Systemic sclerosis is one of the most challenging of rheumatic diseases, often complicated by significant morbidity and leads to irreversible disability in many cases. While new treatments aimed to target major organ damage develop, little success has been achieved in management of skin changes of d…
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If you thought that this study was to help you predict which SSc patient may have rapidly worsening skin fibrosis, so as to focus aggressive immunosuppressive and/or expensive treatment, then you are mistaken, like me. It is actually to identify patients likely to progress, so as to enrol them for clinical trials to test the efficacy of various treatments. Putting it bluntly, it is to enrich the guinea pig pool of likely responders to a potentially effective treatment.
The logic is a little counter-intuitive, so try to follow me on this. Skin fibrosis in SSc follows a “natural” course of rapid worsening (inflammatory phase with swelling/thickening) followed by gradual “improvement” (resolution of inflammation, then scarring/fibrosis). It is somewhat like the stock market: if you are in the throes of a bear market, the only way is up. At the peak of a bull run, it is far more likely to see price declines than an ever higher peak. Likewise, by selecting patients with “mild” skin thickening, they are likely to worsen going forward, so a treatment which can retard or even arrest this progression is likely to be an effective drug. Those with significant and widespread thickening to begin with, their disease may already have run its course, and “spontaneous improvement” should not be misinterpreted as a beneficial treatment effect. Hence “mild” skin thickening at baseline predicts for progression; it’s simply the natural order of things. Likewise, lack of “tendon rubs” and possibly a negative anti-Scl70 seem more indicative of early rather than mild disease.
My approach to this issue as a practising clinician not doing clinical trials is simple (simplistic even): if I see an SSc patient with recent-onset, diffuse skin redness, oedema and itch, that’s my window-of-opportunity to act, aggressively.
PS The authors of this study suggested an arbitrary range of mRSS of 7-18 for trial cohort “enrichment”, because: below 7 may include “limited” skin sclerosis which seldom progresses; above 18, “spontaneous” regressors outnumber progressors.
Yanaba, K. (2016), Strategy for treatment of fibrosis in systemic sclerosis: Present and future. The Journal of Dermatology, 43: 46–55. doi: 10.1111/1346-8138.13026
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Objective Activated T cells are the main component of the inflammatory skin infiltrates that characterise systemic sclerosis (SSc). Our aim was to investigate the efficacy of abatacept, which tempers T-cell activation, in reducing skin fibrosis in complementary mouse models of SSc.
