AB1195 NINTEDANIB RESTORES ENDOTHELIAL FUNCTION IN PATIENTS WITH SYSTEMIC SCLEROSIS: PRELIMINARY FINDINGS OF A MONOCENTRIC STUDY
Authors: D. Benfaremo, V. Zaccone, M. Sistoni Pepparoni, S. Contegiacomo, S. Bigoni, C. Tana, Y. Ferraioli, N. Pacenti, A. Pantaleoni, D. Mea, M. A. Piga, S. Svegliati Baroni, S. Agarbati, C. Paolini, M. Mozzicafreddo, T. Spadoni, M. Fogante, L. Zuccatosta, G. Argalia, G. Moroncini
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Nintedanib is approved for the treatment of interstitial lung disease (ILD) associated with systemic sclerosis (SSc). Some experimental evidence supports the hypothesis that nintedanib may act on the vasculature by attenuating vascular remodeling and improving microvascular architecture<sup>1</sup>, although these effects remain unclear. <h3>Objectives:</h3> The aim of this study was to evaluate the effect of nintedanib on systemic microcirculation and endothelial function assessed by flow-mediated dilation of the brachial artery (FMD) in patients with SSc-ILD. <h3>Methods:</h3> In this prospective observational study, 10 consecutive patients affected by SSc-ILD were enrolled, according to the following inclusion criteria: 1. Age &gt; 18 years; 2. Progressive disease according to INBUILD criteria; 3. Indication for antifibrotic therapy with nintedanib; 4. Signature of the informed consent. There were no exclusion criteria. For each patient, clinical-demographic data were collected including: sex, age, duration and localization of disease, disease subset (limited or diffuse skin subset), antibody specificity, modified Rodnan skin score (mRSS), capillaroscopic pattern (early, active or late), previous and current therapy. All patients were assessed at baseline, 6 months and 12 months with the following tests: FMD, nailfold videocapillaroscopy (NVC), ultra-high frequency skin ultrasound (HFUS), spirometry and DLCO, 6-minute walking test (6MWT) and lung ultrasound. Data were analyzed using the Wilcoxon signed-rank test. <h3>Results:</h3> Of the 10 enrolled patients (10 F, median age 60.5 years), 5 had diffuse SSc and 5 limited SSc, with a median mRSS of 4.5 and median disease duration of 12 years. All patients received nintedanib 150 mg BID. Two patients reduced the dosage to 100 mg BID (after 6 and 9 months, respectively), while one patient definitively stopped treatment after 6 months due to persistent gastrointestinal adverse effects (diarrhea and nausea). At baseline, 90% of patients had FMD values lower than 10% (threshold above which FMD values are considered normal) with a median value of 4.16% (3.03 - 10.34). At 6 months, FMD values increased in 70% of patients, although in 80% of cases the values remained lower than 10%, with a median value of 8.83% (0 - 23.07). At 12 months, FMD values increased in all patients compared to baseline, with a median value of 12% (9.37-18.18) (p &lt; 0.05) (Figure 1). No statistically significant differences were observed in capillaroscopic parameters (i.e. median number of capillaries and giant capillaries) at baseline and after 6 and 12 months. Also, no statistically significant differences were noted with regard to mRSS and skin and lung ultrasound measures. Nintedanib was able to stabilize (&lt; 10% decline) or improve FVC at 12 months in 60% of cases and TLC in 90% of cases. However, a decline in DLCO &gt; 15% was observed in 40% of cases. Finally, there was a statistically significant improvement (p &lt; 0.05) in the 6MWT at 12 months. <h3>Conclusion:</h3> Although nintedanib did not demonstrate a significant impact on the nailfold microcirculation, data from this small pilot study suggest a positive effect on endothelial function assessed by FMD. Further studies should explore the hypothesis of a beneficial effect of nintedanib on endothelial function and vascular remodeling. <h3>REFERENCES:</h3> [1] Tsutsumi T, Nagaoka T, Yoshida T, et al. Nintedanib ameliorates experimental pulmonary arterial hypertension via inhibition of endothelial mesenchymal transition and smooth muscle cell proliferation. PLoS One. 2019 Jul 24;14(7):e0214697. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>