Determinants of neuropsychiatric flares in patients with systemic lupus erythematosus: results from five phase III trials of belimumab

被引:6
|
作者
Palazzo, Leonardo [1 ]
Lindblom, Julius [1 ,2 ]
Cetrez, Nursen [1 ,2 ]
Ala, Henri [1 ]
Parodis, Ioannis [1 ,2 ,3 ,4 ]
机构
[1] Karolinska Inst, Dept Med Solna, Div Rheumatol, Solna, Sweden
[2] Karolinska Univ Hosp, Dept Gastroenterol Dermatol & Rheumatol, Solna, Sweden
[3] Orebro Univ, Fac Med & Hlth, Dept Rheumatol, Orebro, Sweden
[4] Karolinska Univ Hosp, Rheumatol, SE-17176 Stockholm, Sweden
基金
芬兰科学院;
关键词
SLE; neuropsychiatric; flares; determinants; belimumab; NECROSIS-FACTOR FAMILY; B-LYMPHOCYTE STIMULATOR; CENTRAL-NERVOUS-SYSTEM; DISEASE-ACTIVITY; LIGAND APRIL; DIAGNOSIS; INDEX; MANIFESTATIONS; PATHOGENESIS; PREDICTORS;
D O I
10.1093/rheumatology/kead249
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective To identify determinants of neuropsychiatric (NP) flares in patients with SLE treated for active SLE yet no ongoing severe NPSLE with non-biologic standard therapy plus belimumab or placebo. Methods We analysed data from five phase III trials (BLISS-52, BLISS-76, BLISS-NEA, BLISS-SC, EMBRACE; n = 3638) after exclusion of patients with baseline NP BILAG A. Factors associated with NPSLE flare, defined as a new NP BILAG A or B, were investigated using Cox regression. In a subgroup analysis, we studied patients with baseline NP BILAG E for determinants of de novo NPSLE flare. Organ damage was assessed using the SLICC/ACR Damage Index (SDI). Results We documented 105 (2.9%) NPSLE flares. In multivariable analysis, male sex (HR = 2.37; 95% CI: 1.31, 4.28; P = 0.004), baseline NP BILAG B-D (HR = 5.91; 95% CI: 3.86, 9.06; P < 0.001), and increasing SDI scores (HR = 1.35; 95% CI: 1.21, 1.50; P < 0.001) were strongly associated with NPSLE flare. Belimumab use yielded no association at any dose or administration form. In analysis of SDI domains, NP damage was the strongest determinant of NPSLE flare (HR = 3.25; 95% CI: 2.72, 3.88; P < 0.001), holding true for cognitive impairment (HR = 14.29; 95% CI: 9.22, 22.14; P < 0.001), transverse myelitis (HR = 21.89; 95% CI: 5.40, 88.72; P < 0.001), and neuropathy (HR = 8.87; 95% CI: 5.59, 14.09; P < 0.001). Male sex was the strongest determinant of de novo NPSLE flare (HR = 3.26; 95% CI: 1.51, 7.04; P = 0.003). Conclusion Male sex, NPSLE history, and NP damage were strong determinants of impending NPSLE flare. No clear protection or predisposition was conferred from add-on belimumab.
引用
收藏
页码:798 / 808
页数:11
相关论文
共 50 条
  • [31] Effects of belimumab, a B lymphocyte stimulator-specific inhibitor, on disease activity across multiple organ domains in patients with systemic lupus erythematosus: combined results from two phase III trials
    Manzi, Susan
    Sanchez-Guerrero, Jorge
    Merrill, Joan T.
    Furie, Richard
    Gladman, Dafna
    Navarra, Sandra V.
    Ginzler, Ellen M.
    D'Cruz, David P.
    Doria, Andrea
    Cooper, Simon
    Zhong, Z. John
    Hough, Douglas
    Freimuth, William
    Petri, Michelle A.
    ANNALS OF THE RHEUMATIC DISEASES, 2012, 71 (11) : 1833 - 1838
  • [32] Decreased Disease Activity and Corticosteroid Usage and No Renal Flares during Belimumab Treatment in Patients with Systemic Lupus Erythematosus
    Parodis, Ioannis
    Svenungsson, Elisabet
    Axelsson, Magnus
    Gunnarsson, Iva
    ARTHRITIS & RHEUMATOLOGY, 2014, 66 : S292 - S292
  • [33] SPANISH NATIONAL REGISTRY OF BELIMUMAB IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
    Laino, M.
    Enguita, M.
    Castaneda, S.
    Loricera, J.
    Moriano, C.
    Lasa, C.
    Calvo-Rio, V.
    Narvaez, J.
    Navarro Palomo, P.
    Casafont-Sole, I.
    Font, J.
    Gallego, A.
    Carrion Barbera, I.
    Quiroga Colino, P.
    Garcia-Aparicio, A.
    Belzunegui Otano, J. M.
    Lopez, M.
    Jimenez de Aberasturi, J. R. De Dios
    Hernandez, S.
    Heredia, S.
    Farina, A.
    Navarro Blasco, F. J.
    Ortega Castro, R.
    Del Olmo Perez, L.
    Labrador-Sanchez, E.
    Pinillos, V.
    Ortega de la O, M. C.
    Castro, P.
    Blanco, J. M.
    Paulino Huertas, M.
    Matias de la Mano, M. A.
    Peralta-Gines, C.
    Garcia-Cirera, S.
    Camins, J.
    Urruticoechea-Arana, A.
    Medina Malone, M.
    Cossio Jimenez, P. J.
    Perez-Pampin, E.
    Varas, B.
    Vazquez, C.
    Vegas-Revenga, N.
    Rusinovich, O.
    Giner, E.
    Lamua-Riazuelo, J. R.
    Aldasoro, V.
    ANNALS OF THE RHEUMATIC DISEASES, 2023, 82 : 899 - 901
  • [34] Spanish National Registry of Belimumab in Patients with Systemic Lupus Erythematosus
    Aldasoro, Vicente
    Laino, Maria
    Enguita, Monica
    Castaneda, Santos
    Loricera, Javier
    Lasa-Teja, Carmen
    Moriano, Clara
    Rio, Vanesa Calvo
    Casafont-Sole, Ivette
    Font Urgelles, Judit
    Quiroga-Colina, Patricia
    Hernandez, Samuel
    Heredia, Sergi
    Garcia-Aparicio, A.
    Belzunegui Otano, Joaquin Maria
    Farina, Aaron
    Navarro Blasco, Francisco Javier
    Fanlo Mateo, Patricia
    Gallego, Adela
    Blanco Madrigal, Juan M.
    Angeles Matias, Maria
    Peralta, Cilia
    Camins-Fabregas, Jordi
    Paulino, Marcos
    Urruticoechea, Ana
    Cossio Jimenez, Piter Jose
    Medina Malone, Miguel
    Perez Pampin, Eva
    Ortega-Castro, Rafaela
    Varas de Dios, Blanca
    Lamua Riazuelo, Jose Ramon
    Jose Giner, Emilio
    ARTHRITIS & RHEUMATOLOGY, 2022, 74 : 692 - 695
  • [35] Efficacy and safety data of belimumab in patients with systemic lupus erythematosus
    Shakoory, Bita
    Clatham, Winn
    THERAPEUTIC ADVANCES IN MUSCULOSKELETAL DISEASE, 2011, 3 (03) : 159 - 164
  • [36] Belimumab Effects on Skin in Patients with Systemic Lupus Erythematosus: A Pooled Post Hoc Analysis of Five Phase 3, Randomized, Placebo-Controlled Clinical Trials
    Manzi, Susan
    Sanchez-Guerrero, Jorge
    Yokogawa, Naoto
    Wenzel, Joerg
    Ocran-Appiah, Josephine C.
    Khamashta, Munther
    Harris, Julia H. N.
    Rubin, Bernie
    Fox, Norma Lynn
    Levy, Roger A.
    Werth, Victoria
    ARTHRITIS & RHEUMATOLOGY, 2022, 74 : 1933 - 1935
  • [37] COMBINATION THERAPY WITH RITUXIMAB AND BELIMUMAB IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
    Mesnyankina, A.
    Aseeva, E.
    Nikishina, N.
    Torgashina, A.
    ANNALS OF THE RHEUMATIC DISEASES, 2021, 80 : 1168 - 1168
  • [38] IMPROVEMENT OF BELIMUMAB ON QUALITY OF LIFE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
    Yi, G.
    Zheng, S.
    Guo, X.
    Liu, M.
    Li, T.
    ANNALS OF THE RHEUMATIC DISEASES, 2022, 81 : 1351 - 1351
  • [39] Spanish National Registry of Belimumab in Patients with Systemic Lupus Erythematosus
    Laino, Maria
    Enguita, Monica
    Loricera, Javier
    Moriano Morales, Clara
    Lasa, Carmen
    Calvo Rio, Vanesa
    Narvaez, Javier
    Navarro Guerra, Pablo Ignacio
    Casafont-Sole, Ivette
    Font Urgelles, Judit
    Gallego, Adela
    Carrion-Barbera, Irene
    Quiroga, Patricia
    Castaneda, Santos
    Garcia-Aparicio, Angel
    Belzunegui Otano, Joaquin Maria
    Ramon De Dios, Juan
    Lopez, Marta
    Hernandez, Samuel
    Heredia Martin, Sergi
    Farinas, Aaron
    Navarro, Francisco
    Juan Fragio, Jorge
    Escudero, Carmen
    Ortega Castro, Rafaela
    del Olmo Perez, Leticia
    Pinillos, Valvanera
    Labrador, Eztizen
    Ortega, Mamen
    Castro Perez, Patricia
    Blanco-Madrigal, Juan Maria
    Paulino, Marcos
    Angeles Matias, Maria
    Calvo-Aranda, Enrique
    Peralta, Cilia
    Garcia, Silvia
    Camins-Fabregas, Jordi
    Garijo Bufort, Marta
    Fabregas, Dolores
    Urruticoechea, Ana
    Medina Malone, Miguel
    Cossio Jimenez, Piter Jose
    Perez-Pampin, Eva
    Varas de Dios, Blanca
    Vazquez Galeano, Carlos
    Vegas Revenga, Nuria
    Rusinovich, Olga
    Giner-Serret, Emilio
    Ramon Lamua, Jose
    Aldasoro, Vicente
    ARTHRITIS & RHEUMATOLOGY, 2023, 75 : 4639 - 4643