Early recognition of SSc-ILD patients who 'progress faster' crucial to avoid complications
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Early intervention is critical for patients who are likely to progress to serious complications from systemic sclerosis-associated interstitial lung disease, according to a presenter at the Biologic Therapies Summit.
“Pulmonary hypertension and interstitial lung disease are the leading causes of morbidity and mortality in scleroderma,” Kristin Highland, MD, director of the rheumatic lung disease program of the Cleveland Clinic, said in her presentation.
The pathogenesis of SSc-ILD includes the interplay between immunologic and biologic pathways that starts with tissue injury, according to Highland. Gastroesophageal reflux may be a signal, along with activated B cells and T cells resulting in the production of autoantibodies such as interleukin-6. Clinicians should note the presence of inflammation and fibrosis. “All of these work together to produce SSc-ILD,” she said.
Early and regular screening for ILD in patients who are likely to develop this complication is critical, according to Highland. All patients should undergo spirometry, lung diffusion tests and high-resolution computed tomography (HRCT). Pulmonary function tests (PFT) every 3 to 6 months for at least 5 years are also essential.
Understanding how to interpret lung screening parameters and formulating a treatment algorithm is also necessary for clinicians treating scleroderma. “We usually start with Goh staging criteria” to assess risk of severity and progression, Highland said.
If the extent of fibrosis on HRCT is less than 10%, then ILD is defined as limited disease, according to Highland. Fibrosis greater than 30% on HRCT is extensive disease.
“Between 10% and 30%, you look at pulmonary function,” she said. If the patient is between these two parameters and has greater than 70% pulmonary function, then she has limited disease. Less than 70% pulmonary function is extensive disease.
“It is important to recognize distinct patterns of progression,” Highland said. Some patients are slow progressors, while some are medium progressors and others are rapid progressors. “It is really important to identify those patients that are going to progress faster.”
Men are more likely than women to progress, while African American race is also a key risk factor. Genetic polymorphisms also predict progression, along with the diffuse cutaneous scleroderma, digital ulcers, pulmonary hypertension, anti-neutrophil cytoplasmic autoantibody (ANCA), anti-topoisomerase 1, anticardiolipin and anti-Ro52 antibodies, among other factors.
Patients with extensive disease as defined by the aforementioned criteria should be treated. For patients with less extensive disease, those with risk factors for progression should also be treated.
Regarding treatments, Highland reviewed data sets for a number of drugs that may be used to treat SSc-ILD, including pirfenidone, cyclophosphamide, mycophenolate mofetil (MMF), nintedanib (Ofev, Boehringer Ingelheim) and tocilizumab (Actemra, Genentech).
Based on recent data, MMF showed a “modest improvement” over cyclophosphamide in forced vital capacity. “MMF became more or less the standard of care in FVC,” Highland said.
Nintedanib may be used in the first line either as monotherapy or in combination with either MMF or cyclophosphamide, according to Highland. Patients with a more inflammatory phenotype may benefit from nintedanib. “If the CT scan shows predominant fibrotic features, then I may choose to put a patient on nintedanib,” she said. “These patients then need to be followed very carefully every 3 to 6 months.”
For patients with progressive disease who are undergoing nintedanib monotherapy, combination with an immunomodulator should be considered.
In patients who are progressing rapidly with disease that cannot be controlled by combination therapy, rescue therapy with rituximab (Rituxan, Genentech) or even lung transplant is a possibility.
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Highland K. Advances in pulmonary aspects of progressive systemic sclerosis. Presented at: Biologic Therapies Summit IX; May 21-23, 2021 (virtual meeting).
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