Sustained Clinical Remission Research Articles

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 & 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>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 < 0.001). There was also a significant reduction in median coronal tumor surface at 24 months, from 12.6 to 7.1 mm² (p < 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 DA treatment was withdrawn in 53 women (56%) after a median interval of 26 months after menopause (range: 3-262).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 & 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>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 < 0.001). There was also a significant reduction in median coronal tumor surface at 24 months, from 12.6 to 7.1 mm² (p < 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

Clinical Characteristics and Treatment Outcomes of Patients With Newly Diagnosed Takayasu Arteritis in Japan During the First 2 Years of Treatment - A Nationwide Retrospective Cohort Study.

This study aimed to clarify recent clinical features and treatment outcomes in Japanese patients with newly diagnosed Takayasu arteritis (TAK) during the first 2 years of treatment. A nationwide multicenter retrospective cohort study for TAK was implemented to collect data between 2007 and 2014. The primary outcome of the study was clinical remission at Week 24. Of the 184 participants registered, 129 patients with newly diagnosed TAK were analyzed: 84% were female and the mean age at onset was 35 years. Clinical symptoms at diagnosis were mostly associated with large-vessel lesions. Frequent sites of vascular involvement included the carotid artery, subclavian artery, aortic arch, and descending aorta. The mean initial dose of prednisolone administered was 0.68 mg/kg/day, and 59% and 17% of patients received immunosuppressive drugs and biologics, respectively, by Week 104. Clinical remission at Week 24 and sustained clinical remission with daily prednisolone at ≤10 mg at Week 52 were achieved in 107 (82.9%) and 51 (39.5%) patients, respectively. The presence of signs and symptoms linked to large-vessel lesions was associated with failure to achieve sustained clinical remission at Week 52. We elucidated the clinical characteristics, treatment outcomes, and factors associated with failure to achieve sustained clinical remission in patients with newly diagnosed TAK in Japan during the first 2 years of treatment.

External validation of serum biomarkers predicting short-term and mid/long-term relapse in patients with Crohn’s disease stopping infliximab

ObjectiveIn patients with Crohn’s disease (CD) on combination therapy (infliximab and immunosuppressant) and stopping infliximab (cohort from the study of infliximab diSconTinuation in CrOhn’s disease patients in stable Remission on...

Sustained clinical and histopathological remission in a patient with eosinophilic esophagitis and type-2 comorbidities at 18 months after discontinuation of dupilumab

Eosinophilic esophagitis (EoE) is a chronic, allergen-mediated, type-2 inflammatory disease with the potential to significantly impact an individual’s quality of life. Conventional treatments often result in varied responses, prompting the need for novel therapeutic approaches. We present the case of a 19-year-old male with a medical history marked by eosinophilic esophagitis, severe atopic dermatitis (AD), asthma, and allergic rhinitis. Despite undergoing diverse topical and systemic interventions to address his AD and EoE, the patient’s symptoms persisted. However, following the initiation of dupilumab therapy—a dual IL-4 and IL-13 receptor antagonist—the patient experienced a substantial reduction in his Eczema Area and Severity Index score. Notably, a marked improvement was also seen regarding his symptoms of eosinophilic esophagitis. A subsequent esophageal biopsy revealed a significant decrease in eosinophilic inflammation, consistent with established clinical and histologic remission criteria. These findings corroborate the patient’s reported relief from symptoms. This case underscores the potential efficacy of dupilumab as a promising therapeutic agent in managing eosinophilic esophagitis. Dupilumab offers a dual benefit of alleviating symptoms and achieving histologic and clinical remission. This novel approach presents a noteworthy advancement in the treatment of EoE.

Forecasted infliximab concentrations during induction predict time to remission and sustained disease control of inflammatory bowel disease

BackgroundInfliximab (IFX) exposure is established as a predictive factor of pharmacokinetic (PK) origin in inflammatory bowel disease (IBD), and expert consensus is to achieve adequate exposure during induction to achieve and sustain remission. MethodsWe retrospectively evaluated the performance of a Bayesian PK tool in IBD patients starting IFX. Trough IFX serum levels collected immediately before the third (at week 6) and fourth (at week 14) infusions were evaluated from 307 IBD patients (median age=17 years, 50 % females, 83 % with Crohn's disease). Forecasted IFX concentration at the fourth infusion were estimated using serum IFX, antibodies to IFX, albumin and weight determined immediately before the third infusion using population PK calculator with Bayesian prior. The outcome variable was a clinical & biochemical remission status achieved (CRP levels below 3 mg/L in presence of clinical remission). Statistics consisted of Kaplan Meier analysis with calculation of Hazard ratio (HR), and logistic regression. ResultsIFX concentration above 15 µg/mL immediately before the third infusion associated with shorter time to clinical & biochemical remission than concentration below 15 µg/mL without reaching significance (163±14 days vs 200±16 days, respectively; p=0.052). However, using PK parameters at the third infusion, forecasted IFX concentrations above 10 µg/mL immediately before the fourth infusion were significantly associated with a higher rate (HR=1.6 95 %CI: 1.1 to 2.1 p<0.01) and shorter time to remission (148±18 days vs 200±13 days p<0.01). In the presence of IFX concentration above 15 µg/mL at the third infusion, there was a significant 2.5-fold higher likelihood of sustained clinical & biochemical remission status during maintenance as compared to IFX concentrations below 15 µg/mL (p<0.01). Forecasted IFX level above 10 µg/mL at fourth infusion associated with significantly 3.9-fold higher likelihood of clinical & biochemical remission as compared to forecasted IFX concentrations below 10 µg/mL (p<0.01). ConclusionsThese data further support that optimized IFX concentrations during induction are associated with enhanced disease control in IBD.

Precise infliximab exposure and pharmacodynamic control to achieve deep remission in paediatric Crohn’s disease (REMODEL-CD): study protocol for a multicentre, open-label, pragmatic clinical trial in the USA

IntroductionThe only biologic therapy currently approved to treat moderate to severe Crohn’s disease in children (<18 years old) are those that antagonise tumour necrosis factor-alpha (anti-TNF). Therefore, it is critically...

A multiparametric risk table for loss of clinical remission status in patients with rheumatoid arthritis: A starter study post-hoc analysis.

This post-hoc analysis was carried out on data acquired in the longitudinal Sonographic Tenosynovitis/arthritis Assessment in Rheumatoid Arthritis Patients in Remission (STARTER) study. Its primary aim was to determine the predictive clinical and MSUS features factors for disease flare in RA patients in clinical remission, whilst its secondary aim was to evaluate the probability of disease flare based on clinical and MSUS features. The analysis included a total of 389 RA patients in DAS28-defined remission. All patients underwent a MSUS examination according to OMERACT guidelines. Logistic regression and results presented as OR and 95%CI were used for the evaluation of the association between selected variables and disease flare. Significant clinical and MSUS features were incorporated into a risk table to predict disease flare within 12 months in RA remission patients. Within 12 months, 137(35%) RA patients experienced a disease flare. RA patients who experienced a flare disease differed from persistent remission for ACPA positivity (75.9%vs62.3%; p= 0.007), percentage of sustained clinical remission at baseline (44.1%vs68.5%; p= 0.001) and synovium PD signal presence (58.4%vs33.3%; p< 0.001). Based on these results, the three features were considered in a predictive model of disease flare with adjOR 3.064(95%CI 1.728-5.432). Finally, a risk table was constructed including the three significant predictive factors of disease flare within 12 months from the enrolment. An adaptive flare prediction model tool, based on data available in outpatient setting, were developed as a multiparametric risk table. If confirmed by the external validation, this tool might support the definition of therapeutic strategies in RA patients in DAS28-defined remission status.

Treatment of non-systemic juvenile idiopathic arthritis.

In the past two decades, the treatment of juvenile idiopathic arthritis (JIA) has evolved markedly, owing to the availability of a growing number of novel, potent and relatively safe therapeutic agents and the shift of management strategies towards early achievement of disease remission. However, JIA encompasses a heterogeneous group of diseases that require distinct treatment approaches. Furthermore, some old drugs, such as methotrexate, sulfasalazine and intraarticular glucocorticoids, still maintain an important therapeutic role. In the past 5 years, information on the efficacy and safety of drug therapies for JIA has been further enriched through the accomplishment of several randomized controlled trials of newer biologic and synthetic targeted DMARDs. In addition, a more rational therapeutic approach has been fostered by the promulgation of therapeutic recommendations and guidelines. A multinational collaborative effort has led to the development of the recommendations for the treat-to-target strategy in JIA. There is currently increasing interest in establishing the optimal time and modality for discontinuation of treatment in children with JIA who achieve sustained clinical remission. The aim of this Review is to summarize the current evidence and discuss the therapeutic approaches to the management of non-systemic phenotypes of JIA, including oligoarthritis, polyarthritis, enthesitis-related arthritis and psoriatic arthritis.

Long-term sustained clinical remission of peritoneal metastatic pancreatic ductal adenocarcinoma after sequential chemoradiation therapy: a case report

Patients with peritoneal metastatic pancreatic ductal adenocarcinoma (pmPDAC) with high-level serum carbohydrate antigens (CAs) always suffer extremely dismal prognosis, with a median survival of several months. Herein, we reported a case of pmPDAC with high serum CAs who had long-term clinical remission with normalization of CAs after chemoradiation. In November 2019, a 64-year-old male patient was admitted to our center with a solid mass measuring 2.8 × 2.5 × 2.0 cm in the body of the pancreas near the celiac trunk. Positron emission tomography-computed tomography (PET-CT) revealed an standardized uptake value max (SUVmax) of 4.2. The serum CA 242 level exceeded 150.0 U/mL (normal range: 0–20 U/mL), and CA 19-9 was elevated at 975.2 U/mL (normal range: 0–34 U/mL). During laparotomy, the tumor was found to encircle the celiac trunk over 180°, with several small peritoneal nodules in the lesser omental cavity. Pathological examination confirmed the diagnosis of pmPDAC. Next-generation sequencing revealed RAS G12V, EGFR mutation (-), low tumor mutation burden (TMB), and microsatellite stability (MSS). The patient underwent 6 cycles of the AG regimen (gemcitabine plus nab-paclitaxel), resulting in significant tumor shrinkage and a sharp decline in CAs. Partial remission was achieved. However, due to intolerant neurotoxicity, the AG regimen was discontinued. Subsequently, synchronous oral fluorouracil (S1) and radiation therapy were administered. Five months after radiation treatment, all CAs normalized. Oral S1 was continued for an additional 3 months. Eventually, all anti-cancer drugs were stopped. Computed tomography scans indicated that the tumor still surrounded the celiac trunk and common hepatic artery. After a thorough discussion, a wait-and-see strategy was adopted. Remarkably, 32 months after stopping anti-cancer medication, the patient remains in good health, with sustained normalization of CAs. At the last follow-up, he had lived for 50 months, and the normalization of the CAs was sustained for 36 months. Although he still suffers the risk of disease progression, it is a successful case of state-of-the-art chemoradiation for a dismal pmPDAC patient.

Immunotherapy withdrawal by step-down to mesalamine in pediatric patients with ulcerative colitis.

Parents and pediatric patients with ulcerative colitis (UC) who progressed to systemic immunotherapy are concerned about lifelong risks from such treatments. There is limited knowledge about withdrawal of such agents and step-down (SD) to enteral 5-aminosalicylic acid(mesalamine) before transitioning to adult care. We studied nine pediatric cases with moderate to severe UC whoafter a median of 2.18 years of clinical remission on systemic immunotherapy stepped down to oral mesalamine treatment. Average follow-up time from SD was 3.49 years. Five patients (55.5%) had sustained remission (without any flare noted) after SD during follow-up. Sustained clinical remission was 88.9% (8/9) at 1 year, 87.5% (7/8) at 2 years, and 66.7% (4/6) at 3 years after SD. Out of those tested (one patient was not tested), 62.5% (5/8) had fecal calprotectin <50 μg/g. Four out of six patients examined (66.6%) had mucosal healing on post-SD colonoscopy. We propose that SD to mesalamine can be a reasonable therapeutic consideration for pediatric patients with UC before transitioning to adult gastroenterology care. Shared decision-making is important before such treatment changes.

UPADACITINIB AS SECOND- AND THIRD-LINE SALVAGE THERAPY FOR REFRACTORY ACUTE SEVERE ULCERATIVE COLITIS

Abstract INTRODUCTION Intravenous (IV) corticosteroids (CS) remain first line therapy for acute severe ulcerative colitis (ASUC). Up to 40% are CS refractory. Prior biologic exposure, colonic drug loss and systemic toxicities limit their utility. Colectomy rates remain up to 30% in CS refractory cases emphasizing the need for expanding alternative strategies. We report our experience of upadacitinib (UPA) as 2nd and 3rd line salvage in refractory ASUC. METHODS ASUC was defined by Truelove and Witts’ criteria. Travis index was used to assess 3-day response to inpatient (IP) therapies. IP therapeutic non-response was defined as ≥ 8 bowel movements (BM)/day or &amp;gt; 2 BM and CRP &amp;gt; 45 mg/L. IP response was defined as ≤ 4 BM and CRP &amp;lt; 45 mg/L. Primary outcome include response to IP UPA salvage at day 3 and colectomy by week (WK) 16. Patients (pts) undergoing colectomy were followed until time to event. Secondary outcomes include post-discharge clinical and biochemical remission, clinical response and rate of adverse events at WK 8/16. Clinical remission/response was defined by STRIDE-2 guidelines using partial mayo (PM). Biochemical remission was defined as fecal calprotectin (FC) &amp;lt;250 ug/g or CRP &amp;lt;5 mg/L. No cardiovascular, thromboembolic or non-HSV infections were seen. RESULTS Four ASUC pts failing IV CS required inpatient UPA salvage (Table 1). At baseline, all pts had severe pancolonic endoscopic disease (median total mayo 11, median PM 9). Median exposure to prior advanced therapies was 4. Baseline median FC was 3000 ug/g and CRP 167 mg/dL. Pt #1, #2 received UPA as 2nd line salvage due to prior IFX failure (Table 2). Pts #3, #4 received UPA as 3rd line salvage due to IFX failure at index admission (IA). One received UPA 45 mg QD (pt #1) and three received 30 mg BID (pts #2-4). All pts achieved IP response to UPA. No pts needed colectomy at IA. Overall median length of hospital stay was 14 days. Median time to UPA response was 2.5 days. Discharge time post-UPA was 3.5 days. At WK 8, pt #1 attained response with resolution of rectal bleeding (RB), BM (-85%), CRP (-91%), FC (-82%), and PM 3 (Table 3-4). At WK 16, pt #1 met criteria for clinical and biochemical remission with PM 1, normal FC (-95%) and CRP (-98%). Pt #1,#3 achieved complete steroid taper and avoided colectomy over 16 WK. Pt #2 failed CS taper and had colectomy on day 33. Pt #3 achieved clinical and biochemical remission with PM 1 and CRP 5 mg/dL (-94%) at WK 8. At WK 16, pt #3 sustained CS free clinical and biochemical remission with normalized BM (-93%), FC (-92%), CRP (-98%) and sustained resolution of RB. Assessment of pt #4 was limited to IP UPA response pending follow up. Outcomes were similar in pts receiving UPA as 2nd and 3rd line salvage. CONCLUSION We report efficacy and safety of UPA as 2nd and 3rd line salvage for ASUC thus expanding the armamentarium for medical salvage therapy. Table 1 Baseline Disease Characteristics Table 2 Patient Specific Inpatient Therapy Table 3 Comparison of Disease Activity Parameters at Baseline, Discharge, 8 Weeks and 16 Weeks Table 4 Percentage Difference of Disease Activity Parameters at Discharge, 8 Weeks and 16 Weeks in Comparison to Baseline

P1207 Microbiome composition determines sustained remission after the Crohn’s Disease Exclusion Diet (CDED) with or without Partial Enteral Nutrition in adults with mild-moderate Crohn’s disease; Results from the CDED-AD Pilot Randomized Controlled Trial

Abstract Background The Crohn's Disease (CD) Exclusion Diet (CDED) is an established dietary therapy for children with active mild-to-moderate CD. A recent randomized controlled trial showed efficacy in mild-to-moderate CD in adults. We have previously demonstrated the impact of CDED on the microbiome of children. The aim of this work was to assess if we can determine sustained clinical remission (SCR) from the baseline microbiome composition and examine the effect of CDED on microbiome composition in adult CD. Methods This was an open-label, prospective, randomized, controlled pilot trial involving patients with mild-to-moderate CD and evidence of active inflammation. Patients were randomly assigned to receive CDED with partial Enteral Nutrition (PEN) or CDED alone, both for 24 weeks. The V4V5 region of the 16S rRNA gene was amplified and sequenced, and reads were processed using QIIME2 and the SILVA database. Relationships between the microbiome, SCR, and Fecal Calprotectin (FC) were analyzed using logistic regression, Poisson Principal Component Analysis, paired T-Tests and subsampling ranking forward selection. Results Clinical remission (CR) at weeks 6, 12 and 24 was achieved in 62.5%, 52.5%, and 50% of patients, respectively. Week 0, 6, 12 and 24 stool samples were available for 35,32,30 and 26 patients, respectively. In patients with SCR, defined as remission at both weeks 12 and 24, the baseline microbiome revealed lower alpha diversity compared to those without SCR (p=0.018), and differing Microbiome principal components (PC) scores (p &amp;lt; 0.01). PC1 and PC3, characterized mainly by Alistipes, Faecalibacterium and UCG-002 predicted SCR (P&amp;lt;0.01). PC2 predicted elevated FC&amp;gt;250 µg/g at week 12 (p=0.004). Baseline abundance of Haemophilus was associated with decreased SCR probability (p&amp;lt;0.01). At week 6 in the entire cohort, there was a significant decrease in Actinobacteriota (p=0.035) and a significant increase in Bacteroidota (p=0.003). Additionally, there was a significant increase in several genera, including beneficial Alistipes and Oscillibacter (p&amp;lt;0.02) in those who achieved CR after 6, 12, or 24 weeks. Higher Firmicutes at week 6 were associated with FC&amp;lt;250 at week 12 (p=0.031). An uncultured genus from the Oscillospiraceae family was significantly associated with a decrease in the probability of SCR (p&amp;lt;0.01) and was significantly increased at week 6 in patients who did not attain CR (p&amp;lt;0.05). Conclusion The baseline microbiome composition was associated with SCR and FC&amp;lt;250 at week 12 in adult patients treated with CDED (with or without PEN) over 24 weeks. This suggests that the microbiome could be useful tool to identify patients who would benefit from long-term dietary intervention.

P966 The intra-patient variability of adalimumab clearance during an intensive sampling study of Crohn’s disease patients receiving maintenance therapy

Abstract Background Lower adalimumab (ADA) clearance (CL) is associated with improved outcomes in Crohn’s disease (CD) and may be a superior pharmacokinetic (PK) measure than ADA concentrations. We compared intra-patient variability in ADA CL and concentrations within a 14-day treatment cycle and across two consecutive cycles under maintenance treatment. Methods In a previous PK study of CD patients receiving maintenance ADA 40mg fortnightly, samples were collected intensively at 3 visits (day 4-6, 7-9, and 13-14 post dose) across 2 consecutive cycles. Available sera from this cohort were subsequently used to measure ADA concentrations (lower limit quantification: &amp;lt;1.6 µg/mL) and antibody to adalimumab (ATA) status using a drug tolerant homogeneous mobility shift assay, and albumin. Apparent ADA CL (L/day) was calculated incorporating these measure parameters in a nonlinear mixed effect model with Bayesian priors (under steady state assumption) with dose and inter-dose interval with ATA and albumin as covariate. Rates of sustained clinical and biochemical remission (Harvey Bradshaw Index (HBI) score consistently &amp;lt;5 and CRP levels consistently &amp;lt;3 mg/L) were estimated for each patient. Longitudinal changes in PK parameters within-and-across cycles were evaluated using intra-patient coefficient of variation and linear mixed effect models. Results Sera was available from 70 study visits in 12 patients (6 males, mean age 36 years). Median ADA concentrations and CL were 8 µg/mL (IQR 6.0-10.4) and 0.374 L/day (IQR 0.29-0.43), respectively, with ATA detected in one patient (#9). Estimated ADA concentrations and CL is presented in the Table. Intra-patient variability in CL was much lower across the two 14-day cycle (9% and 7%, respectively) compared to intra-patient variability in ADA concentration (15% and 13%, respectively). Linear mixed effect models confirmed these findings with no impact of sampling time on CL (intercept=0.46±0.12 L/day; slope estimate=0.002±0.002 L/day; p=0.16) as compared to significant change in ADA concentrations (intercept=10.6±1.2 µg/mL; slope estimate=-0.25±0.03 µg/mL; p&amp;lt;0.01) over inter-dose interval sampling time. Sustained clinical and biochemical remission was achieved in 5/12 patients (42%); none presented with CL &amp;gt;0.8 L/day (a cut-off previously associated with worse outcomes). Of 7 patients without sustained clinical and biochemical remission, two presented with optimal concentrations (&amp;gt; 10 µg/mL), thus suggestive of mechanistic failure, and one developed ATA, lower concentration and higher ADA CL. Conclusion CL is subject to less intra-patient variability than ADA concentrations, supporting its assessment at any time point within a 14-day treatment cycle.

P630 Identification of specific cell subsets related to treatment response after anti-tumor necrosis factor use in Korean ulcerative colitis patients using single cell RNA sequencing: a preliminary study

Abstract Background The breakdown of the epithelial barrier and mucosal homeostasis plays an important role in the development of ulcerative colitis (UC). Recently, single-cell RNA sequencing (scRNA-seq) has been performed to better understand the gene expression patterns and the characteristics of cells in intestine of UC patients. However, there is a lack of studies focus on Asian UC patients. The aim of this preliminary study was to identify the relevant cellular subsets related to treatment response after anti-tumor necrosis factor (anti-TNF) use in Korean UC patients using scRNA-seq. Methods This prospective study was conducted two University hospitals in Korea. We performed scRNA-seq on sigmoid colon tissue samples collected from one healthy control and nine biologic naïve UC patients scheduled to use anti-TNF due to lack of response to conventional therapy. All mucosal biopsies from active moderate to severe UC were collected at baseline (n=9) and at 52 weeks follow-up after anti-TNF use (n=2), at which time treatment response was assessed. Treatment responder was defined as those with sustained clinical remission (a partial Mayo score of ≤2 with no subscore &amp;gt;1 and a rectal bleeding subscore of 0) at 52 weeks. Results After processing the scRNA-seq data, 13 clusters were discovered and cell clusters were annotated using colon marker gene. Among nine patients, two patients who underwent response evaluation at 52 weeks after anti-TNF use were treatment responder. The normalized proportion of cluster 1 (stem cell-like cluster) in 52 weeks follow-up tissue samples after anti-TNF use was shown to be decreased significantly (p-value=0.03) from that found in the disease tissue samples. A decrease in the proportion of cell cluster 1 from disease tissue samples’ initial average percentage (30.6%) down to an average of 4.8% in the follow-up tissue samples is quite substantial (p-value=0.03). This decrease signifies a notable change in the composition of this specific cell cluster post-anti-TNF treatment. Moreover, reaching a level close to that of the healthy tissue sample (2.7%) suggests a potential restoration of this cell cluster's proportion towards a healthier state (Figure 1). Conclusion In Korean UC patients, this information should be crucial in understanding the impact of anti-TNF treatment on the cellular composition or behavior of this stem cell-like cluster, suggesting a potential effect of anti-TNF treatment on this particular cell population.

P246 Histologic remission is an important therapeutic target in patients who achieve endoscopic remission of ulcerative colitis

Abstract Background Histologic activity has been established as a crucial prognostic determinant in individuals diagnosed with ulcerative colitis(UC), while achieving histologic remission is increasingly recognized as a significant long-term therapeutic goal. However, the available literature still lacks adequate evidence concerning the selection of an optimal histological index and its utility in predicting prognosis Methods This retrospective study involved the analysis of medical records and endoscopic results from patients diagnosed with UC between January 2015 and December 2022. Endoscopic remission was defined as a Mayo endoscopic sub-score of ≤1. Histological assessment utilized the Nancy index, with a score of ≤1 indicating histological remission. Among patients with UC who achieved endoscopic remission, the study assessed the maintenance of remission and the occurrence of recurrence based on histological remission Results A total of 114 patients with UC who achieved mucosal healing were enrolled for histological evaluation. Among them, 16.7% (19/114) experienced flare-ups, and a statistically significant inverse correlation was observed with histologic remission (see Table). Multivariate analysis further identified non-histologic remission (Nancy index &amp;gt;2) as an independent risk factor for recurrence (Hazard ratio: 3.513, CI: 1.334-9.257, P=0.011). Particularly noteworthy was the significantly lower recurrence rate when histologic remission is achieved, especially in patients with MES 1 (see Figure) Conclusion Our study demonstrated a robust correlation between histologic remission assessed by the Nancy index and sustained clinical remission. The Nancy index, reflecting relatively straightforward histological activity, is considered a valuable metric that can aid in establishing treatment goals

P648 Dietary therapy using a short course of Exclusive Enteral Nutrition followed by the Crohn’s Disease Exclusion Diet in children with mild to severe Crohn’s Disease; maintenance update on the DIETOMICS trial

Abstract Background Exclusive enteral nutrition (EEN) is the first-line treatment for active Crohn’s disease (CD) in children. CD Exclusion Diet (CDED) combined with Partial Enteral Nutrition (PEN) has demonstrated better tolerance with a comparable effect in inducing remission among children with mild to moderate CD. This study evaluated the effectiveness of 2 weeks of EEN followed by CDED+PEN for maintaining remission for up to 24 weeks in children with mild-severe disease. Methods We conducted an international, multicenter, randomized controlled trial comparing 2 weeks of EEN using Modulen®, followed by 3 phases of the CDED+PEN (hereafter CDED), to 8 weeks of EEN followed by PEN with a free diet (hereafter EEN), all extended up to week 24 with a follow up till week 52. Children aged 8-18 with luminal CD duration less than 3 years, mild-severe disease [pediatric CD activity index (PCDAI),15-47.5], and active inflammation [elevated C-reactive protein (CRP),or fecal calprotectin (FC)] were included. Remission was defined as PCDAI≤10. Stable immunomodulator (IM) treatment was allowed, and naïve patients could initiate IM from week 4. Results We randomized 56 patients into two groups: Group CDED (n=30) and Group EEN (n=26); mean age 12.7±2.4, 37% female. Intention-to-treat analysis revealed remission in 18/30(60%) patients with CDED compared to 11/26(42%) with EEN at week 24,p=0.18 and 27% in CDED and 23% in EEN at week 52,p=0.75. Per protocol analysis showed 18/20(90%) remission in CDED compared to 11/14(78%) in EEN at week 8, p=0.35. Among patients who achieved remission at week 8, 18/23(78%) with CDED and 9/14(64%) with EEN maintained remission up to week 24, p=0.15. In CDED,15/20(75%) and 100% of EEN used IM, p=0.04. All CDED patients without IM remained in remission. Reduction of &amp;gt;50% in FC from baseline was obtained in 55% in the CDED and 28% in EEN, p=0.12. PCDAI improved from 31.2[20-35.6] to 5[0-12.5] in CDED and from 22.5[20-29.3] to 5[0-15.6] at week 24 in EEN, p&amp;lt;0.001 to all. CRP and FC significantly improved in both groups. Z score BMI improved from -1.3 [-2.1-(-0.1)] to -0.2 [-0.9-0.4], p=0.003 in CDED and from 0.08[-1.1-0.4] to 0.2[-1.7-0.7] at week 24 in EEN,p=0.098. Remission at week 2 (p=0.006) and overall high compliance (p=0.009) were identified as predictors of response at week 24. Conclusion While 2 weeks of EEN followed by CDED+PEN was not superior to EEN at 14 weeks (as previously reported), extending CDED+PEN for 24 weeks successfully maintained remission for up to 52 weeks in children with mild-to-severe CD. Moreover, a subset of patients maintained sustained clinical remission following CDED monotherapy. The long-term implementation of dietary therapy using CDED+PEN resulted in a significant improvement in nutritional status.

P1210 Gut microbiota profiling and disease course in patients with ulcerative colitis in clinical remission

Abstract Background The inflammatory bowel diseases, encompassing ulcerative colitis (UC) and Crohn’s disease (CD) are characterized by a relapsing-remitting disease course. Despite achieving remission, approximately one-third of the patients relapse annually and yet the microbiota associated with relapse remains elusive. We hypothesized that distinctions in gut microbial composition among patients in clinical remission could potentially influence the disease course. We aimed to discern a distinctive microbial signature in patients with UC in clinical remission, which could serve as a predictive marker for the sustained clinical remission. Methods This was a prospective observational cohort study conducted as a collaborative work between Dayanand Medical College and Hospital (DMCH), Ludhiana, and Institute of Microbial Technology (IMTECH), Chandigarh. Adult (≥18 years age) patients with an established diagnosis of mild UC (defined as no previous requirement of immune-modulators or biologics to induce or maintain remission) and in clinical remission, were included between January 2019 and December 2020 and followed for one year. The clinical remission was defined as partial Mayo score &amp;lt;2 for at least 6 months, with endoscopic Mayo score 0 and fecal calprotectin &amp;lt;100 µg/g within 4 weeks of enrolment. Utilizing using 16S rRNA metabarcoding based metagenome analysis, the bacterial composition of the collected stool samples were determined. Results During the study period, 34 patients (mean age 41.41±13.89 years, 20 [58.82%] males) meeting the eligibility criteria were included for analysis and followed up for one year. (Figure 1) The majority of the patients (21, 61.76%) had left sided colitis. On follow-up, 14 patients (41.17%) experienced a disease relapse (median time to relapse 6 [3-8.25] months). The phyla Firmicutes, Actinobacteria, Bacteroidetes and Proteobacteria were abundant in both the groups [sustained remission (n=20) and disease relapse (n=14)], but specific phyla were enriched in each cohort, Actinobacteria in remission and Proteobacteria in relapse groups. The genera Escherichia, Klebsiella, Enterobacter, Enterococcus, Streptococcus were enriched in relapse group. Interestingly the genus Clostridium was enriched in relapsed cohort whereas genera like Bifidobacterium, Prevotella, Bacteroides, Alistipes, Faecalibacterium were abundant in the remission cohorts. Conclusion There are inter-individual differences in the gut microbiota profile of patients with UC in clinical remission. These microbial differences can serve as determinants of the disease course.

Effect of Sustained Clinical Remission on the Risk of Lupus Flares and Impaired Kidney Function in Patients With Lupus Nephritis

This retrospective study on patients with biopsy-proven lupus nephritis (LN) aimed to assess the probability of sustained clinical remission (sCR) and to investigate sCR effects on disease flares and impaired kidney function (IKF). sCR was defined as clinical-Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)= 0 and estimated glomerular filtration rate (eGFR) >60 ml/min per 1.73 m2 lasting≥1 year; IKF: eGFR<60 ml/min per 1.73 m2 for >3 months. We analyzed the probability of achieving and maintaining sCR, and the yearly risk of flare. Cox models were used to identify predictors of sCR and IKF with variables analyzed as time-dependent covariates when appropriate. Of 303 patients followed-up with for 14.8 (interquartile range: 9.8-22) years, 257 (84.8%) achieved sCR. The probability of achieving sCR progressively increased over time reaching 90% at 15 years. Baseline age (hazard ratio [HR]: 1.017; 95% confidence interval [CI]: 0.005-1.029; P= 0.004), hydroxychloroquine intake (HR: 1.385; 95% CI: 1.051-1.825; P= 0.021), and absence of arterial hypertension (HR: 0.699; 95% CI: 0.532-0.921; P= 0.011) were independent predictors of sCR. Among patients who achieved sCR, 142 (55.3%) developed a lupus flare after a median time of 3.6 (2.3-5.9) years. In the remaining 115 patients, sCR persisted for 9.5 (5.8-14.5) years. The probability of sCR to persist at 15 years was 38%. SLE flare risk decreased to 10%, 5%, and 2% in patients with sCR lasting<5, 5 to 10, and >10 years, respectively. At the last observation, 57 patients (18.81%) had IKF. sCR achievement (HR: 0.18, P< 0.001) and its duration (HR: 0.83, P< 0.001) were protective against IKF. sCR is an achievable target in LN management and protects against IKF. The longer the sCR, the higher the chance of its persistence and the lower the risk of SLE flares.

Secondary orofacial granulomatosis due to Crohn's disease.

We report the case of a 34-year-old female with Crohn's disease (CD), was treated with infliximab and ileocecal resection after failure to anti-TNF. She started adalimumab for postoperative recurrence for two years, with sustained clinical and endoscopic remission. She presents with a 1.5-year history of a persistent, asymptomatic, rubbery swelling on the left half of the lower lip.