Patients with systemic lupus erythematosus responded positively to sifalimumab vs. placebo

A majority of patients with seropositive, moderate-to-severe systemic lupus erythematosus responded positively to treatment with sifalimumab in a year-long, phase 2b clinical trial, according to researchers.

The researchers analyzed the efficacy and safety of sifalimumab in 431 patients with moderate-to-severe systemic lupus erythematosus (SLE) who did not respond to previous standard-of-care treatment. The minimum disease activity required for enrollment of SLE Disease Activity Index 2000 (SLEDAI-2K) of 6 or higher and one British Isles Lupus Assessment Group index A or two Bs and Overall Physician’s Global Assessment of Disease Activity score of one or greater.

Patients were randomly assigned to receive monthly intravenous 200 mg, 600 mg or 1,200 mg of sifalimumab or placebo for 1 year. The researchers stratified patient randomization using disease activity, interferon-gamma (IFN) 4-gene and geographic region. The study’s primary endpoint was SLE Responder Index response at day 365.

Patients had similar baseline characteristics across all treatment groups. Median disease duration was 8.2 years, and average Systemic Lupus International Collaborating Clinics / American College of Rheumatology damage score was 0.7 and SLEDAI-2K 11.3, according to the researchers.

Positive interferon gene signatures were present in 81.2%, low C3 was seen in 42.9%, low C4 was seen in 26.7% and elevated double-stranded DNA antibodies were seen in 26.5% of patients at baseline.

At day 365, patients treated with 200 mg, 600 mg and 1,200 mg were more likely to score four or higher on the SLE Responder index (SRI) vs. those who received placebo, according to the researchers. Those who reported SRI score of six and eight at 1 year were also higher than placebo.

Patients with moderate-to-severe mucocutaneous involvement who were treated with sifalimumab showed improvement in Cutaneous Lupus Erythematosus Disease Area and Severity Index scores of four points or more vs. placebo.

Common adverse events included worsening SLE symptoms (30% vs. 34% in the placebo group), urinary tract infections (17.6% vs. 13.9% of placebo arm) and headaches (13.3% vs. 13.9% of placebo arm). Infection with herpes zoster was also more common in the treatment groups (200 mg, 4.6%; 600 mg, 3.7%; 1,200 mg, 8.4% vs. 0.9% in the placebo arm), according to the researchers.

Reference:

Merrill JT. Paper #L4. Presented at: American College of Rheumatology Annual Meeting. Nov. 14-19, 2014; Boston.

Disclosure: See the study for a full list of all authors’ relevant financial disclosures.