Background 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.
Objectives To compare the impact of anifrolumab on individual organ domains in patients with moderate to severe SLE who participated in the Phase IIb study.
Methods 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.
Results 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%; p<0.001) vs. 1000 mg 51/102 (50.0%; p=0.082); BILAG: 24/87 (27.6%) vs. 49/84 (58.3%; p<0.001) vs. 33/82 (40.2%; p=0.069); Musculoskeletal: SLEDAI-2K: 42/99 (42.4%) vs. 55/97 (56.7%; p=0.032) vs. 50/98 (51.0%; p=0.197); BILAG: 47/95 (49.5%) vs. 64/94 (68.1%; p=0.005) vs. 54/91 (59.3%; p=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%; p=0.068); 1000 mg: 18/59 (30.5%; p=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%)].
Conclusions Anifrolumab treatment resulted in greater rates of improvement than placebo in multiple organs, with greatest impact seen with 300 mg anifrolumab.
Acknowledgement Funded by MedImmune. Editorial assistance: K Alexander, QXV Comms, an Ashfield business, UK
Disclosure of Interest 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