Persistent Remission Research Articles

ANTIEPILEPTIC DRUG EFFICACY IN CERTAIN GENETIC TYPES OF CHILDHOOD EPILEPSY

Objective: we aimed to study antiepileptic drug efficacy in achieving seizure remission in certain genetic types of childhood epilepsy.Materials and methods. The authors studied 240 patients aged from 1 month to 18 years with epilepsy between 2019 and 2023. Children with genetic forms of epilepsy accounted for 69 (28,8%). In this group, remission was achieved in 13 (18,8%) of patients. Among them, there were 13 children (%) with certain forms of genetic epilepsy aged 5 to 4 (average 10 ± years), with 7 (53,8%) being girls and 6 (46,2%) being boys. There were 7 (53,8%) children with generalized epilepsy, including 5 (30,8%) cases of childhood absentee epilepsy. 5 (38,5%) patients had focal epilepsy, all of them had self-controlling epilepsy with central temporal adhesions. The study included one patient with an unspecified type of epilepsy (7.7%).Results. The duration of remission ranged from 6 months to 7 years 2 months (me – 3 years 8 months). 11 children (84,6%) were in stable remission for 1 year or longer. Complete clinical electroencephalographic remission was observed in 7 (53,9%) cases. In other cases, regional and diffuse epileptiform activity was recorded in 3 (75,0%) and 1 (25,0%) case, respectively. Remission was achieved in 5 children (38,5%) who were taking levetiracetam, 6 subjects (46,1%) – valproic acid, 1 person – carbamazepine (7,7%). Persistent remission was registered in 4 children (36,3%) who were prescribed levetiracetam, 5 children (45,4%) taking valproic acid and 1 person (9 %) who was administered carbamazepine. 1 person (7,7%) was in stable remission after discontinuation of the antiepileptic drug.Conclusion. Most of the children with certain types of genetic epilepsy under the treatment with antiepileptic drugs were in stable seizure remission. More than half of those observed were in a complete clinical electroencephalographic remission. Predominantly, seizure remission occurred with the administration of valproic acid and levetiracetam, with the same frequency in generalized and focal types of genetic epilepsy.

Role of baseline soluble tumor necrosis factor receptor 2 as a biomarker in primary podocytopathy: Implications for renal impairment and disease progression

BackgroundPodocytopathies, including minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and collapsing glomerulopathy (CG), are kidney diseases that damage glomerular podocytes, leading to heavy proteinuria and nephrotic syndrome (NS). Inflammation plays a critical role in the progression of chronic kidney disease (CKD), with recent studies linking inflammatory biomarkers to declining kidney function. Tumor necrosis factor-alpha (TNF-α), an essential inflammatory cytokine, interacts with its circulating receptors, TNFR1 and TNFR2. The TNF-α pathway has been implicated in the pathogenesis of FSGS and MCD. Increased circulating TNFR2 levels have been associated with worsening renal function in podocytopathies, suggesting that the TNF-α inflammatory pathway significantly contributes to disease progression.MethodsWe conducted a study involving 53 patients with biopsy-proven MCD or FSGS and 53 healthy, age- and gender-matched controls. All patients were followed for 18 months. We analyzed serum and urine TNFR2 levels and gene expression at baseline and after three months. To assess the ability of TNFR2 to predict persistent decline in estimated glomerular filtration rate (eGFR < 30 mL/min/1.73m2), remission, and relapse, we employed Cox regression analysis. Additionally, we evaluated its prognostic utility for predicting progression to stage 4 CKD using ROC curve analysis.ResultsSerum and urine TNFR2 levels were significantly elevated in patients compared to controls. Serum TNFR2 was a significant predictor in univariate Cox regression analysis for persistent eGFR decline (HR 1.017, 95% CI: 1.003 to 1.032, p = 0.018), remission (HR 0.995, 95% CI: 0.992 to 0.999, p = 0.006), and relapse (HR 1.005, 95% CI: 1.001 to 1.010, p = 0.029). The ROC curve analysis demonstrated that serum TNFR2 levels had a strong prognostic ability for predicting progression to stage 4 CKD, with an AUC of 0.848 (95% CI: 0.737—0.960), sensitivity of 81%, and specificity of 71%.ConclusionThis study underscores the critical role of circulating TNFR2 in kidney injury among patients with primary podocytopathy. Elevated TNFR2 levels are significant predictors of persistent eGFR decline and disease relapse, highlighting their potential as biomarkers for disease progression and prognosis.

Sinonasal Outcomes after Endoscopic Pituitary Surgery in Patients With Cushing's Disease.

The endoscopic endonasal approach (EEA) has become the preferred treatment for pituitary tumors, with minimal sinonasal morbidity. However, patients with Cushing's disease (CD) may represent a subgroup with prolonged impairment of sinonasal quality of life (QOL). We retrospectively identified patients with CD who underwent EEA at our institution. Control patients with non-functional tumors were matched by age, gender, and extent of EEA. The primary outcome was post-operative 22-item Sino-Nasal Outcome Test (SNOT-22) scores. Ten patients with CD met the selection criteria and 20 controls were selected for comparison. Nine of the CD patients achieved persistent endocrinologic remission post-operatively. Comparing the CD and control groups, there was no difference in post-operative SNOT-22 score at 1 or 3 months. At 6 months, SNOT-22 scores were significantly worse in the CD group (27.4 ± 21.6 vs. 2.8 ± 2.3, P = .039). SNOT-22 scores improved to normal from 1 to 6 months in the control cohort (P = .007), but not in the Cushing's group (P = .726). Morbidity was present across all SNOT-22 domains, but was highest in the sleep domain (P = .023). Only morbidity in the facial domain improved over time (P = .032). Patients with CD have significantly prolonged postoperative sinonasal QOL impairment following EEA compared to patients with non-functioning tumors, who normalize within 6 months. In CD patients, only morbidity in the facial domain, likely related to post-operative pain and nasal packing, improved over time, while the sleep domain was the most affected.

Long-term outcome of unilateral adrenalectomy for primary bilateral macronodular adrenal hyperplasia.

Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a form of Cushing's syndrome (CS) characterized by heterogeneous cortisol secretion and clinical comorbidities. Previously, bilateral adrenalectomy was the standard treatment for PBMAH, but this approach carried a high risk of primary adrenocortical insufficiency. In recent decades, unilateral adrenalectomy (U-Adx) has emerged as an effective alternative. However, limited research exists on its postoperative efficacy and prognostic predictors. Therefore, the present study aimed to investigate the long-term effectiveness and prognostic predictors of U-Adx in treating PBMAH. A total of 61 patients with PBMAH diagnosis who underwent U-Adx at a single center between 2004 and 2022 were retrospectively evaluated. Patients were categorized into persistent hypercortisolism and remission groups based on postoperative biochemical outcomes at the last follow-up (>12 months after U-Adx). Clinical characteristics, comorbidities, plasma adrenocorticotropic hormone (ACTH), serum cortisol, and 24-h urinary-free cortisol (24-h UFC) levels were analyzed pre- and postoperatively. We further examined whether baseline plasma ACTH, serum cortisol, 24-h UFC levels, and the inhibition of cortisol and 24-h UFC after a low-dose dexamethasone suppression test (LDDST) could predict non-remission following U-Adx. Additionally, we explored the improvements in hypertension, abnormal glucose metabolism, osteoporosis, and other complications in patients with PBMAH post-U-Adx. After U-Adx, 22 of the 45 patients (48.89%) achieved initial remission within 6 months. At the last follow-up, 25 of the 45 patients underwent all required biochemical tests and cortisol assessment tests, among which eight of 25 (32.00%) were in remission and 17 of 25 (68.00%) were experiencing persistent hypercortisolism. Moreover, five of those 25 patients exhibited recurrence after initial remission. Baseline 24-h UFC level > 2 times the upper limit of normal (2ULN) and unsuppressed 24-h UFC after LDDST may predict persistent hypercortisolism postoperatively. Lastly, long-term postoperative follow-up revealed that hypertension decreased with hypercortisolism remission, whereas osteoporosis worsened with persistent hypercortisolism. The short-term remission rate of hypercortisolism was 48.89% in patients with PBMAH treated with U-Adx, while a long-term remission rate of 32.00% was achieved after a median follow-up of 38.58 months. Furthermore, this finding suggests that baseline 24-h UFC level > 2ULN and unsuppressed 24-h UFC after LDDST predict persistent hypercortisolism in the long-term post-U-Adx. Finally, U-Adx improved cortisol circadian rhythm alterations and ACTH suppression in the patients in the remission group, thereby substantially alleviating hypertension and delaying the development of osteoporosis linked to PBMAH.

Prognosis of IgA nephropathy patient with proteinuria remission by supportive therapy: cohort from screening failed Chinese patients in TESTING study

Background During the run-in phase of the TESTING study, approximately half of patients with IgA nephropathy (IgAN) were excluded due to proteinuria below 1 g/24 h after intensive supportive therapy. The long-term prognosis of these patients needs further investigation. Methods 112 screening failed patients in the TESTING study from 10 centers in China were enrolled in this retrospective study. The prognosis of 88 patients, who were excluded because of proteinuria below 1 g/24 h, was analyzed by Landmark Kaplan-Meier analysis. The composite kidney endpoint was defined by a ≥ 50% reduction in eGFR, ESKD (eGFR <15 mL/min per 1.73 m2), chronic dialysis for at least 6 months, or renal transplantation. Results In total, 88 patients were excluded due to proteinuria less than 1 g/24 h. During the follow-up, 73/88 (83.0%) patients received renin-angiotensin system blocker. 72/88 (81.8%) had stable proteinuria remission and did not receive immunosuppressive therapy (IST), and 16/88 (18.2%) received IST because of a relapse of proteinuria. Landmark Kaplan–Meier analysis revealed that, the kidney survival from dialysis or composite kidney outcome of these excluded patients with IST was similar to those without IST during the early stages of follow-up (dialysis, before 60 months, p = 0.778; composite kidney outcome, before 48 months, p = 0.862); whereas the risk for dialysis of patients receiving IST was significantly higher than those without IST after 60 months (OR = 11.3, p = 0.03). Similarly, the risk for the composite kidney outcome of patients receiving IST was also significantly higher than those without IST after 48 months (OR = 5.92, p = 0.029). Conclusions IgAN patients who maintained a persistent remission of proteinuria after intensive supportive therapy had a much better long-term kidney outcome than those who experienced a relapse of proteinuria and needed IST.

Value of histological activity in predicting endoscopic relapse among patients of ulcerative colitis in endoscopic remission

Objective: To investigate the value of histological evaluation in predicting endoscopic relapse among patients with ulcerative colitis (UC) who were in endoscopic remission, and to compare the usefulness of various histological scoring systems. Methods: Histological sections from 61 patients with UC who were in endoscopic remission were retrospectively analyzed, at Peking University Third Hospital, Beijing, China from January 2015 to June 2021. They were subdivided into endoscopic persistent remission group (remission group, n=31, Mayo endoscopic score 0) and endoscopic relapse group (relapse group, n=30, Mayo endoscopic score≥1) according to the results of the first endoscopic reexamination after the biopsy. Histological evaluation was performed using the Geboes score (GS) and its simplified version (SGS), the Nancy index (NI) and the Robarts histopathological index (RHI). The median and maximum histological scores for each case in all biopsies were recorded. Univariate comparisons were performed using chi-squares and multivariate analysis using binary logistic regression. The values of four histological evaluation systems for predicting endoscopic relapse among UC patients in endoscopic remission were analyzed using receiver operating characteristic (ROC) curves. Results: Significant differences were observed between the remission and relapse groups. The differences were more pronounced in the maximum histological scores; the mean and highest results of area under the ROC curve scores (AUC) for GS, SGS, NI, and RHI were 0.657, 0.668, 0.682, 0.691, and 0.866, 0.863, 0.864, 0.869, respectively. The differences were statistically significant (P<0.05). The corresponding best cut-offs were GS≥2B.1, SGS≥2B.1, NI≥2, and RHI≥2.5, respectively, which meant mild active inflammation histologically, while there was no statistical difference of AUC among the four histological scoring indices (P>0.05). Univariate and multivariate analyses revealed statistically significant differences in the number of neutrophils in the epithelium and lamina propria (P<0.05). Conclusions: Biopsies from UC patients in endoscopic remission may still have histological active inflammation which appears to correlate with endoscopic relapse. Four commonly used histological scoring systems can be used to assess the risk of endoscopic relapse among UC patients in endoscopic remission. The patients who more likely have endoscopic relapse seem to have a histological score greater than the cut-off value (i.e., mild histological activity). The maximum histological scores can accurately predict the risk of endoscopic relapse, while the presence of epithelial and laminar propria neutrophil infiltrates can independently predict the endoscopic relapse in these patients. Considering the utility and convenience in routine practice, NI is recommended for evaluating histological inflammatory activity.

Therapeutic challenges and unmet needs in the management of myasthenia gravis: an Italian expert opinion.

Myasthenia gravis (MG) is a rare, autoimmune, neurological disorder. Most MG patients have autoantibodies against acetylcholine receptors (AChRs). Some have autoantibodies against muscle-specific tyrosine kinase (MuSK) or lipoprotein-receptor-related protein 4 (LRP4), and some are seronegative. Standard of care, which includes anti-cholinesterase drugs, thymectomy, corticosteroids (CS), and off-label use of non-steroidal immunosuppressive drugs (NSISTs), is bounded by potential side effects and limited efficacy in refractory generalized MG (gMG) patients. This highlights the need for new therapeutic approaches for MG. Eculizumab, a monoclonal antibody that inhibits the complement system, has been recently approved in Italy for refractory gMG. A panel of 11 experts met to discuss unmet therapeutic needs in the acute and chronic phases of the disease, as well as the standard of care for refractory patients. Survival was emphasized as an acute phase outcome. In the chronic phase, persistent remission and early recognition of exacerbations to prevent myasthenic crisis and respiratory failure were considered crucial. Refractory patients require treatments with fast onset of action, improved tolerability, and the ability to slow disease progression and increase life expectancy. The Panel agreed that eculizumab would presumably meet the therapeutic needs of many refractory gMG patients. The panel concluded that the unmet needs of current standard of care treatments for gMG are significant. Evaluating new therapeutic options accurately is essential to find the best balance between efficacy and tolerability for each patient. Collecting real-world data on novel molecules in routine clinical practice is necessary to address unmet needs.

The prognostic value of IgA anti-citrullinated protein antibodies and rheumatoid factor in an early arthritis population with a treat-to-target approach

The mucosal origin hypothesis of rheumatoid arthritis has renewed the interest in IgA autoantibodies, but their added value over IgG anti-citrullinated protein antibody (ACPA) and IgM rheumatoid factor (RF) for modern treatment outcomes remains unknown. We aimed to investigate the prognostic value of IgA-ACPA and IgA-RF for treatment outcomes in an early arthritis population. IgA-ACPA/RF isotypes were measured in baseline sera from 480 inflammatory arthritis (IA) patients, who were included in the treatment in the Rotterdam Early Arthritis Cohort trial (tREACH). The tREACH trial was a multicentre, stratified, single-blinded trial with a treat-to-target approach. The prognostic value of IgA-ACPA/RF was determined by evaluating differences in (1) quick-attained (< 6 months after diagnosis) and persistent remission rates, (2) DMARD-free remission and (3) biological use between IA patients with and without IgA-ACPA/RF over 3 years of follow-up. IgA-ACPA was present in 23% of patients and overlapped with IgG-ACPA positivity in 94%. Similarly, IgA-RF overlapped with IgM-RF in 90% of patients. IgA-ACPA positivity was associated with lower DFR rates and more biological use, but this effect was largely mediated by the presence of IgG-ACPA, since this effect disappeared after stratification for IgG-ACPA (HR 0.6, 95%CI 0.2-1.6 for DFR). No differences were observed in ‘quick-attained and persistent remission’ rates and for IgA-RF. Their seems to be no additional value of IgA-ACPA and IgA-RF for modern, long-term clinical outcomes. The effects of IgA-ACPA seen in our study are largely mediated by the presence of IgG-ACPA. Based on these results, there is no rationale for measuring these isotypes in daily practice.

Diffuse large B-cell lymphoma and follicular lymphoma: problem state in Russia

Background. Non-Hodgkin's lymphomas (NHL) are a heterogeneous group of hematological malignancies, the vast majority of which are B-cell tumors. The most common variant of NHL is diffuse large B-cell lymphoma (DLBCL), characterized by an aggressive course, which accounts for 30–40% of all NHL. The second most common is follicular lymphoma (FL), traditionally classified as an indolent variant accounting for up to 25% of all NHL. Current therapies for these lymphoproliferative disorders which includes innovative drugs in the 1st line of therapy (LT) have demonstrated high efficacy. However, some patients develop a relapse or a refractory disease. Despite recent significant progress in the development and implementation of innovative targeted drugs, in most cases, it is not possible to achieve persistent long-term remissions after disease relapse, which leaves patients with an unmet need for effective and well-tolerated treatment options. Aim. To obtain objective data on the incidence, clinical course, and effectiveness of therapy for the most common variants of NHL in real-world practice in Russia. Materials and methods. From February to March 2023, 130 hematologists and oncologists from 30 regions of Russia were surveyed to update the data on DLBCL and FL. Results. Over the past 12 months, 5,689 patients with NHL were observed, of which 56% had DLBCL; 62% of them received the 1st LT, 22% received the 2nd LT, 10% received the 3rd LT, and only a few reached later lines. Analysis of the administered treatment options in the 2nd and 3rd LTs shows that there is no standard of care for this population, and the effectiveness of the regimens used in real-world Russian practice is extremely low. FL accounted for 23% of all 5,689 patients with NHL, of which 56% were newly diagnosed and 44% received treatment for relapse. The majority of patients with FL who received ≥3 LTs had an inferior prognosis and rapid disease progression: the median time from diagnosis to the beginning of the 3rd LT was only 26.4 months. The analysis of treatment options for patients with relapsed FL indicates a lack of standard and effective therapies. Conclusion. Relapsed and refractory DLBCL and FL represent a complex clinical situation where the main goal of treatment is disease control due to the impossibility of achieving stable remissions with existing treatment options. Clinicians with great hope are looking to the emergence of new classes of drugs that will be able to improve the prognosis for this complex population.

Characteristics of Adults With Severe Asthma in Childhood: A 60-Year Follow-Up Study

BackgroundChildhood asthma is a prevalent condition with potential impact on adult life. Research QuestionIn a 60-year follow-up study of adults with a history of severe childhood asthma, what are the potential differences in characteristics between individuals with persistent asthma and asthma remission in adulthood? Study Design and MethodsDanish adults with a history of childhood asthma and a 4-month stay in at an asthma care facility in Kongsberg, Norway (1950-1979) in childhood were included. Recruitment was done through social media and personal invitation letters. Participants completed questionnaires and underwent spirometry, bronchial provocation, and bronchodilator reversibility and blood tests. Asthma remission was defined as no use of asthma medication and no asthma symptoms within the past 12 months with the remaining participants being classified as having current asthma. ResultsAmong 1394 eligible participants, 232 completed the follow-up. Ninety percent had current asthma, of whom 26% reported exacerbations in the past year. Only 16% of all the participants were managed in secondary care. Common comorbidities were allergic rhinitis (60%), hypertension (21%), eczema (16%), and cataract (8%). Compared to participants in remission, participants with persistent asthma had higher total immunoglobulin E (p=0.03), and both lower FEV1%pred (p=0.03), and FEV1/FVC ratio (p<0.001), as well as numerically higher fractional exhaled nitric oxide and blood eosinophil count. InterpretationOur 60-year follow-up study of adults with a history of severe childhood asthma revealed that nine out of ten still had current asthma. Persistent asthma was associated with lower lung function and higher levels of type 2 inflammatory biomarkers compared to those with asthma remission.

#2388 Relevance of anti-PLA2R levels in therapy decision and prediction of therapy outcome in patients with membranous nephropathy

Abstract Background and Aims Detection of anti-phospholipase A2 receptor (PLA2R) antibodies in patients with primary membranous nephropathy (MN) supports diagnosis as well as disease monitoring. An individualised therapy approach was introduced for anti-PLA2R positive MN patients at the Radboud University Medical Center. Immunosuppressive treatment (cyclophosphamide combined with steroids) was stopped when anti-PLA2R results by indirect immunofluorescence testing (IIFT) became negative. Here, we evaluated the relevance of anti-PLA2R levels for therapeutic decisions and the outcome of MN, comparing qualitative and quantitative detection methods. Method Stored serum samples were retrieved for beginning of treatment (baseline), decision point, and follow-up. Anti-PLA2R levels were determined qualitatively by IIFT as well as quantitatively by enzyme-linked immunosorbent assay (ELISA) and chemiluminescence immunoassay (ChLIA) at baseline as well as after treatment and correlated to immunological remission and persistence. Results For an evaluation of the relevance of anti-PLA2R levels at the start of therapy, serum samples of 60 patients were available. Patients sampled at the beginning of the therapy were grouped according to tertiles of anti-PLA2R levels determined by ChLIA (n[lowest tertile] = 20, n[middle tertile] = 20, n[highest tertile] = 20). Lower anti-PLA2R levels were seen in patients with relapsing disease. Higher anti-PLA2R levels were associated with more severe proteinuria. Patients in the lowest tertile of anti-PLA2R were more likely to develop immunological remission after 8 weeks of therapy. In total, 90% vs 75% vs 45% of patients in the tertiles turned anti-PLA2R negative after being treated for 8 weeks. Moreover, in this subgroup of patients who showed immunological remission after 8 weeks of therapy, only 11% of the patients in the lowest tertile needed renewed immunosuppressive therapy, while this percentage increased in the middle and highest tertiles (11% vs 53% vs 33%, p=0.033). For the assessment of anti-PLA2R levels before and after therapy, samples at baseline and week 8 of treatment were examined. At baseline, 50/50 (100%) tested positive in IIFT and ChLIA as well as 48/50 (94%) in ELISA. After 8 weeks on treatment, immunological remission based on IIFT was found in 37/51 (73%) patients. At this point, the overall agreement compared to IIFT was 92% for ChLIA and 82% for ELISA. Yet the availability of quantitative levels provided further insight into this group of patients in whom treatment was discontinued. With ChLIA, anti-PLA2R titers &amp;gt;5 RU/mL after 8 weeks of therapy were found in 4% of IIFT negative patients with persistent remission, vs 55% of IIFT negative patients with early relapse (p=0.006). Conclusion Individualised treatment of MN patients with cyclophosphamide and steroids has been recently introduced. In this respect, the quantitative determination of anti-PLA2R levels adds further value. Of the examined quantitative methods, ChLIA demonstrated the highest agreement with IIFT. Additional studies are needed to evaluate the impact on clinical decision making and outcome.

Long-term remission and survival in patients with relapsed or refractory multiple myeloma after treatment with LCAR-B38M CAR T cells: 5-year follow-up of the LEGEND-2 trial

BackgroundThe autologous anti–B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy LCAR-B38M has been approved for the treatment of relapsed and refractory multiple myeloma in many countries across the world under the name ciltacabtagene autoleucel. LEGEND-2 was the first-in-human trial of LCAR-B38M and yielded deep and durable therapeutic responses. Here, we reported the outcomes in LEGEND-2 after a minimal 5-year follow-up.MethodsParticipants received an average dose of 0.5 × 106 cells/kg LCAR-B38M in split or single unfractionated infusions after cyclophosphamide-based lymphodepletion therapy. Investigator-assessed response, survival, safety and pharmacokinetics were evaluated.ResultsSeventy-four participants enrolled and had a median follow-up of 65.4 months. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 21.0% and 49.1%, with progressive flattening of the survival curves over time. Patients with complete response (CR) had longer PFS and OS, with 5-year rates of 28.4% and 65.7%, respectively. Twelve patients (16.2%) remained relapse-free irrespective of baseline high-risk cytogenetic abnormality and all had normal humoral immunity reconstituted. An ongoing CR closely correlated with several prognostic baseline indices including favorable performance status, immunoglobulin G subtype, and absence of extramedullary disease, as well as a combination cyclophosphamide and fludarabine preconditioning strategy. Sixty-two (83.8%) suffered progressive disease (PD) and/or death; however, 61.1% of PD patients could well respond to subsequent therapies, among which, the proteasome inhibitor-based regimens benefited the most. Concerning the safety, hematologic and hepatic function recovery were not significantly different between non-PD and PD/Death groups. A low rate of second primary malignancy (5.4%) and no severe virus infection were observed. The patients who tested positive for COVID-19 merely presented self-limiting symptoms. In addition, a sustainable CAR T population of one case with persistent remission was delineated, which was enriched with indolently proliferative and lowly cytotoxic CD4/CD8 double-negative functional T lymphocytes.ConclusionsThese data, representing the longest follow-up of BCMA-redirected CAR T-cell therapy to date, demonstrate long-term remission and survival with LCAR-B38M for advanced myeloma.Trial registrationLEGEND-2 was registered under the trial numbers NCT03090659, ChiCTRONH-17012285.

Meta-Analysis of the Problem of Rehabilitation of Chemically Dependent Persons in Russian and Foreign Literature

The article analyzes the domestic and foreign literature of recent years, aimed at studying the effectiveness of the rehabilitation process of chemically dependent persons. However, most of the results obtained by the researchers are not comparable with each other. Firstly, the reasons are related to differences in the theoretical approaches of the authors of the goals, objectives and mechanisms of the rehabilitation process, as well as the "blurring" of the effectiveness criteria. In Russian narcology the criterion for the success of the rehabilitation process is the persistence, duration and quality of the achieved remissions. As scientific and practical studies show, the persistence of remission is achievable when the period of abandonment of substance is complemented by a long rehabilitation period, thanks to which the individual's ability to function in society is restored. Foreign researchers who consider recovery as a "process", not as an "end point", come to the conclusion that after all the necessary stages of rehabilitation, it is necessary to provide constant long-term support. A significant amount of international research confirms the need for long-term support in the post-rehabilitation period. From the point of view of some Russian authors, rehabilitation is a multi-level process that includes an environment with a certain atmosphere in which both rehabilitators and specialists interact. However, there are currently no training manuals and recommendations that would collect and systematize scientific and practical information for specialists working in the field of rehabilitation of minors prone to substance use. In modern narcology it is necessary to improve the organizational principles and legislative framework of the entire system of rehabilitation process of chemically dependent persons.

Immunological Remission as a Basis for Dose Reduction of Immunosuppressors in Autoimmune Hepatitis: Results of Monocenter Surveillance Study

Aim of the study: evaluate the role of normalization of humoral immunity to address dose reduction or discontinuation of immunosuppressors in patients with autoimmune hepatitis (AIH).Patients and methods. The data of 47 patients with AIH who received immunosuppressive therapy from April 2001 to August 2023 were analyzed: 10 men (21 %), 37 women (79 %); the average age was 37 (17–66) years. The follow-up period was 10–180 months. Type 1 AIH was diagnosed in 37 patients, type 2 AIH — in 7 patients, seronegative AIH — in 3 patients. The diagnosis was established according to the IAIHG point system. To confirm the diagnosis, a liver biopsy was performed in 17 patients, a histological picture of AIH was detected in all of them. The most used combination was prednisolone and azathioprine — in 25 patients (53.2 %), as well as methylprednisolone and azathioprine — in 8 patients (17 %).Results. In some patients, when the immunosuppressive therapy decreased below the recommended dose, a relapse of the disease developed (Group 1), and in others, remission persisted (Group 2). The concentration of гамма-globulins in patients of Group 1 was 22.5 mg%, in Group 2 — 17.95 mg% (p = 0.00055). IgG level after achieving remission in Group 1 was 1709.7 mg/dL, in Group 2 — 1381.7 mg/dL (p = 0.000001). The terms of ALT normalization in Group 1 were 2.14 months, in Group 2 — 1.47 months (p = 0.037); AST normalization in Group 1 made 2.22 months, in Group 2 — 1.48 months (p = 0.026).Conclusions. Normalization of humoral immunity, as well as rapid normalization of ALT and AST can be considered as markers of maintaining AIH remission when immunosuppressor doses are reduced below standard doses, and in individual patients — the possibility of immunosuppressive therapy withdrawal. This will reduce the risk of adverse events and increase adherence to the therapy. We propose introducing the term “immunological remission” into the clinical lexicon, which, along with biochemical and histological remission, acts as a predictor of persistent remission of AIH.

Experience of using the medical product “Alfasoxx” in treatment of patients with radiation rectit

The radiation rectit is the structural and functional changes in the tissues of the rectum caused by the direct exposure to ionizing radiation. Currently, there is no clear strategy for treating patients with radiation rectit, allowing to achieve a long-term and persistent remission of the disease. The results of comparative research on the using of the developed by us method of treatment of patients with radiation rectit with medical product «Alfasoxx» are presented. The developed technique of complex treatment of radiation rectit with medical product «Alfasoxx» is effective, easy to perform and has reasonable prospects for introduction into the routine practice of a doctor-coloproctologist.

A270 RISK FACTORS FOR COLORECTAL NEOPLASIA DEVELOPMENT IN INFLAMMATORY BOWEL DISEASE PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS: A CASE-CONTROL STUDY

Abstract Background Patients with inflammatory bowel disease (IBD) and concomitant primary sclerosing cholangitis (PSC-IBD) have a 25-year cumulative risk of up to 50% to develop colorectal neoplasia (CRN). Mucosal inflammation is an important driver of CRN development in IBD, but it is unknown whether this also applies to PSC-IBD patients. Aims We aimed to assess the impact of active mucosal inflammation per colonic segment and endoscopic remission on CRN risk. Methods This is a single-center case-control study, including cases with PSC-IBD with CRN, and controls with PSC-IBD without CRN. Exclusion criteria were a CRN diagnosis prior to IBD or PSC diagnosis, familial CRC syndromes, and insufficient endoscopic follow-up (ampersand:003C2 available colonoscopy reports, and for cases, ampersand:003C2 available endoscopy reports before CRN diagnosis). Data was collected on demographics, IBD and PSC disease characteristics, and IBD medication use. Data from all available colonoscopy and sigmoidoscopy reports between 2002 and 2023, including endoscopic and histologic disease severity, disease extent, and CRN lesions, was collected. The primary outcome was a diagnosis of CRN, secondary outcomes included CRN grade and location, inflammatory burden per colonic segment harboring CRN, and colonic surgery. Results We included 247 PSC-IBD patients (163 ulcerative colitis, 80 Crohn’s disease) with a median follow-up of 6.3 years (IQR: 4.1-12.6) and 6 endoscopic procedures (IQR: 4.0-8.0). Median disease duration was 19 years for IBD (IQR: 11.0-26.0) and 13 years for PSC (IQR: 7.0-18.0). In 50 cases a total of 113 CRN lesions were observed, of which 11 (10%) were advanced CRN (aCRN; HGD or CRC). 23 patients (45%) were diagnosed with ampersand:003E 1 lesion while 45 lesions (40%) were identified in the right-sided colon, 27 (24%) in the transverse colon, 28 (25%) in the left-sided colon, and 10 (9%) in the rectum (3 lesions unknown). Endoscopic remission was observed in 24 cases (48%) during the 2 endoscopies prior to lesion detection vs. in 83 controls (42%) for their last 2 endoscopies. Of all CRN lesions, 39 (35%) were found in a colonic segment with confirmed previous endoscopic and/or histologic inflammation during the 1-2 endoscopies prior to lesion detection (31 low-grade and 8 aCRN). Of the 32 patients who underwent (sub)total colectomy or proctocolectomy, 20 (63%) had an indication due to CRN diagnosis. Mortality was 13% (n=32) during follow-up. Conclusions The risk for CRN and associated colectomy is high in PSC-IBD. Active mucosal inflammation preceded CRN in the affected colonic segment in only 35% of the lesions. Future expansion and additional analysis of our cohort will focus on the impact of persistent endoscopic remission and impact of biologic therapy on CRN risk in PSC-IBD. Funding Agencies None

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.

P1091 Cross-domain dynamics of the fungal-bacterial microbiome in patients with ulcerative colitis

Abstract Background Background: Candida in the gut has been recently linked to inflammatory activity in UC. However, the relationship between Candida abundance and the bacterial microbiome remains poorly understood, and how these relationships evolve over disease course in UC is unknown. Methods Methods: We utilized data from the Study of a Prospective Adult Research Cohort with IBD (SPARC-IBD) from IBD Plexus to examine the taxonomic composition of the fungal mycobiome and bacterial microbiome cross-sectionally and longitudinally in time. Differential abundance was assessed using a log-transformed linear model on microbial relative abundances, with a false discovery rate of &amp;lt;0.25. Spearman’s correlations and co-abundance networks were utilized to examine relationships between fungi, bacteria, and disease activity. Changes in fungi and bacteria within-subjects was assessed over 2 timepoints, with respect to clinical inflammatory status, and abundances were compared using Wilcoxon signed rank tests. Results Results: Among 212 patients with UC, 166 patients were in clinical remission (78.3%) while 46 demonstrated clinical activity (21.7%). During clinical activity, there were increases in Candida (q-val&amp;lt;0.05), bacterial family Desulfovibrionaceae (q-val&amp;lt;0.05), and genus Bilophilia (q-val&amp;lt;0.05) [Fig 1A]. During remission, there were reductions in Candida, with increases in family Lachnospiraceae (q-val&amp;lt;0.05), including genus Anaerostipes (q-val=0.09), Blautia (q-val=0.09) and Roseburia (q-val=0.21) [Fig 1B]. Active disease positively correlated with Candida and Desulfovibrionaceae, and negatively correlated with family Lachnospiraceae. During remission, a positive network was present between family Lachnospiraceae, Bifidobacteriaceae, and Eggerthellaceae, which was disrupted during activity, while an antagonistic relationship was evident between Candida and Saccharomyces during remission. Among 25 patients with persistent remission over time (median time interval ~ 4 months), there were no changes in fungal abundances over timepoints. Among patients evolving from activity to remission (n=7), Saccharomyces significantly increased (p-val&amp;lt;0.05), with no significant change in Candida, although there was a trend towards reduction (mean relative abundance at t1=0.28 vs t2=0.11). Concurrently among bacteria, both Bifidobacterium and Anaerostipes significantly increased (p-val&amp;lt;0.05). Conclusions Candida and bacteria from families Lachnospiraceae may have opposing associations with inflammatory status in ulcerative colitis, suggesting they may demonstrate competitive ecological niches. Whether reduction of Candida species may expand protective bacteria should be tested adjunctive to immunosuppressive or microbial modulation therapies.

P877 A comparison of vedolizumab and ustekinumab treatment in patients with Ulcerative Colitis after failure of treatment with tumor necrosis factor inhibitor

Abstract Background Data comparing vedolizumab (VDZ) and ustekinumab (UST) in patients with ulcerative colitis (UC) previously treated with tumor necrosis factor inhibitor (TNFi) and followed with regular serum-drug measurements are scarce. In the national pharmaceutical tender system of Norway, VDZ was listed as the first drug of choice after failed TNFi treatment from 2016 to 2019 and UST from 2020 to 2022. We aimed to compare drug persistence, effectiveness, drug dosing and disease activity in patients treated with VDZ or UST after failed TNFi therapy. Methods We included patients who had failed at least one TNFi and started either VDZ treatment (years 2016-2019) or UST (years 2020-2022). Patients were followed for one year after initiating the treatment or until discontinuation. Prospectively recorded data were obtained from the electronic patient journal (EPJ) and the local IBD-registry. Clinical remission was defined as 6-point Mayo Score ≤1, and biochemical remission was defined as CRP&amp;lt;5 mg/L and FC&amp;lt;250 µg/g. Patients were followed with regular serum-drug measurements and dose adjustments were made at the discretion of the treating physician based on serum-drug measurements and clinical activity at follow-up visits. Wilcoxon signed rank and Mann Whitney U test were used to assess differences in paired and unpaired data, respectively. Results A total of 116 patients were included, 59 treated with VDZ and 57 with UST. At 52 weeks, there was no difference in estimated drug persistence with 85% [73-92] for VDZ and 92% [80-96] for UST. Clinical remission increased significantly in both groups (Table 1), and no difference was found between UST and VDZ for clinical remission at week 0 and 52 (OR=2.1 [0.9-4.5] and OR=0.9 [0.3-2.3]). Contrary to the VDZ group, there was a significant decrease in CRP from week 0 to 52 in the UST group, while FC decreased significantly in both groups (Table 1). The proportion of patients in biochemical remission increased in the UST group while there was no significant change in the VDZ group. Significantly more patients treated with UST received an intensified treatment regime at 52 weeks (interval less than eight weeks) compared to VDZ treated patients (87% (95% CI [74-94]) vs 59% (95% CI [45-72])). Conclusion This study demonstrates that one-year drug persistence and clinical remission were high and comparable in both UST and VDZ treated UC patients with previous TNFi failure. Treatment with UST, but not VDZ, was associated with a significant increase in the proportion of patients in biochemical remission from induction to 52 weeks. However, a significantly larger proportion of patients treated with UST received intensified dosing at 52 weeks compared with VDZ treated patients.

Monocentric study of IL-5 monoclonal antibody induction therapy for eosinophilic granulomatosis with polyangiitis

ObjectiveAlthough sporadic case reports have demonstrated successful management of eosinophilic granulomatosis with polyangiitis (EGPA) by anti-IL-5 therapy, larger-scale monocentric studies for the efficacy of mepolizumab (MEP), an IL-5 monoclonal antibody, are still lacking in Taiwan. MethodsHospitalized EGPA patients aged at least 18 years were enrolled from November 1998 to October 2023, and analyzed for demographic, clinical, laboratory, medication and outcome data, focusing on the efficacy and safety of biologics use, particularly induction therapy with MEP. ResultsTwenty-seven EGPA patients aged 10–70 years (43 ± 15) at disease diagnosis were recruited with 21 under combined corticosteroids/cyclophosphamide induction therapy. Seventeen patients received biologics with 13 under MEP therapy. Ten patients aged 19–71 years (48 ± 15) completed 12-month induction therapy with a 100 mg quadri-weekly subcutaneous injection regimen indicated for active or relapse disease. There were reduced BVAS with complete remission in 6 and partial remission in 4 patients, lower CRP levels, decreased eosinophil counts with an inhibition of 92∼96 %, and tapered prednisolone dosages from 5 to 25 (13.0 ± 6.3) to 0–10 (3.3 ± 3.1) mg/day. Only one patient had an adverse event of injection site reactions. Nine patients received the same regimen for annual maintenance therapy. All had a persistent clinical remission. In these patients, 13–56 injections (41 ± 15) were prescribed with a follow-up period of 12∼52 months (38 ± 14). ConclusionIn this retrospective study, induction therapy with a 12-month 100 mg MEP quadri-weekly subcutaneous injection regimen demonstrates the efficacy and safety for active and relapsing EGPA patients.