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Journal of Crohn's & Colitis Apr 2024Fistulas are a debilitating complication of Crohn's disease [CD]. We conducted a systematic review to assess the efficacy of medical therapies for fistulizing CD. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Fistulas are a debilitating complication of Crohn's disease [CD]. We conducted a systematic review to assess the efficacy of medical therapies for fistulizing CD.
METHODS
MEDLINE, Embase, and CENTRAL were searched on May 26, 2022, for randomized controlled trials [RCTs] of pharmacological therapy in adults with fistulizing CD. The primary outcome was induction and maintenance of fistula response. Pooled risk ratios [RRs] and 95% confidence intervals [CIs] were calculated. GRADE was used to assess the certainty of evidence.
RESULTS
Thirty-eight RCTs were included. Nineteen trials [50%] exclusively involved perianal fistula. The remaining studies included some participants with non-perianal fistula. Pooled RRs for anti-tumour necrosis factor [TNF] agents were not statistically significant for induction [RR 1.36, 95% CI 0.97-1.91] or maintenance of fistula response [RR 1.48, 95% CI 0.97-2.27]. However, in a sensitivity analysis of studies with fistula response as the primary outcome, anti-TNFs were superior to placebo for induction [RR 1.94, 95% CI 1.10-3.41] and maintenance [RR 1.88, 95% CI 1.23-2.88] of fistula response. Oral small molecules [RR 2.56, 95% CI 1.18-5.53] and mesenchymal stem cell [MSC] therapy [RR 1.26, 95% CI 1.01-1.57] were effective for induction of fistula response. Ustekinumab was associated with maintenance of fistula response [RR 1.80, 95% CI 1.04-3.11]. Vedolizumab was not superior to placebo. The certainty of evidence ranged from very low to moderate.
CONCLUSION
Very low- to moderate-certainty evidence suggests that anti-TNF therapy, oral small molecules, ustekinumab, and MSCs are effective for perianal fistulizing CD. Dedicated fistula studies evaluating biologics and small molecules are needed.
Topics: Humans; Crohn Disease; Rectal Fistula; Gastrointestinal Agents; Intestinal Fistula; Randomized Controlled Trials as Topic
PubMed: 37933849
DOI: 10.1093/ecco-jcc/jjad185 -
AJOG Global Reports Feb 2024Obstetrical anal sphincter injury describes a severe injury to the perineum and perianal muscles after birth. Obstetrical anal sphincter injury occurs in approximately... (Review)
Review
OBJECTIVE
Obstetrical anal sphincter injury describes a severe injury to the perineum and perianal muscles after birth. Obstetrical anal sphincter injury occurs in approximately 4.4% of vaginal births in the United States; however, racial and ethnic inequities in the incidence of obstetrical anal sphincter injury have been shown in several high-income countries. Specifically, an increased risk of obstetrical anal sphincter injury in individuals who identify as Asian vs those who identify as White has been documented among residents of the United States, Australia, Canada, Western Europe, and the Scandinavian countries. The high rates of obstetrical anal sphincter injury among the Asian diaspora in these countries are higher than obstetrical anal sphincter injury rates reported among Asian populations residing in Asia. A systematic review and meta-analysis of studies in high-income, non-Asian countries was conducted to further evaluate this relationship.
DATA SOURCES
MEDLINE, Ovid, Embase, EmCare, and the Cochrane databases were searched from inception to March 2023 for original research studies.
STUDY ELIGIBILITY CRITERIA
Observational studies using keywords and controlled vocabulary terms related to race, ethnicity and obstetrical anal sphincter injury. All observational studies, including cross-sectional, case-control, and cohort were included. 2 reviewers followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Meta-analysis of Observational Studies in Epidemiology recommendations.
METHODS
Meta-analysis was performed using RevMan (version 5.4; Cochrane Collaboration, London, United Kingdom) for dichotomous data using the random effects model and the odds ratios as effect measures with 95% confidence intervals. Subgroup analysis was performed among Asian subgroups. The risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal tools. Meta-regression was used to determine sources of between-study heterogeneity.
RESULTS
A total of 27 studies conducted in 7 countries met the inclusion criteria encompassing 2,337,803 individuals. The pooled incidence of obstetrical anal sphincter injury was higher among Asian individuals than White individuals (pooled odds ratio, 1.64; 95% confidence interval, 1.48-1.80). Subgroup analyses showed that obstetrical anal sphincter injury rates were highest among South Asians and among population-based vs hospital-based studies. Meta-regression showed that moderate heterogeneity remained even after accounting for differences in studies by types of Asian subgroups included, study year, mode of delivery included, and study setting.
CONCLUSION
Obstetrical anal sphincter injury is more frequent among Asian versus white birthing individuals in multiple high-income, non-Asian countries. Qualitative and quantitative research to elucidate underlying causal mechanisms responsible for this relationship are warranted.
PubMed: 38283323
DOI: 10.1016/j.xagr.2023.100296 -
Arquivos de Gastroenterologia 2023Fistulizing perianal Crohn's disease poses a treatment challenge, and researchers postulate that this phenotype in young male patients could have a worst outcome.
BACKGROUND
Fistulizing perianal Crohn's disease poses a treatment challenge, and researchers postulate that this phenotype in young male patients could have a worst outcome.
OBJECTIVE
Thus, the aim of this study was to assess whether sex influences the response to treatment for these patients.
METHODS
This systematic review (PROSPERO CRD42022319629) was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. We selected articles published in English, Spanish, Portuguese, and Italian between 2010 and 2020 in the PubMed and Science Direct databases. According to the PICO acronym, prospective studies in patients older than 18 years with the objective of treating fistulizing perianal Crohn's disease were selected. Studies in pediatric populations, retrospective, without treatment objectives, and that included only rectovaginal fistulas or a single sex were excluded. Study quality was assessed using the Cochrane risk of bias tool and Newcastle-Ottawa scale.
RESULTS
Of the 1887 articles found, 33 were included. Most studies used anti-TNF drugs as treatment (n=11). Ten studies had subgroup analyses; of them, the two studies reporting sex differences used infliximab and adalimumab as treatment and showed that women had a longer fistula closure time than men.
CONCLUSION
This systematic review showed that few data corroborate the difference between sexes in the treatment of fistulizing perianal Crohn's disease, possibly having a greater relationship with the phenotype. However, considering the lack of results, further studies with this objective and with standardization of fistulas and response assessment methods are needed.
Topics: Child; Humans; Male; Female; Crohn Disease; Retrospective Studies; Prospective Studies; Tumor Necrosis Factor Inhibitors; Rectal Fistula; Treatment Outcome; Infliximab
PubMed: 38018554
DOI: 10.1590/S0004-2803.230402023-28 -
Cancers Nov 2023Extramammary Paget's disease (EMPD) is subclinical in extent and multifocal in nature. There is no global consensus for treatment, so its management represents a... (Review)
Review
Extramammary Paget's disease (EMPD) is subclinical in extent and multifocal in nature. There is no global consensus for treatment, so its management represents a challenge in clinical practice. Therefore, we conducted a systematic review through the main electronic databases to assess the effectiveness of topical imiquimod in cutaneous EMPD and to discuss its management. Finally, 24 studies involving a total of 233 EMPD patients treated with topical imiquimod were selected. The topical imiquimod response rate was 67%, and the complete response (CR) rate was 48%. Patients were treated with a three-four times a week regimen in most cases, ranging between 2 to 52 weeks. In addition, imiquimod was applied as an adjunctive treatment in 21 patients, achieving a CR rate of 71%. Consequently, imiquimod therapy could achieve a good response ratio as a first-line treatment, as adjuvant and neo-adjuvant therapy, and as a treatment for recurrent disease. The heterogeneity between studies and the lack of a control arm made it impossible to conduct a meta-analysis. To improve the quality of evidence on EMPD, multicenter studies are essential to collect a larger number of patients and, consequently, obtain high-quality evidence to standardize treatment. The Prospero registration number is CRD42023447443.
PubMed: 38067369
DOI: 10.3390/cancers15235665 -
Medicine Jul 2023Traditional Chinese herbal ointment has significant curative effect and few side effects in the treatment of perianal eczema (PE). Currently, there is no systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Traditional Chinese herbal ointment has significant curative effect and few side effects in the treatment of perianal eczema (PE). Currently, there is no systematic evaluation on the treatment of PE with traditional Chinese medicine ointment. The current aim is to systematically evaluate the efficacy of traditional Chinese medicine ointment in the treatment of PE through meta-analysis.
METHODS
Randomized controlled trials on the treatment of PE with Chinese herbal plaster were included in the meta-analysis, which was searched in Chinese and English databases up to March 1, 2023. The search will be conducted in accordance with the object of PICOS framework. Two research will independently use EndnoteX9 to extract the data and evaluate the quality assessment of included trails. Meta-analysis was performed using Revman5.4.1 provided by Cochrane Collaboration; when the outcome indicator is a dichotomous variable, relative risk (RR) was used as the effect size; when the outcome indicator is a continuous variable, weighted mean difference (MD) was used as the effect size, each effect size should be expressed as 95% confidence interval (CI).
RESULTS
The results of meta-analysis showed that: The total effective rate of PE (RR: 1.22, 95% CI: 1.15, 1.30, P < .01; I2 = 32%, Q = 0.17). The cure rate of PE (RR: 3.37, 95% CI: 2.30, 4.94, P < .01; I2 = 21% Q = 0.26). The recurrence rate of PE (RR: 0.25, 95% CI: 0.13, 0.48, P < .01; I2 = 31%Q = 0.23). Itchy points (MD: 0.04, 95% CI: -0.19, 0.27; I2 = 26%) Skin damage area (MD: -0.37, 95% CI: -0.56, -0.19; I2 = 26%). Skin damage form (MD: -0.59, 95% CI: -0.81. -0.36; I2 = 0%).
CONCLUSION
A total of 11 articles were included in this study for meta-analysis, and the results showed that Chinese medicine ointment is more helpful in improving the skin lesion area and skin damage form, significantly improve the response rate and cure rate, reduce the recurrence rate. Chinese herbal ointment has guiding significance for clinical practice which deserve to use ointments by further experimental and clinical investigation.
Topics: Humans; Ointments; Medicine, Chinese Traditional; Eczema; Drugs, Chinese Herbal
PubMed: 37478223
DOI: 10.1097/MD.0000000000034397 -
Journal of Crohn's & Colitis Apr 2024Subcutaneous (SC) infliximab may provide multiple benefits over intravenous (IV) formulations. However, studies for efficacy and safety in inflammatory bowel disease...
BACKGROUND
Subcutaneous (SC) infliximab may provide multiple benefits over intravenous (IV) formulations. However, studies for efficacy and safety in inflammatory bowel disease (IBD) have been constrained by small sizes that limit the interpretation of outcomes, especially for subgroups potentially at high-risk of disease relapse.
METHODS
We conducted a systematic review and random-effects meta-analysis up to January 2023 to evaluate the change in clinical remission after transitioning from IV to SC infliximab in patients with IBD in clinical remission. The primary outcome was measured using the relative risk for meta-analysis.
RESULTS
15 studies of patients established ≥3 months on IV infliximab were identified, consisting of 1371 patients and 840 patient-years of follow-up. There was no loss of clinical remission in the IBD cohort overall, Crohn's disease (CD), and perianal CD p=0.55 & p=0.11 at 9-12 months, and p=0.50 at 6 months respectively). Neither prior IV dose (≤10mg/kg 6-weekly) (p=0.48) nor IBD disease subtype was associated with an increased clinical relapse rate at 6 months (p=0.48 and p=0.45 (UC vs CD), respectively).
CONCLUSION
Changing patients established on IV infliximab to an SC formulation is associated with a high ongoing clinical remission and low adverse event rate. Furthermore, there are no signals for adverse outcomes among different IBD disease subtypes, nor in those on escalated IV infliximab dosing schedules up to 10mg/kg 6-weekly. This data should provide patients and clinicians alike with confidence in SC infliximab use in IBD.
PubMed: 38656784
DOI: 10.1093/ecco-jcc/jjae059 -
Journal of Crohn's & Colitis Aug 2023Ulcerative colitis [UC] and Crohn's disease [CD] can be associated with severe comorbidities, namely opportunistic infections and malignancies. We present the first... (Meta-Analysis)
Meta-Analysis
Anal High-risk Human Papillomavirus Infection, Squamous Intraepithelial Lesions, and Anal Cancer in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.
BACKGROUND
Ulcerative colitis [UC] and Crohn's disease [CD] can be associated with severe comorbidities, namely opportunistic infections and malignancies. We present the first systematic review and meta-analysis evaluating the burden of anal human papillomavirus disease in patients with UC and CD.
METHODS
PubMed, Web of Science, and Scopus were searched until November 2022. Meta-analyses were performed using random effects models. The protocol was recorded at PROSPERO register with the number CRD42022356728.
RESULTS
Six studies, including 78 711 patients with UC with a total follow-up of 518 969 person-years, described the anal cancer incidence rate. For anal cancer incidence rate in CD, six studies were selected, including 56 845 patients with a total follow-up of 671 899 person-years. The incidence of anal cancer was 10.2 [95% CI 4.3 - 23.7] per 100 000 person-years in UC and 7.7 [3.5 - 17.1] per 100 000 person-years in CD. A subgroup analysis of anal cancer in perianal CD, including 7105 patients, was calculated with incidence of 19.6 [12.2 - 31.6] per 100 000 person-years [three studies included]. Few studies described prevalence of anal cytological abnormalities [four studies including 349 patients] or high-risk human papillomavirus [three studies including 210 patients], with high heterogeneity. Prevalence of cytological abnormalities or high-risk human papillomavirus was not associated with pharmacological immunosuppression in the studies included.
CONCLUSION
The incidence of anal cancer is higher in UC than in CD, with the exception of perianal CD. There are limited and heterogeneous data on anal high-risk human papillomavirus infection and squamous intraepithelial lesions prevalence in this population.
Topics: Humans; Papillomavirus Infections; Inflammatory Bowel Diseases; Anus Neoplasms; Anus Diseases; Crohn Disease; Colitis, Ulcerative; Squamous Intraepithelial Lesions
PubMed: 36929761
DOI: 10.1093/ecco-jcc/jjad045 -
Journal of Crohn's & Colitis Mar 2024The optimal treatment of perianal fistulizing Crohn's disease (PFCD) is unknown. We performed a systematic review with meta-analysis to compare combined surgical...
BACKGROUND
The optimal treatment of perianal fistulizing Crohn's disease (PFCD) is unknown. We performed a systematic review with meta-analysis to compare combined surgical intervention and anti-TNF therapy (combined therapy) vs. either therapy alone.
METHODS
MEDLINE, EMBASE, and Cochrane databases were searched systematically through December 2023. Surgical intervention was defined as an exam under anesthesia ± setons. We calculated weighted risk ratios (RR) with 95% confidence intervals (CI) for our co-primary outcomes: fistula response and healing, defined clinically as a reduction in fistula drainage or number of draining fistulas and fistula closure respectively.
RESULTS
Thirteen studies were analysed: 515 patients treated with combined therapy, 330 patients with surgical intervention and 406 patients with anti-TNF therapy with follow-up between 10 weeks and 3 years. Fistula response (RR 1.10; 95% CI, 0.93-1.30, p=0.28) and healing (RR 1.06; 95% CI, 0.86-1.31, p=0.58) was not significantly different when comparing combined therapy with anti-TNF therapy alone. In contrast, combined therapy was associated with significantly higher rates of fistula response (1.25; 95% CI, 1.10-1.41, p<0.001) and healing (RR 1.17; 95% CI, 1.00-1.36, p=0.05) compared with surgical intervention alone. Our results remained stable when limiting to studies that assessed outcomes within 1 year and studies where <10% of patients underwent fistula closure procedures.
CONCLUSION
Combined surgery and anti-TNF therapy was not associated with improved PFCD outcomes compared with anti-TNF therapy alone. Due to an inability to control for confounding and small study sizes, future, controlled trials are warranted to confirm these findings.
PubMed: 38491943
DOI: 10.1093/ecco-jcc/jjae035 -
Acta Obstetricia Et Gynecologica... May 2024It is still unclear whether Crohn's disease (CD) might be associated with diminished ovarian reserve (OvR) and factors influencing anti-Mullerian hormone (AMH) levels in... (Review)
Review
INTRODUCTION
It is still unclear whether Crohn's disease (CD) might be associated with diminished ovarian reserve (OvR) and factors influencing anti-Mullerian hormone (AMH) levels in CD are poorly known.
MATERIAL AND METHODS
We conducted a comprehensive literature search of multiple electronic databases from inception to June 2022 to identify all studies reporting AMH levels or factors associated with diminished OvR in patients with CD.
RESULTS
Of the 48 studies identified in our search, eight (including 418 patients with CD) were finally included. The mean difference (95% confidence interval [CI]) in the AMH level between pooled CD patients and controls was -0.56 (-1.14 to 0.03) (p = 0.06). A history of CD-related surgery was not associated with a lower OvR (odds ratio, OR [95% CI] 1.34, [0.66-2.7]; p = 0.4). While disease activity and perianal disease seems associated with a low OvR, disease location (L2 vs. L1, OR [95% CI] = 95% CI [0.47-7.4]; p = 0.4) and L3 vs. L1 (OR [95% CI] = 1.44 [0.67-3.12]; p = 0.3), CD medication, and disease behavior were not.
CONCLUSIONS
Our systematic review and meta-analysis did not identify a significantly low OvR in patients with CD. Contrary to CD-related surgery risk factor, active disease was associated lower AMH levels.
PubMed: 38803058
DOI: 10.1111/aogs.14853 -
Alimentary Pharmacology & Therapeutics Jun 2024Risk stratification for endoscopic post-operative recurrence (ePOR) in Crohn's disease (CD) is required to identify patients who would benefit most from initiation of... (Review)
Review
BACKGROUND
Risk stratification for endoscopic post-operative recurrence (ePOR) in Crohn's disease (CD) is required to identify patients who would benefit most from initiation of prophylactic medication and intensive monitoring of recurrence.
AIMS
To assess the current evidence on patient-related, microbial, surgical and histopathological risk factors for ePOR in patients with CD after ileocolic (re-)resection.
METHODS
Multiple online databases (Embase, MEDLINE, Web of Science and Cochrane Library) were searched up to March 2024. Studies with reported associations of patient-related, microbial, surgical and/or histopathological factors for ePOR (i.e., Rutgeerts' score ≥i2 or modified Rutgeerts' score ≥i2a) were included. The risk of bias was assessed with the Newcastle-Ottawa Scale for observational cohort studies and case-control studies.
RESULTS
In total, 47 studies were included (four RCTs, 29 cohort studies, 12 case-control studies, one cross-sectional study and one individual participant data meta-analysis) including 6006 patients (median sample size 87 patients [interquartile range 46-170]). Risk of bias assessment revealed a poor quality in 41% of the studies. An association was reported in multiple studies of ePOR with active smoking at and post-surgery, male sex and prior bowel resection. A heterogeneous association with ePOR was reported for other risk factors included in the current guidelines (penetrating disease, perianal disease, younger age, extensive small bowel disease and presence of granulomas in the resection specimen or myenteric plexitis in the resection margin), and other patient-related, microbial, surgical and histopathological factors.
CONCLUSION
Risk factors for ePOR in international guidelines are not consistently reported as risk factors in current literature except for active smoking and prior bowel resection. To develop evidence-based, personalised strategies, large prospective studies are warranted to identify risk factors for ePOR. Validation studies of promising (bio)markers are also required.
PubMed: 38887827
DOI: 10.1111/apt.18040