Mycophenolate Mofetil for First-Line Treatment of Immune Thrombocytopenia

BACKGROUND Immune thrombocytopenia (ITP) is a rare autoimmune thrombocytopenia with associated bleeding risk and fatigue. Recommended first line ITP treatment is with high dose glucocorticoids but side effects, heterogeneous responses and high relapse rates are significant problems. METHODS In this multicenter, UK based, open label, randomized controlled trial, we randomly assigned adult patients with ITP requiring first line treatment to glucocorticoid alone (standard care) versus combined glucocorticoid and mycophenolate (1:1 ratio). The primary efficacy outcome was time from randomization to treatment failure, defined as platelets <30x109/L with initiation of 2nd line treatment. Secondary outcomes included response rates, side effects, bleeding events, patient reported outcome measures and serious adverse events. RESULTS One hundred and twenty ITP patients were recruited and randomized (52.4% male, mean age 54 years, range 17-87, mean platelets = 7x109/L), and followed up for up to 2 years. Fewer treatment failures were seen in patients randomized to mycophenolate (22%, n=13/59 vs 44%, n=27/61, aHR=0.41 [0.21, 0.80], p=0.0064), with higher response rates (91.5% achieving platelets>100x109/L vs 63.9%, p<0.001). We found no evidence of difference between groups in bleeding events, rescue treatments or treatment side effects including infection. However, quality of life measures of physical function and fatigue were worse in the mycophenolate group. CONCLUSIONS Addition of mycophenolate to glucocorticoid for first line ITP treatment results in higher response rates and reduces the risk of refractory or relapsed ITP but with somewhat decreased quality of life. (Funded by the NIHR, ClinicalTrials.gov number: NCT03156452).