Safety and Efficacy of Subcutaneous Tocilizumab in Early Systemic Sclerosis: Results from the Open-Label Period of a Phase 2 Randomized, Controlled Trial

Dinesh Khanna¹, Christopher Denton², Helen Spotswood³, Angelika Jahreis⁴, Jacob M. van Laar⁵, Laura Burke⁶, Celia J. F. Lin⁴, Janet E. Pope⁷, Yannick Allanore⁸, Ulf Müller-Ladner⁹, Jeffrey Siegel⁶, Daniel E. Furst¹⁰ and faSScinate Clinical Trial Investigators, ¹University of Michigan, Ann Arbor, MI, ²Division of Medicine, Centre for Rheumatology and Connective Tissue Disease, University College London, London, United Kingdom, ³Roche Products Ltd., Welwyn Garden City, CA, United Kingdom, ⁴Genentech, South San Francisco, CA, ⁵University Medical Center Utrecht, Utrecht, Netherlands, ⁶Roche Products Ltd., Welwyn Garden City, United Kingdom, ⁷University of Western Ontario, St Joseph's Health Care, London, ON, Canada, ⁸Rheumatology, Paris Descartes University, Paris, France, ⁹Justus-Liebig-University Giessen, Department of Internal Medicine and Rheumatology, Kerckhoff-Klinik, Bad Nauheim, Germany, Bad-Nauheim, Germany, ¹⁰University of California, Los Angeles, Los Angeles, CA

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: clinical trials, IL-6, systemic sclerosis and tocilizumab

Session Information

Date: Sunday, November 13, 2016

Title: Systemic Sclerosis, Fibrosing Syndromes, and Raynaud's – Clinical Aspects and Therapeutics I

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: Systemic sclerosis (SSc) is a debilitating disease with few treatment options. Interleukin-6 (IL-6) appears to play a role in SSc pathogenesis (J Rheumatol 1998;25:308; Pathobiology 1993;61:239). Data from the 48-week, double-blind (DB), placebo (PBO)-controlled period of the faSScinate trial of subcutaneous (SC) tocilizumab (TCZ) in patients with SSc have been published (Lancet 2016: doi: 10.1016/S0140-6736(16)00232-4). Herein we present data on the safety and efficacy of TCZ in SSc patients during 48 weeks of open-label (OL) TCZ treatment.

Methods: Patients ≥18 years of age with active SSc (≤5-year duration, modified Rodnan skin score [mRSS] 15-40, and elevated acute-phase reactants) diagnosed according to 1980 ACR criteria received OL TCZ 162 mg SC weekly from week 48 to week 96. Change from baseline in mRSS, patient-reported outcomes (PROs), and forced vital capacity (FVC) at week 96 were exploratory measures. Observed means used all available data.

Results: In total, 27 of 43 (63%) TCZ and 24 of 44 (55%) PBO patients completed week 96. Baseline (BL) characteristics were similar at BL and at entry into the OL period. Patients who switched from PBO→OL TCZ showed improvement in observed mean change from BL in mRSS at week 96 (–9.4) compared with the end of the 48-week DB period (–3.1). In patients initially randomly assigned to TCZ (TCZ→OL TCZ), mean change in mRSS was –5.6 at week 48 and –9.1 at week 96. In the OL period, improvements in PROs were noted at week 96 compared with week 48 in the PBO→OL TCZ group (mean [SD] change from BL at week 96 vs week 48 in HAQ-DI: –0.3 [0.4] vs 0.2 [0.4]; Patient Global VAS: –23.8 [36.0] vs –4.0 [24.0]; FACIT-Fatigue: 11.3 [12.8] vs 1.4 [7.6]). Of patients who completed the study, none experienced a >10% decline in % predicted FVC during the OL period on TCZ therapy. Rates (95% CI) of serious adverse events/100 patient-years (PY) in the DB period were 76.1 (50.6, 110.0) in PBO patients and 66.7 (42.3, 100.1) in TCZ patients and were 36.0 (18.0, 64.4) in PBO→OL TCZ patients and 16.5 (5.4, 38.5) in TCZ→OL TCZ patients in the OL period. Rates (95% CI)/100PY of serious infections in the DB period were 10.9 (3.0, 27.9) in PBO patients and 34.8 (18.0, 60.8) in TCZ patients. In the OL period they were 19.6 (7.2, 42.7) in PBO→OL TCZ patients and 0.0 (0.0, 12.2) in TCZ→OL TCZ patients. No deaths occurred in the OL period (deaths in DB period: 3 TCZ, 1 PBO).

Conclusion: Although OL data have to be interpreted with caution, efficacy and safety in PBO-treated patients who switched to OL TCZ were generally similar to those observed in patients randomly assigned to TCZ in the DB period. Results over 96 weeks of TCZ treatment suggest maintenance of the clinical response for mRSS in SSc patients. Rates of serious infection increased in PBO patients after they switched to OL TCZ. Long-term safety was consistent with the natural history of SSc and the safety profile of TCZ.

Disclosure: D. Khanna, NIH/NIAMS, NIH/ NIAID, Bayer, BMS, 2,Bayer, BMS, Genetech/Roche, GSK, Genkyotex, Sanofi-Aventis, Actelion, Gilead, 5; C. Denton, GSK, Celgene, Actelion, Bayer, Sanofi, Roche-Genentech, Inventiva, 5,CSL Behring, GSK, Actelion, Roche-Genentech, Inventiva, 2; H. Spotswood, Roche Products Ltd., 1,Roche Products Ltd., 3; A. Jahreis, Roche, 1,Genentech, 3; J. M. van Laar, MSD, 2,MSD, Roche, Pfizer, BMS, Eli Lilly, 5; L. Burke, Roche Products Ltd., 3; C. J. F. Lin, Genentech/Roche, 3; J. E. Pope, AbbVie, Actelion, Amgen, BMS, Hospira, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, UCB, 5; Y. Allanore, Bristol-Myers Squibb, Roche/Genentech, Inventiva, Pfizer, Sanofi, and Servier, 2,Actelion, Bayer, Roche/Genentech, Inventiva, Medac, Pfizer, Sanofi, Servier, and UCB, 5; U. Müller-Ladner, Roche/Chugai, 8,Roche/Chugai, 9; J. Siegel, Roche, 1,Genentech, 3; D. E. Furst, Abbott, Actelion, Amgen, Bristol-Myers Squibb, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB Pharma, 2,Abbott, Actelion, Amgen, Bristol-Myers Squibb, Biogen, Janssen, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB Pharma, 5,Abbott, Actelion, Amgen, Bristol-Myers Squibb, Biogen, Janssen, Gilead, NIH, Roche/Genentech, 9,Abbott, Actelion, UCB Pharma, 8.

To cite this abstract in AMA style:

Khanna D, Denton C, Spotswood H, Jahreis A, van Laar JM, Burke L, Lin CJF, Pope JE, Allanore Y, Müller-Ladner U, Siegel J, Furst DE. Safety and Efficacy of Subcutaneous Tocilizumab in Early Systemic Sclerosis: Results from the Open-Label Period of a Phase 2 Randomized, Controlled Trial [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/safety-and-efficacy-of-subcutaneous-tocilizumab-in-early-systemic-sclerosis-results-from-the-open-label-period-of-a-phase-2-randomized-controlled-trial/. Accessed .

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