Session Type: Late-Breaking Abstract Session
Session Time: 4:00PM-6:00PM
Background/Purpose: Anifrolumab, a human monoclonal antibody to the type I IFN receptor subunit 1, had robust efficacy in a phase 2 study in patients with active SLE. The first phase 3 trial, TULIP-1, did not meet its primary endpoint, SLE responder index (SRI), but multiple other endpoints, including BILAG–based Composite Lupus Assessment (BICLA), suggested clinical benefit. We report results of the second phase 3 trial of anifrolumab.
Methods: TULIP-2 (NCT02446899) is a randomized, double-blind, placebo-controlled trial that evaluated efficacy and safety of IV anifrolumab 300 mg vs placebo every 4 weeks for 48 weeks in patients with moderate to severe SLE despite standard-of-care (SOC) treatment. Patients met ACR SLE criteria and had SLEDAI-2K ≥6 and BILAG >1 A or >2 B. The primary endpoint was BICLA response at week 52. SOC was stable except for mandatory attempts at oral corticosteroid (OCS) tapering to prednisone equivalent ≤7.5 mg/d for patients receiving ≥10 mg/d at baseline. Safety was also assessed.
Results: Of 365 randomized patients, 362 received ≥1 dose of study drug and were included in the analyses (anifrolumab, n=180; placebo, n=182). Baseline demographic and disease characteristics were similar between treatment groups (Table 1). Treatment completion was 85.0% for anifrolumab and 71.4% for placebo.
Anifrolumab was superior to placebo for BICLA response (47.8% vs 31.5%, respectively, P=0.001) and key secondary endpoints: OCS reduction (51.5% vs 30.2%; P=0.014) and Cutaneous Lupus Erythematosus Disease Area and Severity Index response (49.0% vs 25.0%; P=0.039); annualized flare rate was numerically lower in anifrolumab-treated patients (0.43 vs 0.64; rate ratio 0.67 [95% CI: 0.48, 0.94]; P=0.081; Table 2).
Efficacy was further supported by numeric differences favoring anifrolumab in multiple secondary endpoints (unadjusted), including SRI(4) response (55.5% vs 37.3%; nominal P< 0.001) and higher thresholds of SRI(5–8), time to onset of BICLA response sustained to week 52 (hazard ratio [HR], 1.55; 95% CI: 1.11, 2.18; nominal P=0.011; Figure 1A), and time to first flare (HR, 0.65; 95% CI: 0.46, 0.91; nominal P=0.013; Figure 1B). In patients with high baseline IFN gene signature (IFNGS), anifrolumab induced neutralization of IFNGS by week 12 (median suppression 88.0%) that was maintained through week 52. Serum anti-dsDNA trended toward normalization with anifrolumab.
The safety profile of anifrolumab was similar to that of previous trials. Herpes zoster was more common in those receiving anifrolumab (7.2%) than placebo (1.1%). In contrast, serious adverse events were less frequent among anifrolumab- than placebo-treated patients (8.3% and 17.0%, respectively), as were adverse events leading to treatment discontinuation (2.8% and 7.1%). One death occurred in the anifrolumab group (pneumonia). Few patients (0.6%) developed antidrug antibodies.
Conclusion: Anifrolumab was superior to placebo for multiple efficacy endpoints, including overall disease activity, skin disease, and OCS tapering. No new safety signals were identified. TULIP-2 demonstrates efficacy of anifrolumab in moderate to severe SLE.
Writing assistance by Ellen Stoltzfus, PhD (Fishawack).
To cite this abstract in AMA style:Morand E, Furie R, Tanaka Y, Bruce I, Askanase A, Richez C, Bae S, Brohawn P, Pineda L, Berglind A, Tummala R. Efficacy and Safety of Anifrolumab in Patients with Moderate to Severe Systemic Lupus Erythematosus: Results of the Second Phase 3 Randomized Controlled Trial [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/efficacy-and-safety-of-anifrolumab-in-patients-with-moderate-to-severe-systemic-lupus-erythematosus-results-of-the-second-phase-3-randomized-controlled-trial/. Accessed August 8, 2020.
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