Additional data are therefore needed to inform clinical practice on how best to use RTX in this patient population, so that definitive randomized trials can be planned
Additional data are therefore needed to inform clinical practice on how best to use RTX in this patient population, so that definitive randomized trials can be planned. an additional dose 12?months later, in order to examine the benefit of re\treatment. Biochemical and clinical parameters were monitored over an extended follow\up period of up to 43?months. Results Median steroid\free survival after RTX was 25?months (range 4C34). Mean relapse frequency decreased from 2.60??0.28 to 0.4??0.19 (as an option for the treatment of this challenging group of patients 14. In adults, increasing evidence suggests that RTX is capable of reducing relapse frequency and concomitant immunosuppression in 65C85% of patients 15, 16, 17, 18, 19. However, its use has been very varied: different dosage regimes, in mixed populations (steroid dependent and/or steroid resistant) and for differing indications (induction or maintenance of remission). As a result, it is still not clear whether RTX is best used to induce remission or to maintain it, what the optimal dose should be and whether repeated doses improve response rates and prolong remission. Additional data are therefore needed to inform clinical practice Rabbit Polyclonal to AKAP4 on how best to use RTX in this patient population, so that definitive randomized trials can be planned. The aim of this study was to evaluate the efficacy and safety of a standard dose of RTX in maintaining remission, reducing relapse frequency and withdrawing immunosuppression, in a group of adult patients with frequently relapsing and steroid\dependent MCD. Methods Patient population and follow up Fifteen adult patients (18C46?years old), nine male and six female, fulfilling the following criteria were enrolled in this study: Biopsy\proven MCD Frequently relapsing or steroid\dependent disease. Frequent relapse was defined as two or more relapses within 1?year. Steroid dependence was defined as relapse upon tapering steroid therapy or within 4?weeks of discontinuing steroids and need for long\term maintenance steroids Maintenance immunosuppression Tetracaine with a CNI (cyclosporine A or tacrolimus) Remission of NS defined as proteinuria 3.5?g/day No previous RTX treatment We enrolled patients consecutively from December 2011 until July 2014 when funding for RTX, for this indication, was restricted in the UK. Clinical and laboratory data were obtained at baseline, 6, 12, 18?months and every 6?months after that until 36?months. Laboratory data included serum albumin levels, urine protein/creatinine ratio, immunoglobulin levels and CD19 cell counts. Follow\up period for the group as a whole was 12C43?months (median 20) and concluded in July 2015. The study conformed to the ethical standards of the Declaration of Helsinki, and all subjects gave informed consent prior to inclusion in the study. Treatment The protocol for RTX administration is shown in Figure?1. A standard dose of 1 1?gr was used for all patients. Twelve patients received two doses at an interval of 6?months (T0 and T6). Three patients received only a single Tetracaine dose because of funding restrictions. Four patients received an additional RTX dose, at 18?months in order to evaluate the safety and efficacy of re\treatment (T18). Where appropriate, data for these groups are presented separately. Open in a separate window Figure 1 Schematic representation of the treatment protocol. All patients at T0 were given 1?gr rituximab (RTX). Steroids were tapered and withdrawn within 3?months (T3) if applicable. A second RTX dose was given 6?months later (T6). At 1?year (T12), calcineurin inhibitor (CNI) was reduced by 25% if no relapses had occurred. Four patients received an additional RTX dose 18?months after the first dose (T18). In order to minimize infusion reactions, 40?mg methylprednisolone, 10?mg Piriton and 1?gr Paracetamol were administered prior each RTX infusion. B\cell depletion, defined as a peripheral blood CD19 cell count of 5?cells/l, was confirmed 2?weeks post\treatment and at Tetracaine every follow\up visit (normal range in our laboratory Tetracaine defined as 100C500?cells/l). Patients who did not deplete their B cells were re\treated 4?weeks later. If patients were on concomitant steroids, they were tapered and withdrawn by 3?months following the first RTX dose. At 12?months, if no relapse had occurred, CNI dose was reduced by 25%. Following the initial reduction, CNI dose was reduced by 25% at six monthly intervals. NS relapse was treated as per standard protocol in our unit with 1?mg/kg prednisolone (max 60?mg/day) until remission, followed by gradual weaning over 8C12 weeks and reinstatement of the original CNI dose. No change in other medications (ACE inhibitors or ARBs) was introduced throughout the study period. Statistical.