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.

• Authors: Munther Khamashta, Joan T Merrill, Victoria P Werth, Richard Furie, Kenneth Kalunian, Gabor G Illei, Jorn Drappa, Liangwei Wang, Warren Greth, CD1067 study investigators
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 75 Issue 11 Pg. 1909-1916 (Nov 2016) ISSN: 1468-2060 [Electronic] England
• PMID: 27009916 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)
• Copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antigens
• Cytoskeletal Proteins
• IFI27 protein, human
• IFI44 protein, human
• Membrane Proteins
• Proteins
• Oxidoreductases Acting on CH-CH Group Donors
• RSAD2 protein, human
• sifalimumab

Topics

• Adult
• Antibodies, Monoclonal (administration & dosage)
• Antibodies, Monoclonal, Humanized
• Antigens (blood)
• Cytoskeletal Proteins (blood)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Female
• Humans
• Lupus Erythematosus, Systemic (blood, drug therapy)
• Male
• Membrane Proteins (blood)
• Middle Aged
• Oxidoreductases Acting on CH-CH Group Donors
• Proteins (analysis)
• Severity of Illness Index
• Treatment Outcome