Treatment modalities and drug survival in a systemic sclerosis real-life patient cohort

Panopoulos et al. Arthritis Research & Therapy https://doi.org/10.1186/s13075-020-2140-3 (2020) 22:56 RESEARCH ARTICLE Open Access Treatment modalities and drug survival in a systemic sclerosis real-life patient cohort S. Panopoulos1* , Κ. Chatzidionysiou1, M. G. Tektonidou1, V. K. Bournia1, A. A. Drosos2, Stamatis-Nick C. Liossis3, T. Dimitroulas4, L. Sakkas5, D. Boumpas6, P. V. Voulgari2, D. Daoussis3, K. Thomas7, G. Georgiopoulos7, G. Vosvotekas8, Α. Garyfallos4, P. Sidiropoulos9, G. Bertsias9, D. Vassilopoulos7 and P. P. Sfikakis1 Abstract Background: European data indicate that systemic sclerosis (SSc)-related death rates are increasing, thus raising concerns about SSc’s optimal management. Herein, we describe current treatment modalities and drug survival in a real-life SSc cohort. Methods: Details on immunosuppressive/antiproliferative (methotrexate, mycophenolate, cyclophosphamide, azathioprine, rituximab, tocilizumab) and vasoactive agent [(endothelin receptor antagonists (ERAs), sildenafil, iloprost, and calcium channel blockers (CCB)] administration during the disease course (11.8 ± 8.4 years, mean + SD) of 497 consecutive patients examined between 2016 and 2018 were retrospectively recorded. Drug survival was assessed by Kaplan–Meier analysis. Results: Methotrexate was the most frequently administered immunosuppressive/antiproliferative agent (53% of patients), followed by cyclophosphamide (26%), mycophenolate (12%), and azathioprine (11%). Regarding vasoactive agents, CCB had been ever administered in 68%, ERAs in 38%, iloprost in 7%, and sildenafil in 7% of patients; 23% of patients with pulmonary fibrosis had never received immunosuppressive/antiproliferative agents, 33% of those with digital ulcers had never received ERAs, iloprost, or sildenafil, whereas 19% of all patients had never received either immunosuppressive/antiproliferative or other than CCB vasoactive agents. Survival rates of methotrexate, cyclophosphamide, and mycophenolate differed significantly, being 84/75%, 59/43%, and 74/63% at 12/24 months, respectively, with inefficacy being the most frequent discontinuation cause. Conversely, CCB, ERAs, and sildenafil had high and comparable retention rates of 97/91%, 88/86%, and 80/80%, respectively. Conclusions: Existing therapeutic limitations indicate that more evidence-based treatment is warranted for successful management of SSc. Vasculopathy seems to be managed more rigorously, but the low retention rates of immunosuppressive/antiproliferative drugs suggest that effective and targeted disease-modifying agents are warranted. Keywords: Systemic sclerosis, Treatment patterns, Drug survival, Cohort study * Correspondence: 1 Joint Rheumatology Program, 1st Department of Propedeutic Internal Medicine-Rheumatology Unit, National and Kapodistrian University of Athens, School of Medicine, Laikon General Hospital, 17 Agiou Thoma str., 115 27 Athens, Greece Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Panopoulos et al. Arthritis Research & Therapy (2020) 22:56 Background Systemic sclerosis (SSc) is a rare systemic autoimmune disorder that pathogenetically encompasses microvascular damage and fibrosis of the skin and visceral organs, associated with immunological aberrations [1] and presents the highest disease-related mortality among the various rheumatic diseases [2, 3]. Despite the emergence of new therapeutic agents for SSc, mainly targeting inflammatory and vascular pathways, survival has not improved significantly during the last decades [4, 5]. Recently, a study from the EUSTAR group reported that despite a decrease in standardized mortality rate in SSc over time, the rate of deaths directly attributed to SSc has increased [6]. Overall, this lack of improved survival raises concerns about the efficacy of currently available treatments and conveys the need for new, more effective agents. The objectives of the present study are to describe current treatment modalities in a large, multicentre, real-life SSc cohort and to determine the drug survival rate of commonly used immunosuppressive/antiproliferative or vasoactive agents in SSc that reflects their real-world effectiveness and safety. Methods Based on a standardized protocol for data recording procedures and definition of organ involvement, consecutive patients from 8 academic centres across Greece who fulfilled the 1980 American College of Rheumatology classification criteria for SSc [7] and were examined at least once between January 2016 and December 2018, were included in the study. Ethical approval was provided by the Joint Rheumatology Program (Hippokration General Hospital, 64/16-4-2015) as well as by the local institutional boards of participating centres. Informed consent was provided by all patients at baseline. The medical records of all patients were retrospectively analyzed and demographics, SSc clinical manifestations, and any immunosuppressive/antiproliferative or vasoactive treatments administered anytime during the disease course were recorded. Organ involvement was defined in all participating centres according to the following criteria: 1) Arthritis: presence of synovitis in a joint. 2) Pulmonary fibrosis (PF): usual interstitial pneumonia (UIP) or non-specific interstitial pneumonia (NSIP) pattern on high-resolution chest computed tomography (CT). 3) Pulmonary arterial hypertension (PAH): mean pulmonary artery pressure (PAP) ≥ 25 mmHg on cardiac catheterization or systolic PAP > 50 mmHg in echocardiography. 4) Cardiac rhythm disorders: presence of arrhythmias or conduction defects in ECG confirmed by 24 h Holter monitoring. Page 2 of 8 5) Renal crisis: Abrupt onset of rapidly progressive oliguric renal failure that cannot be attributed to any other cause with or without concurrent accelerated arterial hypertension (> 150/90 mmHg) 6) Digital ulcers (DUs): denuded area with w (...truncated)