Background/Purpose:

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is common and when progressive, associated with significant morbidity and mortality. Cyclophosphamide is frequently used as first line therapy but evidence is lacking for sustained benefit and toxicity remains a concern. Consequently, patients are often switched to azathioprine (AZA) for maintenance therapy.

We report the efficacy and tolerability of mycophenolate mofetil (MMF) in the management of SSc-ILD and compare this with AZA.

Methods:

Patients in the Australian Scleroderma Cohort Study treated with at least 3 months of MMF or AZA for SSc-ILD confirmed on high resolution computed tomography were identified. Pulmonary function tests (absolute and percent predicted values) at 6-monthly intervals were retrieved. Stability was defined as <10% change in absolute forced vital capacity (FVC), whilst ≥10% increase or decrease defined improvement or decline respectively.

The Wilcoxon sign-rank test was used to compare lung function at 12 months prior to commencement (T-1), baseline (T0), 12 months (T1) and 24 months (T2).

Results:

17 and 49 patients were treated with MMF or AZA for a mean of 3.7±1.4 and 3.8±3.1 years, respectively, with 66% of both groups previously treated with cyclophosphamide. Patients were treated with an average MMF dose of 1.57g/day and AZA of 100mg/day.

Mean age at commencement was 54.6±9.3 years for MMF and 52.9±12.9 years for AZA (p=0.23). Patients in both groups were predominantly female and Caucasian with long-standing disease (10.9±3.7 years for MMF vs. 12.7±7.3 years for AZA, p=0.28). Disease was diffuse in 65% of patients on MMF and 51% on AZA.

Median absolute FVC at T-1 for MMF treatment was 2.5L, declining to 2.3L at T0 (p=0.02). At T1 and T2, FVC was stable at 2.1L (p=0.63) and 2.1L (p=0.93). Median absolute diffusion capacity (DLCO) also demonstrated decline prior to treatment (12.2 to 9.8, p=0.03), with stability at T1 (10.4, p=0.83) and T2 (11.9, p=0.04). Stability or improvement was seen at T1 in 12/15 and T2 in 9/11 cases. Comparable efficacy was achieved with AZA (16/19 cases were stable or improved at T1 and 14/19 at T2).

Adverse events leading to discontinuation were less common in the MMF group (2/17 vs. 13/49). Gastrointestinal complications were the main cause for discontinuation in both groups.

Conclusion:

In patients with SSc-ILD with declining pulmonary function, MMF treatment was associated with stability in FVC and DLCO comparable to AZA and was better tolerated, suggesting a potentially superior role as maintenance therapy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/mycophenolate-mofetil-versus-azathioprine-in-scleroderma-associated-interstitial-lung-disease-results-from-the-australian-scleroderma-cohort-study/