Introduction

Psychiatric manifestations in individuals with inflammatory bowel disease (IBD) have been the subject of extensive research. Still, uncertainties remain regarding its precise magnitude, its impact on intestinal disease, and the whole burden of psychiatric manifestations.

Aims & Methods

This systematic review aims to synthesize available evidence on the prevalence and impact of psychiatric symptoms, including depression, anxiety, bipolar disorders, and schizophrenia in IBD patients.
A systematic search was conducted in the PubMed/MEDLINE, EMBASE and SCOPUS databases to identify relevant studies published between January 2010 and January 2023. Cross-sectional, case-control, cohort, registry and population studies were selected that addressed the prevalence of depression, anxiety, bipolar disorder, and schizophrenia in people with IBD compared to the general population. A meta-analysis was also conducted to assess the strength of the association. Data extraction and quality assessment were performed.

Results

The search yielded a total of 3209 articles. Although 193 met the inclusion criteria, only 26 studies provided complete data. Overall, the prevalence of psychiatric comorbidities was found to be significantly higher in IBD patients compared to the general population. The analysis revealed a moderate but significant association between IBD and depression, with a calculated pooled odds ratio (OR) of 1.42 (p<.0001). Also, anxiety disorders emerged as a prevalent comorbidity in IBD with a calculated pooled OR of 1.3 (p<.0001). Evidence for the association between bipolar disorders and IBD was limited but significant, with a pooled OR of 1.64 (p<.0001), despite a substantial heterogeneity (I2=94.01%). Only 3 studies examined the association between schizophrenia and IBD, providing widely heterogeneous results, with an inconclusive OR (0.93, p= 0.73).

Conclusion

This systematic review with meta-analysis highlights that psychiatric comorbidities such as depression, anxiety, and bipolar disorders are more prevalent in IBD than in the general population. Depression and anxiety are particularly prevalent. Bipolar disorder is still an under-researched area in the context of IBD. Data on the association between schizophrenia and IBD is sparse and inconclusive and requires further research. Given the findings of this systematic review, there is a need for a deeper understanding of these associations and early detection in order to develop tailored mental health interventions for patients with IBD.

References

1. Jairath V, Feagan BG. Global burden of inflammatory bowel disease. Lancet Gastroenterol Hepatol. 2020;5(1):2-3.
2. Barberio B, Zamani M, Black CJ, Savarino EV, Ford AC. Prevalence of symptoms of anxiety and depression in patients with inflammatory bowel disease: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2021;6(5):359-70.
3. Piovani D, Armuzzi A, Bonovas S. Association of Depression With Incident Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis. Inflamm Bowel Dis. 2023.

Introduction

Disability is a multidimensional concept encompassing physical, psychological, and social limitations that can significantly burden individuals living with inflammatory bowel disease (IBD). However, as disability is shaped by various factors—including cultural, social, and healthcare-related influences that can differ between countries—its prevalence and characteristics may vary globally.

Aims & Methods

We aimed to meta-analyse global data on prevalence of moderate-to-severe disability (MSD) to explore differences in disability prevalence and characteristics by country, IBD subtype, disease activity. MEDLINE EMBASE, EMBASE Classic (from inception to 1^st December 2024) to identify cross-sectional and case-control studies reporting the prevalence of MSD based on validated tools (IBD–Disk and IBD-Disability Index) in adult patients (≥18 years) with confirmed IBD. Data were extracted, and pooled prevalence (PP), odds ratios (OR), and 95% confidence intervals (CIs) were calculated.

Results

The search strategy generated 3089 citations. From these, 160 individual articles appeared to be relevant to the study question and 17 fulfilled the eligibility criteria, containing 8225 patients with IBD recruited from 11 different countries. The pooled prevalence of MSD in patients with IBD was 29.6% (95% CI 22.6-37.1%; I²=98.0%, p<0.01), with no evidence of funnel plot asymmetry (Egger test, p=0.10). The lowest pooled prevalence of MSD was 7.0% in one Dutch study from the Netherlands, and the highest 51% and 52% in two studies from China and Italy, respectively. The pooled prevalence of MSD was higher in patients with IBD with active disease (56.9%, 95% CI 20.3-89.7%, I² = 93.0%, p<0.01) compared with those with inactive disease (27.0%, 95% CI 3.3-62.0%, I² = 93.0%, p<0.01). Based on three studies that reported MSD prevalence in both active and inactive disease, active IBD increased the odds of MSD more than threefold (odds ratio 3.13, 95% CI 1.74-5.64).

Conclusion

The global prevalence of MSD in the IBD population is 29.6%, and even higher among patients with active disease. These findings underscore the value of incorporating disability assessment into both clinical decision-making and routine therapeutic response —especially in the context of disease modification trials.

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

Psychological co-morbidity, including anxiety and depression, is highly prevalent in inflammatory bowel disease (IBD), and associated with worse disease outcomes and increased healthcare utilization. This complex relationship likely arises due to gut-brain axis communication. Treatments targeting this pathway, including psychological therapies, may provide a means of improving psychological health in IBD. However, randomised control trials (RCTs) examining effect of psychological therapies in IBD are conflicting, and a previous meta-analysis demonstrated only short-term improvements in quality of life.

Aims & Methods

To assess whether psychological therapies positively impact psychological health of patients with IBD, we updated our previous systematic review and meta-analysis. RCTs examining the effects of psychological therapies vs. control in adults with IBD were identified by searching MEDLINE, EMBASE, EMBASE Classic, PsychINFO, and the Cochrane central register of controlled trials. Two investigators assessed eligibility of potential studies and extracted data from eligible studies independently. Continuous outcomes assessed included the effect of psychological therapies on measures of psychological health, including depression, anxiety, stress, and quality of life scores. Where data were available, outcomes were assessed both upon completion of therapy, and again at the final point of follow-up. The effect of psychological therapies was summarised using a standardised mean difference (SMD) with 95% confidence intervals (CIs).

Results

In total 25 RCTs were included, reporting data from 2,227 patients with IBD. Nine studies examined effects of psychological therapies in specific populations, including patients with reduced quality of life, elevated stress scores, fatigue, or presence of depressive symptoms. The remaining studies were conducted in unselected patients. In four RCTs, for patients with clinically active IBD, upon completion of treatment, quality of life scores were significantly higher in patients assigned to psychological therapies (SMD = 0.68; 95% CI 0.09 to 1.26, p=0.02), but there was no improvement in anxiety scores (SMD = -1.04; 95% CI -2.46 to 0.39). The effects of psychological therapies for patients with quiescent disease in 21 RCTs are summarized in table 1; psychological therapies led to significantly lower anxiety, depression, and stress scores, and significantly higher quality of life scores at treatment completion. This benefit persisted to final follow-up in trials for depression scores. Effect was strongest with third wave therapies, and in RCTs recruiting selected patients.

Table 1- Effect of Psychological Therapy on measures of psychological health in patients with quiescent IBD.

Conclusion

Psychological therapies exert short-term benefits on all aspects of psychological health for patients with quiescent IBD and improve quality of life in patients with clinically active disease. Future RCTs should examine the effects of these therapies in selected groups of patients with evidence of psychological distress, where benefit is likely to be greatest.

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

In the context of inflammatory bowel diseases (IBD), the involvement of brain-gut interaction has been intensely studied in the last decade. Connections between IBD and mental disorders have been previously studied. Psychiatric symptoms, in particular stress, anxiety, and depression, adversely affect a broad range of outcomes in IBD, including increased risk of disease relapse and poorer response to treatment. Although genetic predisposition is crucial for immune-mediated diseases, it seems that environmental factors could have a great impact. Alterations in circulating miRNA levels have been demonstrated both in IBD and psychiatric diseases, but no study has identified a miRNA pattern underlying the crosstalk between IBD and psychiatric symptoms.

Aims & Methods

The aim of this study was to identify a plasma miRNA-based pattern that could be specific to IBD or associated with the complex phenotypes of IBD in conjunction with stress, anxiety, and depression.
A total of 81 individuals were enrolled in this study. All the patients agreed to undergo a psychiatric consultation and have been screened using the following scales: the Hamilton Anxiety Scale (HAM-A), the Becks Depression Inventory (BDI) and the Perceived Stress Scale (PSS). Based on their IBD diagnosis and psychiatric evaluation, four groups were considered as follows: i) IBD (patients with IBD with no psychiatric symptoms); ii) IBD+SAD (patients with IBD presenting stress, and/or anxiety, and/or depressive symptoms); iii) SAD (patients with a main diagnosis of recurrent depressive disorder); iv) CTRL (individuals without IBD and without psychiatric disorders). The levels of 179 miRNAs have been evaluated by qRT-PCR in the plasma from the entire cohort.

Results

More than 40 miRNAs were identified as differentially expressed among the three patient groups in at least one comparison vs CTRL group.
The IBD vs CTRL comparison demonstrated the differential expression of four miRNAs (miR-333-3p, miR-1260a, miR-320d, miR-423-5p, and miR-486-5p), whereas the SAD vs CTRL comparison indicated an alteration of 28 miRNA levels. Five miRNAs (miR-223-3p, miR-1260a, miR-320d, miR-423-5p, and miR-486-5p) exhibited differential levels across all comparisons, indicating their potential as markers for the complex phenotype combining IBD and SAD. Pearson correlation analyses between the level of miRNAs and psychiatric symptoms evaluated by previously mentioned scales were performed, and several significant correlations were found.

Conclusion

In this study we identified a molecular pattern associated with the complex phenotypes of IBD in comorbidity with psychiatric symptoms. Our results might help to develop new tools for predicting disease evolution and also provide new insights into the gut-brain IBD axis.
This investigation received financial support from ICGEB (Contract No.CRP/22/019, ICGEB Ref. No. CRP/ROU21-01)