OP0206 TAPERING AND DISCONTINUATION OF IMMUNOSUPPRESSIVES IN PATIENTS WITH LUPUS NEPHRITIS
Authors: A. Panagiotopoulos, E. Kapsia, I. Michelakis, J. Boletis, S. Marinaki, P. P. Sfikakis, M. G. Tektonidou
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The optimal duration of immunosuppression (IS) treatment in lupus nephritis (LN) remains uncertain. EULAR's 2023 update and KDIGO 2024 guidelines suggest a minimum of 3 years of continued treatment after renal response, including gradual IS tapering before discontinuation (D/C). <h3>Objectives:</h3> We aimed to evaluate the percentage of successful IS D/C and its determinants in a LN inception cohort, and the predictors of post-D/C renal flares. We also examined the frequency and predictors of flares during IS tapering, and long-term renal outcomes by the end of follow-up (EFU) among those achieving or not IS D/C. <h3>Methods:</h3> We collected clinical, laboratory and histological data from biopsy-proven LN patients who achieved renal response (partial or complete [CR]). Tapering was defined as any IS dose reduction due to stable disease, following renal response. Successful IS D/C was defined as D/C achievement, regardless of any flares before or after D/C. Multivariate regression analyses were applied to evaluate factors influencing the time to IS D/C and potential clinical, laboratory and histological predictors of flares during IS tapering and post-IS D/C. The association between disease modification (DM) [1, 2] and IS D/C was also investigated. <h3>Results:</h3> A total of 137 patients [81.7% females, median age: 32 years, median follow-up time: 124 (IQR: 89) months] were included in the study. IS tapering was attempted in 108 (78.8%) patients, in a median time of 32.5 (IQR: 41) months post-renal response. Among them, 11 (10.1%) patients flared during tapering (7/11 achieved D/C after re-treatment), 65 (60.3%) achieved D/C without flare, and 32 (29.6%) remain on IS tapering (18/32 due to LN-related causes, 11/32 due to extra-renal activity and 3/32 due to non-compliance). Achieving CR within 12 months post-induction treatment (OR=0.29), SLEDAI-2K at 12 months (OR= 1.17 per point increase), SLEDAI-2K (OR= 1.58 per point increase) and hydroxychloroquine (HCQ) use (OR= 0.23) at IS tapering initiation, significantly reduced the risk of flares during the IS tapering (all p&lt;0.05). Seventy-two (52.5%) patients achieved IS D/C in a median 56-month (IQR: 45) interval, post-renal response. Low C3 at baseline was associated with failure to achieve IS D/C (OR: 3.69, p=0.03). DM was significantly associated with IS D/C achievement; 67.2% of patients with successful IS D/C were DM achievers versus 43.2% of those without (p=0.01). Regarding the time to IS D/C, membranous LN (versus proliferative LN) was associated with a 20-month shorter interval between renal response and IS D/C (β=-20, p=0.01), independently of the effect of age, induction treatment and baseline serology (low C3). After IS D/C, flares were observed in 13/72 (18%) patients. Persistent HCQ use (≥2/3 of follow-up period) significantly reduced the risk of post-IS D/C flares (OR: 0.26, p=0.04). No other parameters at baseline or at month-12 were associated with post-IS D/C flares. At the EFU, there was no significant difference in unfavorable outcomes (eGFR decline ≥30% compared to baseline, progression to CKD, ESRD or death) between patients who achieved or not IS D/C. Flare at tapering was associated with 7-fold higher risk for unfavorable outcomes (OR: 7.75, p=0.002). <h3>Conclusion:</h3> For a safe IS tapering strategy, it is important to ensure CR achievement and low SLEDAI-2K at 12 months, along with low SLEDAI-2K and HCQ use at the time of tapering initiation. Baseline C3 and DM achievement correlate with successful IS D/C. Persistent HCQ use offers protection against post-IS D/C flares, while flares during IS tapering increase the risk for unfavorable long-term outcomes. In membranous LN versus proliferative LN, earlier IS tapering and D/C might be considered. <h3>REFERENCES:</h3> [1] van Vollenhoven R, Askanase AD, Bomback AS, et al (2022) Conceptual framework for defining disease modification in systemic lupus erythematosus: a call for formal criteria. Lupus Sci Med 9:e000634. [2] Panagiotopoulos A, Kapsia E, Michelakis I, Boletis J, Marinaki S, Sfikakis PP, Tektonidou MG (2023) Disease modification achievement in patients with lupus nephritis in a real-life setting: mission impossible? RMD Open 9:e003158. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>