Efficacy and safety of an interleukin 6 monoclonal antibody for the treatment of systemic lupus erythematosus: A phase II dose-ranging randomised controlled trial

Daniel J. Wallace, Vibeke Strand, Joan T. Merrill, Serghei Popa, Alberto J. Spindler, Alicia Eimon, Michelle Petri, Josef S. Smolen, Joseph Wajdula, Jared Christensen, Cheryl Li, Annette Diehl, Michael S. Vincent, Jean Beebe, Paul Healey, Sudhakar Sridharan

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Abstract

Objectives This phase II trial evaluated the efficacy and safety of an interleukin (IL) 6 monoclonal antibody for systemic lupus erythematosus (SLE). Methods Patients with active disease were randomised to placebo or PF-04236921 10 mg, 50 mg or 200 mg, subcutaneously, every 8 weeks with stable background therapy. SLE Responder Index (SRI-4; primary end point) and British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) were assessed at week 24. Post hoc analysis identified an enriched population based upon planned univariate analyses. Results 183 patients received treatment (placebo, n=45; 10 mg, n=45; 50 mg, n=47; 200 mg, n=46). The 200 mg dose was discontinued due to safety findings and not included in the primary efficacy analysis. The SRI-4 response rates were not significant for any dose compared with placebo; however, the BICLA response rate was significant for 10 mg (p=0.026). The incidence of severe flares was significantly reduced with 10 mg (n=0) and 50 mg (n=2) combined versus placebo (n=8; p<0.01). In patients with greater baseline disease activity (enriched population), the SRI-4 (p=0.004) and BICLA (p=0.012) response rates were significantly different with 10 mg versus placebo. Four deaths (200 mg, n=3; 10 mg, n=1) occurred. The most frequently reported adverse events included headache, nausea and diarrhoea. Conclusions PF-04236921 was not significantly different from placebo for the primary efficacy end point in patients with SLE. Evidence of an effect with 10 mg was seen in a post hoc analysis. Safety was acceptable for doses up to 50 mg as the 200 mg dose was discontinued due to safety findings.

Original languageEnglish (US)
Pages (from-to)534-542
Number of pages9
JournalAnnals of the Rheumatic Diseases
Volume76
Issue number3
DOIs
StatePublished - Mar 1 2017

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Keywords

  • Autoimmune Diseases
  • Cytokines
  • Systemic Lupus Erythematosus
  • Treatment

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Wallace, D. J., Strand, V., Merrill, J. T., Popa, S., Spindler, A. J., Eimon, A., Petri, M., Smolen, J. S., Wajdula, J., Christensen, J., Li, C., Diehl, A., Vincent, M. S., Beebe, J., Healey, P., & Sridharan, S. (2017). Efficacy and safety of an interleukin 6 monoclonal antibody for the treatment of systemic lupus erythematosus: A phase II dose-ranging randomised controlled trial. Annals of the Rheumatic Diseases, 76(3), 534-542. https://doi.org/10.1136/annrheumdis-2016-209668