Intravenous versus oral cyclophosphamide for lung and/or skin fibrosis in systemic sclerosis: an indirect comparison from EUSTAR and randomised controlled trials.

Objectives: Both intravenous (IV) and oral (PO) cyclophosphamide (CYC) showed beneficial effects on skin and lung involvement in systemic sclerosis (SSc) in placebo-controlled randomised clinical trials and observational studies. Our goal was to compare the relative efficacy and safety of PO- versus IV-CYC for treating interstitial lung disease and/or skin involvement in SSc.

Methods: Patients were derived from the EUSTAR centres and the Scleroderma Lung Studies I and II. A minimum of 6 months of CYC treatment and 12 months follow-up were required. Serious (SAEs) and non-serious adverse events and efficacy data (change in FVC%, DLCO%, mRSS) were analysed at the end of CYC treatment (EoT) and at follow-up (FU). Analysis included descriptive statistics and linear regressions.

Results: Differences in ethnicity, previous DMARD exposure, previous and concomitant steroid exposure/dosage were observed in the PO (n=149) and IV (n=153) CYC groups. Adjusted and unadjusted changes in FVC%, DLCO% and mRSS were similar irrespective of mode of administration. PO patients had more leukopenia (p<0.001), haemorrhagic cystitis (p=0.011) and alopecia (p<0.001) at the EoT visit, while the IV group had more SAEs (p=0.025) and need for oxygen supplementation at FU (p=0.049).

Conclusions: In a comparison of PO- to IV-CYC for SSc, we found no differences in lung function or cutaneous sclerosis after one year. Some differences in side effects were seen. The results need to be considered as preliminary; however, because we needed to use a combination of RCT and registry data, with some differences in demographics and concomitant medications, well-controlled studies are warranted.