Biotherapies in systemic lupus erythematosus: New targets.
Systemic lupus erythematosus (SLE) is an autoimmune disease with a polymorphic presentation. The variability in the clinical expression and severity of SLE makes new treatments both essential and challenging to develop. Several biotherapies targeting different pathophysiological pathways have been developed over the past 15 years. The results of Phase II trials were encouraging but rarely borne out by Phase III trials. Recent data, which are discussed in detail in this review, allowed belimumab - a monoclonal antibody against BLyS (B-lymphocyte stimulator) - to become the first biotherapy approved for use in SLE. Other molecules targeting B cells include the two anti-BLyS antibodies tabalumab and blisibimod; atacicept, which targets both BLyS and APRIL (a proliferation-inducing ligand); and the monoclonal antibody to CD22 epratuzumab. The rekindling of interest in the B-cell pathway has also driven new clinical research into rituximab, a monoclonal antibody targeting CD20 with evaluations of new strategies. A new and promising approach is the use of inhibitors of the type 1 interferon (IFN) pathway, of which the most promising is anifrolumab, a monoclonal antibody targeting the type 1 IFN receptor. In this review, we discuss study findings and their clinical relevance, present the most promising targets, and analyze possible explanations to negative results, such as inappropriate patient selection and treatment response criteria or the erratic use of high-dose glucocorticoid therapy.
Université de Bordeaux, 146, rue Léo-Saignat, 33076 Bordeaux, France; FHU ACRONIM, centre hospitalier universitaire de Bordeaux, place Amélie-Raba-Léon, 33076 Bordeaux, France; CNRS-UMR 5164 Immuno Concept, 146, rue Léo-Saignat, 33076 Bordeaux, France.
Estibaliz
E
Lazaro
Université de Bordeaux, 146, rue Léo-Saignat, 33076 Bordeaux, France; FHU ACRONIM, centre hospitalier universitaire de Bordeaux, place Amélie-Raba-Léon, 33076 Bordeaux, France.
Marc
M
Scherlinger
Université de Bordeaux, 146, rue Léo-Saignat, 33076 Bordeaux, France; FHU ACRONIM, centre hospitalier universitaire de Bordeaux, place Amélie-Raba-Léon, 33076 Bordeaux, France; CNRS-UMR 5164 Immuno Concept, 146, rue Léo-Saignat, 33076 Bordeaux, France.
Marie-Elise
ME
Truchetet
Service de médecine interne, hôpital européen, 6, rue Désirée-Clary, 13003 Marseille, France.
Laurent
L
Chiche
Université de Bordeaux, 146, rue Léo-Saignat, 33076 Bordeaux, France; FHU ACRONIM, centre hospitalier universitaire de Bordeaux, place Amélie-Raba-Léon, 33076 Bordeaux, France.
Thierry
T
Schaeverbeke
Université de Bordeaux, 146, rue Léo-Saignat, 33076 Bordeaux, France; FHU ACRONIM, centre hospitalier universitaire de Bordeaux, place Amélie-Raba-Léon, 33076 Bordeaux, France; CNRS-UMR 5164 Immuno Concept, 146, rue Léo-Saignat, 33076 Bordeaux, France.
Patrick
P
Blanco
Université de Bordeaux, 146, rue Léo-Saignat, 33076 Bordeaux, France; FHU ACRONIM, centre hospitalier universitaire de Bordeaux, place Amélie-Raba-Léon, 33076 Bordeaux, France; CNRS-UMR 5164 Immuno Concept, 146, rue Léo-Saignat, 33076 Bordeaux, France. Electronic address: christophe.richez@u-bordeaux.fr.
Christophe
C
Richez
D001685:Biological Factors / Q000627:therapeutic use*; D001691:Biological Therapy; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000628:therapy*
D001685:Biological Factors
Biotherapies; Glucocorticoids; Interferon; Systemic lupus erythematosus