Authors: Peter Joseph Jongen Ioanna Stavrakaki Bernard Voet Erwin Hoogervorst Erik van Munster Wim H Linssen Ludovicus G Sinnige Wim I Verhagen Leo H Visser Ruud van der Kruijk Freek Verheul Jan Boringa Marco Heerings Werner Gladdines Fredrik Lönnqvist Pieter Gaillard
Publish Date: 2016/06/07
Volume: 263, Issue: 8, Pages: 1641-1651
Abstract
In a prospective multicenter observational study we evaluated the frequency severity and impact on activities of daily living ADL of adverse effects AEs of highdose intravenous methylprednisolone IVMP in relapsing remitting multiple sclerosis MS patients with a relapse Online selfreport questionnaires stating IVMP’s most common AEs were completed at baseline the 2nd day of treatment and 1 day and 1 week after treatment Eightyfive patients were included 66 completed the baseline questionnaire and 59 completed at least one postbaseline questionnaire Patients reported on average 4 median AEs two 34 reported no AE Most frequent was change in taste 61 facial flushing 61 sick/stomach pain 53 sleep disturbance 44 appetite change 37 agitation 36 and behavioral changes 36 Of all AEs 343 were severe and 379 impacted on ADL A 3day course resulted in 4 median AEs and a 5day course in 7 All patients with high disease impact had two or more AEs compared with 79 of those with low impact p 001 Of patients with high disability 45 had severe AEs compared with 16 of those with low disability Severe central nervous system CNSrelated AEs occurred two times more frequently in patients with high disease impact and twoandahalf times more frequently in patients with high disability Therefore in virtually all patients highdose IVMP leads to AEs with about one of three AEs being severe with impact on ADL Patients with high disease impact or high disability may experience more severe AEs due to a higher occurrence of severe CNSrelated AEsMultiple sclerosis MS is a chronic disease of the central nervous system CNS in which immunemediated inflammation and degeneration lead to loss of myelin and axons In four out of five patients the disease course is initially characterized by relapses and remissions relapsingremitting MS RRMS 1 Most patients fully recover after a relapse but this can take weeks or months 2 Treatment with highdose methylprednisolone shortens the relapse duration and increases the chances of recovery 3 A European Federation of Neurological Societies task force recommends treatment with intravenous iv or oral methylprednisolone in a dose of at least 500 mg daily for 5 days or iv methylprednisolone IVMP 1 g daily for 3 days 3Methylprednisolone like other corticosteroids is associated with a number of adverse effects AEs affecting the skin skeleton muscles eyes CNS electrolytes metabolism and the endocrine cardiovascular immune and gastrointestinal systems often in a dosedependent manner 4 In the USA in 2004 corticosteroids were the most common specific cause for drugrelated AEs accounting for 103 of all drugrelated AEs and 141000 hospital stays 5 Although most serious AEs are related to the longterm oral use shortterm steroidinduced symptoms are frequent especially with highdose treatment needed to treat relapses 6Patientreported outcomes PROs receive growing attention in drug research PROs are measurements of any aspect of a patient’s health status that comes directly from the patient and can be used to evaluate how a treatment affects patients’ functioning and wellbeing 7 Studies using PROs to evaluate the AEs of longterm oral corticosteroid treatment showed that patients experience an average of 21–23 treatmentrelated symptoms 8 9Most studies on IVMP treatment in MS did not focus on AEs 10 11 Despite their frequent occurrence the severity of IVMP’s AEs is thought to be minor as they seldom require hospitalization or medical interventions However from a patient perspective this may be questioned as studies of corticosteroids in general show that they may bother patients and affect the quality of life 9 In patients with immune thrombocytopenic purpura AEs of corticosteroids were found to be more bothersome from the patients’ perspectives than from the doctors’ perspectives 9 Moreover in MS patients the distress from CNSrelated AEs like mood change behavioral change and sleep disturbance may add to the burden of MSrelated CNS symptomsIn view of the above we performed the patientreported adverse effects of methylprednisolone for relapse treatment in multiple sclerosis FEEL study We specifically assessed from a patient perspective the occurrence severity bothering and impact of AEs during and after highdose IVMP treatment of an MS relapse We hypothesized that more severe AEs would be reported by patients treated with a 5day course than by those treated with a 3day course and by patients who had not been treated with IVMP in recent years due to them being less acquainted with IVMP’s AEs We also expected that CNSrelated AEs would be more frequent and more severe in patients with high disease impact and high disability as we thought it likely that patients with more MSrelated CNS dysfunction might be especially susceptible to severe AEs affecting the CNS
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