A Comprehensive Assessment of Progression Independent of Relapse Activity in a Cohort of Patients with Secondary Progressive Multiple Sclerosis (P8-6.010)

Tue, 09 Apr 2024 00:00:00 GMT

A Comprehensive Assessment of Progression Independent of Relapse Activity in a Cohort of Patients with Secondary Progressive Multiple Sclerosis (P8-6.010) Zarate, María Agustina; Marrodán, Mariano; Piedrabuena, María Agustina; Fiol, Marcela Paula; Ysrraelit, María Célica; Correale, Jorge Objective: To analyze characteristics of patients with secondary progressive Multiple Sclerosis (SPMS) exhibiting Progression Independent of Relapse Activity (PIRA) and to identify factors contributing to earlier progression Background: Emerging evidence suggests that PIRA is not restricted to progressive MS forms, starting early in the disease and contributing to disability accrual in MS. However, how PIRA starts and the factors accelerating its onset remain uncertain. Design/Methods: A retrospective analysis of clinical and demographic characteristics of SPMS patients was conducted. Parametric and non-parametric tests and multivariate regression analysis were applied according to objectives. Demographics were expressed as median (IQR1–3) Results: 178 SPMS patients were included out of which 108 were females. The median follow-up duration was 11.83 years (4.83–18.58), 139 patients were classified as active. Median time since the first evidence of PIRA was 7.58 years (5–35), and in 43 patients this occurred within 5 years (early PIRA, EP). Patients with EP were older compared to late PIRA (LP) (EP 38, 32–46.5 vs. LP 32, 25–42.75, p=0.02) with female predominance (62% vs. LP 32%, 25–42.7, p=0.02). No increased risk of EP was observed at age 60 or older. Myelitis was the first clinical symptom presented in EP more frequently (70% vs. 36%, p<0.005). EP patients transitioned to SPMS faster (74 vs 162 months, p<0.01). Frequency of EP decreased with age; those initiating treatment between 30–39 years presented OR=6.2 (95% CI=1.8–21.4, p=0.004), at 40–49 years OR=6.1 (95% CI=1.6–23, p=0.007), and at 50–59 years OR=5.77 (95% CI=1.1–28, p=0.03). Conclusions: Early PIRA occurrence is influenced by age, initial symptoms, and treatment onset, highlighting the complexity of MS progression. Disclosure: Miss Zarate has nothing to disclose. Dr. Marrodan has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Marrodan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck, Astra Zeneca, Gador, Biogen, Roche and Novartis. Mrs. Piedrabuena has nothing to disclose. Marcela Fiol has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for merck. The institution of Marcela Fiol has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for biogen. Marcela Fiol has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Merck. Marcela Fiol has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Biogen. Marcela Fiol has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Novartis. Marcela Fiol has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Teva. Marcela Fiol has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Roche. Celica Ysrraelit has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Celica Ysrraelit has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Celica Ysrraelit has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Celica Ysrraelit has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Celica Ysrraelit has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Genzyme. Celica Ysrraelit has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Celica Ysrraelit has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Merck, . Celica Ysrraelit has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Biogen. Celica Ysrraelit has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Bayer. Celica Ysrraelit has received research support from Novartis. The institution of Celica Ysrraelit has received research support from ROCHE. The institution of Celica Ysrraelit has received research support from Roche. Dr. Correale has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Correale has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Correale has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Correale has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Correale has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Correale has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ROche. Dr. Correale has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Correale has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Correale has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Correale has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Genzyme. The institution of Dr. Correale has received research support from Merck. The institution of Dr. Correale has received research support from Biogen. The institution of Dr. Correale has received research support from Novartis.

Long-term Effect of Ofatumumab on Serum Immunoglobulin Levels in Patients with Relapsing Multiple Sclerosis (P9-6.007)

Sat, 09 Mar 2024 00:00:00 GMT

Long-term Effect of Ofatumumab on Serum Immunoglobulin Levels in Patients with Relapsing Multiple Sclerosis (P9-6.007) Bar-Or, Amit; Wiendl, Heinz; de Seze, Jerome; Correale, Jorge; Cross, Anne H.; Derfuss, Tobías; Selmaj, Krzysztof; Winthrop, Kevin; Giacomini, Paul Steven; Sacca, Francesco; Hu, Xixi; Sullivan, Roseanne; Jehl, Valentine; Boer, Ibolya; Bhatt, Alit; Hauser, Stephen L.

Iron metabolism in oligodendrocytes and astrocytes: friend or foe?

Mon, 01 Nov 2021 00:00:00 GMT

Iron metabolism in oligodendrocytes and astrocytes: friend or foe? Pasquini, Juana María; Rosato-Siri, María Victoria; Martino Adami, Pamela V.; Guitart, María Eugenia; Marcora, María Silvina; Morelli, Laura; Correale, Jorge Recent reports show that astrocytes (AST) are able to create a permissive environment for remyelination through their action on oligodendrocyte (OLG) precursor migration, proliferation, and differentiation. When disrupted, iron homeostasis negatively impacts OLG differentiation and impairs myelination. We demonstrate that iron deficiency (ID) affects not only OLG maturation but also AST. Using gestational iron deprivation, we studied OLG requirements for their progression to a mature myelinating state and energy metabolism in primary cultures of OLG and AST from newly born control and ID pups. In particular, oxygen consumption and extracellular acidification rates were measured using a Seahorse extracellular flux analyzer. Both ID AST and OLG exhibited decreased spare respiratory capacity, which indicates that maternal ID effectively induces mitochondrial dysfunction. Absence of glycogen granules was observed in ID AST and an increase in ROS production was detected in ID OLG. Mitochondrial fission was increased in ID AST, while fusion was prevalent in ID OLG. Electron microscopy also showed abnormal cristae in ID mitochondria in OLG as well as in AST. These findings further prove that the regulation of cell metabolism may impact cell fate decisions and maturation. An additional model of ID was developed by knocking down the divalent metal transporter 1 (DMT1), a multi-metal transporter with a primary role in iron transport and present in AST and OLG. OLG maturation was compromised in primary OPC cultures treated with conditioned medium from DMT1-silenced AST, which suggests that molecules secreted by AST may be affected.

Effect of Ofatumumab on Serum Immunoglobulin Levels and Infection Risk in Patients With Relapsing Multiple Sclerosis Over 3.5 Years

Fri, 01 Oct 2021 00:00:00 GMT

Effect of Ofatumumab on Serum Immunoglobulin Levels and Infection Risk in Patients With Relapsing Multiple Sclerosis Over 3.5 Years Wiendl, Heinz; de Seze, Jerome; Bar-Or, Amit; Correale, Jorge; Cross, Anne H.; Kappos, Ludwig; Selmaj, Krzysztof; Winthrop, Kevin; Giacomini, Paul Steven; Sacca, Francesco; Das Gupta, Ayan; Jehl, Valentine; Pingili, Ratnakar; Mancione, Linda; Zielman, Ronald; Hauser, Stephen L. Resumen no disponible

Enfermedades Desmielinizantes.pósters

A Comprehensive Assessment of Progression Independent of Relapse Activity in a Cohort of Patients with Secondary Progressive Multiple Sclerosis (P8-6.010)

Long-term Effect of Ofatumumab on Serum Immunoglobulin Levels in Patients with Relapsing Multiple Sclerosis (P9-6.007)

Iron metabolism in oligodendrocytes and astrocytes: friend or foe?

Effect of Ofatumumab on Serum Immunoglobulin Levels and Infection Risk in Patients With Relapsing Multiple Sclerosis Over 3.5 Years