OP0144 Intravenous versus oral cyclophosphamide (CYC) for the treatment of interstitial lung involvement (ILD) and skin involvement in systemic sclerosis (SSC): safety and efficacy evaluation in a large multi-centre scleroderma cohort
Authors: C. Bruni, D.P. Tashkin, V. Steen, Y. Allanore, O. Distler, J. Grotts, M. Matucci-Cerinic, D.E. Furst
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> In the last decade, oral CYC has shown modest but significant effect on SSc-ILD and skin thickness in two large randomised controlled trials, with superiority to placebo and similar efficacy to mycophenolate. However, many centres give priority to monthly IV CYC for expected milder toxicity. <h3>Objectives</h3> To compare efficacy and safety of oral versus iv CYC for treating ILD and/or skin involvement in SSc. <h3>Methods</h3> SSc patients treated with oral or iv CYC for at least 6 months were followed for 1 year from the last administration. Data were obtained from the EUSTAR database and the Scleroderma Lung Studies I and II regarding safety [both serious (SAEs) and non-serious adverse events (AEs)] and efficacy (%FVC,%DLCO, mRSS) at end of treatment and after one-year follow-up were analysed [mean ±SD or median(IQR) as appropriate]. <h3>Results</h3> 322 patients were eligible: 149 patients received oral CYC with median daily dose 106(93–134) mg, treatment duration 365(364–366) days, while 153 patients received IV CYC median monthly dose 1000(700–1200) mg, treatment duration 335(291–374) days. Ethnicity, previous DMARD exposure, previous and concomitant steroid exposure and dosage, current/previous smoking exposure, prevalence of digital ulcers and arterial hypertension were different between the two groups (see table 1 for further details). For efficacy: despite different baseline%FVC and%DLCO, adjusted changes in pulmonary measures from end of treatment (EOT) vs baseline and follow-up visit (FU) vs EOT were, respectively: %FVC [0(−5–5) vs 0(−7–7) and 1 (−6–4) vs −2(−7–4), p=NS],%DLCO [−4 (−9–3) vs −3 (−9–6), 1(−6–5) vs −1 (−9–6), p=NS] and mRSS [−3 (−5–0) vs −1 (−5–0), −1(−4–1) vs 0(−3–1), p=NS]. In a multivariate analysis, no independent variable significantly influenced%FVC change at any visit.%DLCO change was influenced by baseline%DLCO and history of SSc-related cardiomyopathy at EOT assessment and by history of SSc-muscle involvement at FU visit. Baseline mRSS was the only variable having a significant impact on mRSS change. For safety: in the oral group, there were more leukopenia (WBC &lt;2500 ×10<sup>9</sup>/mm³ at least once – 21.6% vs 1.2%, p&lt;0.001), haemorrhagic cystitis [5.5% (8 instances) vs 0%, p=0.011) at EOT visit. In contrast, there were more SAEs (9% vs 19%, p=0.025), need for oxygen supplementation (5% vs 14%, p=0.016) and SSc-related cardiomyopathy onset (2% vs 9%, p=0.024) during follow-up in the IV group. <h3>Conclusions</h3> In this hypothesis generating study, similar efficacy of one year of oral and iv CYC were seen. In contrast, a different safety profile for AE time courses and types of AEs were seen in the two groups. Although significantly higher dosage of steroids at all visits and prevalence of DMARDs use were present in the IV CYC group (as a post-treatment maintenance), these did not have an impact on either safety or efficacy. Case-control or randomised studies are warranted to extend and confirm our data. <h3>Disclosure of Interest</h3> None declared