Biomarkers of response to ocrelizumab in relapsing-remitting multiple sclerosis
Por:
Rodríguez-Jorge, F, Fernández-Velasco, JI, Villarrubia, N, Gracia-Gil, J, Fernández, E, Meca-Lallana, V, Díaz-Pérez, C, Sainz de la Maza, S, Pacheco, EM, Quiroga, A, Ramió-Torrentà, L, Martínez-Yélamos, S, Bau, L, Monreal, E, López-Real, A, Rodero-Romero, A, Borrega, L, Díaz, S, Eguía, P, Espiño, M, Chico-García, JL, Barrero, FJ, Martínez-Ginés, ML, García-Domínguez, JM, De la Fuente, S, Moreno, I, Sainz-Amo, R, Mañé-Martínez, MA, Caminero, A, Castellanos, F, Gómez López, A, Labiano-Fontcuberta, A, Ayuso, L, Abreu, R, Hernández, MA, Meca-Lallana, J, Martín-Aguilar, L, Muriel García, A, Masjuan, J, Costa-Frossard, L, Villar, LM
Publicada:
12 nov 2024
Resumen:
Objective: To ascertain the changes of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) values in relapsing-remitting multiple sclerosis (RRMS) patients treated with ocrelizumab and their association with treatment response.
Methods: Multicenter prospective study including 115 RRMS patients initiating ocrelizumab treatment between February 2020 and March 2022 followed during a year. Serum samples were collected at baseline and every 3 months to measure sNfL and sGFAP levels using single-molecule array (SIMOA) technology. Based on age and body mass index, sNfL values were standardized using z-score. NEDA (non-evidence of disease activity)-3 status was defined for patients free of disease activity after a year of follow-up. Inflammation (INFL) was considered when new relapses occurred during follow-up or new MRI lesions were found at 1-year exploration. PIRA (progression independent of relapse activity) was defined as disability progression occurring in the absence of relapses or new MRI activity.
Results: After a year on ocrelizumab, 85 patients (73.9%) achieved NEDA-3. Thirty patients did not achieve NEDA: 20 (17.4%) because of INFL and 10 (8.7%) because of PIRA. Of INFL patients, 6 (30.0%) had relapses, and 17 (85.0%) had at least one new MRI lesion at the 12-month examination. At baseline, INFL patients had higher sNfL (p = 0.0003) and sGFAP (p = 0.03) than the NEDA-3 group. PIRA patients mostly exhibited low sNfL and heterogeneous sGFAP levels. After a year, NEDA-3 and INFL patients showed similar decreases in sNfL (p < 0.0001) and sGFAP (p < 0.0001 for NEDA-3 and p = 0.001 for INFL ones). However, the decrease occurred earlier in NEDA-3 patients. Accordingly, sNfL > 1.5 z-score 3 months after ocrelizumab initiation indicated a higher risk of inflammation (OR = 13.6; p < 0.0001). Decrease in sGFAP values occurred later in both groups, with significant reductions observed at 12 months for INFL and 6 and 12 months for NEDA-3. No significant changes in sNfL or sGFAP were observed in PIRA patients.
Conclusion: Ocrelizumab induced normalization of sNfL and sGFAP in the majority of NEDA-3 and inflammatory patients but did not cause changes in the PIRA group. Our data suggest that normalization of sNfL and sGFAP is associated with the lack of inflammatory-associated disease progression but it may not affect non-inflammatory PIRA.
Filiaciones:
Rodríguez-Jorge, F:
Hosp Univ Ramon Cajal, Dept Neurol, Madrid, Spain
Fernández-Velasco, JI:
Hosp Univ Ramon Cajal, Dept Immunol, Madrid, Spain
Villarrubia, N:
Hosp Univ Ramon Cajal, Dept Immunol, Madrid, Spain
Gracia-Gil, J:
Complejo Hosp Univ Albacete, Dept Neurol, Albacete, Spain
Fernández, E:
Complejo Hosp Univ Albacete, Dept Neurol, Albacete, Spain
Meca-Lallana, V:
Hosp Univ Princesa, Dept Neurol, Madrid, Spain
Díaz-Pérez, C:
Hosp Univ Princesa, Dept Neurol, Madrid, Spain
Sainz de la Maza, S:
Hosp Univ Ramon Cajal, Dept Immunol, Madrid, Spain
Pacheco, EM:
Hosp Univ Juan Ramon Jimenez, Dept Neurol, Huelva, Spain
Quiroga, A:
Hosp Univ Gerona Doctor Josep Trueta, Dept Neurol, Girona, Spain
Ramió-Torrentà, L:
Hosp Univ Gerona Doctor Josep Trueta, Dept Neurol, Girona, Spain
Martínez-Yélamos, S:
Hosp Univ Bellvitge, Dept Neurol, Barcelona, Spain
Bau, L:
Hosp Univ Bellvitge, Dept Neurol, Barcelona, Spain
Monreal, E:
Hosp Univ Ramon Cajal, Dept Neurol, Madrid, Spain
López-Real, A:
Complejo Hosp Univ Coruna, Dept Neurol, La Coruna, Spain
Rodero-Romero, A:
Hosp Univ Ramon Cajal, Dept Immunol, Madrid, Spain
Borrega, L:
Hosp Univ Fdn Alcorcon, Dept Neurol, Madrid, Spain
Díaz, S:
Hosp Univ Gran Canaria Doctor Negrin, Dept Neurol, Gran Canaria, Spain
Eguía, P:
Hosp Univ Gran Canaria Doctor Negrin, Dept Neurol, Gran Canaria, Spain
Espiño, M:
Hosp Univ Ramon Cajal, Dept Immunol, Madrid, Spain
Chico-García, JL:
Hosp Univ Ramon Cajal, Dept Neurol, Madrid, Spain
Barrero, FJ:
Hosp Univ Clinico San Cecilio Granada, Dept Neurol, Granada, Spain
Martínez-Ginés, ML:
Hosp Gen Univ Gregorio Maranon, Dept Neurol, Madrid, Spain
García-Domínguez, JM:
Hosp Gen Univ Gregorio Maranon, Dept Neurol, Madrid, Spain
De la Fuente, S:
Hosp Univ Doce Octubre, Dept Neurol, Madrid, Spain
Moreno, I:
Hosp Univ Fdn Jimenez Diaz, Dept Neurol, Madrid, Spain
Sainz-Amo, R:
Hosp Univ Ramon Cajal, Dept Neurol, Madrid, Spain
Hosp Univ Ramon Cajal, Dept Immunol, Madrid, Spain
Mañé-Martínez, MA:
Hosp Univ Joan XXII, Dept Neurol, Tarragona, Spain
Caminero, A:
Dept Neurol, Complejo Asistencial Avila, Avila, Spain
Castellanos, F:
Hosp Virgen Puerto, Dept Neurol, Caceres, Spain
Gómez López, A:
Hosp Univ Doce Octubre, Dept Neurol, Madrid, Spain
Labiano-Fontcuberta, A:
Hosp Univ Doce Octubre, Dept Neurol, Madrid, Spain
Ayuso, L:
Hosp Univ Principe Asturias, Dept Neurol, Madrid, Spain
Abreu, R:
Hosp Univ Nuestra Senora Candelaria, Dept Neurol, Tenerife, Spain
Hernández, MA:
Hosp Univ Nuestra Senora Candelaria, Dept Neurol, Tenerife, Spain
Meca-Lallana, J:
Hosp Clinico Univ Virgen Arrixaca, Dept Neurol, Murcia, Spain
Martín-Aguilar, L:
Hosp Santa Creu & Sant Pau, Dept Neurol, Barcelona, Spain
Muriel García, A:
Hosp Univ Ramon Cajal, Biostat Dept, Madrid, Spain
Masjuan, J:
Hosp Univ Ramon Cajal, Dept Neurol, Madrid, Spain
Costa-Frossard, L:
Hosp Univ Ramon Cajal, Dept Neurol, Madrid, Spain
Villar, LM:
Hosp Univ Ramon Cajal, Dept Immunol, Madrid, Spain
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