patient characteristics. Dose escalation—by increasing dosage or reducing intervals—is commonly used to counteract this loss, especially for anti-TNF therapies guided by therapeutic drug monitoring. Vedolizumab poses a greater challenge in this regard due to the lack of standardized monitoring protocols. We aimed to investigate the effectiveness of dose-escalated infliximab, adalimumab, and vedolizumab in IBD patients who worsened after initial response, evaluating outcomes such as treatment persistence and clinical remission, to guide more personalized, cost-effective treatment strategies.

Aims & Methods

We conducted a retrospective analysis of IBD patients who underwent Infliximab (IFX), vedolizumab, or adalimumab (ADA) therapy dose escalation between 2020-2024 at a tertiary IBD centre. Primary outcomes included clinical remission using disease activity scores (Simple Clinical Colitis Activity/SCCAI Index for UC, Harvey-Bradshaw Index/HBI for CD), biochemical markers (CRP, faecal calprotectin) and treatment persistence, evaluated at 3-12 months, 12 months, and annually up to 36 months post-escalation.

Results

A total of 155 patients (median age 31 years, 46% female) were included, of which 89 patients (57%) were prescribed dose-escalated IFX, 48 patients (31%) were prescribed dose-escalated ADA and 18 patients (12%) were prescribed dose-escalated Vedolizumab. Of those included, 118 patients (76%) had Crohn’s disease, 36 patients (23%) had ulcerative colitis (UC) and 1 patient (1%) had indeterminate disease. Indications for dose escalation included secondary loss of response (SLOR) (105/155; 68%) and/or low drug levels (65/155; 42%). Dose-escalated IFX led to significant improvements in disease activity scores at 3 months (HBI: p=0.002; SCCAI: p=0.0003). Improvement in SCCAI was maintained at 12 months (p=0.00007), 2 years (p=0.0008) and 3 years (p=0.025). Improvement in HBI was maintained at 2 years (p=0.01) and 3 years (p=0.049). Significant improvement in CRP following dose-escalated IFX was reported at 3 months (p=0.011), 12 months (p=0.004), 2 years (p=0.006) and 3 years (p=0.03). Dose-escalated ADA led to a significant improvement in HBI at 3 months (p=0.023). This improvement was maintained at 12 months (p=0.005) and 2 years (p=0.008). Early improvement in faecal calprotectin was reported at 3 months (p=0.046). Significant initial improvement in SCCAI following dose-escalated Vedolizumab was reported at 3 months (p=0.043). This improvement was not maintained at any further follow-up points (p>0.05). Minor adverse events were reported in 3 patients receiving dose escalated ADA and in 6 patients receiving dose escalated IFX.

Conclusion

Our study demonstrates that biologic dose escalation is an effective and safe mechanism to recapture clinical remission, with high rates of treatment persistence.

Introduction

Intestinal Behçet’s disease (BD) is a rare chronic intestinal vasculitic disorder and it is often refractory to conventional therapies such as corticosteroids and immunomodulators. We aimed to assess the efficacy and tolerability of anti-tumor necrosis factor alpha (TNF ɑ) in intestinal BD.

Aims & Methods

We retrospectively reviewed 667 patients with intestinal BD registered at the Inflammatory Bowel Disease Clinic of Severance Hospital, Seoul, Korea. Response rates of anti-TNF ɑ treatment, predictive factors of sustained response and relapse were analyzed.

Results

A total of 46 patients with refractory moderate to severe intestinal BD were selected for the anti-TNF ɑ therapy. According to the intention-to-treat (ITT) principle, clinical remission rates were 8.7%, 21.7%, 6.5%, and 8.7%, clinical response rates were 76.1%, 71.7%, 39.1%, and 26.1%, and biological response rates were 60.9%, 60.9%, 39.1%, and 26.1%, respectively. According to the per-protocol (PP) principle, clinical remission rates were 8.7%, 25.6%, 13.0%, and 28.6%, clinical response rates were 76.1%, 84.6%, 78.3%, and 85.7%, and biological response rates were 60.9%, 71.8%, 78.2%, and 85.7%, respectively. Previous corticosteroid use more than 20 mg per day (HR: 4.781) and multiple number of ulcers (HR: 8.599) were more likely to have relapse of intestinal BD, and clinical response at 1 month (HR: 0.189) was associated with lowering the relapse. One patient had severe sepsis, 1 patient was diagnosed pneumonia and herpes zoster, and 1 patient experienced otitis externa.

Conclusion

Anti-TNF ɑ therapy could be a useful therapeutic option for refractory intestinal BD with an acceptable efficacy and tolerability profiles.

References

1. Fernandes C, Allocca M, Danese S, Fiorino G. Progress with anti-tumor necrosis factor therapeutics for the treatment of inflammatory bowel disease. Immunotherapy 2015;7(2):175-90.
2. Levin AD, Wildenberg ME, van den Brink GR. Mechanism of Action of Anti-TNF Therapy in Inflammatory Bowel Disease. J Crohns Colitis 2016;10(8):989-97.
3. Atreya R, Zimmer M, Bartsch B, Waldner MJ, Atreya I, Neumann H, et al. Antibodies against tumor necrosis factor (TNF) induce T-cell apoptosis in patients with inflammatory bowel diseases via TNF receptor 2 and intestinal CD14(+) macrophages. Gastroenterology 2011;141(6):2026-38.
4. Vos AC, Wildenberg ME, Arijs I, Duijvestein M, Verhaar AP, de Hertogh G, et al. Regulatory macrophages induced by infliximab are involved in healing in vivo and in vitro. Inflamm Bowel Dis 2012;18(3):401-8.
5. Danese S, Vuitton L, Peyrin-Biroulet L. Biologic agents for IBD: practical insights. Nat Rev Gastroenterol Hepatol 2015;12(9):537-45.
6. Criteria for diagnosis of Behcet's disease. International Study Group for Behcet's Disease. Lancet 1990;335(8697):1078-80.
7. Cheon JH, Kim ES, Shin SJ, Kim TI, Lee KM, Kim SW, et al. Development and validation of novel diagnostic criteria for intestinal Behcet's disease in Korean patients with ileocolonic ulcers. Am J Gastroenterol 2009;104(10):2492-9.

Introduction

The clinical course after surgery in Crohn’s Disease (CD) patients ileo-colonic anastomosis (ICA) is well known. Differently, clinical outcome in patients with entero-enteric anastomosis (EEA) after isolated small bowel resection is undefined.

Aims & Methods

The primary aim of the present case-control study was to search for differences in terms of major clinical outcomes at 5 years between CD patients with EEA (Cases), when compared to CD patients with ICA (Controls) matched for age and smoking status before index surgery. Secondary aim was to compare the characteristics of CD and the disease course before index surgery in Cases versus Controls.
All CD patients with EEA were retrospectively enrolled and matched for age at diagnosis (+/- 5 years) and smoking status before index surgery with 2 CD Controls with ICA. Inclusion criteria: 1) age ≥18; 2) EEA or ICA for CD; 3) ≥5-years follow-up after index surgery. Exclusion criteria: 1) missing data; 2) ostomy; 3) stricturoplasty. Data were expressed as median [range]. The Student-t-test, X2 test, Kaplan-Meier curves and logistic regression analyses were used as appropriate.

Results

Cases included 51 CD patients with EEA (ileum-ileum 39 [76.5%], jejunum-ileum 6 [11.8%], jejunum-jejunum 5 [9.8%], duodenum-jejunum 1 [1.9%]). Matched Controls included 102 CD patients with ICA. At 3 and 5 years after surgery, clinical recurrence was more frequent in Cases (28 [54.9%] vs. 37 [36.3%], p=0.04; 34 [66.7%] vs. 43 [42.2%], p=0.007). Cases showed a higher frequency of CD-related hospitalization ≤5 years after surgery (25 [49%] vs. 23 [22.5%], p=0.001]) (Table). In Cases, corticosteroids use was more frequent at 1, 3 and 5 years (14 [27.5%] vs. 8 [7.8%], p=0.002; 21 [41.2%] vs. 15 [14.7%], p=0.0006; 26 [50.9%] vs. 18 [17.6%], p<0.0001) (Table). ISS and biologics use 3 and 5 years after surgery was more frequent in Cases (20 [39.2%] vs. 20 [19.6%], p=0.01; 21 [41.2%] vs. 24 [23.5%], p=0.03; (15 [29.4%] vs. 13 [12.7%], p=0.02 and 23 [45.1%] vs. 15 [14.7%], p=0.03) (Table). Cases showed a shorter time to survival from clinical recurrence and hospitalization (2.36 [1.29-4.35], p=0.0036; 1.71 [1.06-2.77], p=0.02). EEA and ISS use before index surgery were risk factors for CD-related hospitalization and clinical recurrence at 5 years (2.68 [1.11-6.45]; p=0.02, 2.61 [1.21-5.6]; p=0.01 and 2.53 [1.05-6.09]; p=0.03; 2.44 [1.18-5]; p=0.01).

Conclusion

The clinical outcome after surgery is more severe in CD patients with EEA versus ICA, being associated with a higher rate of clinical recurrence, hospitalization and need of major treatments for the disease. This suggests the need of a tight assessment after isolated small bowel surgery, in order to achieve a timely and appropriate treatment and possible prevention of complications.

References

1) Onali S, Petruzziello C, Calabrese E, Condino G, Zorzi F, Sica GS, Pallone F, Biancone L. Frequency, pattern, and risk factors of postoperative recurrence of Crohn's disease after resection different from ileo-colonic. J Gastrointest Surg. 2009; 13 (2): 246-252.
2) Bemelman WA, Warusavitarne J, Sampietro GM, Serclova Z, Zmora O, Luglio G, de Buck van Overstraeten A, Burke JP, Buskens CJ, Francesco C, et al. ECCO-ESCP Consensus on Surgery for Crohn’s Disease. J. Crohns Colitis. 2017; 12: 1-16.

Introduction

Therapeutic progress in inflammatory bowel disease (IBD) is limited by the lack of understanding of the pathophysiology and the mechanisms involved in response or lack/loss of response to treatments. IBD patients are treated with anti-inflammatory drugs, including biologics such as anti-tumor necrosis factor (TNF) agents, which have been crucial in achieving steroid-free remission and prevention of long-term complications. However, a significant subgroup of patients becomes refractory to these biologicals due to the development of immunogenicity, characterized by the presence of anti-drug antibodies (ADAs). The antibody production and peripheral tolerance are initiated and maintained within lymphoid organs, such as the peripheral lymph nodes, but the exact role of immune cells in these lymphoid structures and whether they are involved in anti-drug antibody (ADA) formation is unknown.

Aims & Methods

We aimed to unravel the pathophysiology behind the development of anti-drug antibodies. Therefore, we performed ultrasound-guided inguinal lymph node needle biopsies from which we isolated leukocytes along with PBMCs from the same patients. Leukocyte populations were analyzed at single cell level via high dimensional phenotyping through mass cytometry (CyTOF).

Results

Using this unique approach, we have so far results from 4 Crohn’s Disease (CD) patients with ADAs (75% females, 50% active disease) and 4 without ADAs (50% females, 75% active disease). Active disease was defined, as an observation of an elevated CRP (c-reactive protein) (>5 mg/L) and/or calprotectin >250 (mg/kg), including symptoms (Harvey-Bradshaw index score > 4 or disease activity index score-CDAI >150).
The proportion of CD4⁺ TEMRA (terminally differentiated effector memory T-cells), CD4⁺ effector and central memory T-cells were increased in the peripheral lymph nodes of patients that developed immunogenicity. Mature NK cells, classical and non-classical monocytes were also increased. Furthermore, the levels of the alpha-4 integrin expression were higher in the lymph node T-lymphocytes, as well as, in the lymph node naïve and memory B-cell subsets in the patient group with ADAs.

Table: Cytometry and Biochemical Characteristics.

Parameters	ADAs (n=4)	no ADAs (n=4)	p-value
Proportion of Lymph Node CD4+ TEMRA T-Cells; median (Range)	5.3 (1.05-16.5)	0.16 (0.1-0.39)	0.02
Proportion of Lymph Node CD4+ Effector Memory T-Cells; median (Range)	3.2 (0.64-7.2)	0.5 (0.14-1.37)	0.049
Proportion of Lymph Node Mature NK-Cells; median (Range)	4.04 (0.49-5.17)	0.08 (0.05-0.2)	0.029
Proportion of Lymph Node Classical Monocytes; median (Range)	4.8 (1.47-16.9)	0.8 (0.91-1.1)	0.027
Proportion of Lymph Node Non Classical Monocytes; median (Range)	6.9 (0.99-9.4)	0.9 (0.68- 0.99)	0.026
Mean alpha-4 Integrin Expression Levels (Effector T-cells)	1.61	0.87	0.03
Mean alpha-4 Integrin Expression Levels (Memory B-cells)	1.58	0.94	0.03
CRP (c-reactive protein) (mg/l); median (Range)	2.85 (0.5-8.5)	3.90 (0.7-14.75)	0.396
Calprotectin (mg/kg); median (Range)	650 (228-1130)	1007 (476-2037)	0.17

Conclusion

Lymph node T-helper cells, monocytes and NK cells potentially play a role in the development ADAs in IBD patients treated with biologics. Although, there was no significant difference in the proportion of naïve and memory B-cells, our findings concerning the alpha-4 integrin expression levels also indicate that both lymph node T and B-lymphocytes, are possibly characterized by a higher migratory potential during immunogenicity conditions.

References

1. Stein RE, Lee DY, Leonard MB, et al. The association between drug levels, anti-drug antibodies, and therapeutic response during infliximab therapy in pediatric Crohn’s disease. J Crohns Colitis 2014; 8: S434.
2. Bodini G, Savarino V, Dulbecco P, et al. The influence of anti-adalimumab antibodies on adalimumab trough levels, TNF-alpha levels and clinical outcome. J Crohns Colitis 2014; 8: S42
3. Stefan S, Sandborn WJ, Choi J, et al. Anti-drug antibodies separate responses of markers of inflammation (c-reactive protein, fecal calprotectin) in Crohn’s disease patients treated with certolizumab pegol. Inflamm Bowel Dis 2014; 20: S68.
4. Strand V, Balsa A, Al-Saleh J, et al. Immunogenicity of Biologics in Chronic Inflammatory Diseases: A Systematic Review. BioDrugs. 2017;31(4):299-316. doi:10.1007/s40259-017-0231-8.
5. Brun MK, Goll GL, Jørgensen KK, et al. Risk factors for anti-drug antibody formation to infliximab: Secondary analyses of a randomised controlled trial. J Intern Med. 2022;292(3):477-491. doi:10.1111/joim.13495.

Disclosure

The authors state no conflict of interest.