Ab0661 Tofacitinib Plus Iguratimod in Rheumatoid Arthritis-Related Progressive Fibrosing Interstitial Lung Disease: 13 Cases From a Single Centre in China

Background: Some patients with RA-ILD develop a progressive fibrotic phenotype despite intensive immunosuppressive therapy (1). Furthermore, therapeutic choice for RA-ILD is complex due to potential lung toxicity associated with many csDMARDs and unclear effectiveness on lung involvement (2). Therefore, reversing or stabilizing these progressive fibrotic lesions remains challenging. Currently, in vivo and in vitro researches suggest that TOF and IGU could slow down the progression of rheumatic disease related ILD and may be a possible remedy option for progressive fibrosing RA-ILD (3-6). TOF and IGU were widely taken to cure RA in China. However, we have found no research reports on the efficacy of TOF combined with IGU in the treatment of progressive fibrosing RA-ILD. Therefore, we performed this observational study to understand their safety and effectiveness against progressive fibrosing RA-ILD. Objectives: Our pilot study investigated the efficacy of TOF plus IGU in patients with RA-related progressive fibrosing ILD, providing a new therapeutic option. Methods: This is a retrospective observational, single center study. Some csDMARDs and/or biologics were given to all the thirteen patients with progressive fibrosing RA-ILD before TOF plus IGU treatment. After at least 9 months of treatment with TOF plus IGU, the RA activity, PFTs results, and HRCT scores were evaluated at baseline and each follow-up. Results: Thirteen patients were followed up for 19 [9-24] months. There were significant changes in white blood cells, rheumatoid factor, anti-cyclic citrullinated peptide, and C-reactive protein during the follow-up 1 (P<0.05), but erythrocyte sedimentation rate decreased at follow-up 2 (P<0.05). At the follow-up 1 after TOF plus IGU initiation (3 [2-5] months), 3/13 patients achieved complete remission in RA, 7/13 patients achieved LDA, and 3/13 patients achieved MDA (P<0.001). All the patients in ILD were relieved (P<0.001) (Figure 1 C1, 2). Total GGO score improved significantly (P=0.043). At the follow-up 2 after the treatment (7 [5-9] months), 2/13 patients in LDA achieved remission.1/13 patients showed deterioration after the discontinued TOF plus IGU treatment (Figure 1 A1, 2). Significant changes were revealed in the FVC % (P=0.008), DLCO SB % (P=0.032), and total fibrosis score (P=0.044). At the last follow-up visit (11 [6-12] months), 1/13 patients in MDA, and 1/13 LDA achieved remission. 1/13 patients underwent deterioration (Figure 1 B1, 2) after the discontinued TOF treatment due to varicella zoster virus infection. The deterioration at the follow-up 2 was controlled (Figure 1 A3) after the treatment was continued. The FVC % (P=0.009), DLCO SB % (P=0.040), and total GGO (P=0.022), total fibrosis score (P=0.026) were kept steady compared with at baseline (Figure 1 D1, 2 and Figure 1 E1, 2). All the patients tapered the prednisone and six patients had almost stopped (Table 1). Conclusion: TOF plus IGU may be a potential therapeutic choice for patients with progressive fibrosing RA-ILD refractory to some csDMARDs and/or biologics without severe adverse events. REFERENCES: [1] E. L. Matteson, et al., Nintedanib in patients with autoimmune disease-related progressive fibrosing interstitial lung diseases: subgroup analysis of the inbuild trial. Arthritis Rheumatol. 74, 1039-1047 (2022). [2] G. Cassone, et al., Treatment of rheumatoid arthritis-associated interstitial lung disease: lights and shadows. J. Clin. Med. 9 (2020). [3] M. Tardella, et al., A retrospective study of the efficacy of jak inhibitors or abatacept on rheumatoid arthritis-interstitial lung disease. Inflammopharmacology 30, 705-712 (2022). [4] C. Vacchi, et al., Tofacitinib for the treatment of severe interstitial lung disease related to rheumatoid arthritis. Case Rep. Med. 2021, 1-5 (2021). [5] P. Shu, et al., Iguratimod attenuates general disease activity and improves lung function in rheumatoid arthritis-associated interstitial lung disease patients. Eur. Rev. Med. Pharmacol. Sci. 25, 4687-4692 (2021). [6] Q. Han, et al., Iguratimod reduces b-cell secretion of immunoglobulin to play a protective role in interstitial lung disease. Int. Immunopharmacol. 97, 107596 (2021). Acknowledgements: NIL. Disclosure of Interests: None declared.