The combination of IL-6 and its soluble receptor is associated with the response of rheumatoid arthritis patients to tocilizumab |
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| Affiliation: | 1. Department of Rheumatology, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain;2. Department of Immunology, Institut de Recerca, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain;3. Unit of Rheumatology, Hospital Clinic de Barcelona, Barcelona, Spain;4. Department of Rheumatology, Hospital Moises Broggi, Sant Joan Despí, Spain;5. Unit of Rheumatology, Hospital de la Vall d’Hebron, Barcelona, Spain;6. Department of Rheumatology, Hospital de Viladecans, Viladecans, Spain;1. Department of Onco-Hematology, Division of Medical Oncology, Centro di Riferimento Oncologico della Basilicata, IRCCS, Rionero in Vulture (PZ), Italy;2. Department of Surgery, Oncology and Gastroenterology, Oncology Section, University of Padova, Padova, Italy;3. IOV-IRCCS, Padova, Italy;4. Laboratory of Clinical Research and Molecular Diagnostics, Centro di Riferimento Oncologico della Basilicata, IRCCS, Rionero in Vulture (PZ), Italy;5. Hospital Pharmacy, Centro di Riferimento Oncologico della Basilicata, IRCCS, Rionero in Vulture (PZ), Italy;1. Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, No. 201, Section 2. Shih-Pai Road, Taipei 11217, Taiwan;2. School of Medicine, National Yang-Ming University, Taiwan;3. Cancer Center, Taipei Veterans General Hospital, Taiwan;4. Department of Pathology, Taipei Veterans General Hospital, Taiwan;1. Hospital Moisès Broggi, Sant Joan Despí, Barcelona, España;2. Hospital de l’Hospitalet, Barcelona, España;3. Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, España;4. Hospital Universitari de la Santa Creu, i Sant Pau, Barcelona, España;5. Hospital Universitari Mútua de Terrassa, Barcelona, España;6. Hospital Clínic Universitari, Barcelona, España;7. Hospital de Viladecans, Barcelona, España;8. Hospital Residència Sant Camil, Barcelona, España;9. Hospital de Palamós, Girona, España;10. Hospital Sant Pau i Santa Tecla, Tarragona, España;11. Hospital de Tortosa Verge de la Cinta, Tarragona, España;12. Institut Poal de Reumatologia, Barcelona, España;13. Hospital General Universitari de la Vall d’Hebrón, Barcelona, España;14. Hospital Universitari Parc Taulí de Sabadell, Barcelona, España;15. Hospital General de Granollers, Barcelona, España;p. Parc de Salut Mar, Barcelona, España;q. Hospital de Mollet, Barcelona, España;r. Hospital de Sant Boi, Barcelona, España;s. Centre Internacional de Medicina Avançada (CIMA), Barcelona, España;1. Servicio de Medicina Interna, Hospital Vega Baja de Orihuela (Alicante), España. Residente de Medicina de Familia y Atención Comunitaria;2. Sección de Reumatología. Servicio de Medicina Interna. Hospital Vega Baja de Orihuela (Alicante), España;3. Servicio de Medicina Interna. Hospital Vega Baja de Orihuela (Alicante), España;1. Division of Rheumatology, David Geffen School of Medicine, University of California (UCLA), Los Angeles, USA;2. Dept. of Rheumatology, Sint Maartenskliniek, PO Box 9011, 6500 GM, Nijmegen, The Netherlands;1. F. Hoffman–La Roche Ltd, Basel, Switzerland;2. Genentech Inc, South San Francisco, California;3. Partnership for Health Analytic Research, LLC, Beverly Hills, California |
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| Abstract: | BackgroundIL-6 contributes significantly to the chronic inflammatory process of rheumatoid arthritis (RA). Tocilizumab, a humanized anti-human IL-6 receptor antibody that blocks the signaling originated by the IL-6/IL-6R complex, is an effective treatment. However, predictors of the response to tocilizumab are still required. We aimed to combine IL-6 and soluble IL-6R (sIL-6R) levels to identify groups of responses.MethodsHeparinized blood and clinical data from 63 RA patients were collected before treatment and after 3 and 6 months. Two-step clustering (SPSS v.18) was used to establish the relationship between IL-6 and sIL-6R. Then, we compared European League Against Rheumatism (EULAR) response criteria with remission achievement in the groups of patients.ResultsThree statistical significant clusters of RA patients (i.e., g1, g2, and g3) were defined by serum concentrations of IL-6 and sIL-6R at baseline. All groups of RA patients had higher IL-6 and sIL-6R levels than healthy donors. The levels of IL-6 expressed as median (IQR) in g1 patients were 124(90–183) pg/ml, in g2 12.3(4.4–24) pg/ml, and in g3 60.1(30–146) pg/ml (p < 0.001). The levels of sIL-6R expressed as mean ± sd in g1 patients were 250.5 ± 72 ng/ml, in g2 269.1 ± 125 ng/ml, and in g3 732.7 ± 243 ng/ml (p < 0.001). Disease activity score (DAS)28, C-reactive protein, and erythrocyte sedimentation rate were comparable in the three groups at baseline. Disease duration in g3 was the longest (median(IQR) years: g1 = 11(5–15), g2 = 12(8–20), and g3 23(16–26); p = 0.006), with years of disease evolution being correlated with sIL-6R levels (R = 0.417, p < 0.001). Simple and Clinical Disease Activity Index (SDAI and CDAI) decreased significantly in the three groups. However, EULAR response criteria and remission achievement at 6 m was different in the three groups (p = 0.03 and 0.04, respectively). In all. 17 out of the 18 patients in g1 had a good or moderate response to tocilizumab. Conversely, the percentage of patients with no response to tocilizumab was higher in g3 than in g1 and g2. We also observed different changing patterns of IL-6 and sIL-6R levels among the three groups.ConclusionsRA patients could be easily stratified prior to therapeutic intervention with two molecules related to the pathway blocked by tocilizumab. G1 patients, who had the best response to tocilizumab, had the highest level of IL-6 and the lowest level of sIL-6R. |
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| Keywords: | Rheumatoid arthritis IL-6 sIL-6R Tocilizumab |
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