Comment on: Beneficial effects of nintedanib on cardiomyopathy in patients with systemic sclerosis: a pilot study: reply

Dear Editor, We here respond to the comments by Dr Sfikakis et al. [1] on our recent study [2]. Sfikakis et al., by contrasting the results of two cardiac magnetic resonance (CMR) studies on SSc patients, theirs [3] and ours [2], raised important issues that should be solved in the future management of cardiomyopathy (CM) associated with SSc. Sfikakis et al. [3] observed a decreased T2 ratio and mapping but an unchanged extracellular volume (ECV) following immunosuppressive therapy, whereas we [2] observed both a decreased T2 ratio and a decreased ECV, with a remarkable change in ECV, following nintedanib therapy. These results would support two different potential therapeutic approaches in the management of SSc-CM, anti-inflammation and anti-fibrosis, given that T2 and ECV well reflect myocardial oedema and fibrosis, respectively [4]. Conversely, we face the new issue of ‘how to choose and combine the two different approaches’. This issue also exists in the management of SSc-associated interstitial lung disease (ILD) [5]. Like SSc-ILD, SSc-CM would reflect a heterogeneous pathological condition, including abnormality of the coronary microcirculation, myocarditis with various types of infiltrating immune cells and myocardial fibrosis, with their dominance being different in each patient [6]. In our study [2], unlike Sfikakis’s [3], the change in T2 ratio was not different between patients treated with and without immunosuppressants (P = 0.61). When we conduct a clinical trial on SSc-CM, we need not only to see endpoints but also to carefully analyse baseline data to identify subgroups of good responders to immunosuppressive and/or anti-fibrotic therapy. Particularly, CMR parametric mapping (T1, T2 and ECV) provides us with information at the tissue level and would therefore be a strong point in the study of SSc-CM. However, as Sfikakis et al. [1] pointed out, it is mandatory to use the same scanner with the same magnetic field strength to compare baseline CMR parametric mapping data among subjects, presenting a barrier to a multicentre trial. We completely agree with Sfikakis et al. that a multicentre, randomized study is warranted to confirm the efficacy of immunosuppressive and/or anti-fibrotic therapy for SSc-CM and to identify subgroups of good responders by solving the limitations of CMR parametric mapping.

Data availability

Data are available upon reasonable request by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). All data relevant to the study are included in the article.

Funding

No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article.

Disclosure statement: M.K. has received research grants from AbbVie, Actelion, GlaxoSmithKline, Janssen, Nippon Shinyaku and Novartis, and speaking fees from Astellas and Eli Lilly. T.A. has received research grants from Astellas, Takeda, Mitsubishi Tanabe, Chugai, Daiichi-Sankyo, Otsuka, Pfizer, Alexion, Bayer, Otsuka, Chugai, Takeda, Eisai, Bristol-Myers Squibb, Daiichi Sankyo, Mitsubishi Tanabe and Asahi Kasei, consultant fees from Ono, Sanofi, Daiichi Sankyo and Pfizer, and speaking fees from Mitsubishi Tanabe, Chugai, Astellas, Takeda, Pfizer, Daiichi Sankyo, Bristol-Myers Squibb and Eli Lilly. K.N. has nothing to declare.

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