Immunosuppressants remain ‘cornerstone’ therapy for CTD-ILD as drug options emerge
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Although immunosuppressives remain the cornerstone for managing underlying interstitial lung disease in connective tissue diseases, new drug approvals could help shift the treatment paradigm, according to data presented here.
“As rheumatologists, when we think about ILDs, we are just focused on the connective tissue disease-related ILDs, but pulmonologists look at all the different kinds of interstitial lung diseases,” Dinesh Khanna, MD, MSc, director of the University of Michigan Scleroderma Program, told attendees at the 2021 Congress of Clinical Rheumatology-East. “This is why the multidisciplinary clinic is so important, because while our focus is on CTD, I have seen patients being diagnosed with exposure-related ILDs.”
He added that “about 10% of idiopathic ILD patients actually have a connective tissue disease; that is what I learned from working with Fernando J. Martinez, MD, MS.”
Khanna noted that all connective tissue diseases are associated with ILD, but the three main ones include rheumatoid arthritis, myositis and scleroderma. In RA, the frequency of ILD has been reported at 20% to 30% with a “high relationship with cigarette smoking and active disease,” whereas ILD in myositis has a frequency of 20% to 50% and is more common with anti-synthetase antibodies. Although scleroderma has the highest reported frequency of ILD at 70% to 80%, Khanna noted that only 25% to 30% is “clinically significant”.
“We don’t do lung biopsies in patients with CTD because the pattern is usually not diagnostic of underlying ILD,” Khanna said. “However, the pattern does impact how the patient will respond to the therapies.”
Based on available evidence, treatment with immunosuppressants has remained the “cornerstone” for managing patients with systemic sclerosis-associated ILD, especially those with features indicating a strong likelihood for progression.
“There is no doubt that mycophenolate mofetil has taken over management of interstitial lung disease related to scleroderma in the U.S.,” Khanna told attendees. “About 90% of all the initial prescriptions are mycophenolate mofetil, and that is based on the Scleroderma Lung Study, which showed that cyclophosphamide and mycophenolate mofetil were similar and early on there was a large proportion of patients in both groups that actually had improvement in their lung function. That improvement in the lung function was associated with improvement in skin scores and patient reported outcome measures.”
Again, Khanna highlighted the benefit of a multidisciplinary clinic when choosing therapies for patients with an underlying ILD. “A pulmonologist might say ‘well, I only focus on the ILD,’ whereas a rheumatologist can’t do that,” he said. “I need to focus on musculoskeletal and skin, so when you think about the treatment, you want to have a therapy that may have a beneficial effect on the other aspects of the body.”
For patients with progressive or resistant ILD, Khanna offered rituximab (Rituxan; Genentech, Biogen) as a “go-to” therapy. “There are really no trials for this, but there are a lot of case series of patients who have failed different therapies, then go on rituximab and tend to stabilize.”
In light of the recent approvals of nintedanib (Ofev, Boehringer Ingelheim) and tocilizumab (Actemra, Genentech) for systemic sclerosis-related interstitial lung disease, Khanna detailed how these newer therapies fit into the treatment paradigm.
“The role of tocilizumab is for early ILD with elevated acute phase reactants, early ILD with progressive skin disease, early ILD with anti-topoisomerase I antibodies, and maybe patients who have failed initial MMF therapy,” he said.
However, Khanna noted that he did not have any data regarding combination therapy with tocilizumab plus MMF.
“The role of nintedanib is for progressive ILD on MMF, the most common cause, as well as predominant ILD in which the patient has limited scleroderma and predominant ILD with everything else going fine,” Khanna said.
He also recommended nintedanib for patients with a usual interstitial pneumonia pattern on high-resolution CT, patients who experience recurrent infections with MMF — “we have patients who get UTIs every time I put them on any immunosuppressive therapy” — and those with very aggressive SSc-ILD that are not candidates for stem cell transplantation.
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Khanna D. Interstitial Lung Disease in Connective Tissue Disease Patients. Presented at: Congress of Clinical Rheumatology-East annual symposium; August 12-15, 2021 (hybrid meeting).
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