AB0514 LABORATORY MARKER IMPROVEMENTS FOLLOWING LONG-TERM TREATMENT WITH ANIFROLUMAB IN ADULTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS IN THE PLACEBO-CONTROLLED TULIP EXTENSION STUDY

E Vital; Z Amoura; K Kalunian; I Bruce; Y Tanaka; S Manzi; I Hupka; S Yavuz; G Abreu; C Lindholm; H Al-Mossawi

doi:10.1136/annrheumdis-2023-eular.1534

BackgroundAnifrolumab is a type I interferon (IFN) receptor antagonist approved for treating adults with moderate to severe SLE [1]. The efficacy and safety of anifrolumab was evaluated in two 1-year phase 3 TULIP studies (NCT02446912, NCT02446899), and patients completing treatment in TULIP-1/-2 could enter the 3-year, placebo-controlled long-term extension (LTE) study (NCT02794285) [2-4]. Multiple serological markers are available to monitor SLE; notably, lymphopenia is associated with higher SLE disease activity and damage [5]. Assessing the long-term impact of anifrolumab on lymphocytes and other laboratory markers is of clinical interest.ObjectivesTo compare the change over time of laboratory markers in blood samples from adults with SLE treated with anifrolumab vs placebo over the 4-year TULIP-LTE period.MethodsEligible patients fulfilled 1997 ACR criteria for SLE at TULIP entry, completed the TULIP treatment periods, and reconsented to participate in the LTE study. Here, we analyze data from patients who were randomized to anifrolumab 300 mg or placebo at TULIP entry and who did not change treatment over the TULIP+LTE period. Blood samples were collected from baseline (BL) until Week 208. Laboratory measures (lymphocytes, hemoglobin, platelets, complement C3 and C4, anti–double-stranded DNA antibodies) were analyzed using standard cell count and enzyme-linked immunosorbent assays. Mean changes from BL to Week 208 were analyzed descriptively.ResultsWe present data on 536 patients (anifrolumab 300 mg, n=358; placebo, n=178). Assessing lymphocytes over time revealed a numerically greater increase in the anifrolumab vs placebo group during the TULIP studies which was maintained through the 3-year LTE period (Figure 1). BL laboratory characteristics and changes from BL to Week 208 are shown in the Table 1. Numerically greater increases in hemoglobin levels and platelet counts from BL to Week 208 were observed in patients treated with anifrolumab compared with placebo; mean platelet and hemoglobin levels remained in the normal range at BL and Week 208. Among patients with low C3 levels at BL, there was a numerically greater mean improvement in C3 levels to Week 208 with anifrolumab vs placebo.ConclusionLong-term improvement of lymphocytes and other laboratory markers, compared with placebo, indicates that type I IFN inhibition with anifrolumab normalizes SLE-related hematological parameters in patients with SLE. This normalization may relate to disease activity reduction and be relevant to long-term health outcomes and complications.References[1]AstraZeneca. Anifrolumab SmPC. https://www.ema.europa.eu/en/medicines/human/EPAR/saphnelo. Feb 2022.[2]Furie R. Lancet Rheumatol. 2019;1:e208–19.[3]Morand E. N Engl J Med. 2020;382:211–21.[4]Kalunian K. Arthritis Rheumatol. 2022; doi:10.1002/art.42392.[5]Vilá L. Arthritis Rheum. 2006;55:799–806.Table 1.Laboratory markers from the 4-year TULIP-LTE studyTreatmentAnifrolumab 300 mg (n=358)Placebo (n=178)N (BL, Week 208)BLChange from BL to Week 208n (BL, Week 208)BLChange from BL to Week 208Mean (SE)Mean (SE)Lymphocytes, 109/L358, 1821.27 (0.034)+0.40 (0.048)178, 621.26 (0.048)+0.06 (0.078)Hemoglobin, g/L358, 182125.1 (0.78)+3.8 (0.95)178, 62126.7 (1.18)−2.3 (1.46)Platelets, 109/L358, 182239.9 (4.14)+24.9 (4.38)178, 61248.2 (5.74)+3.6 (6.25)C3, g/La129, 640.690 (0.0132)+0.192 (0.0284)63, 180.712 (0.0187)+0.085 (0.0579)C4, g/Lb83, 360.073 (0.0018)+0.050 (0.0103)37, 100.073 (0.0022)+0.012 (0.0093)Anti-dsDNA, U/mLc165, 79129.6 (20.47)−22.1 (45.64)69, 20115.3 (20.03)+15.6 (28.66)anti-dsDNA, anti–double-stranded DNA; BL, baseline; C3/C4, complement 3/4; LTE, long-term extension; SE, standard error. Baseline is defined as baseline of the phase 3 feeder studies (the last measurement prior to dose administration on Day 1). Only patients with alow C3 [<0.9 g/L], blow C4 [<0.1 g/L], or cpositive anti-dsDNA [>15 U/mL], respectively, at baseline are included in this analysis.AcknowledgementsWriting assistance by Laura Buck, PhD, and Rosie Butler, PhD, of JK Associates Inc., part of Fishawack Health.This study was sponsored by AstraZeneca.Disclosure of InterestsEdward Vital Speakers bureau: AstraZeneca, Paid instructor for: AstraZeneca, Novartis, Consultant of: AstraZeneca, Roche, Pfizer, Novartis, UCB, Aurinia, Lilly, Grant/research support from: AstraZeneca, Zahir Amoura Consultant of: GSK, AstraZeneca, Amgen, Otsuka, Novartis, Kezar, Grant/research support from: GSK, AstraZeneca, Amgen, Otsuka, Novartis, Kezar, Kenneth Kalunian Consultant of: Biogen, AstraZeneca, BMS, Genentech/Roche, Amgen, Equilliumbio, Kezarbio, GSK, Merck, Abbvie, Grant/research support from: UCB, Novartis, Amgen, Lupus Foundation of America, Lupus Research Alliance, NIH, Ian N. Bruce Speakers bureau: GSK, AstraZeneca, Janssen, Consultant of: GSK, AstraZeneca, Aurinia, Lilly, Grant/research support from: GSK, AstraZeneca, Janssen, Yoshiya Tanaka Speakers bureau: Behringer-Ingelheim, Eli Lilly, Abbvie, Gilead, AstraZeneca, Bristol-Myers, Chugai, Daiichi-Sankyo, Eisai, Pfizer, Mitsubishi-Tanabe, GSK, Grant/research support from: Asahi-Kasei, Abbvie, Chugai, Eisai, Takeda, Daiichi-Sankyo, Behringer-Ingelheim, Susan Manzi Consultant of: AstraZeneca, Exagen Diagnostics, Inc, GSK, Lilly, Novartis, UCB, Grant/research support from: HGS/GSK, AstraZeneca, GSK, AbbVie, Ihor Hupka Employee of: AstraZeneca, Sule Yavuz Employee of: AstraZeneca, Gabriel Abreu Employee of: AstraZeneca, Catharina Lindholm Shareholder of: AstraZeneca, Employee of: AstraZeneca, Hussein Al-Mossawi Shareholder of: AstraZeneca, UCB, GSK, Speakers bureau: Novartis, Pfizer, UCB, Consultant of: Novartis, UCB, Abbvie, Grant/research support from: UCB, Employee of: UCB (Previous), AstraZeneca (Current)

AB0514 LABORATORY MARKER IMPROVEMENTS FOLLOWING LONG-TERM TREATMENT WITH ANIFROLUMAB IN ADULTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS IN THE PLACEBO-CONTROLLED TULIP EXTENSION STUDY

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