Background The Lupus Low Disease Activity State (LLDAS) has been prospectively validated as protective from flares, damage accrual, and mortality and is an important treatment goal in patients with SLE. Recent analysis of pooled data from 2 phase 3 trials (TULIP-1 and TULIP-2) found that LLDAS attainment was achieved earlier, more frequently, and for a more sustained period with anifrolumab vs placebo in patients with moderate to severe SLE.

Aims and Objectives We investigated the long-term impact of anifrolumab compared with placebo on LLDAS attainment over the 1-year TULIP-1/TULIP-2 and 3-year long-term extension (LTE) study periods.

Methods TULIP-1 and TULIP-2 (NCT02446912, NCT02446899) were randomized, placebo- controlled, 52-week trials of IV anifrolumab (Q4W, 48 weeks) in patients with moderate to severe SLE despite standard therapy. Following the double-blind treatment period of the TULIP trials, patients could reconsent to participate in the 3-year, randomized, blinded, placebo-controlled LTE study (NCT02794285). Here, data were analyzed by timepoint from TULIP baseline through the end of the LTE (Week 208) for patients who were assigned and received the same study drug (anifrolumab 300 mg or placebo) during the TULIP+LTE periods. LLDAS attainment was defined as all of the following: SLEDAI-2K ≤4 without major organ activity, no new disease activity, Physician Global Assessment [0–3] ≤1, prednisone or equivalent ≤7.5 mg/day, standard immunosuppressant dosing, and no use of restricted medications (considered only during the pooled TULIP-1/TULIP-2 period but not during the LTE period). Patients who discontinued investigational product (IP) prematurely and/or withdrew from the study due to ‘lack of efficacy’ and/or ‘condition under investigation worsened’ are considered nonresponders from the visit of IP discontinuation and/or withdrawal. LLDAS percentages and cumulative time in LLDAS were compared using a Cochran-Mantel-Haenszel approach, and response rates were compared using logistic regression. Last observation carried forward was used to impute missing data for TULIP- 1/TULIP-2, but not for data captured in the LTE. All P-values are nominal.

Results Data from 369 patients (anifrolumab 300 mg, n=257; placebo, n=112) were evaluable for the 4-year TULIP+LTE study period. At the last TULIP visit (Week 52), 39.5% of the anifrolumab group and 28.9% of the placebo group were in LLDAS (odds ratio [OR] 1.6, 95% CI 1.0–2.6, P=0.0713). At the first visit of the LTE (Week 64), 36.5% of the anifrolumab group and 23.5% of the placebo group were in LLDAS (OR 1.9, 95% CI 1.1–3.2, P=0.0185).

The proportion of patients attaining LLDAS was greater in the anifrolumab vs placebo groups from Week 24 through the end of the LTE period (Week 208: OR 2.7, 95% CI 1.3–5.5, P=0.0081; figure 1). For the combined 4-year TULIP+LTE period, greater cumulative time (P=0.0004) and percentage of time (P=0.0013) was spent in LLDAS by patients receiving anifrolumab compared with placebo. Cumulative time in LLDAS at a threshold of ≥20% also favored anifrolumab (OR 2.1, 95% CI 1.3–3.4, P=0.0014); a similar trend was seen with a threshold of ≥50%, although this did not reach statistical significance (OR 1.5, 95% CI 0.9– 2.7, P=0.1249). Compared with placebo, patients treated with anifrolumab were more likely to be in sustained LLDAS for ≥3 consecutive visits (50.9% vs 36.0%; OR 1.8, 95% CI 1.1–2.9, P=0.0144), ≥5 consecutive visits (32.9% vs 21.1%; OR 1.7, 95% CI 1.0–2.9, P=0.0453), or ≥7

consecutive visits (22.9% vs 12.6%; OR 2.0, 95% CI 1.0–3.8, P=0.0352).

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Abstract 1502 Figure 1

Lupus Low Disease Activity State (LLDAS) response rate by randomized treatment in patients with SLE in the TULIP long-term extension study. aResponder rates were calculated using a stratified Cochran-Mantel-Haenszel (CMH) approach, with stratification factors of Systemic Lupus Erythematosus Disease Activity Index 2000 at screening, Day 1 glucocorticoid dosage, type I interferon gene signature at screening, and study. Nominal P values were calculated using logistic regression with the same factors as for the CMH approach. Nominal P values: *<0.05; **<0.01.

Conclusions Anifrolumab 300 mg treatment was associated with more frequent, prolonged, and sustained LLDAS compared with placebo during the 4-year TULIP+LTE period.

Funding This study was sponsored by AstraZeneca.

Writing assistance by Rosie Butler, PhD, of JK Associates Inc., part of Fishawack Health.

Previously presented at EULAR 2023. Adapted by permission from BMJ Publishing Group Limited. [Ann Rheum Dis. Morand EF, Van Vollenhoven R, Furie R, et al, volume 82 (suppl 1), pages 33–34, 2023].