Neopterin production and tryptophan degradation during 24-months therapy with interferon beta-1a in multiple sclerosis patients

BACKGROUND: Increased synthesis of neopterin and degradation of tryptophan to kynurenine, measured as kynurenine/tryptophan ratio (kyn/trp ratio), are considered in vitro markers of interferon beta-1a (IFNβ-1a) activity. The aim of the study was to investigate the dynamic profile of neopterin and kyn/trp ratio in patients with relapsing remitting multiple sclerosis (RRMS) treated with two different doses of IFNβ-1a over a period of 24 months. METHODS: RRMS patients (n = 101) received open-label IFNβ-1a 22 mcg (low dose, LD) or 44 mcg (high dose, HD) subcutaneously (sc), three times weekly for 24 months. Serum measurements of neopterin, kyn/trp ratio and neutralizing antibodies (NAbs) were obtained before treatment (i.e., at baseline) and 48 hours post-injection every 3 months thereafter. Clinical assessments were performed at baseline and every 6 months. Changes in biomarkers over time were compared between LD- and HD-group as well as between patients with/without relapses and with/without NAbs using Analysis of Variance and Mann-Whitney tests. RESULTS: Neopterin (p < 0.001) and kyn/trp ratio (p = 0.0013) values increased over time vs baseline in both treatment groups. Neopterin values were higher (p = 0.046) in the HD-compared to the LD-group at every time point with the exclusion of months 21 and 24 of therapy. Conversely, there were no differences between the two doses groups in the kyn/trp ratio with the exclusion of month 6 of therapy (p < 0.05). Neopterin levels were significantly reduced in NAb-positive patients starting from month 9 of therapy (p < 0.05); the same result was observed for kyn/trp ratio but only at month 9 (p = 0.02). Clinical status did not significantly affect neopterin production and tryptophan degradation. CONCLUSIONS: Although differences in serum markers concentration were found following IFNβ administration the clinical relevance of these findings needs to be confirmed with more detailed studies.