EULAR 2016 | Daily Highlights
SAFETY AND EFFICACY OF SUBCUTANEOUS TOCILIZUMAB IN EARLY SYSTEMIC SCLEROSIS: RESULTS FROM THE OPEN-LABEL PERIOD OF THE FASSCINATE TRIALAbstract: FRI0268
Authors: D. Khanna1,*, C. P. Denton2, A. Jahreis3, J. M. van Laar4, L. Burke5, H. Spotswood5, C. J. Lin3, J. E. Pope6, Y. Allanore7, U. Müller-Ladner8, J. Siegel3, D. E. Furst9 on behalf of faSScinate Clinical Trial Investigators
Co Authors: 1University of Michigan, Ann Arbor, United States, 2University College London Medical School, London, United Kingdom, 3Genentech, South San Francisco, United States, 4University Medical Center Utrecht, Utrecht, Netherlands, 5Roche Products Ltd., Welwyn Garden City, United Kingdom, 6University of Western Ontario, London, Canada, 7Paris Descartes University, Paris, France, 8Justus-Liebig University Giessen, Bad Nauheim, Germany, 9University of California, Los Angeles, United States
Systemic sclerosis (SSc) is a debilitating disease with few treatment options. Interleukin-6 (IL-6) appears to play a role in SSc pathogenesis.1,2 Data from the 48-week, double-blind (DB), placebo (PBO)-controlled period of the faSScinate trial were previously presented,3 and open-label (OL) data are presented herein.
To assess safety and efficacy of tocilizumab (TCZ) in SSc patients during 48 weeks of OL TCZ treatment.
Patients ?18 y with active SSc (?5-year duration, modified Rodnan skin score [mRSS] 15-40, and elevated acute-phase reactants) received OL TCZ 162 mg SC weekly from week 48 to week 96. Change from baseline in mRSS, patient-reported outcomes (PROs), and FVC at week 96 were exploratory measures. Observed means used all available data.
In total, 27/43 (63%) TCZ and 24/44 (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) relative to the end of the 48-week DB period (–3.1). In patients initially randomized 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 vs 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]). In 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).
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 randomized to TCZ in the DB period. Results over 96 weeks of TCZ treatment suggest maintenance of the clinical response for mRSS in SSc patients. Serious infection rates 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.
1. J Rheumatol 1998;25:308. 2. Pathobiology 1993;61:239. 3. Ann Rheum Dis 2015;74(suppl 2):87.
Disclosure of Interest: D. Khanna Grant/research support from: NIH/NIAMS, NIH/ NIAID, Bayer, BMS, Consultant for: Bayer, BMS, Genetech/Roche, GSK, Genkyotex, Sanofi-Aventis, Actelion, Gilead, C. Denton Grant/research support from: GSK, Actelion, CSL Behring, Consultant for: GSK, Bayer, Actelion, Roche, Merck-Serono, MedImmune, A. Jahreis Shareholder of: Roche, Employee of: Genentech, J. van Laar Grant/research support from: MSD, Consultant for: MSD, Roche, Pfizer, BMS, Eli Lilly, L. Burke Employee of: Roche Products Ltd., H. Spotswood Shareholder of: Roche, Employee of: Roche Products Ltd., C. Lin Shareholder of: Amgen, Roche/Genentech, Employee of: Genentech, J. Pope Grant/research support from: Roche, Bayer, BMS, Consultant for: Roche, Actelion, Bayer, BMS, Y. Allanore Grant/research support from: Bristol-Myers Squibb, Roche/Genentech, Inventiva, Pfizer, Sanofi, and Servier, Consultant for: Actelion, Bayer, Roche/Genentech, Inventiva, Medac, Pfizer, Sanofi, Servier, and UCB, U. Müller-Ladner Consultant for: Roche, Chugai Pharma, Speakers bureau: Roche, Chugai Pharma, J. Siegel Shareholder of: Roche, Employee of: Genentech, D. Furst Grant/research support from: AbbVie, Actelion, Amgen, BMS, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB, Consultant for: AbbVie, Actelion, Amgen, BMS, Cytori, Janssen, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB
The diagnosis of interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) is currently mainly based on lung function testing and high-resolution computer tomography (HRCT). Lung function testing has recently been shown to have a remarkable low sensitivity when used for screening of SSc-ILD. HRCT is more sensitive, but still detects SSc-ILD at stages when fibrosis has already developed. Thus, there is a high unmet need for the development of screening and imaging techniques that are able to detect SSc-ILD at earlier stages, before damage to the lungs has occurred. The current study shows first promising pre-clinical results using molecular imaging to detect SSc-ILD at stages when key pathophysiological pathways are already activated, but damage (fibrosis) has not yet occurred. This novel concept needs further testing with additional targets, optimization of image detection methods and most importantly, testing in proof of concept studies before it can be applied to clinical practice.
Prof. Dr. Oliver Distler
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