Probability Of Remission Research Articles

Metabolic targeting of neuroblastoma, an update.

Neuroblastoma is a paediatric cancer of the sympathetic nervous system that originates from the neural crest and can be categorised into stages and risk groups. Risk groups inform treatment options and high-risk cases bear a 50% probability of relapse post-treatment remission. In neuroblastoma, MYCN amplification is the strongest predictor of unfavourable patient prognosis; circa 50% of high-risk cases display MYCN amplification. This dismal prognosis is perhaps influenced by the MYCN-driven metabolic rewiring of these cells since the MYC family is indicated in the regulation of proliferation, cell death, metabolism, differentiation, and protein synthesis. This review aims to capture the most recent studies that investigate metabolic rewiring in MYCN-amplified and MYCN-activated cells from the perspective of alterations to glycolysis, the TCA cycle, and oxidative phosphorylation, in addition to changes to amino acid, nucleotide, and lipid metabolism that can be relevant to therapy. A better understanding of the metabolic profile of MYCN-amplified disease will facilitate the identification of effective treatment options and improve the prognosis of high-risk neuroblastoma patients.

Probability of remission with reinduction with 7+3 versus high-dose cytarabine: analysis of SWOG trial S1203.

Probability of remission with reinduction with 7+3 versus high-dose cytarabine: analysis of SWOG trial S1203.

P0695 Quantifying the benefit-risk trade-offs adult patients and providers are willing to make when considering advanced therapies for moderate to severe Ulcerative Colitis: A discrete choice experiment

Abstract Background As advanced therapy options for ulcerative colitis (UC) increase, it is important to understand the benefit-risk trade-offs patients and providers are willing to make to better inform shared decision making. Methods We used a cross-sectional survey with a discrete choice experiment (DCE) design to quantify advanced UC therapy preferences in patients with moderate to severe UC and practicing providers from the US, UK, France, Germany, Italy and Spain. Respondents chose between hypothetical combinations of attributes that were informed by a targeted literature search and formative qualitative research with patients and clinicians. Attributes comprised of time until symptom improvement, probability of remission at one year, probability of corticosteroid (CS)-free remission at one year, annual risk of serious infection, five-year risk of cancer and annual risk of major adverse cardiovascular event (MACE). Relative importance (RI; scaled 0–100%) for each attribute was calculated as the difference in mean preference weights between the most and least preferred level divided by the sum of the differences; for RI, remission attributes were combined. The maximum-acceptable risk (MAR) for each risk attribute, and the simultaneous MAR thresholds (SMARTs) for all risk attributes considered jointly, in exchange for a 10-percentage point increase in probability of remission at one year were estimated. Results For treatment choices, combined remission and CS-free remission at one year was significantly prioritised by patients (N=557; RI 40.1%) and providers (N=500; RI 51.1%), followed by five-year risk of cancer (RI 31.7% and 25.7%, respectively) (Table). Time to symptom improvement was significantly preferred vs annual risk of MACE and serious infection for providers, but not patients (Table). For a 10-percentage point increase in probability of remission at one year, providers had a higher MAR for five-year risk of cancer vs patients (4.0% vs 2.5%); for the other two risk attributes, reported MARs were beyond the DCE-included limits (Figure). For a 10-percentage point increase in the probability of remission at one year when annual risk of serious infection was 1% or 3%, providers were willing to jointly accept higher annual risk of MACE and five-year risk of cancer vs patients (Figure). Conclusion Combined probability of remission and CS-free remission at one year had the strongest influence on treatment choice. Compared with patients, providers on average placed greater importance on benefits and had a higher tolerance of risks, particularly 5-year risk of cancer. These findings highlight the importance of shared clinical decision making. References Pfizer’s generative artificial intelligence tool MAIA was used to assist production of the abstract first draft. Authors reviewed/edited and take responsibility for the content.

P1051 Establishment and Validation of Prediction Models for Short-term and Long-term Effectiveness of Ustekinumab in Patients with Crohn’s Disease

Abstract Background Ustekinumab (UST), a novel biological agent for Crohn’s disease (CD), has shown efficacy in CD patients. Our objective was to establish clinical prediction models to accurately forecast the short- and long-term effectiveness of UST in individuals diagnosed with CD. Methods We established a derivation cohort comprising patients diagnosed with CD and treated with UST at the Sixth Affiliated Hospital of Sun Yat-sen University from May 2020 to July 2023. The patients were assigned in a 7:3 ratio at random to the training cohort and the validation cohort. Predictors were compressed through the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. Logistic regression analysis was used to create the final prediction models. Results A total of 464 patients with CD were included in the statistical analysis, 171 of whom had complete endoscopic data. Four models were constructed: two to predict the probability of clinical or endoscopic remission at week 16 or 20 based on baseline data, and two to predict the probability of clinical or endoscopic remission at week 52 based on data obtained at week 16 or 20. The C-index was 0.714, 0.866, 0.814 and 0.841, respectively. Because of poor calibration, we constructed another model to predict the probability of endoscopic remission at week 52 based on baseline data (C-index:0.748). In the internal validation, the above models showed good performance. Conclusion We have constructed several models to predict the short- and long-term effectiveness of UST in patients with CD, promising to be a simple and practical clinical tool.

P1323 Differential Microbiome Responses to the Crohn’s Disease Exclusion Diet in Pediatric vs. Adult Populations: Insights from Randomized Controlled Trials

Abstract Background The Crohn’s Disease (CD) Exclusion Diet (CDED) is a recognized dietary therapy for managing mild-to-moderate CD in children and adults1,2. This study aimed to compare the effects of CDED on the microbiome in children and adults, based on randomized controlled trials (RCTs) in both cohorts1,2. Methods We analyzed fecal samples from 2 RCTs; one comparing CDED to exclusive enteral nutrition in children over 12 weeks (n:W0 = 69, n:W06 = 57, n:W12 = 52), and the other examining CDED with or without partial enteral nutrition in adults over 24 weeks (n:W0 = 35, n:W06 = 32, n;W12 = 30, n:W24 = 26). We compared the pediatric CDED group with both adult groups, all with mild-to-moderate disease and active inflammation. The V4-V5 region of the 16S rRNA gene was amplified and sequenced, with reads processed through QIIME2 and the SILVA database. Associations between the microbiome, short-term clinical remission and fecal calprotectin (FC) were analyzed using logistic regression, Poisson Principal Component Analysis, Wilcoxon tests, ANOVA, and subsampling ranking forward selection. Results Pediatric patients had higher baseline alpha diversity, which significantly increased by week 12 and was higher in remission compared to adults, who showed a similar but nonsignificant trend. In both pediatric and adult cohorts, baseline Haemophilus abundance was significantly associated with reduced probability of sustained remission (measured at weeks 6 and 12 [pediatric], and 12 and 24 [adults]). Ruminococcus levels increased from baseline to week 6 in patients who did not achieve remission across both cohorts. At week 12, pediatric patients had more taxa associated with achieving remission, whereas adults showed more taxa linked to non-remission. Prevotella was associated with non-remission in both pediatric and adult cohorts, while Akkermansia was linked to non-remission in adults only. By weeks 6 and 12, both cohorts showed increases in Oscillibacter and decreases in Haemophilus.In adults, Alistipes increased over time and was associated with milder disease at baseline for both cohorts. Higher baseline FC in children suggested more severe initial disease. An increase in Firmicutes was associated with lower FC in both cohorts, indicating beneficial microbiome shift in response to CDED. In patients with more severe disease, higher Proteobacteria prevalence was observed, with a stronger difference observed in pediatric than in adult. Conclusion These finding suggest that key microbiome could serve as biomarkers for predicting responses to CDED, enabling more personalized dietary management for CD. Microbial shifts associated with reduced inflammation after CDED, highlight the potential for tailored dietary approaches for both children and adults.

P0876 One-year effectiveness and safety of ustekinumab treatment in patients with ulcerative colitis: An Asan-Crohn’s and Colitis Association in Daegu-Gyeongbuk (CCAiD) multicentre real-world cohort study

Abstract Background The real-life data on ustekinumab (UST) for Asian patients with ulcerative colitis (UC) are limited. We aimed to assess one-year effectiveness and safety of UST for Korean patients with UC. Methods This was a multicentre retrospective study on patients with UC who received UST at 4 academic centers in Korea between January 2021 and October 2023. The primary endpoint was clinical remission defined as partial Mayo score (PMS) ≤2 and no subscore >1 at week (W) 8 of therapy. Secondary endpoints included clinical remission (W16–20 and W52–56), corticosteroid-free clinical remission (W8, W16–20, and W52–56), clinical response (W8, W16–20, and W52–56), endoscopic remission defined as Mayo endoscopic subscore (MES) 0–1 (W16–20 and W52–56), interval shortening and durability of UST therapy till W52–56, and adverse events. Results A total of 60 patients (Male, 63.3%; Median age, 44.5 years; Disease duration, 6.5 years; Previous exposure to advanced therapies, 70.0%; Extensive colitis, 65.0%; Median baseline Mayo score, 8; Concomitant use of immunomodulators, 40.0%) were included. Excluding one patient in clinical remission at baseline, 49.2% (29/59) achieved clinical remission at W8. At W16–20, and W52–56, 59.3% (35/59), and 55.9% (33/59) achieved clinical remission. The clinical response rates at W8, W16–20, and W52–56 were 67.9% (40/59), 69.5% (41/59), and 66.1% (39/59), respectively (Figure 1). Endoscopic remission rates at W16–20 and W52–56 were 55.9% (33/59) and 37.3% (22/59), respectively (Figure 1). Multivariable analysis identified factors associated with clinical remission at W52–56 (body mass index, adjusted odds ratio [aOR]: 1.26, 95% confidence interval [CI] 1.00–1.57, p<0.05; previous exposure to advanced therapies, aOR: 0.20, 95% CI 0.04–0.98, p<0.05; concomitant use of immunomodulators, aOR: 4.69, 95% CI 1.04–21.06, p=0.04; endoscopic remission at W16–20, aOR: 13.47 95% CI 2.87–63.30, p<0.01). Till W52–56, the interval shortening rate for subcutaneous UST treatment from every 12 to 8 weeks was 20% (12/60). Nine patients (15.0%) stopped UST, primarily due to a secondary loss of response (8.3%, 5/60), followed by a primary non-response (6.7%, 4/60). Adverse events occurred in 24 patients (40.0%) and serious adverse event in one patient (1.7%) (Table 1). Conclusion UST was effective with an acceptable safety profile for Korean patients with UC. Previous exposure to advanced therapies was associated with a lower probability of clinical remission at one year after UST therapy. Financial support This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2021R1A2C2095096).

OP08 Histology-derived cell-cell interaction networks, linked to transcriptome profiling, define path to resolution in UC

Abstract Background Despite therapeutic advancements, the cellular and molecular heterogeneity of UC hinders effective treatment. We applied machine learning-based approaches to whole scanned images (WSI) of H&E stained slides prepared from formalin-fixed, paraffin embedded intestinal mucosal biopsies from the etrolizumab clinical trials, aiming to identify cellular interactions and molecular signatures that define disease subtypes and treatment responses. We hypothesised that the cellular-basis of non-response could be derived by linking cell-cell relationships with paired transcriptomic profiles. Methods We analysed 2297 WSI paired with molecular data from 1272 UC patients from the etrolizumab PhIII clinical trial including various cohorts, treatment arms, and timepoints. Sections were segmented using a convolutional neural network, extracting 8 cell types and their coordinates. For each WSI, ~500 interaction features from an overlaid network were engineered using our developed software, CellMaskProfiler. The topology of the cell-cell interaction networks allowed clustering of WSI with similar profiles. Cell count features and clinical data enabled the annotation of clusters. Paired molecular data was used to perform differential expression. Results Using the cell-cell topology, we identified 7 distinct UC subtypes characterised by specific cellular interactions, molecular profiles and clinical features resolving into, intact, and neutrophil, eosinophil, plasma, or lymphocyte dominated profiles. WSI with a high proportion of epithelial cells and more connections between epithelial cells types were strongly associated with lower Robarts Histology Index, indicating milder disease or intact epithelium, while strong interaction with neutrophils showed the opposite effect. Looking at different treatment arms allowed to relate baseline biopsy WSI characteristics with probability of treatment response highlighting the probability of response based on initial WSI subtype. Using the cellular topology allowed to characterise the transition between diseased and healthier clusters. Adjusting for cellularity effects and comparing baseline data for response at induction revealed genes characterising response. Looking at transitions between clusters revealed similar genes. Conclusion This study introduces a novel feature engineering approach to unravel the cellular and molecular complexity of WSI in UC. The findings underscore the significance of cellular interactions in UC pathology and provide new insights into the molecular mechanisms underlying different disease states and demonstrates that the structural topology (form) derived from WSI can be effectively linked to the transcriptomic profiles (function) to define probability of remission.

Establishment and internal validation of a model to predict the efficacy of Adalimumab in Crohn’s disease

Background: Clinically, the ability to distinguish which Crohn’s disease patients can benefit from Adalimumab is limited. Aims: This study aimed to develop a model for predicting clinical remission probability for Crohn’s disease patients with Adalimumab at 12 weeks. The model assists clinicians in identifying which Crohn’s disease patients are likely to benefit from Adalimumab treatment before starting therapy, thus optimizing individualized treatment strategies. Methods: Demographic and clinical characteristics of Crohn’s disease patients were utilized to develop a model for clinical remission probability. LASSO regression was used to select predictive factors, and predictions were made using a logistic regression model. The model was internally validated using the bootstrap method (resampling 1000 times). Results: 68 patients with Crohn’s disease were enrolled in this study. Clinical remission was observed in 55.9% at 12 weeks. Three variables were selected through the least absolute shrinkage and selection operator regression method, including Adalimumab-positive cell count, disease duration, and neutrophil count of Crohn’s disease patients. A predictive model was constructed by multivariate logistic regression (Adalimumab-positive cell count (OR, 1.143; 95%CI, 1.056–1.261), disease duration (OR, 0.967; 95%CI, 0.937–0.986), and neutrophil count (×109/L) (OR, 1.274; 95%CI,1.014–1.734)). The predictive model yielded an area under the curve of 0.866 (95%CI, 0.776–0.956), and in the internal validation, the area under the curve was 0.870 (95%CI, 0.770–0.940). Conclusions: This model provides a convenient tool to assess the likelihood of patient remission prior to Adalimumab treatment, thereby supporting the development of personalized treatment plans.

Nomogram-Based model accurately predicts disease flare-ups in axial spondyloarthritis

Background: The accuracy of predicting axial spondyloarthritis (axSpA) flares based on clinical experience is limited. Objective: The aim of this study was to evaluate the efficacy of the previously designed nomogram prediction model in forecasting disease flares among rheumatologists and medical students. Methods: Patients who met the classification criteria for axSpA were enrolled in the study. Once a low ankylosing spondylitis disease activity score (ASDAS ≤ 2.1) was achieved, patients were monitored for 12 months to observe any disease flare-ups. Investigators assessed the likelihood of axSpA recurrence using the nomogram prediction model and their clinical experience, respectively. This allowed for a comparison of the predictive efficacy of both methods among the specialists and students. Results: The accuracy, sensitivity, specificity, and Youden index in which disease flare-ups were predicted by the rheumatologist using clinical experience were slightly lower than those obtained using the nomogram prediction model, but the difference was not statistically significant ( P > 0.05). In contrast, the indicators above by medical students using clinical experience were significantly lower compared to those predicted by the nomogram prediction model ( P < 0.05). Conclusion: The nomogram prediction model is effective in predicting the probability of disease remission and flare-ups in axSpA patients with low disease activity, demonstrating good clinical practicality and usability. Medical students can also use this model to significantly enhance the accuracy of predicting axSpA flares.

Serum Albumin and Its Trajectory Are Associated With Therapeutic Outcomes in Ulcerative Colitis.

The relationship between serum albumin levels and therapeutic outcomes in ulcerative colitis (UC) has been debated. Additionally, the dynamic changes in albumin levels remain understudied. We conducted a pooled analysis of 5 clinical trials involving 3268 patients with UC. Short- and long-term therapeutic outcomes were assessed at the end of the induction and maintenance phases. Multivariate logistic regression and random effects models were used to pool the predictive effects of albumin levels. The dynamic trajectory of albumin was fitted using latent class growth mixed models. Baseline and week-2 albumin were independent predictors of short-term outcomes, with pooled adjusted odds ratios (aORs) of 1.07 (95% confidence interval [CI],1.05-1.09) and 1.11 (95% CI, 1.08-1.15) per 1 g/L increase for clinical response, respectively. Higher post-induction albumin levels predicted better long-term outcomes, including clinical (aOR, 1.16; 95% CI, 1.12-1.21), endoscopic (aOR, 1.13; 95% CI, 1.10-1.16), and histologic remission (aOR, 1.11; 95% CI, 1.03-1.18). Furthermore, there are 3 classes of albumin trajectories: sustained medium-to-high, rapidly ascending, and poor response. Compared with the sustained medium-to-high class, patients in the poor response class had a lower probability of long-term endoscopic remission (aOR, 0.35; 95% CI, 0.23-0.50; P < .001), whereas no significant difference was observed between the rapidly ascending class and the sustained medium-to-high class. Higher albumin levels were associated with better therapeutic outcomes in patients with UC. However, patients with low but rapidly ascending albumin levels would achieve outcomes comparable to those with medium-to-high levels of albumin.

Differences in Splicing Factors may predict Type 2 Diabetes Remission in the CORDIOPREV study

Alternative splicing is a post-transcriptional process resulting in multiple protein isoforms from a single gene. Abnormal splicing may lead to metabolic diseases, including type 2 diabetes mellitus (T2DM). To identify splicing factor expression predicts T2DM remission in coronary heart disease (CHD) patients, we identified newly diagnosed T2DM at baseline (n=190) from the CORDIOPREV study. Patients were classified as Responders (T2DM remission during 5 years without antidiabetic drugs) or non-Responders. Baseline dysregulation in 5 splicing factors (MBNL1, RBM5, hnRNP G/RBMX, CD44, NT5E) distinguished Responders from non-Responders. Adding these factors to clinical variables [AUC=0.67], insulin resistance and beta-cell indexes [AUC=0.76], improved T2DM remission prediction [AUC=0.80]. Cox regression analysis showed those with higher remission scores had a 2.63-fold increased remission probability. To conclude, a set of splicing factors contribute to predicting T2DM remission in patients with CHD has been identified. Further research is needed to elucidate these findings’ clinical relevance.

DRAMS — the new system for predicting type 2 diabetes mellitus remission after baritaric surgery

BACKGROUND: Bariatric surgery has proven effective as a treatment for the metabolic complications of obesity, including type 2 diabetes mellitus (T2DM). Nowadays it is important to develop a personalized approach for bariatric patients generally, and for those with T2DM.AIM: Development of a scale for preoperative prediction of remission of T2DM in obese patients Russian population undergoing bariatric surgery (sleeve gastrectomy or gastric bypass).MATERIALS AND METHODS: A retrospective multicenter cohort study was conducted. The study included 112 patients (75 women and 37 men), mean age 46.25±9.29 years, mean BMI 48.71±7.66 kg/m2. A mathematical analysis of 17 preoperative clinical criteria was carried out to search for independent predictors of T2DM remission.RESULTS: A remission of T2DM was verified in 85 subjects, (75.9%), absence of remission of T2DM — in 27 subjects (24.1%). The most important prognostic factors were T2DM experience, age, HOMA-IR insulin resistance index, HbA1c, BMI, metformin therapy, SUs, insulin intake, increased levels of liver transaminases, and total cholesterol levels. The relative importance coefficient of each parameter was calculated. A formula has been developed to predict the high or low probability of T2DM remission after bariatric treatment. An online DRAMS (Diabetes Remission After Metabolic Surgery) calculator was proposed based on this formula so it is easy to use in clinical practice.CONCLUSION: An online calculator has been developed to predict the probability of T2DM remission after bariatric surgery. The received data allow us to construct a qualitative “high risk”/“low risk” scale. A number of identified predictors require further study in larger samples of patients.

Predictors for spontaneous remission in childhood chronic immune thrombocytopenia.

This study examined the factors associated with spontaneous remission in children with chronic immune thrombocytopenia (ITP). We retrospectively analyzed the medical records of patients diagnosed with ITP from January 1988 to December 2019 at our institute. A total of 104 children with chronic ITP were identified. The median follow-up time from diagnosis of chronic ITP was 3.6 years (IQR 1.2-8.3, range 0.1-31.4). Fifteen (14.4%) patients with severe symptoms received specific platelet-elevating therapies, including splenectomy, rituximab, and thrombopoietin receptor agonists. Seven of them achieved remission. Among the patients with a platelet count < 30 × 109/L at the time of diagnosis of chronic ITP, those who received specific platelet-elevating therapies had a higher remission rate compared to those who did not (HR: 4.66, 95% CI: 1.36-16.0). Sixteen patients (15.4%) developed systemic lupus erythematosus, 46 (44.2%) still had thrombocytopenia after a median follow-up of 6.8 years, and 42 (40.4%) achieved remission with a median time to remission of 2.0 years (IQR 0.6-4.1, range 0.1-15.7). The two independent predictive factors for spontaneous remission in childhood chronic ITP were platelet counts > 30 × 109/L at the time of diagnosis of chronic ITP (HR: 3.16, 95% CI: 1.51-6.62) and persistently negative ANA at follow-up (HR: 6.12, 95% CI: 1.46-25.7). The cumulative probabilities of spontaneous remission at 10 years post-diagnosis of chronic ITP were 72.2% for patients without risk factor compared to 0% for patients with two risk factors.

Estimating the benefit of esketamine nasal spray versus real-world treatment on patient-reported functional remission: results from the ICEBERG study.

Treatment resistant depression (TRD) affects approximately 10-30% of patients with major depressive disorder, and most patients with TRD do not respond to real-world treatments (RWT). Treatment with esketamine nasal spray (NS) plus a selective serotonin or serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) has significant long-term clinical benefit over RWT in patients with TRD. However, the impact on patient-reported function remains to be determined. The ICEBERG analysis was an indirect treatment comparison performed using data from two studies of patients with TRD: SUSTAIN-2 (esketamine NS; NCT02497287) and the European Observational TRD Cohort (EOTC; RWT; NCT03373253; clinicaltrials.gov). Here, patient-reported functional remission, assessed using the Sheehan Disability Scale (SDS), was defined as SDS ≤6 at Month 6. Analyses were conducted using propensity score re-weighting and multivariable models based on 18 covariates. At Month 6, the probability of functional remission in esketamine NS-treated patients from SUSTAIN-2 (n=512) was 25.6% (95% confidence interval [CI] 21.8-29.4), while the adjusted probability for RWT patients from the EOTC (n=184) was 11.5% (95% CI 6.9-16.1; relative risk: 2.226 [95% CI 1.451-3.416]; p=0.0003). In the total combined population (N=696), patients who did not achieve clinical response or remission had a low probability of achieving functional remission (5.84% and 8.76%, respectively). However, for patients who did achieve clinical response or remission, the probability of achieving functional remission was greater (43.38% and 54.15%, respectively), although many still did not achieve this status. For patients with TRD, esketamine NS had a significant functional benefit versus RWT after 6 months of treatment. Irrespective of treatment, achievement of clinical response or remission was insufficient to attain functional remission. Nevertheless, clinical remission increased the likelihood of achieving functional remission, further supporting an important role for clinical remission in for the path towards functional recovery.

7220 Menopause Has a Beneficial Influence on the Evolution of Prolactinomas: a Study in 95 Patients

Abstract Disclosure: S. Constantinescu: None. C. Nava: None. F. Chasseloup: None. P. Chanson: Consulting Fee; Self; Eli Lilly &amp; Company, Recordati, Ipsen, Novo Nordisk. O. Alexopoulou: None. D.M. Maiter: Consulting Fee; Self; Ipsen, Recordati, Pfizer, Inc. The natural occurrence of menopause is considered to have beneficial effects in women with a prolactinoma and represents a window of opportunity for successful dopamine agonist (DA) withdrawal. Strong evidence for these effects remains however scarce. We retrospectively analyzed data from 95 women undergoing menopause (Mp) (FSH&amp;gt;35 U/L) while still treated with DA (cabergoline (CAB) in 82) for a prolactinoma diagnosed at a mean age of 38.0 ± 8.0 years. The pituitary tumor was a microadenoma in 66 and a macroadenoma in 29 (invasive in 12). Our objectives were to identify the influence of menopause on the evolution of treated prolactinomas and on the risk of recurrence after DA withdrawal. In post-menopausal women still treated with DA (median dose of 0.50 mg CAB/week or equivalent), a significant decrease in median prolactin (PRL) was observed from a premenopausal value of 15.1 µg/L to 10.7 µg/L 3-6 months after Mp (n=64, P=0.05) and to 7.7 µg/L 24 months after Mp (n=43, P &amp;lt; 0.001). There was also a significant reduction in median coronal tumor surface at 24 months, from 12.6 to 7.1 mm² (p &amp;lt; 0. 01). DA treatment was withdrawn in 53 women (56%) after a median interval of 26 months after menopause (range: 3-262). Strict criteria for discontinuation were fulfilled in 52 of them: a normal PRL for at least 24 months under a cabergoline dose ≤ 0.50 mg/week and a more than 50%-reduction in tumor surface area for macroadenomas. Among them, 37 women (71%) remained in remission during a median follow-up period of 26 months (range: 6-176), while 15 (29%) had an asymptomatic biological recurrence after a median duration of 6 months (range: 2-47). Only one woman showed minimal tumor regrowth. 12/15 of the biological recurrences of hyperprolactinemia occurred within the first year after withdrawal and the estimated probability of remission at 5 years was 66%. Multivariate analysis showed that the only independent predictor of recurrence was the PRL value observed 3 to 6 months after DA discontinuation (p = 0.028). Estrogen-progestin replacement therapy, given in 21 women, did not influence these outcomes. In conclusion, we confirm that menopause has a beneficial effect on the evolution of treated and untreated prolactinomas. When using strict criteria for DA withdrawal in the post-menopausal period, a sustained clinical and biological remission can be expected in two-thirds of women, and when recurrence occurs, it is usually mild and asymptomatic. Presentation: 6/2/2024

9281 Menopause Has a Beneficial Influence on the Evolution of Prolactinomas: a Study in 95 Patients

Abstract Disclosure: S. Constantinescu: None. C. Nava: None. F. Chasseloup: None. P. Chanson: Consulting Fee; Self; Eli Lilly &amp; Company, Recordati, Ipsen, Novo Nordisk. O. Alexopoulou: None. D.M. Maiter: Consulting Fee; Self; Ipsen, Recordati, Pfizer, Inc. The natural occurrence of menopause is considered to have beneficial effects in women with a prolactinoma and represents a window of opportunity for successful dopamine agonist (DA) withdrawal. Strong evidence for these effects remains however scarce. We retrospectively analyzed data from 95 women undergoing menopause (Mp) (FSH&amp;gt;35 U/L) while still treated with DA (cabergoline (CAB) in 82) for a prolactinoma diagnosed at a mean age of 38.0 ± 8.0 years. The pituitary tumor was a microadenoma in 66 and a macroadenoma in 29 (invasive in 12). Our objectives were to identify the influence of menopause on the evolution of treated prolactinomas and on the risk of recurrence after DA withdrawal. In post-menopausal women still treated with DA (median dose of 0.50 mg CAB/week or equivalent), a significant decrease in median prolactin (PRL) was observed from a premenopausal value of 15.1 µg/L to 10.7 µg/L 3-6 months after Mp (n=64, P=0.05) and to 7.7 µg/L 24 months after Mp (n=43, P &amp;lt; 0.001). There was also a significant reduction in median coronal tumor surface at 24 months, from 12.6 to 7.1 mm² (p &amp;lt; 0. 01). DA treatment was withdrawn in 53 women (56%) after a median interval of 26 months after menopause (range: 3-262). Strict criteria for discontinuation were fulfilled in 52 of them: a normal PRL for at least 24 months under a cabergoline dose ≤ 0.50 mg/week and a more than 50%-reduction in tumor surface area for macroadenomas. Among them, 37 women (71%) remained in remission during a median follow-up period of 26 months (range: 6-176), while 15 (29%) had an asymptomatic biological recurrence after a median duration of 6 months (range: 2-47). Only one woman showed minimal tumor regrowth. 12/15 of the biological recurrences of hyperprolactinemia occurred within the first year after withdrawal and the estimated probability of remission at 5 years was 66%. Multivariate analysis showed that the only independent predictor of recurrence was the PRL value observed 3 to 6 months after DA discontinuation (p = 0.028). Estrogen-progestin replacement therapy, given in 21 women, did not influence these outcomes. In conclusion, we confirm that menopause has a beneficial effect on the evolution of treated and untreated prolactinomas. When using strict criteria for DA withdrawal in the post-menopausal period, a sustained clinical and biological remission can be expected in two-thirds of women, and when recurrence occurs, it is usually mild and asymptomatic. Presentation: 6/2/2024

One-year Safety and Effectiveness of Ustekinumab in Patients With Crohn's Disease: The K-STAR Study.

This study investigated the safety and effectiveness of ustekinumab (UST) in Korean patients with Crohn's disease (CD). Adult patients with CD treated with UST were prospectively enrolled in the K-STAR (Post-MarKeting Surveillance for Crohn's Disease patients treated with STelARa) study between April 2018 and April 2022. Both the clinical effectiveness and adverse effects of UST therapy were analyzed. Missing data were handled using nonresponder imputation (ClinicalTrials.gov Identifier: NCT03942120). Of the 464 patients enrolled from 44 hospitals across Korea, 457 and 428 patients (Crohn's disease activity index ≥150) were included in the safety analysis and effectiveness analysis sets, respectively. At weeks 16 to 20 after initiating UST, clinical response, clinical remission, and corticosteroid-free remission rates were 75.0% (321 of 428), 64.0% (274 of 428), and 61.9% (265 of 428), respectively. At week 52 to 66, clinical response, clinical remission, and corticosteroid-free remission rates were 62.4% (267 of 428), 52.6% (225 of 428), and 50.0% (214 of 428), respectively. Combined effectiveness (clinical response + biochemical response) was achieved in 40.0% (171 of 428) and 41.6% (178 of 428) at week 16 to 20 and week 52 to 66, respectively. Biologic-naïve patients exhibited significantly higher rates of combined effectiveness than biologic-experienced patients (50.3% vs 30.7% at week 16-20, P < .001; 47.7% vs 36.0% at week 52-66, P = .014). No additional benefits were observed with the concomitant use of immunomodulators. Ileal location was independently associated with a higher probability of clinical remission compared with colonic or ileocolonic location at week 52 to 66. Adverse and serious adverse events were observed in 28.2% (129 of 457) and 12.7% (58 of 457), respectively, with no new safety signal associated with UST treatment. Ustekinumab was well-tolerated, effective, and safe as induction and maintenance therapy for CD in Korea.

An online tool using clinical factors to estimate the probability of partial clinical remission of adult-onset Type 1 diabetes

A type 1 diabetes (T1D) diagnosis is often followed by a period of reduced exogenous insulin requirement, with acceptable glucose control, called partial clinical remission (pCR). Various criteria exist to define pCR, which is associated with better clinical outcomes.We aimed to develop formulae and a related online calculator to predict the probability of pCR at 3- and 12-months post-T1D diagnosis.We analysed data from 133 adults at their T1D diagnosis (mean ± SD age: 27 ± 6 yrs., HbA1c 11.1 ± 2.0 %, 98 ± 22 mmol/mol), 3- and 12-months later. All patients were enrolled in the prospective observational InLipoDiab1 study (NCT02306005). We compared four definitions of pCR: 1) stimulated C-peptide >300 pmol/l; 2) insulin dose-adjusted HbA1c ≤9 %; 3) insulin dose <0.3 IU/kg/24 h; and HbA1c ≤6.4 % (46 mmol/mol); and 4) insulin dose <0.5 IU/kg/24 h and HbA1c <7 % (53 mmol/mol). Using readily available demographics and clinical chemistry data exhaustive search methodology was used to model pCR probability.There was low concordance between pCR definitions (kappa 0.10). The combination of age, HbA1c, diastolic blood pressure, triglycerides and smoking at T1D onset predicted pCR at 12-months with an area under the curve (AUC) = 0.87. HbA1c, triglycerides and insulin dose 3-mths post-diagnosis had an AUC = 0.89. A related calculator for pCR in adult-onset T1D is available at http://www.bit.ly/T1D-partial-remission.

Safety and tolerability of esketamine nasal spray versus quetiapine extended release in patients with treatment resistant depression

In ESCAPE-TRD (NCT04338321), esketamine nasal spray (NS) significantly increased the probability of remission at Week 8, and of being relapse-free through Week 32 after remission at Week 8, versus quetiapine extended release (XR) in patients with treatment resistant depression (TRD). Here, we explore the time course, burden and consequences of treatment emergent adverse events (TEAEs) in the phase IIIb ESCAPE‑TRD trial. Patients with TRD were randomised 1:1 to esketamine NS or quetiapine XR, dosed per label alongside an ongoing selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor. In this secondary publication, safety analyses (comprising patients who received ≥1 dose of study treatment) included incidence, severity and durations (Kaplan‑Meier method) of TEAEs, and subsequent dispositional changes. P values were not adjusted for multiple testing. 336 patients were randomised to esketamine NS and 340 to quetiapine XR; 334 and 336 received ≥1 dose of study treatment, respectively. TEAEs were significantly more common with esketamine NS than quetiapine XR (91.9 % versus 78.0 %; p < 0.001), but were typically mild/moderate and transient in nature: a greater proportion resolved on the same-day (92.0 % versus 12.1 %) and lead to treatment discontinuation in significantly fewer patients (4.2 % versus 11.0 %, respectively; p < 0.001). The proportion of days spent with TEAEs was significantly lower with esketamine NS than quetiapine XR (median: 11.9 % versus 21.3 %; p < 0.001). Although more frequent with esketamine NS, TEAEs were typically transient and mild, with discontinuation less likely versus quetiapine XR. Data were consistent with established safety profiles, with no new safety signals identified. Alongside greater efficacy, the demonstrably more favourable tolerability profile of esketamine NS versus quetiapine XR further supports its use for TRD.

Predicting treatment response in multicenter non-small cell lung cancer patients based on federated learning

BackgroundMulticenter non-small cell lung cancer (NSCLC) patient data is information-rich. However, its direct integration becomes exceptionally challenging due to constraints involving different healthcare organizations and regulations. Traditional centralized machine learning methods require centralizing these sensitive medical data for training, posing risks of patient privacy leakage and data security issues. In this context, federated learning (FL) has attracted much attention as a distributed machine learning framework. It effectively addresses this contradiction by preserving data locally, conducting local model training, and aggregating model parameters. This approach enables the utilization of multicenter data with maximum benefit while ensuring privacy safeguards. Based on pre-radiotherapy planning target volume images of NSCLC patients, a multicenter treatment response prediction model is designed by FL for predicting the probability of remission of NSCLC patients. This approach ensures medical data privacy, high prediction accuracy and computing efficiency, offering valuable insights for clinical decision-making.MethodsWe retrospectively collected CT images from 245 NSCLC patients undergoing chemotherapy and radiotherapy (CRT) in four Chinese hospitals. In a simulation environment, we compared the performance of the centralized deep learning (DL) model with that of the FL model using data from two sites. Additionally, due to the unavailability of data from one hospital, we established a real-world FL model using data from three sites. Assessments were conducted using measures such as accuracy, receiver operating characteristic curve, and confusion matrices.ResultsThe model’s prediction performance obtained using FL methods outperforms that of traditional centralized learning methods. In the comparative experiment, the DL model achieves an AUC of 0.718/0.695, while the FL model demonstrates an AUC of 0.725/0.689, with real-world FL model achieving an AUC of 0.698/0.672.ConclusionsWe demonstrate that the performance of a FL predictive model, developed by combining convolutional neural networks (CNNs) with data from multiple medical centers, is comparable to that of a traditional DL model obtained through centralized training. It can efficiently predict CRT treatment response in NSCLC patients while preserving privacy.