Cesar Diaz-Torne1, Maria Dels Angels Ortiz2, Patricia Moya3, Maria Victoria Hernandez4, Delia Reina5, Ivan Castellvi3, Juan Jose De Agustin6, Diana de la Fuente7, Hector Corominas5, Raimon Sanmarti4, Carlos Zamora2, Elisabet Cantó2, Silvia Vidal8. 1. Department of Rheumatology, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain. Electronic address: cesardiaztorne@gmail.com. 2. Department of Immunology, Institut de Recerca, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain. 3. Department of Rheumatology, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain. 4. Unit of Rheumatology, Hospital Clinic de Barcelona, Barcelona, Spain. 5. Department of Rheumatology, Hospital Moises Broggi, Sant Joan Despí, Spain. 6. Unit of Rheumatology, Hospital de la Vall d'Hebron, Barcelona, Spain. 7. Department of Rheumatology, Hospital de Viladecans, Viladecans, Spain. 8. Department of Immunology, Institut de Recerca, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain. Electronic address: svidal@santpau.cat.
Abstract
BACKGROUND: IL-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. METHODS: Heparinized 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. RESULTS: Three 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 ± 72ng/ml, in g2 269.1 ± 125ng/ml, and in g3 732.7 ± 243ng/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 6m 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. CONCLUSIONS: RA 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.
BACKGROUND:IL-6 contributes significantly to the chronic inflammatory process of rheumatoid arthritis (RA). Tocilizumab, a humanized anti-humanIL-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. METHODS: Heparinized blood and clinical data from 63 RApatients 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. RESULTS: Three statistical significant clusters of RApatients (i.e., g1, g2, and g3) were defined by serum concentrations of IL-6 and sIL-6R at baseline. All groups of RApatients 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 ± 72ng/ml, in g2 269.1 ± 125ng/ml, and in g3 732.7 ± 243ng/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 6m 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. CONCLUSIONS:RApatients 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.
Authors: Aly M Abdelrahman; Yousuf Al Suleimani; Asem Shalaby; Mohammed Ashique; Priyadarsini Manoj; Badreldin H Ali Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2019-04-25 Impact factor: 3.000
Authors: Jessica D Murillo-Saich; Cesar Diaz-Torne; M Angeles Ortiz; Roxana Coras; Paulo Gil-Alabarse; Anders Pedersen; Hector Corominas; Silvia Vidal; Monica Guma Journal: Metabolomics Date: 2021-08-16 Impact factor: 4.747
Authors: Anita Boyapati; Sergio Schwartzman; Jérôme Msihid; Ernest Choy; Mark C Genovese; Gerd R Burmester; Gordon Lam; Toshio Kimura; Jonathan Sadeh; David M Weinreich; George D Yancopoulos; Neil M H Graham Journal: Arthritis Rheumatol Date: 2020-08-25 Impact factor: 10.995