Source:

Highland KB. ILD in the Era of Anti-Fibrotics. Presented at: American College of Rheumatology State-of-the-Art Clinical Symposium. April 9-11, 2021 (virtual meeting).

Disclosures: Highland reports receiving grant or research support from, consulting for, being a steering committee member of or being on the speakers’ bureau of Acceleron, Actelion Pharmaceuticals, Bayer Healthcare, Boehringer Ingelheim, Eiger Pharmaceuticals, Genentech, Gossamer Bio, Reata Pharmaceuticals, United Therapeutics and Viela Bio.
April 15, 2021
2 min read
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Novel therapies, combinations show 'increasing evidence' for role in SSc-ILD

Source:

Highland KB. ILD in the Era of Anti-Fibrotics. Presented at: American College of Rheumatology State-of-the-Art Clinical Symposium. April 9-11, 2021 (virtual meeting).

Disclosures: Highland reports receiving grant or research support from, consulting for, being a steering committee member of or being on the speakers’ bureau of Acceleron, Actelion Pharmaceuticals, Bayer Healthcare, Boehringer Ingelheim, Eiger Pharmaceuticals, Genentech, Gossamer Bio, Reata Pharmaceuticals, United Therapeutics and Viela Bio.
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A number of new therapies, including immunosuppressive drugs and drug combinations, have shown efficacy in mitigating scleroderma-associated interstitial lung disease, according to a speaker at the ACR State-of-the-Art Clinical Symposium.

Kristin B. Highland, MD, director of the Rheumatic Lung Disease Program at the Cleveland Clinic, aimed to provide a comprehensive overview of scleroderma-associated interstitial lung disease (SSc-ILD) and review current data on the treatment of this patient population.

Interstitial lung disease
“There is increasing evidence for the role of immunosuppressive therapy in SSc-ILD,” Kristin B. Highland, MD, told attendees. Source: Adobe Stock

“When I am thinking about treating patients with scleroderma ILD, I use Goh staging criteria,” she said. Patients with less than 10% fibrosis are defined as having limited ILD, while those with more than 30% fibrosis are defined as having “extensive” ILD.

“If the fibrosis is between 10% and 30%, then you look at pulmonary function testing,” Highland said. More than 70% forced vital capacity (FVC) means the patient has limited ILD, while less than 70% function means extensive disease.

Kristin B. Highland

Highland then offered a clear warning for clinicians managing this patient population: “Fibrosis begets fibrosis,” she said.

More fibrosis, of course, means disease progression. Highland added that progression is also defined as 10% or more decline in FVC.

There is a long list of risk factors for ILD progression, ranging from demographic factors such as Black race to male gender, to the presence of diffuse cutaneous scleroderma and digital ulcers, to longer disease duration and pulmonary hypertension.

Pathogenesis of scleroderma ILD is “multifactorial,” according to Highland. She noted that genetic predisposition is often present, while tissue injury can result in vascular and epithelial injury. Patients often have B-cell and T-cell abnormalities.

A number of key data sets have provided the basis for treatment paradigms in this complicated patient population.

The LOTUSS trial investigated various dosing and titration approaches for the anti-fibrotic drug pirfenidone (Esbriet, Genentech). Results showed that the drug was well tolerated. In addition, patients who were more slowly up titrated did better in terms of efficacy and safety than those who underwent more rapid escalation, according to Highland.

Both the INBUILD and SENSCIS studies demonstrated the efficacy of the kinase inhibitor nintedanib, the first drug approved by the FDA for scleroderma ILD, according to Highland. For clinicians who find monotherapy insufficient to manage certain patients, SENSCIS demonstrated that the addition of nintedanib to background mycophenolate mofetil (MMF) therapy has become a viable option for rheumatologists.

Based on findings from the focuSSced study, tocilizumab (Actemra, Genentech) underwent a somewhat unusual approval process. While the drug failed to meet its primary endpoint of skin improvement in early scleroderma patients with diffuse disease, improvement in FVC as a key secondary endpoint was enough for the FDA.

“The FDA approached Genentech and said these data are impressive enough to get approval for SSc-ILD,” Highland said, noting that the approval is for a “very specific” patient population: those with early disease inflammatory phenotype.

“There is increasing evidence for the role of immunosuppressive therapy in SSc-ILD,” Highland concluded.