Anifrolumab failed to meet the primary endpoint of SRI(4) in the phase 3 TULIP-1 trial.
A potential efficacy of anifrolumab was seen in steroid reduction, CLASI, BICLA, and joint score.
Anifrolumab 300 mg was generally well tolerated.
However, post hoc analyses using modified restricted medication rules showed better improvement in SRI(4) rates at week 52 for anifrolumab, suggesting that this is a critical aspect for clinical trials on SLE.
Substantial efficacy was observed in a phase 2 study investigating anifrolumab, a human monoclonal antibody that binds the type I interferon (IFN) receptor subunit 1, in patients with systemic lupus erythematosus (SLE).  TULIP-1 (NCT02446912) is a phase 3 randomized, double-blind, placebo-controlled trial that investigated the efficacy and safety of anifrolumab in moderate to severe SLE.
SLE patients meeting ACR criteria with SLEDAI (Systemic Lupus Erythematosus Disease Activity Index)-2K ≥6 and BILAG (British Isles Lupus Assessment Group) >1 A or >2B were randomized 2:1:2 to receive IV anifrolumab 300 or 150 mg or placebo Q4W in addition to standard-of-care (SOC).
Stable SOC was required throughout the study except for mandatory attempts at oral corticosteroid (OCS) tapering for patients receiving ≥10 mg/day prednisone or equivalent at entry.
Post hoc analyses used modified restricted medication rules that were revised after unblinding to be more clinically appropriate.
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.
The primary endpoint was the difference between week 52 SRI (Systemic Lupus Erythematosus Responder Index)(4) rates in anifrolumab 300 mg vs placebo.
Key secondary endpoints included OCS dosage reduction (baseline ≥10 mg/day to ≤7.5 mg/day), week 12 CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index) response, and annualized flare rates.
BICLA (British Isles Lupus Assessment Group-based composite lupus assessment), joint count, interferon gene signature (IFNGS), and safety were assessed.
All randomized pts received ≥1 dose of study drug and were included in the analyses (anifrolumab 300 mg, n = 180; anifrolumab 150 mg, n = 93; placebo, n = 184).
Baseline characteristics and treatment completion rates were similar across groups.
No difference in week 52 SRI(4) response rates was observed for anifrolumab 300 mg (36.2% vs. placebo (40.4%); SRI(4) rates in the IFNGS test–high subgroup were 35.9% and 39.3%, respectively.
In these post hoc analyses, week 52 SRI(4) rates were 46.9% (84/180) for anifrolumab 300 mg vs. 43.0% for placebo; SRI(4) rates in the IFNGS test–high subgroup were 48.2% vs. 41.8%, respectively.
Differences favored anifrolumab 300 mg over placebo for BICLA in all pts (46.1% vs. 29.6%, diff: 16.4%; 95% CI: 6.7, 26.2) and in the IFNGS test–high subgroup (45.9% vs. 27.5%, diff: 18.4%; 7.7, 29.1).
Differences favoring anifrolumab 300 mg vs. placebo also occurred for OCS dosage reduction (48.8% vs. 32.1%, diff: 16.7%; 95% CI: 3.5, 29.8) and CLASI (43.6% vs. 24.9%, diff: 18.7%; 1.4, 36.0) (Figure).
IFNGS was suppressed by anifrolumab 300 mg but by placebo; serologic changes showed trends toward normalization for anifrolumab 300 mg.
Serious AEs occurred in 13.9% and 10.8% of patients with anifrolumab 300 and 150 mg vs. 16.3% with placebo.
Herpes zoster was more common in the anifrolumab groups 300 and 150 mg vs. placebo (5.6% and 5.4% vs. 1.6%, respectively).
Post hoc analyses suggested a potential efficacy of anifrolumab in steroid reduction, CLASI, BICLA, and joint scores.
Anifrolumab 300 mg suppressed IFNGS and was generally well tolerated.
Inclusion criteria pertaining to concomitant medications allowed as well as suitable endpoint are critical for clinical trials on SLE.
Key messages/Clinical perspectives
While the primary endpoint of SRI(4) at week 52 was not achieved for anifrolumab 300 mg, post hoc analyses suggested potential efficacy of the drug in steroid reduction, CLASI, BICLA, and joint scores.