Olfactory threshold as a biomarker predicting treatment response in relapsing multiple sclerosis
Gabriel Bsteh1, Harald Hegen2, Klaus Berek2, Anne Zinganell2, Sebastian Wurth2, Michael Auer2, Franziska Di Pauli2, Florian Deisenhammer2, Thomas Berger1
1Neurology, Medical University Vienna, 2Neurology, Medical University Innsbruck
Objective:
We aimed to investigate the potential of olfactory threshold for prediction of treatment response in relapsing multiple sclerosis (RMS).
Background:
Olfactory threshold impairment is transiently occurring in patients with active MS and during acute MS relapse resolving in phases of clinical stability and after initiation of disease-modifying treatment (DMT). Thus, threshold impairment is a marker of short-term inflammatory activity in MS.
Design/Methods:
In this 5-year prospective observational study on 113 RMS patients, olfactory threshold was measured at DMT initiation (M0) and after 3 (M3) and 12 months (M12) of follow-up by the Sniffin’ Sticks test. Inclusion criteria included adherence to DMT for at least 2 years. Treatment response was defined as absence of relapse during the observation period. Best possible cut-off values of olfactory threshold for predicting treatment response were determined by receiver-operating characteristics (ROC) analyses. Odds ratios (OR) for treatment response were calculated by stepwise multivariate logistic regression models correcting for age, sex and disease duration at baseline.
Results:
A combination of threshold score ≥6.0 at M3 and ≥1.0 points improvement from M0 to M3 sustained to M12 displayed the best prediction of treatment response (OR 5.1; 95% CI: 2.3 – 7.8; p<0.001; specificity 90%, sensitivity 83%) followed by threshold score ≥6.0 at M3 alone (OR 3.6; 95% CI: 1.3 – 7.0; p<0.001; specificity 83%, sensitivity 76%), ≥1.0 points improvement from M0 to M3 sustained to M12 alone (OR 3.5; 95% CI: 1.2 – 6.8; p<0.001; specificity 82%, sensitivity 70%).Threshold score at M12 alone and improvement from M3 to M12 was not significantly predictive. Also, adding threshold score at M12 to the model did not improve predictive accuracy.
Conclusions:
Olfactory threshold impairment predicts relapse activity upon DMT initiation. Pending validation, olfactory threshold may be a useful and easily obtainable biomarker of treatment response in RMS.