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

Abstract

ObjectivesThe 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).Methods431 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.ResultsCompared 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.ConclusionsSifalimumab 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 numberNCT01283139; Results.

The Future of B-cell Activating Factor Antagonists in the Treatment of Systemic Lupus Erythematosus

“…The primary endpoint was not achieved in the phase-II trial of the anti-IFNα mAb, rontalizumab [79], whereas the primary endpoint (assessed at week 52) was achieved in the phase-IIb trial of a different anti-IFNα mAb, sifalimumab. In this latter trial, the absolute percentage difference in clinical response between patients treated with the highest dose of sifalimumab and those treated with placebo was 14% [80], similar to the absolute percentage differences observed in the successful trial with belimumab or tabalumab. Of note, however, were results from the phase-IIb trial of the anti-IFNα receptor mAb, anifrolumab, in which the absolute percentage difference in clinical response between patients treated with the optimal dose of anifrolumab and those treated with placebo being 26% [81].…”

Effects of Hydroxychloroquine in Patients With Cutaneous Lupus Erythematosus: A Multicenter, Double‐Blind, Randomized, Parallel‐Group Trial

“…Since the registration of our study, another randomized clinical trial using the CLASI score as an end point has been published (26). In patients with moderateto-severe skin disease (CLASI score $10), it was shown that 50% of patients had improvement in the CLASI activity score.…”

The interferon paradox: can inhibiting an antiviral mechanism advance an HIV cure?

“…This has led to the development of several clinical interventions that include the use of antibodies to block IFNs and their downstream target genes to treat these autoimmune diseases (22). Emerging phase II/III clinical trial data suggest that these pathways can be inhibited therapeutically in an effective and safe manner (23,24). Should these agents continue to show a favorable safety profile, we believe that efforts should be made to move these interventions into the HIV cure arena.…”