Anifrolumab Reduces Disease Activity, Skin Lesion Severity, and Corticosteroid Use in SLE Patients, Phase 3 Trial Shows

Adding anifrolumab to standard-of-care treatment significantly reduced disease activity, corticosteroid use, and severity of skin lesions in people with moderate-to-severe systemic lupus erythematosus (SLE), according to data from a Phase 3 trial.

The research, “Efficacy and Safety of Anifrolumab in Patients with Moderate to Severe Systemic Lupus Erythematosus: Results of the Second Phase 3 Randomized Controlled Trial,” was presented at the 2019 American College of Rheumatology and the Association of Rheumatology Professionals Annual Meeting, in Atlanta.

AstraZeneca’s anifrolumab is a monoclonal antibody that blocks the activity of all types of type I interferon (IFN) molecules, including IFN-alpha, IFN-beta, and IFN-omega. These pro-inflammatory molecules are produced in excess by 60% to 80% of adults with SLE and are thought to be directly associated with disease activity.

The multicenter, double-blind TULIP 2 trial (NCT02446899; sponsored by AstraZeneca) evaluated the safety and efficacy of anifrolumab in 365 adults with moderate-to-severe SLE. (TULIP stands for Treatment of Uncontrolled Lupus via the Interferon Pathway).

Participants were randomly assigned to receive either anifrolumab (300 mg) or a placebo by intravenous infusion every four weeks, over one year (52 weeks). All were on standard of care with corticosteroids, antimalarials (such as hydroxychloroquine), and/or immunosuppressants.

The study’s main goal was to assess whether anifrolumab would reduce disease activity. This was determined with the British Isles Lupus Assessment Group based Composite Lupus Assessment (BICLA), which requires improvement in all organs showing disease activity at baseline, and no new flares.

Secondary goals included measuring the the effects of anifrolumab on the use of corticosteroids and on skin lesions associated with SLE.

Previously reported top-line data had revealed that TULIP 2 trial met its primary goal. Newly available findings show that 47.8% of the patients treated with anifrolumab experienced a clinically meaningful reduction of disease activity within one year, compared with 31.5% of those treated with a placebo.

These positive results were in agreement with those of the Phase 3 TULIP 1 (NCT02446912) and the Phase 2 MUSE (NCT01438489) trials when using BICLA as a measure of disease activity to assess anifrolumab’s efficacy in SLE. (However, TULIP 1 did not reach its primary goal of reduction in disease activity assessed with a different tool, called the SLE Responder Index).

“The results across the MUSE and TULIP trials are very important because they support anifrolumab’s potential to address [SLE],” Richard Furie, chief of rheumatology at Northwell Health, and principal investigator on TULIP 1 and MUSE, said in a press release.

Updated findings from TULIP 2 also showed that anifrolumab significantly improved several key secondary goals. For instance, more than half (51.5%) of patients treated with this experimental medication were able to lower their daily doses of prednisone, a corticosteroid often used to control inflammation in SLE. Less than a third (30.2%) of the people on the placebo reached this goal.

In addition, after 12 weeks of treatment, 49% of those receiving anifrolumab experienced a significant reduction of degree and severity of their skin lesions (measured by the Cutaneous Lupus Erythematosus Disease Area and Severity Index), a benefit seen in 25% of those receiving a placebo.

“The TULIP 2 results demonstrated that, by targeting the type I interferon receptor, anifrolumab reduces overall disease activity, reduces corticosteroid use and improves skin manifestations,” said Eric F. Morand, professor at Monash University, in Australia, and principal investigator of TULIP 2.

The safety profile of anifrolumab was consistent with data from previous trials. As reported in TULIP 1, viral infections caused by herpes zoster were more frequent among patients treated with anifrolumab (7.2%) than among those taking a placebo (1.1%).

In contrast, more patients on the placebo than on anifrolumab had serious adverse events (17% vs. 8.3%), and side effects requiring treatment discontinuation (7.1% vs. 2.8%).

Most adverse events were all mild or moderate in severity and easily resolved with antiviral treatment. No new safety concerns were identified.

“This is the first Phase 3 to successfully show effectiveness since [SLE treatment] Benlysta and is welcome news to a community waiting for more treatment options,” Kenneth M. Farber, president and CEO of the Lupus Research Alliance, said in another press release.

“The results of the TULIP-2 trial validate years of research by our funded scientists on understanding the interferon pathway which anifrolumab targets,” he said.

Morand added: “These results finally and definitively prove the interferon hypothesis for lupus, potentially unlocking a host of new treatment approaches.”

“We all hope this leads to approval of anifrolumab and great outcomes for patients with lupus,” he said.

Mary K. Crow, MD, an expert who characterized the role of IFN in lupus and suggested that it could be a therapeutic target, added: “I am particularly gratified to see these positive results in a late-stage study.”

Besides the two TULIP trials, anifrolumab is being tested in a Phase 3 long-term extension trial in SLE (NCT02794285) and a Phase 2 trial in lupus nephritis (NCT02547922).