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AB1053 (2024)
FOLLOW-UP DATA ON DRUG-INDUCED LUPUS CASES DURING TNF-ALPHA INHIBITOR TREATMENT
Keywords: Autoantibodies, Biological DMARD
F. Cosan1, A. Kimiaei1, S. Safaei1, I. E. Uluisik1, M. M. Sonkaya1
1Bahcesehir University, Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Istanbul, Turkey

Background: Drug-induced lupus (DIL) is a common term for lupus that can develop during the use of certain medications. Although exact diagnostic criteria have not been established, the widely accepted definition is the presence of at least one clinical and one laboratory finding associated with lupus. DIL exhibits different characteristics than systemic lupus erythematosus, and major organ involvement is generally not observed. Numerous agents have been reported to cause DIL, and TNF inhibitors (TNFI) are among them. Although cases of DIL associated with TNFI have been reported, there is limited data on follow-up and treatment.


Objectives: We aimed in this study to analyze the treatment and follow-up data of patients who developed DIL during the use of TNF inhibitors.


Methods: We retrospectively analyzed the electronic medical records of 590 patients prescribed bDMARDs from 2015–2023, who underwent assessments of anti-dsDNA levels due to non-specific reasons such as arthritis, fatigue, hair loss, elevated acute-phase reactants, dryness, or those who had previously tested positive for ANA. The clinical manifestations, treatments, and post-treatment clinical and laboratory parameters of patients with positive anti-dsDNA were analyzed by reviewing their files.


Results: Among the patients treated with bDMARDs, 15 patients demonstrated anti-dsDNA positivity following TNFI usage. The mean age of the patients was 42.13 years (2 male and 13 female). Diagnoses included 7 cases of AS, 6 cases of RA, and 2 cases of PSA, with an average disease duration of 8 years. The mean duration from initiating the first TNFI therapy to the onset of positive anti-dsDNA was 5.13 years, with a median of 4 years and a range of 2–14 years. Among the 15 patients, adalimumab was used by 9, certolizumab by 3, infliximab by 2, and golimumab by 1. Six patients had a history of previous TNFI use, with exposure ranging from 1 to 4 different TNFI, while nine patients had not used any TNFI before. The average duration between the first TNFI usage and the detection of anti-dsDNA positivity was 41.53 months, with a median of 24 months (3–156 months range). The average duration between the last TNFI usage and the detection of anti-dsDNA positivity was 21.8 months, with a median of 12 months (3–92 months range). Throughout the follow-up period after the onset of anti-dsDNA positivity (mean 14.06 months, median 8 months, range 1-56 months), anti-dsDNA levels remained stable in 40% of patients while becoming negative in 60% of patients. Notably, two patients exhibited clinical manifestations of DIL, with one presenting with malar rash, lupus dermatitis, and arthritis, and the other displaying only malar rash. No major organ involvement was observed in any patient. ANA titers were negative in 3 patients and positive in 12 patients, with 3 of them exhibiting high titers. Extractable nuclear antigens were positive in 7 patients (Table 1 ).

During follow-up, hydroxychloroquine was given to all DIL patients, and close monitoring was maintained as patients exhibited very mild symptoms. 60% of patients continued the same TNFI without experiencing disease activation. In 33% of the patients, a medication switch was performed due to the activation of the primary disease. In one case (6%), the drug was changed to rituximab. In patients who switched to the second TNFI, anti-dsDNA positivity persisted; however, no flares, major organ involvement, or new lupus developments were observed.

Extractable Nuclear Antigen Profiles

Patient Extractable Nuclear Antigens
1 Anti-histone, Anti-nucleosome, Anti-Sm
2 Anti-histone, Anti-nucleosome
3 Anti-nucleosome, Anti-RNP, Anti-mitochondrial M2 (AMA-M2), Anti-Ku
4 Anti-DFS70
5 Anti-nucleosome, AMA-M2
6 Anti-Sm, Anti-RNP
7 Anti-Ro

Conclusion: In patients who develop positive ds-DNA during the use of TNF inhibitors and exhibit mild symptoms, close monitoring while continuing the TNF inhibitor appears to be safe. Larger-scale studies are needed to establish a diagnosis, treatment, and follow-up algorithm in this field.


REFERENCES: [1] G, K. (2019). Drug-induced lupus. Indian Journal of Rheumatology, 14(5), 10. https://doi.org/10.4103/0973-3698.272154


Acknowledgements: This research has received no external funding.


Disclosure of Interests: None declared.


DOI: 10.1136/annrheumdis-2024-eular.4018
Keywords: Autoantibodies, Biological DMARD
Citation: , volume 83, supplement 1, year 2024, page 1840
Session: Systemic lupus erythematosus (Publication Only)