Olfactory threshold predicts treatment response in relapsing multiple sclerosis

Abstract

Background: Olfactory threshold (OT) is associated with short-term inflammatory activity in relapsing multiple sclerosis (RMS). Objective: We aimed to investigate OT for prediction of treatment response in RMS. Methods: In this 5-year prospective study on 123 RMS patients, OT was measured at disease-modifying treatment (DMT) initiation (M0), after 3 months (M3), and 12 months (M12) by Sniffin’ Sticks test. Primary endpoint was defined as an absence of relapse during the observation period, with Expanded Disability Status Scale (EDSS) progression and magnetic resonance imaging (MRI) activity being the secondary endpoints. Optimal cutoff values were determined by receiver operating characteristic analyses and their predictive value assessed by multivariable Cox regression models. Results: Higher OT scores at M0, M3, and M12 were independently associated with decreased relapse probability with the strongest risk reduction at M3 (hazard ratio (HR) = 0.44, p < 0.001). Improvement of OT scores from M0 to M3 (ΔOTM3) was also associated with reduced relapse risk (HR = 0.12, p < 0.001). OT score > 6.5 at M3 was the strongest predictor of relapse freedom (HR = 0.10, p < 0.001) with high diagnostic accuracy (positive predictive value (PPV) = 87%), closely followed by ΔOTM3 ⩾ 0.5 (HR = 0.12, p < 0.001, PPV = 86%). Conclusions: OT is an independent predictor of freedom of disease activity upon DMT initiation within 5 years and may be a useful biomarker of treatment response.

Olfactory threshold as a biomarker of disease activity

“…First, we completely agree that OT is indeed a biomarker of disease activity, which has been shown in previous studies. [2][3][4][5] As Santos et al correctly point out, OT scores in the present study significantly differed already at baseline, that is, before disease-modifying therapy (DMT) initiation, between patients with and without treatment response. We also agree that, in line with previous studies, this is in all likelihood explained by the influence of recent disease activity.…”

“…Date received: 9 July 2022; revised: 14 July 2022; accepted: 14 July 2022 Dear Editor, Olfactory dysfunction has been studied in multiple sclerosis (MS). 1 We have recently read the paper by Bsteh et al, 2 stating that olfactory threshold (OT) predicts treatment response in relapsing multiple sclerosis (RMS). Absolute OT score (hazard ratio (HR) = 0.44, p < 0.001) and OT score improvement (HR = 0.12, p < 0.001) at 3 months after disease modifying treatment (DMT) initiation were associated with reduced relapse risk in the following 5 years.…”

“…Ruth Geraldes https://orcid.org/0000-0001-5829-808X Mónica Santos 1,2 , Ruth Geraldes 2,3 and Jacqueline Palace 1 The authors express concerns essentially hypothesizing that olfactory threshold (OT) may rather be a biomarker of disease activity than of treatment response.…”

Non-invasive in vivo imaging of brain and retinal microglia in neurodegenerative diseases

“…Multiple sclerosis also affects the eyes, causing thinning of the nerve fiber layer (NFL), ganglion cell layer (GCL), inner plexiform layer (IPL) and inner nuclear layer (INL) of the retina, reduced macular volume and optic neuritis (Cennamo et al, 2016;Petzold et al, 2017;Pearson et al, 2022;Usta and Gunay, 2023;Vujosevic et al, 2023) (summarized in Figure 1). Therefore, retinal imaging biomarkers are a growing area of interest for early detection and monitoring of MS. Spectral domain OCT has emerged as a valuable tool for investigating neurodegeneration in the retina and has demonstrated that increased thinning of the inner retinal layers is associated with worsening long-term disability in MS (Lambe et al, 2021;Bsteh et al, 2023;Gernert et al, 2023). OCT studies have also revealed that atrophy of the retinal NFL and GCL reflect brain atrophy in MS patients, particularly grey matter loss (Saidha et al, 2015;Cagol et al, 2023).…”

Reply to letter to the editor: Olfactory threshold as a biomarker of disease activity

“…concerning our manuscript ‘Olfactory threshold as a biomarker of disease activity’, we appreciate the interest in our work. 1…”