Background/Purpose: In the TULIP-2 and TULIP-1 trials of patients with SLE, the type I IFN receptor mAb anifrolumab resulted in higher BILAG–based Composite Lupus Assessment (BICLA) response rates vs placebo at Week 52.^1,2 Subgroup analyses revealed concordant BICLA response rates across clinically distinct SLE subgroups, including disease severity and SLE therapies.³ Here, we compare BICLA response rates in serological subgroups (low complement, anti-dsDNA positivity, or both).

Methods: TULIP-2 (NCT02446899) and TULIP-1 (NCT02446912) were phase 3, randomized, placebo-controlled, 52-week trials of intravenous anifrolumab every 4 weeks for 48 weeks in eligible patients who fulfilled the ACR 1997 criteria for SLE and had moderate to severe SLE despite standard therapy.^1,2 BICLA response rates at Week 52 for anifrolumab vs placebo groups were compared across patient subgroups of baseline complement C3/C4 levels (low/normal) and anti-dsDNA antibody status (positive/negative).

Results: In TULIP-2 and TULIP-1, 180 patients in each trial received anifrolumab 300 mg, and 182 and 184 patients received placebo, respectively. BICLA response rates in the overall anifrolumab groups were similar in TULIP-2 (47.8%) and TULIP-1 (47.1%), with treatment differences (Δ) favoring anifrolumab over placebo (Δ=16.3% and 17.0%, respectively) (Figure). Anifrolumab response rates were generally higher in serologically abnormal vs normal subgroups in TULIP-2 (47.7%–52.9% vs 43.3%–47.9%) and TULIP-1 (50.6%–53.0% vs 42.8%–45.5%); the greatest anifrolumab response rate was seen in the low C3/C4 subgroup (TULIP-2: 52.9%; TULIP-1: 53.0%), while anifrolumab response rates were similar regardless of anti-dsDNA positivity. In contrast, placebo response rates were generally lower in serologically abnormal vs normal subgroups in TULIP-2 (26.0%–31.6% vs 31.8%–35.8%) and TULIP-1 (24.7%–29.3% vs 28.7%–34.3%), although placebo responses were similar regardless of anti-dsDNA positivity. Anifrolumab and placebo subgroup response rates did not vary by more than ±6% from the overall population. These variations in response rates led to greater treatment differences favoring anifrolumab in patients with low C3/C4, alone or in combination with anti-dsDNA positivity, vs the overall population; the largest difference was seen for patients with low C3/C4 (TULIP-2: Δ=26.9%; TULIP-1: Δ=28.4%). In the subgroups with normal serology, treatment differences ranged from 7.5%–16.2% in TULIP-2 and 8.5%–15.8% in TULIP-1; thus, treatment differences favored anifrolumab vs placebo in all evaluated serology subgroups.

Conclusion: BICLA response rates in clinically distinct subgroups of SLE were generally consistent with the overall TULIP-2 and TULIP-1 results.³ Patients with low complement at baseline appeared to have a greater treatment effect than those with normal complement, while anti-dsDNA antibody status did not associate with response. The subgroup analyses indicate efficacy of anifrolumab 300 mg across all evaluated serological subgroups of SLE.

1. Furie, Lancet Rheumatol 2019;1:e208-10.
2. Morand. N Engl J Med 2020;382:211–21.
3. Morand. Ann Rheum Dis 2020(S1);79:32.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-of-anifrolumab-in-serological-subgroups-of-patients-with-sle-participating-in-2-phase-3-trials/