Background/Purpose: In the phase 3 TULIP-1 and TULIP-2 trials, anifrolumab, a type I IFN receptor mAb, improved disease activity versus placebo in patients with moderate to severe SLE despite standard therapy with oral glucocorticoids (GCs), antimalarials, and/or immunosuppressants.^1,2 We investigated prior standard therapy use, and whether baseline standard therapy impacted anifrolumab efficacy in pooled data from TULIP-1 and TULIP-2.

Methods: TULIP-1 (NCT02446912) and TULIP-2 (NCT02446899) were 52-week trials of intravenous anifrolumab 300 mg or placebo every 4 weeks for 48 weeks, in which eligible patients fulfilled the ACR 1997 criteria for SLE. At screening, patients had moderate to severe SLE (SLEDAI-2K ≥6, ≥1 A or ≥2 B BILAG-2004 organ domain scores, Physician’s Global Assessment ≥1) and were required to be receiving ≥1 of the following standard therapies: oral GCs, antimalarials, immunosuppressants (azathioprine, mizoribine, mycophenolate mofetil, mycophenolic acid, and/or methotrexate). Patients were divided into subgroups depending on which standard therapies they were receiving at baseline; BILAG–based Combined Lupus Assessment (BICLA) response at Week 52 was compared across subgroups using a stratified Cochran–Mantel–Haenszel approach.

Results: Overall, 726 patients received anifrolumab 300 mg (n=360) or placebo (n=366) in TULIP-1 and TULIP-2. Demographics and baseline disease characteristics were generally balanced between treatment groups. The median time from SLE diagnosis to randomization was 84.5 months, during which most patients had received GCs (89.5%), antimalarials (84.3%), and immunosuppressants (68.0%), and 100%, 34.3%, or 57.3% of patients had received ≥1, 2, or ≥3 SLE-related immunomodulatory therapies, respectively. At baseline, patients were receiving GCs (82.0%), antimalarials (70.2%), and/or immunosuppressants (48.2%), with most patients receiving combinations of the three (Table). Anifrolumab 300 mg was associated with higher BICLA response rates versus placebo across all evaluated baseline standard therapy subgroups (Figure); however, the impact of differing dosages of standard therapy on efficacy was not investigated. The positive treatment differences ranged from 6.9% (antimalarial + immunosuppressant) to 50.8% (immunosuppressant only), but these groups had small sample sizes (n=42 and n=15, respectively), which may limit interpretation of these treatment differences. Clear positive treatment differences favoring anifrolumab 300 mg vs placebo were observed in the 190 patients who were likely to have refractory or severe disease, as they were receiving GCs + antimalarials + immunosuppressants at baseline (53.6% vs 32.2%; Δ=21.4%; 95% CI: 7.4−35.4).

Conclusion: In 2 phase 3 trials, anifrolumab 300 mg was associated with consistently higher BICLA response rates than placebo, regardless of baseline standard therapy usage, including in patients with potentially more treatment-refractory SLE, requiring treatment with GCs, immunosuppressants, and antimalarials.

1. Furie RA. Lancet Rheumatol. 2019;1:e208–19.

2. Morand EF. N Engl J Med. 2020;382:211–21.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/sle-treatment-history-and-anifrolumab-efficacy-by-baseline-standard-therapies-in-patients-with-sle-from-2-phase-3-trials/