Search

Objectives: To assess the risk of flare and damage accrual after tapering glucocorticoids (GCs) in modified serologically active clinically quiescent (mSACQ) patients with systemic lupus erythematosus (SLE)., Methods: Data from a 12-country longitudinal SLE cohort, collected prospectively between 2013 and 2020, were analysed. SLE patients with mSACQ defined as the state with serological activity (increased anti-dsDNA and/or hypocomplementemia) but without clinical activity, treated with ≤7.5 mg/day of prednisolone-equivalent GCs and not-considering duration, were studied. The risk of subsequent flare or damage accrual per 1 mg decrease of prednisolone was assessed using Cox proportional hazard models while adjusting for confounders. Observation periods were 2 years and censored if each event occurred., Results: Data from 1850 mSACQ patients were analysed: 742, 271 and 180 patients experienced overall flare, severe flare and damage accrual, respectively. Tapering GCs by 1 mg/day of prednisolone was not associated with increased risk of overall or severe flare: adjusted HRs 1.02 (95% CI, 0.99 to 1.05) and 0.98 (95% CI, 0.96 to 1.004), respectively. Antimalarial use was associated with decreased flare risk. Tapering GCs was associated with decreased risk of damage accrual (adjusted HR 0.96, 95% CI, 0.93 to 0.99) in the patients whose initial prednisolone dosages were >5 mg/day., Conclusions: In mSACQ patients, tapering GCs was not associated with increased flare risk. Antimalarial use was associated with decreased flare risk. Tapering GCs protected mSACQ patients treated with >5 mg/day of prednisolone against damage accrual. These findings suggest that cautious GC tapering is feasible and can reduce GC use in mSACQ patients., Competing Interests: Competing interests: YK received honoraria from Asahi Kasei Pharma, Astellas Pharma, AstraZeneca K.K., Chugai Pharmaceutical, GlaxoSmithKline KK, Janssen Pharmaceutical KK, Mitsubishi Tanabe Pharma Corporation, Pfizer Japan, Sanofi KK. EI received honoraria from Bristol-Myers Squibb KK, Eisai and consulting fees from Nippontect Systems. MH received honoraria from AbbVie GK, Ayumi Pharmaceutical, Bristol-Myers Squibb K.K., Chugai Pharmaceutical, Eisai, Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical, Nippon Boehringer Ingelheim, Pfizer Japan, Takeda Pharmaceutical, Teijin Pharma, consulting fees from AbbVie GK, Bristol-Myers Squibb K.K., Kissei Pharmaceutical, Nippon Boehringer Ingelheim, Teijin Pharma, grant/research support from AbbVie GK, Asahi Kasei Pharma, Astellas Pharma, Ayumi Pharmaceutical, Bristol-Myers Squibb K.K., Chugai Pharmaceutical, Daiichi-Sankyo, Eisai, Kissei Pharmaceutical, Mitsubishi Tanabe Pharma, Nippon Kayaku, Sekisui Medical, Shionogi, Taisho Pharmaceutical, Takeda Pharmaceutical, Teijin Pharma. AH received honoraria from UCB, Janssen, Sandoz, Eli Lilly, consulting fees from AbbVie, GSK and grant/research support from AstraZeneca, GSK, Bristol Myers Squibb, Janssen, Merck Serono. CSL received honoraria from AstraZeneca UK and consulting fee from AstraZeneca Pharmaceuticals LP. ZL received honoraria from Pfizer, Roche, Janssen, Abbott, AbbVie, Bristol Myers Squibb, MSD, Celgene, Eli Lilly, GSK, Novartis, UCB Pharma and consulting fees from Pfizer, Roche, Janssen, Abbott, AbbVie, Bristol Myers Squibb, MSD, Celgene, Eli Lilly, GSK, Novartis, UCB Pharma. SS received consulting fees from Pfizer, AstraZeneca, ZP Therapeutics and grant/research support from Pfizer, AstraZeneca, ZP Therapeutics. SVN received consulting fees from Biogen, Boehringer Ingelheim, AstraZeneca, grant/research support from Jannsen, Novartis, Pfizer, GSK and support for attending meetings from Biogen. SOon received royalty from Venetoclax. KN is on the advisory board for AbbVie. TT received honoraria from AbbVie GK, Chugai Pharmaceutical, Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma, consulting fees from AbbVie GK, Chugai Pharmaceutical, Mitsubishi Tanabe Pharma and grant/research support from AbbVie GK, Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma. YT received honoraria from AbbVie GK, Asahi Kasei Pharma, AstraZeneca K.K., Bristol-Myers Squibb K.K., Chugai Pharmaceutical, Eisai, Eli Lilly Japan K.K., Gilead Sciences, GlaxoSmithKline K.K., Nippon Boehringer Ingelheim, Pfizer Japan, Taiho Pharmaceutical, Taisho Pharmaceutical and grant/research support from Asahi Kasei Pharma, Chugai Pharmaceutical, Eisai, Mitsubishi Tanabe Pharma, Taisho Pharmaceutical. MN received honoraria from Actelion, GSK, Janssen, Pfizer, UCB, consulting fees from Boehringer Ingelheim, Certa Therapeutics, Eli Lilly, GSK, Janssen, Pfizer, UCB and grant/research support from Actelion, AstraZeneca, Bristol Myers Squibb, GSK, Janssen, UCB. EFM received honoraria from AstraZeneca, EMD Serono, Gilead, consulting fees from AstraZeneca, Bristol Myers Squibb, Biogen, Eli Lilly, EMD Serono, Novartis and grant/research support from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Biogen, Eli Lilly, EMD Serono, Genentech, GSK, Janssen, UCB. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Background: This study examines the association of standard-of-care systemic lupus erythematosus (SLE) medications with key outcomes such as low disease activity attainment, flares, damage accrual, and steroid-sparing, for which there is current paucity of data., Methods: The Asia Pacific Lupus Collaboration (APLC) prospectively collects data across numerous sites regarding demographic and disease characteristics, medication use, and lupus outcomes. Using propensity score methods and panel logistic regression models, we determined the association between lupus medications and outcomes., Results: Among 1707 patients followed over 12,689 visits for a median of 2.19 years, 1332 (78.03%) patients achieved the Lupus Low Disease Activity State (LLDAS), 976 (57.18%) experienced flares, and on most visits patients were taking an anti-malarial (69.86%) or immunosuppressive drug (76.37%). Prednisolone, hydroxychloroquine and azathioprine were utilised with similar frequency across all organ domains; methotrexate for musculoskeletal activity. There were differences in medication utilisation between countries, with hydroxychloroquine less frequently, and calcineurin inhibitors more frequently, used in Japan. More patients taking leflunomide, methotrexate, chloroquine/hydroxychloroquine, azathioprine, and mycophenolate mofetil/mycophenolic acid were taking ≤ 7.5 mg/day of prednisolone (compared to > 7.5 mg/day) suggesting a steroid-sparing effect. Patients taking tacrolimus were more likely (Odds Ratio [95% Confidence Interval] 13.58 [2.23-82.78], p = 0.005) to attain LLDAS. Patients taking azathioprine (OR 0.67 [0.53-0.86], p = 0.001) and methotrexate (OR 0.68 [0.47-0.98], p = 0.038) were less likely to attain LLDAS. Patients taking mycophenolate mofetil were less likely to experience a flare (OR 0.79 [0.64-0.97], p = 0.025). None of the drugs was associated with a reduction in damage accrual., Conclusions: This study suggests a steroid-sparing benefit for most commonly used standard of care immunosuppressants used in SLE treatment, some of which were associated with an increased likelihood of attaining LLDAS, or reduced incidence of flares. It also highlights the unmet need for effective treatments in lupus., (© 2024. The Author(s).)

Background: Treat-to-target goals for patients with systemic lupus erythematosus (SLE) have been validated to protect against organ damage and to improve quality of life. We aimed to investigate the association between lupus low disease activity state (LLDAS) and remission and risk of mortality in patients with SLE. We hypothesised that LLDAS has a protective association with mortality risk., Methods: In this prospective, multinational, longitudinal cohort study, we used data from patients with SLE in the Asia Pacific Lupus Collaboration cohort collected between May 1, 2013, and Dec 31, 2020. Eligible patients were adults (aged ≥18 years) who met either the 1997 American College of Rheumatology modified classification criteria for SLE or the 2012 Systemic Lupus International Collaborating Clinics classification criteria. The primary outcome was all-cause mortality, and LLDAS, remission, and variations of remission with lower glucocorticoid thresholds were the primary exposure variables. Survival analyses were used to examine longitudinal associations between these endpoints and risk of mortality. This study is registered with ClinicalTrials.gov, NCT03138941., Findings: Among a total of 4106 patients in the cohort, 3811 (92·8%) patients were included in the final analysis (median follow-up 2·8 years [IQR 1·0-5·3]; 3509 [92·1%] women and 302 [7·9%] men), of whom 80 died during the observation period (crude mortality rate 6·4 deaths per 1000 person-years). LLDAS was attained at least once in 43 (53·8%) of 80 participants who died and in 3035 (81·3%) of 3731 participants who were alive at the end of the study (p<0·0001); 22 (27·5%) participants who died versus 1966 (52·7%) who were alive at the end of the study attained LLDAS for at least 50% of observed time (p<0·0001). Remission was attained by 32 (40·0%) of 80 who died and in 2403 (64·4%) of 3731 participants who were alive at the end of the study (p<0·0001); 14 (17·5%) participants who died versus 1389 (37·2%) who were alive at the end of the study attained remission for at least 50% of observed time (p<0·0001). LLDAS for at least 50% of observed time (adjusted hazard ratio 0·51 [95% CI 0·31-0·85]; p=0·010) and remission for at least 50% of observed time (0·52 [0·29-0·93]; p=0·027) were associated with reduced risk of mortality. Modifying the remission glucocorticoid threshold (<5·0 mg/day prednisolone) was more protective against mortality than current remission definitions (0·31 [0·12-0·77]; p=0·012), and glucocorticoid-free remission was the most protective (0·13 [0·02-0·96]; p=0·046)., Interpretation: LLDAS significantly reduced the risk of mortality in patients with SLE. Remission did not further reduce the risk of mortality compared with LLDAS, unless lower glucocorticoid thresholds were used., Funding: The Asia-Pacific Lupus Collaboration received funding from Janssen, Bristol Myers Squibb, Eli Lilly, and UCB for this study., Competing Interests: Declaration of interests SVN has received consulting fees from Biogen and Boehringer Ingelheim; lecture or speaker fees from Janssen, Novartis, Pfizer, and GlaxoSmithKline; conference registration fees from Pfizer; and payment from Biogen for participation on an advisory board. YK has received payment or honouria from GlaxoSmithKline, AstraZeneca, Sanofi, Pfizer Japan, Janssen Pharmaceutical, Chugai Pharmaceutical, Asahi Kasei Pharma, Astellas Pharma, and Mitsubishi Tanabe Pharma Corporation. MH has received payment for post-marketing surveillance from GlaxoSmithKline; research grants from Novartis Pharma; and honoraria for lectures for GlaxoSmithKline, AstraZeneca, and Astellas Pharma. TT has received grants from Astellas, Asahi Kasei, Chugai, and Mitsubishi Tanabe; and consulting fees from Astellas and Chugai. KPLN has received advisory board participation fees from AbbVie. DYY is an employee of Janssen. CSK is a stock owner and an employee of Janssen. MN has received research grants from Janssen; and consulting fees from AstraZeneca, Boehringer & Ingelheim, GlaxoSmithKline, and Janssen. EFM has received consulting fees from AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, Genetech, Janssen, Novartis, Servier, and EMD Serono. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)