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Objective To evaluate the safety and durability of telitacicept treatment in patients with SLE by identifying the reasons for treatment discontinuation and potential risk factors for subsequent disease recurrence.Methods This retrospective study included 48 lupus patients who discontinued telitacicept and were under long-term follow-up at Peking Union Medical College Hospital. The underlying causes for treatment discontinuation and the subsequent disease outcomes were analysed.Results This study found that, among 48 patients who discontinued telitacicept, 18 (37.5%, 18/48) did so due to achieving a lupus low disease activity state (LLDAS), based on physician recommendations. Primary adverse discontinuation reasons included disease status changes necessitating treatment adjustment (16.7%, 8/48), decreased immunoglobulin G levels (6.2%, 3/48) and infection/fever (6.2%, 3/48). Among the 40 patients without changes to concomitant therapies post discontinuation, 30 (75%) maintained relatively stable Systemic Lupus Erythematosus Disease Activity Index scores, while 10 (25%) showed increased scores during the 12-month follow-up. Based on the characteristics at the time of telitacicept withdrawal, a high rate of central nervous system involvement was observed among patients who exhibited active disease after discontinuation. No significant fluctuations in serological markers were observed during the 12-month postdiscontinuation period (p>0.05 for all comparisons).Conclusions The majority of patients (37.5%) discontinued telitacicept due to achieving LLDAS. During the 12-month follow-up after drug withdrawal, 75% (30/40) of patients remained stable, whereas 25% had disease progression. A higher proportion of neurological involvement was observed in patients with disease changes after drug withdrawal, suggesting that patients with major organ involvement should be carefully evaluated following treatment cessation.