Glucocorticoid dose at 26 weeks and subsequent relapse in anti-ARS antibody-positive antisynthetase syndrome under concomitant immunosuppressive therapy: a retrospective cohort study

Background Glucocorticoids (GCs) remain central to antisynthetase syndrome (ASSD) treatment, but relapse during tapering and GC-related adverse effects remain important concerns. Because GC-related morbidity may emerge early, minimizing GC exposure while maintaining disease control is important. Whether the GC dose during early tapering is associated with subsequent relapse remains unclear. We investigated whether a GC dose of ≤5 mg/day at approximately 6 months was associated with subsequent relapse in anti-aminoacyl-tRNA synthetase (ARS) antibody-positive ASSD receiving concomitant immunosuppressive therapy. Methods We retrospectively analyzed 45 patients with anti-ARS antibody-positive ASSD treated with systemic GCs and concomitant immunosuppressive therapy. We performed a week-26 landmark analysis, representing approximately 6 months after treatment initiation, among patients who remained relapse-free and under observation through the landmark. Subsequent relapse-free survival was compared between patients receiving GC ≤5 and >5 mg/day in prednisolone equivalents at the landmark. Results During overall follow-up, 26 of 45 patients (58%) experienced relapse, whereas only 4 (8.9%) relapsed before week 26. Among 41 patients who remained relapse-free and under observation through the landmark, 17 were receiving GC ≤5 mg/day and 24 were receiving >5 mg/day. During post-landmark follow-up, 22 patients experienced subsequent relapse. Patients receiving GC ≤5 mg/day at week 26 had higher subsequent relapse-free survival than those receiving >5 mg/day (log-rank p = 0.007). In multivariable analyses, GC ≤5 mg/day at week 26 was associated with a lower risk of subsequent relapse after adjustment for Raynaud phenomenon and initial GC dose (HR 0.27, 95% CI 0.08–0.86; p = 0.027) and after adjustment for Raynaud phenomenon and anti-Jo-1 positivity (HR 0.32, 95% CI 0.10–0.99; p = 0.047). Conclusion Among patients with anti-ARS antibody-positive ASSD receiving concomitant immunosuppressive therapy who remained relapse-free and under observation through the week-26 landmark, a GC dose ≤5 mg/day was associated with a lower risk of subsequent relapse. Although these findings should not be generalized to all patients or interpreted as establishing an optimal tapering target, the GC dose at this landmark may serve as a clinically useful marker of early disease control or treatment response. Prospective studies are warranted to validate its clinical significance.