title: Low-dose pulse cyclophosphamide in interstitial lung disease associated with systemic sclerosis (SSc-ILD): efficacy of maintenance immunosuppression in responders and non-responders.
abstract: OBJECTIVE
  To 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.
  
  
  METHODS
  A total of 45 consecutive SSc patients were treated with weekly pulses of 500mg 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).
  
  
  RESULTS
  Overall, 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).
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Rheumatology Unit, Second University of Naples, II Policlinico, Via Pansini 5, Naples 80131, Campania, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Iudici
authors.affiliation: Rheumatology Unit, Second University of Naples, II Policlinico, Via Pansini 5, Naples 80131, Campania, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cuomo
authors.affiliation: Rheumatology Unit, Second University of Naples, II Policlinico, Via Pansini 5, Naples 80131, Campania, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Vettori
authors.affiliation: Respiratory Medicine Section, Department of Clinical Medicine and Surgery, "Federico II" University of Naples, Naples, Campania, Italy.
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Bocchino
authors.affiliation: Respiratory Medicine Section, Department of Clinical Medicine and Surgery, "Federico II" University of Naples, Naples, Campania, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sanduzzi Zamparelli
authors.affiliation: Radiology, Radiotherapy and Nuclear Medicine Unit, Second University of Naples, Campania, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cappabianca
authors.affiliation: Rheumatology Unit, Second University of Naples, II Policlinico, Via Pansini 5, Naples 80131, Campania, Italy. Electronic address: gabriele.valentini@unina2.it.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Valentini
mesh_terms: D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D017563:Lung Diseases, Interstitial / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000150:complications*; D013997:Time Factors; D016896:Treatment Outcome; D014797:Vital Capacity / Q000502:physiology
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D001379:Azathioprine
keywords: Interstitial lung disease; Systemic sclerosis