THU0295 Anifrolumab Reduces Disease Activity in Multiple Organ Domains in Moderate To Severe Systemic Lupus Erythematosus (SLE)
Authors: J.T. Merrill, R. Furie, V.P. Werth, M. Khamashta, J. Drappa, L. Wang, G. Illei
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> As reported elsewhere, anifrolumab was evaluated in a Phase IIb study of SLE patients with moderate to severe disease activity, in which 305 patients received intravenous infusions of anifrolumab (300 mg, 1000 mg) or placebo every 4 weeks for 1 year. Both doses demonstrated increased rates of reduction in global disease activity, although a more favorable risk-benefit profile was observed with the 300-mg dose. <h3>Objectives</h3> To compare the impact of anifrolumab on individual organ domains in patients with moderate to severe SLE who participated in the Phase IIb study. <h3>Methods</h3> At Week 52, changes from baseline in organs domain activity were assessed using the British Isles Lupus Assessment Group (BILAG) and SLE Disease Activity Index 2000 (SLEDAI-2K). Improvement in a BILAG organ domain was defined as the transitioning from “A” or “B” to a lower score. Improvement in a SLEDAI domain required a lower score at Day 365 compared with baseline in at least one of its components. <h3>Results</h3> The majority of patients had baseline involvement of the mucocutaneous and/or musculoskeletal domains of SLEDAI-2K and BILAG. Compared with placebo, a greater percentage of patients in the anifrolumab-treated group improved in these frequently involved organs: [Mucocutaneous: SLEDAI-2K: placebo 38/100 (38.0%) vs. 300 mg 61/99 (61.6%; <i>p</i>&lt;0.001) vs. 1000 mg 51/102 (50.0%; <i>p</i>=0.082); BILAG: 24/87 (27.6%) vs. 49/84 (58.3%; <i>p</i>&lt;0.001) vs. 33/82 (40.2%; <i>p</i>=0.069); Musculoskeletal: SLEDAI-2K: 42/99 (42.4%) vs. 55/97 (56.7%; <i>p</i>=0.032) vs. 50/98 (51.0%; <i>p</i>=0.197); BILAG: 47/95 (49.5%) vs. 64/94 (68.1%; <i>p</i>=0.005) vs. 54/91 (59.3%; <i>p</i>=0.149)]. Trends suggesting potential benefits were observed in most of the other less frequently active domains including SLEDAI-2K cardiorespiratory, vascular, hematological, and constitutional, and BILAG cardiorespiratory and constitutional domains. Of those patients who had involvement in the SLEDAI-2K immunological domain at baseline [positive anti-double-stranded-DNA (anti-dsDNA) and/or low complement level], a greater number of patients in the anifrolumab groups [placebo: 4/53 (7.5%); 300 mg: 9/43 (20.9%; <i>p</i>=0.068); 1000 mg: 18/59 (30.5%; <i>p</i>=0.004)] had lower scores at Day 365, representing a normalization of anti-dsDNA and/or hypocomplementemia. However, among patients who had a normal anti-dsDNA and/or normal complements at baseline a slightly greater number of patients treated with 300 mg anifrolumab had an increase in the score representing the development of a new anti-dsDNA or hypocomplementemia compared with baseline [placebo: 7/79 (8.9%); 300 mg: 11/82 (13.4%), 1000 mg: 6/79 (7.6%)]. <h3>Conclusions</h3> Anifrolumab treatment resulted in greater rates of improvement than placebo in multiple organs, with greatest impact seen with 300 mg anifrolumab. <h3>Acknowledgement</h3> Funded by MedImmune. Editorial assistance: K Alexander, QXV Comms, an Ashfield business, UK <h3>Disclosure of Interest</h3> J. Merrill Grant/research support from: MedImmune; Genentech/Roche, Consultant for: MedImmune, Genentech/Roche, Neovacs, R. Furie Consultant for: MedImmune, V. Werth Consultant for: MedImmune, M. Khamashta Grant/research support from: Bayer, Consultant for: INOVA diagnostics, Medimmune, GSK, UCB outside submitted work, J. Drappa Shareholder of: AstraZeneca, Employee of: MedImmune, L. Wang Employee of: MedImmune, G. Illei Shareholder of: AstraZeneca, Employee of: MedImmune