Eric F Morand1, Richard Furie1, Yoshiya Tanaka1, Ian N Bruce1, Anca D Askanase1, Christophe Richez1, Sang-Cheol Bae1, Philip Z Brohawn1, Lilia Pineda1, Anna Berglind1, Raj Tummala1. 1. From the Centre for Inflammatory Disease, Monash University, Melbourne, VIC, Australia (E.F.M.); the Division of Rheumatology, Zucker School of Medicine at Hofstra-Northwell, Great Neck (R.F.), and the Department of Medicine, Division of Rheumatology, Columbia University College of Physicians and Surgeons, New York (A.D.A.) - both in New York; the First Department of Internal Medicine and Graduate School of Medical Science, University of Occupational and Environmental Health Japan, Kitakyushu (Y.T.); the Arthritis Research UK Centre for Epidemiology, Faculty of Biology, Medicine, and Health, University of Manchester and National Institute for Health Research Manchester Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom (I.N.B.); the Rheumatology Department, Centre Hospitalier Universitaire de Bordeaux-Groupe Hospitalier Pellegrin, and Unité Mixte de Recherche-Centre National de la Recherche Scientifique 5164, Bordeaux University, Bordeaux, France (C.R.); the Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea (S.-C.B.); AstraZeneca, Gaithersburg, MD (P.Z.B., L.P., R.T.); and AstraZeneca, Gothenburg, Sweden (A.B.).
Abstract
BACKGROUND: Anifrolumab, a human monoclonal antibody to type I interferon receptor subunit 1 investigated for the treatment of systemic lupus erythematosus (SLE), did not have a significant effect on the primary end point in a previous phase 3 trial. The current phase 3 trial used a secondary end point from that trial as the primary end point. METHODS: We randomly assigned patients in a 1:1 ratio to receive intravenous anifrolumab (300 mg) or placebo every 4 weeks for 48 weeks. The primary end point of this trial was a response at week 52 defined with the use of the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA). A BICLA response requires reduction in any moderate-to-severe baseline disease activity and no worsening in any of nine organ systems in the BILAG index, no worsening on the Systemic Lupus Erythematosus Disease Activity Index, no increase of 0.3 points or more in the score on the Physician Global Assessment of disease activity (on a scale from 0 [no disease activity] to 3 [severe disease]), no discontinuation of the trial intervention, and no use of medications restricted by the protocol. Secondary end points included a BICLA response in patients with a high interferon gene signature at baseline; reductions in the glucocorticoid dose, in the severity of skin disease, and in counts of swollen and tender joints; and the annualized flare rate. RESULTS: A total of 362 patients received the randomized intervention: 180 received anifrolumab and 182 received placebo. The percentage of patients who had a BICLA response was 47.8% in the anifrolumab group and 31.5% in the placebo group (difference, 16.3 percentage points; 95% confidence interval, 6.3 to 26.3; P = 0.001). Among patients with a high interferon gene signature, the percentage with a response was 48.0% in the anifrolumab group and 30.7% in the placebo group; among patients with a low interferon gene signature, the percentage was 46.7% and 35.5%, respectively. Secondary end points with respect to the glucocorticoid dose and the severity of skin disease, but not counts of swollen and tender joints and the annualized flare rate, also showed a significant benefit with anifrolumab. Herpes zoster and bronchitis occurred in 7.2% and 12.2% of the patients, respectively, who received anifrolumab. There was one death from pneumonia in the anifrolumab group. CONCLUSIONS: Monthly administration of anifrolumab resulted in a higher percentage of patients with a response (as defined by a composite end point) at week 52 than did placebo, in contrast to the findings of a similar phase 3 trial involving patients with SLE that had a different primary end point. The frequency of herpes zoster was higher with anifrolumab than with placebo. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT02446899.).
BACKGROUND: Anifrolumab, a human monoclonal antibody to type I interferon receptor subunit 1 investigated for the treatment of systemic lupus erythematosus (SLE), did not have a significant effect on the primary end point in a previous phase 3 trial. The current phase 3 trial used a secondary end point from that trial as the primary end point. METHODS: We randomly assigned patients in a 1:1 ratio to receive intravenous anifrolumab (300 mg) or placebo every 4 weeks for 48 weeks. The primary end point of this trial was a response at week 52 defined with the use of the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA). A BICLA response requires reduction in any moderate-to-severe baseline disease activity and no worsening in any of nine organ systems in the BILAG index, no worsening on the Systemic Lupus Erythematosus Disease Activity Index, no increase of 0.3 points or more in the score on the Physician Global Assessment of disease activity (on a scale from 0 [no disease activity] to 3 [severe disease]), no discontinuation of the trial intervention, and no use of medications restricted by the protocol. Secondary end points included a BICLA response in patients with a high interferon gene signature at baseline; reductions in the glucocorticoid dose, in the severity of skin disease, and in counts of swollen and tender joints; and the annualized flare rate. RESULTS: A total of 362 patients received the randomized intervention: 180 received anifrolumab and 182 received placebo. The percentage of patients who had a BICLA response was 47.8% in the anifrolumab group and 31.5% in the placebo group (difference, 16.3 percentage points; 95% confidence interval, 6.3 to 26.3; P = 0.001). Among patients with a high interferon gene signature, the percentage with a response was 48.0% in the anifrolumab group and 30.7% in the placebo group; among patients with a low interferon gene signature, the percentage was 46.7% and 35.5%, respectively. Secondary end points with respect to the glucocorticoid dose and the severity of skin disease, but not counts of swollen and tender joints and the annualized flare rate, also showed a significant benefit with anifrolumab. Herpes zoster and bronchitis occurred in 7.2% and 12.2% of the patients, respectively, who received anifrolumab. There was one death from pneumonia in the anifrolumab group. CONCLUSIONS: Monthly administration of anifrolumab resulted in a higher percentage of patients with a response (as defined by a composite end point) at week 52 than did placebo, in contrast to the findings of a similar phase 3 trial involving patients with SLE that had a different primary end point. The frequency of herpes zoster was higher with anifrolumab than with placebo. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT02446899.).
Authors: Salina Gairhe; Keytam S Awad; Edward J Dougherty; Gabriela A Ferreyra; Shuibang Wang; Zu-Xi Yu; Kazuyo Takeda; Cumhur Y Demirkale; Parizad Torabi-Parizi; Eric D Austin; Jason M Elinoff; Robert L Danner Journal: Proc Natl Acad Sci U S A Date: 2021-03-16 Impact factor: 11.205
Authors: Ying Wang; Mei Han; Christopher E Pedigo; Zhi-Min Xie; Wei-Jie Wang; Jian-Ping Liu Journal: Chin J Integr Med Date: 2021-07-28 Impact factor: 1.978