OBJECTIVE: To verify the hypothesis of an age-dependent increase of infections and neoplasms in patients with multiple sclerosis (MS) under disease-modifying treatments (DMTs) with different mechanisms of action. METHODS: We extracted relevant data from 45 randomized clinical trials (RCTs) on currently licensed DMTs. We fitted inverse-variance weighted meta-regressions with random-effects models to estimate whether age and/or mechanism of action (immunomodulatory, sequestrating, and depletive) of currently licensed DMTs influenced the difference between experimental arm and control arm in the incidence of specific adverse events, namely, overall infections, opportunistic infections, and neoplasms. RESULTS: A higher incidence of overall infections was observed in RCTs with depletive DMTs (event-rate ratio = 1.25, p < 0.001). Herpetic infections were more frequently observed in RCTs with both depletive (event-rate ratio = 3.51, p < 0.001) and, to a lesser extent, sequestrating DMTs (event-rate ratio = 1.52, p = 0.078). The interaction of age with depletive DMTs was associated with higher incidence of neoplasms (p = 0.017), especially above 45 years of age. DISCUSSION: Our study supports a detrimental effect of age on the safety profile of depletive DMTs, with an increased incidence of neoplasms especially over 45 years of age. We failed to demonstrate an age-related increased incidence of infections, possibly due to latency in their occurrence.
OBJECTIVE: To verify the hypothesis of an age-dependent increase of infections and neoplasms in patients with multiple sclerosis (MS) under disease-modifying treatments (DMTs) with different mechanisms of action. METHODS: We extracted relevant data from 45 randomized clinical trials (RCTs) on currently licensed DMTs. We fitted inverse-variance weighted meta-regressions with random-effects models to estimate whether age and/or mechanism of action (immunomodulatory, sequestrating, and depletive) of currently licensed DMTs influenced the difference between experimental arm and control arm in the incidence of specific adverse events, namely, overall infections, opportunistic infections, and neoplasms. RESULTS: A higher incidence of overall infections was observed in RCTs with depletive DMTs (event-rate ratio = 1.25, p < 0.001). Herpetic infections were more frequently observed in RCTs with both depletive (event-rate ratio = 3.51, p < 0.001) and, to a lesser extent, sequestrating DMTs (event-rate ratio = 1.52, p = 0.078). The interaction of age with depletive DMTs was associated with higher incidence of neoplasms (p = 0.017), especially above 45 years of age. DISCUSSION: Our study supports a detrimental effect of age on the safety profile of depletive DMTs, with an increased incidence of neoplasms especially over 45 years of age. We failed to demonstrate an age-related increased incidence of infections, possibly due to latency in their occurrence.
Authors: Dimitrios Papadopoulos; Panagiotis Gklinos; Giorgos Psarros; Konstantina Drellia; Eumorphia Maria Delicha; Tim Friede; Dimos D Mitsikostas; Richard S Nicholas Journal: J Neurol Date: 2022-01-23 Impact factor: 4.849
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Authors: Huah Shin Ng; Jonas Graf; Feng Zhu; Elaine Kingwell; Orhan Aktas; Philipp Albrecht; Hans-Peter Hartung; Sven G Meuth; Charity Evans; John D Fisk; Ruth Ann Marrie; Yinshan Zhao; Helen Tremlett Journal: Front Immunol Date: 2022-01-13 Impact factor: 7.561
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Authors: Carmen Picón; Amalia Tejeda-Velarde; José Ignacio Fernández-Velasco; Manuel Comabella; Roberto Álvarez-Lafuente; Ester Quintana; Susana Sainz de la Maza; Enric Monreal; Noelia Villarrubia; José Carlos Álvarez-Cermeño; María Inmaculada Domínguez-Mozo; Lluís Ramió-Torrentà; Eulalia Rodríguez-Martín; Ernesto Roldán; Yolanda Aladro; Silvia Medina; Mercedes Espiño; Jaime Masjuan; Clara Matute-Blanch; Marta Muñoz-San Martín; Carmen Espejo; Carmen Guaza; Alfonso Muriel; Lucienne Costa-Frossard; Luisa María Villar Journal: Front Immunol Date: 2021-07-12 Impact factor: 7.561