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Arthritis Res Ther ; 22(1): 5, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915059


OBJECTIVE: To describe successful therapeutic strategies in statin-induced anti-HMGCR myopathy. METHODS: Retrospective data from a cohort of 55 patients with statin-induced anti-HMGCR myopathy, sequentially stratified by the presence of proximal weakness, early remission, and corticosteroid and IVIG use at treatment induction, were analyzed for optimal successful induction and maintenance of remission strategies. RESULTS: A total of 14 patients achieved remission with a corticosteroid-free induction strategy (25%). In 41 patients treated with corticosteroids, only 4 patients (10%) failed an initial triple steroid/IVIG/steroid-sparing immunosuppressant (SSI) induction strategy. Delay in treatment initiation was independently associated with lower odds of successful maintenance with immunosuppressant monotherapy (OR 0.92, 95% CI 0.85 to 0.97, P = 0.015). While 22 patients (40%) presented with normal strength, only 9 had normal strength at initiation of treatment. CONCLUSION: While corticosteroid-free treatment of anti-HMGCR myopathy is now a safe option in selected cases, initial triple steroid/IVIG/SSI was very efficacious in induction. Delays in treatment initiation and, as a corollary, delays in achieving remission decrease the odds of achieving successful maintenance with an SSI alone. Avoiding such delays, most notably in patients with normal strength, may reset the natural history of anti-HMGCR myopathy from a refractory entity to a treatable disease.

Clin Rheumatol ; 36(6): 1341-1348, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28130685


6-Thioguanine nucleotide (6-TGN) is the active metabolite of thiopurine drugs azathioprine and 6-mercaptopurine. 6-Methylmercaptopurine (6-MMP) is an inactive and potentially hepatotoxic metabolite. A subgroup of patients (shunters) preferentially produce 6-MMP instead of 6-TGN, therefore displaying thiopurine resistance and risk for hepatotoxicity. Outside inflammatory bowel disease literature, few data exist regarding individualized thiopurine therapy based on metabolite monitoring. This study sought to describe metabolite monitoring in patients receiving weight-based thiopurine for systemic autoimmune diseases. Patients were enrolled using a laboratory database, and data were retrospectively collected. The correlation between the highest thiopurine dose (mg/kg) and the 6-TGN concentration (pmol/8 × 108 erythrocytes) was estimated with Pearson's correlation coefficient. Seventy-one patients with various systemic autoimmune conditions were enrolled. The correlation between the thiopurine dose and the 6-TGN level was weak for the overall patient sample (r = 0.201, p = 0.092) and for the subgroup of non-shunters (r = 0.278, p = 0.053). Subjects with 6-MMP levels >5700 pmol/8 × 108 erythrocytes had more hepatic cytolysis compared to subjects with 6-MMP <5700, OR = 4.36 (CI 95% 1.18-16.13, p = 0.027). Twenty-two patients (31%) were identified as shunters. Six shunters developed hepatotoxicity, five of which had 6-MMP concentration >5700. Eleven non-shunters had hepatotoxicity, one of which had 6-MMP >5700. Thiopurine metabolite monitoring shows wide variability in 6-TGN levels among patients treated with weight-based thiopurine for systemic autoimmune diseases. Thirty-one percent of the patients in our series fulfilled the shunter definition. Thiopurine metabolite monitoring and dose adjustment to improve maintenance of remission and avoid hepatotoxicity should be studied prospectively.

Antirreumáticos/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Azatioprina/uso terapêutico , Hipersensibilidade a Drogas/sangue , Nucleotídeos de Guanina/sangue , Erros Inatos do Metabolismo da Purina-Pirimidina/sangue , Tionucleotídeos/sangue , Adulto , Idoso , Antirreumáticos/metabolismo , Doenças Autoimunes/complicações , Azatioprina/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Hipersensibilidade a Drogas/complicações , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Feminino , Humanos , Leucopenia , Masculino , Mercaptopurina/sangue , Metiltransferases/sangue , Pessoa de Meia-Idade , Prevalência , Erros Inatos do Metabolismo da Purina-Pirimidina/complicações , Erros Inatos do Metabolismo da Purina-Pirimidina/diagnóstico , Erros Inatos do Metabolismo da Purina-Pirimidina/epidemiologia , Quebeque/epidemiologia , Estudos Retrospectivos
Can J Cardiol ; 31(5): 691.e5-7, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25818529


Right-sided valvular disease is characteristic of the carcinoid syndrome. In contrast, myocardial involvement is unusual. We present a case of an asymptomatic patient who had a myocardial carcinoid tumor discovered during surgery for coronary artery disease. The clinical presentation, diagnostic tests and modalities, and outcomes after surgery are discussed in this case report.

Doença Cardíaca Carcinoide/diagnóstico , Ponte de Artéria Coronária/métodos , Estenose Coronária/cirurgia , Neoplasias Cardíacas/diagnóstico , Achados Incidentais , Octreotida/administração & dosagem , Idoso , Doença Cardíaca Carcinoide/tratamento farmacológico , Angiografia Coronária/métodos , Estenose Coronária/diagnóstico por imagem , Feminino , Seguimentos , Neoplasias Cardíacas/tratamento farmacológico , Humanos , Cuidados Pré-Operatórios/métodos , Radiografia Torácica/métodos , Doenças Raras , Medição de Risco , Toracotomia/métodos , Resultado do Tratamento
Ann Pharmacother ; 48(5): 648-51, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24523395


OBJECTIVE: To report the use of febuxostat in order to potentiate thiopurines' metabolism in a patient on azathioprine (AZA) therapy with low metabolite 6-thioguanine nucleotides (6-TGN) levels and elevated metabolite 6-methylmercaptopurine (6-MMP) levels. CASE SUMMARY: A 44-year-old woman with a history of anti-signal recognition particle necrotizing myopathy was treated with AZA-allopurinol combination therapy. When she developed an atypical drug-induced hypersensitivity syndrome, allopurinol was replaced by the new xanthine oxidase (XO) inhibitor febuxostat, at a daily dose of 40 mg. Febuxostat-AZA combination was successful with 6-TGN reaching therapeutic levels while 6-MMP levels remained low. After 5 months, she developed similar manifestations that she had presented on AZA-allopurinol combination. Febuxostat and AZA were then stopped. DISCUSSION: AZA and 6-MP are both inactive pro-drugs that undergo a complex metabolic transformation leading to active 6-TGN and potentially hepatotoxic 6-MMP. Some patients with unfavorable thiopurine metabolism might benefit from addition of XO inhibitor allopurinol in order to potentiate 6-TGN and reduce 6-MMP levels. It is likely that febuxostat, via its XO inhibition, would exhibit the same effect on thiopurines' metabolism. CONCLUSION: It has been shown that low dose of febuxostat was able to prevent hypermethylation and to potentiate 6-TGN levels in an AZA-treated patient. Thus, febuxostat could be useful in optimizing thiopurines' metabolism, but more data are needed before this practice can be recommended. The mechanisms by which febuxostat optimizes thiopurines' metabolism remain to be confirmed. Also, the optimal dose of febuxostat for this use remains to be determined.

Azatioprina/administração & dosagem , Inibidores Enzimáticos/administração & dosagem , Nucleotídeos de Guanina/sangue , Imunossupressores/administração & dosagem , Mercaptopurina/análogos & derivados , Doenças Musculares/tratamento farmacológico , Tiazóis/administração & dosagem , Tionucleotídeos/sangue , Adulto , Interações de Medicamentos , Febuxostat , Feminino , Humanos , Mercaptopurina/sangue , Xantina Oxidase/antagonistas & inibidores