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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1486588

Tocilizumab modulates the activity of the classical and alternative complement pathways in rheumatoid arthritis patients

Provisionally accepted
Iván Ferraz-Amaro Iván Ferraz-Amaro 1,2Sergio Santos-Concepción Sergio Santos-Concepción 3Javier Castro Hernández Javier Castro Hernández 3Maria Vanesa Hernández-Hernández Maria Vanesa Hernández-Hernández 1Beatriz Tejera Segura Beatriz Tejera Segura 4Cristina Luna Cristina Luna 5Esmeralda Delgado-Frias Esmeralda Delgado-Frias 1Federico Diaz-Gonzalez Federico Diaz-Gonzalez 1,2,6*
  • 1 Servicio de Reumatología. Hospital Universitario de Canarias, La Laguna, Spain
  • 2 Departamento de Medicina Interna, Dermatología y Psiquiatría. Universidad de La Laguna, La Laguna, Spain
  • 3 Departamento de Farmacologia. Universidad de La Laguna, La Laguna, Spain
  • 4 Servicio de Reumatología. Hospital Universitario Insular-Materno infantil de Canarias, Las Palmas de Gran Canaria, Spain
  • 5 Servicio de Reumatología. Hospital Nuestra Señora de la Candelaria, Santa Cruz de Tenerife, Spain
  • 6 Instituto Universitario de Tecnología Biomédica (ITB). Universidad de La Laguna, La Laguna, Spain

The final, formatted version of the article will be published soon.

    Background: Tocilizumab (TCZ) is a monoclonal antibody that neutralizes interleukin (IL)-6 and is indicated for diseases characterized by markedly elevated inflammatory markers, such as rheumatoid arthritis (RA). The complement system has been implicated in the etiopathogenesis of RA.Objective: To evaluate the effect of systemic IL-6 inhibition on complement pathways functional activity in RA patients treated with TCZ.Desing: Prospective non-interventional study.Methods. Twenty-seven RA patients included in the TOCRIVAR study who received TCZ (8mg/kg IV/q4w) were evaluated at baseline and at weeks 12, 24 and 52 of treatment. Disease activity, as assessed by composite indices, acute phase reactants, and new-generation functional assays of the three complement pathways, was evaluated at baseline and at each follow-up visit. Multivariable linear mixed models were used to determine changes in the complement system cascades over time.Results: After adjustment for disease activity, basal levels of the classical and alternative pathways decreased significantly after TCZ treatment. The effect on the classical pathway remained significant after 52 weeks. The decrease in the alternative pathway was significant at weeks 12 and 24, but not at week 52 of TCZ treatment. TCZ had no effect on the lectin cascade throughout the follow-up.TCZ reduces the activity of the classical and alternative pathways of the complement system in RA patients regardless of the improvement in disease activity. This finding may contribute to a better understanding of the mechanisms by which the IL-6 blockade reduces disease activity in RA patients..

    Keywords: tocilizumab, Rheumatoid arthritis, disease activity, classical complement system activity, alternative complement system activity

    Received: 26 Aug 2024; Accepted: 08 Jan 2025.

    Copyright: © 2025 Ferraz-Amaro, Santos-Concepción, Castro Hernández, Hernández-Hernández, Tejera Segura, Luna, Delgado-Frias and Diaz-Gonzalez. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Federico Diaz-Gonzalez, Departamento de Medicina Interna, Dermatología y Psiquiatría. Universidad de La Laguna, La Laguna, Spain

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.