Abstract
BackgroundMounting evidence indicates that inflammatory mechanisms drive systemic sclerosis (SSc) vasculopathy and fibrosis, especially early in the disease. Therefore, patients with very early SSc could benefit from early treatments targeting inflammation. Glucocorticoids are among the most potent anti-inflammatory and immunosuppressive agents. Several studies have demonstrated a mixed response to treatment with glucocorticoids in SSc, probably because it is seldom initiated at very early stages of the disease. We hypothesise that by inhibiting the inflammatory process driving SSc disease progression, glucocorticoid treatments will induce remission in patients with very early SSc.Methods/designThis study is a 12-week, randomised, double-blind, placebo-controlled trial analysing the effects of high-dose intravenous methylprednisolone in very early SSc. Thirty patients who fulfil the criteria for very early SSc will be randomly assigned in a 2:1 ratio to receive either intravenous methylprednisolone or a placebo on three consecutive days over three consecutive months. In this study, the primary endpoint will be the change in capillary density between the baseline and after 12 weeks of treatment. The secondary outcomes of this study are a change in selected biomarkers, other changes in the nailfold capillaries, signs of established SSc and changes in physical function, general health and utilities, as reported through questionnaires.DiscussionThis trial is the first aiming to treat very early SSc and is promising because it targets the very early stages of the disease process by using an inexpensive and relatively safe treatment known to be highly effective against inflammation. The use of vasculopathy and inflammatory biomarkers as well as clinical signs and symptoms as the endpoints in our study enables us to meet the patient need for markers of disease activity. If it is possible to prevent clinically significant disease in patients with very early SSc by using a safe treatment, this will cause a paradigm shift in scleroderma care and research.Trial registrationClinicalTrials.gov Identifier: NCT03059979. Registered on 20 February 2017.
Highlights
Mounting evidence indicates that inflammatory mechanisms drive systemic sclerosis (SSc) vasculopathy and fibrosis, especially early in the disease
The use of vasculopathy and inflammatory biomarkers as well as clinical signs and symptoms as the endpoints in our study enables us to meet the patient need for markers of disease activity
Patients who are still in the inflammatory phase of the disease are more likely to respond to treatment with glucocorticoids; the choice was made to include only patients who fulfil the very early diagnosis of systemic sclerosis (VEDOSS) criteria, but not the 2013 American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) classification criteria, for SSc [28]
Summary
Mounting evidence indicates that inflammatory mechanisms drive systemic sclerosis (SSc) vasculopathy and fibrosis, especially early in the disease. Several studies have indicated that inflammatory mechanisms drive SSc vasculopathy and fibrosis, especially at the early stages of the disease [2,3,4,5,6,7]. Glucocorticoids, some of the most potent anti-inflammatory and immunosuppressive agents, can induce remission in systemic autoimmune diseases, including lupus nephritis and dermatomyositis, and have an immediate and profound effect on the trafficking of leucocytes [9,10,11].
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