Background: Tadalafil is an approved drug for the treatment of Raynaud’s phenomenon and digital ulcers in systemic sclerosis (SSc). From our previous in vitro work, we have observed anti-fibrotic potential of tadalafil in SSc dermal fibroblasts. Herein we have carried out an in vivo study to evaluate its anti-fibrotic effect on skin fibrosis in SSc.

Objectives: To compare the change from baseline, in modified Rodnan skin score (mRSS) and mRNA expression of pro-fibrotic genes at 6 months in SSc patients receiving standard of care plus tadalafil vs those receiving standard of care but not tadalafil.

Methods: Adult patients fulfilling the 2013 ACR classification criteria for SSc who were tadalafil naïve or have received it more than 6 months prior were recruited in this open label randomized prospective observational study. A 4 mm ² forearm lesional skin punch biopsy was obtained at baseline and after 6 months of treatment. mRSS and expression of transcripts of nine profibrotic genes including cartilage oligomeric matrix protein (COMP), thrombospondin-1 (THS1), interferon induced 44 (IFI44), sialic acid binding immunoglobulin like lectin 1 (SIGLEC1), connective tissue growth factor (CTGF), collagen type1 α1 and α2 (COL1A1 and COL1A2), actin α2 (ACTA2) and tenascin C (TN-C) were recorded. Data analysis was done using student’s t test and Wilcoxon signed rank test.

Results: Initially 45 patients were enrolled, however 4 patients were lost to follow up and one patient died secondary to pneumonia and sepsis. Of the remaining 40 patients, 35 (87.5%) were females and 27 (67.5%) belonged to diffuse phenotype, with a median age of 35 (28.5-39.25) years and median duration of skin thickening of 24 (12- 48) months. 25 patients received tadalafil while 15 received other drugs as per the disease manifestations. The baseline characteristics were similar between the groups (Table 1). The median mRSS decreased from 12 to 6 (p<0.001) in the tadalafil group, while in the non-tadalafil group, there was a non- statistically significant increase from 14 to 15 (p= 0.8). The median change in mRSS (ΔmRSS) at 6 months was -7 (-13 - -3) in the tadalafil group and -1 (-2 - 4) in the non tadalafil group (p=0.005). There was a significant reduction in the expression of profibrotic genes in those receiving tadalafil compared to baseline as well as those not receiving tadalafil. An increase in the expression of TN-C was seen in patients not receiving tadalafil (Table 2). There was statistically significant moderate positive correlation of ΔmRSS with change in expression of THS1, IFI44, SIGLEC1 and CTGF.

Conclusion: Tadalafil significantly reduced the skin fibrosis and mRNA expression of profibrotic genes in systemic sclerosis. It is a potential therapeutic option for skin fibrosis in systemic sclerosis.

REFERENCES: [1] Farina G, Lafyatis D, Lemaire R, Lafyatis R. A four-gene biomarker predicts skin disease in patients with diffuse cutaneous systemic sclerosis. Arthritis Rheum. 2010 February; 62(2): 580–588.

[2] Kazaz İO, Özgür GK, Çobanoğlu Ü, Kalyoncu Nİ, Karagüzel E, Topbaş M, Eren H, Kazaz SN, Özyavuz R. Investigation of the effects of tadalafil and telmisartan in bleomycin-induced pulmonary fibrosis on rats. J Surg Med. 2020;4(8):689-692.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.