POS0528 LUPUS LOW DISEASE ACTIVITY STATE ATTAINMENT AND REDUCED GLUCOCORTICOID USE IN PATIENTS WITH SLE IN THE TULIP LONG-TERM EXTENSION TRIAL OF ANIFROLUMAB

Background:

Previous prospective analyses in patients with systemic lupus erythematosus (SLE) showed that attainment of Lupus Low Disease Activity State (LLDAS) is associated with reduced disease flares, less damage accrual, lower oral glucocorticoid (GC) dosing, and reduced mortality.^1,2 In the 52-week phase 3 TULIP-1/-2 trials, a post hoc analysis of pooled data found that patients with SLE treated with anifrolumab were more likely to attain LLDAS compared with patients who received placebo.³ Although criteria for attainment of LLDAS includes a ceiling GC (prednisone equivalent) dose of ≤7.5 mg/day, the updated EULAR 2023 guidelines have a lower recommended target dose of ≤5 mg/day in patients with SLE overall.^1,4

Objectives:

To evaluate the long-term impact of anifrolumab 300 mg compared with placebo on attainment of LLDAS together with reduction in GC dose to ≤5 mg/day in patients with moderate to severe SLE during the 3-year TULIP long-term extension (LTE) study.

Methods:

In the 3-year, randomized, blinded, placebo-controlled TULIP-LTE study (NCT02794285), patients with moderate to severe SLE despite standard therapy received anifrolumab 300 mg or placebo as an extension of their assigned treatment in the 52-week TULIP-1/-2 trials.⁵ Patients were followed from baseline (of TULIP-1/-2) through the end of the LTE (Week 208). Response was defined as LLDAS attainment together with GC dose reduction to ≤5 mg/day (LLDAS+GC≤5) at the same visit; response rates were analyzed using a stratified Cochran–Mantel–Haenszel method. Responses were also analyzed by disease onset (established [SLE diagnosis >2 years prior to randomization] vs recent onset [SLE diagnosis ≤2 years prior to randomization]). LLDAS attainment was defined as all of the following: SLE Disease Activity Index 2000 ≤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 (during the TULIP-1/-2 52-week period only), and no investigational product discontinuation.

Results:

Of 369 patients (anifrolumab 300 mg, n=257; placebo, n=112) evaluable for the TULIP-1/-2/-LTE study period, 33.1% (81/254) in the anifrolumab group vs 23.2% (25/108) in the placebo group achieved LLDAS+GC≤5 at the final TULIP-1/-2 visit (Week 52), and 30.3% (75/251) in the anifrolumab group vs 17.8% (18/104) in the placebo group achieved LLDAS+GC≤5 at the first LTE LLDAS assessment (Week 64; Figure 1). Rates of LLDAS+GC≤5 remained higher through Week 208 in patients treated with anifrolumab (22.8% [42/194]) compared with patients who received placebo (8.6% [6/65]). Patients with established disease who received anifrolumab (n=212) had higher rates of LLDAS+GC≤5 compared with those who received placebo (n=86) through Week 208 (23.2% [36/162] and 5.5% [3/53], respectively; Figure 1). In patients treated with anifrolumab, LLDAS+GC≤5 response rates were similar between patients with established and recent-onset disease through Week 208 (23.2% [36/162] and 20.9% [6/32], respectively). In contrast, in patients who received placebo, LLDAS+GC≤5 response rates were lower in patients who had established disease compared with those who had recent-onset disease through Week 208 (5.5% [3/53] and 27.9% [3/12], respectively).

Conclusion:

In the placebo-controlled TULIP-LTE study, anifrolumab 300 mg treatment was associated with higher rates of LLDAS attainment together with GC reduction to ≤5 mg/day compared with placebo, overall and in patients with established disease.

REFERENCES:

[1] Golder V. Lancet Rheumatol. 2019;1(2):e95–e102. [2] Kandane-Rathnayake R. Arthritis Res Ther. 2022;24(1):70. [3] Morand EF. Ann Rheum Dis. 2023;82(5):639–645. [4] Fanouriakis A. Ann Rheum Dis. 2024;83(1):15–29. [5] Kalunian KC. Arthritis Rheumatol. 2023;75(2):253–265.

Acknowledgements:

This study was sponsored by AstraZeneca. Writing assistance was provided by Andrea Angstadt, PhD of JK Associates Inc., part of Avalere Health, and funded by AstraZeneca.

Disclosure of Interests:

Eric Morand Speakers bureau: AstraZeneca, Consultant: AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Genentech, GSK, Gilead, Janssen, Novartis, Takeda, Grant/research support: AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Genentech, GSK, Eli Lilly, EMD Serono, Janssen, Takeda, UCB, Ronald F. van Vollenhoven Speakers bureau: AbbVie, AstraZeneca, BMS, Galapagos, GSK, Janssen, Pfizer, UCB, Consultant: AbbVie, AstraZeneca, Biogen, BMS, Galapagos, GSK, Janssen, Pfizer, RemeGen, UCB, Grant/research support: Institutional grants for research and/or education from AstraZeneca, BMS, Galapagos, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, Richard A. Furie Speakers bureau: AstraZeneca, Consultant: AstraZeneca, Grant/research support: AstraZeneca, Ian N. Bruce Speakers bureau: UCB, AstraZeneca, Janssen and GSK, Consultant: AstraZeneca, UCB, Aurinia, Takeda, GSK, Lilly, Horizon Therapeutics, Dragonfly Therapeutics, Grant/research support: AstraZeneca, GSK, Janssen, Novartis, Yoshiya Tanaka Speakers bureau: Eli Lilly, AstraZeneca, Abbvie, Asahikasei, Gilead, Chugai, Behringer-Ingelheim, GlaxoSmithKline, Eisai, Taisho, Bristol-Myers, Pfizer, Taiho, Grant/research support: Asahikasei, Mitsubishi-Tanabe, Eisai, Chugai, Taisho, Jacob Knagenhjelm Shareholder: Indirectly own shares of AstraZeneca through mutual fund., Employee: AstraZeneca, Micki Hultquist Shareholder: AstraZeneca, Employee: AstraZeneca, Raj Tummala Shareholder: AstraZeneca, Employee: AstraZeneca, Catharina Lindholm Shareholder: Own AstraZeneca shares, Employee: AstraZeneca.