POS0539 PREDICTORS AND IMPACT OF DRUG SURVIVAL OF ANTI-MALARIAL AND IMMUNOSUPPRESSIVE THERAPIES IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: DATA FROM A LARGE MULTINATIONAL COHORT
Authors: T.M. Shuen, M. S. Tang, X. Hu, Z. Lin, 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. Oon, S. C. Bae, S. O’neill, F. Goldblatt, K. P. L. Ng, N. Tugnet, S. Kumar, M. Tee, C. Tee, N. Ohkubo, Y. Tanaka, C. S. Lau, M. Nikpour, E. Morand, A. Lateef, J. Cho
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> In patients with systemic lupus erythematosus (SLE), treatment options are limited. Anti-malarials and immunosuppressive therapies are widely used even though toxicity and intolerance may limit treatment persistence, or 'survival'. The predictors and impact of drug survival of anti-malarials and immunosuppressive therapies in SLE are unknown. <h3>Objectives:</h3> We sought to identify patient and disease-related factors that are associated with drug survival of anti-malarial (AM) and immunosuppressant agents (IS) in stable SLE. We also analysed the impact of drug survival on disease flares. <h3>Methods:</h3> Patients aged 18 years or older with SLE based on the ACR/SLICC criteria from 13 Asia-Pacific countries were followed prospectively from 2013 to 2020. Laboratory variables, Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), AM and IS doses were recorded at each visit. We identified periods of ≥1 visit with disease at target state (defined as attainment of lupus low disease activity state (LLDAS), DORIS remission or DORIS complete remission). Drug survival was defined as the period of use starting from the first visit with inactive disease at which the drug was prescribed until it was discontinued, regardless of disease activity. Therefore, each patient could contribute more than one IS or AM drug survival period. The IS agents analysed included azathioprine, mycophenolate mofetil, mycophenolic acid, methotrexate, leflunomide, cyclosporine, tacrolimus and combinations of the above, but excluded cyclophosphamide and biological therapies. We used multivariable Cox regression to determine the predictors of AM and IS drug survival. We then analysed the impact of AM and IS drug survival on disease flares defined by SELENA-SLEDAI Flare Index (SFI), modified to exclude addition of non-steroidal anti-inflammatory drugs, hydroxychloroquine (HCQ) or increase in prednisolone dose as a definition for mild flares and the introduction of new immunosuppressive therapy as a definition of severe flares. In all multivariable models, drug survival periods with missing data were excluded. <h3>Results:</h3> We studied 4106 patients. The median (IQR) age was 39 (30-50) years. At baseline, the median (IQR) SLEDAI-2K score was 4.0 (1.0-6.0) and median (IQR) disease duration was 2.47 (0.97-5.05) years. 2980 (72.6%) were on AM and 2240 (54.6%) were on immunosuppressive therapy, of which azathioprine (22.4%) and mycophenolate mofetil (17.8%) were the most commonly used agents. The median drug survival for AM and any IS therapy were 378 (0-1267) and 332 (0-992) days respectively. Positive antiphospholipid antibody was associated with shorter AM drug survival, whereas patients with higher prior cumulative doses of AM had longer AM drug survival. On multivariable Cox regression analysis, the highest tertile of AM survival was associated with reduced rates of flare compared to the lowest tertile [HR (95% CI) 0.63 (0.50-0.80), p&lt;0.001, Table 1]. Patients with tertiary education had longer IS drug survival [HR (95% CI) 0.78 (0.63-0.96), p=0.021], whereas mycophenolate mofetil had shorter drug survival compared to azathioprine [HR (95% CI) 1.44 (1.18-1.76), p&lt;0.001]. Patients who previously received higher cumulative exposure to IS had longer IS survival [HR (95% CI) 0.996 (0.995-0.996), p&lt;0.001]. The highest tertile of IS survival from the inactive disease visit was not associated with flares as compared to the lowest tertile [HR (95% CI) 0.92 (0.57-1.49), p=0.734, Table 2]. <h3>Conclusion:</h3> Among patients with SLE who achieved treatment targets, increased drug survival of anti-malarials, but not immunosuppressive therapy, was associated with reduced flares. Our results reemphasize the importance of anti-malarial therapy in SLE, including in patients who have achieved target states. <h3>REFERENCES:</h3> <b>NIL.</b> <b>Table 1.</b> Multivariable Cox Regression of Anti-malarial Drug Survival for the Outcome of Flares (N=2043) <b>Table 2.</b> Multivariable Cox Regression of Immunosuppressive Therapy Drug Survival for the Outcome of Flares (N=1591) <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Jiacai Cho: None declared, May Shuen Tang: None declared, Xiaoyu Hu: None declared, Zhenhua Lin: None declared, Rangi Kandane-Rathnayake GSK, Novartis (all institutional research grants), Vera Golder: None declared, Alberta Hoi On the advisory board for AbbVie and GSK, AstraZeneca, GSK, BMS, Janssen, and 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 AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Pfizer, AstraZeneca, Biogen, Boehringer Ingelheim, Aurinia, Biogen, Idorsia, Novartis, Leonid Zamora: None declared, Zhanguo Li: None declared, Sargunan Sockalingam: None declared, Yasuhiro Katsumata Asahi Kasei Pharma, Astellas Pharma Inc., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., GlaxoSmithKline K.K., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, Pfizer Japan Inc., Sanofi K.K., Masayoshi Harigai MH has received speaker's fee from AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., AbbVie, Boehringer-Ingelheim, Bristol Mysers Squibb Co., Kissei Pharmaceutical Co.,Ltd. and Teijin Pharma., AbbVie Japan GK, Asahi Kasei Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Daiichi-Sankyo, Inc., Eisai Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., Sekiui Medical, Shionogi &amp; Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Yanjie Hao: None declared, Zhuoli Zhang: None declared, Duminda Basnayake: None declared, Madelynn Chan: None declared, Jun Kikuchi: None declared, Tsutomu Takeuchi Bristol-Myers Squibb, Eli Lilly Japan, Mitsubishi-Tanabe Pharma Corp., Sanofi K.K., Eli Lilly Japan, Astellas Pharma, Inc., Mitsubishi-Tanabe Pharma Corp., Shionogi &amp; Co., Ltd., Shereen Oon: None declared, Sang-Cheol Bae: 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, Michael Tee: None declared, Cherica Tee: None declared, Naoaki Ohkubo: None declared, Yoshiya Tanaka Eli Lilly, AstraZeneca, AbbVie, Gilead, Chugai, Boehringer Ingelheim, GlaxoSmithKline, Eisai, Taisho, Bristol-Myers, Pfizer, Taiho, Mitsubishi-Tanabe, Eisai, Chugai, Taisho, Chak Sing Lau: None declared, Mandana Nikpour AstraZeneca, Boehringer Ingelheim, GSK, Janssen, AstraZeneca, Boehringer Ingelheim, GSK, Janssen, Boehringer Ingelheim, Janssen, Eric Morand AstraZeneca, Merck, Gilead, Roche, EMD Serono, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, Genentech, GlaxoSmithKline, Janssen, Novartis, AbbVie, Galapagos, IgM, AbbVie, Amgen, AstraZeneca, Biogen, BMS, Eli Lilly, EMD Serono, Genetech, GSK, Janssen, UCB (all institutional), Aisha Lateef: None declared.