Knowledge About Effective Therapies for Interstitial Lung Disease Lacking, Review Says


Interstitial lung disease requires a multidisciplinary clinical approach, though little is known about effective therapeutic treatments.

Interstitial lung disease (ILD) should be treated with a multidisciplinary clinical and therapeutic approach but treatment with conventional drugs may be based on studies with insufficient research, according to a literature review.

Investigators from Italy gathered and summarized the available related literature in order to organize the available data and recent advances about therapeutic strategies for ILD in the context of other connective tissue diseases (CTDs). ILD may be the first manifestation of CTD, the study authors wrote, but ILD may be diagnosed many years before CTD. ILD can be confirmed by patterns of fibrosis on CT scans and after lung biopsies, as well as history of pneumonia for patients.

The study authors noted a lack of randomized controlled trials (RCTs) leading to difficulties in a standard recommendation of therapy. Thus, they narrowed their focus to therapeutic strategies for ILD in the context of systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIM), primary Sjogren syndrome (pSS), systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD) and undifferentiated connective tissue disease (UCTD), and interstitial pneumonia with autoimmune features (IPAF).

ILD can affect between 70-90% of SSc patients, the study authors wrote, and ILD is the leading SSc-related cause of death. For patients with low or no disease progression, the current treatment includes routine follow-up. One observational study examining the efficacy of glucocorticoid therapy found that the effect on lung function was only slightly positive in patients with FVC > 75%.

The study authors said that there were 2 “high-quality” RCTs that looked at cyclophosphamide, which should be considered for SSc-related ILD cases despite its toxicity. There were many studies that demonstrated “encouraging results” for the use of mycophenolate mofetil (MMF), including lost-lasting efficacy on lung function and a high safety profile. In the first open-label, randomized, controlled study of rituximab, patients showed improvement but deteriorated after drug cessation.

Only one study looked at azathioprine, which was well-tolerated.

The initial evidence for pirfenidone was weak, though showed an acceptable tolerability in patients. There was poor data regarding survival after a lung transplant, and what exists was contradictory, the study authors found.

For IIM, most of the evidence from observational studies shows that the first therapeutic choice should depend on ILD severity and modality of presentation. No agent appeared superior to any other, the study authors said.

While rituximab seemed safe and useful for pSS treatment, lung improvement was only reported in a small series of cases. Glucocorticoids and conventional immunosuppressants are often used here as a first-line therapy also, the study authors learned.

Treating SLE-ILD is currently based on expert opinion as there are no evidence-based guidelines or clinical trials, the study authors said. Corticosteroids may be used alone or in combination with other immunosuppressive agents, and rituximab has been used as a second-line therapy.

ILD is usually SSc-like with MCTD, though progression is often slow in patients. Again, there are no controlled data available but immunosuppressive agents are used as in other CTDs. A combination of corticosteroids is often effective, the study authors wrote.

“A multidisciplinary approach, including rheumatologists, pulmonologists, radiologists, and pathologists, is mandatory to correctly classify these patients and set up an appropriate immunosuppressive treatment strategy,” the study authors wrote about UCTD patients. The existing literature has little about UCTD, which doesn’t fulfil any of the existing classification criteria for CTDs.

Acute exacerbation of ILD can be fatal but management requires a global approach, the study authors said. It is usually based on high-dose corticosteroids alongside immunosuppressants and broad-spectrum antibiotics.

There were no available studies about non-pharmacological treatments for ILD, though pulmonary rehabilitation seems safe, the study authors said.

Ongoing RCTs for ILD include the RECOVER trial which focuses on rituximab; RECITAL which focuses on intravenous rituximab; SLS III which focuses on MMF or MMF plus pirfenidone; and ATtackMy-ILD which examines subcutaneous abatacept compared to placebo.

“ILD represents one of the most severe clinical manifestation of CTDs with a deep impact on the prognosis in terms of morbidity and mortality,” the study authors concluded. “Nevertheless, with the exception of Ssc, in CTDs validated screening program for early detection of ILD is not available with a significant delay of diagnosis and underestimation of the prevalence and incidence. Furthermore, although CTD-ILD represents an important current field of study for both rheumatologists and pulmonologists, there is still lack of prospective data about prevalence, follow-up, and therapeutic approach.”

The study, titled “Therapeutic Options for the Treatment of Interstitial Lung Disease Related to Connective Tissue Diseases. A Narrative Review,” was published in the Journal of Clinical Medicine.


Vacchi C, Sebastiani M, Cassone G, et al. Therapeutic options for the treatment of interstitial lung disease related to connective tissue diseases: A narrative review [published February 3, 2020]. J. Clin. Med.

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