{ "abstract": "Objectives To evaluate the dynamics of C3, C4 and anti-dsDNA antibody levels and their association with clinical activity and flares in patients with systemic lupus erythematosus (SLE) treated with belimumab (BEL).Methods Retrospective longitudinal cohort study from the BELILES-GEAS registry. Serological markers were assessed at the time of SLE diagnosis, at baseline, at each follow-up visit (months 3, 6, 12, 18, and 24 after treatment initiation) and during disease flares.Results A total of 371 patients were included, with a median drug exposure of 13.2 months. At baseline, 70.1% of patients were seropositive. SLE Disease Activity Index 2000 (SLEDAI-2K) and cSLEDAI scores and prednisone doses decreased significantly over time, whereas serum C3 and C4 levels, anti-dsDNA positivity and immunosuppressant use remained stable. Among 95 (25.6%) patients who experienced 139 (14.5%) flares, longitudinal analysis adjusted by immunosuppressant use and prednisone dose revealed no association between flare occurrence and low C3 or C4, whereas anti-dsDNA antibody positivity was (C3 OR=1.31, 95% CI 0.82 to 2.09; C4 OR=1.08, 95% CI 0.62 to 1.86, and anti-dsDNA OR=1.81, 95% CI 1.09 to 3.01, respectively). When stratified by flare severity, low C3 levels showed a borderline association with moderate-to-severe flares (OR=1.82, 95% CI 0.99 to 3.31), while no significant associations were observed for C4 or for mild flares. There was no association between serum level of C3 or C4 and cSLEDAI. The flare-discriminative performance of SLEDAI-2K and cSLEDAI was similar (AUC-ROCs 0.779 vs 0.781, p=0.88).Conclusion In SLE patients treated with BEL, the clinical utility of serological markers appears dissociated from disease activity. While C3 and C4 levels were not clearly related to disease activity or flares, low C3 levels showed a borderline association with moderate-to-severe flares, and anti-dsDNA positivity remained associated with increased flare risk, supporting a clinical assessment–driven approach with complementary use of anti-dsDNA.", "authors": [ { "affiliations": [ "Internal Medicine, Puerta de Hierro University Hospital of Majadahonda, Majadahonda, Spain", "Health Sciences School & Medical Center, UNIR, Logroño, Spain" ], "name": "Víctor Moreno-Torres" }, { "affiliations": [ "Biostatistics Unit, Fundación para la Investigación Biomédica del Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Spain" ], "name": "Ana Royuela" }, { "affiliations": [ "Internal Medicine, Girona Clinic, Girona, Spain" ], "name": "Guillem Policarpo-Torres" }, { "affiliations": [ "Internal Medicine, Cruces University Hospital, Barakaldo, Spain", "Autoimmune Diseases Research Unit, Instituto de Investigación Sanitaria Biobizkaia, Barakaldo, Spain" ], "name": "Diana Paredes Ruiz" }, { "affiliations": [ "Internal Medicine, Hospital La Fe, Valencia, Spain" ], "name": "María Calabuig" }, { "affiliations": [ "Unidad de Enfermedades Autoinmunes Sistémicas. Servicio de Medicina Interna, Hospital Universitario Virgen de las Nieves, Granada, Spain", "MP03-Medicina Interna-HVN Investiga, Instituto de Investigación Biosanitaria de Granada, Granada, Spain" ], "name": "Isabel Sánchez Berná" }, { "affiliations": [ "Internal Medicine, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Spain" ], "name": "Olga Capdevila Pons" }, { "affiliations": [ "Internal Medicine, Hospital Universitario de Jaén, Jaén, Spain" ], "name": "Augustín Colodro" }, { "affiliations": [ "Internal Medicine, Hospital Universitario Virgen del Rocío, Seville, Spain" ], "name": "José Salvador García-Morillo" }, { "affiliations": [ "Internal Medicine, Hospital Universitari Son Espases, Palma de Mallorca, Spain" ], "name": "Lucio Pallarés" }, { "affiliations": [ "Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain" ], "name": "Luis Trapiella" }, { "affiliations": [ "Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain" ], "name": "Adela Marin Ballvé" }, { "affiliations": [ "Internal Medicine, Hospital General Universitario Gregorio Marañón, Madrid, Spain" ], "name": "Cristina Lavilla-Olleros" }, { "affiliations": [ "Internal Medicine, Hospital Universitario San Cecilio, Granada, Spain" ], "name": "Jose Luis Callejas-Rubio" }, { "affiliations": [ "Internal Medicine, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain" ], "name": "Fernando Tornero" }, { "affiliations": [ "Hospital Universitario Sant Joan de Reus, Reus, Spain" ], "name": "Sandra Parra" }, { "affiliations": [ "Internal Medicine, Hospital de Terrassa, Terrassa, Spain" ], "name": "Ignasi Rodríguez-Pintó" }, { "affiliations": [ "Internal Medicine, Rio Hortega University Hospital, Valladolid, Spain" ], "name": "Julia Barbado Ajo" }, { "affiliations": [ "Internal Medicine, Hospital Virgen de la Luz, Cuenca, Spain" ], "name": "Ismael Calero-Paniagua" }, { "affiliations": [ "Internal Medicine, Hospital Universitario Nuestra Señora de la Candelaria, Santa Cruz de Tenerife, Spain" ], "name": "Esther Rubio" }, { "affiliations": [ "Internal Medicine, Hospital Álvaro Cunqueiro, Vigo, Spain" ], "name": "Ana Argibay" }, { "affiliations": [ "Internal Medicine, Hospital General Universitario José M Morales Meseguer, Murcia, Spain" ], "name": "José M Gómez-Verdú" }, { "affiliations": [ "Internal Medicine, Hospital Universitari de Tarragona Joan XXIII, Tarragona, Spain" ], "name": "Jesús Miguel López-Dupla" }, { "affiliations": [ "Internal Medicine, Hospital Universitario Insular de Gran Canaria, Las Palmas de Gran Canaria, Spain" ], "name": "Carlos Jorge Ripper" }, { "affiliations": [ "Internal Medicine, La Paz University Hospital, Madrid, Spain" ], "name": "Angel Robles-Marhuenda" }, { "affiliations": [ "Internal Medicine, San Jorge University General Hospital of Huesca, Huesca, Spain" ], "name": "Eva Calvo-Begueria" }, { "affiliations": [ "Internal Medicine, Hospital Universitario de Cabueñes, Gijon, Spain" ], "name": "Eva Fonseca" }, { "affiliations": [ "Internal Medicine, Hospital Universitario Ramón y Cajal, Madrid, Spain" ], "name": "Andrés González-García" }, { "affiliations": [ "Internal Medicine, Hospital de Galdakao-Usansolo, Galdakao, Spain" ], "name": "Kima López-Aldabe" }, { "affiliations": [ "Internal Medicine, Hospital de Fuenlabrada, Fuenlabrada, Spain" ], "name": "Begoña Frutos- Pérez" }, { "affiliations": [ "Internal Medicine, Hospital Vega Baja, San Bartolomé, Spain" ], "name": "Robert Hurtado-García" }, { "affiliations": [ "Internal Medicine, Hospital de Viladecans, Viladecans, Spain" ], "name": "Ana Ponce" }, { "affiliations": [ "Internal Medicine, Hospital Universitario Infanta Leonor, Madrid, Spain" ], "name": "Gabriela Artinyan" }, { "affiliations": [ "Internal Medicine, Hospital Universitario de Salamanca, Salamanca, Spain" ], "name": "Angel Pedro Crisolino Pozas" }, { "affiliations": [ "Internal Medicine, Hospital Universitario 12 de Octubre, Madrid, Spain" ], "name": "Borja De Miguel-Campo" }, { "affiliations": [ "Internal Medicine, Hospital de Poniente de Almería, El Ejido, Spain" ], "name": "Joaquín Pousibet" }, { "affiliations": [ "Autoimmune Diseases, Hospital Clinic de Barcelona, Barcelona, Spain" ], "name": "Gerard Espinosa" }, { "affiliations": [], "name": "on behalf of the Autoimmune Diseases Study Group (GEAS), Spanish Society of Internal Medicine (SEMI)" } ], "title": "Impact of belimumab on the utility of serological markers for assessing systemic lupus erythematosus activity", "uid": "b55d654e-a8e7-529c-a054-7ce914a8792f" }