POS0541 GLUCOCORTICOID REDUCTION AND WITHDRAWAL IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS RECEIVING LONG-TERM ANIFROLUMAB TREATMENT
Authors: R. A. Furie, I. N. Bruce, K. C. Kalunian, E. Morand, S. Manzi, Y. Tanaka, J. Knagenhjelm, R. Tummala, C. Lindholm
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Anifrolumab is a fully human monoclonal antibody targeting the type I interferon receptor that is approved for patients with moderate to severe systemic lupus erythematosus (SLE).<sup>1</sup> The phase 3 TULIP-1/-2 and long-term extension (LTE) trials demonstrated the efficacy of anifrolumab in reducing disease activity and tapering glucocorticoid (GC) use (prednisone equivalent) to ≤7.5 mg/day.<sup>2</sup> The updated EULAR 2023 guidelines recommend a GC maintenance dose of ≤5 mg/day and encourage GC withdrawal, if possible, to minimize the risk of toxicity.<sup>3</sup> <h3>Objectives:</h3> In this post hoc analysis of the TULIP-1/-2 and LTE trials, we evaluated the long-term impact of anifrolumab 300 mg compared with placebo (both treatments added to standard therapy) on GC tapering and withdrawal. The simultaneous achievement of disease activity (SLE Disease Activity Index 2000 [SLEDAI-2K]) improvement and GC tapering to ≤5 mg/day was also assessed in the anifrolumab 300 mg and placebo groups. <h3>Methods:</h3> Adult patients with moderate to severe SLE despite standard therapy who completed treatment in the 52-week TULIP-1/-2 trial (NCT02446912, NCT02446899) could enroll in the 3-year double-blind, randomized, placebo-controlled LTE (NCT02794285) upon reconsent. This analysis included patients randomized to receive intravenous anifrolumab 300 mg or placebo every 4 weeks in TULIP-1/-2 who continued the same treatment in the LTE. GC use was assessed for up to 208 weeks of treatment duration. Dual SLEDAI-2K and GC response was defined as achieving both ≥4-point SLEDAI-2K reduction from TULIP-1/-2 baseline and GC ≤5 mg/day. Patients who discontinued investigational product prematurely and/or withdrew from the study due to lack of efficacy and/or worsened condition were considered nonresponders from that visit onward. Responder rates were calculated using a stratified Cochran–Mantel–Haenszel approach. All <i>P</i>-values were nominal. <h3>Results:</h3> Of 366 patients included in the analyses, similar proportions of patients were receiving GC ≥7.5 mg/day at baseline in the anifrolumab 300 mg and placebo groups (55.9% [142/254] vs 57.1% [64/112]). Among these patients, the mean (standard error) GC dosage at Week 208 was 4.98 (0.46) mg/day for patients treated with anifrolumab, whereas the mean GC dosage for patients receiving placebo was 8.05 (1.11) mg/day. At Week 208, a greater proportion of anifrolumab-treated patients had tapered their GC dosage from ≥7.5 to ≤5 mg/day compared with placebo (58.2% [39/67] vs 47.8% [11/23]), and a greater proportion stopped GCs (22.4% [15/67] vs 8.7% [2/23]) (Figure 1). Irrespective of baseline GC dosage, a greater proportion of patients achieved dual SLEDAI-2K + GC ≤5 mg/day response at Week 208 with anifrolumab vs placebo (39.2% [67/173] vs 17.4% [12/66]; nominal <i>P</i>&lt;0.001). A similar trend in the proportion of dual responders at Week 208 was seen in patients with baseline GC ≥7.5 mg/day (anifrolumab: 47.0% [30/65]; placebo: 31.0% [7/23]; 95% CI: −6.9 to 39.1; nominal <i>P</i>=0.171). <h3>Conclusion:</h3> Long-term use of anifrolumab alongside standard therapy in the 4-year TULIP-1/-2 plus LTE trials was associated with higher proportions of patients able to reduce their GC dosage from ≥7.5 mg/day at baseline to ≤5 mg/day, including complete GC withdrawal, compared with placebo (standard therapy alone). A greater proportion of patients treated with anifrolumab achieved both SLEDAI-2K improvement and GC taper to ≤5 mg/day compared with placebo. The long-term reduction of GC use and disease activity seen with anifrolumab treatment may protect against organ damage. <h3>REFERENCES:</h3> [1] SAPHNELO (anifrolumab) Prescribing Information. AstraZeneca; 2023. [2] Kalunian KC, et al. <i>Arthritis Rheumatol</i>. 2023;75(2):253–265. [3] Fanouriakis A, et al. <i>Ann Rheum Dis</i>. 2023; doi: 10.1136/ard-2023-224762. <h3>Acknowledgements:</h3> This study was sponsored by AstraZeneca. Writing assistance was provided by Vasileios Stamou, PhD, and Rosie Butler, PhD, of JK Associates Inc., part of Avalere Health, and funded by AstraZeneca. <h3>Disclosure of Interests:</h3> Richard A. Furie Speakers bureau: AstraZeneca, Consultant of: AstraZeneca, Grant/research support from: AstraZeneca, Ian N. Bruce Speakers bureau: AstraZeneca, GlaxoSmithKline, Janssen, UCB, Consultant of: AstraZeneca, Aurinia, Dragonfly Therapeutics, GlaxoSmithKline, Horizon Therapeutics, Lilly, Takeda, UCB, Grant/research support from: AstraZeneca, GlaxoSmithKline, Janssen, Novartis, Kenneth C. Kalunian Consultant of: AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Equilliumbio, Genentech/Roche, GlaxoSmithKline, Kezarbio, Merck, Grant/research support from: Amgen, Lupus Foundation of America, Lupus Research Alliance, NIH, Novartis, UCB, Eric Morand Speakers bureau: AstraZeneca, Consultant of: AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Genentech, Gilead, GlaxoSmithKline, Janssen, Novartis, Takeda, Grant/research support from: AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Genentech, GlaxoSmithKline, Janssen, Takeda, UCB, Susan Manzi Consultant of: AstraZeneca, Cartesian, Cuegene, Exagen, GlaxoSmithKline, Lilly, Grant/research support from: AstraZeneca, Cartesian, Cuegene, Exagen, GlaxoSmithKline, Lilly, Yoshiya Tanaka Speakers bureau: Abbvie, Asahikasei, AstraZeneca, Behringer-Ingelheim, Bristol Myers Squibb, Chugai, Eisai, Eli Lilly, Gilead, GlaxoSmithKline, Pfizer, Taiho, Taisho, Grant/research support from: Asahikasei, Chugai, Eisai, Mitsubishi-Tanabe, Taisho, Jacob Knagenhjelm Shareholder of: AstraZeneca, Employee of: AstraZeneca, Raj Tummala Shareholder of: AstraZeneca, Employee of: AstraZeneca, Catharina Lindholm Shareholder of: AstraZeneca, Employee of: AstraZeneca.