Low-dose pulse cyclophosphamide in interstitial lung disease associated with systemic sclerosis (SSc-ILD): Efficacy of maintenance immunosuppression in responders and non-responders

ObjectiveTo investigate the long-term disease course of patients with recently deteriorated systemic sclerosis (SSC)-interstitial lung disease (ILD) undergoing continuous immunosuppressive treatment with cyclophosphamide (CYC) as induction therapy.MethodsA total of 45 consecutive SSc patients were treated with weekly pulses of 500 mg of CYC up to 10-g cumulative dose followed by azathioprine (AZA) in those experiencing improvement (>10% increase) or stabilization of both forced vital capacity and diffusion lung capacity for carbon dioxide and by micophenolic acid (MMF) in those experiencing deterioration (>10% decrease of either parameter). The follow-up ranged from 6 to 62 months post-CYC regimen (median = 36 months).ResultsOverall, 39 patients completed the CYC regimen. Of them, 24 (61.5%) experienced improvement or stabilization of lung function parameters and received AZA; the remaining 15 received MMF. During follow-up, lung function parameters improved in 3 (12.5%), remained stable in 18 (75%), and worsened in 3 (12.5%) AZA-treated patients, whereas they worsened in 8 (67%) and remained stable in 4 (33%) MMF-treated patients. The incidence of improvement or stabilization was significantly higher in AZA-treated than in MMF-treated patients (p = 0.001). The time to the decline of lung function was significantly shorter in CYC non-responders, and CYC unresponsiveness was predictive of lung function worsening over time in a multivariate analysis (HR = 9.14; 95% CI: 2.28-36.64; p = 0.0018).ConclusionOur study supports the use of low-dose pulse CYC as induction therapy of recently deteriorated SSc-ILD. Moreover, it suggests that AZA should be administered to CYC-responsive patients but does not show any definite effect of MMF in unresponsive patients.