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Current and future prospects in the management of granulomatosis with polyangiitis (Wegener's granulomatosis).

ABSTRACT: Granulomatosis with polyangiitis (GPA, formerly Wegener's granulomatosis) is a multisystem autoimmune condition associated with anti-neutrophil cytoplasm antibodies. Management of GPA can be complex, owing to the sometimes fulminant and multisystem nature of the presentation, the age demographics of the affected population, and a significant incidence of disease relapse. In this paper, we discuss how some of the challenges in the management of GPA have been and continue to be addressed including: reducing the toxicity of induction therapy; developing biomarkers to determine who can safely stop maintenance immunosuppression; improving the efficacy of maintenance therapy for relapsing patients; managing localized disease; and management of disease and treatment-associated comorbidity. Consideration is also given to emerging therapeutics in the treatment of GPA.

SUBMITTER: Tarzi RM

PROVIDER: S-EPMC4000246 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Current and future prospects in the management of granulomatosis with polyangiitis (Wegener's granulomatosis).

Tarzi Ruth M RM Pusey Charles D CD

Therapeutics and clinical risk management 20140417

Granulomatosis with polyangiitis (GPA, formerly Wegener's granulomatosis) is a multisystem autoimmune condition associated with anti-neutrophil cytoplasm antibodies. Management of GPA can be complex, owing to the sometimes fulminant and multisystem nature of the presentation, the age demographics of the affected population, and a significant incidence of disease relapse. In this paper, we discuss how some of the challenges in the management of GPA have been and continue to be addressed including ...[more]

PMID: 24790453

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Project description:The objective of this study is to assess the relationship between inflammatory disease in granulomatosis with polyangiitis (GPA, Wegener's) and the development of subclinical atherosclerosis. A total of 46 adult patients with GPA were enrolled. Disease status was measured by Birmingham vasculitis assessment scores as modified for GPA, vasculitis damage index, disease duration, and number of relapses. Classic atherosclerotic risk factors, platelet aggregation responses, and circulating microparticle (MP) levels were recorded. All patients underwent carotid artery intima-media thickness (IMT) measurement as outcome for subclinical atherosclerosis. In univariate analyses, systolic and diastolic blood pressure, creatinine, and age were significantly associated with higher IMT (ρ values 0.37, 0.38, 0.35, and 0.054, respectively [P < 0.02 for all]). In a multiple regression model, greater number of relapses, older age at the onset of disease, and higher diastolic blood pressure were found to be associated with higher IMT (P values 0.003, <0.001, and 0.031, respectively). MP counts and platelet reactivity correlated well with disease activity in GPA. Furthermore, MPs were found to activate vascular endothelial cells and platelets in vitro. The cumulative burden of systemic inflammation in GPA correlated with the development of subclinical atherosclerosis. The correlation with subclinical atherosclerosis could be because of glucocorticoid use and not the inflammatory process in GPA, giving the inherent bias that exits with the use of glucocorticoid with each relapse. The findings of increased levels of circulating leukocyte-derived MPs and enhanced platelet reactivity during relapse suggest possible roles for MPs and platelets in disease pathogenesis and support a growing literature that links inflammation, atherosclerosis, and platelet activation. This hypothesis is further substantiated by our demonstration that MPs isolated from plasma of GPA patients can activate platelets and vascular endothelial cells.

Project description:This paper reviews the current management of onchocerciasis and its future prospects. Onchocerciasis is a disease affecting millions of people in Africa, South and Central America, and Yemen. It is spread by the blackfly as a vector and caused by the filarial nematode, Onchocerca volvulus. A serious attempt was made by the Onchocerciasis Control Program between 1975 and 2002 to eliminate the vector in eleven of the endemic countries in West Africa, and with remarkable success. Formerly, the treatment was with diethyl carbamazine for the microfilaria and suramin for the adult worm. These drugs are now known to be toxic and unsuitable for mass distribution. In particular, they precipitate optic nerve disease. With the discovery of ivermectin, a much safer microfilaricide, and the decision of Merck to distribute the drug free of charge for as long as needed, the strategy of control switched to mass drug administration through community-directed treatment with ivermectin. So far, millions have received this annual or biannual treatment through the African Program for Onchocerciasis Control and the Onchocerciasis Elimination Program for the Americas. However, the problem with ivermectin is that it is a monotherapy microfilaricide which has limited effect on the adult worm, and thus will need to be continued for the life span of the adult worm, which may last up to 15 years. There are also early reports of resistance. Serious encephalopathy and death may occur when ivermectin is used in subjects heavily infested with loiasis. It seems unlikely that a break in transmission will occur with community-directed treatment with ivermectin in Africa because of population migrations and the highly efficient vector, but in the Americas some countries such as Columbia and the Oaxaca focus in Mexico have reported eradication. Vector control is only now applicable in selected situations, and particularly to control the nuisance value of the blackfly. Trials are ongoing for alternatives to ivermectin. Candidate drugs include moxidectin, a macrofilaricide, doxycycline which targets the Wolbachia endosymbiont, and flubendazole, which shows promise with the newer oral cyclodextrin formulation.

Dataset Information

Current and future prospects in the management of granulomatosis with polyangiitis (Wegener's granulomatosis).

Publications

Current and future prospects in the management of granulomatosis with polyangiitis (Wegener's granulomatosis).

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