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Ann Rheum Dis. 2018 Feb;77(2):212-220. doi: 10.1136/annrheumdis-2017-211682. Epub 2017 Oct 24.

Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial (faSScinate).

Author information

1
University of Michigan Scleroderma Program, Ann Arbor, Michigan, USA.
2
University College London Medical School, London, UK.
3
Genentech, South San Francisco, California, USA.
4
University Medical Center Utrecht, Utrecht, Netherlands.
5
University of Utah, Veterans Affairs Medical Center, Salt Lake City, Utah, USA.
6
University of Liverpool and Aintree University Hospital, Liverpool, UK.
7
Jewish General Hospital, Montreal, Canada.
8
Stanford University School of Medicine and Palo Alto VA Health Care System, Palo Alto, California, USA.
9
University of Tübingen, Tübingen, Germany.
10
University of Connecticut Health Center, Farmington, Connecticut, USA.
11
Paris Descartes University, Paris, France.
12
Schulich School of Medicine and Dentistry, University of Western Ontario, St Joseph's Health Care, London, Canada.
13
University of Lübek and Charité University Hospital, Berlin, Germany.
14
Georgetown University, Washington, DC, USA.
15
Justus-Liebig University Giessen, Kerckhoff Clinic, Bad Nauheim, Germany.
16
Roche Products Ltd, Welwyn Garden City, UK.
17
University of California, Los Angeles, California, USA.

Abstract

OBJECTIVES:

Assess the efficacy and safety of tocilizumab in patients with systemic sclerosis (SSc) in a phase II study.

METHODS:

Patients with SSc were treated for 48 weeks in an open-label extension phase of the faSScinate study with weekly 162 mg subcutaneous tocilizumab. Exploratory end points included modified Rodnan Skin Score (mRSS) and per cent predicted forced vital capacity (%pFVC) through week 96.

RESULTS:

Overall, 24/44 (55%) placebo-tocilizumab and 27/43 (63%) continuous-tocilizumab patients completed week 96. Observed mean (SD (95% CI)) change from baseline in mRSS was -3.1 (6.3 (-5.4 to -0.9)) for placebo and -5.6 (9.1 (-8.9 to-2.4)) for tocilizumab at week 48 and -9.4 (5.6 (-8.9 to -2.4)) for placebo-tocilizumab and -9.1 (8.7 (-12.5 to -5.6)) for continuous-tocilizumab at week 96. Of patients who completed week 96, any decline in %pFVC was observed for 10/24 (42% (95% CI 22% to 63%)) placebo-tocilizumab and 12/26 (46% (95% CI 27% to 67%)) continuous-tocilizumab patients in the open-label period; no patients had >10% absolute decline in %pFVC. Serious infection rates/100 patient-years (95% CI) were 10.9 (3.0 to 27.9) with placebo and 34.8 (18.0 to 60.8) with tocilizumab during the double-blind period by week 48 and 19.6 (7.2 to 42.7) with placebo-tocilizumab and 0.0 (0.0 to 12.2) with continuous-tocilizumab during the open-label period.

CONCLUSIONS:

Skin score improvement and FVC stabilisation in the double-blind period were observed in placebo-treated patients who transitioned to tocilizumab and were maintained in the open-label period. Safety data indicated increased serious infections in patients with SSc but no new safety signals with tocilizumab.

TRIAL REGISTRATION NUMBER:

NCT01532869; Results.

KEYWORDS:

DMARDs (biologic); interleukin-6; scleroderma; systemic sclerosis (SSc); tocilizumab; treatment

Conflict of interest statement

Competing interests: DK reports personal fees from Actelion, Boehringer-Ingelheim, Covis, CSL Behring, Corbus, Cytori, EMD Serono, Genentech/Roche, GSK, Inventiva, Medac, Sanofi-Aventis and UCB; grants from BMS, Bayer and Pfizer; stocks in Eicos Sciences, Inc, during the conduct of the study; and personal fees from Astra Zeneca outside the submitted work. CPD reports personal fees from Roche, Actelion, EMD Serono, Sanofi and Boehringer Ingelheim; grants and personal fees from GSK and Inventiva; and grants from CSL Behring during the conduct of the study. CJFL is an employee of Genentech. JMvL reports grants and personal fees from MSD and Genentech and personal fees from BMS, Eli Lilly and Pfizer outside the submitted work. MEA reports funding to Hospital Trust from Roche during the conduct of the study and personal fees from Actelion Pharmaceuticals outside the submitted work. YA has received research support and grants related to the submitted work from BMS, Roche/Genentech, Inventiva, Pfizer and Sanofi; consulting honoraria and personal fees related to the current work from Actelion, Bayer, Boehringer, Roche/Genentech, Galapagos, Inventiva, Medac, Pfizer, Sanofi, Servier and UCB; and personal fees outside the submitted work from Sandoz. JEP reports funding for the current trial by Roche. GR has received lecturer’s fees from Roche and Chugai outside the submitted work. UM-L is a speaker and advisor to Roche and Chugai related to the submitted work. HS is an employee of and has non-voting shares in Roche Products Limited. LB is an employee of Roche. JS is an employee of Genentech. AJ is an employee of Genentech, owns stock and options in Roche and owns a patent for subcutaneous tocilizumab. All other authors have no conflicts of interest to disclose.

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