Urinary neopterin and nitric oxide metabolites as markers of interferon β-1a activity in primary progressive multiple sclerosis.

Background: Interferon beta has not been demonstrated to be effective in exploratory phase 2 clinical trials in primary progressive multiple sclerosis. However, using more sensitive indicators of a treatment response, such as biomarkers, might help to identify sub-groups of patients who may benefit from therapy.Objective: To assess the utility of measuring urinary neopterin and nitric oxide metabolite excretion for monitoring interferon β-1a (IFNβ-1a) treatment in patients with primary progressive multiple sclerosis.Methods: Fifty patients from a phase II trial of IFNβ-1a (Placebo n = 20; Avonex® 1 × 30 μg/week (IFN-30), n = 15; Avonex® 1 × 60 μg/week (IFN-60), n = 15), were enrolled. Patients were assessed using the Expanded Disability Status Scale. Urine samples were collected on each visit, 3 months apart, for a period of 24 months. Nitric oxide metabolites, nitrite/nitrate (NOx), were measured by colorimetric assay and neopterin and creatinine (Cr) were assayed using a high-performance liquid chromatography technique. NOx/creatinine ratio (NOxCR) and urinary neopterin/creatinine ratio (UNCR) quotients were calculated.Results: There was no significant difference between pre-dose, baseline levels of UNCR or NOxCR between the study groups. On the intention-to-treat analysis, there was a significant difference in UNCR levels between the placebo compared with IFN-30 (p = 0.03) or IFN-60 (p = 0.002) groups. The IFN-30 and IFN-60 groups did not differ. Within IFNβ-1a-treated patients with primary progressive multiple sclerosis, median UNCR values were significantly higher in clinically stable (no Expanded Disability Status Scale change) compared with progressive patients (p = 0.002). IFNβ-1a treatment did not significantly influence NOx excretion in patients with primary progressive multiple sclerosis.Conclusions: Urinary neopterin is a potential biomarker to monitor the in vivo effects of IFNβ-1a in primary progressive multiple sclerosis and other multiple sclerosis sub-types. [ABSTRACT FROM PUBLISHER]