Higher mycophenolic acid levels correlate with 12-fold higher odds of clinical response in SLEHigher Mycophenolic Acid Levels Linked to Better Lupus Response

OBJECTIVE: Clinical response to mycophenolic acid (MPA) is highly heterogeneous; thus, therapeutic drug level monitoring (TDM) may help improve treatment efficacy. This systematic review and meta-analysis examined therapeutic ranges for MPA levels associated with better outcomes and safety in patients with systemic lupus erythematosus (SLE), particularly those with extrarenal manifestations. METHODS: We performed a comprehensive search of studies evaluating associations between MPA levels and clinical SLE response. Using forest plots, we calculated pooled odds of clinical response by MPA levels and measured the weighted mean differences across outcomes. Analysis was performed in all patients with SLE and separately in patients with extrarenal manifestations. RESULTS: Among 459 reviewed abstracts, 24 met inclusion. Summarized evidence supported that clinical response was observed at MPA area under the curve at 0 to 12 hours (AUC) ≥30 to 35 mg hr/L or trough concentration (C) ≥1.5 mg/L. At these thresholds, therapeutic MPA levels were associated with 12-fold higher odds (95% confidence interval [CI] 5.44-27.35; P < 0.0001; I = 41%) of overall clinical SLE response and 15-fold higher odds (95% CI 4.74-46.89; P < 0.0001; I = 61%) of response in patients with extrarenal manifestations. Additionally, MPA levels were 32 units higher (95% CIs 17.35-45.67) in overall responders with SLE and 39 units (95% CI 15.05-62.53) higher in patients with extrarenal manifestations. Although pooled analysis did not show a significant increase in adverse events, individual studies suggested safety concerns at MPA AUC >60 mg hr/L or C ≥2.5 to 3 mg/L CONCLUSION: This study highlights the clinical utility of TDM to guide MPA dosing to balance efficacy versus safety in all patients with SLE, including those with extrarenal manifestations.