POS1431 POTENTIAL DISEASE-MODIFYING EFFECT OF EARLY USE OF METHOTREXATE IN GIANT CELL ARTERITIS
Authors: J. Berry, C. Mun Alice Lin, J. Weightman, J. Casement, B. Thompson, J. Heaney, K. Baker, A. Lorenzi, G. Reynolds
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Glucocorticoids remain the principal treatment for giant cell arteritis (GCA), despite causing significant comorbidity including osteoporosis, infection, and diabetes. The anti-IL6 receptor inhibitor tocilizumab has demonstrated benefit as a steroid-sparing agent, though its use in many countries including the UK is limited to a minority of patients with relapsing or refractory disease. Methotrexate is commonly used in practice but evidence for its effectiveness as a steroid-sparing agent or in maintaining remission is equivocal. In other immune-mediated rheumatic diseases, early treatment with methotrexate can improve long-term outcomes and rates of remission. In this cohort study, we aimed to assess whether early use of methotrexate in GCA influences the long-term prognosis including rates of relapse following completion of glucocorticoid taper. <h3>Objectives:</h3> The primary outcome was time to first relapse following completion of glucocorticoid taper. <h3>Methods:</h3> We included all consecutive patients referred to the Fast Track GCA service at the Freeman Hospital in Newcastle and given a diagnosis of GCA between December 2016 to December 2020 (Newcastle and North Tyneside Research Ethics Committee, 16/NE/0319). Methotrexate is not a standard of care in our service, with the decision to initiate treatment influenced by both physician and patient preference and comorbidities. Baseline clinical data is prospectively recorded in a clinical database and longitudinal outcome data is captured through retrospective case notes review. <h3>Results:</h3> 124 consecutive patients with confirmed GCA were included in analyses, of which 77 (62%) started methotrexate during glucocorticoid taper. Median follow-up was 41.8 months (IQR 32.5 - 56.1) for the entire cohort. There was no significant difference in daily prednisolone dose between those treated with or without methotrexate at 6 months (8mg vs. 9mg, p = 0.56) and 12 months (3mg vs 3mg, p = 0.71) after diagnosis. Completion of glucocorticoid taper was achieved by 97 patients, of which subsequent relapse occurred in 42/97 (43%). Whereas there was no significant difference in relapse rate during the follow-up period between patients taking methotrexate at completion of glucocorticoid taper versus patients who were not (34.15% vs. 42.86%, χ<sup>2</sup> = 0.754, p = 0.3852), the time to relapse was significantly longer in the methotrexate group (median 14.0 vs 3.5 months, Wilcoxon test p = 0.04). In a Cox regression model, methotrexate use at completion of glucocorticoid taper was associated with a significantly reduced hazard ratio for relapse (HR = 0.42, 95% CI 0.20 to 0.87, p = 0.02). <h3>Conclusion:</h3> The influence of early treatment of GCA with methotrexate on long-term prognosis is unclear. We found that patients taking methotrexate at the completion of their initial glucocorticoid taper had a significantly longer time to relapse. Our method of retrospective case review has limitations and there are likely uncontrolled factors that influence methotrexate exposure. Despite this, our study demonstrating benefit in a large cohort suggests that further investigation into the role of early treatment with methotrexate is warranted.REFERENCES: NIL. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Joe Berry: None declared, Chung Mun Alice Lin: None declared, Jessica Weightman: None declared, John Casement: None declared, Ben Thompson: None declared, Jonathan Heaney: None declared, Kenneth Baker Consultancy fees from Modern Biosciences Ltd, Clinical service improvement grant from Pfizer, Alice Lorenzi: None declared, Gary Reynolds: None declared.