Remission Of Symptoms In Patients Research Articles

P905 Symptomatic remission and IUS improvements in a multi-national real-world cohort of UC patients treated with Upadacitinib - First results from the IBD-DACH study EUROPE

Abstract Background Upadacitinib (UPA) is an oral, reversible and selective Januskinase-inhibitor (JAKi) that was approved for the treatment of several immune-mediated inflammatory diseases, including moderate to severe ulcerative colitis (UC) (1). While the efficacy of UPA has been demonstrated in clinical trials in UC, real-word (RW) evidence on the effectiveness and safety of UPA in UC remains scarce (2). Here, we shed light on the clinical and sonographic results after 2 and 8 weeks of UPA induction in a large, multinational RW cohort of UC patients. Methods EUROPE is an ongoing, prospective, non-interventional, multi-country study in patients with active UC who initiate therapy with UPA. The study assesses the early clinical effectiveness and the predictive value of early disease improvements including sonographic parameters for the long-term outcome after 52 and 104 weeks. For this interim analysis, we report clinical and sonographic results at baseline (BL), week 2 (2W) and week 8 (8W) of 124 UC patients with a visit after 8W until August 2023. For 75 patients, sonographic BL data for the most affected bowel segment was available. Results Of the 124 UC patients, most were male (60.5%, n = 75) with a median age and disease duration of 37.5 years (27.5 – 50.9) and 6.58 years (2.40–12.13). Almost half of all patients had a pancolitis (48.4%, n = 60) The vast majority of patients was bio-experienced (85.5%, n = 106), a third had been exposed to ≥ 3 biologicals (28.2%, n = 35). At BL, patients had a median bowel wall thickness (BWT) of 5.0 mm (3.8-7.0) in the sigmoid colon. It was the most affected segment in 44.4% of patients (n = 55). Disease activity per paMayo score was 3.0 (2.0-5.0) points, with 72.6% (n = 90) and 38.8% (n = 48) of patients reporting ≥ 3 more stools than usual/day and blood in most stools or bleeding without stool, respectively. At 2W after UPA induction, stool frequency and rectal bleeding substantially improved as reflected by the rate of patients in symptomatic remission significantly increasing from 16.9% (n = 21) at BL to 43.5% (n = 54) at 2W and to 64.5% (n = 80) at W8 (both p < 0.001 vs. BL, fig.1). BWT was reduced significantly as early as 2W (n = 48; p < 0.001) and was ≤ 3mm in more than half of all patients. Considering the overall population, 156 patients were included in the safety analysis. Of these, 23.7% (n = 37) experienced an adverse event of which most were non-serious. Conclusion In this first interim analysis of the EUROPE study, UPA treatment in UC was associated with early clinical and sonographic improvement, with most patients achieving symptomatic remission and/or normalization of BWT by week 8 of treatment. 1-SmPC Upadacitinib 2-Danese, Vermeire et al. Lancet. 2022 Jun 4;399(10341):2113-2128

Efficacy and Safety of Ustekinumab for Ulcerative Colitis Through 4 Years: Final Results of the UNIFI Long-Term Maintenance Study.

Ulcerative colitis (UC) is a chronic condition that may require long-term treatment. We report the final efficacy and safety results of the UNIFI long-term extension study of ustekinumab in patients with UC through 4 years. Ustekinumab induction responders who completed 44 weeks of maintenance treatment and agreed to enter the long-term extension continued their subcutaneous maintenance therapy (90 mg ustekinumab every 8 or 12 weeks [q8w or q12w] or placebo). Starting at week 56, randomized patients could receive dose adjustment to 90 mg q8w. Symptoms and adverse events were assessed through the study; endoscopic assessment was conducted at week 200. Of the 348 patients randomized to subcutaneous ustekinumab at maintenance baseline (q8w and q12w combined), 55.2% were in symptomatic remission at week 200. A greater proportion of biologic-naive patients (67.2% [117/174]) were in symptomatic remission than those with a history of biologic failure (41.6% [67/161]). Among patients in symptomatic remission at week 200, 96.4% were corticosteroid-free. Of the 171 patients with endoscopic evaluation at week 200, 81.6% (71/87) in the q12w group and 79.8% (67/84) in the q8w group had endoscopic improvement. From weeks 156 to the final safety visit (up to week 220), no deaths, major adverse cardiovascular events, or tuberculosis occurred in patients receiving ustekinumab. Nasopharyngitis, UC worsening, and upper respiratory tract infections were the most frequently reported adverse events. The long-term efficacy of ustekinumab maintenance in patients with UC was confirmed through 4 years. No new safety signals were observed. ClinicalTrials.gov number NCT02407236.

Inflammatory markers of symptomatic remission at 6 months in patients with first-episode schizophrenia

Neuroinflammation contributes to the pathophysiology of various mental illnesses including schizophrenia. We investigated peripheral inflammatory cytokines as a biomarker for predicting symptomatic remission in patients with first-episode schizophrenia. The study included 224 patients aged 15–60 years who fulfilled the criteria for schizophrenia spectrum disorder with a treatment duration ≤6 months. Serum levels of tumor necrosis factor (TNF) -α, interferon-γ, interleukin (IL)-1α, IL-1β, IL-6, IL-8, IL-10, and IL-12 were measured. Psychotic symptoms, depressive symptoms, and general functioning were assessed using the Positive and Negative Syndrome Scale, Beck Depression Inventory (BDI), Calgary Depression Scale for Schizophrenia, and Personal and Social Performance scale, respectively. Duration of untreated psychosis (DUP) was also recorded. We investigated the factors associated with remission for each sex in logistic regression analysis. In total, 174 patients achieved remission at the 6-month follow-up (females, 83.5%; males, 70.9%). Remission was associated with older age and lower BDI scores in male patients and with lower TNF-α levels and shorter DUP in female patients. Our findings suggest that peripheral inflammatory cytokines may impede early symptomatic remission in female patients with schizophrenia. In addition, depressive symptoms in males and long DUP in females may be poor prognostic factors for early remission in patients with first-episode psychosis.

Dupilumab Can Induce Remission of Eosinophilic Gastritis and Duodenitis: A Retrospective Case Series.

Noneosinophilic esophagitis eosinophilic gastrointestinal disorders (non-EoE-EGIDs) have limited treatment options to induce histologic and clinical remission. Dupilumab is a human monoclonal antibody against the interleukin-4 receptor ɑ subunit, which has been reported to induce improvement in pediatric patients with non-EoE-EGIDs. We conducted a retrospective chart review to identify if patients with eosinophilic gastritis (EoG) and/or eosinophilic duodenitis (EoD) experience clinical and histologic remission with dupilumab. Twelve patients were included (2 patients with EoG and EoD, 3 patients with EoG only, and 7 patients with EoD only). All patients experienced improvement of at least 1 symptom on dupilumab, 3 patients (25%) had no change in severity of 1 or more of their symptoms, and no patients had worsening symptoms. On dupilumab, 2 patients with EoG (40%) and 3 patients with EoD (33.3%) were completely asymptomatic. Histologic changes were investigated in a subanalysis including 8 patients (2 patients with EoG and EoD, 2 patients with EoG only, and 4 patients with EoD only). Median peak gastric eosinophil counts in patients with EoG reduced from 80.5 eos/hpf (min-max 32-150, Q1-Q3 45.5-111) to 7.5 eos/hpf (min-max 0-28, Q1-Q3 1.5-16.8). Median peak duodenal eosinophil counts in patients with EoD reduced from 39 eos/hpf (min-max 30-50, Q1-Q3 37.3-46.3) to 16.5 eos/hpf (min-max 0-50, Q1-Q3 8-38.5). All 4 patients (100%) with EoG and 4 patients (66.6%) with EoD had histologic remission on dupilumab. In this retrospective case series, we showed preliminary evidence that dupilumab may be effective in inducing histologic and symptomatic remission in patients with non-EoE-EGIDs.

Exploring cross-sectional and longitudinal symptomatic remission and subjective quality of life in schizophrenia

Achieving symptomatic remission, as defined by the Remission in Schizophrenia Working Group, is intended to be a meaningful outcome for individuals with schizophrenia, resulting in enhanced well-being. Cross-sectional studies have reported an association between symptomatic remission and subjective quality of life (QoL). Longitudinal studies aimed at examining this association have showed mixed results. The aim of this study was to explore the relationship between symptomatic remission and subjective QoL, both cross-sectionally and longitudinally.The study comprised data from what were at most 386 patients with schizophrenia, of whom 122–140 were followed over a period of four years. Based on cross-sectional remission status and longitudinal remission pattern, differences in subjective QoL were explored. Remission status was assessed using the Positive and Negative Syndrome Scale (PANSS), and subjective QoL using the Short Form-36 Health Survey (SF-36).Both the cross-sectional and the longitudinal approach showed that patients in symptomatic remission had significantly higher subjective QoL. Patients who were in non-remission at baseline, but who achieved remission at follow-up, also had significantly higher subjective QoL at follow-up compared with baseline.The results from the study show a clear association between symptomatic remission and subjective QoL. However, achieving symptomatic remission does not appear to be a guarantee of sustained subjective QoL, and only continued stable remission appears to result in such an outcome.

Pharmacogenomic Testing and Depressive Symptom Remission: A Systematic Review and Meta-Analysis of Prospective, Controlled Clinical Trials.

Pharmacogenomic (PGx) testing has emerged as a compelling strategy that clinicians can use to inform antidepressant medication selection and dosing, but the clinical efficacy of this strategy has been questioned. We systematically reviewed and meta-analyzed clinical trials for an association between the use of PGx-guided antidepressant therapy and depressive symptom remission in patients with major depressive disorder (MDD). We included prospective, controlled clinical trials published in English up to July 12, 2022. Data extraction and synthesis adhered to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Each trial was assessed for risk of bias and a random-effects model was used to estimate pooled risk ratios. Thirteen trials comprising 4,767 patients were analyzed, including 10 randomized controlled trials, and three open label trials. Across all included trials, those that received PGx-guided antidepressant therapy (n=2,395) were 1.41 (95% confidence interval (CI)=1.15-1.74, P=0.001) more likely to achieve remission compared with those that received unguided antidepressant therapy (n=2,372). Pooled risk ratios for randomized controlled trials and open label trials were 1.46 (95% CI: 1.13-1.88) and 1.26 (95% CI=0.84-1.88), respectively. These results suggest that PGx-guided antidepressant therapy is associated with a modest but significant increase in depressive symptom remission in adults with MDD. Efforts to address the heterogeneity in PGx test composition (i.e., genes and alleles tested) and accompanying prescribing recommendations across trials will likely reduce the uncertainty about the efficacy of PGx-guided antidepressant therapy in the literature.

Prognostic Value of Fecal Calprotectin to Inform Treat-to-Target Monitoring in Ulcerative Colitis

We evaluated the value of post-induction fecal calprotectin (FCP) concentration as a biomarker in patients with ulcerative colitis (UC) treated with a biologic. This post hoc analysis of the GEMINI 1/GEMINI LTS (N= 620) and VARSITY (N= 771) trials evaluated the cross-sectional accuracy of post-induction FCP in identifying endoscopic activity and histologic inflammation, and the prognostic performance of FCP in identifying patients most likely to achieve endoscopic and histologic remission or require colectomy and UC-related hospitalization. The cross-sectional accuracy of FCP in identifying endoscopic activity and histologic inflammation was modest (63%-79%). However, a post-induction FCP concentration of ≤250 μg/g vs >250 μg/g was associated with a substantially higher probability of achieving clinical remission (odds ratio [OR], 4.03; 95% confidence interval [CI], 2.78-5.85), endoscopic remission (OR, 4.26; 95% CI, 2.83-6.40), and histologic remission (Robarts Histopathology Index: OR, 5.54; 95% CI, 3.77-8.14; Geboes grade: OR, 6.42; 95% CI, 4.02-10.26) at week 52 and a lower probability of colectomy over 7 years (hazard ratio, 0.296; 95% CI, 0.130-0.677) and UC-related hospitalization (hazard ratio, 0.583; 95% CI, 0.389-0.874). The association with colectomy was significant even among patients in symptomatic remission or with endoscopic improvement post-induction, and among patients with elevated FCP at baseline. Although FCP had only modest cross-sectional accuracy in identifying disease activity, an FCP concentration of ≤250 μg/g vs >250 μg/g was associated with increased probability of achieving long-term clinical, endoscopic, and histologic remission, and reduced probability of colectomy and UC-related hospitalization (ClinicalTrials.gov: NCT00783718, NCT00790933, NCT02497469).

Efficacy and Safety of Maintenance Ustekinumab for Ulcerative Colitis Through 3 Years: UNIFI Long-term Extension.

Background and AimsThe UNIFI long-term extension [LTE] study reports the efficacy and safety of subcutaneous 90 mg ustekinumab through 3 years of maintenance therapy.MethodsPatients randomised to ustekinumab every 12 weeks [q12w] or every 8 weeks [q8w] at maintenance baseline [N = 348] and randomised ustekinumab-treated patients in the LTE [N = 284] were evaluated. Symptomatic remission [Mayo stool frequency = 0/1, rectal bleeding = 0] was assessed. Safety included all LTE patients [N = 188 placebo and N = 457 ustekinumab].ResultsAmong patients randomised to the ustekinumab q12w and q8w groups at maintenance baseline, 54.1% and 56.3% achieved symptomatic remission at Week 152, respectively. Overall, 20% of patients discontinued ustekinumab, 10% of biologic-naïve and 30% of biologic-exposed patients. Among patients in symptomatic remission at Year 3, 94.6% and 98.0% of patients were also corticosteroid free, respectively. Corticosteroid-free symptomatic remission rates in the ustekinumab q12w and q8w groups were 51.2% and 55.1% at Week 152, respectively. Remission rates were higher for biologic-naïve patients than for those with a history of biologic failure. Biochemical evidence of response was demonstrated by stable, decreased C-reactive protein and faecal calprotectin measurements over 3 years. From Weeks 96 to 156, no deaths, major adverse cardiovascular events, or tuberculosis occurred. Nasopharyngitis, ulcerative colitis, and upper respiratory tract infection were most frequently reported. One ustekinumab-treated patient with a history of basal cell carcinoma [BCC] reported two BCCs. One patient in the q8w ustekinumab group, who was receiving concomitant 6-mercaptopurine, experienced serious adverse events of neutropenic sepsis and oral herpes.ConclusionsEfficacy of ustekinumab in patients with ulcerative colitis was confirmed through 3 years. No new safety signals were observed.

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BACKGROUND:Negative symptoms are characterized by a reduction of normal functions. They have been appreciated as core features of schizophrenia but remain under-recognized and poorly treated. They include – affective flattening, alogia, avolition, apathy, anhedonia, asociality, and impairment of attention. Initially thought to be specific to schizophrenia, they are also seen in other disorders – schizoaffective disorder, neuropsychiatric disorders, and bipolar affective disorder.AIMS:To assess various negative symptoms in Schizophrenia and Bipolar affective disorder patients in remission.METHODS:100 patients in symptomatic remission were included in this cross sectional study. Remission was assessed using the Clinical Global Impression Scale (CGI). The Scale for assessment of Negative Symptoms (SANS) was used to evaluate negative symptoms.RESULTS:Negative symptoms were present in 84% of patients in the schizophrenia group and 56% in the bipolar affective disorder group. The overall negative symptom frequency and severity was higher in the schizophrenia group.The mean SANS summary score was 7.38±4.46 in the schizophrenia group, which was higher than the BPAD group(4.80±2.69) and the difference was statistically significant (p=0.005). Affective flattening, alogia, and attentional impairment were significantly impaired in patients with Schizophrenia. Although mean scores were higher on the Anhedonia and avolition domains, the difference was statistically insignificant.CONCLUSION:Residual negative symptoms are frequently present in bipolar disorder and schizophrenia patients in remission and need to be addressed as important treatment goals for better functional recovery and outcome.

Social withdrawal as a trans-diagnostic predictor of short-term remission: a meta-analysis of five clinical cohorts.

Social withdrawal is an early manifestation of several neuropsychiatric disorders, and it is characterised by a gradual disengagement from social interactions, potentially leading to complete isolation. This study investigated the association between social withdrawal at baseline and short-term symptom remission in five independent cohorts, including patients with major depressive disorder (MDD), bipolar spectrum disorders, and schizophrenia. Measures of social withdrawal were derived in each study, and clinical remission was estimated based on the psychopathological severity assessed after short-term psychopharmacological treatment (12 weeks). Logistic regression was performed in each sample, adjusting for age and baseline psychopathological severity residualised for social withdrawal. Results were then meta-analysed across samples within a random-effect framework. A total of 4461 patients were included in the analyses (3195 patients with MDD, 655 with bipolar spectrum disorders and 611 with schizophrenia). The meta-analysis showed that higher baseline levels of social withdrawal were associated with a decreased likelihood of short-term remission (ORadj = 0.67, 95% CI, 0.58-0.79, P = 5.28 × 10-7), with the strongest effect in patients with schizophrenia. Overall, our study highlighted the need to address social withdrawal in the early phases of the disease to promote symptom remission in patients with major psychiatric disorders. Understanding the neurobiology underlying social withdrawal may aid the development of medications that can specifically reverse social impairment, thereby fostering clinical remission.

Proportion and predictors of remission and recovery in first-episode psychosis: Systematic review and meta-analysis.

To determine the proportion of patients in symptomatic remission and recovery following a first-episode of psychosis (FEP). A multistep literature search using the Web of Science database, Cochrane Central Register of Reviews, Ovid/PsychINFO, and trial registries from database inception to November 5, 2020, was performed. Cohort studies and randomized control trials (RCT) investigating the proportion of remission and recovery following a FEP were included. Two independent researchers searched, following PRISMA and MOOSE guidelines and using a PROSPERO protocol. We performed meta-analyses regarding the proportion of remission/recovery (symptomatic plus functional outcomes). Heterogeneity was measured employing Q statistics and I2 test. To identify potential predictors, meta-regression analyses were conducted, as well as qualitative reporting of studies included in a systematic review. Sensitivity analyses were performed regarding different times of follow-up and type of studies. One hundred articles (82 cohorts and 18 RCTs) were included in the meta-analysis. The pooled proportion of symptomatic remission was 54% (95%CI [30, 49-58]) over a mean follow-up period of 43.57months (SD=51.82) in 76 studies. After excluding RCT from the sample, the proportion of remission remained similar (55%). The pooled proportion of recovery was 32% (95%CI [27-36]) over a mean follow-up period of 71.85months (SD=73.54) in 40 studies. After excluding RCT from the sample, the recovery proportion remained the same. No significant effect of any sociodemographic or clinical predictor was found. Half of the patients are in symptomatic remission around 4years after the FEP, while about a third show recovery after 5.5years.

Effect of Originator Infliximab Treatment on Disease-Related Hospitalizations, Work Productivity and Activity Impairment, and Health Resource Utilization in Patients with Crohn’s Disease in a Real-Life Setting: Results of a Prospective Multicenter Study in Germany

Introduction: Infliximab (IFX) therapy is efficacious for inducing and maintaining symptomatic remission in patients with Crohn’s disease (CD), but whether this benefit results in reduced hospitalization rates and therefore may improve patients’ quality of life in an economically sensible way is conflicting so far. Methods: We conducted a noninterventional, multicenter, open-label, prospective study to evaluate the effect of originator IFX treatment on patient-reported outcomes and disease-related hospitalizations in adult CD patients in Germany treated for the first time with IFX according to label. Results: Two hundred and ninety-four patients were included in the study. We observed a statistically significant reduction in the number of CD-related hospitalizations from the year before baseline (mean 1.00 per patient, SD ± 0.93) to the mean value of the 1st (0.62, SD ± 0.95) and 2nd year (0.32, SD ± 0.75) of the observation period (p < 0.0001). After 3 months of IFX therapy, work productivity and activity increased by an average of 12.6 and 17.1%, respectively. Patient’s clinical outcome was markedly improved as the total CD activity index (CDAI) sum score continuously decreased from baseline to month 24 and the mean score of the total inflammatory bowel disease questionnaire (IBDQ) changed substantially from 141 at baseline to 172 after 24 months of IFX treatment. Additionally, the number of work incapacity days declined. Recently, no new safety issues of IFX have been identified. Conclusion: In this large, prospective, multicenter study on disease-related hospitalization rates, work productivity, capacity for daily activities, and HRQoL in patients with CD, IFX significantly reduces their hospitalization rates and improves work productivity, daily activity, and quality of life over 24 months.

Ustekinumab is effective and safe for ulcerative colitis through 2 years of maintenance therapy.

The ongoing UNIFI long-term extension evaluates subcutaneous ustekinumab for moderate-to-severe ulcerative colitis (UC) from weeks 44 through 220. To assess efficacy (through week 92) and safety (through week 96) during the long-term extension METHODS: Overall, 399 responders to intravenous ustekinumab induction and who were randomised to maintenance therapy were treated in the long-term extension (115 received subcutaneous placebo, 141 received ustekinumab 90mg every 12weeks [q12w], and 143 received ustekinumab 90mg q8w). Placebo treatment was discontinued at unblinding after week 44. Partial Mayo scores were collected every 12weeks and at each dosing visit after unblinding. Safety was evaluated throughout. Among all patients randomised in maintenance, symptomatic remission rates (stool frequency=0/1; rectal bleeding=0) at week 92 were, 64.5% and 67.6% in the ustekinumab q12w and q8w groups, respectively. Among randomised patients treated in the long-term extension, 78.7% and 83.2% of patients receiving q12w and q8w, respectively, attained symptomatic remission at week 92; >95% of patients in symptomatic remission at week 92 were corticosteroid-free. Both ustekinumab groups maintained efficacy through week 92. From weeks 44 to 96, adverse events (AEs) per hundred patient-years (PY) of follow-up for combined ustekinumab vs placebo were: 255.68 vs 267.93; serious AEs, 9.34 vs 12.69; malignancies (including non-melanoma skin cancers), 0.93 vs 1.49; and serious infections, 2.33 vs 2.99. One patient with multiple comorbidities who received one ustekinumab dose after dose adjusting from placebo experienced a fatal cardiac arrest. The efficacy of ustekinumab in patients with UC was sustained through 92weeks. No new safety signals were observed (ClinicalTrials.gov number, NCT02407236).

The New Proactive Approach and Precision Medicine in Crohn's Disease.

The proactive approach to Crohn’s disease (CD) management advocates moving toward algorithmic tight-control scenarios that are designed for each CD phenotype to guide remission induction, maintenance therapy, active monitoring, and multidisciplinary care to manage the complexities of each inflammatory bowel disease (IBD) patient. This requires accurate initial clinical, laboratory, radiological, endoscopic, and/or tissue diagnosis for proper phenotypic stratification of each CD patient. A substantial proportion of patients in symptomatic remission have been reported to demonstrate evidence of active disease, with elevated fecal calprotectin(FC) and C-reactive protein (CRP) levels as a hallmark for mucosal inflammation. Active mucosal inflammation, and elevated CRP and fecal calprotectin (FC) have been shown to be good predictors of clinical relapse, disease progression, and complications in IBD patients. The next frontier of treatment is personalized medicine or precision medicine to help solve the problem of IBD heterogeneity and variable responses to treatment. Personalized medicine has the potential to increase the efficacy and/or reduce potential adverse effects of treatment for each CD phenotype. However, there is currently an unmet need for better elucidation of the inflammatory biopathways and genetic signatures of each IBD phenotype, so personalized medicine can specifically target the underlying cause of the disease and provide maximal efficacy to each patient.

S48. INSIGHT VS COGNITION AND SYMPTOMATIC REMISSION AMONG PATIENTS WITH SCHIZOPHRENIA- THE INFLUENCE OF TRAIT VS STATE PHENOMENON?

BackgroundA high ability to understand symptoms and conceptualize illness, schizophrenia, may play a central role for long-term outcome. This based on the assumption that better insight will promote increased adherence. In this work insight is defined as patients′ ability to experience symptoms and furthermore understand what causes them. Cognitive performance and symptomatic remission are analyzed to explore in what way they are contributing to the level of insight.MethodsThe study population is 294 patients with schizophrenia spectrum disorder. Two items with focus on insight, each 1 to 4 points, are used to decide level of insight. The first item “Experience of symptom” and the second item “Understanding the reason for symptoms”, where 1 point representing high and 4 point low level of insight and with a total of 8 points. Patients are then divided into three groups, Good (2 points), Moderate (3 – 5 points) and Poor (6 –8 points). Cognitive domains identified to be impaired in schizophrenia are analyzed related to the three groups of insight. Symptomatic remission is compared to the total score of insight with a Mann-Whitney test and then the different categories of insight in a cross-tabulation and Chi-square test.ResultsDifferences were found in insight between patients in symptomatic remission and those who are not. This in contrast to when patients were divided into the three insights groups and compared on cognitive performance. Only working memory and neurocognitive flexibility showed significant differences to insight. However, crystalized intelligence, as an expression of over-all cognitive ability, did not.DiscussionIn conclusion, only symptomatic remission seems to be related to insight indicating more of a state than a trait phenomenon. Surprisingly could not different levels of insight be connected to differences in cognitive ability. As this is a cross-sectional study, further research are needed where insight and symptomatic remission are analyzed in longitudinal conditions. Such a study has to focus on if successful treatment promote insight or the other way around.

P081 Rapid Symptomatic Remission in Patients With Ulcerative Colitis Treated With the Anti-MAdCAM-1 Antibody Ontamalimab: Results From TURANDOT and TURANDOT II

BACKGROUND: Treatment of ulcerative colitis (UC) aims to induce and maintain both endoscopic and symptomatic remission. While assessment of endoscopic remission is limited by timing of endoscopy, symptomatic remission can be assessed at any clinical visit, thus potentially allowing a more granular assessment of the time to onset of efficacy of a therapeutic agent. Ontamalimab (SHP647), a monoclonal IgG2 antibody against mucosal addressin cell adhesion molecule-1, can induce endoscopic remission in patients with moderate-to-severe UC after 12 weeks of treatment (1), but its effects on symptomatic remission at earlier timepoints remain unexplored. We aimed to determine rates of clinical and symptomatic remission in patients with UC during ontamalimab induction treatment. METHODS: Two phase 2 studies (TURANDOT, NCT01620255 and TURANDOT II, NCT01771809) were conducted. Patients who completed TURANDOT, a 12-week, double-blind, placebo-controlled trial of ontamalimab (7.5, 22.5, 75 and 225 mg s.c. every 4 weeks [Q4W]), who had discontinued immunosuppressants could enter TURANDOT II, the open-label extension study. TURANDOT II consisted of two open-label periods followed by a 24-week follow-up period. At baseline (TURANDOT week 12), patients were randomized to ontamalimab 75 or 225 mg s.c. Q4W for 72 weeks. Dose escalation from 75 to 225 mg was permitted between weeks 8 and 72 in cases of clinical exacerbation or no response. Partial Mayo scores (PMS), assessed in both trials, were used to determine proportions of patients with clinical remission (PMS of ≤2 with no individual subscore >1 and a rectal bleeding [RB] subscore of ≤1) and symptomatic remission (an RB subscore of 0 and stool frequency subscore of ≤1). RESULTS: In total, 357 patients received placebo (n = 73) or ontamalimab (7.5 mg, n = 71; 22.5 mg, n = 72; 75 mg, n = 71; 225 mg, n = 70) in TURANDOT. At week 4, the proportions of patients with clinical remission were greater in the treated groups than the placebo group, particularly the 22.5 mg (difference vs placebo [90%CI] 11.2% [0.4, 21.9]) and 75 mg groups (10.3% [–0.5, 20.9]). The proportions with clinical remission at week 8 were 19.2%, 19.7%, 36.1%, 32.4% and 34.3%, and by week 12 were 16.4%, 23.9%, 40.3%, 36.6% and 25.7%, in the placebo, 7.5, 22.5, 75 and 225 mg groups, respectively. A total of 330 patients completed TURANDOT and were randomized and treated in TURANDOT II. All patients received open-label ontamalimab (75 mg, n = 164; 225 mg, n = 166) in TURANDOT II; 68 had previously received placebo, and 262 had received ontamalimab in TURANDOT. In patients who previously received placebo, there was a rapid increase in the proportion with clinical remission from baseline (75 mg, 24.2%; 225 mg, 11.4%) to week 4 (48.5%; 42.9%), week 8 (51.5%; 42.9%) and week 12 (63.6%; 57.1%). Similar patterns were observed in the results for symptomatic remission both in TURANDOT and TURANDOT II. CONCLUSION(S): The ability of ontamalimab to induce clinical and symptomatic remission is rapid and robust, as shown initially in patients in TURANDOT (particularly at doses of 22.5 and 75 mg, with differences versus placebo as early as week 4) and confirmed in those who received ontamalimab for the first time in TURANDOT II.

Allopregnanolone and progesterone in estradiol treated severe postpartum depression and psychosis – Preliminary findings

BackgroundPostpartum affective disorders may be associated with dysregulation of gonadal steroids. We investigated peripheral levels of allopregnanolone and progesterone in a combined group of women with postpartum onset of severe depression and/or psychosis who, as previously reported, responded with rapid symptom remission during sublingual estradiol treatment. The aim was to assess differences in allopregnanolone and progesterone between patients and healthy controls at baseline, and hormonal changes during estradiol treatment and symptom remission in patients. MethodsAllopregnanolone and progesterone in serum were analyzed with radioimmunoassay before and four weeks after initiation of sublingual estradiol treatment in ten women with postpartum depression and four women with postpartum psychosis (ICD-10). Twenty-eight healthy postpartum controls were included for baseline comparison. ResultsAllopregnanolone declined significantly during estradiol treatment while there was a trend for lower baseline allopregnanolone levels in patients compared with healthy postpartum controls. The ratio between allopregnanolone and progesterone was significantly lower in patients compared with controls and it remained unchanged after clinical recovery. LimitationsThis study is a secondary analysis of two estradiol treatment studies based on availability of samples for the analysis of allopregnanolone. Healthy controls were assessed earlier after delivery. Data on potential confounders (somatic health, breastfeeding, other medication) were not available. ConclusionsThese preliminary findings suggest that clinical recovery of severe postpartum depression and psychosis during estradiol treatment does not seem to depend on increasing levels of allopregnanolone. Differences in progesterone metabolism may constitute a risk factor for severe postnatal affective dysregulation.

A process approach to verbal memory assessment: Exploratory evidence of inefficient learning in women remitted from anorexia nervosa

ABSTRACTIntroduction: Anorexia nervosa (AN) is associated with deficits in set-shifting and cognitive flexibility, yet less is known about the persistence of these deficits after recovery and how they might contribute to reported difficulties organizing and learning new information. To address this question, the current study applied a process-focused approach, that accounts for errors and strategies by which a score is achieved, to investigate the relationship between verbal memory and executive function in women remitted from AN.Method: Twenty-six women remitted from anorexia nervosa (RAN) and 25 control women (CW) aged 19–45 completed the California Verbal Learning Test, Second edition (CVLT-II) and the Wisconsin Card Sorting Test (WCST). Groups were compared on overall achievement scores, and on repetition, intrusion, and perseverative errors on both tests. Associations between learning and memory performance and WCST errors were also examined.Results: RAN and CW groups did not differ on overall CVLT-II learning and memory performance or errors on the WCST, though the RAN group trended towards greater WCST non-perseverative and total errors. On the CVLT-II, the RAN group made significantly more repetition errors than CW (p = 0.010), and within-trial perseveration (WTP) errors (p = 0.044). For the CW group, CVLT-II learning and memory performance were negatively associated with errors on the WCST, whereas among RAN, primarily delayed memory was negatively correlated with WCST errors. Notably, for RAN, greater WCST perseverative responses were correlated with greater CVLT-II repetition and WTP errors, showing the convergence of perseverative responding across tasks.Conclusions: Despite similar overall learning and memory performance, difficulties with executive control seem to persist even after symptom remission in patients with AN. Results indicate an inefficient learning process in the cognitive phenotype of AN and support the use of process approaches to refine neuropsychological assessment of AN by accounting for strategy use.

Predicting one-year outcome in first episode psychosis using machine learning.

BackgroundEarly illness course correlates with long-term outcome in psychosis. Accurate prediction could allow more focused intervention. Earlier intervention corresponds to significantly better symptomatic and functional outcomes. Our study objective is to use routinely collected baseline demographic and clinical characteristics to predict employment, education or training (EET) status, and symptom remission in patients with first episode psychosis (FEP) at one-year.Methods and findings83 FEP patients were recruited from National Health Service (NHS) Glasgow between 2011 and 2014 to a 24-month prospective cohort study with regular assessment of demographic and psychometric measures. An external independent cohort of 79 FEP patients were recruited from NHS Glasgow and Edinburgh during a 12-month study between 2006 and 2009. Elastic net regularised logistic regression models were built to predict binary EET status, period and point remission outcomes at one-year on 83 Glasgow patients (training dataset). Models were externally validated on an independent dataset of 79 patients from Glasgow and Edinburgh (validation dataset). Only baseline predictors shared across both cohorts were made available for model training and validation. After excluding participants with missing outcomes, models were built on the training dataset for EET status, period and point remission outcomes and externally validated on the validation dataset. Models predicted EET status, period and point remission with receiver operating curve (ROC) area under the curve (AUC) performances of 0.876 (95%CI: 0.864, 0.887), 0.630 (95%CI: 0.612, 0.647) and 0.652 (95%CI: 0.635, 0.670) respectively. Positive predictors of EET included baseline EET and living with spouse/children. Negative predictors included higher PANSS suspiciousness, hostility and delusions scores. Positive predictors for symptom remission included living with spouse/children, and affective symptoms on the Positive and Negative Syndrome Scale (PANSS). Negative predictors of remission included passive social withdrawal symptoms on PANSS. A key limitation of this study is the small sample size (n) relative to the number of predictors (p), whereby p approaches n. The use of elastic net regularised regression rather than ordinary least squares regression helped circumvent this difficulty. Further, we did not have information for biological and additional social variables, such as nicotine dependence, which observational studies have linked to outcomes in psychosis.Conclusions and relevanceUsing advanced statistical machine learning techniques, we provide the first externally validated evidence, in a temporally and geographically independent cohort, for the ability to predict one-year EET status and symptom remission in individual FEP patients.

Shared and distinct alterations of white matter tracts in remitted and nonremitted patients with schizophrenia.

Patients with schizophrenia do not usually achieve remission state even after adequate antipsychotics treatment. Previous studies found significant difference in white matter integrity between patients with good outcomes and those with poor outcomes, but difference is still unclear at individual tract level. This study aimed to use a systematic approach to identify the tracts that were associated with remission state in patients with schizophrenia. We evaluated 91 patients with schizophrenia (remitted, 50; nonremitted, 41) and 50 healthy controls through diffusion spectrum imaging. White matter tract integrity was assessed through an automatic tract-specific analysis method to determine the mean generalized fractional anisotropy (GFA) values of the 76 white matter tract bundles in each participant. Analysis of covariance among the 3 groups revealed 12 tracts that were significantly different in GFA values. Post-hoc analysis showed that compared with the healthy controls, the nonremission group had reduced integrity in all 12 tracts, whereas the remission group had reduced integrity in only 4 tracts. Comparison between the remission and nonremission groups revealed 4 tracts with significant difference (i.e., the right fornix, bilateral uncinate fasciculi, and callosal fibers connecting the temporal poles) even after adjusting age, sex, education year, illness duration, and medication dose. Furthermore, all the 4 tracts were correlated with negative symptoms scores of the positive and negative syndrome scale. In conclusion, our study identified the tracts that were associated with remission state of schizophrenia. These tracts might be a potential prognostic marker for the symptomatic remission in patients with schizophrenia.