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

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Clinical and epidemiological research
Extended report
Sifalimumab, an anti-interferon-α monoclonal antibody, in moderate to severe systemic lupus erythematosus: a randomised, double-blind, placebo-controlled study
  1. Munther Khamashta1,
  2. Joan T Merrill2,
  3. Victoria P Werth3,4,
  4. Richard Furie5,
  5. Kenneth Kalunian6,
  6. Gabor G Illei7,
  7. Jorn Drappa7,
  8. Liangwei Wang8,
  9. Warren Greth7
  10. on behalf of the CD1067 study investigators
  1. 1Graham Hughes Lupus Research Laboratory, Division of Women's Health, King's College London, The Rayne Institute, St Thomas’ Hospital, London, UK
  2. 2Clinical Pharmacology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
  3. 3Lupus Research Institute, Philadelphia VA Medical Center, Philadelphia, Pennsylvania, USA
  4. 4University of Pennsylvania, Philadelphia, Pennsylvania, USA
  5. 5Division of Rheumatology, Northwell Health, Great Neck, New York, USA
  6. 6Department of Rheumatology, UCSD School of Medicine, La Jolla, California, USA
  7. 7Clinical Development, Respiratory, Inflammation and Autoimmunity, MedImmune, Gaithersburg, Maryland, USA
  8. 8Department of Biostatistics, MedImmune, Gaithersburg, Maryland, USA
  1. Correspondence to Professor Munther Khamashta, Graham Hughes Lupus Research Laboratory, Division of Women's Health, King's College London, The Rayne Institute, Lambeth Wing 4th Floor, St Thomas’ Hospital, London SE1 7EH, UK; munther.khamashta{at}kcl.ac.uk

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.

  • Systemic Lupus Erythematosus
  • Treatment
  • Autoimmune Diseases

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/annrheumdis-2015-208562

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    Footnotes

    • Handling editor Tore K Kvien

    • Contributors Representatives of MedImmune conducted the data analyses. The first draft of this manuscript was written by WG, and all authors interpreted the data and participated in the preparation of the manuscript with support from professional medical writers. All of the authors made the decision to submit the manuscript for publication, and confirm the veracity and completeness of the data and analyses, as well as the ethical conduct and reporting of the study according to its trial protocol.

    • Funding The study was funded by MedImmune.

    • Competing interests MK received a grant for this study from MedImmune/AstraZeneca; grants for other work from Bayer; and personal consultancy fees from INOVA Diagnostics, MedImmune, GlaxoSmithKline and UCB. JTM reports personal fees from MedImmune/AstraZeneca; and grants and personal fees from Genentech/Roche outside of the submitted work. VPW received personal fees from MedImmune/AstraZeneca, during the conduct of this study. RF, KK, GGI, JD, LW and WG received personal fees from AstraZeneca/MedImmune. WG and GGI hold stocks in AstraZeneca/MedImmune. JD has a patent pending. VPW is a named inventor and holds a patent for the CLASI copyright owned by the University of Pennsylvania. GGI, JD, LW and WG are employees of MedImmune.

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

    • Ethics approval This study was conducted in accordance with the principles of the Declaration of Helsinki and the International Conference on Harmonisation Guidance for Good Clinical Practice. Independent ethics committee approval was obtained and all patients provided written informed consent in accordance with local requirements.

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