The researchers documented an inverse relationship between baseline percentage of FVC and degree of quantitative ILD. The analysis revealed that early diffuse cutaneous SSc is associated with a high prevalence of ILD—77% of these patients had moderate to severe ILD. The patients’ characteristics surprised study author Dinesh Khanna, MBBS, MSc, a rheumatologist at University of Michigan, Ann Arbor, who expected a larger, mild ILD subset in the phase 3 trial.
The focuSSced study randomized patients to receive tocilizumab or placebo, and the investigators analyzed well-characterized data from the clinical trial using serial spirometry plus diffusing capacity for carbon monoxide corrected for hemoglobin to provide finer granularity for understanding the lung preservation effect of tocilizumab. They found higher quantitative ILD and quantitative lung fibrosis scores at baseline translated into higher quantitative ILD and quantitative lung fibrosis scores at 48 weeks. Patients in the tocilizumab arm had preserved percent FVC over 48 weeks with a difference of 6.2% (P<0.00001) between treatment group and placebo group. The least square mean change was 0.1% for tocilizumab and -6.3% for placebo.
The effect of tocilizimab was statistically significant and consistent across the spectrum of mild to severe ILD compared with placebo, which resulted in a consistent decline in FVC irrespective of the degree of ILD. The mean ± standard deviation changes in percent FVC in the tocilizumab arm at 48 weeks were −4.1 ± 2.5% (n=11) in mild ILD, 0.7 ± 1.9% (n=19) in moderate ILD and 2.1 ± 1.6% (n=26) in severe ILD. In the placebo group the changes were −10.0 ± 2.6% (n=11) in mild ILD, −5.7 ± 1.6% (n=26) in moderate ILD and −6.7 ± 2.0% (n=16) in severe ILD. Although the investigators documented treatment-related preservation findings that were independent of fibrosis severity, patients with severe lung involvement showed the largest improvement of any of the subsets.
“The decline in placebo group was surprising,” says Dr. Khanna, “especially in those with mild ILD or lung fibrosis.”
Dr. Khanna says a high-risk or at-risk phenotype for progressive decline in FVC exists in SSc-associated ILD. Patients at risk include those with early ILD, progressive skin disease and elevated acute phase reactants. He notes the current results underscore the fact that early SSc-associated ILD is not just mild SSc-associated ILD.
“SSc-associated ILD is an irreversible disease,” says Dr. Khanna. “This study highlights that there is a window of opportunity in which we can screen and treat early and preserve/conserve lung function.”
