Background/Purpose: In a phase 2 study in SLE patients (pts), substantial efficacy was observed with anifrolumab, a human monoclonal antibody that binds the type I IFN receptor subunit 1. TULIP-1, a phase 3 randomized, double-blind, placebo-controlled trial (NCT02446912), evaluated efficacy and safety of anifrolumab in pts with moderate to severe SLE.

Methods: SLE pts meeting ACR criteria with SLEDAI-2K ≥6 and BILAG >1 A or >2 B were randomized 2:1:2 to receive IV anifrolumab 300 or 150 mg or placebo (PBO) Q4W and background standard-of-care (SOC) therapy. Stable SOC was required throughout the study except for mandatory attempts at oral corticosteroid (OCS) tapering for pts receiving ≥10 mg/d prednisone or equivalent at entry. The primary endpoint was the difference between Week (W) 52 SRI(4) rates for anifrolumab 300 mg and PBO. Key secondary endpoints included OCS dosage reduction (baseline ≥10 mg/d to ≤7.5 mg/d), W12 CLASI response, and annualized flare rates. BICLA, joint counts, IFN gene signature (IFNGS), and safety were assessed. Post hoc analyses used modified restricted medication rules that were revised after unblinding to be more clinically appropriate.

Results: All 457 randomized pts received ≥1 dose of study drug and were included in the analyses (anifrolumab 300 mg, n=180; anifrolumab 150 mg, n=93; PBO, n=184). Baseline characteristics (Table) and treatment completion rates (~80%) were similar across groups. No difference in W52 SRI(4) response rates was observed for anifrolumab 300 mg (36.2% [65/180]) vs PBO (40.4% [74/184]); SRI(4) rates in the IFNGS test–high subgroup were 35.9% (53/148) and 39.3% (59/151), respectively. In prespecified analyses, any increase in NSAID dose or new NSAID use inadvertently resulted in nonresponse classification. Post hoc analyses, therefore, used modified restricted medication rules. In these post hoc analyses, W52 SRI(4) rates were 46.9% (84/180) for anifrolumab 300 mg vs 43.0% (79/184) for PBO; SRI(4) rates in the IFNGS test–high subgroup were 48.2% (71/148) vs 41.8% (63/151), respectively. Differences favored anifrolumab 300 mg over PBO for BICLA in all pts (46.1% [83/180] vs 29.6% [54 /184], diff: 16.4%; 95% CI: 6.7, 26.2) and in the IFNGS test–high subgroup (45.9% [68/148] vs 27.5% [41/151], diff: 18.4%; 7.7, 29.1). Differences favoring anifrolumab 300 mg vs PBO also occurred for OCS dosage reduction (48.8% [50/103] vs 32.1% [33/102], diff: 16.7%; 95% CI: 3.5, 29.8) and CLASI (43.6% [25/58] vs 24.9% [14/54], diff: 18.7%; 1.4, 36.0) as well as joint activity and flare reduction. IFNGS was suppressed with anifrolumab 300 mg but not PBO. Serologic changes showed trends toward normalization for anifrolumab 300 mg. Serious AEs occurred in 13.9% and 10.8% of pts with anifrolumab 300 and 150 mg vs 16.3% with PBO. Herpes zoster was more common in the anifrolumab groups vs PBO (5.6% and 5.4% vs 1.6%).

Conclusion: Although the primary endpoint, SRI(4), was not achieved in TULIP-1,  numeric improvements achieving thresholds associated with clinical benefit were observed for BICLA, OCS, and other organ-specific endpoints. Anifrolumab 300 mg suppressed IFNGS and was generally well tolerated.

Writing assistance by Ellen Stoltzfus, PhD (Fishawack).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-phase-3-randomized-controlled-trial-of-anifrolumab-in-patients-with-moderate-to-severe-systemic-lupus-erythematosus/