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Eric Morand, MD, discusses “Attainment of the Lupus Low Disease Activity State in Response to Anifrolumab in 2 Phase 3 Trials.”
Rheumatology Network interviewed Eric Morand, MD, about his ACR presentation entitled, “Attainment of the Lupus Low Disease Activity State in Response to Anifrolumab in 2 Phase 3 Trials.” Morand is Professor of Medicine at Monash University and Head of Rheumatology at Monash Health.
RN: Why is the lupus low disease activity state (LDAS) a treat-to-target endpoint for patients with lupus?
Eric Morand, MD: So, prior to 5 years ago, there were no validated treat-to-target endpoints for lupus, unlike in rheumatoid arthritis, psoriatic arthritis, etc, where treat-to-target has become standard of care. There was no way to make that standard of care in lupus until you first devised endpoints to treat towards. So, low disease activity is a good target. Although of course, remission is the ideal target. Remission attainment in lupus is extremely rare. So, the group of us who devised lupus low disease activity state set out to devise an endpoint which would be associated with protection from long-term outcomes. And that's been shown to be the case in multiple retrospective cohort studies, but also in a prospective validation study. Attainment of low disease activity states is protected from flare, protected from damage accrual, protective of health-related quality of life. And in a separate abstract at this ACR meeting, we'll also show it's protected from mortality. So, it's a highly validated treat to target endpoint state for lupus.
RN: Can you tell me a bit about the TULIP-1 and TULIP-2 study designs?
EM: So both studies were 52-week studies done globally, in multiple countries with multiple ancestral backgrounds of patients with moderate-to-severe active lupus that were randomized to receive either placebo or anifrolumab in addition to standard care. Patients who entered the study had to have active disease. The 2 studies were identical apart from 2 differences: firstly, in TULIP-1, there were 2 doses of anifrolumab 300 milligram per month and 150 milligram per month, whereas in TULIP-2, there was only 300 milligrams a month. And also, they had different primary outcome measures. And both trials had multiple hits on goal with significant differences between anifrolumab and placebo, though into TULIP-1, the primary outcomes were not significantly different between anifrolumab and placebo. But the totality of evidence illustrates that anifrolumab is effective in the treatment of active lupus.
RN: What were the the clinical significance of these results?
EM: In the TUPLIP-2 abstract, we took the endpoint and applied it to the pooled TULIP-1 and TULIP-2 datasets to evaluate LDAS as a clinical trial endpoint per se, and, secondly, to evaluate whether any follow up treatment resulted in higher attainment of low disease activity state. The findings were firstly that LDAS payment was observed. And that fits with our hypothesis of low disease activity being a stringent endpoint and that analysis was done regardless of therapy. Then we split the patients into anifrolumab-treated and placebo-treated and found highly significant difference in LDAS attainment for anifrolumab-treated patients compared to placebo. So, basically we found that anifrolumab was more likely to put patients into LDAS than placebo. The significance of this is that LDAS has been shown to be protected from damage of, health-related quality of life reduction, and death. And these data show that anifrolumab puts more patients into that favorable treat-to-target state.
RN: Does your team plan on doing any further research on this topic?
EM: Yes, we would like to analyze these data for proportion of patients attaining remission. We'd also like to see the LDAS endpoint tested in other clinical trial cohorts that's already been done retrospectively in a few examples. But we'd like to see it adopted as a standard outcome measure for lupus clinical trials.