Naturalistic Study on the Effects of Electroconvulsive Therapy (ECT) on Depressive Symptoms

Objective The effectiveness of ECT under naturalistic conditions has not been well-studied. The current study aimed to 1) characterize a naturalistic sample of ECT patients; and 2) examine the long-term outcomes of ECT on depressive symptoms (Beck Depression Inventory-II; BDI-II) and functional disability symptoms (WHO Disability Assessment Schedule 2.0) in this sample. Methods Participants were adults who received ECT for a major depressive episode at an ambulatory ECT clinic between September 2010 and November 2020. Clinical and cognitive assessments were completed at baseline ( n = 100), mid-ECT ( n = 94), 2–4 weeks post-ECT ( n = 64), 6-months post-ECT ( n = 34), and 12-months post-ECT ( n = 19). Results At baseline, participants had severe levels of depressive symptoms (BDI-II: M = 41.0, SD = 9.4), and 62.9% screened positive for multiple psychiatric diagnoses on the MINI International Neuropsychiatric Interview. Depressive symptoms ( F(4,49.1) = 49.92, P < 0.001) and disability symptoms ( F(3,40.72) = 12.30, P < 0.001) improved significantly following ECT, and this was maintained at 12-months follow-up. Improvement in depressive symptoms trended towards significantly predicting reduction in disability symptoms from baseline to post-ECT, ( F(1,56) = 3.67, P = 0.061). Although our clinical remission rate of 27% (BDI-II score [Formula: see text] 13 and [Formula: see text] 50% improvement) and overall response rate of 41.3% ([Formula: see text]50% improvement in BDI-II score) were lower than the rates reported in the extant RCT and community ECT literature, 36% of those treated with ECT were lost to follow-up and did not complete post-ECT rating scales. At baseline, remitters had significantly fewer psychiatric comorbidities, lower BDI-II scores, and lower disability symptoms than non-responders ( P < 0.05). Conclusions Participants were severely symptomatic and clinically complex. ECT was effective at reducing depressive symptoms and functional disability in this heterogeneous sample. Although a large amount of missing data may have distorted our calculated response/remission rates, it is also likely that clinical heterogeneity and severity contribute to lower-than-expected remission and response rates to ECT.

Influence of Vitamin D3 Supplementation on Infliximab Efficacy in Chinese Patients With Crohn’s Disease: A Retrospective Cohort Study

Background: It remains uncertain whether vitD3 supplementation is beneficial for remission of Crohn’s disease (CD). The influence of vitD3 supplementation on Infliximab (IFX) efficacy was retrospectively analyzed in Chinese CD patients.Methods: Patients with moderate-to-severe CD, who were bio-naïve and prescribed with IFX treatment for at least 54 weeks were recorded. VitD3 supplementation was defined as patients additionally took oral vitD3 (125 IU/d) within 3 days after the first infusion and persisted in the whole follow-up period. Disease activity was assessed using Harvey-Bradshaw Index (HBI). Serum cytokine profiles were quantitatively analyzed in a subset of all patients at baseline and 54-week after intervention.Results: Among 73 enrolled patients, 37 took vitD3 regularly (D3-patients), the others (non-D3-patients) did not. At 54-week, the mean 25-hydroxyvitaminD level increased in D3-patients (P<0.001). The clinical remission rate was higher in D3-patients compared to non-D3-patients (P=0.030). The decrease of HBI from baseline to 54-week was more in D3-patients than non-D3-patients (P=0.023). Furthermore, vitD3 supplementation was independently related to the increase of remission rate at 54-week in D3-patients (P=0.015). The benefit of vitD3 supplementation was significant only in patients with deficient vitD3, but not in non-deficient vitD3. In non-D3-patients, the decreases of IL-6 and TNF-α at 54-week were more obvious than at baseline (both P<0.05). In D3-patients, however, only IL-10 increased at 54-week compared with its baseline value (P=0.037).Conclusions: VitD3 supplementation could not only improve IFX efficacy, especially for patients with vitD3 deficiency, but also affected the cytokine profiles in CD patients. (Clinical Trials. Gov NCT04606017)

OP35 Effect of maintenance ustekinumab on corticosteroid-free endoscopic and clinical outcomes in patients with Crohn’s Disease - Week 48 analysis of the STARDUST trial

Background The STARDUST study demonstrated that ustekinumab (UST), using either a treat-to-target (T2T) or standard of care (SoC) strategy, may induce and maintain endoscopic and clinical response and remission in Crohn’s disease (CD). Primary endpoint, safety, and efficacy have been reported previously.1 Because corticosteroid (CS) sparing is an important aim of CD management, we compared the efficacy of UST T2T vs SoC in achieving CS-free clinical remission and endoscopic response. Methods Adult patients (pts) with moderate–severely active CD who were CDAI 70 responders after 16 weeks (W) of induction, comprising a single dose of UST 6 mg/kg iv followed by UST 90 mg SC at W8, were randomized to either T2T or SoC arms. In the T2T arm, choice of UST maintenance dosage (q12w or q8w) was based on endoscopic improvement at W16, followed by clinical and biomarker-directed dose escalation up to q4w; in the SoC arm, UST q12w or q8w dosage was based on EU SmPC. Primary endpoint was endoscopic response (Simple Endoscopic Score in CD [SES-CD] decrease from baseline [BL] ≥50%) at W48. For pts on CS at W16, CS tapering was mandatory. At W48, CS-free clinical remission (CDAI &lt;150 and no CS for ≥30 days) and CS-free endoscopic response (reduction from BL in SES-CD ≥50% and no CS for ≥30 days) were evaluated. Results Of 500 pts enrolled, 441 achieved a CDAI 70 response at W16 and were randomized to T2T (n=220) or SoC (n=221); 79.1% and 87.3%, respectively, completed W48. Among clinical remitters and responders at W16 (start of CS tapering), in both T2T and SoC arms more than 70% were still in remission or response at W48 (Figure 1). CS use throughout 48 weeks of treatment is summarized in Table 1. At W48, in T2T and SoC arms similar rates were noted for CS-free endoscopic response (33.6% and 28.5%, respectively) and CS-free clinical remission (56.4% and 63.3%, respectively). Notably, in T2T and SoC arms the CS-free clinical remission rate among pts on CS at BL was 44.1% and 45.1%, respectively (Figure 2). Among W48 endoscopic responders (T2T, n=83; SoC, n=66), CS-free endoscopic response rate was 89.2% and 95.5%, respectively; among W48 clinical remitters (T2T, n=135; SoC, n=154), CS-free clinical remission rate was 91.9% and 90.9%, in T2T and SoC arms, respectively. Conclusion Pts treated with UST under T2T or SoC strategies achieved similar rates of CS-free clinical remission and endoscopic response over 48 weeks. Overall for pts on CS at BL, UST reduced the need for CS while achieving response/remission. Most (&gt;89%) pts with endoscopic response/clinical remission at W48 were also CS-free responders/remitters. Reference

P375 A simulation study to evaluate the performance of a multiple imputation method to address missing data in an analysis of clinical effectiveness using the ImproveCareNow Registry of pediatric patients with Crohn’s disease

Background Patient registries are a source of real-world data (RWD) that are increasingly used to generate real-world evidence (RWE) for the safety and effectiveness of medical therapies. However, in registries, outcome data typically collected in clinical trials may be missing in some patients, creating a major challenge in evaluating RWD reliably. Clinical remission in pediatric Crohn’s disease (PCD), defined by the Short Pediatric Crohn’s disease Activity Index (sPCDAI) &lt;10, is routinely collected in the ImproveCareNow (ICN) Registry, the world’s largest registry of pediatric patients with inflammatory bowel disease (IBD). A feasibility analysis of ICN as a RWD source to estimate the efficacy of therapies in PCD found about one-third of patients were missing at least 1 of the 6 components needed to calculate the sPCDAI scores at Week 52. We conducted a simulation study to evaluate the performance of the multiple imputation (MI) method in addressing the missing data issue. Methods A Starting Dataset from the ICN registry included CD patients age 2 to &lt;18 yr when beginning treatment with a biologic agent other than ustekinumab during 2014 to 2019, who had a baseline visit and a “Week 52” visit. A Complete Dataset included only patients in the Starting Dataset who had all components required to calculate a sPCDAI score at the Week 52 visit. The true remission rate was calculated for the Complete Dataset. For the simulation, missing data patterns for individual sPCDAI components that were observed in the Starting Dataset were randomly imposed in the Complete Dataset. Variables that were predictive of sPCDAI scores, its components, and sPCDAI missingness were included. Ten thousand datasets were simulated for each of three scenarios: base case of the observed missingness in the Starting Dataset, 1.5 times the base case and 2 times the base case. The MI method was applied to the simulated datasets to estimate the remission rate. MI performance was measured by bias and coverage of the true remission rate from the Complete Dataset. Results The Starting and Complete Datasets included 1,458 and 1,212 patients, respectively. The true clinical remission rate in the Complete Dataset was 75.1% (95% CI: 72.6%-77.5%). Analysis without MI for the missing sPCDAI data resulted in underestimation of clinical remission rate, with bias about -2% to -5% (Table 1). The MI method eliminated the bias and had 100% coverage in all simulation scenarios by using a large number of independent predictors. Conclusion The MI method improved the validity, reliability, and efficiency of using RWD for estimating clinical remission in pediatric patients with CD and could be valuable in other registry studies.

Efficacy and tolerability of infliximab retreatment in patients with inflammatory bowel disease: a systematic review and meta-analysis

Background: A large proportion of patients with inflammatory bowel disease (IBD) relapse after drug discontinuation despite achieving a stable state of infliximab-induced clinical remission. Resuming the use of the same tumor necrosis factor-alpha (TNF-α) inhibitors in patients who relapse following TNF-α inhibitor discontinuation was suggested as a treatment strategy. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of infliximab retreatment in patients with IBD. Methods: A systematic literature search to shortlist relevant studies was conducted using the MEDLINE, Embase, CINAHL, and SCOPUS databases for studies published from inception to August 2020. Results: Nine studies were included in the meta-analysis. The pooled clinical remission rate of infliximab retreatment in patients with IBD was 85% (95% confidence interval (CI), 81–89%) for induction treatment and 73% (95% CI, 66–80%) for maintenance treatment. A clinical remission rate following infliximab reintroduction was achieved in a greater proportion of patients with Crohn’s disease (87%; 95% CI, 83–91%) than in those with ulcerative colitis (78%; 95% CI, 61–91%) for induction treatment, but the difference was not statistically significant. Infusion-related reactions after infliximab retreatment occurred in 9% of patients with IBD (95% CI, 3–16%). Conclusion: Infliximab retreatment showed high clinical remission rates with tolerable infusion-related reactions in patients with IBD who achieved remission with initial infliximab treatment but relapsed after its discontinuation. We suggest infliximab as a viable alternative in patients with IBD who previously responded well to infliximab treatment.

A Randomized, Double-Blind, Multicenter, Open Phase IV Clinical Trial to Evaluate The Efficacy and Safety of A Chinese Patent Medicine Combined With Mesalazine for Ulcerative Colitis

Background: Enteric-coated HuDi capsules（HuDi）have been approved for the treatment of ulcerative colitis (UC) in China. In this clinical trial, we objectively evaluated the clinical efficacy and safety of HuDi combined with enteric-coated mesalazine tablets in the treatment of active UC.Methods: A total of 355 patients from 18 hospitals in China were randomly divided into the HuDi group, enteric-coated mesalazine tablet group (mesalazine group) or combined group with randomized, controlled double-blinding and double-modeling methods. The patients were followed every two weeks and reexamined by endoscopy at the end of six weeks of treatment. The clinical response; clinical remission rate; endoscopic response rate; mucosal healing rate; erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP); and safety indicators were evaluated after treatment.Results: The clinical response rate was 58% in the HuDi group and 58.82% in the mesalazine group, while the clinical effective rate in the combined group was 82.46%. A total of 32% of the patients receiving the enteric-coated HuDi capsules and 29.41% of the patients receiving the enteric-coated mesalazine tablets achieved clinical remission. The clinical remission rate in the combined group was 52.63%, which was better than that in the mesalazine group (P = 0.0145)and HuDi group(P = 0.0315). Moreover, the endoscopic response rates were 50% in the HuDi group, 47.06% in the mesalazine group and 64.91% in the combined group, with no significant difference among the three groups (P > 0.05). Further, the mucosal healing rates in the three groups were 44%, 41.18% and 63.16%, respectively, the combined group was better than that in the HuDi group(P=0.0472) and mesalazine group (P=0.0223). Finally, there was no significant difference in the normalization rates of the ESR and CRP among the three groups (P > 0.05).There were no serious adverse events in the combined drug group. Conclusions: In patients with mild and moderate active UC, combined treatment with enteric-coated mesalazine tablets and enteric-coated HuDi capsules improved the Clinical response and induced clinical remission. However, further studies need extended follow-up periods to determine the efficacy.Trial registration: Chinese It was registered in Clinical Trial Registry on 2015-01-14.

DOP80 Effectiveness of ustekinumab and vedolizumab in patients with Crohn’s disease refractory to anti-tumour necrosis factor: A multi-centre comparative study

Background There is no head-to-head trial comparing ustekinumab and vedolizumab in patients with Crohn’s disease (CD) refractory to anti-TNF. In France between May 2014 and November 2016, vedolizumab (and not ustekinumab) was reimbursed for patients who had failed anti-TNF. Then, between December 2016 and August 2018, ustekinumab (and not vedolizumab) was reimbursed for this category of patients. Since September 2018, both ustekinumab and vedolizumab are reimbursed in patients who are refractory to anti-TNF. The aim of this study was to compare effectiveness and safety of ustekinumab and vedolizumab in patients with CD refractory to anti-TNF. Methods We studied all consecutive patients with active CD who were refractory to at least one anti-TNF, and were treated either with vedolizumab or ustekinumab, in five university hospitals of the Paris area, between May 2014 and August 2018. The primary endpoint was clinical remission rate at week 48. Adjustment according to propensity scores with inverse probability of treatment weighting was performed. Results 239 patients were included, 107 received ustekinumab and 132 received vedolizumab. After propensity scoring with IPTW, there was no difference between the two groups (Figure 1). At week 48, the clinical remission rate was higher with ustekinumab than with vedolizumab (54.4% vs. 38.3%; OR =1.92, 95% CI [1.09–3.39]). At week 48, corticosteroid-free remission rate tended to be numerically higher with ustekinumab than with vedolizumab (44.7% vs. 34.0%; OR = 1.57, 95% CI [0.88–2.79]). Treatment persistence was significantly more frequent in the ustekinumab group (71.5% vs. 49.7%; OR = 2.54, 95% CI [1.40–4.62]). The dose optimisation rate at week 48 was higher with vedolizumab than with ustekinumab (53.5% vs. 30.1%; OR = 0.37, 95% Cl [0.21–0.67]). Subgroup analyses showed that ustekinumab was associated with higher clinical remission rates at week 48 in patients with ileal CD (OR = 3.49; 95% CI [1.33–9.17]), a penetrating phenotype (OR = 6.58; 95% CI [1.91–22.68]) and a history of perianal disease (OR = 2.48; 95% CI [1.04–5.93]). Regardless of treatment group, combotherapy was associated with a higher clinical remission rate at week 48 (OR = 1.93; 95% CI [1.09–3.43]). Conclusion This study suggests that, after 1 year of follow-up, ustekinumab is associated with a higher rate of clinical remission than vedolizumab in CD patients refractory to anti-TNF, particularly in those with ileal and penetrating disease.

Serum anti-phospholipase A2 receptor (PLA2R) antibody detected at diagnosis as a predictor for clinical remission in patients with primary membranous nephropathy: a meta-analysis

Background The diagnostic value of serum M-type phospholipase A2 receptor antibody (sPLA2R-ab) expression in patients with primary membranous nephropathy (PMN) has been established. However, the association between sPLA2R-ab and clinical remission remains uncertain. Methods We systematically searched the literature for clinical trials regarding the correlation between sPLA2R-ab expression and clinical remission of PMN patients. Meta-analysis was performed to determine this association. Subgroup analysis, funnel plots, and sensitivity analysis were also performed to investigate heterogeneity or bias. Results A total of 11 trials involving 824 patients were included. Patients with positive sPLA2R-ab had a poor clinical remission rate (RR = 0.76, 95%CI 0.68–0.86, P < 0.0001; I2 = 39%), a higher titer of sPLA2R-ab had a lower chance of clinical remission (RR = 0.72, 95%CI 0.59–0.87, P = 0.0006; I2 = 42%),and a higher risk of renal failure (RR = 4.85, 95% CI, 1.83–12.85, P = 0.002; I2 = 0%), without affecting relapse (RR = 0.97, 95% CI, 0.55–1.70; P = 0.92, I2 = 0%). Subgroup analysis by treatment strategies, assay methods, ethnicity, gender, renal function, the approach of ruling out SMN, and the ratio of patients with nephrotic-range proteinuria at baseline showed no significant association between these factors with the prognostic value of sPLA2R-ab for PMN patients. No significant publication bias was found. Conclusion This meta-analysis adds to the evidence for current guidelines that sPLA2R-ab acts as not only a diagnostic marker but also a pivotal predictor for clinical remission. Therefore, sPLA2R-ab can be considered as a prognostic factor for stratifying PMN patients.

Probiotics combined with aminosalicylic acid affiliates remission of ulcerative colitis: a meta-analysis of randomized controlled trial

We conducted a meta-analysis to evaluate the effect of probiotic combined with aminosalicylic on induction remission maintenance treatment of ulcerative colitis (UC). We conducted systematic searches in several Chinese and English databases from inception to June 2018, screening randomized controlled trials about effect of probiotics combined with aminosalicylic acid on UC. The evaluation indicator was the rate of remission. The relative risk (RR) and 95% confidence interval (CI) were calculated. A total of 27 studies with 1942 patients were included. The results indicated that the remission rate was significantly higher in the group using probiotics combined with aminosalicylic acid than that in the group using aminosalicylic acid alone (RR = 1.40, 95% CI: 1.27–1.53, P=0.000). The subgroup analysis indicated that probiotics combined with aminosalicylic acid can significantly elevate the remission rate in both mild to moderate (RR = 1.33, 95% CI: 1.16–1.54, P=0.000) and active stage (RR = 1.40, 95% CI: 1.27–1.64, P=0.000) UC. In different number of bacterium, drug types and treatment periods, the combination with probiotics can significantly increase the remission rate UC. The funnel plot shows slight publication bias. Probiotics in conjunction with aminosalicylic can obviously increase the clinical remission rate of activity UC than drug alone. There was no significant difference between combined with mesalazine group and salicylazosulfapyridine group.

Protocol for Fecal Microbiota Transplantation in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

Background. Fecal microbiota transplantation (FMT) is an emerging treatment approach for inflammatory bowel disease (IBD). The donor selection, the separation of fecal bacteria, the frequency of FMT, the way of infusion, the long-term safety, and efficacy are still uncertain. Aim. To further study the efficacy and safety and protocol of FMT for IBD. Methods. A systematic review and meta-analysis were conducted until February, 2018. Clinical remission was established as the primary outcome. Results. A total of 596 paediatric and adult IBD patients were enrolled, and 459 patients received FMT therapy. 28.8% (132/459) patients achieved clinical remission during follow-up. 53% (241/459) patients achieved clinical response. The pooled estimated clinical remission for ulcerative colitis (UC) was 21% (95% CI: 8%-37%) and 30% (95% CI: 11%-52%) for Crohn’s disease (CD), both with a risk of heterogeneity; 10% (95% CI: 0%-43%) for paediatric UC; 26% (95% CI: 10%-48%) for adult UC; 45% for paediatric CD (95% CI: 24%-66%); 22% (95% CI: 3%-52%) for adult CD. Meta-analysis of cohort studies showed that moderate-severe IBD patients could achieve more significant remission from FMT than mild-moderate patients (P=0.037). Delivery route has no impact on the efficacy of FMT in UC and CD. Based on current available evidence, a trend was observed towards higher clinical remission rate of frozen stool FMT than that of fresh stool for UC, while there was no significant difference between fresh and frozen FMT for CD. The optimal donor stool for FMT is still uncertain. Meta-analysis of RCTs showed that FMT treatment achieved significantly higher clinical remission rate than placebo for UC (28% versus 9%, P=0.0003). Conclusion. FMT is an effective and safe therapy for both paediatric and adult IBD; fresh or frozen donor stool, delivery route, and antibiotic pretreatment or not have no impact on the efficacy of FMT in IBD. FMT might be a potential rescue therapy and even an initial standardized therapy for IBD. However, few data exist on long-term safety and efficacy and further validation is needed.