Introduction

Looking for reliable markers in the evaluation of nutritional and inflammatory status in the course of inflammatory bowel disease (IBD) constitutes a critical goal in he management of patients. Bioelectrical impedance analysis (BIA) is nowadays believed to serve an important role in the evaluation of body composition in the course of IBD. Simultaneously, noninvasive hematological markers are explored as easy to obtain potential indicators of inflammation. Nevertheless, reliable anthropometric measurements might constitute troublesome parameters to be evaluated in everyday clinical practice and even if we manage to obtain them - it is hard to interpret them in the context of underlying inflammation in the natural history of IBD. Thus, we aimed to explore a new potential model for the estimation of nutritional and inflammatory status in the course of IBD. In the light of the current knowledge, body composition assessed with BIA was not evaluated together with hematological indices in the single study on IBD patients, so far.

Aims & Methods

We decided to look for relationships between parameters of BIA and the results of hematological scales in IBD patients treated with biological agents. We enrolled 93 participants to the survey: 54 patients with Crohn’s diseases (CD) and 39 - with ulcerative colitis (UC). They were treated with one of biologics: infliximab (n=48) or vedolizumab (n=45). We tried to look for notable associations between BIA measurements, clinical scales (CDAI, SES-CD, MAYO) and hematological markers (red blood cell distribution width to platelet ratio - RPR, red blood cell distribution width to lymphocyte ratio - RLR, neutrophil to lymphocyte ratio - NLR and mean platelet volume to platelet ratio - MPR) together with CRP.

Results

Significant dependences were noticed between BIA results, clinical IBD scales, hematological indices and CRP. We did not observe any notable differences according to the type of administered biological agent. In CD group body cell mass (BCM) correlated positively with SES-CD (p<0.05). On the other hand, there was a positive correlation between reactance (Xc) and total MAYO score among UC patients (p<0.05). Furthermore, Xc correlated negatively with MPR in the course of UC (p<0.05). Finally, two more significant relationships were observed in UC group: a positive one between BCM and RPR (p<0.05) and a negative one between extracellular water (ECW) and NLR (p<0.05). Finally, phase angle (PhA) correlated notably in the positive manner with CRP (p<0,005).

Conclusion

Our results give new perspectives for exploring combinations between two different diagnostic strategies in the evaluation of nutritional status in IBD. Achieved results suggest that changes in body composition in IBD patients can be reflected by deviations in hematological scales. Of note, our study group was administered biologics. Perhaps, further investigations could show some kind of certain relationships between the pattern of response on biological agents and the character of results in BIA analysis and hematological indices.

References

1. Kim, Seung Hyuk et al. “Evaluation of nutritional status using bioelectrical impedance analysis in patients with inflammatory bowel disease.” Intestinal research vol. 20,3 (2022): 321-328. doi:10.5217/ir.2021.00022
2. Al-Rshaidat, Mamoon M D et al. “Evaluating the clinical application of the immune cells' ratios and inflammatory markers in the diagnosis of inflammatory bowel disease.” Pharmacy practice vol. 21,1 (2023): 2755. doi:10.18549/PharmPract.2023.1.2755
3. Gold, Stephanie L et al. “Review article: Putting some muscle into sarcopenia-the pathogenesis, assessment and clinical impact of muscle loss in patients with inflammatory bowel disease.” Alimentary pharmacology & therapeutics, 10.1111/apt.17498. 13 Apr. 2023, doi:10.1111/apt.17498
4. Soufli, Imene et al. “Nitric Oxide, Neutrophil/Lymphocyte, and Platelet/Lymphocyte Ratios as Promising Inflammatory Biomarkers in Complicated Crohn's Disease: Outcomes of Corticosteroids and Anti-TNF-α Therapies.” Inflammation, 10.1007/s10753-023-01796-4. 4 Mar. 2023, doi:10.1007/s10753-023-01796-4
5. Zalizko, Polina et al. “The role of body muscle mass as an indicator of activity in inflammatory bowel disease patients.” Clinical nutrition ESPEN vol. 40 (2020): 193-200. doi:10.1016/j.clnesp.2020.09.023

Introduction

The combination of two biological agents or a biological agent with novel small molecules, known as advanced combination therapy (ACT), for inflammatory bowel disease (IBD) has shown promising results in phase II studies as well as in real world studies. We describe the real-world experience of 2 Swiss IBD referral centers.

Aims & Methods

A chart review of all IBD patients on ACT from June 2020 to December 2023 was performed in Bern University hospital and the Crohn and Colitis Center Lausanne (Gastro-entérologie Beaulieu SA). Data on disease duration, extension, previous or concomitant treatments as well as efficacy and safety were collected prospectively.

Results

Disease	Combination of advanced therapy (number of patients)	Partial or complete Clinical or biological response	Adverse effects, Infections
Ulcerative colitis (N=11)	Vedolizumab / Tofacitinib (5)	2/5 (40%)	none
	Vedolizumab / Anti-TNFs (3)	2/3 (50%)	none
	Vedolizumab /Cyclosporin or Tacrolimus (2) Ustekinumab / Tacrolimus (1)	1/2 (50%) 1/1 (100%)	none
Crohn’s disease (N= 17)	ustekinumab (5)/ Anti-TNFs(infliximab (1), adalimumab (4))	5/ 5 (100%)	Eczema, tumefaction left parotide
	ustekinumab (4) / JAK inhibitors Upadacitinib,(3) , Tofacitinib (1)	4/4 (100%)	Lymphoma, mycosis, otitis media, lymphopenia, CMV ileitis
	Vedolizumab / Infliximab (1) Vedolizumab / Tacrolimus	0/1 (0%) 1/1 (100%)	none
	Vedolizumab / Upadacitinib (3)	3/3 (100%)	Acnea, Headache, nausea
	Anti-TNF(adalimumab (2), cimzia (1) / Upadacitinib (3)	2/3 (66%)	Ophthalmic zona
Total		21/28 (75%)	11 events (14%)

A total of 25 IBD patients (48% women, 10 ulcerative colitis, 15 Crohn’s disease) received 28 ACT. The indications were extended and refractory luminal disease and/or extraintestinal manifestations. The 25 patients were all steroid dependent or refractory and half of them were either refractory or intolerant to at least two anti-TNF alpha agents. These treatments were started after a median disease duration of 5 years (range 1-31). The mean duration of ACT was 10 months (range 1-40). Most frequent ACT combinations were vedolizumab or ustekinumab combined with either JAK inhibitors or TNF- alpha inhibitors. A partial or complete response was observed in 21/28 therapies (75%) with a mean decrease of CRP of 9,4 mg/l (range - 23 to + 59). Among responders, a median decrease of calprotectin by 871 mcg/g (range 0 – 4002; N=8, skewed) was observed. Concerning safety, 3 infections (ophthalmic herpes zoster, otitis media, cutaneous fungal infection) and 1 case of Non-Hodgkin Lymphoma, were reported. 8 minor adverse events (left parotid gland, tumefaction, eczema, 2 patients with lymphopenia, acne nausea and headaches) were reported, with mostly small molecules implicated. One patient had a successful pregnancy and delivery on combined adalimumab and ustekinumab ACT.

Conclusion

Vedolizumab or ustekinumab combined with either JAK or TNF- alpha inhibitors were the most frequent combinations of ACT in this cohort of severe and steroid-dependent/refractory IBD patients. 75% of patients achieved a clinical /biological response. Small molecules appear to be associated with of lymphopenia, and minor infections. There was one case of Non-Hodgkin Lymphoma while receiving ustekinumab and tofacitinib ACT in the context of previous long exposure to adalimumab.

Disclosure

Marianne Vuillèmoz and Maude Martinho Grueber disclose consulting fees from Bristol Myers Squibb. Giulia Santi has nothing to disclose. Pascal Juillerat discloses consulting and speaker fees from AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Ferring Pharmaceuticals, Gilead Sciences, Janssen, Merck Sharp & Dohme, Pfizer, Pierre Fabre, Sandoz, Takeda, Tillotts Pharma AG, and UCB Pharma. Pierre Michetti discloses a grant form Iqone and personal fees from Takeda, Ferring, Hospira, Janssen, Pfizer, UCB Pharma, Vifor Pharma, Nestlé Health Sciences, MSD.

Introduction

Corticosteroid tapering over a period of 6-8 weeks effectively induces remission in inflammatory bowel disease (IBD). However, prolonged corticosteroid use (lasting more than 3 months) is linked to severe side effects.

Aims & Methods

Detecting and mitigating prolonged use is crucial for optimal care. We conducted a prospective study in 2018 involving 116 IBD patients undergoing biologic therapy at an IBD referral center in Montenegro. We utilized the Steroid Assessment Tool (SAT) as described by Selinger et al., 2017, to assess corticosteroid usage in this cohort.

Results

Of the patients, 61% had ulcerative colitis (UC) and 39% had Crohn's disease (CD). 53% of patients received anti TNF biologics (adalimumab or infliximab), and 47% received anti-integrin therapy (vedolizumab) in the current therapy. In the preceding year 32 patients (28%) had used corticosteroids. Most of those patients (78%) received a single course of steroids, while 19% received two courses, and 3% received three. The duration of steroid use was predominantly three months (78% of patients), with the longest duration being nine months (1 patient). Among steroid users, 81% (26/32) did not develop dependency or relapse after three months, while 19% (6/32) were steroid resistant/dependent.

Conclusion

Our study identified corticosteroid excess in 6.0% of patients. While our findings suggest adherence to corticosteroid recommendations in IBD patients undergoing biologic therapy, there's a need to expand routine monitoring of steroid dependency or excess to all IBD patients, regardless of their biologic therapy history.