Tocilizumab stabilizes lung function in SSc-related interstitial lung disease
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Tocilizumab treatment in early interstitial lung disease, with progressive skin involvement related to systemic sclerosis, was able to stabilize forced vital capacity over 48 weeks, according to data published in Arthritis & Rheumatology.
“The majority of systemic sclerosis patients will develop interstitial lung disease (SSc-ILD),” David Roofeh, MD, of the University of Michigan, and colleagues wrote. “Those at risk for progressive disease have an archetype: Early, diffuse cutaneous systemic sclerosis (dcSSc), with elevated acute phase reactants like C-reactive protein (CRP) and topoisomerase-1 antibody positivity. Patients with these high-risk features, especially those with disease in the initial phase of development, represent an important target for early intervention as ILD is largely irreversible in SSc.”
“Tocilizumab (TCZ) is an anti-[interleukin]-6 agent (IgG1 humanized anti-IL-6 receptor monoclonal antibody), approved for the use of rheumatoid arthritis, giant cell arteritis, juvenile idiopathic arthritis, Castleman’s disease, and other immune-mediated diseases,” they added. “Two well-designed randomized controlled trials of TCZ in early dcSSc demonstrated a significant lung preservation effect in the treatment arm compared to placebo (PBO). This effect has yet to be characterized in terms of quantitative radiographic lung involvement.”
To examine tocilizumab’s (Actemra, Genentech) affect on the preservation of lung function among patients with SSc and progressive skin disease, Roofeh and colleagues conducted a post-hoc analysis of the phase 3 FocuSSced trial. According to the researchers, this multicenter, randomized, double-blind, placebo‐controlled trial recruited 210 patients with SSc and early progressive skin disease with diffuse cutaneous distribution. Participants were assigned 1:1 to receive either 162 mg of subcutaneous tocilizumab weekly or a placebo for 48 weeks.
All participants of the trial had baseline and serial spirometry, as well as high-resolution chest CT at baseline and week 48. For their own study, Roofeh and colleagues identified 136 participants with interstitial lung disease. They divided quantitative interstitial lung disease into three categories based on lung involvement, with 5% to 10% defined as mild, greater than 10% to 20% as moderate, and greater than 20% as severe.
According to the researchers, 77% of participants with interstitial lung disease demonstrated moderate-to-severe lung involvement. Patients treated with tocilizumab managed to preserve forced vital capacity over 48 weeks (least squared mean change in percent predicted = –0.1), compared with those in the placebo group (–6.3%). The mean declines in predicted forced vital capacity among patients with mild, moderate and severe interstitial lung disease were –4.1%, 0.7% and 2.1%, respectively, in the tocilizumab group, and –10%, –5.7% and –6.7%, respectively, in the placebo group.
The researchers noted similar treatment‐related preservation findings independent of fibrosis severity.
“Early dcSSc is associated with high prevalence of ILD, with 77% having moderate-to severe ILD (defined as [quantitative] ILD>10%),” Roofeh and colleagues wrote. “TCZ was effective in preserving the lung function, irrespective of the degree of [quantitative] ILD and [quantitative lung fibrosis] at baseline. This likely represents targeting of the immunoinflammatory, early fibrotic phase of the disease and may be a window of therapeutic opportunity to preserve lung function in early dcSSc. We also highlight the natural history of early ILD that may serve as a template for other fibrotic diseases.”
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