Introduction

Patients with inflammatory bowel disease (IBD) have a 2-3 fold increased risk of venous thromboembolic events (VTE) compared to the general population. The relevance of this complication is underlined by increased morbidity, longer hospitalization, additional healthcare cost, the tendency of recurrence, and the potentially fatal outcome.
The etiology of VTE in IBD is complex, modulated by the interplay of disease- and treatment-specific factors. The additive effect of these may be supposed; the role of medication is not precisely defined.

Aims & Methods

The aim of our study was to assess the proportion of VTE in IBD patients treated with anti-tumor necrosis factor-alfa (anti-TNF-α) drugs and conventional anti-inflammatory therapy, namely corticosteroids (CS), immunomodulators (IM) and 5-aminosalicylates (5-ASA).
A systematic search was performed in 5 databases (Pubmed, Embase, Cochrane Library, Scopus, Web of Science) on the 22nd of November, 2022. Population-based data, retrospective cohort, and case-control studies were found eligible for inclusion. Our protocol was prospectively registered on PROSPERO (CRD42022376118).
Based on the number of VTE we determined the proportion of this complication in the mentioned treatment groups. We calculated the odds ratio (OR) with 95% confidence intervals (CI) in the distinct categories of medications. The Joanna Briggs Institute Critical Appraisal Checklist for Prevalence Studies and the Risk of Bias in Non-randomized Studies of Interventions tool were used for quality evaluation.

Results

Out of 10.209 articles, 16 were included in the meta-analysis. A preliminary summary of analyzed data showed, that patients on anti-TNFs had less VTE compared with those treated with CS (proportion: 5%, 95%CI: 3-10 and 15%, 95%CI: 7-29, respectivelly). Comparing these treatments, the OR of VTE was 0.37 (95% CI: 0.21-0.66).
Among patients treated with anti-TNFs or IM we found similar proportions (5%, 95%CI: 3-10 vs. 7%, 95% CI: 4-11) and odds (OR: 0.88, 95% CI: 0.70-1.11) of VTE.
9% (95% CI: 5-17) of patients on 5-ASA medication had VTE; compared with TNF-inhibitors, OR was found to be 1.04 (95% CI: 0.75-0.44).

Conclusion

TNF-α is a driver of inflammation in IBD and may trigger coagulation as well. Inhibition of this key cytokine with biologicals is effective in induction and maintenance of remission in moderate and severe IBD. It may be presumed to have an effect on the risk of VTE as well.
Available literature and our summary of clinical data indicate, that CS therapy may increase the risk of VTE, while anti-TNF agents seem to be linked with decreased odds of these events. As a possible association between TNF-inhibitors and decreased risk of VTE compared with CS, we would like to underline the importance of „steroid-sparing” therapy in patients with high risk of VTE.
The rate of VTE was similar in patients on IM and 5-ASA, relative to TNF-inhibitors. This may be explained by the long-term disease remission maintained with conventional IBD therapy.
Prevention and treatment of VTE should always follow the recommandations of current guidelines.
Our work is limited by the retrospective desing of the studies, the relatively low number of VTE events, the heterogeneity of the IBD population, and the effect of concurrent anti-inflammatory medication used in IBD. To precisely assess the correlation between medication and VTE risk prospective, large, well-conducted studies are needed.

References

References:

1. Yuhara, H.; Steinmaus, C.; Corley, D.; Koike, J.; Igarashi, M.; Suzuki, T.; Mine, T. Meta-analysis: The risk of venous thromboembolism in patients with inflammatory bowel disease. Aliment. Pharmacol. Ther. 2013, 37, 953–962.
2. Fumery, M.; Xiaocang, C.; Dauchet, L.; Gower-Rousseau, C.; Peyrin-Biroulet, L.; Colombel, J.F. Thromboembolic events and cardiovascular mortality in inflammatory bowel diseases: A meta-analysis of observational studies. J. Crohns Colitis 2014, 8, 469–479.
3. Nguyen GC, Bernstein CN, Bitton A, et al. Consensus statements on the risk, prevention, and treatment of venous thromboem‐ bolism in inflammatory bowel disease: Canadian Association of Gastroenterology. Gastroenterology. 2014;146:835–848.e6.
4. Nguyen, G.C.; Sam, J. Rising prevalence of venous thromboembolism and its impact on mortality among hospitalized inflammatory bowel disease patients. Am. J. Gastroenterol. 2008, 103, 2272–2280.
5. Murthy SK, Nguyen GC. Venous thromboembolism in inflammatory bowel disease: an epidemiological review. Am J Gastroenterol. 2011;106:713–718.

Introduction

Proactive therapeutic drug monitoring (TDM) has been suggested to improve outcomes in patients with inflammatory bowel disease (IBD) treated with anti-tumour necrosis factor (anti-TNFα) therapy. A systematic review and a meta-analysis of the literature was conducted to assess treatment efficacy and safety, and a systematic review to compare the cost-effectiveness of proactive TDM versus conventional management during maintenance treatment with anti-TNFα.

Aims & Methods

A search was conducted of MEDLINE, EMBASE, and the Cochrane Library up to January 2022. The primary outcome was the ability to maintain clinical remission at 12 months. The certainty of evidence was determined using the GRADE approach.

Results

Nine studies were identified: one systematic review, six randomised clinical trials, and two cohort studies (for safety evaluation). The analysis of the clinical trials showed no superior efficacy of proactive TDM [relative risk 1.16; 95% confidence interval (CI): 0.98–1.37, n=528; I²=55%]. In contrast, the analysis of the cohort studies and systematic review revealed that proactive TDM could improve the durability of anti-TNFα treatment [odds ratio (OR) 0.12; 95%CI: 0.05–0.27; n=390; I²=45%), prevent acute infusion reactions (OR 0.21; 95%CI: 0.05–0.82; n=390; I²=0%), decrease adverse events (OR 0.38; 95%CI: 0.15–0.98; n=390; I²=14%), and reduce the probability of surgery, at lower economical expenditure.

Conclusion

The analysed evidence did not confirm the superiority of proactive TDM of anti-TNFα agents over conventional management. Therefore, proactive TDM should not be recommended for the management of IBD patients receiving maintenance anti-TNFα treatment.

References

1. Vande Casteele N, et al. Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. Gastroenterology. 2015;148(7):1320-1329.
2. D’Haens G, et al. Increasing Infliximab Dose Based on Symptoms, Biomarkers, and Serum Drug Concentrations Does Not Increase Clinical, Endoscopic, and Corticosteroid-Free Remission in Patients With Active Luminal Crohn’s Disease. Gastroenterology. 2018;154(5):1343-1351.
3. Assa A, et al. Proactive Monitoring of Adalimumab Trough Concentration Associated With Increased Clinical Remission in Children With Crohn’s Disease Compared With Reactive Monitoring. Gastroenterology. 2019;157(4):985-996.
4. Syversen SW, et al. Effect of Therapeutic Drug Monitoring vs Standard Therapy During Maintenance Infliximab Therapy on Disease Control in Patients With Immune-Mediated Inflammatory Diseases: A Randomized Clinical Trial. JAMA. 2021;326(23):2375-84.
5. Strik AS, et al. Efficacy of dashboard driven dosing of infliximab in inflammatory bowel disease patients; a randomized controlled trial. Scand J Gastroenterol. 2021;56(2):145-54.
06. D’Haens GR, et al. Higher vs Standard Adalimumab Induction Dosing Regimens and Two Maintenance Strategies: Randomized SERENE CD Trial Results. Gastroenterology. 2022;162(7):1876-90.
07. Papamichael K, et al. Improved Long-term Outcomes of Patients With Inflammatory Bowel Disease Receiving Proactive Compared With Reactive Monitoring of Serum Concentrations of Infliximab. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2017;15(10):1580-1588.e3.

Disclosure

B Novella Arribas, F Rodríguez Salvanés, and P Loeches Belinchón have no conflict of interest. N Manceñido Marcos has served as a speaker and consultant for or received financial support for educational activities from Janssen, Abbvie, Pfizer, Takeda, Ferring, Faes Farma, Dr. Falk Pharma, and Tillots Pharma. G Mora Navarro has served as a speaker and consultant for or has received research and training funding from Sanofi, Lilly, ESTEVE, and AstraZeneca. JP Gisbert has served as a speaker, consultant, and advisory member for or has received research funding from MSD, Abbvie, Hospira, Pfizer, Kern Pharma, Biogen, Takeda, Janssen, Roche, Sandoz, Celgene, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, and Vifor Pharma.

Introduction

Biologic therapies are commonly used for inflammatory bowel disease (IBD) patients. Multiple biologic medicines can now be given both intravenously and subcutaneously. The different administration routes present provide different advantages regarding dose escalation, healthcare resource utilisation, pharmacokinetics, convenience, and safety.^1,2 Comparator effectiveness studies between intravenous and subcutaneous administration are lacking.

Aims & Methods

Our primary outcome was to compare the effectiveness between intravenous (IV) and subcutaneous (SC) biologics in rates of clinical remission. We performed a systematic review and meta-analysis to include all relevant articles from MEDLINE (Ovid), EMBASE, PubMed, and Cochrane central register of controlled trials from January 1^st, 1946 to January 28th, 2024. Studies that compared intravenous and subcutaneous administration of the same biologic therapy in IBD patients and reported effectiveness outcomes were included. Eligible studies had to include one of the following outcomes: [a] Clinical remission or response with a formalised clinical scoring system as defined by each study; [b] CRP remission; [c] faecal calprotectin remission. This study was registered on PROSPERO (CRD42023442675).

Results

Twenty studies met the inclusion criteria for the systematic review. There were only two randomised controlled trials and therefore were not analysed. There were eighteen cohort studies. One study was a prospective clinical trial switch from IV to SC vedolizumab. Twelve were prospective cohort studies. Five were retrospective cohort studies. Ten studies compared vedolizumab, seven studies compared infliximaband one study compared ustekinumab. We excluded the ustekinumab study given it was the only study evaluating ustekinumab. Of the 17 included studies, 15 were whole cohort switches from IV to SC formulations, with only 2 studies having both IV and SC arms. Nine vedolizumab cohort studies were meta-analysed for clinical remission and no difference was found in clinical remission rates between IV and SC administration (RR 0.99; 95% CI 0.88, 1.11). Six infliximab cohort studies were meta-analysed for clinical remission and no difference was found in rates of clinical remission between IV and SC administration (RR 0.91; 95% CI 0.77, 1.08). Four studies reported CRP remission rates (1 infliximab study and 3 vedolizumab studies), and the vedolizumab studies were meta-analysed. Seventy one percent (159/224) of the SC group and 71% (207/291) of the IV group were in CRP remission. The pooled RR was 0.88 (95% CI 0.88, 1.07; p=0.09). We observed a high degree of heterogeneity (I² = 76%). Four studies, all studying vedolizumab, reported faecal calprotectin remission, and they were meta-analysed. Seventy six percent (158/207) of the SC group and 76% (140/183) of the IV group were in faecal calprotectin remission. The pooled RR was 0.99 (95% CI 0.90, 1.09). We observed no heterogeneity (I² = 0%). The quality of the cohort studies was high, with no studies found to be at a high risk of bias.

Conclusion

There was no difference in the effectiveness between subcutaneous and intravenous administration of infliximab and vedolizumab respectively. However, further high-quality studies, particularly head-to-head studies are required to confirm this finding.

References

1. Little RD, Ward MG, Wright E, Jois AJ, Boussioutas A, Hold GL, Gibson PR, Sparrow MP. Therapeutic Drug Monitoring of Subcutaneous Infliximab in Inflammatory Bowel Disease-Understanding Pharmacokinetics and Exposure Response Relationships in a New Era of Subcutaneous Biologics. J Clin Med. 2022 Oct 19;11(20):6173. doi: 10.3390/jcm11206173. PMID: 36294494; PMCID: PMC9605309.
2. Heald A, Bramham-Jones S, Davies M. Comparing cost of intravenous infusion and subcutaneous biologics in COVID-19 pandemic care pathways for rheumatoid arthritis and inflammatory bowel disease: A brief UK stakeholder survey. Int J Clin Pract. 2021 Sep;75(9):e14341. doi: 10.1111/ijcp.14341. Epub 2021 Jul 8. PMID: 33963659; PMCID: PMC8236906.

Disclosure

Dr. Alexander Elford is supported by the Australian Commonwealth government via a Research Training Program Scholarship. Dr Shahed Kamal and Miss Rishni Heldt have no conflicts of interest. A/Prof Christensen has received speaking fees from Abbvie, Janssen, Pfizer, Takeda and Ferring; research grants from Janssen and Ferring Pharmaceuticals and served on the advisory board of Gilead and Novartis. A/Prof. Jonathan P. Segal received speaker fees for Takeda and Abbvie, BMS and Falk Pharma and has a non-restricted grant from Tillots.

Introduction

Inflammatory bowel disease (IBD) and atopic diseases, namely asthma, atopic dermatitis (AD), and atopic rhinoconjunctivitis (AR) show a rising prevalence worldwide and share some genetic and epidemiological risk factors. Consequently, observational studies have explored the potential association between IBD and atopic diseases, with some conflicting data.

Aims & Methods

The objective of this study was to systematically review and summarize the current evidence on the co-occurrence of IBD and these atopic diseases.
We searched Medline, Embase, Web of Science and CENTRAL (from inception to August 14, 2022) to identify observational studies on the incidence or prevalence of IBD in atopic diseases (asthma, AD; AR) and vice versa.

Results

We included 23 observational studies (17 cohort, 4 case-control, 2 cross-sectional) on the association between IBD and asthma, comprising approximately 2 million patients; 17 of them showed a positive association and only one study showed a negative association. Nineteen studies (12 cohort, case-controls, 4 cross-sectional) on the association between IBD and AD were included, with approximately 2,6 million patients; 16 showed a positive association and 3 showed no association. We included 4 cohort studies on the association between IBD and AR, covering approximately 2,2 million patients which all showed a positive statistically significant association.

Conclusion

Published literature supports that IBD is associated with asthma, AD and AR, and vice versa. These results may increase gastroenterologists’ awareness for these diagnoses so that timely management can be initiated. Additional research is needed to determine if one disease influences the risk of developing the other or if the frequent co-occurrence of these diseases results from shared genetic, environmental and microbial factors. As far as the author’s know, this is the first systematic review that reports the association between IBD and the three main atopic diseases.

Introduction

Microscopic colitis (MC) is a chronic inflammatory disease of the large bowel characterized by watery diarrhea, stool leakage, and nightly defecation, leading to impaired quality of life. Scarce consistent data suggest the association of MC with certain risk factors.

Aims & Methods

We aimed to assess MC’s lifestyle and medical risk factors.
Our protocol was prospectively registered with PROSPERO (CRD42022286624). We systematically searched three medical databases from inception to the 18th of December 2021 (Pubmed, Embase, and Cochrane). Cohort, case-control, and cross-sectional studies, reporting on the number of risk factors in MC patients compared to controls with or without a histopathological examination, were included. We used the random-effect model to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs). The risk of bias assessment was made with the aid of the QUIPS tool.

Results

The systematic search yielded 7174 articles, and 43 were eligible for the study. Investigating lifestyle factors, current smoking was associated with a 1.64 odd (CI:1.06–2.52), while past smoking had a 1.28 odd (CI: 0.91–1.81) of MC compared to both types of controls. Regarding alcohol consumption, we could only do a comparison to controls who were not examined histologically, and no significant association with MC was found. Similarly, we could not show a significant association between MC and patients’ level of education.
When investigating medical risk factors, we found a twofold increased chance of MC diagnosis in the case of non-steroidal anti-inflammatory drug (NSAID) use (OR =2.07, CI: 1.31–3.27), but the odds of MC were not significantly increased neither in the case of proton pump inhibitors (OR =1.59, CI: 0.65–3.90) nor in the case of selective serotonin reuptake inhibitors (OR =2.10, CI: 0.73–5.98), compared to the overall control group.
Most of the articles were deemed moderate or high risk of bias due to the low number of patients and the lack of confounding factors assessment.

Conclusion

Our data demonstrate a 64% increase in the odds of MC in the case of current smoking, and NSAID use is associated with a twofold risk for MC. Further prospective studies with longer follow-ups are needed to further investigate these associations.

Disclosure

None to declare

Introduction

Patients with inflammatory bowel disease (IBD) can face various challenges, including sexual dysfunction, which refers to any physical or psychological perturbation of sexual health. This can manifest through symptoms such as reduced libido, erectile dysfunction, discomfort during intercourse, and other psychosocial issues that negatively impact patients' quality of life. However, uncertainties remain about the magnitude of this problem

Aims & Methods

Therefore, we aimed to assess prevalence of sexual dysfunction in adult patients with IBD. We conducted a systematic review and meta-analysis examining this issue. MEDLINE EMBASE, EMBASE Classic (from inception to 30th March 2023) were searched to identify observational studies that reported prevalence of sexual dysfunction in adult patients with IBD based on validated screening instruments (Female Sexual Function Index (FSFI) and International Index of Erectile Function (IIEF) for women and men respectively). Data were extracted from published study reports, and pooled prevalence, odds ratios (OR), and 95% confidence intervals (CIs) were calculated.

Results

Of 1017 citations evaluated, 18 articles fulfilled eligibility criteria, containing 2,694 patients with IBD recruited from 13 different countries. The pooled prevalence of sexual dysfunction in patients with IBD, was 50.6% (95% CI 40.8% to 60.5%; I2=96.3%). The OR for sexual dysfunction in patients with IBD versus healthy controls was 2.94 (95% CI 1.99 to 4.35, I2=73.4%). When we considered UC or CD separately, the pooled prevalence of sexual dysfunction was 64.8% (95% CI 45.1% to 82.1%; I2=88.8%) in patients with UC, and 58.3% (95% CI 36.0% to 79.0%; I2=95.3%) in patients with CD. When we conducted subgroup analyses based on sex, the pooled prevalence of sexual dysfunction was higher in females with IBD compared with males (62.7% versus 34.0%), with a four-times higher odds of sexual dysfunction. Similar trends were observed when analysing CD and UC patients separately by sex, although limited data were available for this subgroup analysis. Finally, the pooled prevalence of sexual dysfunction was higher in patients with IBD with active disease compared with inactive disease (75.1% vs 34.2%), with a nine-fold higher odds of sexual dysfunction.

Conclusion

We demonstrated a high prevalence of symptoms of sexual dysfunction in patients with IBD, especially in women with CD. Encouraging gastroenterologists to screen for, and treat, these disorders with a holistic approach might improve quality of life of patients with IBD.

Introduction

The use of biologics has become an increasingly common treatment option for inflammatory bowel disease (IBD). However, data on maternal and fetal exposure to ustekinumab (UST) and vedolizumab (VDZ) remain scarce.

Aims & Methods

This systematic review and meta-analysis aimed to assess the safety of UST and VDZ in pregnant women with IBD. We systematically searched PubMed, Embase, and Cochrane Library databases in March 2025. The inclusion criteria were randomized and non-randomized studies comparing UST and VDZ for the treatment of IBD in pregnant patients and evaluating at least one predefined outcome of interest. Primary outcomes were spontaneous abortion and preterm delivery. Secondary outcomes included live birth, low birth weight, serious infections, neonatal intensive care unit (NICU) admission, and malignancies. Statistical analysis was performed using RStudio, applying a random-effects model to calculate the pooled risk ratios (RRs) for binary outcomes.

Results

This systematic review included six studies. Median maternal age ranged from 30 to 33 years, with similar distributions between groups. The average disease duration ranged from 8 to 14 years. Crohn’s disease was more prevalent in the ustekinumab group, while ulcerative colitis was more common in the vedolizumab group. No statistically significant differences were observed in spontaneous abortion (RR 1.66; 95% CI 0.89–3.10), preterm delivery (RR 0.60; 95% CI 0.31–1.16), live birth (RR 0.97; 95% CI 0.90–1.05), low birth weight (RR 0.65; 95% CI 0.31–1.40), serious infections (RR 1.34; 95% CI 0.39–4.66), NICU admission (RR 1.02; 95% CI 0.56–1.85), or malignancies (RR 1.25; 95% CI 0.67–2.32) between UST and VDZ treatments.

Conclusion

No significant differences were observed across the outcomes analyzed when comparing ustekinumab and vedolizumab for the treatment of pregnant patients with IBD.