TULIP-1: Anifrolumab fails primary endpoint, confers clinical benefit in SLE
ATLANTA — Although a 300 mg dose of anifrolumab failed to meet the primary endpoint of systemic lupus erythematosus responder index, a post-hoc analysis showed possible clinical benefit of the drug, according to a speaker at ACR/ARP 2019.
“It is so rare for a lupus clinical trial to make it to a plenary, so cherish the moment,” Richard Furie, MD, chief of rheumatology at the Zucker School of Medicine at Hofstra/Northwell in New York, said in his presentation.
The current phase 3 study included patients with SLE Disease Activity Index 2000 (SLEDAI-2K) 6 and British Isles Lupus Assessment Group (BILAG) > 1 A or > 2B criteria. Eligible participants were randomly assigned, in a 2:1:2 ratio, to IV anifrolumab 300 mg, anifrolumab 150 mg, or placebo every 4 weeks, along with background standard of care therapy.
The difference between SLE Responder Index [SRI(4)] rates at week 52 between the placebo and 300 mg dose served as the primary endpoint. The researchers also assessed for secondary endpoints, including oral corticosteroid dosage reduction (baseline 10 mg/day to 7.5 mg/day), Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) response, annualized flare rates, BILAG-based Composite Lupus Assessment (BICLA), joint counts, interferon gene signature and safety outcomes. A post-hoc analysis was also performed to further elucidate potential clinical outcomes.
Furie presented findings for 75 patients in the low-dose anifrolumab group, 144 treated with the high dose, and 146 patients in the placebo group who finished the trial.
Results showed that 36.2% of patients in the 300 mg group and 40.4% of those in the placebo group met the primary endpoint (P = .41).
Similarly, no difference was reported for SRI(4) in interferon gene signature test high patients, in annualized flare rate, or in terms of sustained OCS reduction as defined by clinical parameters.
A slightly better result was observed for the outcome of a more than 50% reduction in CLASI activity from baseline (P = .05). Also, BICLA response rates were 27% for the placebo group and 37.1% for anifrolumab 300 mg (P = N/A).
The post-hoc analysis, however, told a slightly different story, according to Furie. “Eight percent of patients were misclassified as nonresponders because of NSAID use,” he said. “When we did the post-hoc analysis, CLASI activity moved far to the right, BICLA response showed a fairly significant change, and we saw steroid reduction and modest changes in serologies.”
The annualized flare rate, however, did not change.
Adverse event data showed a slight increase in herpes zoster with the 300 mg dose. “Other than that, there were no major standouts as far as the safety profile goes,” Furie said.
Despite the failure to reach the primary endpoint, Furie believes that the 300 mg dose of anifrolumab can have clinical benefit in these patients.
“Medication rules and endpoint selection are critical for SLE trials,” he said. “There is still a lot to learn. We need to look at the totality of the data in this study to understand the possible effects of SLE treatments.” – by Rob Volansky
Furie R. Abstract #1763. A phase 3 randomized controlled trial of anifrolumab in patients with moderate to severe systemic lupus erythematosus. Presented at: American College of Rheumatology/Association of Rheumatology Professionals Annual Meeting; Nov. 9-13, 2019; Atlanta.
Disclosure: Furie reports associations with AstraZeneca/MedImmune.