High resolution CT image of diffuse lung disease in a patient with lung-dominant connective tissue disease. Courtesy of A. Fischer.

The largest study to date of the effect of mycophenolate mofetil (MMF) in connective tissue disease-associated interstitial lung disease (CTD-ILD) has found the drug to be well tolerated and associated with improved or stable lung function. “Immunosuppression is a frequent treatment strategy for clinically significant CTD-ILD,” says lead investigator Aryeh Fischer, “but there have been few systematic, prospective studies of the safety or efficacy of this approach.” Despite promising data for drugs such as cyclophosphamide, he explains, enthusiasm for them has been “blunted by the potential for serous toxicity.”

MMF is generally associated with fewer adverse events than cyclophosphamide and has been used in a number of small case series in CTD-ILD. To consolidate data in support of this strategy, the investigators retrospectively examined the responses of 125 patients with CTD-ILD who were treated with MMF for a median of 897 days. The clinically heterogenous cohort included patients with systemic sclerosis (n = 44), polymyositis or dermatomyositis (n = 32), lung-dominant connective tissue disease (n = 19) and rheumatoid arthritis (n = 18).

Concomitant corticosteroid use was reduced for many patients; the median daily dose of prednisone decreased from 20 mg at baseline to 5 mg after 9–12 months of MMF treatment. Nevertheless, pulmonary function, as measured by forced vital capacity and diffusing capacity, improved or was stable in patients treated with MMF. “I believe our findings help further support the role of MMF in treatment of CTD-ILD,” says Fischer. The drug was discontinued in 13 patients (10%) for reasons such as gastrointestinal intolerance (n = 3), ILD progression (n = 2) and elevated levels of hepatic transaminase enzymes (n = 2), a low rate according to Fischer.

Although these findings are the most extensive available for MMF in CTD-ILD, “many questions remain unanswered,” notes Fischer. Data to guide decision-making on duration of immunomodulatory therapy are lacking; also unknown is “whether specific histopathological patterns of ILD should be managed differently, or whether underlying CTD should impact choice of therapy,” he concludes.