Can we identify who gets benefit or harm from mycophenolate mofetil in systemic lupus erythematosus? A systematic review

Objectives: We aimed to summarize the evidence examining factors that predict differential response to mycophenolate mofetil (MMF) in systemic lupus erythematosus (SLE). Methods: Systematic searches of randomized clinical trials (RCT) to identify predictors of the effects of MMF (moderators), and cohort studies to explore prognostic factors associated with MMF outcomes (response, relapse, or adverse events) were performed. Two reviewers independently assessed the methodological quality of RCTs using the Cochrane Collaboration risk of bias tool and cohort studies using the QUality In Prognosis Studies tool. The quality of subgroup analysis, providing evidence for moderation, was evaluated. The Grading of Recommendations Assessment, Development, and Evaluation working group approach summarized the quality of evidence (QoE), considering the risk of bias, imprecision, inconsistency, indirectness, and publication bias. Results: From 26 studies (13 from 7 RCTs and 13 cohort studies) we found low QoE evidence for Black/Hispanic race/ethnicity predicting better renal responses to MMF in lupus nephritis (LN) from one RCT. There was low QoE evidence from cohort studies that a higher baseline creatinine and membranous features on renal biopsy were associated with poorer responses in LN. There was very low QoE for other moderators or prognostic factors associated with MMF treatment outcomes. QoE from RCTs was affected by exploratory or insufficient evidence from subgroup analysis and in both study types high risk of bias, indirectness and imprecision also affected QoE. Conclusions: In SLE, evidence for predictors of response to MMF is limited and none can be recommended for use in routine clinical practice. Specific studies of predictors measured at baseline and during treatment are needed with a priori hypotheses based on preliminary evidence to date and with sufficient power to determine which factors can be employed in clinical decision making. (C) 2017 The Authors. Published by Elsevier HS Journals, Inc.