Background and objectives: Cyclophosphamide has been the mainstay of treatment of ANCA-associated vasculitis. However, cyclophosphamide has unfavorable side effects and alternatives are needed. Evidence suggests that mycophenolate mofetil can induce sustained remission in nonlife-threatening disease. The purpose of this study was to compare the efficacy and safety of mycophenolate mofetil versus cyclophosphamide for the induction treatment of nonlife-threatening relapses of proteinase 3-ANCA– and myeloperoxidase-ANCA–associated vasculitis. Design, setting, participants, & measurements: We conducted a multicenter randomized, controlled trial. Participants with a first or second relapse of ANCA-associated vasculitis were randomized to induction treatment with cyclophosphamide or mycophenolate mofetil both in combination with glucocorticoids. Maintenance therapy consisted of azathioprine in both arms. Primary outcome was remission at 6 months, and secondary outcomes included disease-free survival at 2 and 4 years. Results: Eighty-four participants were enrolled, of whom 41 received mycophenolate mofetil and 43 received cyclophosphamide. Eighty-nine percent of participants were proteinase 3-ANCA positive. At 6 months, 27 (66%) mycophenolate mofetil–treated participants versus 35 (81%) cyclophosphamide-treated participants were in remission (P=0.11). Disease-free survival rates at 2 and 4 years were 61% and 39% for cyclophosphamide, respectively, and 43% and 32% for mycophenolate mofetil, respectively (at 4 years, log rank test, P=0.17). Conclusions: We did not demonstrate mycophenolate mofetil to be similarly effective as cyclophosphamide in inducing remission of relapsed ANCA-associated vasculitis. However, mycophenolate mofetil might be an alternative to cyclophosphamide for the treatment of selected patients with nonlife-threatening relapses.

The programming of deep brain stimulation (DBS) parameters for tremor is laborious and empirical. Despite extensive efforts, the end-result is often suboptimal. One reason for this is the poorly understood relationship between the stimulation parameters’ voltage, pulse width, and frequency. In this study, we aim to improve DBS programming for essential tremor (ET) by exploring a new strategy. At first, the role of the individual DBS parameters in tremor control was characterized using a meta-analysis documenting all the available parameters and tremor outcomes. In our novel programming strategy, we applied 10 random combinations of stimulation parameters in eight ET-DBS patients with suboptimal tremor control. Tremor severity was assessed using accelerometers and immediate and sustained patient-reported outcomes (PRO’s), including the occurrence of side-effects. The meta-analysis showed no substantial relationship between individual DBS parameters and tremor suppression. Nevertheless, with our novel programming strategy, a significantly improved (accelerometer p = 0.02, PRO p = 0.02) and sustained (p = 0.01) tremor suppression compared to baseline was achieved. Less side-effects were encountered compared to baseline. Our pilot data show that with this novel approach, tremor control can be improved in ET patients with suboptimal tremor control on DBS. In addition, this approach proved to have a beneficial effect on stimulation-related complications.