The interleukin-6 inhibitor tocilizumab (Actemra) substantially reduced skin thickening in patients with systemic sclerosis in the “proof-of concept” faSScinate trial, the results of which have now been published in the Lancet.
The mean change in the primary endpoint of a modified Rodnan skin score at 24 weeks was –3.92 in the tocilizumab group and –1.22 in the placebo group, with an overall difference of –2.70 (95% confidence interval, –5.85-0.45; P = .0915). The effect was sustained at 48 weeks’ follow-up (–6.33 vs. –2.77; 95% CI, –7.2-0.12; P = .0579).
“This study is the first placebo-controlled trial in patients with early systemic sclerosis to show a clinically significant – albeit not statistically significant – amelioration of skin sclerosis, and clinically relevant improvement in lung function in patients treated with tocilizumab,” Dr. Dinesh Khanna, director of the University of Michigan Scleroderma Program, Ann Arbor, and his associates report (Lancet. 2016 May 5;387:2630-40).
Assessment of lung function was one of several exploratory analyses conducted and showed fewer tocilizumab- than placebo-treated patients had worsening of the percent predicted forced vital capacity at 48 weeks’ follow-up (P = .0373).
“We were very interested to see the potential impact of tocilizumab on lung function,” said study author Christopher P. Denton, Ph.D. of University College London at the recent British Society of Rheumatology Meeting in Glasgow. It perhaps signals “that IL-6 might be key in the pathogenesis of scleroderma lung fibrosis.”
FaSScinate was a double-blind, placebo-controlled phase II trial conducted at 35 hospitals in Canada, France, Germany, the United Kingdom, and the United States. A total of 87 adults were recruited, all had progressive systemic sclerosis for a duration of 5 years or less from the first appearance of a non–Raynaud’s sign or symptom. Tocilizumab and matched placebo were given subcutaneously at a dose of 162 mg/day.
“Given the lack of disease-modifying treatment options for patients with systemic sclerosis, combined with the morbidity and mortality associated with this disease, data from our trial provide hope for a potential future treatment,” Dr. Khanna and his associates observed in their article. “The safety profile was consistent with complications of systemic sclerosis, including osteomyelitis, and with the safety profile of tocilizumab,” they add.
The U.S. Food and Drug Administration gave tocilizumab a breakthrough therapy designation in systemic sclerosis following the preliminary release of the data in 2015. A phase III trial is now underway.
F Hoffmann-La Roche and Genentech funded the study. The authors disclosed financial relationships with multiple pharmaceutical companies, including the study sponsor.