Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis (faSScinate): a phase 2, randomised, controlled trial.

Abstract

BACKGROUND:

Systemic sclerosis is a rare disabling autoimmune disease with few treatment options. The efficacy and safety of tocilizumab, an interleukin 6 receptor-α inhibitor, was assessed in the faSScinate phase 2 trial in patients with systemic sclerosis.

METHODS:

We did this double-blind, placebo-controlled study at 35 hospitals in Canada, France, Germany, the UK, and the USA. We enrolled adults with progressive systemic sclerosis of 5 or fewer years' duration from first non-Raynaud's sign or symptom. Patients were randomly assigned (1:1) to weekly subcutaneous tocilizumab 162 mg or placebo. The primary endpoint was the difference in mean change from baseline in modified Rodnan skin score at 24 weeks. This study is registered with ClinicalTrials.gov, number NCT01532869.

FINDINGS:

We enrolled 87 patients: 43 assigned to tocilizumab and 44 assigned to placebo. The least squares mean change in modified Rodnan skin score at 24 weeks was -3·92 in the tocilizumab group and -1·22 in the placebo group (difference -2·70, 95% CI -5·85 to 0·45; p=0·0915). The least squares mean change at 48 weeks was -6·33 in the tocilizumab group and -2·77 in the placebo group (treatment difference -3·55, 95% CI -7·23 to 0·12; p=0·0579). In one of several exploratory analyses, fewer patients in the tocilizumab group than in the placebo group had a decline in percent predicted forced vital capacity at 48 weeks (p=0·0373). However, we detected no significant difference in disability, fatigue, itching, or patient or clinician global disease severity. 42 (98%) of 43 patients in the tocilizumab group versus 40 (91%) of 44 in the placebo group had adverse events. 14 (33%) versus 15 (34%) had serious adverse events. Serious infections were more common in the tocilizumab group (seven [16%] of 43 patients) than in the placebo group (two [5%] of 44). One patient died in relation to tocilizumab treatment.

INTERPRETATION:

Tocilizumab was not associated with a significant reduction in skin thickening. However, the difference was greater in the tocilizumab group than in the placebo group and we found some evidence of less decline in forced vital capacity. The efficacy and safety of tocilizumab should be investigated in a phase 3 trial before definitive conclusions can be made about its risks and benefits.

FUNDING:

F Hoffmann-La Roche, Genentech.

• Authors: Dinesh Khanna, Christopher P Denton, Angelika Jahreis, Jacob M van Laar, Tracy M Frech, Marina E Anderson, Murray Baron, Lorinda Chung, Gerhard Fierlbeck, Santhanam Lakshminarayanan, Yannick Allanore, Janet E Pope, Gabriela Riemekasten, Virginia Steen, Ulf Müller-Ladner, Robert Lafyatis, Giuseppina Stifano, Helen Spotswood, Haiyin Chen-Harris, Sebastian Dziadek, Alyssa Morimoto, Thierry Sornasse, Jeffrey Siegel, Daniel E Furst
• Journal: Lancet (London, England) (Lancet) Vol. 387 Issue 10038 Pg. 2630-2640 (Jun 25 2016) ISSN: 1474-547X [Electronic] England
• PMID: 27156934 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Biomarkers
• Interleukin-6
• tocilizumab

Topics

• Adult
• Aged
• Antibodies, Monoclonal, Humanized (administration & dosage, therapeutic use)
• Biomarkers (metabolism)
• Canada
• Double-Blind Method
• Europe
• Female
• Humans
• Injections, Subcutaneous
• Interleukin-6 (physiology)
• Male
• Middle Aged
• Scleroderma, Systemic (complications, drug therapy, metabolism)
• Treatment Outcome
• United Kingdom
• Vital Capacity