First-line nintedanib feasible for SSc-ILD with extrapulmonary disease, progression risk
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Following the recent approvals of nintedanib and tocilizumab for systemic sclerosis-related interstitial lung disease, providers should manage the disease based on severity, progression risk and extrapulmonary activity, noted researchers.
“Well-conducted phase 3 RCTs have led to the approval of two targeted therapies for [SSc-related interstitial lung disease (SSc-ILD)] by the U.S. Food and Drug Administration,” Dinesh Khanna, MD, MSc, of the University of Michigan Scleroderma Program, and colleagues wrote in a review published in Arthritis & Rheumatology. “Nintedanib is a tyrosine kinase inhibitor; in 2019 it became the first medication approved to slow the rate of decline in pulmonary function in patients with SSc-ILD, based on the results of the SENSCIS trial.”
“Tocilizumab is a monoclonal antibody targeting the interleukin (IL)-6 receptor; in 2021 it became the first biologic medication approved for the same indication, based on the results of the faSScinate and focuSSced trials,” they added. “Despite these recent FDA approvals, the optimal therapeutic strategy for the management of patients with SSc-ILD is yet to be determined, especially given the heterogeneity of the disease.”
To develop a practical strategy for the diagnosis, stratification, management and treatment of SSc-related interstitial lung disease — considering the recent approvals of nintedanib (Ofev, Boehringer Ingelheim) and tocilizumab (Actemra, Genentech), as well as promising data on mycophenolate mofetil and cyclophosphamide — Khanna and colleagues conducted a review of the current body of research. This included the faSScinate and focuSSced trials, as well as a phase 2 trial in which mycophenolate mofetil and cyclophosphamide demonstrated efficacy in SSc-related interstitial lung disease.
Additionally, in developing their management strategy, the authors reported reflecting on their own “opinions, experience and clinical practice.”
According to the authors, patients who demonstrate subclinical interstitial lung disease and a high risk for progression should be placed on a strategy to prevent lung function loss. Rheumatologists should also remember that “early ILD is not necessarily mild ILD,” they wrote. Tocilizumab has demonstrated benefit in those with high risk for progression and, is effective in attenuating lung function loss along a wide spectrum of lung involvement on high resolution computed tomography. This, the researchers wrote, suggests it can be use in clinical interstitial lung disease “with a spectrum of degree of underlying lung involvement.”
Meanwhile, although rheumatologists can consider nintedanib as first-line therapy in SSc-related interstitial lung disease, there should be a preference for patients with limited extrapulmonary disease, or it should be used as part of upfront combination therapy for progressive disease in those who are candidates for high resolution computed tomography.
Although not FDA-approved for SSc-related interstitial lung disease, rheumatologists should also consider immunosuppressive therapy with mycophenolate mofetil as a primary treatment approach for clinical disease, especially in patients with other active manifestations. In these cases, according to the authors, mycophenolate mofetil may improve pulmonary function over time in most patients. It is similarly effective at improving skin disease, dyspnea and health-related quality of life over time.
However, the researchers also noted that current immunomodulatory and anti-fibrotic treatments “have yet to demonstrate long-lasting benefit on how patients feel, function, or survive.”
“The current review provides a state-of-art practical overview of the management of SSc-ILD,” Khanna and colleagues wrote. “As therapeutic options expand, expert perspective remains an important source of treatment guidance. The recent addition of two FDA-approved medications for SSc-ILD have broadened the cache of available treatments; management should be determined by stratifying patients in terms of disease severity, risk of progression, and activity of extrapulmonary disease.”
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