Background

Red blood cell distribution width (RDW) is an objective measured value, which reflects the variability of circulating red blood cells (RBCs). In the past years, RDW has raised attention in the field of inflammation as it was associated with the outcomes of patients with autoimmune and cardiovascular diseases. Immune and inflammatory factors are involved in the pathogenesis of multiple sclerosis (MS) and loss of polyunsaturated fatty acids from plasma and blood cell membranes has been reported in MS patients, contributing to the variation of erythrocyte deformability. The relationship between MS and RDW is not well study.

Objectives

This investigation aimed to assess the association between RDW and MS. Our goal was to compare baseline RDW to EDSS at 5 years of diagnosis and verify if it predicts worse disability.

Methods

A retrospective observational study was performed. We studied patients with Relapsing-remitting MS (RRMS) followed in the Neuroimmunology Clinic of a Portuguese Hospital that had at least one measuring of RDW at baseline. We included patients diagnosed with RRMS (between 2005-2015) according to the McDonald 2017 criteria. Patients with hematologic, oncological, infectious, and thyroid diseases, renal or hepatic dysfunction, or other autoimmune diseases were excluded.

Results

82 patients with RRMS were included. 60 (73,2%) female, aged from 14 to 55 years old at diagnosis, with a mean of 33,56 (SD=20,21) years old. Eight (9,8%) patients had new T2 lesions in MRI at 5 years and 4 (4,9%) shown lesions capturing contrast at 5 years. Two (2,4%) patients had no treatment at 5 years, 62 (77,5%) first-line treatment and 18 (22,5%) second-line treatment. Correlations showed positive association of EDSS at 5 years with RDW at baseline (r=,451; p<,01), EDSS at baseline (r=,596; p<,01), age at diagnosis (r=,339; p<,01) and platelets at baseline (r=,401; p<,01). Multiple linear regression found increased disability (EDSS at 5 years) for patients undergoing second-line treatment (β=0,86; p=,003), and higher RDW at baseline (β=0,47; p=,007). Analyzing RDW results for quartiles, it was statistically significant for quartile 4 [13,5; 16,4[ (β=0,74; p=,039), suggesting that a very increased RDW at baseline is strongly associated with higher EDSS at 5 years.

Conclusions

Higher RDW at baseline is a predictor of worse disability at 5 years in RRMS patients. Furthermore, RDW equal to or higher than 13,5% is useful in identifying patients that will have a worse disability at 5 years in this study. Second-line treatment is also a determining factor of worse EDSS which is expected due to the use of these lines of treatment for the more aggressive disease. We believe more studies should be held to confirm this association once biomarkers determining disability can have an impact on the therapeutic approach and in this sense, are imperious.

Background

Therapeutic inertia is defined as a failure to initiate or intensify treatments despite clinical and paraclinical evidence of disease activity. Its prevalence and determining factors in Relapsing-Remitting Multiple Sclerosis (RRMS) patients in Portugal are not known.

Objectives

Our primary goal was to determine the frequency of therapeutic inertia in our RRMS patients; our secondary goal was to describe therapeutic inertia predisposing factors.

Methods

A multicentre retrospective observational study was performed. We studied patients with RRMS followed in MS Clinics of six Portuguese hospitals with at least one medical appointment during the study period (January 1^st to December 31^st 2018).

Results

We included 427 patients with RRMS, 69.6% females, with a mean age of 41.66 years-old and a mean age at diagnosis of 33.17 years-old. The average number of years since diagnosis was 8.72. MS relapses were reported on 54 patients. Median EDSS score was 1.5 (IQR=1.5). Among the 365 patients who underwent MRI during the study period, 23.8% had new T2 lesions and 7.4% had lesions with contrast enhancement. Therapeutic inertia was present in 80 patients, representing 18.7% of the total sample and 54.8% of the patients with potential to inertia (indication for treatment escalation). Patients with no more than one new T2 lesion, no gadolinium-enhancing lesions, already on a DMT, without adverse events from their current DMT and who were followed in higher care level centres were more likely to have therapeutic inertia (p<0.05). In a binary logistic regression model, the current treatment with DMT (p=0.050), the absence of adverse events (p<0.001), the higher care level (p=0.015) as defined in the Hospital Referral Network in Neurology, and the absence of relapses (p=0.021) or the presence of mild relapses (p=0.027) had an independent effect in therapeutic inertia.

Conclusions

Therapeutic inertia was present in about 1 in 5 patients, exceeding half of the population when considering all the patients with potential to inertia. The subgroup of patients with indication for therapeutic escalation and which also have less active radiological disease was associated with more therapeutic inertia, although these results were not confirmed in a multivariate analysis. Attending a higher care level center, being under DMT, absence of adverse events, and having none or mild relapses, were determining factors for therapeutic inertia.

We believe this study raises awareness to therapeutic inertia as an important problem, providing further knowledge on predisposing factors that may be adressed in MS care.