Long-Term Efficacy and Low Adverse Events of Methylprednisolone Pulses Combined to Low-Dose Glucocorticoids for Systemic Sclerosis: A Retrospective Clinical Study of 10 Years’ Follow-Up [Letter]

Dear editor

I read with great interest the research article by Cheng et al¹ on long-term low dose glucocorticoid treatment for systemic sclerosis (SSc). Rheumatic diseases can be debilitating, often only controlled by high dose steroids which comes with its own toxicity profile. It is encouraging to see research into limiting detrimental side effects of treatment for these patients, hence I would like to share my thoughts on this.

It is impressive that the authors thought of alternative steroid regimens in order to bring maximal benefits to patients. However, even low dose corticosteroids can be detrimental and an article the authors cited also reported the same, where fractures have occurred quite early on even in patients on low doses.² Thus, it is highly commendable that although the authors’ main focus is on steroids, they have taken other steroid-sparing agents into consideration. Unfortunately, as they mentioned, none of the conventional immunosuppressive therapies for SSc have shown to be effective for skin fibrosis, but nintedanib could be helpful for SSc with pulmonary involvement such as interstitial lung disease. This brings to mind the GiACTA trial³ which showed tocilizumab as a successful agent to maintain remission for giant cell arteritis, another rheumatic disease, leading to it being licensed for use in several countries. Similarly, there are early trials showing benefits of tocilizumab for SSc.⁴ Another drug worth considering is rituximab, where small trials have shown benefits⁵ and even resulted in regulatory approval for SSc in Japan. These are all promising and I hope there can be more investigations into them in future.

I appreciate the authors noting the limits of the study, one of which is the lack of blinding, and I am curious as to why it was not done. Although most of the clinical evaluations are quite objective, the modified Rodnan skin score could still be subjective despite efforts to standardize it, and not having blinding could definitely bias the assessor.

Even though this study only reports the result of 46 patients, which seems like a small sample size, I note that the authors started off with more and 128 patients were lost to follow up during the 10 years. It would be helpful to know the reasons for that as it would give a clearer picture on how patients tolerated steroids long term.

I also note the authors excluded SSc patients with any other organ involvement other than skin and lungs. I hope they can elaborate on the reason as SSc can affect the heart, kidneys, bowel, and muscles, in order to help readers understand the population of the trial better.

Therefore, it is good that alternative steroid regimens that seemingly have a lower rate of adverse effects are being studied. However, because of the well-documented toxicity of steroids and having seen many examples of that in my own clinical practice, I eagerly await further studies of a larger sample size and also potentially other steroid-sparing anti-inflammatory agents.