Background Mycophenolate mofetil (MMF) has been shown to be a good therapeutic option in systemic lupus erythematosus (SLE), particularly lupus nephritis (LN). There is, however, evidence of variation in the response. Knowledge of predictors of response could aid patient selection for this therapy.

Objectives The aim of this systematic review was to summarize the evidence examining factors measured at baseline and during treatment associated with a response to MMF in SLE.

Methods We searched Medline, Embase, Web of Science and Cochrane Central Registers for Controlled Trials until November 2015 for relevant studies (Fig. 1). Studies included were randomized clinical trials (RCTs) with subgroup analysis and cohort studies involving SLE patients administered MMF with factors measured at baseline and during treatment that may predict treatment outcome. The overall quality of studies included was assessed independently by two reviewers. The quality of RCTs and cohort studies was assessed using the Cochrane Collaboration risk of bias tool and the QUality In Prognosis Studies (QUIPS) assessment tool, respectively. The quality of subgroup analysis was also evaluated. The Grading of Recommendations Assessment, Development, and Evaluation working group approach summarized the quality of evidence (QoE).

Results Although the methodological quality of RCTs was good for primary outcome, most were compromised by lack of power for subgroup analyses and lack of an explicit test of the interaction. Very-low to low QoE suggested a comparable efficacy and safety of MMF among White, Black, Hispanic and Asian patients. Very- low to low QoE indicated that adolescent patients had neither a better LN response at 24 weeks or treatment failure rates at 36 months compared with adults. Patients with membranous LN or poor renal function (<30 mL/min/1.73 m²) may have a renal improvement at 6 months with MMF according to low QoE. Moderate QoE suggested patients with extrarenal manifestations may show control of disease activity and significant reduction in corticosteroid dose at 6 and 12 months. One moderate QoE study showed that LN patients with a mycophenolic acid area under the curve (MPA AUC) ≥30 mg/h/L-1 may have a better renal response at 1 year. Several studies of varying quality indicated a better response to therapy at 6 and 12 months in LN patients with an early reduction in proteinuria or early normalization of C3 and C4. However, an early reduction in anti–double-stranded DNA was not predictive of the renal response at 6 months.

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Conclusions In SLE patients, evidence for predictors of outcomes with MMF is limited. The results of this review should be treated with caution due to the heterogeneity of studies, and the risks of bias identified. Future studies of predictors measured at baseline and during treatment should be designed with “a priori” hypotheses and adequate statistical power.

1. Pincus T, et al. Methodological criteria for the assessment of moderators in systematic reviews of randomised controlled trials: a consensus study. BMC Med Res Methodol. 2011;11:14

2. Huguet A, et al. Judging the quality of evidence in reviews of prognostic factors research: adapting the GRADE framework. Syst Rev. 2013;2:71

Acknowledgement We would like to thank Danielle Van Der Windt and Mary Ingram; Supported by CONACYT (250783)

Disclosure of Interest None declared