Introduction

Inflammatory digestive diseases can have a major impact on the physical and mental wellbeing of affected patients. Psychosocial factors can alter the behaviour linked to disease and influence treatment outcomes.

Aims & Methods

The aim of this systematic review and meta-analysis was to assess the efficacy and safety of psychological interventions on depression, anxiety, and stress in patients with inflammatory digestive diseases. The study protocol was prospectively registered on PROSPERO (CRD42021282965). The systematic search was conducted on April 1st, 2023 in three medical databases (PubMed, CENTRAL, Embase). Randomized controlled trials (RCTs) that investigated the effects of various psychological interventions on mental and physical health in patients with all types of inflammatory digestive diseases were included. Outcomes were assessed at the end of therapy and at various timepoints during the follow-up period (short-, mid- and long-term follow-up). Owing to the differences in scales and questionnaires, the standardised mean difference (SMD) was used to pool effect sizes, with its corresponding 95% confidence interval (CI). Higgins and Thompson's I² statistics were used to assess heterogeneity.

Results

We included 24 RCTs that investigated the effect of psychological interventions on depressive symptoms, totalling 1572 participants. The pooled analysis found that psychological interventions resulted in a moderate reduction of depression compared to controls (SMD -0.46; 95% CI: -0.75; -0.18; I² 87%). Data from 19 RCTs with 1593 patients also demonstrated a moderate reduction in anxiety symptoms in subjects undergoing psychological interventions (SMD -0.58; 95% CI: -0.94; -0.22; I² 90%). The pooled analysis of 13 RCTs totalling 772 participants found that psychological therapy was associated with a moderate decrease in stress (SMD -0.53; 95% CI: -1.04; -0.03; I² 85%). Additional analysis of follow-up data showed that benefits resulting from treatment gradually decrease, showing no significant difference at the end of the long-term follow-up period.

Conclusion

Psychological interventions effectively improve mental health-related outcomes in patients with inflammatory digestive diseases. Since benefits from therapy seem to decrease during the follow-up period, repeated interventions may be necessary.

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

Thiopurines are widely used for treating inflammatory bowel disease, either alone or in combination with anti-tumor necrosis factor alpha therapy. However, intolerance to thiopurines is common, leading to discontinuation of treatment in over 30% of individuals.

Aims & Methods

This study aims to evaluate the effectiveness of combined therapy of allopurinol with low-dose azathioprine concerning therapeutic response and improvement of therapy tolerance. We performed a systematic review in PubMed, Embase, Cochrane and Web of Science databases, searching for randomized studies that evaluated low-dose azathioprine therapy plus allopurinol versus azathioprine monotherapy. The primary outcome was clinical remission at weeks 14-16. The secondary outcomes were 6-TGN, 6-MMP and FC (fecal calprotectin) levels and FC lesser than 50ug/g rate. The odds ratio (OR) was used for binary outcomes with their respective 95% confidence interval (CI). Heterogeneity was assessed using the Cochran Q test and I² statistics.

Results

The meta-analyses included 3 studies and 237 patients. There was a significant difference favoring low-dose azathioprine plus allopurinol in clinical remission (OR 2.46; 95% CI 1.43 to 4.25; p=0.001; I2=0%) and in 6-MMP levels (MD -2,329.89; 95% CI -3,869.68 to -790.11; p<0.01; I2=94%). There is no difference in 6-TGN levels (p=0.05) and FC levels (p=0.68).

Conclusion

Patients using allopurinol plus low-dose azathioprine showed improved therapeutic adherence while maintaining superior clinical remission rates compared to azathioprine monotherapy.

References

1. Kiszka-Kanowitz M, Theede K, Thomsen SB, Bjerrum JT, Brynskov J, Gottschalck IB, et al. Low-dose azathioprine and allopurinol versus azathioprine monotherapy in patients with ulcerative colitis (AAUC): An investigator-initiated, open, multicenter, parallel-arm, randomised controlled trial. EClinicalMedicine. 2022 Mar;45:101332.
2. Kiszka-Kanowitz M, Theede K, Mertz-Nielsen A. Randomized clinical trial: a pilot study comparing efficacy of low-dose azathioprine and allopurinol to azathioprine on clinical outcomes in inflammatory bowel disease. Scand J Gastroenterol. 2016 Dec;51(12):1470–5.
3. Vasudevan A, Con D, De Cruz P, Sparrow MP, Friedman AB, Garg M, et al. Clinical trial: Combination allopurinol-thiopurine versus standard thiopurine in patients with IBD escalating to immunomodulators (the DECIDER study). Aliment Pharmacol Ther. 2024 Feb;59(4):504–14.

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

Pro-inflammatory diets have been associated with increased depression and anxiety in general populations. Patients with inflammatory bowel disease (IBD) have higher rates of depression and anxiety as compared to the healthy population. Whether the dietary patterns impact mental health outcomes in patients with IBD remains unclear.

Aims & Methods

This study was performed as part of a randomized controlled trial (RCT) designed to identify the impact of a dietary intervention in ulcerative colitis (UC). The goal of this sub-study was to determine if there is a relationship between mental health and dietary patterns in patients with UC utilizing baseline data from the RCT. Patients over the age of 18 years with UC either in clinical remission or with active disease were recruited in Calgary, Alberta. Clinical and demographic data were collected including IBD activity utilizing the partial Mayo score. At enrollment, all patients completed a validated 24-hour dietary recall questionnaire, the Patient Health Questionnaire-8 (PHQ) to assess for depression and the General Anxiety Disorder-7 (GAD) to evaluate for anxiety. In addition, serum and intestinal inflammatory markers (c-reactive protein [CRP]) and stool calprotectin were collected at the time of enrollment. Utilizing this information, the healthy eating index (HEI) and Mediterranean Diet Score (MDS) were calculated. A higher HEI score indicates greater adherence to a general healthy eating pattern while a higher MDS is suggestive of adherence to a Mediterranean diet. Bivariate comparisons were made using Chi-squared and student t-tests. Multivariable regression was also performed controlling for potential confounders.

Results

In total, 30 patients were recruited for this study; 16(53%) were male with a mean age of 38.6 years (standard deviation [SD] =12.0). At the time of enrollment, 12(40%) patients were on corticosteroids for treatment of their UC, 8(27%) were on a biologic, and 5(17%) on an immunomodulator. The mean partial Mayo score in the cohort was 4.5 (SD=3.6, range 0-11) and 13(43%) had a fecal calprotectin greater than 250 μg/g. Among participants, the mean PHQ score was 6.6 (13 with no depression, 8 with mild depression, 4 with moderate, 3 with moderate/severe and no one with severe depression). The mean GAD score was 5.0 (15 with no anxiety, 9 with mild anxiety, 3 with moderate anxiety and none with severe anxiety). In this study, the mean total MDS was 4.8 (SD =1.6, range 1-8) and mean total HEI was 69.0 (SD=9.1, range 53-85). When controlling for age, sex, body mass index, disease activity and corticosteroid use, severity of depression (p=0.03, 95% Confidence interval [CI] -.26 to -.01) and anxiety (p=0.02 95%CI -.34 to -.03) was inversely correlated with total MDS. Of interest, similar associations were not seen with the HEI.

Conclusion

The impact of diet and nutrition on mental health illness is increasingly being recognized in patients with IBD. Patients with UC in this study who had a lower prevalence of anxiety and depression were more likely to be eating a Mediterranean style diet. In contrast, there was no significant association between mental health disease and HEI, suggesting that the Mediterranean diet score is potentially identifying different dietary behaviors. Future studies to establish causality are necessary to better elucidate these relationships.

References

1: 31735529
2: 31294351
3: https://www.frontiersin.org/articles/10.3389/fnut.2021.662357/full
4: Sanada K, Nakajima S, Kurokawa S., Barcelo-Soler A, Ikuse D, Hirata A, et al. Gut microbiota and major depressive disorder: a systematic review and meta-analysis. J Affect Disord. (2020) 266:1–13. doi: 10.1016/j.jad.2020.01102

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.