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Retrospective comparative study of the efficacy of JAK inhibitor (tofacitinib) in the treatment of systemic sclerosis-associated interstitial lung disease

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Abstract

The oral Janus kinases inhibitor (JAKi) has improved the management of skin manifestations in systemic sclerosis (SSc), and our study aimed to explore the efficacy of non-selective JAKi tofacitinib in ameliorating interstitial lung disease (ILD) in the patients with SSc. The hospitalization data of the SSc-ILD patients from April 2019 to April 2021 were collected, and the changes of pulmonary function and the radiological findings in pulmonary high-resolution CT (HRCT) from the 9 patients who received tofacitinib for at least 6 months and a matched group of 35 SSc-ILD patients treated with conventional immunosuppressants or glucocorticoids, were compared and analyzed. There were no significant differences in demographic data and clinical characteristics between the tofacitinib-treated group (tofa-group) and the matched group. However, in the tofa-group, the changes in serum lactate dehydrogenase (LDH) concentration and serum interleukin-6 levels were significantly lower than those in the matched group. Moreover, the tofa-group showed amelioration in decreased diffusing capacity of the lung for carbon monoxide (DLCO) (62.05 ± 9.47 vs. 66.61 ± 12.39, p = 0.046), reductions in ground-glass attenuation involvement (1.00 ± 0.86 vs. 0.33 ± 0.50, p = 0.024) and irregular pleural thickening (1.33 ± 0.50 vs. 0.67 ± 0.51, p = 0.004) in pulmonary HRCTs, alleviated modified Rodnan skin score (mRSS) of skin sclerosis (9.22 ± 3.81 vs. 7.11 ± 3.92, p = 0.048), and reduced HRCT scores of pulmonary fibrosis (15.00 ± 3.87 vs. 12.66 ± 4.92, p = 0.009). Logistic regression analysis showed that the involvement of ground-glass attenuation (OR 11.43) and the add-on therapy of tofacitinib (OR 9.98) were the relevant factors in the amelioration of HRCT. Our results indicate that the use of JAKi (tofacitinib) may be relevant to significant improvement of the sclerosis and early radiological abnormalities in SSc-ILD patients. Further studies are needed to confirm these findings and to explore its efficacy more precisely.

Key Points

• The currently available therapies for SSc-ILD have limited therapeutic benefits.

• The add-on therapy of the oral JAK inhibitor is available in the real world.

• The tofacitinib was promising in the improvement of the sclerosis and early radiological abnormalities in SSc-ILD patients.

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Data Availability

The researchers affirm that the data backing the conclusions of this study can be found within the article [and/or its supplementary materials]. Additionally, further data supporting the findings can be obtained by contacting the corresponding author, Junfei Zhou, at 15003990860@163.com or ZJF2021@zzu.edu.cn, upon a reasonable request.

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Funding

This work was supported by the Beijing Bethune Foundation (grant 2017YFC0907600).

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Authors and Affiliations

Authors

Contributions

Development of study: Tianshu Chu, Shi Lipu. Clinical data acquisition: Zhou Junfei, Gao Meihua, Zhang Shuai, Lu Xiangting, Lei Zhidan, Cheng Tianming, and Liu Yajing. Data analysis: Zhou Junfei, Gao Meihua. Interpretation of results: Zhou Junfei, Gao Meihua. Manuscript preparation and review: Zhou Junfei, Gao Meihua, Zhang Shuai, Lu Xiangting, Lei Zhidan, Cheng Tianming, Liu Yajing, Tianshu Chu, and Shi Lipu. Manuscript revision and correspondence: Zhou Junfei, Tianshu Chu, and Shi Lipu. All authors reviewed, revised, and approved the manuscript for submission.

Corresponding authors

Correspondence to Zhou Junfei or Tianshu Chu.

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Ethics approval and consent to participate

The study protocol was reviewed and approved by the local Ethics Committees of People’s Hospital of Zhengzhou University with the reference number: HNEECKY-2020(31), and the written informed consents were obtained from the patients prior to submission of this article.

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Zhou Junfei and Gao Meihua are co-first authors.

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Junfei, Z., Meihua, G., Shuai, Z. et al. Retrospective comparative study of the efficacy of JAK inhibitor (tofacitinib) in the treatment of systemic sclerosis-associated interstitial lung disease. Clin Rheumatol 42, 2823–2832 (2023). https://doi.org/10.1007/s10067-023-06660-2

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