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Safety profile and clinical activity of sifalimumab, a fully human anti-interferon α monoclonal antibody, in systemic lupus erythematosus: a phase I, multicentre, double-blind randomised study
  1. Joan T Merrill1,
  2. Daniel J Wallace2,
  3. Michelle Petri3,
  4. Kyriakos A Kirou4,
  5. Yihong Yao5,
  6. Wendy I White5,
  7. Gabriel Robbie5,
  8. Robert Levin6,
  9. Seth M Berney7,
  10. Vishala Chindalore8,
  11. Nancy Olsen9,10,
  12. Laura Richman5,
  13. Chenxiong Le5,
  14. Bahija Jallal5,
  15. Barbara White5,11 for the Lupus Interferon Skin Activity (LISA) Study Investigators
  1. 1Department of Clinical Pharmacology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
  2. 2Wallace Rheumatic Study Center, Los Angeles, California, USA
  3. 3Division of Rheumatology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  4. 4Mary Kirkland Center for Lupus Care, Hospital for Special Surgery, New York, NY, USA
  5. 5MedImmune, LLC, Gaithersburg, Maryland, USA
  6. 6Clinical Research of West Florida Inc., Clearwater, Florida, USA
  7. 7Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA
  8. 8Pinnacle Research Group, LLC, Anniston, Alabama, USA
  9. 9Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
  10. 10Penn State Hershey Medical Center, Hershey, Pennsylvania, USA
  11. 11UCB Biosciences, Raleigh, North Carolina, USA
  1. Correspondence to Joan T. Merrill, MD, Department of Clinical Pharmacology, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA; jtmmail{at}


Background Type I interferons (IFNs) appear to play a central role in disease pathogenesis in systemic lupus erythematosus (SLE), making them potential therapeutic targets.

Methods Safety profile, pharmacokinetics, immunogenicity, pharmacodynamics and clinical activity of sifalimumab, an anti-IFNα monoclonal antibody, were assessed in a phase I, multicentre, randomised, double-blind, dose-escalation study with an open-label extension in adults with moderately active SLE. Subjects received one intravenous dose of sifalimumab (n=33 blinded phase, 0.3, 1, 3, 10 or 30 mg/kg; n=17 open-label, 1, 3, 10 or 30 mg/kg) or placebo (n=17). Each phase lasted 84 days.

Results Adverse events (AEs) were similar between groups; about 97% of AEs were grade 1 or 2. All grade 3 and 4 AEs and all serious AEs (2 placebo, 1 sifalimumab) were deemed unrelated to the study drug. No increase in viral infections or reactivation was observed. Sifalimumab caused dose-dependent inhibition of type I IFN-induced mRNAs (type I IFN signature) in whole blood and corresponding changes in related proteins in affected skin. Exploratory analyses showed consistent trends toward improvement in disease activity in sifalimumab-treated versus placebo-treated subjects. A lower proportion of sifalimumab-treated subjects required new or increased immunosuppressive treatments (12% vs 41%; p=0.03) and had fewer Systemic Lupus Erythematosus Disease Activity Index flares (3% vs 29%; p=0.014).

Conclusions Sifalimumab had a safety profile that supports further clinical development. This trial demonstrated that overexpression of type I IFN signature in SLE is at least partly driven by IFNα, and exploratory analyses suggest that IFNα inhibition may be associated with clinical benefit in SLE.

Trial registration number NCT00299819.

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  • JTM and DJW contributed equally to this study.

  • Funding This study and manuscript preparation were funded by MedImmune, LLC.

  • Competing interests JTM, DJW, MP, KAK, RL, SMB, VC and NO received research funding from MedImmune. JTM has received consulting fees from MedImmune, Biogen Idec, Genentech and Roche. Louisiana State University Health Sciences Center has received research funding on behalf of SMB from Biogen Idec, Genentech and Roche. YY, WIW, GR, LR, CL and BJ are employees of MedImmune. BW is a former employee of MedImmune.

  • Ethics approval This study was conducted with the approval of the institutional review boards at participating sites.

  • Provenance and peer review Not commissioned; externally peer reviewed.