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1. Elevated pulse pressure and cardiovascular risk associated in Spanish population attended in primary care: IBERICAN study

Author

Ana Moyá-Amengual, Antonio Ruiz-García, Vicente Pallarés-Carratalá, Adalberto Serrano-Cumplido, Miguel Ángel Prieto-Díaz, Antonio Segura-Fragoso, Sergio Cinza-Sanjurjo, the researchers of the IBERICAN study, Alfonso Barquilla García, Ángel Díaz Rodríguez, Carlos Escobar Cervantes, Francisco Javier Alonso Moreno, Jesús Vergara Martín, Juan José Badimón, José Polo García, Luis Rodríguez Padial, Miguel Ángel Prieto, Rafael Vidal Pérez, Sergio Cinza Sanjurjo, Sònia Miravet Jiménez, Sonsoles Velilla Zancada, José Ramón Banegas, Vicente Martín Sánchez, Vicente Pallares Carratalá, Antonio Segura Fragoso y Rafael Manuel Micó Pérez, Antonio López Téllez, Jesús Vergara Martin, María De Los Ángeles Ortega Osuna, Cristóbal Prieto Cid, Mª José Hidalgo Fajardo, José Lorente Serna, Ángel Domínguez Requena, Ricardo Alberola Cañizares, Manuel Ruiz Peña, Filomena Herrero Collado, Marcela Montes Vázquez, Rafael Ángel Carrascal Garrido, María Reyes Herrera Lozano, Beatriz Ortiz Oliva, Francisco José Anguita, Carmen Pérez Ibáñez, Carlos Alberto Cabrera Rodríguez, María José Cruz Rodríguez, Sandra Bonilla Ruiz, Rocio Reina González, Salome Abad Sánchez, Inmaculada Santana Martínez, Rafael Sánchez Jordán, Juan Mª Ramos Navas-Parejo, José Manuel Ramírez Torres, José María Beltrán Poveda, María Adoración De Cruz Benayas, Carmen Fernández Gil, Jon Iñaki Esturo Alcaine, Antonio Mora Quintero, Fernando Leiva Cepas, José Luis Carrasco Martín, Emilio García Criado, Mercedes Vázquez Blanco, Isabel Mora Ortiz, Leovigildo Ginel Mendoza, Juan Carlos Aguirre Rodríguez, Esperanza María Romero Rodríguez, José Acevedo Vázquez, Juan Gabriel García Ballesteros, María De La Paz Fernández Lara, Patricia Agüera Moreno, Eduardo Paños Maturana, Juan Manuel Ignacio Expósito, Noelia Carrillo Peñas, Carmen María Abad Faya, Ana Marina Almagro Duque, Rubén Torrescusa Camisón, Paloma Menéndez Polo, Marina Peña García, Cristina López Fernández, Ascensión Estepa Torres, Miguel Gutiérrez Jansen, Esperanza Loizaga González, Lisardo García Matarín, Enrique José Gamero De Luna, Javier Benítez Rivero, María José Gómez González, Carmen Gómez Montes, Juan Carlos Rodríguez Rodríguez, Juana María González Barranco, Josefa Ramírez Vizcaíno, María Ángeles Miranda Sánchez, Eva Trillo Calvo, Concepción Bayod Calvo, Susana Larripa De La Natividad, German Grasa Lambea, Emilio Jiménez Marín, Ana Cristina Navarro Gonzalvo, Antonio Pablo Martínez Barseló, Irene Peña León, Ángel González Pérez, Liliana Mahulea, María José Pérez Martínez, Ana Piera Carbonell, Margarita Alonso Fernández, María Montserrat Rueda Cuadrado, Rodrigo Abad Rodríguez, José Miguel Álvarez Cabo, Rubén Sánchez Rodríguez, Eva María Cano Cabo, Anny Romero Secin, Miguel Ángel Prieto Díaz, Juan Jesús García Fernández, Saúl Suárez García, Fernando García Romanos, Antonia Moreno González, María Lara Amengual Sastre, Susana Martínez Palli, José Alfonso Ramón Bauza, Jose Ortiz Bolinches, Carmen Fernández Fernández, María Isabel Orlandis Vázquez, Ana Sanchís Mezquita, Fernando Unceta Aramburu, Juan Fernando Peiró Morant, Ana Moyá Amengual, Matéu Seguí-Díaz, José Félix Zuazagoitia Nubla, Ana Echevarría Ituiño, Gregorio Mediavilla Tris, María Carmen Noriega Bosch, Esther González, María Luisa Ruiz Macho, Ruth Sendino Del Olmo, Asunción Olagorta De Prado, Ana López De Viñaspre Muguerza, Jesús Iturralde Iriso, Mª Rosario Virtus Iñurrieta, Lucas Ulloa Bahamonde, Isidro Godoy García, Fernando Rubio Sevillano, María Isabel González González, Marta Pérez Souto, Raquel De León Contreras, Sara Isabel Almeida González, Irene Almería Diez, Virginia Maria Mirabal Sánchez, Francisco José Escobar Lavado, Yoel Anta Pérez, Nayra Sánchez Hernández, Juan Luis Alonso Jerez, Ricardo Koch, Nayra Ramírez Mendoza, Héctor Suárez Hernández, Francisco Jesús Morales Escobar, E Lidia Gutiérrez Fernández, Fernando Andrés Mantecón, Ana Belén García Garrido, Asunción Vélez Escalante, Luisa Alonso Rentería, Jesús Sainz Jiménez, Guillermo Pombo Alles, Esperanza Rueda Alonso, Juan Antonio Divisón Garrote, Pedro Martínez Sotodosos, Juan Antonio Vivancos Fuster, María García Palencia, José Ambrosio Torres Moraleda, Sara González Ballesteros, Ana Carmen Gil Adrados, Antonio González Cabrera, Miguel Ángel Babiano Fernández, Guillermo Rico García, Juan José Criado-Álvarez, Pilar Torres Moreno, Francisco Javier Arribas Aguirregaviria, Alicia Sahuquillo Martínez, Lourdes Maria Santos Bejar, Miguel Laborda Peralta, Raúl Piedra Castro, Carlos Santos Altozano, Lucia González-Tarrio Polo, Pedro Valiente Maresca, Reinilda Mota Santana, Noemi Elizabeth Terrero Ledesma, Noelia Garrido Espada, Gabriela Delia Rosa Zambrana Calvi, Cristina de Castro Mesa, Blanca Cordero García, Pilar Sorrius Sitges, Ana María de Santiago Nocito, César Lozano Suárez, Juan Lorenzo Gutiérrez Montero, Juan Ignacio López Gil, María Dolores Fernández Ortega, Miren Elizari Roncal, María Ascensión López Serrano, Nuria Esther Adrián De La Fuente, Belén Angulo Fdez. De Larrea, Naiara Cubelos Fernández, Guiomar Luz Ferreiro Gómez, Diana Gómez Rodríguez, Sonia María Andrés Tuñón, María Ajenjo González, Serafín De Abajo Olea, Juan José León Regueras, César Manuel Gallego Nieto, Delio Vázquez Mallada, Maria De La O Gutiérrez García, Pablo Baz Rodríguez, José Ignacio Ferradal García, Blanca Delia De Román Martínez, Ana Arconada Pérez, Omar Mahmoud Atoui, Álvaro Morán Bayón, María Teresa Armenteros Del Olmo, Francisco Javier García-Norro Herreros, Enrique Méndez Rodríguez, Diana María Narganes Pineda, Verónica Ortiz Ainaga, Milagros Sonlei Sánchez Guevara, Laura Villota Ferreiro, M Teresa Grande Grande, Francisco Vicente Martínez Gracia, Jesús Palomo del Arco, María Dolores Moriano García, Beatriz Jiménez Muñoz, Gemma Rovira Marcelino, Diana Elizabeth Fernández Valverde, Roser Rodó Bernadó, Maria Teresa Ortiz Lupiañez, Najlaa Najih, José María Diéguez Parra, Mª Rosa Benedicto Acebo, Mari Luz Bravo Vicien, Alberto Ramón León Estella, Juan Antonio Muñoz Gómez, Alicia Mostazo Muntané, Isabel Ortega Abarca, Anna Gasol Fargas, Brenda Elizabeth Riesgo Escudero, Susana Elizabeth Riesgo, Edgar Zaballos Castellvi, Celia Cols Sagarra, Marta Herranz Fernández, Josep Alins Presas, Idaira Damas Pérez, Rosa M Alcolea Garcia, Ines Monte Collado, Roberto Genique Martínez, María José Guasch Villanueva, Teresa Rama Martínez, Lucio Pinto Pena, Josefa María Panisello Royo, Inés Gil Gil, Carlos Gómez Ruiz, Rita Sahun Font, Anna Fuentes Lloveras, Alberto Calderón Montero, María Del Mar Zamora Gómez, Elena Alarcón Cebrián, Mª José Piñero Acin, Celia Pecharroman Sacristán, M Soledad Mayayo Vicente, Mª Paz Pérez Unanua, Nuria Marañón Henrich, Saray Gómez Monreal, Sonia Redondo De Pedro, Blanca Sanz Pozo, Irene Moreno Martínez, Beatriz Lopez Uriarte, Carmelina Sanz Velasco, Amaya Gárriz Aguirre, Montserrat Rivera Teijido, German Reviriego Jaén, Jose Ignacio Aza Pascual-Salcedo, Josefa Vázquez Gallego, Julia Caballer Rodilla, Aida Herrera, Ezequiel Arranz Martínez, Ana María Gómez Calvo, Paula Morán Oliva, Mª Milagros González Béjar, Julio Antonio Heras Hitos, Olga García Vallejo, Manuel De Jesús Frías Vargas, María Jesús Castillejo Boguerin, Aurora García Lerín, Miguel Ángel María Tablado, Elena Concepción García García, Leticia De Miguel Acero, Carmen Zárate Oñate, Aránzazu Barranco Apoita, María Ester Montes Belloso, Ana María Huertas Velasco, Rafael Sáez Jiménez, Julia Natividad García Pascual, María Clemencia Zuluaga Zuluaga, Mª Cruz Díez Pérez, Antonio Ruiz García, Cristina Murillo Jelsbak, Virginia Lasso Oria, Amelia González Gamarra, Elena Rodilla Rodilla, Alberto Galgo Nafría, María Mestre de Juan, Mª Carmen García Albiñana, Mª del Pilar Moreno Cano, Paula Hernanz López, Paloma Casado Pérez, Jacinto Espinosa García, José Ignacio Prieto Romo, Leandro Fernández Fernández, Javier Sierratapia, Nieves Moreno Regidor, Francisco Javier Zaballos Sánchez, Ana Moreno Moreno, Francisco Carramiñana Barrera, Juan Jose Torres Vázquez, María José Gamero Samino, Miguel Ángel De Santiago Rodríguez, Pablo Rafael Gómez Martínez, Antonio Carlos Elías Becerra, Javier Soto Olivera, Víctor Cambero, Julián Domínguez Ávila, Andrés Simón Fuentes, Jorge Manuel De Nicolás Jiménez, Dimas Igual Fraile, Guadalupe Nieto Barco, Ignacio Araujo Ramos, Mª Luz Serrano Berrocal, Francisco Buitrago Ramírez, Minerva Gallego Marcos, Félix Suarez González, Victoriano Chavero Carrasco, Francisco Guerra Peguero, Francisco Javier Sánchez Vega, Manuel Tejero Mas, Alba Palmerín Donoso, Miguel Turégano Yedro, María Beatriz Esteban Rojas, Fátima Cabezudo Moreno, Nawson Elver Quevedo Saldaña, María Del Mar García Fenés, Timotea Garrote Florencio, José María Fernández Toro, Vicente Caballero Pajares, María José Gómez Barquero, Alejandra Rey Rañal, Elena García Del Río, Enrique Nieto Pol, Julio Álvarez Fernández, Pilar Alonso Álvarez, Mª Luisa Jorge Gómez, Antonio Calvo Guerrero, Isabel Celemín Colomina, Lucia Barreiro Casal, Juana Fernández Moreno, Mª Angelines Carballal Martínez, Nabor Díaz Rodríguez, Carlos Moral Paredes, Dolores Recarey García, Francisco Javier Iglesias Mato, Antonio Fouz Ulloa, Amparo Fidalgo González, Noelia Dios Parada, Patricia Conde Sabarís, Ana Isabel Rodríguez Pérez, Ana Inés García Palacio, Víctor Julio Quesada Varela, Lidia Romero Iglesias, Ángel Lado Llerena, Carmen Lires Rodríguez, María Luisa Carretero Díaz, José Carreira Arias, José Luís Vázquez Camino, María Del Carmen Torreiro Penas, Sandra Yáñez Freire, Daniel Rey Aldana, Carlos Piñeiro Díaz, Portal González Lorenzo, José Rodríguez Campos, Rubén Blanco Rodríguez, Manuel Portela Romero, Lucía Vilela de Castro, Sonsoles María Velilla Zancada, Rafael Crespo Sabarís, Oscar Fernando Isaula Jiménez, Jesús Manuel González Puga, Jorge Antonio Benaín Ávila, Óscar Del Toro González, Vicente Llorca Bueno, Ana María Ballesteros Pérez, Domingo J Rubira López, Mª Dolores Esteve Franco, Elena Sánchez Pablo, María Teresa Palacios López, Juan Castillo Meroño, José María Lobo Martínez, Isabel María Peral Martínez, J Eduardo Carrasco Carrasco, Armando Santo González, Juan Gomáriz García, Beatriz Ríos Morata, Laura Sánchez Iñigo, Inés Sanz Pérez, Vicente Pascual Fuster, Mª Dolores Aicart Bort, Natividad Vázquez Gómez, Carlos Lluna Gasco, Teresa Amorós Barber, Pedro Antonio Medina Cano, Miguel Monteagudo Moncho, María Jesús Larré Muñoz, Raquel Navarro Hernández, Francisco José Martínez Egea, Antonio Tramontano, Marta Ferrer Royo, Belén Persiva Saura, Juan A Contreras Torres, José Mª Tirado Moliner, Alejandro Salanova Penalba, Ariadna Cucó Alberola, Fernando María Navarro I Ros, Enrique Beltrán Llicer, Ana Seoane Novás, Inmaculada Martín Valls, Gracia Verdú Mahiques, Enrique Peña Forcada, Nieves Aguilar Gómez, Francisco Javier Sanz García, María Dolores Paradís Bueso, María Eugenia Alegre Romero, Antonio Francés Camus, María Amparo Antón Peinado, Rosa Latorre Santos, Mª Asunción Palomar Marín, María Carmen Botella García, Eva Sánchez Fresquet, Pedro Sala Paños, Tomás Sánchez Ruiz, Rosa Ana Valero Valero, María Seoane Vicente, Magdalena Martin Llinares, Antonio Masiá Alegre, José Luis Llisterri Caro, Irene Lluch Verdu, Vicente Pallarés Carratalá, Francisco Valls Roca, Rafael Manuel Micó Pérez, Carmen Barceló Dupuy, Elena Benages Vicente, María José Gimeno Tortajada, Mercedes Calleja del Ser, Martín Menéndez Rodríguez, and Rosalía Victoria Carbonell Castelló

Subjects
hypertension, pulse pressure, cardiovascular risk factors, subclinical target organ damage, hypertensive cardiovascular disease, cardiovascular disease, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

IntroductionElevated pulse pressure (ePP) is an independent marker of cardiovascular risk (CVR) in people older than 60, and a functional marker of subclinical target organ damage (sTOD) which can predict cardiovascular events in patients with hypertension (HTN), regardless of sTOD.ObjectiveTo evaluate the prevalence of ePP in adult population seen in primary care and its association with other vascular risk factors, sTOD and with cardiovascular disease (CVD).Materials and methodsObservational multicentre study conducted in Spain (8,066 patients, 54.5% women) from the prospective cohort study IBERICAN recruited in Primary Care. Pulse pressure (PP) was defined as the difference between the systolic blood pressure (SBP) and the diastolic blood pressure (DBP) ≥60 mmHg. Adjusted (for age and sex) ePP prevalence were determined. Bivariate and multivariate analyses of the possible variables associated with ePP were carried out.ResultsThe mean of PP was 52.35 mmHg, and was significantly higher (p

Published
2023
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2. Machine-learning-based prediction of disability progression in multiple sclerosis: An observational, international, multi-center study

Author

McGinnis, RS, De Brouwer, E, Becker, T, Werthen-Brabants, L, Dewulf, P, Iliadis, D, Dekeyser, C, Laureys, G, Van Wijmeersch, B, Popescu, V, Dhaene, T, Deschrijver, D, Waegeman, W, De Baets, B, Stock, M, Horakova, D, Patti, F, Izquierdo, G, Eichau, S, Girard, M, Prat, A, Lugaresi, A, Grammond, P, Kalincik, T, Alroughani, R, Grand'Maison, F, Skibina, O, Terzi, M, Lechner-Scott, J, Gerlach, O, Khoury, SJ, Cartechini, E, Van Pesch, V, Sà, MJ, Weinstock-Guttman, B, Blanco, Y, Ampapa, R, Spitaleri, D, Solaro, C, Maimone, D, Soysal, A, Iuliano, G, Gouider, R, Castillo-Triviño, T, Sánchez-Menoyo, JL, van der Walt, A, Oh, J, Aguera-Morales, E, Altintas, A, Al-Asmi, A, de Gans, K, Fragoso, Y, Csepany, T, Hodgkinson, S, Deri, N, Al-Harbi, T, Taylor, B, Gray, O, Lalive, P, Rozsa, C, McGuigan, C, Kermode, A, Sempere, AP, Mihaela, S, Simo, M, Hardy, T, Decoo, D, Hughes, S, Grigoriadis, N, Sas, A, Vella, N, Moreau, Y, Peeters, L, McGinnis, RS, De Brouwer, E, Becker, T, Werthen-Brabants, L, Dewulf, P, Iliadis, D, Dekeyser, C, Laureys, G, Van Wijmeersch, B, Popescu, V, Dhaene, T, Deschrijver, D, Waegeman, W, De Baets, B, Stock, M, Horakova, D, Patti, F, Izquierdo, G, Eichau, S, Girard, M, Prat, A, Lugaresi, A, Grammond, P, Kalincik, T, Alroughani, R, Grand'Maison, F, Skibina, O, Terzi, M, Lechner-Scott, J, Gerlach, O, Khoury, SJ, Cartechini, E, Van Pesch, V, Sà, MJ, Weinstock-Guttman, B, Blanco, Y, Ampapa, R, Spitaleri, D, Solaro, C, Maimone, D, Soysal, A, Iuliano, G, Gouider, R, Castillo-Triviño, T, Sánchez-Menoyo, JL, van der Walt, A, Oh, J, Aguera-Morales, E, Altintas, A, Al-Asmi, A, de Gans, K, Fragoso, Y, Csepany, T, Hodgkinson, S, Deri, N, Al-Harbi, T, Taylor, B, Gray, O, Lalive, P, Rozsa, C, McGuigan, C, Kermode, A, Sempere, AP, Mihaela, S, Simo, M, Hardy, T, Decoo, D, Hughes, S, Grigoriadis, N, Sas, A, Vella, N, Moreau, Y, and Peeters, L

Abstract

BACKGROUND: Disability progression is a key milestone in the disease evolution of people with multiple sclerosis (PwMS). Prediction models of the probability of disability progression have not yet reached the level of trust needed to be adopted in the clinic. A common benchmark to assess model development in multiple sclerosis is also currently lacking. METHODS: Data of adult PwMS with a follow-up of at least three years from 146 MS centers, spread over 40 countries and collected by the MSBase consortium was used. With basic inclusion criteria for quality requirements, it represents a total of 15, 240 PwMS. External validation was performed and repeated five times to assess the significance of the results. Transparent Reporting for Individual Prognosis Or Diagnosis (TRIPOD) guidelines were followed. Confirmed disability progression after two years was predicted, with a confirmation window of six months. Only routinely collected variables were used such as the expanded disability status scale, treatment, relapse information, and MS course. To learn the probability of disability progression, state-of-the-art machine learning models were investigated. The discrimination performance of the models is evaluated with the area under the receiver operator curve (ROC-AUC) and under the precision recall curve (AUC-PR), and their calibration via the Brier score and the expected calibration error. All our preprocessing and model code are available at https://gitlab.com/edebrouwer/ms_benchmark, making this task an ideal benchmark for predicting disability progression in MS. FINDINGS: Machine learning models achieved a ROC-AUC of 0⋅71 ± 0⋅01, an AUC-PR of 0⋅26 ± 0⋅02, a Brier score of 0⋅1 ± 0⋅01 and an expected calibration error of 0⋅07 ± 0⋅04. The history of disability progression was identified as being more predictive for future disability progression than the treatment or relapses history. CONCLUSIONS: Good discrimination and calibration performance on an external validation s

Published
2024

3. Comparative effectiveness and cost-effectiveness of natalizumab and fingolimod in rapidly evolving severe relapsing-remitting multiple sclerosis in the United Kingdom

Author

Spelman, T, primary, Herring, WL, additional, Acosta, C, additional, Hyde, R, additional, Jokubaitis, VG, additional, Pucci, E, additional, Lugaresi, A, additional, Laureys, G, additional, Havrdova, EK, additional, Horakova, D, additional, Izquierdo, G, additional, Eichau, S, additional, Ozakbas, S, additional, Alroughani, R, additional, Kalincik, T, additional, Duquette, P, additional, Girard, M, additional, Petersen, T, additional, Patti, F, additional, Csepany, T, additional, Granella, F, additional, Grand’Maison, F, additional, Ferraro, D, additional, Karabudak, R, additional, Jose Sa, M, additional, Trojano, M, additional, van Pesch, V, additional, Van Wijmeersch, B, additional, Cartechini, E, additional, McCombe, P, additional, Gerlach, O, additional, Spitaleri, D, additional, Rozsa, C, additional, Hodgkinson, S, additional, Bergamaschi, R, additional, Gouider, R, additional, Soysal, A, additional, Castillo-Triviño, T, additional, Prevost, J, additional, Garber, J, additional, de Gans, K, additional, Ampapa, R, additional, Simo, M, additional, Sanchez-Menoyo, JL, additional, Iuliano, G, additional, Sas, A, additional, van der Walt, A, additional, John, N, additional, Gray, O, additional, Hughes, S, additional, De Luca, G, additional, Onofrj, M, additional, Buzzard, K, additional, Skibina, O, additional, Terzi, M, additional, Slee, M, additional, Solaro, C, additional, Oreja-Guevara, C, additional, Ramo-Tello, C, additional, Fragoso, Y, additional, Shaygannejad, V, additional, Moore, F, additional, Rajda, C, additional, Aguera Morales, E, additional, and Butzkueven, H, additional

Published
2023
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4. The risk of secondary progressive multiple sclerosis is geographically determined but modifiable

Author

Sharmin, S, Roos, I, Simpson-Yap, S, Malpes, C, Sanchez, MM, Ozakbas, S, Horakova, D, Havrdova, EK, Patti, F, Alroughani, R, Izquierdo, G, Eichau, S, Boz, C, Zakaria, M, Onofrj, M, Lugaresi, A, Weinstock-Guttman, B, Prat, A, Girard, M, Duquette, P, Terzi, M, Amato, MP, Karabudak, R, Grand'Maison, F, Khoury, SJ, Grammond, P, Lechner-Scott, J, Buzzard, K, Skibina, O, van der Walt, A, Butzkueven, H, Turkoglu, R, Altintas, A, Maimone, D, Kermode, A, Shalaby, N, Pesch, VV, Butler, E, Sidhom, Y, Gouider, R, Mrabet, S, Gerlach, O, Soysal, A, Barnett, M, Kuhle, J, Hughes, S, Sa, MJ, Hodgkinson, S, Oreja-Guevara, C, Ampapa, R, Petersen, T, Ramo-Tello, C, Spitaleri, D, McCombe, P, Taylor, B, Prevost, J, Foschi, M, Slee, M, McGuigan, C, Laureys, G, Hijfte, LV, de Gans, K, Solaro, C, Oh, J, Macdonell, R, Aguera-Morales, E, Singhal, B, Gray, O, Garber, J, Wijmeersch, BV, Simu, M, Castillo-Trivino, T, Sanchez-Menoyo, JL, Khurana, D, Al-Asmi, A, Al-Harbi, T, Deri, N, Fragoso, Y, Lalive, PH, Sinnige, LGF, Shaw, C, Shuey, N, Csepany, T, Sempere, AP, Moore, F, Decoo, D, Willekens, B, Gobbi, C, Massey, J, Hardy, T, Parratt, J, Kalincik, T, Sharmin, S, Roos, I, Simpson-Yap, S, Malpes, C, Sanchez, MM, Ozakbas, S, Horakova, D, Havrdova, EK, Patti, F, Alroughani, R, Izquierdo, G, Eichau, S, Boz, C, Zakaria, M, Onofrj, M, Lugaresi, A, Weinstock-Guttman, B, Prat, A, Girard, M, Duquette, P, Terzi, M, Amato, MP, Karabudak, R, Grand'Maison, F, Khoury, SJ, Grammond, P, Lechner-Scott, J, Buzzard, K, Skibina, O, van der Walt, A, Butzkueven, H, Turkoglu, R, Altintas, A, Maimone, D, Kermode, A, Shalaby, N, Pesch, VV, Butler, E, Sidhom, Y, Gouider, R, Mrabet, S, Gerlach, O, Soysal, A, Barnett, M, Kuhle, J, Hughes, S, Sa, MJ, Hodgkinson, S, Oreja-Guevara, C, Ampapa, R, Petersen, T, Ramo-Tello, C, Spitaleri, D, McCombe, P, Taylor, B, Prevost, J, Foschi, M, Slee, M, McGuigan, C, Laureys, G, Hijfte, LV, de Gans, K, Solaro, C, Oh, J, Macdonell, R, Aguera-Morales, E, Singhal, B, Gray, O, Garber, J, Wijmeersch, BV, Simu, M, Castillo-Trivino, T, Sanchez-Menoyo, JL, Khurana, D, Al-Asmi, A, Al-Harbi, T, Deri, N, Fragoso, Y, Lalive, PH, Sinnige, LGF, Shaw, C, Shuey, N, Csepany, T, Sempere, AP, Moore, F, Decoo, D, Willekens, B, Gobbi, C, Massey, J, Hardy, T, Parratt, J, and Kalincik, T

Abstract

Geographical variations in the incidence and prevalence of multiple sclerosis have been reported globally. Latitude as a surrogate for exposure to ultraviolet radiation but also other lifestyle and environmental factors are regarded as drivers of this variation. No previous studies evaluated geographical variation in the risk of secondary progressive multiple sclerosis, an advanced form of multiple sclerosis that is characterized by steady accrual of irreversible disability. We evaluated differences in the risk of secondary progressive multiple sclerosis in relation to latitude and country of residence, modified by high-to-moderate efficacy immunotherapy in a geographically diverse cohort of patients with relapsing-remitting multiple sclerosis. The study included relapsing-remitting multiple sclerosis patients from the global MSBase registry with at least one recorded assessment of disability. Secondary progressive multiple sclerosis was identified as per clinician diagnosis. Sensitivity analyses used the operationalized definition of secondary progressive multiple sclerosis and the Swedish decision tree algorithm. A proportional hazards model was used to estimate the cumulative risk of secondary progressive multiple sclerosis by country of residence (latitude), adjusted for sex, age at disease onset, time from onset to relapsing-remitting phase, disability (Multiple Sclerosis Severity Score) and relapse activity at study inclusion, national multiple sclerosis prevalence, government health expenditure, and proportion of time treated with high-to-moderate efficacy disease-modifying therapy. Geographical variation in time from relapsing-remitting phase to secondary progressive phase of multiple sclerosis was modelled through a proportional hazards model with spatially correlated frailties. We included 51 126 patients (72% female) from 27 countries. The median survival time from relapsing-remitting phase to secondary progressive multiple sclerosis among all patients wa

Published
2023

5. Variability of the response to immunotherapy among subgroups of patients with multiple sclerosis

Author

Diouf, I, Malpas, CB, Sharmin, S, Roos, I, Horakova, D, Havrdova, EK, Patti, F, Shaygannejad, V, Ozakbas, S, Izquierdo, G, Eichau, S, Onofrj, M, Lugaresi, A, Alroughani, R, Prat, A, Girard, M, Duquette, P, Terzi, M, Boz, C, Grand'Maison, F, Hamdy, S, Sola, P, Ferraro, D, Grammond, P, Turkoglu, R, Buzzard, K, Skibina, O, Yamout, B, Altintas, A, Gerlach, O, van Pesch, V, Blanco, Y, Maimone, D, Lechner-Scott, J, Bergamaschi, R, Karabudak, R, Iuliano, G, McGuigan, C, Cartechini, E, Barnett, M, Hughes, S, Sa, MJ, Solaro, C, Kappos, L, Ramo-Tello, C, Cristiano, E, Hodgkinson, S, Spitaleri, D, Soysal, A, Petersen, T, Slee, M, Butler, E, Granella, F, de Gans, K, McCombe, P, Ampapa, R, Van Wijmeersch, B, van der Walt, A, Butzkueven, H, Prevost, J, Sinnige, LGF, Sanchez-Menoyo, JL, Vucic, S, Laureys, G, Van Hijfte, L, Khurana, D, Macdonell, R, Gouider, R, Castillo-Trivino, T, Gray, O, Aguera-Morales, E, Al-Asmi, A, Shaw, C, Deri, N, Al-Harbi, T, Fragoso, Y, Csepany, T, Sempere, AP, Trevino-Frenk, I, Schepel, J, Moore, F, Kalincik, T, Diouf, I, Malpas, CB, Sharmin, S, Roos, I, Horakova, D, Havrdova, EK, Patti, F, Shaygannejad, V, Ozakbas, S, Izquierdo, G, Eichau, S, Onofrj, M, Lugaresi, A, Alroughani, R, Prat, A, Girard, M, Duquette, P, Terzi, M, Boz, C, Grand'Maison, F, Hamdy, S, Sola, P, Ferraro, D, Grammond, P, Turkoglu, R, Buzzard, K, Skibina, O, Yamout, B, Altintas, A, Gerlach, O, van Pesch, V, Blanco, Y, Maimone, D, Lechner-Scott, J, Bergamaschi, R, Karabudak, R, Iuliano, G, McGuigan, C, Cartechini, E, Barnett, M, Hughes, S, Sa, MJ, Solaro, C, Kappos, L, Ramo-Tello, C, Cristiano, E, Hodgkinson, S, Spitaleri, D, Soysal, A, Petersen, T, Slee, M, Butler, E, Granella, F, de Gans, K, McCombe, P, Ampapa, R, Van Wijmeersch, B, van der Walt, A, Butzkueven, H, Prevost, J, Sinnige, LGF, Sanchez-Menoyo, JL, Vucic, S, Laureys, G, Van Hijfte, L, Khurana, D, Macdonell, R, Gouider, R, Castillo-Trivino, T, Gray, O, Aguera-Morales, E, Al-Asmi, A, Shaw, C, Deri, N, Al-Harbi, T, Fragoso, Y, Csepany, T, Sempere, AP, Trevino-Frenk, I, Schepel, J, Moore, F, and Kalincik, T

Abstract

BACKGROUND AND PURPOSE: This study assessed the effect of patient characteristics on the response to disease-modifying therapy (DMT) in multiple sclerosis (MS). METHODS: We extracted data from 61,810 patients from 135 centers across 35 countries from the MSBase registry. The selection criteria were: clinically isolated syndrome or definite MS, follow-up ≥ 1 year, and Expanded Disability Status Scale (EDSS) score ≥ 3, with ≥1 score recorded per year. Marginal structural models with interaction terms were used to compare the hazards of 12-month confirmed worsening and improvement of disability, and the incidence of relapses between treated and untreated patients stratified by their characteristics. RESULTS: Among 24,344 patients with relapsing MS, those on DMTs experienced 48% reduction in relapse incidence (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.45-0.60), 46% lower risk of disability worsening (HR = 0.54, 95% CI = 0.41-0.71), and 32% greater chance of disability improvement (HR = 1.32, 95% CI = 1.09-1.59). The effect of DMTs on EDSS worsening and improvement and the risk of relapses was attenuated with more severe disability. The magnitude of the effect of DMT on suppressing relapses declined with higher prior relapse rate and prior cerebral magnetic resonance imaging activity. We did not find any evidence for the effect of age on the effectiveness of DMT. After inclusion of 1985 participants with progressive MS, the effect of DMT on disability mostly depended on MS phenotype, whereas its effect on relapses was driven mainly by prior relapse activity. CONCLUSIONS: DMT is generally most effective among patients with lower disability and in relapsing MS phenotypes. There is no evidence of attenuation of the effect of DMT with age.

Published
2023

6. Comparative effectiveness in multiple sclerosis: A methodological comparison

Author

Roos, I, Diouf, I, Sharmin, S, Horakova, D, Havrdova, EK, Patti, F, Shaygannejad, V, Ozakbas, S, Izquierdo, G, Eichau, S, Onofrj, M, Lugaresi, A, Alroughani, R, Prat, A, Girard, M, Duquette, P, Terzi, M, Boz, C, Grand'Maison, F, Sola, P, Ferraro, D, Grammond, P, Turkoglu, R, Buzzard, K, Skibina, O, Yamou, B, Altintas, A, Gerlach, O, van Pesch, V, Blanco, Y, Maimone, D, Lechner-Scott, J, Bergamaschi, R, Karabudak, R, McGuigan, C, Cartechini, E, Barnett, M, Hughes, S, Sa, MJ, Solaro, C, Ramo-Tello, C, Hodgkinson, S, Spitaleri, D, Soysal, A, Petersen, T, Granella, F, de Gans, K, McCombe, P, Ampapa, R, Van Wijmeersch, B, van der Walt, A, Butzkueven, H, Prevost, J, Sanchez-Menoyo, JL, Laureys, G, Gouider, R, Castillo-Trivino, T, Gray, O, Aguera-Morales, E, Al-Asmi, A, Shaw, C, Deri, N, Al-Harbi, T, Fragoso, Y, Csepany, T, Sempere, AP, Trevino-Frenk, I, Schepel, J, Moore, F, Malpas, C, Kalincik, T, Roos, I, Diouf, I, Sharmin, S, Horakova, D, Havrdova, EK, Patti, F, Shaygannejad, V, Ozakbas, S, Izquierdo, G, Eichau, S, Onofrj, M, Lugaresi, A, Alroughani, R, Prat, A, Girard, M, Duquette, P, Terzi, M, Boz, C, Grand'Maison, F, Sola, P, Ferraro, D, Grammond, P, Turkoglu, R, Buzzard, K, Skibina, O, Yamou, B, Altintas, A, Gerlach, O, van Pesch, V, Blanco, Y, Maimone, D, Lechner-Scott, J, Bergamaschi, R, Karabudak, R, McGuigan, C, Cartechini, E, Barnett, M, Hughes, S, Sa, MJ, Solaro, C, Ramo-Tello, C, Hodgkinson, S, Spitaleri, D, Soysal, A, Petersen, T, Granella, F, de Gans, K, McCombe, P, Ampapa, R, Van Wijmeersch, B, van der Walt, A, Butzkueven, H, Prevost, J, Sanchez-Menoyo, JL, Laureys, G, Gouider, R, Castillo-Trivino, T, Gray, O, Aguera-Morales, E, Al-Asmi, A, Shaw, C, Deri, N, Al-Harbi, T, Fragoso, Y, Csepany, T, Sempere, AP, Trevino-Frenk, I, Schepel, J, Moore, F, Malpas, C, and Kalincik, T

Abstract

BACKGROUND: In the absence of evidence from randomised controlled trials, observational data can be used to emulate clinical trials and guide clinical decisions. Observational studies are, however, susceptible to confounding and bias. Among the used techniques to reduce indication bias are propensity score matching and marginal structural models. OBJECTIVE: To use the comparative effectiveness of fingolimod vs natalizumab to compare the results obtained with propensity score matching and marginal structural models. METHODS: Patients with clinically isolated syndrome or relapsing remitting MS who were treated with either fingolimod or natalizumab were identified in the MSBase registry. Patients were propensity score matched, and inverse probability of treatment weighted at six monthly intervals, using the following variables: age, sex, disability, MS duration, MS course, prior relapses, and prior therapies. Studied outcomes were cumulative hazard of relapse, disability accumulation, and disability improvement. RESULTS: 4608 patients (1659 natalizumab, 2949 fingolimod) fulfilled inclusion criteria, and were propensity score matched or repeatedly reweighed with marginal structural models. Natalizumab treatment was associated with a lower probability of relapse (PS matching: HR 0.67 [95% CI 0.62-0.80]; marginal structural model: 0.71 [0.62-0.80]), and higher probability of disability improvement (PS matching: 1.21 [1.02 -1.43]; marginal structural model 1.43 1.19 -1.72]). There was no evidence of a difference in the magnitude of effect between the two methods. CONCLUSIONS: The relative effectiveness of two therapies can be efficiently compared by either marginal structural models or propensity score matching when applied in clearly defined clinical contexts and in sufficiently powered cohorts.

Published
2023

7. Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis

Author

Daruwalla, C, Shaygannejad, V, Ozakbas, S, Havrdova, EK, Horakova, D, Alroughani, R, Boz, C, Patti, F, Onofrj, M, Lugaresi, A, Eichau, S, Girard, M, Prat, A, Duquette, P, Yamout, B, Khoury, SJ, Sajedi, SA, Turkoglu, R, Altintas, A, Skibina, O, Buzzard, K, Grammond, P, Karabudak, R, van der Walt, A, Butzkueven, H, Maimone, D, Lechner-Scott, J, Soysal, A, John, N, Prevost, J, Spitaleri, D, Ramo-Tello, C, Gerlach, O, Iuliano, G, Foschi, M, Ampapa, R, van Pesch, V, Barnett, M, Shalaby, N, D'hooghe, M, Kuhle, J, Sa, MJ, Fabis-Pedrini, M, Kermode, A, Mrabet, S, Gouider, R, Hodgkinson, S, Laureys, G, Van Hijfte, L, Macdonell, R, Oreja-Guevara, C, Cristiano, E, McCombe, P, Sanchez-Menoyo, JL, Singhal, B, Blanco, Y, Hughes, S, Garber, J, Solaro, C, McGuigan, C, Taylor, B, de Gans, K, Habek, M, Al-Asmi, A, Mihaela, S, Castillo Trivino, T, Al-Harbi, T, Rojas, JI, Gray, O, Khurana, D, Van Wijmeersch, B, Grigoriadis, N, Inshasi, J, Oh, J, Aguera-Morales, E, Fragoso, Y, Moore, F, Shaw, C, Baghbanian, SM, Shuey, N, Willekens, B, Hardy, TA, Decoo, D, Sempere, AP, Field, D, Wynford-Thomas, R, Cunniffe, NG, Roos, I, Malpas, CB, Coles, AJ, Kalincik, T, Brown, JWL, MSBase, SG, Daruwalla, C, Shaygannejad, V, Ozakbas, S, Havrdova, EK, Horakova, D, Alroughani, R, Boz, C, Patti, F, Onofrj, M, Lugaresi, A, Eichau, S, Girard, M, Prat, A, Duquette, P, Yamout, B, Khoury, SJ, Sajedi, SA, Turkoglu, R, Altintas, A, Skibina, O, Buzzard, K, Grammond, P, Karabudak, R, van der Walt, A, Butzkueven, H, Maimone, D, Lechner-Scott, J, Soysal, A, John, N, Prevost, J, Spitaleri, D, Ramo-Tello, C, Gerlach, O, Iuliano, G, Foschi, M, Ampapa, R, van Pesch, V, Barnett, M, Shalaby, N, D'hooghe, M, Kuhle, J, Sa, MJ, Fabis-Pedrini, M, Kermode, A, Mrabet, S, Gouider, R, Hodgkinson, S, Laureys, G, Van Hijfte, L, Macdonell, R, Oreja-Guevara, C, Cristiano, E, McCombe, P, Sanchez-Menoyo, JL, Singhal, B, Blanco, Y, Hughes, S, Garber, J, Solaro, C, McGuigan, C, Taylor, B, de Gans, K, Habek, M, Al-Asmi, A, Mihaela, S, Castillo Trivino, T, Al-Harbi, T, Rojas, JI, Gray, O, Khurana, D, Van Wijmeersch, B, Grigoriadis, N, Inshasi, J, Oh, J, Aguera-Morales, E, Fragoso, Y, Moore, F, Shaw, C, Baghbanian, SM, Shuey, N, Willekens, B, Hardy, TA, Decoo, D, Sempere, AP, Field, D, Wynford-Thomas, R, Cunniffe, NG, Roos, I, Malpas, CB, Coles, AJ, Kalincik, T, Brown, JWL, and MSBase, SG

Abstract

BACKGROUND: The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear. OBJECTIVE: To determine whether early non-disabling relapses predict disability accumulation in RRMS. METHODS: We redefined mild relapses in MSBase as 'non-disabling', and moderate or severe relapses as 'disabling'. We used mixed-effects Cox models to compare 90-day confirmed disability accumulation events in people with exclusively non-disabling relapses within 2 years of RRMS diagnosis to those with no early relapses; and any early disabling relapses. Analyses were stratified by disease-modifying therapy (DMT) efficacy during follow-up. RESULTS: People who experienced non-disabling relapses within 2 years of RRMS diagnosis accumulated more disability than those with no early relapses if they were untreated (n = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00-1.68) or given platform DMTs (n = 1074 vs 7262; HR = 1.33, 95% CI = 1.15-1.54), but not if given high-efficacy DMTs (n = 572 vs 3534; HR = 0.90, 95% CI = 0.71-1.13) during follow-up. Differences in disability accumulation between those with early non-disabling relapses and those with early disabling relapses were not confirmed statistically. CONCLUSION: This study suggests that early non-disabling relapses are associated with a higher risk of disability accumulation than no early relapses in RRMS. This risk may be mitigated by high-efficacy DMTs. Therefore, non-disabling relapses should be considered when making treatment decisions.

Published
2023

8. Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis

Author

Altıntaş, Ayşe (ORCID 0000-0002-8524-5087 & YÖK ID 11611), Daruwalla, C.; Shaygannejad, V.; Ozakbas, S.; Havrdova, EK.; Horakova, D.; Alroughani, R.; Boz, C.; Patti, F.; Onofrj, M.; Lugaresi, A.; Eichau, S.; Girard, M.; Prat, A.; Duquette, P.; Yamout, B.; Khoury, S.J.; Sajedi, S.A.; Turkoglu, R.; Skibina, O.; Buzzard, K.; Grammond, P.; Karabudak, R.; van der Walt, A.; Butzkueven, H.; Maimone, D.; Lechner-Scott, J.; Soysal, A.; John, N.; Prevost, J.; Spitaleri, D.; Ramo-Tello, C.; Gerlach, O.; Iuliano, G.; Foschi, M.; Ampapa, R.; van Pesch, V.; Barnett, M.; Shalaby, N.; D'hooghe, M.; Kuhle, J.; Sa, M.J.; Fabis-Pedrini, M.; Kermode, A.; Mrabet, S.; Gouider, R.; Hodgkinson, S.; Laureys, G.; Van Hijfte, L.; Macdonell, R.; Oreja-Guevara, C.; Cristiano, E.; McCombe, P.; Sanchez-Menoyo, J.L.; Singhal, B.; Blanco, Y.; Hughes, S.; Garber, J.; Solaro, C.; McGuigan, C.; Taylor, B.; de Gans, K.; Habek, M.; Al-Asmi, A.; Mihaela, S.; Castillo Triviño, T.; Al-Harbi, T.; Rojas, J.I.; Gray, O.; Khuran,a D.; Van Wijmeersch, B.; Grigoriadis, N.; Inshasi, J.; Oh, J.; Aguera-Morales, E.; Fragoso, Y.; Moore, F.; Shaw, C.; Baghbanian, S.M.; Shuey, N.; Willekens, B.; Hardy, T.A.; Decoo, D.; Sempere, A.P.; Field, D.; Wynford-Thomas, R.; Cunniffe, NG.; Roos, I.; Malpas, C.B.; Coles, A.J.; Kalincik, T.; Brown, J.W.L., Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), School of Medicine, Altıntaş, Ayşe (ORCID 0000-0002-8524-5087 & YÖK ID 11611), Daruwalla, C.; Shaygannejad, V.; Ozakbas, S.; Havrdova, EK.; Horakova, D.; Alroughani, R.; Boz, C.; Patti, F.; Onofrj, M.; Lugaresi, A.; Eichau, S.; Girard, M.; Prat, A.; Duquette, P.; Yamout, B.; Khoury, S.J.; Sajedi, S.A.; Turkoglu, R.; Skibina, O.; Buzzard, K.; Grammond, P.; Karabudak, R.; van der Walt, A.; Butzkueven, H.; Maimone, D.; Lechner-Scott, J.; Soysal, A.; John, N.; Prevost, J.; Spitaleri, D.; Ramo-Tello, C.; Gerlach, O.; Iuliano, G.; Foschi, M.; Ampapa, R.; van Pesch, V.; Barnett, M.; Shalaby, N.; D'hooghe, M.; Kuhle, J.; Sa, M.J.; Fabis-Pedrini, M.; Kermode, A.; Mrabet, S.; Gouider, R.; Hodgkinson, S.; Laureys, G.; Van Hijfte, L.; Macdonell, R.; Oreja-Guevara, C.; Cristiano, E.; McCombe, P.; Sanchez-Menoyo, J.L.; Singhal, B.; Blanco, Y.; Hughes, S.; Garber, J.; Solaro, C.; McGuigan, C.; Taylor, B.; de Gans, K.; Habek, M.; Al-Asmi, A.; Mihaela, S.; Castillo Triviño, T.; Al-Harbi, T.; Rojas, J.I.; Gray, O.; Khuran,a D.; Van Wijmeersch, B.; Grigoriadis, N.; Inshasi, J.; Oh, J.; Aguera-Morales, E.; Fragoso, Y.; Moore, F.; Shaw, C.; Baghbanian, S.M.; Shuey, N.; Willekens, B.; Hardy, T.A.; Decoo, D.; Sempere, A.P.; Field, D.; Wynford-Thomas, R.; Cunniffe, NG.; Roos, I.; Malpas, C.B.; Coles, A.J.; Kalincik, T.; Brown, J.W.L., Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), and School of Medicine

Abstract

Background: the prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear. Objective: to determine whether early non-disabling relapses predict disability accumulation in RRMS. Methods: we redefined mild relapses in MSBase as 'non-disabling', and moderate or severe relapses as 'disabling'. We used mixed-effects Cox models to compare 90-day confirmed disability accumulation events in people with exclusively non-disabling relapses within 2 years of RRMS diagnosis to those with no early relapses; and any early disabling relapses. Analyses were stratified by disease-modifying therapy (DMT) efficacy during follow-up. Results: people who experienced non-disabling relapses within 2 years of RRMS diagnosis accumulated more disability than those with no early relapses if they were untreated (n = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00-1.68) or given platform DMTs (n = 1074 vs 7262; HR = 1.33, 95% CI = 1.15-1.54), but not if given high-efficacy DMTs (n = 572 vs 3534; HR = 0.90, 95% CI = 0.71-1.13) during follow-up. Differences in disability accumulation between those with early non-disabling relapses and those with early disabling relapses were not confirmed statistically. Conclusion: this study suggests that early non-disabling relapses are associated with a higher risk of disability accumulation than no early relapses in RRMS. This risk may be mitigated by high-efficacy DMTs. Therefore, non-disabling relapses should be considered when making treatment decisions., The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was financially supported by National Health and Medical Research Council of Australia (fellowship nos.1140766 and 1080518, project grant nos. 1129189 and 1083539), the University of Melbourne (Faculty of Medicine, Dentistry and Health Sciences research fellowship), National Institute for Health and Care Research (UK) Advanced Fellowship (grant no. 301728; recipient JWLB) and Academic Clinical Fellowship (grant no. EAN/ACA-006/7488627/C; recipient CD). The MSBase Foundation is a not-for-profit organization that receives support from Roche, Merck, Biogen, Novartis, Bayer Schering, Sanofi Genzyme, and Teva. Role of the Funder/Sponsor: The National Health and Medical Research Council of Australia, the University of Melbourne and the National Institute for Health and Care Research (UK) had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Published
2023

9. Real-world experience with ocrelizumab in primary Progressive multiple sclerosis: Insights from the MSOCR-P cohort, a MSBase Registry sub-study

Author

Terzi, M., Rojas, J. I., Barnett, M., Fragoso, Y., Cartechini, E., Pucci, E., Willekens, B., Butler, E., Blanco, Y., Grigoriadis, N., Van Hijfte, L., Dirks, P., Liu, C., Rouzic, E. Muros-Le, Butzkueven, H., Al-Harbi, T., Laureys, G., Ozakbas, S., Spelman, T., Alroughani, R., Menoyo, J. L. Sanchez, Van Pesch, V., Kalincik, T., Lechner-Scott, J., Van der Walt, A., Grand'Maison, F., Boz, C., Buzzard, K., and Skibina, O.

Published
2022

10. Confirmed disability progression as a marker of permanent disability in multiple sclerosis.

Author

Sharmin S., Bovis F., Malpas C., Horakova D., Havrdova E., Izquierdo G., Eichau S., Trojano M., Prat A., Girard M., Duquette P., Onofrj M., Lugaresi A., Grand'Maison F., Grammond P., Sola P., Ferraro D., Terzi M., Gerlach O., Alroughani R., Boz C., Shaygannejad V., van Pesch V., Cartechini E., Kappos L., Lechner-Scott J., Bergamaschi R., Turkoglu R., Solaro C., Iuliano G., Granella F., Van Wijmeersch B., Spitaleri D., Slee M., McCombe P., Prevost J., Ampapa R., Ozakbas S., Sanchez-Menoyo J., Soysal A., Vucic S., Petersen T., de Gans K., Butler E., Hodgkinson S., Sidhom Y., Gouider R., Cristiano E., Castillo-Trivino T., Saladino M., Barnett M., Moore F., Rozsa C., Yamout B., Skibina O., van der Walt A., Buzzard K., Gray O., Hughes S., Sempere A.P., Singhal B., Fragoso Y., Shaw C., Kermode A., Taylor B., Simo M., Shuey N., Al-Harbi T., Macdonell R., Dominguez J.A., Csepany T., Sirbu C., Sormani M.P., Butzkueven H., Kalincik T., Sharmin S., Bovis F., Malpas C., Horakova D., Havrdova E., Izquierdo G., Eichau S., Trojano M., Prat A., Girard M., Duquette P., Onofrj M., Lugaresi A., Grand'Maison F., Grammond P., Sola P., Ferraro D., Terzi M., Gerlach O., Alroughani R., Boz C., Shaygannejad V., van Pesch V., Cartechini E., Kappos L., Lechner-Scott J., Bergamaschi R., Turkoglu R., Solaro C., Iuliano G., Granella F., Van Wijmeersch B., Spitaleri D., Slee M., McCombe P., Prevost J., Ampapa R., Ozakbas S., Sanchez-Menoyo J., Soysal A., Vucic S., Petersen T., de Gans K., Butler E., Hodgkinson S., Sidhom Y., Gouider R., Cristiano E., Castillo-Trivino T., Saladino M., Barnett M., Moore F., Rozsa C., Yamout B., Skibina O., van der Walt A., Buzzard K., Gray O., Hughes S., Sempere A.P., Singhal B., Fragoso Y., Shaw C., Kermode A., Taylor B., Simo M., Shuey N., Al-Harbi T., Macdonell R., Dominguez J.A., Csepany T., Sirbu C., Sormani M.P., Butzkueven H., and Kalincik T.

Abstract

Background and purpose: The prevention of disability over the long term is the main treatment goal in multiple sclerosis (MS); however, randomized clinical trials evaluate only short-term treatment effects on disability. This study aimed to define criteria for 6-month confirmed disability progression events of MS with a high probability of resulting in sustained long-term disability worsening. Method(s): In total, 14,802 6-month confirmed disability progression events were identified in 8741 patients from the global MSBase registry. For each 6-month confirmed progression event (13,321 in the development and 1481 in the validation cohort), a sustained progression score was calculated based on the demographic and clinical characteristics at the time of progression that were predictive of long-term disability worsening. The score was externally validated in the Cladribine Tablets Treating Multiple Sclerosis Orally (CLARITY) trial. Result(s): The score was based on age, sex, MS phenotype, relapse activity, disability score and its change from baseline, number of affected functional system domains and worsening in six of the domains. In the internal validation cohort, a 61% lower chance of improvement was estimated with each unit increase in the score (hazard ratio 0.39, 95% confidence interval 0.29-0.52; discriminatory index 0.89). The proportions of progression events sustained at 5 years stratified by the score were 1: 72%; 2: 88%; 3: 94%; 4: 100%. The results of the CLARITY trial were confirmed for reduction of disability progression that was >88% likely to be sustained (events with score >1.5). Conclusion(s): Clinicodemographic characteristics of 6-month confirmed disability progression events identify those at high risk of sustained long-term disability. This knowledge will allow future trials to better assess the effect of therapy on long-term disability accrual.Copyright © 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behal

Published
2022

11. Confirmed disability progression as a marker of permanent disability in multiple sclerosis

Author

Sharmin, S., Bovis, F., Malpas, C., Horakova, D., Havrdova, E.K., Izquierdo, G., Eichau, S., Trojano, M., Prat, A., Girard, M., Duquette, P., Onofrj, M., Lugaresi, A., Grand'Maison, F., Grammond, P., Sola, P., Ferraro, D., Terzi, M., Gerlach, O., Alroughani, R., Boz, C., Shaygannejad, V., van Pesch, V., Cartechini, E., Kappos, L., Lechner‐Scott, J., Bergamaschi, R., Turkoglu, R., Solaro, C., Iuliano, G., Granella, F., Van Wijmeersch, B., Spitaleri, D., Slee, M., McCombe, P., Prevost, J., Ampapa, R., Ozakbas, S., Sanchez‐Menoyo, J.L., Soysal, A., Vucic, S., Petersen, T., de Gans, K., Butler, E., Hodgkinson, S., Sidhom, Y., Gouider, R., Cristiano, E., Castillo‐Triviño, T., Saladino, M.L., Barnett, M., Moore, F., Rozsa, C., Yamout, B., Skibina, O., van der Walt, A., Buzzard, K., Gray, O., Hughes, S., Sempere, A.P., Singhal, B., Fragoso, Y., Shaw, C., Kermode, A., Taylor, B., Simo, M., Shuey, N., Al‐Harbi, T., Macdonell, R., Dominguez, J.A., Csepany, T., Sirbu, C.A., Sormani, M.P., Butzkueven, H., Kalincik, T., Sharmin, S., Bovis, F., Malpas, C., Horakova, D., Havrdova, E.K., Izquierdo, G., Eichau, S., Trojano, M., Prat, A., Girard, M., Duquette, P., Onofrj, M., Lugaresi, A., Grand'Maison, F., Grammond, P., Sola, P., Ferraro, D., Terzi, M., Gerlach, O., Alroughani, R., Boz, C., Shaygannejad, V., van Pesch, V., Cartechini, E., Kappos, L., Lechner‐Scott, J., Bergamaschi, R., Turkoglu, R., Solaro, C., Iuliano, G., Granella, F., Van Wijmeersch, B., Spitaleri, D., Slee, M., McCombe, P., Prevost, J., Ampapa, R., Ozakbas, S., Sanchez‐Menoyo, J.L., Soysal, A., Vucic, S., Petersen, T., de Gans, K., Butler, E., Hodgkinson, S., Sidhom, Y., Gouider, R., Cristiano, E., Castillo‐Triviño, T., Saladino, M.L., Barnett, M., Moore, F., Rozsa, C., Yamout, B., Skibina, O., van der Walt, A., Buzzard, K., Gray, O., Hughes, S., Sempere, A.P., Singhal, B., Fragoso, Y., Shaw, C., Kermode, A., Taylor, B., Simo, M., Shuey, N., Al‐Harbi, T., Macdonell, R., Dominguez, J.A., Csepany, T., Sirbu, C.A., Sormani, M.P., Butzkueven, H., and Kalincik, T.

Abstract

Background and purpose The prevention of disability over the long term is the main treatment goal in multiple sclerosis (MS); however, randomized clinical trials evaluate only short-term treatment effects on disability. This study aimed to define criteria for 6-month confirmed disability progression events of MS with a high probability of resulting in sustained long-term disability worsening. Methods In total, 14,802 6-month confirmed disability progression events were identified in 8741 patients from the global MSBase registry. For each 6-month confirmed progression event (13,321 in the development and 1481 in the validation cohort), a sustained progression score was calculated based on the demographic and clinical characteristics at the time of progression that were predictive of long-term disability worsening. The score was externally validated in the Cladribine Tablets Treating Multiple Sclerosis Orally (CLARITY) trial. Results The score was based on age, sex, MS phenotype, relapse activity, disability score and its change from baseline, number of affected functional system domains and worsening in six of the domains. In the internal validation cohort, a 61% lower chance of improvement was estimated with each unit increase in the score (hazard ratio 0.39, 95% confidence interval 0.29–0.52; discriminatory index 0.89). The proportions of progression events sustained at 5 years stratified by the score were 1: 72%; 2: 88%; 3: 94%; 4: 100%. The results of the CLARITY trial were confirmed for reduction of disability progression that was >88% likely to be sustained (events with score ˃1.5). Conclusions Clinicodemographic characteristics of 6-month confirmed disability progression events identify those at high risk of sustained long-term disability. This knowledge will allow future trials to better assess the effect of therapy on long-term disability accrual.

Published
2022

12. SARS-CoV-2 serology after COVID-19 in multiple sclerosis: An international cohort study

Author

Sormani, M. P., Schiavetti, I., Landi, D., Carmisciano, L., De Rossi, N., Cordioli, C., Moiola, L., Radaelli, M., Immovilli, P., Capobianco, M., Brescia Morra, V., Trojano, M., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Fragoso, Y. D., Sen, S., Siva, A., Furlan, R., Salvetti, M., Abbadessa, G., Aguglia, U., Allegorico, L., Allegri, R. B. M., Amato, M. P., Annovazzi, P., Antozzi, C., Appendino, L., Arena, S., Baione, V., Balgera, R., Barcella, V., Baroncini, D., Barrila, C., Bellacosa, A., Bellucci, G., Bergamaschi, R., Bergamaschi, V., Bezzini, D., Biolzi, B., Bisecco, A., Bonavita, S., Borriello, G., Bosa, C., Bosco, A., Bovis, F., Bozzali, M., Brambilla, L., Brescia, M. V., Brichetto, G., Buccafusca, M., Bucciantini, E., Bucello, S., Buscarinu, M. C., Cabboi, M. P., Calabrese, M., Calabria, F., Caleri, F., Camilli, F., Caniatti, L. M., Cantello, R., Capra, R., Capuano, R., Carta, P., Cavalla, P., Celani, M. G., Cellerino, M., Cerqua, R., Chisari, C., Clerici, R., Clerico, M., Cocco, E., Cola, G., Confalonieri, P., Conte, A., Conti, M. Z., Cordano, C., Cordera, S., Corea, F., Correale, C., Cottone, S., Crescenzo, F., Curti, E., D'Ambrosio, A., D'Amico, E., Danni, M. C., D'Arma, A., Dattola, V., de Biase, S., De Luca, G., De Mercanti, S. F., De Mitri, P., De Stefano, N., Della Cava, M., di Napoli, M., Di Sapio, A., Docimo, R., Dutto, A., Evangelista, L., Fanara, S., Ferraro, D., Ferro, M. T., Filippi, M., Fioretti, C., Fratta, M., Frau, J., Fronza, M., Gajofatto, A., Gallo, A., Gallo, P., Gasperini, C., Ghazaryan, A., Giometto, B., Gobbin, F., Govone, F., Granella, F., Grange, E., Grasso, M. G., Guareschi, A., Guaschino, C., Guerrieri, S., Guidetti, D., Iaffaldano, P., Ianniello, A., Iasevoli, L., Imperiale, D., Infante, M. T., Inglese, M., Iodice, R., Iovino, A., Konrad, G., Lanzillo, R., Lapucci, C., Lavorgna, L., L'Episcopo Maria, R., Leva, S., Liberatore, G., Lo Re, M., Longoni, M., Lopiano, L., Lorefice, L., Lucchini, Matteo, Lus, G., Maimone, D., Malentacchi, M., Mallucci, G., Malucchi, S., Mancinelli, C. R., Mancinelli, L., Manganotti, P., Maniscalco, T. G., Mantero, V., Marangoni, S., Marastoni, D., Marfia, A. G., Marinelli, F., Marti, A., Martinelli Boneschi, F., Masserano Zoli, F., Matta, F., Mendozzi, L., Meucci, G., Miante, S., Miele, G., Milano, E., Mirabella, Massimiliano, Missione, R., Moccia, M., Montepietra, S., Monti Bragadin, M., Montini, F., Motta, R., Nardone, R., Nicoletti, C. G., Nobile-Orazio, E., Nozzolillo, A., Onofrj, M., Orlandi, R., Palmieri, A., Paolicelli, D., Pasquali, L., Pasto, L., Pedrazzoli, E., Perini, P., Pesci, I., Petracca, M., Petrone, A., Piantadosi, C., Pietroboni, A. M., Pinardi, F., Ponzano, M., Portaccio, E., Pozzato, M., Pozzilli, C., Prosperini, L., Protti, A., Ragonese, P., Rasia, S., Realmuto, S., Repice, A., Rigoni, E., Rilla, M. T., Rinaldi, F., Romano, C. M., Ronzoni, M., Rovaris, M., Ruscica, F., Sabattini, L., Salemi, G., Saraceno, L., Sartori, A., Sbragia, E., Scandellari, C., Scarano Giuditta, I., Scarano, V., Schillaci, V., Sessa, M., Sgarito, C., Sibilia, G., Siciliano, G., Signori, A., Signoriello, E., Sinisi, L., Sireci, F., Sola, P., Solaro, C., Sotgiu, S., Sparaco, M., Stromillo, M. L., Strumia, S., Susani, L. E., Tabiadon, G., Teatini, F., Tomassini, V., Tonietti, S., Torri, C. V., Tortorella, C., Toscano, S., Totaro, R., Trotta, M., Turano, G., Ulivelli, M., Valentino, M., Vaula, G., Vecchio, D., Vercellino, M., Verrengia, E. P., Vianello, M., Virgilio, E., Vitetta, F., Vollaro, S., Zaffaroni, M., Zampolini, M., Zarbo, I. R., Zito, A., Zuliani, L., Lucchini M. (ORCID:0000-0002-0447-2297), Mirabella M. (ORCID:0000-0002-7783-114X), Sormani, M. P., Schiavetti, I., Landi, D., Carmisciano, L., De Rossi, N., Cordioli, C., Moiola, L., Radaelli, M., Immovilli, P., Capobianco, M., Brescia Morra, V., Trojano, M., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Fragoso, Y. D., Sen, S., Siva, A., Furlan, R., Salvetti, M., Abbadessa, G., Aguglia, U., Allegorico, L., Allegri, R. B. M., Amato, M. P., Annovazzi, P., Antozzi, C., Appendino, L., Arena, S., Baione, V., Balgera, R., Barcella, V., Baroncini, D., Barrila, C., Bellacosa, A., Bellucci, G., Bergamaschi, R., Bergamaschi, V., Bezzini, D., Biolzi, B., Bisecco, A., Bonavita, S., Borriello, G., Bosa, C., Bosco, A., Bovis, F., Bozzali, M., Brambilla, L., Brescia, M. V., Brichetto, G., Buccafusca, M., Bucciantini, E., Bucello, S., Buscarinu, M. C., Cabboi, M. P., Calabrese, M., Calabria, F., Caleri, F., Camilli, F., Caniatti, L. M., Cantello, R., Capra, R., Capuano, R., Carta, P., Cavalla, P., Celani, M. G., Cellerino, M., Cerqua, R., Chisari, C., Clerici, R., Clerico, M., Cocco, E., Cola, G., Confalonieri, P., Conte, A., Conti, M. Z., Cordano, C., Cordera, S., Corea, F., Correale, C., Cottone, S., Crescenzo, F., Curti, E., D'Ambrosio, A., D'Amico, E., Danni, M. C., D'Arma, A., Dattola, V., de Biase, S., De Luca, G., De Mercanti, S. F., De Mitri, P., De Stefano, N., Della Cava, M., di Napoli, M., Di Sapio, A., Docimo, R., Dutto, A., Evangelista, L., Fanara, S., Ferraro, D., Ferro, M. T., Filippi, M., Fioretti, C., Fratta, M., Frau, J., Fronza, M., Gajofatto, A., Gallo, A., Gallo, P., Gasperini, C., Ghazaryan, A., Giometto, B., Gobbin, F., Govone, F., Granella, F., Grange, E., Grasso, M. G., Guareschi, A., Guaschino, C., Guerrieri, S., Guidetti, D., Iaffaldano, P., Ianniello, A., Iasevoli, L., Imperiale, D., Infante, M. T., Inglese, M., Iodice, R., Iovino, A., Konrad, G., Lanzillo, R., Lapucci, C., Lavorgna, L., L'Episcopo Maria, R., Leva, S., Liberatore, G., Lo Re, M., Longoni, M., Lopiano, L., Lorefice, L., Lucchini, Matteo, Lus, G., Maimone, D., Malentacchi, M., Mallucci, G., Malucchi, S., Mancinelli, C. R., Mancinelli, L., Manganotti, P., Maniscalco, T. G., Mantero, V., Marangoni, S., Marastoni, D., Marfia, A. G., Marinelli, F., Marti, A., Martinelli Boneschi, F., Masserano Zoli, F., Matta, F., Mendozzi, L., Meucci, G., Miante, S., Miele, G., Milano, E., Mirabella, Massimiliano, Missione, R., Moccia, M., Montepietra, S., Monti Bragadin, M., Montini, F., Motta, R., Nardone, R., Nicoletti, C. G., Nobile-Orazio, E., Nozzolillo, A., Onofrj, M., Orlandi, R., Palmieri, A., Paolicelli, D., Pasquali, L., Pasto, L., Pedrazzoli, E., Perini, P., Pesci, I., Petracca, M., Petrone, A., Piantadosi, C., Pietroboni, A. M., Pinardi, F., Ponzano, M., Portaccio, E., Pozzato, M., Pozzilli, C., Prosperini, L., Protti, A., Ragonese, P., Rasia, S., Realmuto, S., Repice, A., Rigoni, E., Rilla, M. T., Rinaldi, F., Romano, C. M., Ronzoni, M., Rovaris, M., Ruscica, F., Sabattini, L., Salemi, G., Saraceno, L., Sartori, A., Sbragia, E., Scandellari, C., Scarano Giuditta, I., Scarano, V., Schillaci, V., Sessa, M., Sgarito, C., Sibilia, G., Siciliano, G., Signori, A., Signoriello, E., Sinisi, L., Sireci, F., Sola, P., Solaro, C., Sotgiu, S., Sparaco, M., Stromillo, M. L., Strumia, S., Susani, L. E., Tabiadon, G., Teatini, F., Tomassini, V., Tonietti, S., Torri, C. V., Tortorella, C., Toscano, S., Totaro, R., Trotta, M., Turano, G., Ulivelli, M., Valentino, M., Vaula, G., Vecchio, D., Vercellino, M., Verrengia, E. P., Vianello, M., Virgilio, E., Vitetta, F., Vollaro, S., Zaffaroni, M., Zampolini, M., Zarbo, I. R., Zito, A., Zuliani, L., Lucchini M. (ORCID:0000-0002-0447-2297), and Mirabella M. (ORCID:0000-0002-7783-114X)

Abstract

Background: The MuSC-19 project is an Italian cohort study open to international partners that collects data on multiple sclerosis (MS) patients with COVID-19. During the second wave of the pandemic, serological tests became routinely available. Objective: To evaluate the seroprevalence of anti-SARS-CoV-2 antibodies according to the use of disease-modifying therapy (DMT) in a subset of patients included in the MuSC-19 data set who had undergone a serological test. Methods: We evaluated the association between positive serological test results and time elapsed since infection onset, age, sex, Expanded Disability Status Scale score, comorbidities and DMT exposure using a multivariable logistic model. Results: Data were collected from 423 patients (345 from Italy, 61 from Turkey and 17 from Brazil) with a serological test performed during follow-up. Overall, 325 out of 423 tested patients (76.8%) had a positive serological test. At multivariate analysis, therapy with anti-CD20 was significantly associated with a reduced probability of developing antibodies after COVID-19 (odds ratio (OR) = 0.20, p = 0.002). Conclusion: Patients with MS maintain the capacity to develop humoral immune response against SARS-COV-2, although to a lesser extent when treated with anti-CD20 drugs. Overall, our results are reassuring with respect to the possibility to achieve sufficient immunization with vaccination.

Published
2022

13. Burden and attitude to resistant and refractory migraine: a survey from the European Headache Federation with the endorsement of the European MigraineHeadache Alliance

Author

Sacco S., Lampl C., Maassen van den Brink A., Caponnetto V., Braschinsky M., Ducros A., Little P., Pozo-Rosich P., Reuter U., Ruiz de la Torre E., Sanchez Del Rio M., Sinclair A. J., Martelletti P., Katsarava Z., Cakciri G., Djamandi P., Grabova S., Halili G., Kruja J., Kuqo A., Naco D., Quka A., Stefanidhi L., Vyshka G., Zekja I., Bruera O., Gomez D., Guitian B., Roma J. C., Chen I. L., Bashirova S., Linkov M., Van Den Abbeele D., Vanderschueren G., Araujo R., Arruda R., Catharino A., Ciriaco J., Dalla Corte A., Dornas R., Felsenfeld B., Fonseca Taufner A., Fragoso Y., Hurtado R., Isoni Martins D., Londero R., Melo L., Mignoni K. S., Sgobbi De Souza P. V., Souza M. N., Osman S., Baltzer V., Pacheco Mosquera L. F., Dubroja I., Hucika Z., Lisak M., Lovrencic-Huzjan A., Lusic I., Mahovic Lakusic D., Mikulenka P., Rehulka P., Amin F. M., Antic S., Fakhril-Din Z., Moeller-Hansen J., Munksgaard S., Nan A. M., Pellesi L., Schytz H., Vides M., Braschinsky K., Krikmann U., Roos C., Cauchie A., Christian L., Guegan-Massardier E., Demarquay G., Gilles G., Mawet J., Kuhn E., Lanteri Minet M., Bustuchina Vlaicu M., Moisset X., Muresan M., Najjar-Ravan M., Giraud P., Simonin S., De Gaalon S., Chakhava G., Demuria M., Gegelashvili G., Kapanadze N., Antonakakis A., Gaul C., Forderreuther S., Huhn J. -I., Ibragimov S., Kamm K., Raffaelli B., Czaniera R., Ruscheweyh R., Gavanozi E., Karagiorgis G., Mavridism T., Ertsey C., Shubham D., Callista Tanowi A. D., Erdana Putra S., Hadi D. W., Kurnia L., Nasrul M., Albanese M., Antonaci F., Asioli G. M., Baschi R., Bentivegna E., Brunelli N., Caratozzolo S., Catarci T., Cherchi A., Corbelli I., Costa A., De Luca C., Doretti A., Favoni V., Ghiotto N., Giamberardino M. A., Giani L., Zanchin G., Govone F., Grillo G., Mampreso E., Negro A., Ornello R., Pasculli M., Pensato U., Prudenzano M. P. A., Quintana S., Rapisarda R., Romoli M., Russo A., Russo M., Spuntarelli V., Tiseo C., Torrente A., Vacca A., Vaula G., Vigano A., Vigneri S., Freimane A., Slosberga E., Zvaune L., Tan H. J., Fenech C., Cobilt-Catana R., De La Garza Neme Y., Martinez M., Proano Narvaez J. V., Rodriguez Herrera A., Vazquez D., Grosu O., Jakupi A., Kristoffersen E. S., Tronvik E., Winsvold B. S., Azhar M., Reyes Alvarez M. T., Vilchez Fernandez L., Dayrit G. D., Czapinska-Ciepiela E. K., Fila M., Gryglas-Dworak A., Couto M., Esperanca P., Ferreira A., Gil-Gouveia R., Goncalves A., Lopes M., Lourenco M., Machado J., Marinho M., Miranda M. A., Palavra F., Parreira E., Pavao Martins I., Pereira L., Pereira Monteiro J. M., Leahu P., Aloman S., Abramova E., Akhmadeeva L., Belopasova A., Bogdanova I., Chernyak M., Epifanova M., Fedorova E., Felbush A., Karpova M., Korobkova D., Korotkova D., Latysheva N., Makeeva T., Mikhalkina K., Osipova V., Roshchina O., Serga A., Serousova O. V., Sidorova Y., Skiba I., Skorobogatykh K., Vashchenko N., Apostolski S., Buder N., Kopitovic A., Mirjana J., Podgorac A., Rakic D., Simic S., Zarko M., Trajkovic J. Z., Beltran-Blasco I., Calabria Gallego M. D., Diaz Insa S., Ezpeleta D., Fernandez M., Garcia-Azorin D., Gonzalez-Garcia N., Guerrero A. L., Guillamon E., Herreros Rodriguez J., Layos-Romero A., Medrano V., Minguez-Olaondo A., Navarro Munoz S., Pare Curell M., Ruibal M., Sanchez Alvarez J. M., Santos S., Soler R., Viguera J., Zabalza R., Abdelrahman T., Abobaker Hamza S. B., Mustafa M. N., Edvinsson L., Gantenbein A., Maraffi I., Couturier E., Dirkx T., Hoebert M., Van Oosterhout W., Wim M., Zwartbol R., Bakir M., Demirel H., Erdemoglu A. K., Ertem D. H., Gonullu S., Ilgaz Aydinlar E., Inan L. E., Olmez B., Ozbenli T., Ozge A., Uluduz D., Uyar Cankay T., Yalinay Dikmen P., Saxena A. B., Bozhenko M., Bozhenko N., Bubnov R., Tsurkalenko O., Abu-Arafeh I., Idrovo L., Miller S., Nirmalananthan N., Sinclair A., Taleti E., Valori A., Whitehouse W., Zermansky A., Thura M., Institut Català de la Salut, [Sacco S, Caponnetto V] Neuroscience section – Department of Biotechnological and Applied Clinical Sciences and (Edificio Coppito 2), University of L’Aquila, Via Vetoio, 67100 L’Aquila, Italy. Regional Referral Headache Center of the Abruzzo Region, ASL Avezzano-Sulmona-L’Aquila, L’Aquila, Italy. [Lampl C] Department of Neurology, Headache Medical Centre Linz, Hospital Barmherzige Brüder, Centre of Integrative Medicine (ZiAM) Ordensklinikum Linz, Linz, Austria. [Maassen van den Brink A] Division of Pharmacology, Department of Internal Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. [Braschinsky M] Headache Clinic, Department of Neurology, Tartu University Clinics, Tartu, Estonia. [Ducros A] Headache Unit, Neurology Department, Montpellier University Hospital and Montpellier University, Montpellier, France. [Pozo-Rosich P] Unitat de Cefalea, Servei de Neurologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. Grup d'Investigació en Cefalees i Dolors Neurològics, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Sacco, S., Lampl, C., Maassen van den Brink, A., Caponnetto, V., Braschinsky, M., Ducros, A., Little, P., Pozo-Rosich, P., Reuter, U., Ruiz de la Torre, E., Sanchez Del Rio, M., Sinclair, A. J., Martelletti, P., Katsarava, Z., Cakciri, G., Djamandi, P., Grabova, S., Halili, G., Kruja, J., Kuqo, A., Naco, D., Quka, A., Stefanidhi, L., Vyshka, G., Zekja, I., Bruera, O., Gomez, D., Guitian, B., Roma, J. C., Chen, I. L., Bashirova, S., Linkov, M., Van Den Abbeele, D., Vanderschueren, G., Araujo, R., Arruda, R., Catharino, A., Ciriaco, J., Dalla Corte, A., Dornas, R., Felsenfeld, B., Fonseca Taufner, A., Fragoso, Y., Hurtado, R., Isoni Martins, D., Londero, R., Melo, L., Mignoni, K. S., Sgobbi De Souza, P. V., Souza, M. N., Osman, S., Baltzer, V., Pacheco Mosquera, L. F., Dubroja, I., Hucika, Z., Lisak, M., Lovrencic-Huzjan, A., Lusic, I., Mahovic Lakusic, D., Mikulenka, P., Rehulka, P., Amin, F. M., Antic, S., Fakhril-Din, Z., Moeller-Hansen, J., Munksgaard, S., Nan, A. M., Pellesi, L., Schytz, H., Vides, M., Braschinsky, K., Krikmann, U., Roos, C., Cauchie, A., Christian, L., Guegan-Massardier, E., Demarquay, G., Gilles, G., Mawet, J., Kuhn, E., Lanteri Minet, M., Bustuchina Vlaicu, M., Moisset, X., Muresan, M., Najjar-Ravan, M., Giraud, P., Simonin, S., De Gaalon, S., Chakhava, G., Demuria, M., Gegelashvili, G., Kapanadze, N., Antonakakis, A., Gaul, C., Forderreuther, S., Huhn, J. -I., Ibragimov, S., Kamm, K., Raffaelli, B., Czaniera, R., Ruscheweyh, R., Gavanozi, E., Karagiorgis, G., Mavridism, T., Ertsey, C., Shubham, D., Callista Tanowi, A. D., Erdana Putra, S., Hadi, D. W., Kurnia, L., Nasrul, M., Albanese, M., Antonaci, F., Asioli, G. M., Baschi, R., Bentivegna, E., Brunelli, N., Caratozzolo, S., Catarci, T., Cherchi, A., Corbelli, I., Costa, A., De Luca, C., Doretti, A., Favoni, V., Ghiotto, N., Giamberardino, M. A., Giani, L., Zanchin, G., Govone, F., Grillo, G., Mampreso, E., Negro, A., Ornello, R., Pasculli, M., Pensato, U., Prudenzano, M. P. A., Quintana, S., Rapisarda, R., Romoli, M., Russo, A., Russo, M., Spuntarelli, V., Tiseo, C., Torrente, A., Vacca, A., Vaula, G., Vigano, A., Vigneri, S., Freimane, A., Slosberga, E., Zvaune, L., Tan, H. J., Fenech, C., Cobilt-Catana, R., De La Garza Neme, Y., Martinez, M., Proano Narvaez, J. V., Rodriguez Herrera, A., Vazquez, D., Grosu, O., Jakupi, A., Kristoffersen, E. S., Tronvik, E., Winsvold, B. S., Azhar, M., Reyes Alvarez, M. T., Vilchez Fernandez, L., Dayrit, G. D., Czapinska-Ciepiela, E. K., Fila, M., Gryglas-Dworak, A., Couto, M., Esperanca, P., Ferreira, A., Gil-Gouveia, R., Goncalves, A., Lopes, M., Lourenco, M., Machado, J., Marinho, M., Miranda, M. A., Palavra, F., Parreira, E., Pavao Martins, I., Pereira, L., Pereira Monteiro, J. M., Leahu, P., Aloman, S., Abramova, E., Akhmadeeva, L., Belopasova, A., Bogdanova, I., Chernyak, M., Epifanova, M., Fedorova, E., Felbush, A., Karpova, M., Korobkova, D., Korotkova, D., Latysheva, N., Makeeva, T., Mikhalkina, K., Osipova, V., Roshchina, O., Serga, A., Serousova, O. V., Sidorova, Y., Skiba, I., Skorobogatykh, K., Vashchenko, N., Apostolski, S., Buder, N., Kopitovic, A., Mirjana, J., Podgorac, A., Rakic, D., Simic, S., Zarko, M., Trajkovic, J. Z., Beltran-Blasco, I., Calabria Gallego, M. D., Diaz Insa, S., Ezpeleta, D., Fernandez, M., Garcia-Azorin, D., Gonzalez-Garcia, N., Guerrero, A. L., Guillamon, E., Herreros Rodriguez, J., Layos-Romero, A., Medrano, V., Minguez-Olaondo, A., Navarro Munoz, S., Pare Curell, M., Ruibal, M., Sanchez Alvarez, J. M., Santos, S., Soler, R., Viguera, J., Zabalza, R., Abdelrahman, T., Abobaker Hamza, S. B., Mustafa, M. N., Edvinsson, L., Gantenbein, A., Maraffi, I., Couturier, E., Dirkx, T., Hoebert, M., Van Oosterhout, W., Wim, M., Zwartbol, R., Bakir, M., Demirel, H., Erdemoglu, A. K., Ertem, D. H., Gonullu, S., Ilgaz Aydinlar, E., Inan, L. E., Olmez, B., Ozbenli, T., Ozge, A., Uluduz, D., Uyar Cankay, T., Yalinay Dikmen, P., Saxena, A. B., Bozhenko, M., Bozhenko, N., Bubnov, R., Tsurkalenko, O., Abu-Arafeh, I., Idrovo, L., Miller, S., Nirmalananthan, N., Sinclair, A., Taleti, E., Valori, A., Whitehouse, W., Zermansky, A., Thura, M., and Internal Medicine

Subjects
Investigative Techniques::Epidemiologic Methods::Data Collection::Surveys and Questionnaires [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], medicine.medical_specialty, Pediatrics, Neurology, Consensus, enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos con cefaleas::cefaleas primarias::trastornos migrañosos [ENFERMEDADES], migraine, migraine care, refractory migraine, resistant migraine, consensus, cross-sectional studies, headache, humans, surveys and questionnaires, migraine disorders, Pain medicine, Moderate confidence, Migraine Disorders, Medizin, Consensu, Migranya - Tractament, Qüestionaris, Refractory, Surveys and Questionnaires, medicine, Surveys and Questionnaire, Humans, Clinical significance, Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Headache Disorders::Headache Disorders, Primary::Migraine Disorders [DISEASES], Otros calificadores::/terapia [Otros calificadores], Migraine, Cross-Sectional Studie, business.industry, Headache, técnicas de investigación::métodos epidemiológicos::recopilación de datos::encuestas y cuestionarios [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], General Medicine, Other subheadings::/therapy [Other subheadings], medicine.disease, Refractory migraine, Anesthesiology and Pain Medicine, Cross-Sectional Studies, Burden, Medicine, Neurology (clinical), Level of care, business, Resistant migraine, Migraine care, Human, Research Article
Abstract

Background New treatments are currently offering new opportunities and challenges in clinical management and research in the migraine field. There is the need of homogenous criteria to identify candidates for treatment escalation as well as of reliable criteria to identify refractoriness to treatment. To overcome those issues, the European Headache Federation (EHF) issued a Consensus document to propose criteria to approach difficult-to-treat migraine patients in a standardized way. The Consensus proposed well-defined criteria for resistant migraine (i.e., patients who do not respond to some treatment but who have residual therapeutic opportunities) and refractory migraine (i.e., patients who still have debilitating migraine despite maximal treatment efforts). The aim of this study was to better understand the perceived impact of resistant and refractory migraine and the attitude of physicians involved in migraine care toward those conditions. Methods We conducted a web-questionnaire-based cross-sectional international study involving physicians with interest in headache care. Results There were 277 questionnaires available for analysis. A relevant proportion of participants reported that patients with resistant and refractory migraine were frequently seen in their clinical practice (49.5% for resistant and 28.9% for refractory migraine); percentages were higher when considering only those working in specialized headache centers (75% and 46% respectively). However, many physicians reported low or moderate confidence in managing resistant (8.1% and 43.3%, respectively) and refractory (20.7% and 48.4%, respectively) migraine patients; confidence in treating resistant and refractory migraine patients was different according to the level of care and to the number of patients visited per week. Patients with resistant and refractory migraine were infrequently referred to more specialized centers (12% and 19%, respectively); also in this case, figures were different according to the level of care. Conclusions This report highlights the clinical relevance of difficult-to-treat migraine and the presence of unmet needs in this field. There is the need of more evidence regarding the management of those patients and clear guidance referring to the organization of care and available opportunities.

Published
2021

14. Early predictors of disability in paediatric multiple sclerosis: evidence from a multi-national cohort

Author

Sharmin, S., Malpas, C., Izanne Roos, Diouf, I., Alroughani, R., Ozakbas, S., Izquierdo, G., Eichau, S., Horakova, D., Havrdova, E. K., Patti, F., Terzi, M., Boz, C., Yamout, B., Khoury, S. J., Onofrj, M., Lugaresi, A., Altintas, A., Prat, A., Girard, M., Duquette, P., Sa, M. J., Spitaleri, D., Sidhom, Y., Gouider, R., Soysal, A., Turkoglu, R., Amato, M. P., Fragoso, Y., and Kalincik, T.

Published
2021

16. Variability of the response to immunotherapy among subgroups of patients with multiple sclerosis.

Author

Van Pesch V., Eichau S., Zakaria M., Onofrj M., Lugaresi A., Alroughani R., Prat A., Girard M., Duquette P., Terzi M., Boz C., Grand'Maison F., Hamdy S., Sola P., Ferraro D., Grammond P., Turkoglu R., Butzkueven H., Yamout B., Altintas A., Maimone D., Lechner-Scott J., Bergamaschi R., Karabudak R., Giuliano F., Mcguigan C., Cartechini E., Barnett M., Hughes S., Sa M., Kappos L., Ramo-Tello C., Cristiano E., Hodgkinson S., Spitaleri D., Soysal A., Petersen T., Slee M., Butler E., Granella F., Verheul F., Mccombe P., Ampapa R., Skibina O., Prevost J., Sinnige L.G.F., Sanchez-Menoyo J.L., Vucic S., Laureys G., Van Hijfte L., Khurana D., Macdonell R., Castillo-Trivino T., Gray O., Aguera E., Kister I., Shaw C., Deri N., Al-Harbi T., Fragoso Y., Csepany T., Sempere A., Kalincik T., Diouf I., Malpas C., Horakova D., Kubala Havrdova E., Patti F., Shaygannejad V., Ozakbas S., Izquierdo G., Van Pesch V., Eichau S., Zakaria M., Onofrj M., Lugaresi A., Alroughani R., Prat A., Girard M., Duquette P., Terzi M., Boz C., Grand'Maison F., Hamdy S., Sola P., Ferraro D., Grammond P., Turkoglu R., Butzkueven H., Yamout B., Altintas A., Maimone D., Lechner-Scott J., Bergamaschi R., Karabudak R., Giuliano F., Mcguigan C., Cartechini E., Barnett M., Hughes S., Sa M., Kappos L., Ramo-Tello C., Cristiano E., Hodgkinson S., Spitaleri D., Soysal A., Petersen T., Slee M., Butler E., Granella F., Verheul F., Mccombe P., Ampapa R., Skibina O., Prevost J., Sinnige L.G.F., Sanchez-Menoyo J.L., Vucic S., Laureys G., Van Hijfte L., Khurana D., Macdonell R., Castillo-Trivino T., Gray O., Aguera E., Kister I., Shaw C., Deri N., Al-Harbi T., Fragoso Y., Csepany T., Sempere A., Kalincik T., Diouf I., Malpas C., Horakova D., Kubala Havrdova E., Patti F., Shaygannejad V., Ozakbas S., and Izquierdo G.

Abstract

Background: Our current understanding of demographic and clinical modifiers of the effectiveness of multiple sclerosis (MS) therapies is limited. Objective(s): To assess whether patients' response to disease modifying therapies (DMT) in MS varies by disease activity (annualised relapse rate, presence of new MRI lesions), disability, age, MS duration or disease phenotype. Method(s): Using the international MSBase registry, we selected patients with MS followed for >=1 year, with >=3 visits, >=1 visit per year. Marginal structural models (MSMs) were used to compare the hazard ratios (HR) of 6-month confirmed worsening and improvement of disability (EDSS), and the incidence of relapses between treated and untreated periods. MSMs were continuously re-adjusted for patient age, sex, pregnancy, date, time from first symptom, prior relapse history, disability and MRI activity. Result(s): Among 23 687 patients with relapsing MS, those on DMT experienced 20% greater chance of disability improvement [HR 1.20 (95% CI 1.0-1.5)], 47% lower risk of disability worsening [HR 0.53 (0.39-0.71)] and 51% reduction in relapses [HR 0.49 (0.43-0.55)]. The effect of DMT on relapses and EDSS worsening was attenuated with longer MS duration and higher prior relapse rate. The effect of DMT on EDSS improvement and relapses was more evident in low EDSS categories. DMT was associated with 51% EDSS improvement in patients without new MRI lesions [HR 1.51 (1.00-2.28)] compared to 4% in those with MRI activity [HR 1.04 (0.88-1.24)]. Among 26329 participants with relapsing or progressive MS, DMT was associated with 25% reduction in EDSS worsening and 42% reduction in relapses in patients with relapsing MS [HR 0.75 (0.65-0.86) and HR 0.58 (CI 0.54-62), respectively], while evidence for such beneficial effects of treatment in patients with progressive MS was not found [HR 1.11 (0.91-1.46) and HR 1.16 (0.91-1.46), respectively]. Conclusion(s): DMTs are associated with reduction in relapse frequency, pro

Published
2021

17. Variability of the Response to Immunotherapy among Sub-groups of Patients with Multiple Sclerosis.

Author

Diouf I., Malpas C., Horakova D., Havrdova E., Patti F., Shaygannejad V., Ozakbas S., Ayuso G.I., Madueno S.E., Zakaria M., Onofrj M., Lugaresi A., Alroughani R., Prat A., Girard M., Duquette P., Terzi M., Cavit B., GrandaMaison F., Hamdy S., Sola P., Ferraro D., Grammond P., Turkoglu R., Butzkueven H., Yamout B., Altintas A., VanPesch V., Maimone D., Lechner-Scott J., Bergamaschi R., Karabudak R., Iuliano G., McGuigan C., Cartechini E., Barnett M., Hughes S., Sa M.J., Kappos L., Ramo-Tello C., Cristiano E., Hodgkinson S., Spitaleri D.L.A., Soysal A., Petersen T., Slee M., Butler E., Granella F., Verheul F., McCombe P., Ampapa R., Skibina O., Prevost J., Sinnige L., Sanchez-Menoyo J.L., Vucic S., Laureys G., VanHijfte L., Khurana D., MacDonell R., Castillo-Trivino T., Gray O., Aguera-Morales E., Kister I., Shaw C., Deri N., Al-Harbi T., Fragoso Y., Csepany T., Sempere A., Kalincik T., Diouf I., Malpas C., Horakova D., Havrdova E., Patti F., Shaygannejad V., Ozakbas S., Ayuso G.I., Madueno S.E., Zakaria M., Onofrj M., Lugaresi A., Alroughani R., Prat A., Girard M., Duquette P., Terzi M., Cavit B., GrandaMaison F., Hamdy S., Sola P., Ferraro D., Grammond P., Turkoglu R., Butzkueven H., Yamout B., Altintas A., VanPesch V., Maimone D., Lechner-Scott J., Bergamaschi R., Karabudak R., Iuliano G., McGuigan C., Cartechini E., Barnett M., Hughes S., Sa M.J., Kappos L., Ramo-Tello C., Cristiano E., Hodgkinson S., Spitaleri D.L.A., Soysal A., Petersen T., Slee M., Butler E., Granella F., Verheul F., McCombe P., Ampapa R., Skibina O., Prevost J., Sinnige L., Sanchez-Menoyo J.L., Vucic S., Laureys G., VanHijfte L., Khurana D., MacDonell R., Castillo-Trivino T., Gray O., Aguera-Morales E., Kister I., Shaw C., Deri N., Al-Harbi T., Fragoso Y., Csepany T., Sempere A., and Kalincik T.

Abstract

Objective: To assess whether patients' response to disease modifying therapies (DMT) in multiple sclerosis (MS) varies by disease activity (annualised relapse rate, presence of new MRI lesions), disability, age, MS duration or disease phenotype. Background(s): Our understanding of demographic and clinical modifiers of the effectiveness of MS therapies is limited. Design/Methods: Using the international MSBase registry, we selected patients with MS followed for >=1 year, with >=3 visits, >=1 visit per year. Marginal structural models were used to compare the hazard ratios (HR) of 6-month confirmed worsening and improvement of disability (EDSS), and the incidence of relapses between treated and untreated periods. Models were continuously re-adjusted for patient age, sex, pregnancy, date, time from first symptom, prior relapse history, disability and MRI activity. Result(s): Among 23687 patients with relapsing MS, those on DMTs experienced 48% reduction in relapse incidence [HR=0.52 (0.44-0.61)], 48% lower risk of disability worsening [HR=0.52 (0.38-0.71)] and 33% greater chance of disability improvement [HR=1.33 (95%CI 1.0-1.5)]. The effect of DMTs on EDSS worsening and improvement and the risk of relapses was attenuated with more severe disability. The effect of DMTs on reducing relapses declined with higher prior relapse rate and in patients with prior cerebral MRI activity. Among 26329 participants with relapsing or progressive MS, DMTs were associated with 25% reduction in EDSS worsening and 42% reduction in relapses in patients with relapsing MS [HR=0.75 (0.65-0.86) and HR=0.58 (0.54-62), respectively], while evidence for such beneficial effects of treatment in patients with progressive MS was not found [HR=1.11 (0.91-1.46) and HR=1.16 (0.91-1.46), respectively]. Conclusion(s): DMTs are associated with reduction in relapse frequency, progression of disability, and increased chance of recovery from disability. The DMTs are most effective among patients with lower

Published
2021

18. Association of latitude and exposure to ultraviolet B radiation with severity of multiple sclerosis.

Author

Vitkova M., Diouf I., Malpas C., Horakova D., Havrdova E.K., Patti F., Ozakbas S., Ayuso G.I., Madueno S.E., Shaygannejad V., Onofrj M., Lugaresi A., Alroughani R., Prat A., Larochelle C., Girard M., Duquette P., Terzi M., Boz C., GrandaMaison F., Sola P., Ferraro D., Grammond P., Butzkueven H., Buzzard K., Skibina O., Yamout B., Karabudak R., Gerlach O.H.H., Lechner-Scott J., Maimone D., Bergamaschi R., VanPesch V., Iuliano G., Cartechini E., Sa M.J., Ampapa R., Barnett M., Hughes S., Ramo-Tello C., Hodgkinson S., Spitareli D., Petersen T., Butler E., Slee M., McGuigan C., McCombe P., Granella F., Cristiano E., Prevost J., Taylor B., Sanchez-Menoyo J.L., Laureys G., VanHijfte L., Vucic S., MacDonell R., Gray O., Urtaza F.J.O., Deri N., Fragoso Y., Shaw C., Kalincik T., Vitkova M., Diouf I., Malpas C., Horakova D., Havrdova E.K., Patti F., Ozakbas S., Ayuso G.I., Madueno S.E., Shaygannejad V., Onofrj M., Lugaresi A., Alroughani R., Prat A., Larochelle C., Girard M., Duquette P., Terzi M., Boz C., GrandaMaison F., Sola P., Ferraro D., Grammond P., Butzkueven H., Buzzard K., Skibina O., Yamout B., Karabudak R., Gerlach O.H.H., Lechner-Scott J., Maimone D., Bergamaschi R., VanPesch V., Iuliano G., Cartechini E., Sa M.J., Ampapa R., Barnett M., Hughes S., Ramo-Tello C., Hodgkinson S., Spitareli D., Petersen T., Butler E., Slee M., McGuigan C., McCombe P., Granella F., Cristiano E., Prevost J., Taylor B., Sanchez-Menoyo J.L., Laureys G., VanHijfte L., Vucic S., MacDonell R., Gray O., Urtaza F.J.O., Deri N., Fragoso Y., Shaw C., and Kalincik T.

Abstract

Objective: The aim of this study was to investigate the association between latitude of residence, ultraviolet B radiation exposure (UVB) and the severity of multiple sclerosis (MS). Background(s): Severity of (MS) varies widely among individuals. Understanding of determinants of this heterogeneity will help clinicians optimize the management of MS in individual patients. Design/Methods: This observational study used the global MSBase registry. Disease severity was quantified with MS Severity Score (MSSS, a decile of disability relative to a normative cohort with similar disease duration). The latitude of each study center (stratified by hemisphere) and cumulative annualized UVB dose at study center (calculated from from NASA's Total Ozone Mapping Spectrometer) at ages 6 and 18 and the year of disability assessment were calculated. Quadratic regression was used to model the associations between latitude, UVB and MSSS. Result(s): 46,128 patients (70% women, mean age 39+/-12, resident between latitudes 19degree35' and 56degree16', cumulative follow-up 351,196 patient-years) were included. Latitude showed a non-linear association with MS severity. Above 40degree of latitude, more severe disease was associated with higher latitudes (beta= 0.08, 95%CI: 0.04, 0.12). For example, this translates into a mean difference of 1.3 points of MSSS between patients living in Madrid and Copenhagen. No such association was observed in latitudes <40degree (beta= 0.02, 95%CI: 0.06, 0.03). The overall disability accrual was faster in those with a lower level of estimated UVB exposure before the age of 6 (beta= 0.5, 95%CI: 0.6, 0.4) and 18 years (beta= 0.6, 95%CI: 0.7, 0.4) as well as with lower life-time UVB exposure at the time of disability assessment (beta= 1.0, 95%CI: 1.1, 0.9). Conclusion(s): In temperate zones, MS severity is associated with latitude. This association is mainly, but not exclusively, driven by UVB exposure. Thus, UVB exposure contributes to both MS susceptibility a

Published
2021

19. The MSBase pregnancy, neonatal outcomes, and women's health registry

Author

Jokubaitis, VG, Skibina, O, Alroughani, R, Altintas, A, Butzkueven, H, Eichau, S, Fragoso, Y, Hellwig, K, Hughes, SE, Rath, L, van der Walt, A, Gray, O, Jokubaitis, VG, Skibina, O, Alroughani, R, Altintas, A, Butzkueven, H, Eichau, S, Fragoso, Y, Hellwig, K, Hughes, SE, Rath, L, van der Walt, A, and Gray, O

Abstract

BACKGROUND: Family planning and pregnancy decisions are key considerations in the management of women with multiple sclerosis (MS), who are typically diagnosed between the ages of 20-40 years. Despite a strong evidence base that pregnancy is not harmful for women with MS, many knowledge gaps remain. These include: best management strategies through pregnancy in the era of highly effective disease-modifying therapies (DMT); foetal risks associated with DMT exposure in utero or in relation to breastfeeding; knowledge base around the use of assisted reproductive technologies; the long-term impact of pregnancy on disease outcomes, as well as the impact of long-term DMT use on women's health and cancer risk. METHODS: Here, we describe the new MSBase pregnancy, neonatal outcomes and women's health registry. We provide the rationale for, and detailed description of, the variables collected within the registry, together with data acquisition details. CONCLUSION: The present paper will act as a reference document for future studies.

Published
2021

20. The MSBase pregnancy, neonatal outcomes, and women’s health registry

Author

Altıntaş, Ayşe (ORCID 0000-0002-8524-5087 & YÖK ID 11611), Jokubaitis, V. G.; Skibina, O.; Alroughani, R.; Butzkueven, H.; Eichau, S.; Fragoso, Y.; Hellwig, K.; Hughes, S. E.; Rath, L.; van der Walt, A.; Gray, O., School of Medicine, Altıntaş, Ayşe (ORCID 0000-0002-8524-5087 & YÖK ID 11611), Jokubaitis, V. G.; Skibina, O.; Alroughani, R.; Butzkueven, H.; Eichau, S.; Fragoso, Y.; Hellwig, K.; Hughes, S. E.; Rath, L.; van der Walt, A.; Gray, O., and School of Medicine

Abstract

Background: family planning and pregnancy decisions are key considerations in the management of women with multiple sclerosis (MS), who are typically diagnosed between the ages of 20–40 years. Despite a strong evidence base that pregnancy is not harmful for women with MS, many knowledge gaps remain. These include: best management strategies through pregnancy in the era of highly effective disease-modifying therapies (DMT); foetal risks associated with DMT exposure in utero or in relation to breastfeeding; knowledge base around the use of assisted reproductive technologies; the long-term impact of pregnancy on disease outcomes, as well as the impact of long-term DMT use on women’s health and cancer risk. Methods: here, we describe the new MSBase pregnancy, neonatal outcomes and women’s health registry. We provide the rationale for, and detailed description of, the variables collected within the registry, together with data acquisition details. Conclusion: the present paper will act as a reference document for future studies., National Health and Medical Research Council of Australia; MSBase Foundation; Roche; Merck; Biogen; Novartis; Bayer-Schering; Sanofi Genzyme; Teva

Published
2021

21. Increased john cunningham virus seroconversion rates seen in a southern hemisphere international cohort of natalizumab treated patients.

Author

Dwyer C., Butler E., Haartsen J., Butzkueven H., Cartwright A., Shuey N., Coleman J., Macdonell R., Rath L., Fragoso Y., Van Der Walt A., Carey J., Kilpatrick T., Jokubaitis V., Stankovich J., Baker J., Fryer K., Dwyer C., Butler E., Haartsen J., Butzkueven H., Cartwright A., Shuey N., Coleman J., Macdonell R., Rath L., Fragoso Y., Van Der Walt A., Carey J., Kilpatrick T., Jokubaitis V., Stankovich J., Baker J., and Fryer K.

Abstract

Objective: To assess factors associated with John Cunningham virus (JCV) seroconversion in natalizumab-treated patients. Background(s): Natalizumab is a highly effective treatment for relapsing-remitting multiple sclerosis (RRMS), but its use is complicated by JCV co-infection. This virus can result in progressive multifocal leukoencephalopathy (PML), a devastating infection of the central nervous system. Serial assessment of JCV serostatus is therefore mandated during natalizumab treatment Design/Methods: Patients treated with natalizumab for RRMS at six tertiary hospitals in Melbourne, Australia (n=869) and eleven MS treatment centres in Brazil (n=137) were assessed for change in JCV serostatus, duration of natalizumab exposure and prior immunosuppression. Sensitivity analyses examined whether sex, age, hospital, prior immunosuppression or number of JCV tests affected time to seroconversion. Result(s): From a cohort of 1001 natalizumab-treated patients (510 with multiple measures of JCV serostatus), durable positive seroconversion was observed in 83 of 345 initially JCV negative patients (24.1%; 7.3% per year). Conversely, 16 of 165 initially JCV positive patients experienced durable negative seroconversion (9.7%; 3.8% per year). Forty (3.9%) patients had fluctuating serostatus. Time-to-event analysis did not identify a relationship between JCV seroconversion and duration of natalizumab exposure or prior immunosuppressive use. Male sex was associated with a greater risk of JCV seroconversion (adjusted hazard ratio 2.09 (95% CI 1.17-3.71) p=0.012). Conclusion(s): In this large cohort of natalizumab-treated patients we observed durable positive seroconversion at an annualised rate of 7.3%. This rate exceeds that noted in registration and post-marketing studies for natalizumab and is consistent with increased rates of seroconversion reported recently by European centres. This rate also greatly exceeds that predicted by epidemiological studies of JCV seroconversion in

Published
2020

22. Predicting long-term sustained disability progression in multiple sclerosis.

Author

Van Wijmeersch B., Malpas C., Hupperts R.M.M., Alroughani R., Boz C., Shaygannejad V., Van Pesch V., Kappos L., Lechner-Scott J., Bergamaschi R., Turkoglu R., Solaro C., Ramo-Tello C., Iuliano G., Granella F., Spitaleri D.L.A., Bolanos R.F., Slee M., McCombe P., Prevost J., Ampapa R., Ozakbas S., Sanchez-Menoyo J.L., Soysal A., Vucic O., Petersen T., Verheul F., Butler E., Hodgkinson S., Sidhom Y., Gouider R., Cristiano E., Urtaza F.J.O., Saladino M.L., Barnett M., Deri N., Moore F., Rozsa C., Yamout B., Skibina O., Gray O., Campbell J., Sempere A., Singhal B., Fragoso Y., Shaw C., Kermode A., Petkovska-Boskova T., Taylor B., Simo M., Vella N., Shuey N., Alkhaboori J., Al-Harbi T., Macdonell R., Dominguez J.A., Kister I., Csepany T., Vrech C., Kovacs K., Sirbu C.A., Hughes S., Sormani M.P., Butzkueven H., Kalincik T., Sharmin S., Bovis F., Horakova D., Havrdova E., Ayuso G.I., Eichau S., Trojano M., Prat A., Girard M., Duquette P., Onofrj M., Lugaresi A., Grand'Maison F., Grammond P., Sola P., Ferraro D., Terzi M., Van Wijmeersch B., Malpas C., Hupperts R.M.M., Alroughani R., Boz C., Shaygannejad V., Van Pesch V., Kappos L., Lechner-Scott J., Bergamaschi R., Turkoglu R., Solaro C., Ramo-Tello C., Iuliano G., Granella F., Spitaleri D.L.A., Bolanos R.F., Slee M., McCombe P., Prevost J., Ampapa R., Ozakbas S., Sanchez-Menoyo J.L., Soysal A., Vucic O., Petersen T., Verheul F., Butler E., Hodgkinson S., Sidhom Y., Gouider R., Cristiano E., Urtaza F.J.O., Saladino M.L., Barnett M., Deri N., Moore F., Rozsa C., Yamout B., Skibina O., Gray O., Campbell J., Sempere A., Singhal B., Fragoso Y., Shaw C., Kermode A., Petkovska-Boskova T., Taylor B., Simo M., Vella N., Shuey N., Alkhaboori J., Al-Harbi T., Macdonell R., Dominguez J.A., Kister I., Csepany T., Vrech C., Kovacs K., Sirbu C.A., Hughes S., Sormani M.P., Butzkueven H., Kalincik T., Sharmin S., Bovis F., Horakova D., Havrdova E., Ayuso G.I., Eichau S., Trojano M., Prat A., Girard M., Duquette P., Onofrj M., Lugaresi A., Grand'Maison F., Grammond P., Sola P., Ferraro D., and Terzi M.

Abstract

Objective: Using global MSBase registry, this study establishes 6-month confirmed disability progression events as indicators of long-term disability worsening suitable for use in randomized clinical trials in multiple sclerosis (MS). Background(s): Randomized clinical trials evaluate short-term treatment effect on disability in the form of 3-6-month confirmed disability progression, but whether these translate into long-term disability outcomes is unknown. Design/Methods: A Cox proportional hazards model identified associations between patients' demographic and clinical characteristics and the probability of recovery from disability progression events. The coefficients from this model were used to calculate a sustained progression score, which was evaluated in a validation cohort and applied to a trial cohort. Result(s): 902 patients (development cohort), patient characteristics at the time of progression associated with lower probability of subsequent improvement were age (hazard ratio (HR)=0.98), primary progressive (HR=0.37) and progressive-relapsing (HR=0.36) MS, expanded disability status scale score >=6 (HR=0.71) and its change from baseline (HR=0.67), number of affected functional system scores (HR=0.92) and pyramidal (HR=0.79) functional system score (p<0.05). The strength of the association with pyramidal score decreased with time (HR=1.01). A relapse within previous month (HR=1.46) and worsening in sensory functional system score (HR=1.17) were associated with higher probability of improvement after progression. The sustained progression score (range 0.39-4.79) in the validation cohort with 1,271 progression events, estimated a 53% lower chance of improvement for each unit increase in the score (HR=0.47). The proportions of progression events sustained at 5 years stratified by the score were 1: 68%, 2: 79%, 3: 94%, 4: 100%. The progression scores were then applied to the CLARITY trial data. Conclusion(s): Estimate of the probability of disability progress

Published
2020

23. Delay from treatment start to full effect of immunotherapies for multiple sclerosis

Author

Roos, I, Leray, E, Frascoli, F, Casey, R, Brown, WJL, Horakova, D, Havrdova, EK, Trojano, M, Patti, F, Izquierdo, G, Eichau, S, Onofrj, M, Lugaresi, A, Prat, A, Girard, M, Grammond, P, Sola, P, Ferraro, D, Ozakbas, S, Bergamaschi, R, Sá, MJ, Cartechini, E, Boz, C, Granella, F, Hupperts, R, Terzi, M, Lechner-Scott, J, Spitaleri, D, van Pesch, V, Soysal, A, Olascoaga, J, Prevost, J, Aguera-Morales, E, Slee, M, Csepany, T, Turkoglu, R, Sidhom, Y, Gouider, R, van Wijmeersch, B, McCombe, P, Macdonell, R, Coles, A, Malpas, CB, Butzkueven, H, Vukusic, S, Kalincik, T, Duquette, P, Grand'Maison, F, Iuliano, G, Ramo-Tello, C, Solaro, C, Cabrera-Gomez, JA, Rio, ME, Bolaños, RF, Shaygannejad, V, Oreja-Guevara, C, Sanchez-Menoyo, JL, Petersen, T, Altintas, A, Barnett, M, Flechter, S, Fragoso, Y, Amato, MP, Moore, F, Ampapa, R, Verheul, F, Hodgkinson, S, Cristiano, E, Yamout, B, Laureys, G, Dominguez, JA, Zwanikken, C, Deri, N, Dobos, E, Vrech, C, Butler, E, Rozsa, C, Petkovska-Boskova, T, Karabudak, R, Rajda, C, Alkhaboori, J, Saladino, ML, Shaw, Cameron, Shuey, N, Vucic, S, Sempere, AP, Campbell, J, Piroska, I, Taylor, B, van der Walt, A, Kappos, L, Roullet, E, Gray, O, Simo, M, Sirbu, CA, Brochet, B, Cotton, F, de Sèze, J, Dion, A, Douek, P, Roos, I, Leray, E, Frascoli, F, Casey, R, Brown, WJL, Horakova, D, Havrdova, EK, Trojano, M, Patti, F, Izquierdo, G, Eichau, S, Onofrj, M, Lugaresi, A, Prat, A, Girard, M, Grammond, P, Sola, P, Ferraro, D, Ozakbas, S, Bergamaschi, R, Sá, MJ, Cartechini, E, Boz, C, Granella, F, Hupperts, R, Terzi, M, Lechner-Scott, J, Spitaleri, D, van Pesch, V, Soysal, A, Olascoaga, J, Prevost, J, Aguera-Morales, E, Slee, M, Csepany, T, Turkoglu, R, Sidhom, Y, Gouider, R, van Wijmeersch, B, McCombe, P, Macdonell, R, Coles, A, Malpas, CB, Butzkueven, H, Vukusic, S, Kalincik, T, Duquette, P, Grand'Maison, F, Iuliano, G, Ramo-Tello, C, Solaro, C, Cabrera-Gomez, JA, Rio, ME, Bolaños, RF, Shaygannejad, V, Oreja-Guevara, C, Sanchez-Menoyo, JL, Petersen, T, Altintas, A, Barnett, M, Flechter, S, Fragoso, Y, Amato, MP, Moore, F, Ampapa, R, Verheul, F, Hodgkinson, S, Cristiano, E, Yamout, B, Laureys, G, Dominguez, JA, Zwanikken, C, Deri, N, Dobos, E, Vrech, C, Butler, E, Rozsa, C, Petkovska-Boskova, T, Karabudak, R, Rajda, C, Alkhaboori, J, Saladino, ML, Shaw, Cameron, Shuey, N, Vucic, S, Sempere, AP, Campbell, J, Piroska, I, Taylor, B, van der Walt, A, Kappos, L, Roullet, E, Gray, O, Simo, M, Sirbu, CA, Brochet, B, Cotton, F, de Sèze, J, Dion, A, and Douek, P

Published
2020

24. Sex effects across the lifespan in women with multiple sclerosis

Author

Krysko, KM, Graves, JS, Dobson, R, Altintas, A, Amato, MP, Bernard, J, Bonavita, S, Bove, R, Cavalla, P, Clerico, M, Corona, T, Doshi, A, Fragoso, Y, Jacobs, D, Jokubaitis, V, Landi, D, Llamosa, G, Longbrake, EE, Maillart, E, Marta, M, Midaglia, L, Shah, S, Tintore, M, van der Walt, A, Voskuhl, R, Wang, Y, Zabad, RK, Zeydan, B, Houtchens, M, Hellwig, K, Krysko, KM, Graves, JS, Dobson, R, Altintas, A, Amato, MP, Bernard, J, Bonavita, S, Bove, R, Cavalla, P, Clerico, M, Corona, T, Doshi, A, Fragoso, Y, Jacobs, D, Jokubaitis, V, Landi, D, Llamosa, G, Longbrake, EE, Maillart, E, Marta, M, Midaglia, L, Shah, S, Tintore, M, van der Walt, A, Voskuhl, R, Wang, Y, Zabad, RK, Zeydan, B, Houtchens, M, and Hellwig, K

Abstract

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating central nervous system disorder that is more common in women, with onset often during reproductive years. The female:male sex ratio of MS rose in several regions over the last century, suggesting a possible sex by environmental interaction increasing MS risk in women. Since many with MS are in their childbearing years, family planning, including contraceptive and disease-modifying therapy (DMT) counselling, are important aspects of MS care in women. While some DMTs are likely harmful to the developing fetus, others can be used shortly before or until pregnancy is confirmed. Overall, pregnancy decreases risk of MS relapses, whereas relapse risk may increase postpartum, although pregnancy does not appear to be harmful for long-term prognosis of MS. However, ovarian aging may contribute to disability progression in women with MS. Here, we review sex effects across the lifespan in women with MS, including the effect of sex on MS susceptibility, effects of pregnancy on MS disease activity, and management strategies around pregnancy, including risks associated with DMT use before and during pregnancy, and while breastfeeding. We also review reproductive aging and sexual dysfunction in women with MS.

Published
2020

28. Disability outcomes in patients with early cerebellar symptoms in multiple sclerosis

Author

Le, M. V. H., Malpas, C., Sharmin, S., Horakova, D., Havrdova, E. K., Trojano, M., Izquierdo, G., Eichau, S., Ozakbas, S., Lugaresi, A., Prat, A., Girard, M., Duquette, P., Alroughani, R., Bergamaschi, R., Sola, P., Grammond, P., Grand Maison, F., Terzi, M., Boz, C., Hupperts, R., Butzkueven, H., Walt, A., Pucci, E., Granella, F., Pesch, V., Soysa, A., Yamout, B., Lechner-Scott, J., Spitaleri, D., Ampapa, R., Recai Turkoglu, Iuliano, G., Ramo-Tello, C., Sanchez-Menoyo, J. L., Gouider, R., Shaygannejad, V., Prevost, J., Altintas, A., Fragoso, Y., Mccombe, P., Petersen, T., Slee, M., Barnett, M., Vucic, S., and Kalincik, T.

Published
2018

30. Halting disability progression in multiple sclerosis with immunomodulatory injectable treatments: Is it achievable?

Author

Fragoso, Y. D., Spelman, T., Duquette, P., Girard, M., Trojano, M., Izquierdo, G., Butzkueven, H., and Ondokuz Mayıs Üniversitesi

Abstract

7th Joint European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS)-Americas-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ACTRIMS) -- OCT 25-28, 2017 -- Paris, FRANCE Oreja-Guevara, Celia/0000-0002-9221-5716; Lugaresi, Alessandra/0000-0003-2902-5589 WOS: 000413730205114 … European Comm Treatment & Res Multiple Sclerosis, Americas Comm Treatment & Res Multiple Sclerosis Biogen IdecBiogen; NovartisNovartis; MerckSeronoMerck SeronoMerck & Company; GenzymeGenzyme Corporation Yara Dadalti Fragoso, Tim Spelman, Pierre Duquette, Marc Girard, Maria Trojano, Guillermo Izquierdo, Pierre Grammond, Alessandra Lugaresi, Vincent Van Pesch, Francois Grand'Maison, Celia Oreja-Guevara, Gerardo Iuliano, Roberto Bergamaschi, Maria Edite Rio, Ricardo Fernandez Bolanos, Murat Terzi, and Helmut Butzkueven, have no particular conflicts of interest to declare for this abstract. The work was carried out on behalf of MSBase study group, which receives unconditional grants from pharmaceutical industries (Biogen Idec, Novartis, MerckSerono, Genzyme) to support the existence of the database.

Published
2017

31. Lymphocyte count in peripheral blood is not associated with the level of clinical response to treatment with fingolimod [Meeting Abstract]

Author

Fragoso, Y. D., Alroughani, R., Barnett, M., Brooks, J. B., Butzkueven, H., Boz, C., Ticha, V., and Ondokuz Mayıs Üniversitesi

Abstract

32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) -- SEP 14-17, 2016 -- London, ENGLAND Havrdova, Eva Kubala/0000-0002-9543-4359; Lugaresi, Alessandra/0000-0003-2902-5589 WOS: 000383267201435 … European Comm Treatment & Res Multiple Sclerosis Biogen-IdecBiogen; Merck-SeronoMerck SeronoMerck & Company; NovartisNovartis; GenzymeGenzyme Corporation; BiogenBiogen; MerckMerck & Company; Oxford PharmaGenesis; Biogen IdecBiogen; Merck SeronoMerck SeronoMerck & Company; Almirall; BayerBayer AG; SanofiSanofi-Aventis; Teva; Fondazione Italiana Sclerosi MultiplaFondazione Italiana Sclerosi Multipla (FISM); Biogen IncBiogen; Bayer-ScheringBayer AG Michael Barnett has served on scientific advisory boards for Biogen-Idec, Novartis and Genzyme and has received conference travel support from Biogen-Idec and Novartis. His institution has received research support from Biogen-Idec, Merck-Serono and Novartis.; Helmut Butzkueven has received consulting fees from Genzyme, Biogen, Novartis, Merck and Oxford PharmaGenesis; and grant/ research support from Biogen, Novartis, Merck and Genzyme Cavit Boz has nothing to disclose; Franco Granella has served on scientific advisory boards for Biogen Idec, Novartis and Sanofi Aventis and has received funding for travel and speaker honoraria from Biogen Idec, Merck Serono, and Almirall; Alessandra Lugaresi has served as a Bayer, Biogen, Merck Serono, Novartis and Genzyme Advisory Board Member. She received travel grants and honoraria from Bayer, Biogen, Merck Serono, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla and research grants for her Institution from Bayer, Biogen, Merck Serono, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla.; Tim Spelman received compensation for serving on scientific advisory boards, honoraria for consultancy and funding for travel from Biogen Inc; speaker honoraria from Novartis.; Murat Terzi received travel grants from Merck Serono, Novartis, Bayer-Schering, Merck-Serono and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.

Published
2016

32. Odors as triggering and worsening factors for migraine in men

Author

Lima, A M, Sapienza, G B, Giraud, V O, and Fragoso, Y D

Subjects
enxaqueca, fatores ambientais, osmophobia, environmental factors, olfactory stimuli, estímulo olfatório, migraine, osmofobia, psychological phenomena and processes
Abstract

OBJECTIVE: To assess the role of odors in triggering or worsening migraine in men. METHOD: Ninety-eight male migraineurs from the general population were assessed individually through questionnaires. Environmental factors relating to their migraine were reported, with special focus on the role of odors. RESULTS: Odors were the second most frequent triggering factor for migraine attacks (48%), behind stressful situations (59%). Likewise, odors were the second most frequent worsening factor (73%), just behind excessive light (74%). Thirty-three individuals (33.4%) stated that odors were both triggering and worsening factors for their migraine attacks. Perfume, cigarette smoke and cleaning products were the most frequent migraine-related odors reported by these male migraineurs. CONCLUSION: This was the first study to assess the role of odors in migraine exclusively in men. There was a high degree of odor-related migraine among these men, thus suggesting that patient education could alert such individuals to gender-related factors, since different triggering and worsening factors have been reported by males and females. OBJETIVO: Avaliar o papel dos odores como fatores desencadeantes e de piora da enxaqueca em homens. MÉTODO: Noventa e oito homens com enxaqueca na população geral foram avaliados individualmente por questionários. Os fatores ambientais relacionados à enxaqueca foram relatados, com foco especial no papel dos odores. RESULTADOS: Os odores foram o segundo fator mais frequente no desencadeamento de crise de enxaqueca (48%), atrás das situações de estresse (59%). Da mesma forma, os odores foram a segunda causa mais frequente de piora das crises (73%), apenas atrás do excesso de luminosidade (74%). Trinta e três indivíduos (33,4%) relataram que os odores eram tanto fatores desencadeantes quanto fatores de piora de suas crises de enxaqueca. Perfume, fumaça de cigarro e produtos de limpeza foram os odores mais relatados como sendo relacionados a enxaqueca pelos homens. CONCLUSÃO: Este foi o primeiro estudo que avaliou o papel dos odores exclusivamente em homens com enxaqueca. Houve um alto índice de enxaqueca relacionada a odores, sugerindo que a educação dos pacientes poderia alertar fatores dependentes do gênero do paciente, uma vez que diferentes fatores desencadeantes e de piora das crises tem sido relatados por homens e mulheres.

Published
2011

33. Association between multiple sclerosis prevalence and environmental and genetic factors in Latin America and the Caribbean: An ecological study

Author

Ketzoian, C.N., primary, Hackembruch, H.J., additional, Melcon, M.O., additional, Melcon, C.M., additional, Bartoloni, L., additional, Cristiano, E., additional, Durán, J.C., additional, Kuntz Grzesiuk, A., additional, Dadalti Fragoso, Y., additional, Bidin Brooks, J.B., additional, Díaz, V., additional, Romero García, K., additional, Cabera Gómez, J.A., additional, Abad, P., additional, Macías Islas, M.A., additional, Gracia, F., additional, Hamuy Díaz de Bedoya, V.F., additional, Córdoba Ruiz, M.E., additional, Oehninger, C., additional, and Soto, A., additional

Published
2013
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39. Clinical and therapeutic predictors of relapse and disability outcomes in neuromyelitis optica spectrum disorder

Author

Kunchok, A., Malpas, C., Horakova, D., Havrdova, E., Alroughani, R., Terzi, M., Yamout, B., Karabudak, R., Boz, C., Ozakbas, S., Olascoagam, J., Simon, M., Granellau, F., Mccombe, P., Csepanym, T., Bergamaschi, R., Fragoso, Y., Al-Harbin, T., Recai Turkoglu, Lechner-Scott, J., Laureys, G., Pucci, E., Sola, P., Ferraro, D., Altintas, A., Grand Maison, F., Izquierdo, G., Eichau, S., Lugaresi, A., Marriott, M., Kister, I., Butzkueven, H., and Kalincik, T.

40. The BCTRIMS expanded consensus on treatment of multiple sclerosis. I. The evidences for the use of immunossupressive agents, plasma exchange and autologous hematopoietic stem cell transplantation,Consenso expandido do BCTRIMS para o tratamento da esclerose múltipla. I. As evidências para o uso de imunossupressores, plasmaférese e transplante autólogo de células tronco

Author

Callegaro, D., Lana-Peixoto, M. A., Moreira, M. A., Marchiori, P. E., Bacheschi, L. A., Arruda, W. O., Campos, G. B., Martins Lino, A. M., Souza Melo, A., Gomes Da Rocha, F. C., Brito Ferreira, M. L., Ataíde Jr, L., Kaiman Maciel, D. R., Gabbai, A. A., Teixeira Jr, A. L., Da Fonseca Filho, A. G., Santos Oliveira, B. E., Stella, C. V., Almeida Boer, C. A., Silveira Pagliuso, C. A., Brandão, C. O., Araújo, C. R., Botelho, C. M., Pirani Jr, C., Diniz, D. S., Comini Frota, E. R., Tosta Da Silva, E. D., Bahadian Bardy, F., Di Biase, F., Silva Malveira, G. L., Reis, I. L., Urbano Da Silva, J., Coral, L. C., Antônio Da Silva, M., Peterlevitz, M. A., Amaral Lorenti, M. Â, Mendes, M. F., Guimarães Rocha, M. S., Da Cunha, M. P., Goulart, N. T., Discher Sá, P. N., Da Nóbrega, P. V., Domingues, R. B., Buainain, R. P., Rizo Morales, R., Ferreira Rezende, R., Melo Souza, S. E., Haussen, S. R., Fenelon, S. B., Lacerda, S. S., Gomes, S., Nunes Machado, S. C., Oliveira Yokomizo, T., Haase, V. G., Góes Horta, W., Teixeira, W. R., Fragoso, Y. D., and Ribeiro Araújo, Y.

41. Aggressive form of multiple sclerosis can be predicted early after disease onset

Author

Malpas, C. B., Manouchehrinia, A., Sharmin, S., Izanne Roos, Horakova, D., Havrdova, E. K., Trojano, M., Izquierdo, G., Eichau, S., Bergamaschi, R., Sola, P., Ferraro, D., Lugaresi, A., Prat, A., Girard, M., Duquette, P., Grammond, P., Grand Maison, F., Ozakbas, S., Pesch, V., Granella, F., Hupperts, R., Pucci, E., Boz, C., Iuliano, G., Sidhom, Y., Gouider, R., Spitaleri, D., Butzkueven, H., Soysal, A., Petersen, T., Verheul, F., Karabudak, R., Turkoglu, R., Ramo-Tello, C., Terzi, M., Cristiano, E., Slee, M., Mccombe, P., Macdonell, R., Fragoso, Y., Olascoaga, J., Altintas, A., Olsson, T., Hillert, J., and Kalincik, T.

42. Early clinical predictors of severe MS

Author

Malpas, C., Sharmin, S., Horakova, D., Havrdova, E. K., Trojano, M., Izquierdo, G., Bergamaschi, R., Sola, P., Ferraro, D., Lugaresi, A., Prat, A., Girard, M., Duquette, P., Grammond, P., Grand Maison, F., Ozakbas, S., Pesch, V., Granella, F., Hupperts, R., Pucci, E., Boz, C., Iuliano, G., Sidhom, Y., Gouider, R., Spitaleri, D., Butzkueven, H., Soysal, A., Petersen, T., Verheul, F., Karabudak, R., Recai Turkoglu, Ramo-Tello, C., Terzi, M., Cristiano, E., Slee, M., Mccombe, P., Macdonell, R., Fragoso, Y., Olascoaga, J., Altintas, A., and Kalincik, T.

43. Variability of the response to immunotherapy among subgroups of patients with multiple sclerosis

Author

Diouf, I, Malpas, C, Horakova, D, Havrdova, EK, Patti, F, Shaygannejad, V, Ozakbas, S, Izquierdo, G, Eichau, S, Zakaria, M, Onofrj, M, Lugaresi, A, Alroughani, R, Prat, A, Girard, M, Duquette, P, Terzi, M, Boz, C, Grand'Maison, F, Hamdy, S, Sola, P, Ferraro, D, Grammond, P, Turkoglu, R, Butzkueven, H, Yamout, B, Altintas, A, Van Pesch, V, Maimone, D, Lechner-Scott, J, Bergamaschi, R, Karabudak, R, Giuliano, F, Mcguigan, C, Cartechini, E, Barnett, M, Hughes, S, Sa, M, Kappos, L, Ramo-Tello, C, Cristiano, E, Hodgkinson, S, Spitaleri, D, Soysal, A, Petersen, T, Slee, M, Butler, E, Granella, F, Verheul, F, Mccombe, P, Ampapa, R, Skibina, O, Prevost, J, Sinnige, LGF, Sanchez-Menoyo, JL, Vucic, S, Laureys, G, Van Hijfte, L, Khurana, D, Macdonell, R, Castillo-Trivino, T, Gray, O, Aguera, E, Kister, I, Shaw, C, Deri, N, Al-Harbi, T, Fragoso, Y, Csepany, T, Sempere, A, and Kalincik, T

48. The MSBase pregnancy, neonatal outcomes, and women’s health registry

Author

Anneke van der Walt, Kerstin Hellwig, Ayse Altintas, Sara Eichau, Olga Skibina, Vilija Jokubaitis, Orla Gray, Helmut Butzkueven, Louise Rath, Raed Alroughani, Yara Dadalti Fragoso, Stella Hughes, Altıntaş, Ayşe (ORCID 0000-0002-8524-5087 & YÖK ID 11611), Jokubaitis, V. G., Skibina, O., Alroughani, R., Butzkueven, H., Eichau, S., Fragoso, Y., Hellwig, K., Hughes, S. E., Rath, L., van der Walt, A., Gray, O., and School of Medicine

Subjects
Registry, medicine.medical_specialty, Multiple Sclerosis, Women’s Health, MSBase, lcsh:RC346-429, Study Protocol, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, medicine, Neurosciences, Neurology, lcsh:Neurology. Diseases of the nervous system, Pharmacology, 030219 obstetrics & reproductive medicine, business.industry, Multiple sclerosis, Neonatal outcomes, Women’s health, medicine.disease, Clinical neurology, Family planning, Family medicine, Neonatal Outcomes, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Background: family planning and pregnancy decisions are key considerations in the management of women with multiple sclerosis (MS), who are typically diagnosed between the ages of 20–40 years. Despite a strong evidence base that pregnancy is not harmful for women with MS, many knowledge gaps remain. These include: best management strategies through pregnancy in the era of highly effective disease-modifying therapies (DMT); foetal risks associated with DMT exposure in utero or in relation to breastfeeding; knowledge base around the use of assisted reproductive technologies; the long-term impact of pregnancy on disease outcomes, as well as the impact of long-term DMT use on women’s health and cancer risk. Methods: here, we describe the new MSBase pregnancy, neonatal outcomes and women’s health registry. We provide the rationale for, and detailed description of, the variables collected within the registry, together with data acquisition details. Conclusion: the present paper will act as a reference document for future studies., National Health and Medical Research Council of Australia; MSBase Foundation; Roche; Merck; Biogen; Novartis; Bayer-Schering; Sanofi Genzyme; Teva

Published
2021

49. SARS-CoV-2 serology after COVID-19 in multiple sclerosis: An international cohort study

Author

Maria Pia Sormani, Irene Schiavetti, Doriana Landi, Luca Carmisciano, Nicola De Rossi, Cinzia Cordioli, Lucia Moiola, Marta Radaelli, Paolo Immovilli, Marco Capobianco, Vincenzo Brescia Morra, Maria Trojano, Gioacchino Tedeschi, Giancarlo Comi, Mario Alberto Battaglia, Francesco Patti, Yara Dadalti Fragoso, Sedat Sen, Aksel Siva, Roberto Furlan, Marco Salvetti, Gianmarco Abbadessa, Umberto Aguglia, Lia Allegorico, Rossi Beatrice Maria Allegri, Maria Pia Amato, Pietro Annovazzi, Carlo Antozzi, Lucia Appendino, Sebastiano Arena, Viola Baione, Roberto Balgera, Valeria Barcella, Damiano Baroncini, Caterina Barrilà, Mario A. Battaglia, Alessandra Bellacosa, Gianmarco Bellucci, Roberto Bergamaschi, Valeria Bergamaschi, Daiana Bezzini, Beatrice Biolzi, Alvino Bisecco, Simona Bonavita, Giovanna Borriello, Chiara Bosa, Antonio Bosco, Francesca Bovis, Marco Bozzali, Laura Brambilla, Morra Vincenzo Brescia, Giampaolo Brichetto, Maria Buccafusca, Elisabetta Bucciantini, Sebastiano Bucello, Maria Chiara Buscarinu, Maria Paola Cabboi, Massimiliano Calabrese, Francesca Calabria, Francesca Caleri, Federico Camilli, Luisa Maria Caniatti, Roberto Cantello, Ruggero Capra, Rocco Capuano, Patrizia Carta, Paola Cavalla, Maria Grazia Celani, Maria Cellerino, Raffaella Cerqua, Clara Chisari, Raffaella Clerici, Marinella Clerico, Eleonora Cocco, Gaia Cola, Paolo Confalonieri, Antonella Conte, Marta Zaffira Conti, Christian Cordano, Susanna Cordera, Francesco Corea, Claudio Correale, Salvatore Cottone, Francesco Crescenzo, Erica Curti, Alessandro d’Ambrosio, Emanuele D’Amico, Maura Chiara Danni, Alessia d’Arma, Vincenzo Dattola, Stefano de Biase, Giovanna De Luca, Stefania Federica De Mercanti, Paolo De Mitri, Nicola De Stefano, Marco Della Cava, Mario di Napoli, Alessia Di Sapio, Renato Docimo, Anna Dutto, Luana Evangelista, Salvatore Fanara, Diana Ferraro, Maria Teresa Ferrò, Massimo Filippi, Cristina Fioretti, Mario Fratta, Jessica Frau, Marzia Fronza, Alberto Gajofatto, Antonio Gallo, Paolo Gallo, Claudio Gasperini, Anna Ghazaryan, Bruno Giometto, Francesca Gobbin, Flora Govone, Franco Granella, Erica Grange, Maria Grazia Grasso, Angelica Guareschi, Clara Guaschino, Simone Guerrieri, Donata Guidetti, Pietro Iaffaldano, Antonio Ianniello, Luigi Iasevoli, Daniele Imperiale, Maria Teresa Infante, Matilde Inglese, Rosa Iodice, Aniello Iovino, Giovanna Konrad, Roberta Lanzillo, Caterina Lapucci, Luigi Lavorgna, Rita L’Episcopo Maria, Serena Leva, Giuseppe Liberatore, Marianna Lo Re, Marco Longoni, Leonardo Lopiano, Lorena Lorefice, Matteo Lucchini, Giacomo Lus, Davide Maimone, Maria Malentacchi, Giulia Mallucci, Simona Malucchi, Chiara Rosa Mancinelli, Luca Mancinelli, Paolo Manganotti, Teresa Giorgia Maniscalco, Vittorio Mantero, Sabrina Marangoni, Damiano Marastoni, Alessandra Girolama Marfia, Fabiana Marinelli, Alessandro Marti, Filippo Martinelli Boneschi, Federco Masserano Zoli, Francesca Matta, Laura Mendozzi, Giuseppe Meucci, Silvia Miante, Giuseppina Miele, Eva Milano, Massimiliano Mirabella, Rosanna Missione, Marcello Moccia, Sara Montepietra, Margherita Monti Bragadin, Federico Montini, Roberta Motta, Raffaele Nardone, Carolina Gabri Nicoletti, Eduardo Nobile-Orazio, Agostino Nozzolillo, Marco Onofrj, Riccardo Orlandi, Anna Palmieri, Damiano Paolicelli, Livia Pasquali, Luisa Pastò, Elisabetta Pedrazzoli, Paola Perini, Ilaria Pesci, Maria Petracca, Alfredo Petrone, Carlo Piantadosi, Anna M. Pietroboni, Federica Pinardi, Marta Ponzano, Emilio Portaccio, Mattia Pozzato, Carlo Pozzilli, Luca Prosperini, Alessandra Protti, Paolo Ragonese, Sarah Rasia, Sabrina Realmuto, Anna Repice, Eleonora Rigoni, Maria Teresa Rilla, Francesca Rinaldi, Calogero Marcello Romano, Marco Ronzoni, Marco Rovaris, Francesca Ruscica, Loredana Sabattini, Giuseppe Salemi, Lorenzo Saraceno, Alessia Sartori, Arianna Sartori, Elvira Sbragia, Cinzia Scandellari, Ilaria Scarano Giuditta, Valentina Scarano, Valentina Schillaci, Maria Sessa, Caterina Sgarito, Grazia Sibilia, Gabriele Siciliano, Alessio Signori, Elisabetta Signoriello, Leonardo Sinisi, Francesca Sireci, Patrizia Sola, Claudio Solaro, Stefano Sotgiu, Maddalena Sparaco, Maria Laura Stromillo, Silvia Strumia, Laura Emanuela Susani, Giulietta Tabiadon, Francesco Teatini, Valentina Tomassini, Simone Tonietti, Clerici Valentina Torri, Carla Tortorella, Simona Toscano, Rocco Totaro, Maria Trotta, Gabriella Turano, Monica Ulivelli, Manzo Valentino, Giovanna Vaula, Domizia Vecchio, Marco Vercellino, Elena Pinuccia Verrengia, Marika Vianello, Eleonora Virgilio, Francesca Vitetta, Stefano Vollaro, Mauro Zaffaroni, Mauro Zampolini, Ignazio Roberto Zarbo, Antonio Zito, Luigi Zuliani, Sormani, M. P., Schiavetti, I., Landi, D., Carmisciano, L., De Rossi, N., Cordioli, C., Moiola, L., Radaelli, M., Immovilli, P., Capobianco, M., Brescia Morra, V., Trojano, M., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Fragoso, Y. D., Sen, S., Siva, A., Furlan, R., Salvetti, M., Bisecco, Alvino, Pia Sormani, Maria, Schiavetti, Irene, Landi, Doriana, Carmisciano, Luca, De Rossi, Nicola, Cordioli, Cinzia, Moiola, Lucia, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, Brescia Morra, Vincenzo, Trojano, Maria, Tedeschi, Gioacchino, Comi, Giancarlo, Alberto Battaglia, Mario, Patti, Francesco, Dadalti Fragoso, Yara, Sen, Sedat, Siva, Aksel, Furlan, Roberto, Salvetti, Marco, Study Group Gianmarco Abbadessa, MuSC-19, Aguglia, Umberto, Allegorico, Lia, Beatrice Maria Allegri, Rossi, Pia Amato, Maria, Annovazzi, Pietro, Antozzi, Carlo, Appendino, Lucia, Arena, Sebastiano, Baione, Viola, Balgera, Roberto, Barcella, Valeria, Baroncini, Damiano, Barrilà, Caterina, A Battaglia, Mario, Bellacosa, Alessandra, Bellucci, Gianmarco, Bergamaschi, Roberto, Bergamaschi, Valeria, Bezzini, Daiana, Biolzi, Beatrice, Bonavita, Simona, Borriello, Giovanna, Bosa, Chiara, Bosco, Antonio, Bovis, Francesca, Bozzali, Marco, Brambilla, Laura, Vincenzo Brescia, Morra, Brichetto, Giampaolo, Buccafusca, Maria, Bucciantini, Elisabetta, Bucello, Sebastiano, Chiara Buscarinu, Maria, Paola Cabboi, Maria, Calabrese, Massimiliano, Calabria, Francesca, Caleri, Francesca, Camilli, Federico, Maria Caniatti, Luisa, Cantello, Roberto, Capra, Ruggero, Capuano, Rocco, Carta, Patrizia, Cavalla, Paola, Grazia Celani, Maria, Cellerino, Maria, Cerqua, Raffaella, Chisari, Clara, Clerici, Raffaella, Clerico, Marinella, Cocco, Eleonora, Cola, Gaia, Confalonieri, Paolo, Conte, Antonella, Zaffira Conti, Marta, Cordano, Christian, Cordera, Susanna, Corea, Francesco, Correale, Claudio, Cottone, Salvatore, Crescenzo, Francesco, Curti, Erica, D'Ambrosio, Alessandro, D'Amico, Emanuele, Chiara Danni, Maura, D'Arma, Alessia, Dattola, Vincenzo, de Biase, Stefano, De Luca, Giovanna, Federica De Mercanti, Stefania, De Mitri, Paolo, De Stefano, Nicola, Della Cava, Marco, di Napoli, Mario, Di Sapio, Alessia, Docimo, Renato, Dutto, Anna, Evangelista, Luana, Fanara, Salvatore, Ferraro, Diana, Teresa Ferrò, Maria, Filippi, Massimo, Fioretti, Cristina, Fratta, Mario, Frau, Jessica, Fronza, Marzia, Gajofatto, Alberto, Gallo, Antonio, Gallo, Paolo, Gasperini, Claudio, Ghazaryan, Anna, Giometto, Bruno, Gobbin, Francesca, Govone, Flora, Granella, Franco, Grange, Erica, Grazia Grasso, Maria, Guareschi, Angelica, Guaschino, Clara, Guerrieri, Simone, Guidetti, Donata, Iaffaldano, Pietro, Ianniello, Antonio, Iasevoli, Luigi, Imperiale, Daniele, Teresa Infante, Maria, Inglese, Matilde, Iodice, Rosa, Iovino, Aniello, Konrad, Giovanna, Lanzillo, Roberta, Lapucci, Caterina, Lavorgna, Luigi, L'Episcopo Maria, Rita, Leva, Serena, Liberatore, Giuseppe, Lo Re, Marianna, Longoni, Marco, Lopiano, Leonardo, Lorefice, Lorena, Lucchini, Matteo, Lus, Giacomo, Maimone, Davide, Malentacchi, Maria, Mallucci, Giulia, Malucchi, Simona, Rosa Mancinelli, Chiara, Mancinelli, Luca, Manganotti, Paolo, Giorgia Maniscalco, Teresa, Mantero, Vittorio, Marangoni, Sabrina, Marastoni, Damiano, Girolama Marfia, Alessandra, Marinelli, Fabiana, Marti, Alessandro, Martinelli Boneschi, Filippo, Masserano Zoli, Federco, Matta, Francesca, Mendozzi, Laura, Meucci, Giuseppe, Miante, Silvia, Miele, Giuseppina, Milano, Eva, Mirabella, Massimiliano, Missione, Rosanna, Moccia, Marcello, Montepietra, Sara, Monti Bragadin, Margherita, Montini, Federico, Motta, Roberta, Nardone, Raffaele, Gabri Nicoletti, Carolina, Nobile-Orazio, Eduardo, Nozzolillo, Agostino, Onofrj, Marco, Orlandi, Riccardo, Palmieri, Anna, Paolicelli, Damiano, Pasquali, Livia, Pastò, Luisa, Pedrazzoli, Elisabetta, Perini, Paola, Pesci, Ilaria, Petracca, Maria, Petrone, Alfredo, Piantadosi, Carlo, M Pietroboni, Anna, Pinardi, Federica, Ponzano, Marta, Portaccio, Emilio, Pozzato, Mattia, Pozzilli, Carlo, Prosperini, Luca, Protti, Alessandra, Ragonese, Paolo, Rasia, Sarah, Realmuto, Sabrina, Repice, Anna, Rigoni, Eleonora, Teresa Rilla, Maria, Rinaldi, Francesca, Marcello Romano, Calogero, Ronzoni, Marco, Rovaris, Marco, Ruscica, Francesca, Sabattini, Loredana, Salemi, Giuseppe, Saraceno, Lorenzo, Sartori, Alessia, Sartori, Arianna, Sbragia, Elvira, Scandellari, Cinzia, Scarano Giuditta, Ilaria, Scarano, Valentina, Schillaci, Valentina, Sessa, Maria, Sgarito, Caterina, Sibilia, Grazia, Siciliano, Gabriele, Signori, Alessio, Signoriello, Elisabetta, Sinisi, Leonardo, Sireci, Francesca, Sola, Patrizia, Solaro, Claudio, Sotgiu, Stefano, Sparaco, Maddalena, Laura Stromillo, Maria, Strumia, Silvia, Emanuela Susani, Laura, Tabiadon, Giulietta, Teatini, Francesco, Tomassini, Valentina, Tonietti, Simone, Valentina Torri, Clerici, Tortorella, Carla, Toscano, Simona, Totaro, Rocco, Trotta, Maria, Turano, Gabriella, Ulivelli, Monica, Valentino, Manzo, Vaula, Giovanna, Vecchio, Domizia, Vercellino, Marco, Pinuccia Verrengia, Elena, Vianello, Marika, Virgilio, Eleonora, Vitetta, Francesca, Vollaro, Stefano, Zaffaroni, Mauro, Zampolini, Mauro, Roberto Zarbo, Ignazio, Zito, Antonio, Zuliani, Luigi, Abbadessa, Gianmarco, Trotta, Maria Consiglia, and Zito, Guido Antonio

Subjects
0301 basic medicine, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), immunosuppressive therapie, coronavirus, Settore MED/26, medicine.disease_cause, Antibodies, Viral, immunosuppressive therapies, Antibodies, Serology, Cohort Studies, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Seroepidemiologic Studies, Pandemic, Medicine, Humans, Multiple sclerosi, Viral, Coronavirus, business.industry, immunomodulatory therapie, immunomodulatory therapies, COVID-19, medicine.disease, Virology, coronaviru, Settore MED/26 - NEUROLOGIA, Sars-COV-2, 030104 developmental biology, Neurology, Neurology (clinical), business, SARS-CoV-2, Multiple Sclerosis, 030217 neurology & neurosurgery, Cohort study
Abstract

Background: The MuSC-19 project is an Italian cohort study open to international partners that collects data on multiple sclerosis (MS) patients with COVID-19. During the second wave of the pandemic, serological tests became routinely available. Objective: To evaluate the seroprevalence of anti-SARS-CoV-2 antibodies according to the use of disease-modifying therapy (DMT) in a subset of patients included in the MuSC-19 data set who had undergone a serological test. Methods: We evaluated the association between positive serological test results and time elapsed since infection onset, age, sex, Expanded Disability Status Scale score, comorbidities and DMT exposure using a multivariable logistic model. Results: Data were collected from 423 patients (345 from Italy, 61 from Turkey and 17 from Brazil) with a serological test performed during follow-up. Overall, 325 out of 423 tested patients (76.8%) had a positive serological test. At multivariate analysis, therapy with anti-CD20 was significantly associated with a reduced probability of developing antibodies after COVID-19 (odds ratio (OR) = 0.20, p = 0.002). Conclusion: Patients with MS maintain the capacity to develop humoral immune response against SARS-COV-2, although to a lesser extent when treated with anti-CD20 drugs. Overall, our results are reassuring with respect to the possibility to achieve sufficient immunization with vaccination.

Published
2021

50. Early clinical markers of aggressive multiple sclerosis

Author

Tomas Kalincik, Marc Girard, Guillermo Izquierdo, Cristina Ramo-Tello, Francois Grand'Maison, Ali Manouchehrinia, Youssef Sidhom, Charles B Malpas, Alexandre Prat, Maria Trojano, Franco Granella, Pamela A. McCombe, Rana Karabudak, Murat Terzi, Eugenio Pucci, Raymond Hupperts, Vincent Van Pesch, Pierre Grammond, Sifat Sharmin, Richard A L Macdonell, Ayse Altintas, Riadh Gouider, Recai Turkoglu, Diana Ferraro, Alessandra Lugaresi, Pierre Duquette, Helmut Butzkueven, Serkan Ozakbas, Sara Eichau, Izanne Roos, Daniele Spitaleri, Yara Dadalti Fragoso, Mark Slee, Roberto Bergamaschi, Jan Hillert, Edgardo Cristiano, Thor Petersen, Eva Havrdova, Javier Olascoaga, Cavit Boz, Patrizia Sola, Freek Verheul, Aysun Soysal, Tomas Olsson, Dana Horakova, Ondokuz Mayıs Üniversitesi, Malpas C.B., Manouchehrinia A., Sharmin S., Roos I., Horakova D., Havrdova E.K., Trojano M., Izquierdo G., Eichau S., Bergamaschi R., Sola P., Ferraro D., Lugaresi A., Prat A., Girard M., Duquette P., Grammond P., Grand'Maison F., Ozakbas S., van Pesch V., Granella F., Hupperts R., Pucci E., Boz C., Sidhom Y., Gouider R., Spitaleri D., Soysal A., Petersen T., Verheul F., Karabudak R., Turkoglu R., Ramo-Tello C., Terzi M., Cristiano E., Slee M., McCombe P., Macdonell R., Fragoso Y., Olascoaga J., Altintas A., Olsson T., Butzkueven H., Hillert J., Kalincik T., Altıntaş, Ayşe (ORCID 0000-0002-8524-5087 & YÖK ID 11611), School of Medicine, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, and UCL - (SLuc) Service de neurologie

Subjects
Male, PROGRESSION, Disease, multiple sclerosis, 01 natural sciences, THERAPY, Severity of Illness Index, Aggressive disease, 010104 statistics & probability, Disability Evaluation, 0302 clinical medicine, PROGNOSTIC-FACTORS, Multiple Sclerosi, Disability, Multiple sclerosis, Precision medicine, Prediction, R PACKAGE, Age of Onset, AcademicSubjects/SCI01870, Neurosciences and neurology, IMPAIRMENT, Cohort, Disease Progression, RELAPSE RATE, Female, Cohort study, Human, Adult, medicine.medical_specialty, Multiple Sclerosis, precision medicine, BRAIN MRI, Sensitivity and Specificity, 03 medical and health sciences, Internal medicine, Severity of illness, medicine, Humans, 0101 mathematics, Letters to the Editor, Expanded Disability Status Scale, business.industry, NATURAL-HISTORY, prediction, medicine.disease, PREDICTIVE-VALUE, Confidence interval, disability, AcademicSubjects/MED00310, Neurology (clinical), Age of onset, business, aggressive disease, 030217 neurology & neurosurgery, LONG-TERM DISABILITY
Abstract

Patients with the 'aggressive' form of multiple sclerosis accrue disability at an accelerated rate, typically reaching Expanded Disability Status Score (EDSS) ≥ 6 within 10 years of symptom onset. Several clinicodemographic factors have been associated with aggressive multiple sclerosis, but less research has focused on clinical markers that are present in the first year of disease. The development of early predictive models of aggressive multiple sclerosis is essential to optimize treatment in this multiple sclerosis subtype. We evaluated whether patients who will develop aggressive multiple sclerosis can be identified based on early clinical markers. We then replicated this analysis in an independent cohort. Patient data were obtained from the MSBase observational study. Inclusion criteria were (i) first recorded disability score (EDSS) within 12 months of symptom onset; (ii) at least two recorded EDSS scores; and (iii) at least 10 years of observation time, based on time of last recorded EDSS score. Patients were classified as having 'aggressive multiple sclerosis' if all of the following criteria were met: (i) EDSS ≥ 6 reached within 10 years of symptom onset; (ii) EDSS ≥ 6 confirmed and sustained over ≥6 months; and (iii) EDSS ≥ 6 sustained until the end of follow-up. Clinical predictors included patient variables (sex, age at onset, baseline EDSS, disease duration at first visit) and recorded relapses in the first 12 months since disease onset (count, pyramidal signs, bowel-bladder symptoms, cerebellar signs, incomplete relapse recovery, steroid administration, hospitalization). Predictors were evaluated using Bayesian model averaging. Independent validation was performed using data from the Swedish Multiple Sclerosis Registry. Of the 2403 patients identified, 145 were classified as having aggressive multiple sclerosis (6%). Bayesian model averaging identified three statistical predictors: age > 35 at symptom onset, EDSS ≥ 3 in the first year, and the presence of pyramidal signs in the first year. This model significantly predicted aggressive multiple sclerosis [area under the curve (AUC) = 0.80, 95% confidence intervals (CIs): 0.75, 0.84, positive predictive value = 0.15, negative predictive value = 0.98]. The presence of all three signs was strongly predictive, with 32% of such patients meeting aggressive disease criteria. The absence of all three signs was associated with a 1.4% risk. Of the 556 eligible patients in the Swedish Multiple Sclerosis Registry cohort, 34 (6%) met criteria for aggressive multiple sclerosis. The combination of all three signs was also predictive in this cohort (AUC = 0.75, 95% CIs: 0.66, 0.84, positive predictive value = 0.15, negative predictive value = 0.97). Taken together, these findings suggest that older age at symptom onset, greater disability during the first year, and pyramidal signs in the first year are early indicators of aggressive multiple sclerosis., National Health and Medical Research Council of Australia; Roche; Merck; Biogen; Novartis; Bayer Schering; Sanofi Genzyme; Teva

Published
2020

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