Background:Co-prescribing 2-mercaptoethane sodium sulfonate (mesna) with cyclophosphamide (CYC) for ANCA-associated vasculitis (AAV) aims to prevent the potential urotoxic effects of CYC. The evidence for this practice is often considered weak, and there may be some diversity in what practitioners do in clinical practice.Objectives:To investigate current clinical practice related to prescribing mesna prophylaxis or not and the underlying rationale for CYC-treated patients with AAV.Methods:We searched MEDLINE for publications with the MeSH term “ANCA-associated vasculitis” over a 10-year period up to October 2020. Email addresses of authors of these publications were extracted from the online information available in MEDLINE. These authors were invited by email to participate in an anonymous online SurveyMonkey survey of 21 to 24 questions asking about the characteristics of the respondent, their experience with AAV, and their practice in using CYC to treat AAV and using mesna in CYC-treated patients with AAV and the underlying rationale. Respondents were eligible to take the full survey if they were involved in deciding and/or monitoring therapy with CYC for patients with AAV. We compared 15 response variables to identify factors associated with the use or not of mesna. Response variables with multiple categories were first analyzed across all categories; if the omnibus test result was significant, additional analyses were used to identify the categories, which were the sources of group separation. We analyzed by-country variations for only countries with ≥ 10 respondents. Statistical analyses involved Pearson’s chi-square test or Fisher’s exact test, as appropriate. For multiple-response variables, the Rao-Scott correction was applied.Results:The invitation for the electronic survey was emailed twice in October 2020 to 1,374 unique email addresses; 156 individuals responded; 139 were eligible and completed the survey. The 139 participants were from 34 countries and were essentially MDs (98%) who mainly worked in rheumatology (50%), nephrology (25%) or internal medicine/clinical immunology (18%). Mesna was given in conjunction with CYC systematically, never, or on a case-by-case basis by 68%, 19% and 13% of respondents, respectively. As compared with systematic mesna-prescribers, never/occasional mesna-prescribers reported a longer time since receiving their degree as a health professional (≥ 15 years: 80% vs 50%, P<0.001), were more frequently based in England/United States (than in France/Germany/Italy) (78% vs 21%, P<0.001), had longer involvement in care of patients with AAV (≥ 15 years: 62% vs 37%, P=0.006), had less practice in using intermittent pulse therapy as the exclusive/predominant CYC administration scheme (62% vs 89%, P<0.001), and, as a rationale underpinning their mesna practice, had less adherence to local operational procedures (47% vs 73%, P=0.002) or (inter)national management guidelines for AAV (16% vs 49%, P<0.001). Never/occasional versus systematic use of mesna did not differ across medical specialties (5 categories, P=0.192) or healthcare settings (3 categories, P=0.437), and was not associated with prior experience of CYC-related urotoxic events (3 categories, P=0.495) or severe mesna toxicity issues (3 categories, P=0.957). The confidence that their practice reflected the best possible patient care did not differ between never/occasional and systematic mesna-prescribers (7-point Likert scale, P=0.794).Conclusion:Practice with regard to prescribing mesna in conjunction with CYC to treat AAV is heterogeneous, although systematic mesna use prevailed over never or occasional use. The decision to prescribe or not mesna may be based more on circumstantial than structural reasons.Disclosure of Interests:Lukas Joos: None declared, Solange Gonzalez Chiappe: None declared, Thomas Neumann Speakers bureau: GSK, Grant/research support from: Xifor, Alfred Mahr Speakers bureau: Amgen, Celgene, Roche, Chugai, Consultant of: Amgen, Celgene, Roche, Chugai
Clinical practice audit on the management of ANCA-associated vasculitis in the Netherlands
