Stability of serial platelet and urine protein measurements in patients receiving nusinersen for spinal muscular atrophy

Abstract

Introduction/Aims: Patients undergoing nusinersen treatment for spinal muscular atrophy are subject to measurements of platelet count and urine protein before each injection due to concern for platelet depletion and renal dysfunction according to the prescribing information. These tests may be uncomfortable or inconvenient and may cause delays in treatment. However, it is still unclear whether these values have been significantly affected by nusinersen treatment. Our aim in this study was to determine whether these measurements ever reached critical values that necessitated withholding treatment at our center.Methods: Records from 57 patients treated with nusinersen at our institution between 2017 and 2020 were retrospectively analyzed. Laboratory values for platelet count, random urine protein, and total urine protein:creatinine ratio were collected from all patients before each procedure.Results: Mean patient age was 28.9 years (range, 2-76 years). Mean platelet count was 307 Â 10 9 /L (range, 96-755 Â 10 9 /L; normal lab limits, 150-450 Â 10 9 /L), mean random urine protein was 0.164 g/L (range, <0.05-0.73 g/L), and mean total urine protein:creatinine ratio was 0.885 g per gram creatinine (range, 0.12-9.71 g per gram creatinine). No laboratory values precluded continuing treatment for any patient.Discussion: Although further study on a larger cohort is warranted for more definitive conclusions, it may not be necessary to measure platelet count and urine protein before each nusinersen treatment, particularly in the maintenance phase.

Study on the efficacy, safety, and biomarkers of nusinersen in type II and III spinal muscular atrophy in children

“…Renal toxicity is the main problem with nusinersen. Nagarajan et al found that most patients had proteinuria before treatment, and this proteinuria characterization did not increase because of the use of drugs ( 21 ). But the specific mechanism is not yet clear.…”

“…Both preclinical animal testing and clinical trials have reported that nusinersen may cause thrombocytopenia, but most of this reduction is mild and reversible, and this reduction is dose related ( 28 ). Therefore, it may be more important to monitor platelets at the load stage of treatment than at the maintenance stage ( 21 ). Nagarajan et al found that on the 28th day of treatment with nusinersen, platelet reduction is the most obvious ( 21 ).…”

“…Therefore, it may be more important to monitor platelets at the load stage of treatment than at the maintenance stage ( 21 ). Nagarajan et al found that on the 28th day of treatment with nusinersen, platelet reduction is the most obvious ( 21 ). We monitored the platelet changes before and 2 days after treatment during the loading phase and found that there was a decreasing trend in platelets after each injection of nusinersen.…”