OP0200 IMPACT OF TAPERING OF IMMUNOSUPPRESSIVE THERAPY OR GLUCOCORTICOIDS ON DAMAGE ACCRUAL AFTER ACHIEVING LOW DISEASE ACTIVITY OR REMISSION IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: DATA FROM A LARGE MULTINATIONAL COHORT
Authors: J. Cho, L. Shen, R. Kandane-Rathnayake, V. Golder, A. Hoi, W. Louthrenoo, Y.H. Chen, L. Hamijoyo, S.F. Luo, Y.J. Jan Wu, S. Navarra, L. Zamora, Z. Li, S. Sockalingam, Y. Katsumata, M. Harigai, Y. Hao, Z. Zhang, D. Basnayake, M. Chan, J. Kikuchi, T. Takeuchi, S.C. Bae, S. Oon, S. O ’neill, F. Goldblatt, K.P.L. Ng, N. Tugnet, S. Kumar, C. Tee, M. Tee, N. Ohkubo, Y. Tanaka, C.S. Lau, M. Nikpour, E. Morand, A. Lateef
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> While glucocorticoids and immunosuppressive therapies are key treatment approaches in SLE, these therapies may contribute to damage accrual. Given the long treatment horizon of SLE, tapering of glucocorticoids and immunosuppressive therapy in stable SLE is often considered, but whether this approach impacts damage accrual is unknown. <h3>Objectives:</h3> We aim to compare the time to new damage accrual among stable SLE patients whose immunosuppressive therapy and/or glucocorticoids were tapered after achieving target, versus those whose therapy was continued on the same doses. <h3>Methods:</h3> We followed SLE patients (ACR/SLICC criteria) from 13 Asia-pacific countries prospectively between 2013 to 2020. SLEDAI-2K and physician global assessment (PGA) were collected at each visit and disease-related damage was collected annually using SLICC Damage Index (SDI). We studied the first visit which the patient that had achieved target, including LLDAS, DORIS remission (clinical SLEDAI=0, PGA&lt; 0.5, prednisolone ≤5mg/day) or DORIS complete remission (SLEDAI-2K=0, PGA&lt; 0.5, prednisolone ≤5mg/day). All consecutive visits that continued to be in target were included together into a "period". We then determined whether tapering had occurred in each of these periods. Tapering was defined as any decrease in dose of glucocorticoids or immunosuppressive therapy (mycophenolate mofetil, cyclosporine, azathioprine, leflunomide, methotrexate or tacrolimus). Because we studied tapering only in stable disease, periods needed to have at least 2 consecutive visits at that target: the first visit at target and the subsequent visit with tapering commenced. We then used multivariable COX regression to analyse the time to first increase in SDI after attaining stable disease targets, comparing patients tapering versus those continuing therapy within the period. We fitted flares, glucocorticoid tapering and immunosuppressive therapy tapering as separate time-dependent covariates. Flares were defined using the SELENA-SLEDAI flare index (modified to exclude addition of non-steroidal anti-inflammatory drugs/ hydroxychloroquine or increase in prednisolone dose as a definition for mild flares and the introduction of new immunosuppressive therapy as a definition of severe flares). <h3>Results:</h3> Out of 4106 patients, 1634 were excluded as they had never achieved target for 2 consecutive visits. We analysed 2472 patients, of whom tapering occurred in 1228 (49.7%), whereas 1244 (50.3%) did not taper. 1019 (41.2%) subsequently flared and 438 (17.7%) accrued new damage. On multivariable COX regression, age and baseline SDI scores were associated with higher hazards of damage accrual (Table 1). Additionally, flares and glucocorticoid doses &gt;5mg/day were associated with higher hazards of damage accrual [HR (95% CI) 1.29 (1.04-1.61), p=0.023 and HR (95% CI) 1.90 (1.38-2.62), p&lt;0.001 respectively]. Glucocorticoid tapering was not significantly associated with reduction in damage accrual [HR (95% CI) 0.84 (0.66-1.07), p=0.166]. However, tapering of immunosuppressive therapy was associated with increased damage accrual [HR (95% CI) 1.57 (1.21-2.02), p&lt;0.001]. We checked the interaction terms between (i) tapering of immunosuppressive therapy and tapering of glucocorticoids and (ii) SDI score and tapering of immunosuppressive therapy. Both interaction terms were not statistically significant. <h3>Conclusion:</h3> After achieving treatment targets, the proportion of SLE patients who flare or accrue new damage remain substantial. Tapering of glucocorticoids did not impact time to damage accrual. However, tapering of immunosuppressive therapy was independently associated with increased damage accrual, possibly suggesting an under-evaluated protective effect of immunosuppressive therapies against incident damage even in stable disease. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Jiacai Cho: None declared, Liang Shen: None declared, Rangi Kandane-Rathnayake GSK and Novartis (Institutional research grants), Vera Golder: None declared, Alberta Hoi On advisory board for GSK and Abbvie, Astra Zeneca, GSK, Janssen, BMS, Merck Serono, Worawit Louthrenoo: None declared, Yi-Hsing Chen: None declared, Laniyati Hamijoyo: None declared, Shue-Fen Luo: None declared, Yeong-Jian Jan Wu: None declared, Sandra Navarra Astra Zeneca, Boehringer Ingelheim, GSK, Pfizer, Astra Zeneca, Biogen, Boehringer Ingelheim,, Biogen, Novartis, Idorsia, Aurinia, Leonid Zamora: None declared, Zhanguo Li: None declared, Sargunan Sockalingam: None declared, Yasuhiro Katsumata Asahi Kasai, Astealla, Astra Zeneca KK, Chugai Pharmaceutical, GSK, Janssen, Mitsubishi Tanabe Pharma, Pfizer Japan, Sanofi KK, Masayoshi Harigai Abbvie Japan GK, Ayumi Pharmaceutical, Boehringer Ingelheim Japan, BMS, Chugai Pharmaceuticals, Eisai Co Ltd, Eli Lilly Japan, GSK, Kissei Pharmaceutical, Pfizer Japan, Takeda Pharmaceutical, Teijin Pharma, Boehringer Ingelheim Japan, BMS, Abbive, Kissei Pharmaceutical, Teijin Pharma, Abbvie Japan, Asahi Kasei, Astellas Pharma, BMS, Ayumi Pharmaceutical, Chugai Pharmaceuticals, Daiichi-Sankyo Inc, Eisai Co Ltd, Kissei Pharmaceutical, Mitsubishi Tanabe Pharma, Nippon Kayaku Co Ltd, Shionogi Co Ltd, Taisho Pharmaceutical, Takeda Pharmaceutical, Teijin Pharma, Yanjie Hao: None declared, Zhuoli Zhang: None declared, Duminda Basnayake: None declared, Madelynn Chan: None declared, Jun Kikuchi: None declared, Tsutomu Takeuchi BMS, Eli Lilly Japanl, Sanofi KK, Mitsubishi-Tanabe Pharmaceuticals, Eli Lilly Japan, Astellas Pharma, Shionogi &amp; Co, Mitsubishi-Tanabe Pharmaceuticals, Sang-Cheol Bae: None declared, Shereen Oon: None declared, Sean O'Neill: None declared, Fiona Goldblatt: None declared, Kristine Pek Ling Ng: None declared, Nicola Tugnet: None declared, Sunil Kumar: None declared, Cherica Tee: None declared, Michael Tee: None declared, Naoaki Ohkubo: None declared, Yoshiya Tanaka Eli Lilly, Astra Zeneca, Abbvie, Chugai, Gilead, GSK, Eisai, Boehringer Ingelheim, Taisho, BMS, Pfizer, Taiho, Mitsubishi Tanabe, Eisai, Chugai, Taisho, Chak Sing Lau: None declared, Mandana Nikpour GSK, Janssen, Boehringer Ingelheim, Astra Zeneca, GSK, Janssen, Boehringer Ingelheim, Astra Zeneca, Janssen, Boehringer Ingelheim, Eric Morand Astra Zeneca, Merck, Gilead, Roche,, EMD Serono, Astra Zeneca, Biogen, BMS, Eli Lilly, Genentech, GSK, Janssen, Novartis, Galapagos, Abbvie, IgM, Abbvie, Amgen, Astra Zeneca, Biogen, BMS, Eli Lilly, EMD Serono, Genetech, GSK, Janssen, UCB (all institutional), Aisha Lateef: None declared.