Tocilizumab modulates the activity of the classical and alternative complement pathways in rheumatoid arthritis patients
BackgroundTocilizumab (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.ObjectiveTo evalu...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1486588/full |
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| author | Iván Ferraz-Amaro Iván Ferraz-Amaro Sergio Santos-Concepción Javier Castro-Hernández Maria Vanesa Hernández-Hernández Beatriz Tejera Segura Cristina Luna Esmeralda Delgado-Frias Federico Díaz-González Federico Díaz-González Federico Díaz-González |
| author_facet | Iván Ferraz-Amaro Iván Ferraz-Amaro Sergio Santos-Concepción Javier Castro-Hernández Maria Vanesa Hernández-Hernández Beatriz Tejera Segura Cristina Luna Esmeralda Delgado-Frias Federico Díaz-González Federico Díaz-González Federico Díaz-González |
| author_sort | Iván Ferraz-Amaro |
| collection | DOAJ |
| description | BackgroundTocilizumab (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.ObjectiveTo evaluate the effect of systemic IL-6 inhibition on complement pathways functional activity in RA patients treated with TCZ.DesingProspective non-interventional study.MethodsTwenty-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.ResultsAfter 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.ConclusionTCZ 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. |
| format | Article |
| id | doaj-art-8cb2e0be3fc5432889692f94a87ebf76 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-8cb2e0be3fc5432889692f94a87ebf762025-01-30T05:10:07ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.14865881486588Tocilizumab modulates the activity of the classical and alternative complement pathways in rheumatoid arthritis patientsIván Ferraz-Amaro0Iván Ferraz-Amaro1Sergio Santos-Concepción2Javier Castro-Hernández3Maria Vanesa Hernández-Hernández4Beatriz Tejera Segura5Cristina Luna6Esmeralda Delgado-Frias7Federico Díaz-González8Federico Díaz-González9Federico Díaz-González10Servicio de Reumatología, Hospital Universitario de Canarias, San Cristóbal de La Laguna, SpainDepartamento de Medicina Interna, Dermatología y Psiquiatría, Universidad de La Laguna (ULL), San Cristóbal de La Laguna, SpainDepartamento de Medicina Física y Farmacología, Área de Farmacología Universidad de La Laguna (ULL), San Cristóbal de La Laguna, SpainDepartamento de Medicina Física y Farmacología, Área de Farmacología Universidad de La Laguna (ULL), San Cristóbal de La Laguna, SpainServicio de Reumatología, Hospital Universitario de Canarias, San Cristóbal de La Laguna, SpainServicio de Reumatología, Hospital Universitario Insular-Materno infantil de Canarias, Las Palmas de Gran Canarias, SpainServicio de Reumatología, Hospital Nuestra Señora de la Candelaria, Santa Cruz de Tenerife, SpainServicio de Reumatología, Hospital Universitario de Canarias, San Cristóbal de La Laguna, SpainServicio de Reumatología, Hospital Universitario de Canarias, San Cristóbal de La Laguna, SpainDepartamento de Medicina Interna, Dermatología y Psiquiatría, Universidad de La Laguna (ULL), San Cristóbal de La Laguna, SpainInstituto Universitario de Tecnología Biomédica (ITB), Universidad de La Laguna, San Cristóbal de La Laguna, SpainBackgroundTocilizumab (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.ObjectiveTo evaluate the effect of systemic IL-6 inhibition on complement pathways functional activity in RA patients treated with TCZ.DesingProspective non-interventional study.MethodsTwenty-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.ResultsAfter 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.ConclusionTCZ 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1486588/fulltocilizumabrheumatoid arthritisdisease activityclassical complement system activityalternative complement system activity |
| spellingShingle | Iván Ferraz-Amaro Iván Ferraz-Amaro Sergio Santos-Concepción Javier Castro-Hernández Maria Vanesa Hernández-Hernández Beatriz Tejera Segura Cristina Luna Esmeralda Delgado-Frias Federico Díaz-González Federico Díaz-González Federico Díaz-González Tocilizumab modulates the activity of the classical and alternative complement pathways in rheumatoid arthritis patients Frontiers in Immunology tocilizumab rheumatoid arthritis disease activity classical complement system activity alternative complement system activity |
| title | Tocilizumab modulates the activity of the classical and alternative complement pathways in rheumatoid arthritis patients |
| title_full | Tocilizumab modulates the activity of the classical and alternative complement pathways in rheumatoid arthritis patients |
| title_fullStr | Tocilizumab modulates the activity of the classical and alternative complement pathways in rheumatoid arthritis patients |
| title_full_unstemmed | Tocilizumab modulates the activity of the classical and alternative complement pathways in rheumatoid arthritis patients |
| title_short | Tocilizumab modulates the activity of the classical and alternative complement pathways in rheumatoid arthritis patients |
| title_sort | tocilizumab modulates the activity of the classical and alternative complement pathways in rheumatoid arthritis patients |
| topic | tocilizumab rheumatoid arthritis disease activity classical complement system activity alternative complement system activity |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1486588/full |
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