Experience with azathioprine in systemic sclerosis associated with interstitial lung disease

Abstract

The aim of this study was to evaluate the safety and efficacy of azathioprine in the treatment of interstitial lung disease (ILD) associated with systemic sclerosis (SSc). The records of patients with SSc with ILD who were treated with azathioprine were reviewed. Patients were treated with azathioprine and low-dose prednisone if they had progressive pulmonary symptoms (deterioration in the dyspnea score) or poor or deteriorating lung function. Response was classified as improved if the FVC increased more than 10% from baseline, and stable if it remained within 10% of baseline. Serial dyspnea scores were recorded. Eleven patients were treated with azathioprine, three of whom received treatment for 6 months or less owing to adverse effects (nausea, leukopenia and pulmonary tuberculosis in one patient each). The remaining eight patients received at least 12 months' treatment and the results suggested an improvement in the mean percent predicted FVC from a baseline value of 54.25+/-3.53 to 63.38+/-6.15 after 12 months ( p=0.101). Overall, five patients improved and three remained stable. The mean dyspnea score ( n=8) improved from a baseline of 1.55+/-0.19 to 0.50+/-0.19 at 12 months ( p=0.011). This is the first case series of patients with SSc-associated ILD treated with azathioprine. Our results suggest that azathioprine may have a role in stabilizing lung function and improving symptoms in SSc, although this needs confirmation by a randomized controlled trial.

Interstitial lung disease in South Africans with systemic sclerosis

“…Much of the rationale behind treatment comes from therapies used for idiopathic pulmonary fibrosis (18) Some of the studies reviewed by Matucci-Cerinic et al, (2007) (44) and Nannini et al, (45) , used stabilisation of FVC as an outcome measure rather than improvement of FVC, which appears to be achieved by both oral and intravenous cyclophosphamide regimes. In a local study, Dheda et al, (2004) (46) also found some success with stabilisation of lung function and improvement of dyspnoeic symptoms using azathioprine and low-dose corticosteroids. Additionally, there have been studies into the use of mycophenolate mofetil (MMF) (39) , and rituximab (47) , which seem to show similar results.…”

Immunomodulatory therapy for SSc: Will high-intensity immunosuppression with stem cell rescue improve outcome?

“…There are no randomized trials of azathioprine in patients with SSc, however this agent is used frequently in patients with idiopathic interstitial lung disease and was recently evaluated in an open study of 11 patients with SSc and pulmonary disease [15]. Patients who remained on therapy at 12 months (n = 8) or 18 months (n = 7) were classified as stable or improved with respect to functional vital capacity.…”

Monitoring of Nonsteroidal Immunosuppressive Drugs in Patients With Lung Disease and Lung Transplant Recipients

“…308 It has also been used for prophylactic treatment of heart, liver, pancreas, and lung transplantation. [309][310][311][312][313][314][315][316][317] Additionally, azathioprine has been used to treat pulmonary and extrapulmonary sarcoidosis, [318][319][320] cryptogenic organizing pneumonia, 321 idiopathic pulmonary fi brosis, 322 interstitial lung disease (ILD) associated with systemic sclerosis, 323,324 and radiation pneumonitis. 325 A summary of 11 studies supporting recommendations for the monitoring of AZA in patients with lung disease and organ transplant recipients is provided in Table 28 .…”

“…325 A summary of 11 studies supporting recommendations for the monitoring of AZA in patients with lung disease and organ transplant recipients is provided in Table 28 . [310][311][312]314,316,317,320,[322][323][324]326 3.5.1.1 Toxicity-Common adverse reactions associated with azathioprine include leukopenia, 327 pancreatitis, 328 and hepatitis. 329 Other effects of bone marrow toxicity include thrombocytopenia, anemia, megaloblastic anemia, aplastic anemia, eosinophilia, myelodysplastic syndrome, and fatal acute myeloid leukemia.…”