Introduction

Several viral respiratory infections have been implicated in the exacerbation of immune mediated inflammatory diseases (IMID)^1-3. There has however been limited investigation and conflicted findings of the long-term outcomes in inflammatory bowel disease (IBD) following COVID-19⁴. We therefore performed a systematic review and meta-analysis of the long-term impact of SARS-CoV-2 infection on the disease course of IBD.

Aims & Methods

To understand the impact of early SARS-CoV-2 variants and to be better prepared for future variants, we aimed to carry out a meta-analysis of the available evidence. We searched MEDLINE and EMBASE for studies investigating the risk of adverse IBD-related outcomes (IBD flares, change in disease activity, change in medication, IBD-related hospitalization, and surgery) following a SARS-CoV-2 infection, compared to IBD patients without a SARS-CoV-2 infection. ROBINS-E for observational studies was used to assess the risk of bias in the included studies. We used random effects model (REM) meta-analysis to calculate pooled hazard ratios (HR) for the risk of adverse IBD outcomes following the acute phase of COVID-19 infection. Subgroup meta-analysis was carried out to assess the risk of the outcomes by IBD subtype (Crohn’s disease (CD) and ulcerative colitis (UC)). Meta-regression was undertaken to assess whether sex or duration of follow-up were significant predictors of IBD-related outcomes.

Results

A total of 3119 studies were identified of which 5 studies were eligible for inclusion after screening using the pre-defined inclusion criteria. The studies were based on cohorts from Denmark, Italy, the US, and a pan-European consortium including a total of 34,977 SARS-CoV-2 positive IBD patients and 53,270 IBD patients without a recorded SARS-CoV-2 infection. Two studies were assessed as having a high risk of bias. REM meta-analysis did not show an increased risk of adverse IBD-related outcomes in IBD patients with a recorded SARS-CoV-2 infection compared to those without (HR:1.05, 95% CI:0.75-1.46) and substantial between-study heterogeneity was identified in the included studies (I2=91%, p<0.01). There was no significant difference in adverse IBD-related outcomes between CD and UC patients (CD HR: 0.91, 95% CI: 0.82-1.02; UC HR: 0.83, CI: 0.75-0.90). Following meta-regression, neither sex nor duration of follow-up were found to be significant predictors of individual study effect size.

Study	Country	Source Population	Study Period	COVID-19 cohort	Reference cohort	Summary estimates with 95% CI: type of relative estimate	Adverse IBD-outcome	ROBINS-E overall Risk of Bias (RoB)‡
Papa et al., (2022)	Italy	IBD patients from 5 Italian treatment centers	Oct 2020 -Mar 2021 (6)	95	190	0.42 (0.08- 2.15): HR	Need for therapy intensification	High RoB
Hadi et al., (2022)	USA	TriNetX (40+ US Health Care Organizations)	Jan 2020 – Mar 2021 (3)	4310	22508	1.33 (1.18-1.51): RR	Inpatient hospitalisation along with a collection of stool studies, intravenous methylprednisolone requirement or flexible sigmoidoscopy	High RoB
Hong et al., (2022)	USA	5 academic medical centers within New York's Crohn's & Colitis Organization	Feb 2020 – Dec 2021 (11)	251	251	0.84 (0.44–1.42): HR	IBD-related hospitalisation/surgery	Low RoB
Bezzio et al., (2022)	Italy	IG-IBD Italian cohort	Mar 2020 – Dec 2020(7)	219	219	1.48 (0.90-2.42): OR	Change in HBI or PMS	Some concerns
Nørgård et al., (2023)	Denmark	Danish National IBD Cohort	Mar 2020 – Jul 2022(6)	30102	30102	0.85 (0.79-0.91): IRR	Corticosteroid prescription	Some concerns
Amiot et al., (2022)	EU I-CARE cohort†	I-CARE European prospective longitudinal multicenter cohort	Apr 2020 – Dec (9)	233	5224		Change in HBI or SCCAI	Some concerns
Lukin et al., (2021)	USA	I-CARE European prospective longitudinal multicenter cohort	(6 months)	118	118		Change in HBI or PMS	Some concerns

Abbreviations: HR- Hazard Ratio, RR – Relative Risk, OR – Odds Ratio, IRR – Incidence Rate Ratio, HBI – Harvey Bradshaw Index, SCCAI – Simple Clinical Colitis Activity Index, PMS – Partial Mayo Score.
^† Belgium, Denmark, France, Germany, Greece, Hungary, Ireland, Israel, Italy, the Netherlands, Poland, Portugal, Spain, Sweden and the United Kingdom.
^‡The studies are rated as having a high risk of bias, some concerns or low risk of bias.

Conclusion

In this systematic review and meta-analysis, we find that SARS-CoV-2 infection does not increase the risk of long-term adverse IBD-related outcomes. High-quality studies with longer follow-up periods are required to understand the long-term impact of SARS-CoV-2 infection on IBD outcomes.

References

1. Khan RR, Lawson AD, Minnich LL, Martin K, Nasir A, Emmett MK, et al. Gastrointestinal Norovirus Infection Associated With Exacerbation of Inflammatory Bowel Disease. J Pediatr Gastroenterol Nutr. 2009 Mar;48(3):328.
2. Ozdemir B, Atay A, Kayhan MA, Ozin YO, Gokce DT, Altunsoy A, et al. Tissue quantitative RT–PCR test for diagnostic significance of cytomegalovirus infection in patients with inflammatory bowel disease and treatment response: Cytomegalovirus infection in patients with inflammatory bowel disease. Medicine (Baltimore). 2023 Aug 4;102(31):e34463.
3. Dimitroulia E, Pitiriga VC, Piperaki ET, Spanakis NE, Tsakris A. Inflammatory Bowel Disease Exacerbation Associated With Epstein-Barr Virus Infection. Dis Colon Rectum. 2013 Mar;56(3):322.
4. Zollner A, Koch R, Jukic A, Pfister A, Meyer M, Rossler A, et al. Postacute COVID-19 is Characterized by Gut Viral Antigen Persistence in Inflammatory Bowel Diseases. Gastroenterology. 2022;163(2):495–506.

Disclosure

Professor Charlie Lees has acted as a speaker and/or consultant to AbbVie, Janssen, Takeda, Pfizer, Galapagos, GSK, Gilead, Vifor Pharma, Ferring, Dr Falk, BMS, Boehringer Ingelheim, Novartis, Sandoz, Celltrion, Cellgene, Amgen, Samsung Bioepis, Fresenius Kabi, Tillotts, Trellus Health and Iterative Health.

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

The management of patients with inflammatory bowel disease (IBD) during the coronavirus disease 2019 (COVID-19) pandemic has been a challenge, as immunosuppressant therapies comprise the cornerstone of IBD treatment and social distancing is recommended to diminish the virus spread. The aim of this study is to investigate the impact of COVID-19 on the therapeutic decisions and management of patients with IBD.

Aims & Methods

Records from patients diagnosed with ulcerative colitis (UC), Crohn’s disease (CD) and unclassified-IBD (IBD-u), under follow-up by a single IBD center, were retrospectively screened from March 2020 to May 2021. Primary and secondary outcomes were predetermined to be changes in therapeutic decisions and monitoring respectively, during the pandemic.

Results

A total of 201 patients were included in the study [125 (62%) UC, 69 (34%) CD and 7 (3%) IBD-U]. Patients with UC were treated with 5-aminosalicylic acid [(5-ASA), 89], infliximab [(IFX), 21], combination therapy with 5-ASA and azathioprine (AZA), (11) and adalimumab [(ADA), 4)]. To avoid hospital environment, two patients under IFX (10%) switched to subcutaneous home-infusions with ADA and in eight patients treated with IFX (38%), infusion intervals increased to ten weeks (drug holiday). No complications were observed. Patients with CD were treated with IFX (39), ADA (12), vedolizumab (8), AZA (4), combination therapy with AZA or methotrexate (4) and ustekinumab (2). To avoid hospital environment, two patients under IFX (5%) switched to subcutaneous home-infusions with ADA and in 12 patients treated with IFX (30%), infusion intervals increased to ten weeks (drug holiday). One patient in clinical remission discontinued IFX and received AZA. Although a significant number of outpatient visits, endoscopic procedures and non-urgent surgeries were postponed, two patients with CD (IFX) required emergency surgery which was performed without delay. Patients’ monitoring was carried out through telemedicine (remote monitoring, intangible prescription and drug home delivery).

Conclusion

The vast majority of patients treated with biologics did not discontinue maintenance therapy and a significant number extended intravenous infusion intervals. The setting of this critical and unprecedented situation has led to significant changes in decision making in IBD management, based on patients’ preferences aiming an efficient and safer care.

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

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.