The immunomodulatory drugs mycophenolate mofetil (MMF) and azathioprine (AZA) are associated with a low incidence of malignancy in patients treated for fibrotic interstitial lung disease (FILD)—an incidence similar to that found in patients not treated with either medication. This was among the findings of a study by Canadian and Australian researchers that was recently published in Chest.
Mycophenolate mofetil and AZA commonly are administered for the treatment of ILDs, such as connective-tissue disease-associated ILD (CTD-ILD) and fibrotic hypersensitivity pneumonitis (HP). Hematologic and solid-organ malignancies have been described following MMF or AZA therapy, but the attributable risk data were obtained mainly from patients with organ transplants, in whom baseline malignancy risk is higher than in patients with ILD.
To better identify the malignancy risk associated with MMF and AZA in patients with ILD, investigators for the current study sought to depict and compare such risk in patients with fibrotic HP and CTD-ILD. The retrospective observational cohort study used data from the Canadian Registry for Pulmonary Fibrosis, a multicenter, prospective registry designed to study fibrotic ILD.
Of the 3883 registry patients, 1157 (903 with CTD-ILD and 254 with fibrotic HP) were eligible for inclusion. In 74 patients (6.4%), at least 1 malignancy developed during follow-up; 10 patients had more than 1 malignancy. This total included 27 patients (5.8%) in the MMF group, 7 patients (4.6%) in the AZA group, and 40 untreated patients (7.4%). Lung and skin malignancies were most commonly observed. In the untreated group, 5 cases of lymphoma were found; none occurred in either treatment group. The higher rate of malignancy in MMF-treated patients than in those treated with AZA may result from the differences between the groups, including more smokers and more patients with prior malignancy in the group treated with MMF, according to the researchers. No relation of malignancy risk to the cumulative MMF dose was detected; however, too few events were available to evaluate this possibility in the AZA group.
Limitations of the study include a lack of long-term safety data and the inability to evaluate the dose-related risk for AZA. Residual confounding may have occurred based on the study’s retrospective design, possibly including variations in comorbidities, ILD progression, medication tolerance, disease severity, patient preference, or concurrent treatment with other drugs unknown to the investigators. Higher incidences of prior malignancy in the untreated group also may have affected pharmacotherapeutic decisions, the researchers noted.
“These findings support [the] short-term safety of these medications in patients with CTD-ILD and fibrotic HP and may help guide treatment decision-making,” the authors wrote. They recommended lengthier studies to clarify the long-term safety of the drugs in people with fibrotic ILD.
Disclosure: Multiple authors declared affiliations with the pharmaceutical and biopharmaceutical industries. Please refer to the original article for a full list of disclosures. CARE-PF is funded by Boeheringer-Ingelheim. The funder was not involved in the study design, data analysis, data interpretation, or manuscript preparation.
Lok SD, Wong AW, Khor YH, Ryerson CJ, Johannson KA; CARE-PF Investigators. Malignancy risk associated with mycophenolate mofetil or azathioprine in patients with fibrotic interstitial lung disease. Chest. Published online December 15, 2021. doi:10.1016/j.chest.2021.12.636