Sifalimumab, an anti-interferon-α monoclonal antibody, in moderate to severe systemic lupus erythematosus: a randomised, double-blind, placebo-controlled study

Abstract

Objectives: The efficacy and safety of sifalimumab were assessed in a phase IIb, randomised, double-blind, placebo-controlled study (NCT01283139) of adults with moderate to severe active systemic lupus erythematosus (SLE).

Methods: 431 patients were randomised and received monthly intravenous sifalimumab (200 mg, 600 mg or 1200 mg) or placebo in addition to standard-of-care medications. Patients were stratified by disease activity, interferon gene-signature test (high vs low based on the expression of four genes) and geographical region. The primary efficacy end point was the percentage of patients achieving an SLE responder index response at week 52.

Results: Compared with placebo, a greater percentage of patients who received sifalimumab (all dosages) met the primary end point (placebo: 45.4%; 200 mg: 58.3%; 600 mg: 56.5%; 1200 mg 59.8%). Other improvements were seen in Cutaneous Lupus Erythematosus Disease Area and Severity Index score (200 mg and 1200 mg monthly), Physician's Global Assessment (600 mg and 1200 mg monthly), British Isles Lupus Assessment Group-based Composite Lupus Assessment (1200 mg monthly), 4-point reductions in the SLE Disease Activity Index-2000 score and reductions in counts of swollen joints and tender joints. Serious adverse events occurred in 17.6% of patients on placebo and 18.3% of patients on sifalimumab. Herpes zoster infections were more frequent with sifalimumab treatment.

Conclusions: Sifalimumab is a promising treatment for adults with SLE. Improvement was consistent across various clinical end points, including global and organ-specific measures of disease activity.

Trial registration number: NCT01283139; Results.

Keywords: Autoimmune Diseases; Systemic Lupus Erythematosus; Treatment.

Figure 1

Primary end point: patients achieving a SRI(4) at week 52 (mITT population). Treatment was administered on days 1, 15 and 29, and then every 28 days thereafter. mITT, modified intention-to-treat; SRI(4), systemic lupus erythematosus responder index.

Figure 2

Patients achieving an mSRI response with 5-, 6-, 7-, or 8-point decreases in SLEDAI-2K scores (mITT population). *Primary end point. Treatment was administered on days 1, 15 and 29, and then every 28 days thereafter. mITT, modified intention-to-treat; mSRI, modified systemic lupus erythematosus responder index; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000.

Figure 3

Secondary end point. Panel A shows CLASI responder rate (patients with a CLASI activity score greater ≥10 at baseline who achieved a ≥4-point reduction) (mITT population). Panel B shows examples from the 600 mg and 1200 mg groups of skin response following sifalimumab treatment. (Full permission for use of these images has been granted by patients.) Treatment was administered on days 1, 15 and 29, and then every 28 days thereafter. CLASI, Cutaneous Lupus Erythematosus Disease Area and Severity Index; mITT, modified intention-to-treat; SLEDAI, Systemic Lupus Erythematosus Disease Activity Index.