Treatment response in relation to inflammatory and axonal surrogate marker in multiple sclerosis

Abstract

Background: This study aimed to investigate if treatment response could retrospectively be related to inflammatory or axonal pathology as measured by plasma surrogate markers. Methods:In this 1-year observational study 30 MS patients with relapsingremitting disease were treated with intra-muscular IFNβ-1a or subcutaneous IFNβ-1b. Responders and non-responders were defined according to clinical and MRI criteria. The control group consisted of 14 healthy subjects. Plasma levels of surrogate markers for inflammation (nitric oxide metabolites (NO x )), astrocytic activation (S100B) and axonal damage (NfH SMI35 ) were measured using standard assays.Results: There were 11 non-responders and 19 responders to IFNβ treatment. Median S100B levels were elevated in a higher proportion of treatment responders (63%, 42.9 pg/mL) compared to non-responders (18%, 11.7 pg/mL, p<0.05, Fisher's exact test) and controls (0%, 2 pg/mL, p< 0.001). Levels of NO x were found to be more frequently elevated in non-responders (72%, 39 µM) compared to healthy controls (0%, 37 µM, p<0.05). Levels of NfH SMI35 were more frequently elevated in responders (58%, 300 pg/mL, p<0.001) and non-responders (72%, 500 pg/mL, p<0.001) compared to controls (0%, 4.5 pg/mL). Conclusion:Patients with relapsing-remitting MS who had surrogate marker supported evidence for astrocytic activation responded more frequently to treatment with IFNβ.

Serum GFAP levels in optic neuropathies

“…In addition, there are many extracranial sources of S100B [35] likely to introduce measurement noise. The data on higher serum S100B levels in patients with more active MS is consistent with previous studies suggesting serum S100B to be a biomarker for micro-and macroglial activity [29,36]. Because the more disseminated pathology in the MS brain compared to local pathology in optic neuropathies, serum S100B levels may be investigated as a potential biomarker for controlling inflammatory disease activity in RR or SP MS, but not PPMS [37].…”

MS treatment: Postmarketing studies

“…Relapses and disability progression are the two basic clinical phenomena of MS, and clinical response to IFNβ is based on these two measures. In the literature, different definitions of non-responders have been proposed [8,[29][30][31][32][33][34], although none have been validated in the long-term follow-up. Long-term disability data are crucial in order to set the most clinically meaningful definition of non-response.…”

Astrocytes in the tempest of multiple sclerosis

“…Further, elevated levels of a putative astrocytic paracrine neurotrophic factor S100B are also observed in MS patients treated with IFN-b [108]. Glatiramer acetate (GA, Copaxone, Copolymer 1) also elevates expression of neurotrophic factors and anti-inflammatory cytokines in the CNS of EAE mice [109].…”