Adding investigational anifrolumab to standard therapy lowers disease activity, limits the need for corticosteroids, and eases skin symptoms in people with moderate to severe systemic lupus erythematosus (SLE), a Phase 3 clinical trial shows.
Trial results were discussed in a presentation titled “A Phase 3 Randomized Controlled Trial of Anifrolumab in Patients with Moderate to Severe Systemic Lupus Erythematosus” at the 2019 American College of Rheumatology and Association of Rheumatology Professionals (ACR/ARP) Annual Meeting, recently held in Atlanta.
AstraZeneca‘s anifrolumab is an experimental monoclonal antibody that blocks the activity of all types of type I interferons, which are pro-inflammatory molecules that are excessively produced by as many as 4 in 5 people with SLE.
In TULIP 1, 457 people with SLE were randomly assigned to treatment with anifrolumab at one of two doses — 300 mg (180 people) or 150 mg (93 people) — or a placebo (184 people). Characteristics at the start of the study were similar across the groups. About 80% of participants completed the trial.
Treatment was given intravenously (into the vein) every four weeks, for a total of 13 doses. All participants continued to receive standard treatment, such as corticosteroids.
Prior reports showed that the trial did not meet its primary goal, as the proportion of disease activity reduction at week 52 (one year) — measured by an SLE Responder Index of 4 or higher — was similar between anifrolumab (36.2% with the higher dose) and placebo (40.4%).
However, using a different tool to measure SLE disease activity — the British Isles Lupus Assessment Group based Composite Lupus Assessment (BICLA) — the new analysis showed significantly superior response rates with 300 mg of anifrolumab (46.1%) than with a placebo (29.6%). This difference was similar in participants with high interferon levels, with response rates of 45.9% with anifrolumab and 27.5% with placebo.
For reference, clinical benefits with BICLA require improvement in all organs showing disease activity at baseline (study start), and no new flares.
In addition, a higher percentage of participants treated with 300 mg of anifrolumab decreased their use of corticosteroids compared with those on placebo (48.8% vs. 32.1%).
The higher anifrolumab dose also led to more patients whose skin symptoms were relieved, compared with placebo (43.6% vs. 24.9%), assessed by the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). The experimental treatment also resulted in less joint activity and fewer flares.
Results of TULIP 2 were also presented at the meeting. These data supported the reductions in SLE disease activity (assessed with BICLA), corticosteroid use, and severity of skin lesions with add-on anifrolumab.
Previously, a Phase 2 trial (NCT01438489) showed that anifrolumab is well-tolerated and decreases disease activity in the same patient population.
“Let’s hope that the totality of the phase 2 and 3 data will be looked upon favorably and provide the lupus community with an additional therapy,” Richard Furie, MD, principal investigator of TULIP 1 and a professor at the Feinstein Institutes for Medical Research, said in a press release.