SAT0186 DEVELOPING PREDICTORS OF GLOBAL BILAG TREATMENT RESPONSE IN PATIENTS WITH LUPUS NEPHRITIS: MORE LESSONS FROM THE ASPREVA LUPUS MANAGEMENT STUDY GROUP (ALMS) DATA. (2nd June 2020) - Mcdonald, S.
Abstract : Background: Lupus Nephritis (LN) occurs in up to 60% of patients with SLE and is often associated with other organ involvement, morbidity and mortality. Treatment response and clinical improvement rates are limited with conventional therapy. Little is known about clinical predictors of response in SLE overall or in LN. The ALMS induction trial compared mycophenolate mofetil (MMF) to IV cyclophosphamide (CYC) as induction for LN. MMF was deemed non-superior. The ALMS maintenance trial randomised responders to induction treatment at 6 months to MMF or Azathioprine, with MMF superior during follow-up. Objectives: To identify predictors of overall clinical response at 6 and 12 months, in a cohort of SLE patients with LN. Methods: Using the ALMS trial cohort, we analysed predictors of response in all the patients as a single cohort. 'Classic' BILAG scores were used to assess organ responses over time. Endpoints analysed were: 1) Improvement: defined as reduction in BILAG score to ≤ one BILAG B and no new BILAG organ domains involved, no increase in steroids from baseline and no increase in SLEDAI from baseline. 2) Major Clinical Response (MCR): defined as reduction in BILAG score to BILAG C in all domains, a reduction in steroid dose to ≤ 7.5mg daily and a SLEDAI score ≤ 4. Potential predictors examined included baseline demographics, medication, disease activity (BILAG, SLEDAI), SLICC/ACR damage index (SDI) and serology. Univariate logistic regressions were used to provide odds ratios of predictors. Multivariate logistic regressions with LASSO and cross-validation in randomly split samples were utilised to build prediction models. Predictors were ranked by the percentage of times they were selected by LASSO. Results: 370 patients enrolled in the ALMS induction trial. 227 patients were randomised at 6 months to maintenance. 313(84.59%) patients were female. 147(39.72%) patients were Caucasian. The mean age was 31.9 years. 236(63.78%) patients had a disease duration of LN of < 1 year. Baseline mean(± SD) SLEDAI score was 15.28 (±6.78) and mean(± SD) numerical BILAG score was 19.61(±7.67). Improvement at 6 months was attained by 180 (48.65%). Predictors included older age (OR=1.03 [95% CI: 1.01, 1.05] per year) and normal haemoglobin (OR=1.90 [95% CI: 1.19, 3.05] vs low hb). Activity (BILAG A or B) in haematological and mucocutaneous domains predicted less improvement (OR [95% CI] = 0.59 [95% CI: 0.38, 0.94] and 0.50 [95% CI: 0.31, 0.82] respectively). Baseline damage (SDI >1) negatively predicted improvement (OR 0.54 [95% CI: 0.31, 0.92]). Improvement at 12 months was acheived by 139 (37.57%). Low IgG predicted improvement (OR 4.66 [95% CI: 1.34, 16.23]. Black US patients were less likely to improve (OR 0.29 [95% CI: 0.06, 0.90] vs Asian patients). MCR was achieved by 14(3.79%) and 40(10.81%) at 6 and 12 months. We found regional and racial differences in 12-month MCR responses (Figure 1 ). Baseline normal C4 predicted a decreased likelihood of MCR (OR 0.37 [95% CI: 0.17, 0.64] vs normal C4). Results of multivariate logistic regression with LASSO were consistent with the univariate analyses. Conclusion: A number of factors were related to improvement and MCR in conventionally treated LN patients. Those with damage and active non-renal disease were less likely to improve at 6 months. Baseline low C4 increased MCR likelihood at 12 months. These factors may help stratify patients based on likelihood of response and help select patients who may need alternative treatment strategies. Disclosure of Interests: Stephen McDonald: None declared, Sean Yiu: None declared, Li Su: None declared, Caroline Gordon Grant/research support from: UCB, Consultant of: UCB, BMS, EMD Serono, Speakers bureau: UCB, Neil Solomons Shareholder of: Aurinia Pharmaceuticals, Inc. stock, Employee of: Employed currently by Aurinia Pharmaceuticals Previous employee of Aspreva Pharmaceuticals, Ian N. Bruce Grant/research support from: Genzyme Sanofi, GSK, and UCB, Consultant of: Eli Lilly, AstraZeneca, UCB, Iltoo, and Merck Serono, Speakers bureau: UCB