Pooled Remission Rates Research Articles

Efficacy and safety of different dosing regimens of rituximab in primary membranous nephropathy: protocol for a systematic review and meta-analysis

IntroductionPrimary membranous nephropathy (PMN) is a major cause of nephrotic syndrome in adults. Rituximab has been recommended in the treatment of PMN by the updated Kidney Disease Improved Outcome guideline....

Efficacy and safety of vedolizumab for pediatrics with inflammatory bowel disease: a systematic review

BackgroundVedolizumab use in pediatrics is still off-label and the data are limited. We conducted a systematic review evaluating the efficacy and safety of vedolizumab in children and adolescents with inflammatory bowel disease (IBD).MethodsPubMed, EMBASE and Cochrane databases were systematically searched for studies of vedolizumab in children and adolescents with IBD reporting clinical remission, response, corticosteroid-free (CS-free) remission, mucosal healing, or safety up to December 3rd 2021.ResultsTen studies, comprising 455 patients were included. For CD, the pooled clinical remission rates were 25% (19/75) at 6 weeks, 28% (25/85) at 14 weeks, 32% (17/53) at 22 weeks, and 46% (43/92) at 1 year. For UC/IBD-U, the pooled clinical remission rates were 36% (25/70) at 6 weeks, 48% (52/101) at 14 weeks, 53% (24/45) at 22 weeks, and 45% (50/112) at 1 year. Mucosal healing was found in 17%-39% of CD and 15%-34% of UC/IBD-U respectively. Six percent of patients reported serious adverse events.ConclusionsAccording to low-quality evidence based on case series, approximately one-third and one-half of patients for CD and UC/IBD-U respectively achieved remission within 22 weeks, and about half of patients achieved remission at 1 year with reasonable safety profile. Long-term benefit profile data and high quality evidence are still needed.

Efficacy and safety of rituximab for IgG4-related pancreato-biliary disease: A systematic review and meta-analysis

BackgroundType I autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-SC) belong to the IgG4-related disease (IgG4-RD) spectrum. Both entities respond to glucocorticoids, but iatrogenic toxicity associated with prolonged steroid therapy and relapse represent relevant clinical concerns in the long-term. Rituximab is increasingly used as an effective alternative strategy to induce remission but data regarding the safety and efficacy of B-cell depletion therapy for pancreato-biliary involvement of IgG4-RD are limited. We performed a systematic review and meta-analysis to estimate the rate of remission, flare, and adverse events (AEs) occurring in pancreato-biliary IgG4-RD following rituximab treatment. MethodsThe MEDLINE, SCOPUS, and EMBASE databases were searched from inception to December 2020 to identify studies reporting the outcomes of IgG4-related pancreato-biliary disease after treatment with rituximab. Studies involving ≥2 patients were selected. In case of duplicated studies, the most recent or the one with the biggest N were chosen. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled effects were calculated using a random-effect model and expressed in terms of pooled remission, relapse, and AEs rates. ResultsSeven cohort studies met inclusion criteria and 101 patients were included. Reasons for rituximab administration were new disease onset (18.5%), disease flare after glucocorticoids (63.5%), and glucocorticoids intolerance (17.9%). The median follow-up time was 19 months. The pooled rate of complete response at 6 months was 88.9% (95%CI 80.5–93.9) with no heterogeneity (I2 = 0%). The pooled estimate of relapse rate was 21% (95%CI 10.5–40.3) with moderate heterogeneity (I2 = 51%). A higher rate of relapse (35.9%, 95%CI 17.3–60.1) was reported in studies including patients with multiorgan involvement (OOI). The median time to relapse was 10 months. The pooled estimate of rituximab-related AEs was 25% (95%CI 8.8–53) with substantial heterogeneity (I2 = 73.6%). No publication bias was observed. ConclusionTreatment of IgG4-related pancreato-biliary disease with rituximab is associated with high remission rate, a higher relapse rate in the presence of OOI, and limited AEs. Randomized controlled trials with adequate power are needed to confirm these findings.

Methimazole-induced remission rates in pediatric Graves' disease: a systematic review.

Comparison of studies on remission rates in pediatric Graves' disease is complicated by lack of uniformity in treatment protocols, remission definition, and follow-up duration. We performed a systematic review on remission rates in pediatric Graves' disease and attempted to create uniformity by recalculating remission rates based on an intention-to-treat analysis. PubMed and Embase were searched in August 2020 for studies on patients with Graves' disease: (i) 2 to 18 years of age, (ii) initially treated with methimazole or carbimazole for at least 18 months, (iii) with a follow-up duration of at least 1 year after cessation of methimazole or carbimazole. All reported remission rates were recalculated using an intention-to-treat analysis. Of 1890 articles, 29 articles consisting of 24 patient cohorts were included with a total of 3057 patients (82.6% female). Methimazole or carbimazole was initially prescribed in 2864 patients (93.7%). Recalculation based on intention-to-treat analysis resulted in an overall remission rate of 28.8% (829/2880). Pooled remission rates based on treatment duration were 23.7, 31.0, 43.7, and 75% respectively after 1.5-2.5 years, 2.5-5 years, 5-6 years (two studies), and 9 years (single study) treatment duration. The occurrence of adverse events was 419 in 2377 patients (17.6%), with major side effects in 25 patients (1.1%). Using a standardized calculation, the overall remission rate in methimazole-treated pediatric GD is 28.8%. A few small studies indicate that longer treatment increases the remission rate. However, evidence is limited and further research is necessary to investigate the efficacy of longer treatment durations.

Long-Term Outcome of Pediatric Obsessive-Compulsive Disorder: A Meta-Analysis.

Objective: The outcome of pediatric obsessive-compulsive disorder (OCD) is still unclear. In the present study, long-term rates and predictors of remission were used to identify potential factors influencing the outcome of pediatric OCD. Methods: Using meta-analysis techniques, we calculated the pooled rate of remission and performed subgroup analyses to identify potential heterogeneities, and the meta-regression analysis was used as a predictor. Results: A total of 18 studies including 1389 participants were identified, and the follow-up periods ranged from 1 to 16 years. The pooled remission rate of pediatric OCD was 62% (95% confidence interval: 52-72). Shorter duration of OCD at baseline (R2 = 78.04%, p < 0.0001) predicted higher rates of remission. Conclusions: The outcome of pediatric OCD seems to be better than the past. Shorter duration of illness appears to be related to a better outcome. Early detection of pediatric OCD and early intervention play an important role in good prognosis. In the future, studies based on multicenter, longer follow-up studies with larger samples were needed to confirm these issues for the outcome of pediatric OCD.

Efficacy and safety of biological agents in the treatment of patients with Takayasu arteritis: a systematic review and meta-analysis.

We aimed to systematically review biological agents' efficacy and safety in patients with Takayasu arteritis (TAK). A systematic literature search of 7 electronic databases, including MEDLINE (via PubMed), EMBASE, Elsevier ScienceDirect, EBSCO, Springer Link, Web of Science, and Cochrane Library on the efficacy of biological agents on patients with TAK was conducted. Only studies published in English and with a sample size >5 patients with TAK were included. Two reviewers independently selected studies, extracted data and assessed its methodological quality. Random effects meta-analyses of various effect measures were performed. According to the title and abstract, 961 studies were identified and screened. Subsequently, 31 studies from 29 observational studies and 2 randomized-controlled trials (RCTs), which included a total of 517 patients with TAK that met the inclusion and exclusion criteria, were selected. Observational studies showed a high risk of bias. Pooled remission rates of biological agents were 66% (95% CI: 58%-73%; I2=59%), and the remission rates of anti-tumor necrosis factor (TNF) agents and tocilizumab (TCZ) were similar: 65% (95% CI: 56%-73%; I2=49%) and 70% (95% CI: 55%-86%; I2=69%), respectively. Pooled relapse rates were 23% (95% CI: 15%-31%; I2=66%). The relapse rate was 28% (95% CI: 16%-40%; I2=68%) for anti-TNF agents and 17% (95% CI: 7%-26%; I2=49%) for TCZ. The remission rate of TCZ was slightly higher (p>0.05), but the relapse rate was statistically significantly lower than that of anti-TNF agents (p=0.017). Furthermore, biological agents significantly decreased the doses of glucocorticoid (GC) and levels of acute phase inflammation markers (ESR, CRP) while the proportion of patients with new angiographic lesions or progression of previously noted lesions were 11% (95% CI: 4%-18%; I2=59%). RCTs with a small sample size showed abatacept was ineffective, and TCZ was underpowered to detect a difference in time to relapse compared to placebo. The most common adverse event of biological agents was infection (6%, 95%CI: 2%-10%). No deaths were reported. Although the beneficial effects of biological agents are encouraging in enhancing disease remission, reducing the levels of acute phase inflammation markers and decreasing the treatment doses of GC in patients with TAK, there is still a risk of relapse. More refined studies with larger cohorts are necessary before drawing a definitive opinion.

Association between asthma control trajectories in preschoolers and disease remission.

Early disease morbidity has been associated with asthma persistence in wheezing preschoolers; however, whether asthma control trajectories shortly after diagnosis could influence remission is unknown. We examined the association between asthma control trajectories 2 years post-diagnosis in preschoolers and subsequent disease remission. We conducted a multicentre population-based retrospective cohort study consisting of 48 687 children with asthma diagnosed before 5 years old and born between 1990 and 2013 in four Canadian provinces who had prolonged disease activity post-diagnosis. Prolonged disease activity was defined as one or more medical visits or medications for asthma every 6-month period for at least four of the six periods post-diagnosis. Follow-up began at 3 years post-diagnosis (at cohort entry). Remission was defined as 2 consecutive years without drug claims or medical visits for asthma or asthma-like conditions following cohort entry. Asthma control trajectories, ascertained over four 6-month periods following diagnosis using a validated index, were classified as: "controlled throughout", "improving control", "worsening control", "out of control throughout" and "fluctuating control". Adjusted Cox models estimated associations between asthma control trajectories and time to remission. A random effects meta-analysis summarised province-specific hazard ratios (HRs). The pooled remission rate was 8.91 (95% CI 8.80-9.02) per 100 person-years. Compared with children controlled throughout, poorer asthma control was associated with incrementally lower hazard ratios of remission in four other trajectories: improving control (HR 0.89, 95% CI 0.82-0.96), fluctuating control (HR 0.78, 95% CI 0.71-0.85), worsening control (HR 0.68, 95% CI 0.62-0.75) and out of control throughout (HR 0.52, 95% CI 0.45-0.59). Asthma control trajectories 2 years following a diagnosis in preschoolers were associated with remission, highlighting the clinical relevance of documenting control trajectories in early life.

Abstract P388: Childhood Obstructive Sleep Apnea May Track Into Adolescence and Role of Weight Dynamics

Introduction: Childhood and adolescent OSA share certain pathophysiological mechanisms. Thus, adolescent OSA may be in a continuum of childhood OSA. However, this hypothesis remains controversial. Hypotheses: Childhood OSA is associated with higher odds of adolescent OSA. Weight changes in this transitional period are associated with the development of OSA. Methods: We, firstly, conducted a meta-analyses to associate childhood and adolescent OSA based on literatures in which apnea hypopnea index (AHI) and/or OSA during both childhood and adolescence were reported. Major search engines were used to identify relevant reports. An AHI ≥ 1 was used as homologized definition of OSA at childhood and adolescence periods across all studies. From eligible studies, numbers of participants with none, remitted, incident, and persistent OSA from childhood to adolescence were abstracted. Crude relative risks (RRs) between childhood and adolescence OSA were computed by using Cochran-Mantel-Haenszel tests. A random-effects model, based on the DerSimonian and Laird method, was used to summarize the findings across studies. We, then, used data from the Penn State Child Cohort (PSCC) to analyze the association between weight changes from childhood to adolescent and incident/persistent OSA. Based on the changes of participants’ weight status (normal: BMI percentile &lt; 85 vs. overweight/obese: BMI percentile ≥ 85) during childhood and adolescence, 4 mutually exclusive groups were formed and compared. Logistic regressions were used to associate weight gain (normal to overweight/obese) and weight loss (overweight/obese to normal) during this development stage and incident/persistent OSA. Sensitivity analyses were performed by using an AHI ≥ 5 to define OSA. Results: Four cohort studies, which included a total of 1473 participants, were included in the meta-analyses. The mean age during childhood and adolescence examinations were 8.5-9.8 years and 13.7-20.2 years. The pooled remission rate of childhood OSA was 52.8% (31.6%, 74.1%), while the incidence of adolescent OSA was 31.6% (15.8%, 47.4%). After weighing and summarizing RRs from individual studies, the overall RR was 1.54 (1.14, 2.08). The association was stronger [RR: 2.51 (1.65, 3.82)] in the sensitivity analysis. Based on PSCC data, we found a significant association between weight gain from childhood to adolescence and higher odds of incident OSA [OR: 2.61 (1.01, 6.81)] and a non-significant trend between weight loss and lower odds of incident OSA [OR: 0.23 (0.05, 1.06)]. Conclusion: While a substantial proportion of childhood OSA remits in the transition to adolescence, children with OSA are more likely to have adolescent OSA than those without OSA in childhood. Weight gain and loss may contribute to the natural course of OSA during transition from childhood to adolescent, especially the onset of incident OSA.

207 Fecal Microbiota Transplantation With Oral Capsules for Clostridium difficile Infection: Inconsistencies Among Reporting and Impact on Remission Rates

INTRODUCTION: Fecal microbiota transplantation (FMT) has emerged as a safe and effective treatment for recurrent Clostridium difficile infection (rCDI). FMT can be delivered via the upper gastrointestinal tract (UGIT) or lower GIT. Recently, oral capsule delivery has been demonstrated to be non-inferior to other routes. However, oral administration lends the capsule susceptible to pH changes and intestinal microbiota exposures prior to reaching the colon. There is a lack of consistency between studies evaluating FMT capsules with respect to multiple factors. This systematic review aimed at identifying factors within these studies that could impact remission rates such as type of capsule preparation, prior acid suppression therapy and colon preparation before treatment. METHODS: An electronic search was conducted using PubMed, Scopus, EMBASE and Cochrane Central Register of Controlled Trials. The search strategy was not limited by language. Search terms for both the free text and medical subject heading (MeSH) included “fecal microbiota transplantation” and “capsule.” Eligibility criteria included clinical trials using FMT for rCDI and delivery by capsule. Exclusion criteria included lack of capsule manufacturing description or endpoints related to CDI resolution. RESULTS: The initial search strategy yielded 93 publications. 30 duplicates were removed. 37 were excluded after screening titles and abstracts. 26 full papers were reviewed and of these, 11 met our eligibility criteria (See Table 1). A total of 425 patients were evaluated who underwent FMT via capsule delivery. Remission rates among studies ranged from 68% to 100%. Timeframe defining remission varied among studies, though 10/11 defined remission as resolution of diarrhea at least 8 weeks after FMT. The pooled remission rate was 86.6% in those receiving colon prep prior to FMT, 83.9% in those who received double-encapsulated formulations and 75.4% in those using PPIs prior to FMT (See Table 2). Heterogeneity among reported study protocols prohibited statistical analysis of these factors. CONCLUSION: Oral administration of FMT capsules greatly simplifies this treatment option for patients with rCDI. This systematic review highlights inconsistencies in reporting of the methodology used in FMT capsule studies, which can be contributing to variable remission rates. Future randomized trials are needed to compare the various factors outlined above.

Effectiveness and safety of Ustekinumab for Crohn's disease; systematic review and pooled analysis of real-world evidence

BackgroundUstekinumab [UST] is effective in Crohn’s disease (CD) in the UNITI studies. Several real-world experience (RWE) studies with UST have been published to date. Our aim was to summarize the available RWE data for UST effectiveness and safety. MethodsA systematic review of the available RWE studies of UST for CD and pooled analysis of the available effectiveness and safety data was performed. ResultsEight relevant studies of 6 RWE were included for analysis. Data from 578 patients were pooled for analysis. Most patients (97.7%) were anti-TNF experienced. Pooled clinical response rate was 60%, 62%, 49% at 12, 24 and 52 weeks respectively (95% CI (0.42–0.77), (0.48–0.75), (0.37–0.62)). Pooled remission rate was 39% (95% CI (0.18–0.65)) at 24 weeks and pooled endoscopic response rate was 63% (95% CI (0.53–0.72)) after approximately one year of UST; 134 adverse events (AE) were reported in total, pooled proportion 21% (95% CI (0.12–0.35)). Serious AE were reported in 19 patients, pooled proportion 5% (95% CI (0.03–0.08)). Infections were reported in 38, pooled proportion 6% (95% CI (0.04–0.11)). ConclusionPooled analysis of the RWE data suggests that the real-world effectiveness and safety are comparable to that reported in the randomized control trials.

Natural Regression of Frailty Among Community-Dwelling Older Adults: A Systematic Review and Meta-Analysis.

Frailty is a dynamic process with potential transitions over time. However, there is limited understanding of the patterns of frailty improvement. We conducted a systematic review and meta-analysis to estimate the natural rate of frailty regression among community-dwelling older adults aged at least 60 years. Systematic searches for studies reporting frailty improvement were performed in 5 databases (Medline, Embase, CINAHL plus, Web of Science, and PsycINFO) from inception until January 2019. Twenty-five studies from 26 countries were included. Among a baseline population of more than 50,000 individuals, the pooled prevalence of pre-frailty and frailty was 50.5% (95% confidence interval [CI] 47.8-53.3) and 12.8% (95% CI 9.1-17.0), respectively. During a median follow-up of 3.0 (range 1-10.0) years, 23.3% of surviving pre-frail individuals regressed to a robust state and 35.2% of surviving frail individuals reversed to a pre-frail or robust state. The pooled remission rates among people with pre-frailty and frailty were 80.4 (95% CI 61.7-104.6) and 135.3 (95% CI 98.1-186.5) per 1,000 person-years, respectively. Frailty and pre-frailty improvement rates varied by sex, diagnostic criteria, study region, and follow-up duration. The remission rates were significantly reduced when accounting for progressions to death. The heterogeneity of included studies was high which reflected considerable differences in methodological approach. Although frailty is highly prevalent in older people, natural remission is possible and common. Improved understanding of the factors that confer increased likelihood of frailty regression may support the design of interventions to reduce the burden of frailty.

Unilateral and bilateral repetitive transcranial magnetic stimulation for treatment-resistant depression: a meta-analysis of randomized controlled trials over 2 decades

Approximately 35% of people with depression do not respond to 2 courses of antidepressant medications of adequate dosage, and treatment-resistant depression (TRD) is still a major clinical concern with a great impact on patients, their families, society and the health system. The present meta-analysis evaluates antidepressant efficacy of unilateral and bilateral repetitive transcranial magnetic stimulation (rTMS) in patients with unipolar TRD. We searched for randomized controlled trials that compared rTMS with sham treatment and were published by Apr. 3, 2017. The primary outcome was improvement in depression scores measured using the Hamilton Rating Scale for Depression. The secondary outcomes were remission and response rates. Two independent review authors screened the studies and extracted the data. Twenty-three studies met the inclusion criteria. Meta-analysis of the depression scores showed a weighted mean difference (WMD) of 3.36 (95% confidence interval [CI] 1.85–4.88) between unilateral rTMS and sham treatment. Stratified data showed that the effect was relatively higher when rTMS was used as an add-on to antidepressant medications (WMD 3.64, 95% CI 1.52–5.76) than when it was used as a stand-alone treatment (WMD 2.47, 95% CI 0.90–4.05). The WMD between bilateral rTMS and sham was 2.67 (95% CI 0.83–4.51), and all studies that contributed to this outcome used rTMS while participants were taking antidepressant medications. The pooled remission and response rates for unilateral rTMS versus sham treatment were 16.0% and 25.1% for rTMS and 5.7% and 11.0% for sham treatment, respectively. The pooled remission and response rates for bilateral rTMS versus sham treatment were 16.6% and 25.4% for rTMS and 2.0% and 6.8% for sham treatment, respectively. This study suggests that rTMS has moderate antidepressant effects and appears to be promising in the short-term treatment of patients with unipolar TRD.

Non-glucocorticoid drugs for the treatment of Takayasu's arteritis: A systematic review and meta-analysis

Takayasu's Arteritis (TAK) affects mostly young women and causes significant morbidity. Most patients are refractory to glucocorticoids (GC) or relapse when GC doses are reduced. The objective of this study is to summarize the literature pertaining to the effectiveness of non-GC drugs for the treatment of TAK. MEDLINE and Embase were searched for English-language studies of TAK patients with a sample size >5. Studies were included if the effectiveness of non-GC drugs for the treatment of TAK was reported. Random effects meta-analyses of various effect measures were performed. Of the 915 studies identified by the search, 14 of small molecule immunosuppressants (IS) and 25 of biologic therapies were included. Studies had a high risk of bias. Pooled remission rates were similar for both categories of non-GC drugs: 58% (95% CI: 40-74%) and 64% (95% CI: 56-72%), respectively. The relapse rate was 54% (95% CI: 39-68%) for IS therapies and 31% (95% CI: 22-41%) for biologics. Both significantly decreased GC doses and acute phase reactants. Observational studies suggested that anti-TNF agents were more effective than IS at maintaining remission. Randomized-controlled trials (RCTs) of biologics were of small sample size: abatacept was not effective and the trial of tocilizumab was underpowered to detect a difference in time to relapse versus placebo. Serious adverse events were uncommon. Non-GC agents were moderately effective in inducing remission in TAK, but relapse rates were high. Larger, better designed studies are required to determine the optimal treatment regimen for TAK.

Efficacy and safety of tocilizumab with inhibition of interleukin-6 in adult-onset Still’s disease: A meta-analysis

Objectives: Tocilizumab (TCZ) is the only available biologics inhibiting interleukin-6 presently, and emerging evidences have figured that elevated serum level of interleukin-6 is a crucial link of the pathogenesis of adult-onset Still’s disease (AOSD). However, evidence about the efficacy and safety of TCZ in AOSD with strong power is still scarce. Thus, this meta-analysis was conducted to synthetically assess the efficacy and safety of TCZ on AOSD.Methods: PubMed, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, and Chinese Biological Medical Literature database were comprehensively searched up to 31 July 2017 for the pertinent studies. The pooled remission rates were synthesized by fixed effect model or randomized effects model, depended on heterogeneity.Results: Ten original studies contained 147 individuals were included in our analysis. The overall partial and complete remission rates were 85.38 (95% CI: 69.32–96.88%) and 77.91% (95% CI: 57.91–90.04%), respectively, and the remission rate of refractory patients was 87.92% (95% CI: 56.53–100.00%).Conclusion: The use of TCZ could significantly reduce the need of corticosteroids for AOSD patients. Impressive improvements were attained in both clinical and laboratory parameters. Compared with conventional therapy, TCZ treatment was safety. In conclusion, TCZ was effective and well tolerated for the treatment of AOSD.

Remission and recovery from first-episode psychosis in adults: A systematic review and meta-analysis of long-term outcome studies

IntroductionRemission and recovery rates for people who have had a first episode psychosis (FEP) remain uncertain.ObjectivesWe conducted a systematic review and meta-analysis to assess pooled prevalence rates of remission and recovery in FEP in longitudinal studies and conducted meta regression analyses to investigate potential moderators.MethodsA systematic literature search of major electronic databases without language restrictions was conducted from database inception until July 1, 2016. Longitudinal studies with follow up greater than 1 year reporting data on remission or recovery rates in FEP were included.ResultsSeventy-nine studies were included representing 19,072 FEP patients (mean age = 26.9 years, male = 59.5%). The pooled rate of remission among 12,301 individuals with FEP was 57.9% (95%CI: 52.7–62.9, Q = 1536.3, P&lt; 0.001, n = 60 studies, mean follow up = 5.5 years). Restricting the analysis to studies, which used the remission in schizophrenia working group (RSWG) criteria (n = 25 studies, n = 6909 patients), the pooled remission rate was 56.9% (95%CI: 48.9–64.5, Q = 656.9). Higher remission rates were moderated by studies from more recent years. The pooled prevalence of recovery among 9642 individuals with FEP was 37.9% (95%CI: 30.0–46.5, Q = 1450.8, studies = 35, P = 0.006, average follow up = 7.2 years). Recovery rates were higher (P&lt; 0.05) in North America compared to other regions.ConclusionsOur data suggest that remission and recovery rates in FEP may be more favorable than previously thought. We observed stability of recovery rates after the first two years, suggesting that a progressive deteriorating course of illness is not typical. While remission rates have improved over time, recovery rates have not, raising questions about the effectiveness of specialist early intervention services in achieving improved recovery.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Fecal transplantation: any real hope for inflammatory bowel disease?

Fecal microbiota transplant (FMT) has emerged as an important treatment for antibiotic resistant or recurrent Clostridium difficile infection. There has been a great deal of media coverage of the efficacy of FMT, and patients with inflammatory bowel disease (IBD) understandably wonder if this approach would also work for them. There are also instructions on 'do it yourself' FMT therapy on the web. It is important to understand whether there is evidence that this approach is effective in IBD so that we can advise our patients appropriately. Systematic reviews have identified four case series involving 27 ulcerative colitis patients with a pooled remission rate of 24% (95% confidence interval (CI) = 11-45%). Two randomized controlled trials evaluating a total of 123 active ulcerative colitis patients have given conflicting results but the pooled data do suggest benefit with a number needed to treat of 6 (95% CI = 3-33). There are four case series involving 38 patients with Crohn's disease with a clinical response in 60.5% (95% CI = 28-86%). There are no randomized trials in Crohn's disease. At present there are insufficient data to recommend FMT in IBD, and patients certainly should not be administering this themselves. This remains an interesting approach to treating IBD and more studies are needed to establish the optimal method of delivery as well as randomized, placebo controlled trials to establish the efficacy of FMT.

Efficacy and Safety of Adalimumab for Paediatric Crohn's Disease: A Systematic Review.

Adalimumab is well-established therapy for adults with Crohn's disease [CD]. The aim of the study was to systematically assess the published evidence on the efficacy and safety of adalimumab for Crohn's disease in children. MEDLINE, EMBASE, the Cochrane Library, and abstracts from the main gastroenterological meetings in the past 5 years were systematically searched up to July 2015 for randomised controlled trials and observational studies on the efficacy and safety of adalimumab for Crohn's treatment in children and adolescents. A total of 14 studies [1 randomised controlled trial, 13 case series], altogether including 664 patients [age: 1.9 to 21 years] were available for analysis. The studies differed with respect to patients' characteristics, including percentage of infliximab-naïve patients, disease duration, site of the disease, adalimumab doses, treatment duration, and follow-up period. The pooled remission rates were: 30% [n = 93/309] at 4 weeks, 54% [n = 79/145] at 3 months, 45% [n = 18/40] at 4 months, 42% [n = 146/345] at 6 months, 57% [n = 20/35] at 8 months, and 44% [n = 169/383] at 12 months. Of the total patients, 6% [n = 13/207] were classified as primary non-responders and 12% [n = 69/599] had severe adverse events reported including 2 deaths and 1 medulloblastoma. Withdrawal rate due to adverse events reported in one study was 35% [n = 64/182]. According to low-quality evidence based mainly on case series, approximately half of children with Crohn's disease on adalimumab therapy achieve remission during the first year of the therapy with reasonable safety profile. There is still a need for high-quality evidence on effectiveness and safety of adalimumab for paediatric Crohn's disease.

Diagnosis and Treatment of Autoimmune Pancreatitis in China: A Systematic Review.

AimsTo provide comprehensive data on the diagnosis and treatment of autoimmune pancreatitis (AIP) patients in China.DesignA systematic review.MethodsAll clinical studies concerning AIP from China published between January 2006 and June 2014 were retrospectively reviewed and analyzed.ResultsA total of 26 original articles involving 706 AIP patients were included with an estimated proportion of type 2 AIP as 4.7%. In the 706 AIP patients, the range of mean/median age was 48.6–67.0 years old and the male to female ratio was 4.47:1. The common presentations included obstructive jaundice (pooled rate: 63.4%, 95%CI: 55.4%–71.0%) and abdominal symptoms (pooled rate: 62.3%, 95%CI: 52.4%–71.7%). Biliary involvement was the most common extrapancreatic manifestations, especially the lower part of the common bile duct (pooled rate: 62.3%, 95%CI: 49.9%–73.9%). According to the imaging examinations, 53.8% and 41.6% patients were classified into focal-type and diffuse-type, respectively. Notably, upstream pancreatic duct dilatation was found in parts of patients (pooled rate: 13.8%, 95%CI: 6.6%–23.1%). The levels of serum IgG4 were elevated in most patients (pooled rate: 86.0%, 95%CI: 74.2%–94.6%). Nearly three tenths AIP patients received surgery (pooled rate: 29.7%, 95%CI: 18.1%–42.8%) due to mimicked malignancy. Steroid treatment was given to 78.4% patients (95%CI: 65.3%–89.1%) with a pooled remission rate of 96.2% (95%CI: 94.0%–97.9%). The pooled relapse rate was 13.8% (95%CI: 7.2%–22.0%) with the mean follow-up time ranging from 12 to 45 months.ConclusionType 1 is the predominant type of Chinese AIP patients and the clinical features, diagnostic modalities and therapeutic regimen were similar with those in other countries. Knowledge of AIP should be more widespread to avoid unnecessary surgery.

Systematic review: thalidomide and thalidomide analogues for treatment of inflammatory bowel disease.

It has been reported that thalidomide may be effective in treating inflammatory bowel disease (IBD). To review the evidence examining the efficacy and safety of thalidomide for inducing and maintaining remission in Crohn's disease (CD) and ulcerative colitis (UC). The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PubMed (1950-August 2014), EMBASE (1984-August 2014), Scopus, and Web of knowledge were searched for randomised controlled trials (RCTs), observational studies and case series. The primary outcomes were induction of remission or response for active IBD or relapse rate for patients in remission and subsequently on thalidomide/analogues for at least 3months. Twelve studies (2 RCTs and 10 case series) met the inclusion criteria for inducing remission and included 248 patients (10 with UC, 238 with CD). Only one RCT of paediatric CD achieved high quality scores (remission rate thalidomide: 46%, placebo: 12%; p=0.01). The crude pooled remission rate for thalidomide was 49% and 25% in luminal and perianal CD respectively. For UC, 50% achieved remission and 10% had partial response. One case series reported 21 patients (17 CD, four UC) who maintained remission for 6months. Many adverse events were reported including sedation (32%) and peripheral neuropathy (20%). One high quality RCT showed that thalidomide is effective for inducing remission in paediatric CD. The current evidence is insufficient to support using thalidomide to induce remission in UC or adult CD, or to maintain remission in IBD. Significant adverse events may occur, necessitating discontinuation of thalidomide.

Long-term outcome of obsessive-compulsive disorder in adults: a meta-analysis.

To study the long-term rate and predictors of remission in adults with obsessive-compulsive disorder (OCD), using meta-analysis. The MEDLINE database was searched to May 2013 using the search terms obsessive-compulsive disorder, prospective, outcome study, clinical course, remission, prognosis, follow-up, and long-term and limits for language (English), species (humans), and age (adults). This was supplemented by manual bibliographic cross-referencing. English-language studies from peer-reviewed journals on adults with DSM-III-R, DSM-IV, DSM-IV-TR, ICD-9, or ICD-10 diagnosis of OCD followed up for ≥ 1 year and treated with serotonin reuptake inhibitors and/or cognitive-behavioral therapy that reported rate of remission (Yale-Brown Obsessive Compulsive Scale [YBOCS] score < 16 at longest follow-up) were included. Data were gathered as numbers/means/percentages/categories on sample size, study design, follow-up duration, age at assessment, illness duration, age at illness onset, gender, marital status, inpatient/outpatient status, family history, baseline YBOCS score, comorbidities, and remission. Seventeen studies (pooled N = 1,265) fit the selection criteria and were used for the meta-analysis. The pooled sample had a mean follow-up duration 4.91 years and was predominantly male and outpatient and had onset of illness in the second decade, illness duration more than 10 years, and moderate-to-severe OCD. Pooled remission rate was 53% (95% CI, 42%-65%). Prospective studies showed higher pooled remission rate than retrospective studies (55% [95% CI, 45%-65%] vs 50% [95% CI, 27%-73%], P < .001). Indian studies showed higher pooled remission rate than others (71% [95% CI, 59%-83%] vs 48% [95% CI, 37%-59%], P < .001). Age at onset (t = -7.08, P = .019), illness duration (t = -8.13, P = .015), baseline YBOCS score (t = -6.81,P = .021), and male gender (t = -5.92, P = .027) had significant negative association with remission on meta-regression. A high long-term remission rate found in this meta-analysis is contrary to generally held beliefs about poor outcome of individuals with OCD. Multicenter, prospective, long-term studies should systematically examine course and outcome in larger samples, emphasizing symptomatic and functional recovery.