medwireNews: Anifrolumab has shown clinical efficacy in systemic lupus erythematosus (SLE), based on BICLA response as the primary outcome, TULIP-2 results show.
This phase III study, the second to be presented on the subject at the 2019 ACR/ARP Annual Meeting in Atlanta, Georgia, USA, supports the secondary endpoint findings from TULIP-1, already reported by medwireNews.
Unlike TULIP-1, which failed to meet its primary endpoint based on SRI-4 response, TULIP-2 shows “a statistically and clinically meaningful increase in BICLA response [with anifrolumab] versus placebo,” Eric Morand, from Monash University in Melbourne, Victoria, Australia, told delegates at the late-breaking abstract session.
At week 52, 47.8% of 180 patients with moderate-to-severe SLE randomly assigned to receive anifrolumab 300 mg intravenously every 4 weeks for 48 weeks had achieved BICLA response, compared with 31.5% of 182 patients assigned to placebo, giving a significant treatment difference of 16.3 percentage points after multiplicity testing.
“Separation between the treatment arms occurred early and was maintained across the duration of the trial,” Morand pointed out.
The treatment effect of anifrolumab, a human monoclonal antibody to the type I interferon (IFN) receptor subunit 1, was even more evident in the 301 patients who scored high on tests for the type 1 IFN gene signature, with a 17.3% difference in BICLA response between the 150 taking anifrolumab and the 151 taking placebo.
The study included mandatory tapering of oral corticosteroids for patients taking 10 mg/day or above to no more than 7.5 mg/day between weeks 8 and 40, and Morand noted that significantly more patients in the anifrolumab group sustained this low level of steroids than those in the placebo group, at 51.5% versus 30.2%, respectively.
Skin disease outcomes were also significantly improved with anifrolumab, with significantly more patients with a baseline Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) score of 10 or above achieving at least a 50% reduction, with a treatment difference at 12 weeks of 24 percentage points that was sustained for the duration of the trial.
Additional supportive evidence in favor of anifrolumab included numeric improvement in yearly flare rates and time to first flare, early and sustained BICLA response, and significant SRI-4, 5, 6, 7, and 8 responses, but these outcomes were not adjusted for multiple testing.
Presenting the safety data, Morand pointed out that serious adverse events were more frequent in the placebo group; these included pneumonia and SLE worsening. There was one death in the anifrolumab group from community-acquired suspected bacterial pneumonia.
Adverse events of special interest were “largely balanced between the groups,” said Morand. The only exception was herpes zoster, which was seen in 7% of anifrolumab-treated patients, compared with 1% of placebo-treated patients, but Morand noted that all cases responded to antiviral therapy and none required discontinuation of treatment.
Morand concluded that “the primary endpoint of TULIP-2 was achieved,” saying: “TULIP-2 was a positive phase III trial in lupus, and there aren’t many times that that sentence has been spoken.
“This result adds to cumulative evidence identifying anifrolumab as a potential new treatment option for SLE.”
By Lucy Piper
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