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

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• 作者：Prof Dinesh Khanna ; MD^a ; ^{khannad@med.umich.edu" class="auth_mail" title="E-mail the corresponding author} ; Prof Christopher P Denton ; PhD^b ; Angelika Jahreis ; MD^c ; Prof Jacob M van Laar ; MD^d ; Tracy M Frech ; MD^e ; Marina E Anderson ; FRCP^f ; Murray Baron ; MD^g ; Lorinda Chung ; MD^h ; Gerhard Fierlbeck ; MDⁱ ; Santhanam Lakshminarayanan ; MD^j ; Prof Yannick Allanore ; PhD^k ; Janet E Pope ; MD^l ; Prof Gabriela Riemekasten ; PhD^m ; Prof Virginia Steen ; MDⁿ ; Prof Ulf Mü ; ller-Ladner ; MD^o ; Robert Lafyatis ; MD^p ; Giuseppina Stifano ; MD^p ; Helen Spotswood ; PhD^q ; Haiyin Chen-Harris ; PhD^c ; Sebastian Dziadek ; PhD^r ; Alyssa Morimoto ; PhD^c ; Thierry Sornasse ; PhD^c ; Jeffrey Siegel ; MD^c ; Prof Daniel E Furst ; MD^s
• 刊名：The Lancet
• 出版年：2016
• 出版时间：25 June-1 July 2016
• 年：2016
• 卷：387
• 期：10038
• 页码：2630-2640
• 全文大小：863 K

文摘

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.