AB0993 LUPUS LOW DISEASE ACTIVITY STATE ATTAINMENT WITH ANIFROLUMAB IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND LYMPHOPENIA
Authors: E. Morand, E. M. Vital, S. Manzi, J. Knagenhjelm, C. Lindholm
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Patients with systemic lupus erythematosus (SLE) frequently present with lymphopenia, which is associated with increased disease activity and use of standard therapies and is negatively associated with attainment of Lupus Low Disease Activity State (LLDAS).<sup>[1]</sup> Anifrolumab, a type I interferon receptor–blocking antibody that is approved for the treatment of patients with moderate to severe SLE, has been shown to improve lymphocyte counts relative to placebo.<sup>[2,3]</sup> However, no studies have investigated clinical benefit in patients with lymphopenia who received treatment with anifrolumab. <h3>Objectives:</h3> To investigate LLDAS attainment among patients with or without lymphopenia who received anifrolumab or placebo alongside standard therapy in pooled data from the phase 3 TULIP-1 and TULIP-2 trials. <h3>Methods:</h3> TULIP-1 and TULIP-2 were randomized, placebo-controlled, 52-week trials of intravenous anifrolumab (once every 4 weeks for 48 weeks) in patients with moderate to severe SLE despite standard therapy (NCT02446912, NCT02446899).<sup>[4,5]</sup> In this post hoc analysis of pooled TULIP-1/2 data, LLDAS response rates were evaluated over time in patients receiving anifrolumab 300 mg or placebo among subgroups of patients with or without lymphopenia (defined as lymphocyte count ≤1.2 GI/L) at baseline. LLDAS was defined as all of the following: SLEDAI-2K ≤4 without major organ activity, no new disease activity, Physician's Global Assessment [0–3] ≤1, prednisone or equivalent ≤7.5 mg/day, standard immunosuppressant dosing, no use of restricted medications, and no investigational product discontinuation. Responder rates, treatment differences, and nominal <i>P</i> values were calculated using a stratified Cochran–Mantel–Haenszel approach. <h3>Results:</h3> At baseline, 51% of patients had lymphopenia (367/726; anifrolumab, n=186; placebo, n=181). Rates of LLDAS attainment by Week 52 were numerically similar in the anifrolumab groups, regardless of lymphopenia status (lymphopenia: 27.9%, 53/186; without lymphopenia: 31.9%, 55/174) (<b>Figure 1</b>). Patients with lymphopenia in the placebo group had low rates (14.5%, 26/181) of LLDAS attainment through Week 52; LLDAS response rate for patients without lymphopenia in the placebo group was 24.8% (46/185). Among patients with lymphopenia, the treatment difference in LLDAS attainment favored anifrolumab as early as Week 12 and was maintained through Week 52 (treatment difference=13.4%; nominal <i>P</i>=0.0021). <h3>Conclusion:</h3> In patients receiving standard therapy plus placebo, rates of LLDAS attainment were low in the subgroup with baseline lymphopenia. LLDAS attainment rates during 1 year of treatment with anifrolumab were similar regardless of baseline lymphopenia status. Our results suggest that anifrolumab treatment is associated with clinical benefit among patients with lymphopenia. <h3>REFERENCES:</h3> [1] Kandane-Rathnayake R, et al. <i>Rheumatol</i>. 2021;60:5185–93. [2] SAPHNELO (anifrolumab) Prescribing Information. AstraZeneca; 2023. [3] Vital E, et al. <i>Ann Rheum Dis</i>. 2023;82:1451–52. [4] Furie R, et al. <i>Lancet Rheumatol.</i> 2019;1:e208–19. [5] Morand EF, et al. <i>N Engl J Med.</i> 2020;382:211–21. <h3>Acknowledgements:</h3> This study was sponsored by AstraZeneca. Writing assistance was provided by Rosie Butler, PhD, of JK Associates Inc., part of Avalere Health, and funded by AstraZeneca. <h3>Disclosure of Interests:</h3> Eric Morand Speakers bureau: AstraZeneca, Consultant of: AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Genentech, GSK, Gilead, Janssen, Novartis, Takeda, Grants/research support from: AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Genentech, GSK, Eli Lilly, EMD Serono, Janssen, Takeda, UCB, Edward M. Vital Speakers bureau: AstraZeneca, Novartis, UCB, Lilly, Otsuka, Consultant of: AstraZeneca, Novartis, Roche, Lilly, Merck, UCB, Pfizer, Abbvie, Grants/research support from: Research grants paid to my employer from AstraZeneca and Sandoz, Susan Manzi Consultant: GSK, Cartesian, Exagen, Lilly, AstraZeneca, and Cuegene, Grants/research support: Participation in a number of clinical trials for testing new therapeutic agents and diagnostic tests for lupus for GSK, Cartesian, Exagen, Lilly, AstraZeneca, and Cuegene, Jacob Knagenhjelm Shareholder: Indirectly own shares of AstraZeneca through mutual fund, Employee: AstraZeneca, Catharina Lindholm Shareholder: AstraZeneca, Employee: AstraZeneca.