TULIP-2: Anifrolumab meets BICLA endpoint, confers higher skin response rates in SLE
Patients with systemic lupus erythematosus had a higher rate of British Isles Lupus Assessment Group-based Composite Lupus Assessment, or BICLA, response with anifrolumab compared with placebo, according to data from the TULIP-2 study, published in The New England Journal of Medicine.
Anifrolumab (AstraZeneca) also resulted in higher rates of skin response and steroid tapering.
These data follow the failure of the TULIP-1 study to meet its primary endpoint for anifrolumab in SLE. The new, composite primary outcome of TULIP-2 was initially a secondary outcome in TULIP-1.
“This is only the second drug to have a positive phase 3 trial in SLE in the last 60 years,” Eric F. Morand MBBS, PhD, FRACP, of Monash University, Melbourne, Australia, told Healio Rheumatology. “As biological uptake in SLE management remains low, patients are still mostly treated with steroids and immunosuppressive drugs. Little has changed since the 1950s; there remains huge unmet need for medicines addressing validated targets. It is a breakthrough finding supporting efficacy of anifrolumab, validating the type I interferon pathway in the pathogenesis of SLE, and informing on measurement in SLE trials.”
To study the efficacy and safety of anifrolumab with the new primary outcome, Morand and colleagues randomly assigned 362 patients with SLE to receive either 300 mg of the drug or placebo every 4 weeks for a total of 48 weeks. Among the participants, 180 were treated with IV anifrolumab and 182 received placebo. The complete primary endpoint was a BICLA response at week 52. This included a reduction of moderate-to-severe baseline disease activity as well as no worsening of any of the nine organ systems in the BILAG index.
The primary outcome also required no disease worsening based on the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), no increase of 0.3 points or more in the Physician Global Assessment score of disease activity, no discontinuation of the trial drug, and no use of medications restricted by the protocol. The secondary outcomes included a BICLA response in patients with a high interferon gene signature at baseline, as well as reductions in glucocorticoid doses, the severity of skin disease, counts of swollen and tender joints, and annual flare rate.
According to the researchers, 47.8% of participants in the anifrolumab group achieved a BICLA response, compared with 31.5% of those treated with placebo (difference of 16.3; 95% CI, 6.3-26.3). Among patients with a high interferon gene signature, 48% of patients treated with anifrolumab demonstrated a BICLA response, compared with 30.7% in the placebo group. In patients with a low interferon gene signature, the percentages were 46.7% and 35.5%, respectively.
Regarding the secondary end points, patients treated with anifrolumab demonstrated significant benefit in glucocorticoid dose and skin disease severity, but not in counts of swollen and tender joints and annual flare rate. Herpes zoster occurred in 7.2% of participants treated with anifrolumab, and bronchitis occurred in 12.2%. There was one death, from pneumonia, in the anifrolumab group.
“New medicines are desperately needed in SLE,” Morand said. “If this drug receives regulatory approval, as up to 80% of patients carry a positive interferon signature, large numbers of patients not well-controlled with other drugs stand to benefit. Reducing disease activity while simultaneously reducing steroids is the number-one goal of SLE management, and that is what was achieved in this trial.” – by Jason Laday
Disclosure: The researchers report funding from AstraZeneca. Please see the study for all other authors’ relevant financial disclosures.