Decisional Conflict Regarding Disease-Modifying Treatment Choices Among Patients with Mid-Stage Relapsing-Remitting Multiple Sclerosis.

Purpose: Shared decision-making is critical in multiple sclerosis (MS) due to the uncertainty of the disease trajectory over time and the large number of treatment options with differing efficacy, safety and administration characteristics. The aim of this study was to assess patients' decisional conflict regarding the choice of a disease-modifying therapy and its associated factors in patients with mid-stage relapsing-remitting multiple sclerosis (RRMS). Methods: A multicenter, non-interventional study was conducted. Adult patients with a diagnosis of RRMS (2017 revised McDonald criteria) and disease duration of 3 to 8 years were included. The level of uncertainty experienced by a patient when faced with making a treatment choice was assessed using the 4-item Decisional Conflict Scale. A battery of patient-reported and clinician-rated measures was administered to obtain information on symptom severity, illness perception, illness-related uncertainty, regret, MS knowledge, risk taking behavior, preferred role in the decision-making process, cognition, and self-management. Patients were recruited during routine follow-up visits and completed all questionnaires online using electronic tablets at the hospital. A multivariate logistic regression analysis was conducted. Results: A total of 201 patients were studied. Mean age (Standard deviation) was 38.7 (8.4) years and 74.1% were female. Median disease duration (Interquartile range) was 6.0 (4.0-7.0) years. Median EDSS score was 1.0 (0-2.0). Sixty-seven (33.3%) patients reported a decisional conflict. These patients had lower MS knowledge and more illness uncertainty, anxiety, depressive symptoms, fatigue, subjective symptom severity, a threatening illness perception, and poorer quality of life than their counterparts. Lack of decisional conflict was associated with MS knowledge (Odds ratio [OR]=1.195, 95% CI 1.045, 1.383, p=0.013), self-management (OR=1.049, 95% CI 1.013, 1.093, p=0.018), and regret after a healthcare decision (OR=0.860, 95% CI 0.756, 0.973, p=0.018) in the multivariate analysis. Conclusion: Decisional conflict regarding the selection of a disease-modifying therapy was a common phenomenon in patients with mid-stage RRMS. Identifying factors associated with decisional conflict may be useful to implement preventive strategies that help patients better understand their condition and strengthen their self-management resources.

Assessing illness-related uncertainty in relapsing-remitting multiple sclerosis: A psychometric analysis of the Mishel Uncertainty of Illness Scale.

A multicenter study involving 204 adults with relapsing-remitting multiple sclerosis (RRMS) assessed the dimensionality and item characteristics of the Mishel-Uncertainty of Illness Scale (MUIS), a generic self-assessment tool. Mokken analysis identified two dimensions in the MUIS with an appropriate item and overall scale scalability after excluding nonclassifiable items. A refined 12-item MUIS, employing a grade response model, effectively discriminated uncertainty levels among RRMS patients (likelihood ratio test p-value = .03). These findings suggest the potential value of the 12-item MUIS as a reliable measure for assessing uncertainty associated with the course of illness in RRMS.

Real-world experience of ocrelizumab in multiple sclerosis in a Spanish population.

OBJECTIVE: Pivotal trial have shown that patients with multiple sclerosis (MS) receiving ocrelizumab had better outcomes. However, data on ocrelizumab in clinical practice are limited. The aim of this study was to evaluate the preliminary safety profile and effectiveness of ocrelizumab treatment for multiple sclerosis (MS) in a real-world clinical setting. METHODS: We conducted a retrospective study including consecutive patients from nine public hospitals in south-eastern Spain who received ocrelizumab after it was approved. RESULTS: A total of 228 MS patients were included (144 with relapsing-remitting MS [RRMS], 25 secondary progressive MS [SPMS], and 59 primary progressive MS [PPMS]). Median follow-up period was 12 months (range, 1-32). No evidence of disease activity (NEDA) status at year 1 was achieved in 91.2% of the relapsing MS (RMS) population, while disability progression was detected in 37.5% of the PPMS patients (median follow-up period, 19 months). The most common adverse events reported were infusion-related reactions and infections, with the most common infections being urinary tract infections followed by upper respiratory infections and COVID-19. INTERPRETATION: The preliminary results in our real-world setting show that ocrelizumab presented excellent results in suppressing disease activity with a favorable and consistent safety profile.

Discontinuation of disease-modifying treatments in multiple sclerosis to plan a pregnancy: A retrospective registry study.

BACKGROUND: For safety reasons multiple sclerosis (MS) treatment guidelines recommend stopping or delaying the onset of disease-modifying therapies (DMT) before a planned pregnancy, but disease stability after DMT discontinuation is not well studied. The objective of this study is to describe the course of MS in patients who interrupted DMT before a planned pregnancy. METHODS: This was a retrospective study using 2008-2016 data from a multicenter register of pregnancies in women with MS. In this paper, we present data from the subgroup of women with relapsing-remitting MS (RRMS) who interrupted DMT to try to conceive. Data from 1 and 3 years before DMT interruption, the period between DMT interruption and conception or resuming DMT, during pregnancy and one year postpartum were analyzed. Annualized relapse rates (ARR), Expanded Disability Status Scale (EDSS) scores, and magnetic resonance imaging (MRI), obstetric, and neonatal data were collected. RESULTS: Twenty-seven women interrupted DMT (19 ß-interferon, 5 glatiramer acetate, 2 natalizumab and 1 fingolimod) to try to conceive. After a mean of 10.6 months 6 women stopped trying to conceive and resumed DMT, while 21 women became pregnant after a mean of 7.0 months. In the overall cohort, in the period from when DMT was discontinued to when pregnancy was confirmed or DMT resumed, the ARR was 1.08, which was significantly higher than the ARR 1 year (0.44; p = 0.01) and 3 years (0.4; p = 0.06) before DMT discontinuation. The mean EDSS score when pregnancy was confirmed or DMT resumed was significantly higher than at DMT discontinuation (1.8 vs 1.36, p = 0.011). In the subgroup of patients who became pregnant, the ARR in the untreated period before pregnancy was 0.98, which was significantly higher than the ARR 1 year (0.38; p = 0.03) and 3 years (0.39; p = 0.0077) before DMT discontinuation. The ARR decreased to 0.51 during pregnancy and then increased to 0.76 during the first postpartum trimester (not significant). One year after delivery, the mean EDSS score (1.86) was significantly higher than at DMT cessation (1.35, p = 0.027) or pregnancy confirmation (1.45, p = 0.026). Patients who suffered relapses following DMT cessation before becoming pregnant had an 11-fold higher risk of relapse during pregnancy (relative risk [RR] = 11.1 [95%CI 1.6, 75], p = 0.002) and a 3-fold higher risk during the postpartum year (RR = 3.0 [95%CI 1.3,6.6], p = 0.007) than those who did not suffer relapses in period between DMT withdrawal and pregnancy. CONCLUSIONS: In this retrospective registry study, discontinuation of DMT (mostly immunomodulatory drugs), to try to conceive resulted in an increase in MS relapse rates and disability progression.

Therapeutic status quo in patients with relapsing-remitting multiple sclerosis: A sign of poor self-perception of their clinical status?

BACKGROUND: Status quo (SQ) bias is defined as patient´s tendency to continue taking a previously selected but inferior therapeutic option. OBJECTIVE: To assess the presence of SQ bias and its associated factors in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: A multicenter, non-interventional study involving 211 patients with RRMS was conducted. Participants answered questions regarding risk preferences and management of simulated MS case-scenarios. The SymptoMScreen (SMSS) questionnaire was used to assess the perception of severity from the patients´ perspective. SQ bias was defined as patients' preference to maintain the current treatment despite evidence of disease activity. Mixed linear models adjusting for clustering assessed the association of candidate predictors with the outcome of interest. RESULTS: The mean age (SD) was 39.1 (9.5) years and 70.6% were women. SQ bias was observed in 74.4% (n=161) participants. Univariate analysis showed that SMSS score was associated with SQ bias (OR 1.04; 95% CI 1.01-1.07). Mixed linear regression models suggest that for every point increase in SMSS, there was a 4% increase in the likelihood of SQ bias (ß 0.04; 95%CI 0.015-0.06; p<0.002). Among the different symptomatic dimensions included in the SMSS, only vision impairment (ß 0.32; 95%CI 0.05-0.50) and depression (ß 0.29; 95%CI 0.006-0.58) remained associated with SQ bias in the multivariate analysis. There was no association between participants' risk preferences and SQ bias. CONCLUSIONS: Unwillingness to pursue treatments that are more effective is a common phenomenon affecting over 7 out of 10 patients with RRMS. This phenomenon appears to be driven by patients' negative self-perception of their clinical status.

Assessing fatigue in multiple sclerosis: Psychometric properties of the five-item Modified Fatigue Impact Scale (MFIS-5).

Fatigue in multiple sclerosis is a key symptom associated with work-related problems and poor quality of life outcomes. The five-item Modified Fatigue Impact Scale is a brief self-assessment tool for measuring the impact of fatigue on cognitive, physical and psychosocial function. A non-interventional, cross-sectional study was conducted to assess dimensionality and item characteristics of the five-item Modified Fatigue Impact Scale in multiple sclerosis. A total of 302 subjects were studied. Mokken analysis found the five-item Modified Fatigue Impact Scale is a strong one-dimensional scale (overall scalability index H = 0.67) with high reliability (Cronbach's alpha = 0.90). The confirmatory factor analysis model confirmed the one-dimensional structure (comparative fit index = 1.0, root-mean-square error of approximation = 0.035). Samejima's model fitted well as an unconstrained model with different item difficulties. The five-item Modified Fatigue Impact Scale shows appropriate psychometric characteristics and may constitute a valuable and easy-to-implement addition to measure the impact of fatigue in clinical practice.

Observational Study of Switching from Natalizumab to Immunomodulatory Drugs.

OBJECTIVE: To determine the effect of disease-modifying drugs (DMDs) on disease activity rebound in patients discontinuing natalizumab (NTZ). METHODS: Twenty-one patients with relapsing-remitting multiple sclerosis (RRMS) treated with NTZ for ≥1 year and who switched to DMDs (glatiramer acetate [GA] or interferon) were followed up for 12 months in clinical practice. Clinical outcomes after NTZ cessation were assessed every 3 months for 1 year and MRI was performed at 12 months. RESULTS: Twelve months after switching from NTZ to DMDs, there were no significant differences in the annualized relapse rate (ARR) compared to the days that NTZ was used (0.3 vs. 0.1; p = 0.083); and the ARR never reached similar values to those prior to NTZ use (1.61; p < 0.001). The percentage of relapse-free patients after switching from NTZ was 71.4%. These patients did not have lower disease activity before NTZ compared with those with clinical relapses (1.3 vs. 1.7; p = 0.302), but they had lower Expanded Disability Status Scale scores (3.4 vs. 5.7; p = 0.001). DMDs had beneficial effects on MRI parameters, as 10 of 16 patients (62.5%) presented no evidence of radiological activity 12 months after NTZ discontinuation. CONCLUSIONS: Patients with RRMS and moderate disability who discontinued NTZ for safety reasons may benefit from the DMDs GA and interferon with no known risk for progressive multifocal leukoencephalopathy.

Prevalence of multiple sclerosis in Health District III, Murcia, Spain.

BACKGROUND: The prevalence of multiple sclerosis (MS) varies throughout the world, and available epidemiological data suggest a progressively increasing prevalence of MS in Spain. The objective of this study was to calculate MS prevalence in Health District III of the autonomous community of Murcia in Spain. METHODS: This is an observational, cross-sectional, descriptive study. The prevalence of MS in Health District III in the Region of Murcia, which includes the municipalities of Lorca, Totana, Águilas, Puerto Lumbreras and Aledo, was calculated from the total population (171,040 inhabitants), and among native Spanish citizens only (137,659 persons). Healthcare and demographic data were obtained from three sources: 1) OMI-AP: the local primary care computer system containing the medical records of all subscribers; 2) the medical record database of the Hospital Rafael Mendez (the single hospital in the district); and 3) the records of the AEMA III Multiple Sclerosis Association to which patients from this healthcare district belong. Data from these three sources were combined to check the accuracy and completeness of the patient records. RESULTS: The prevalence of MS among the general population of this district, including non-Spanish individuals, was 71.9 per 100,000 inhabitants (95% CI=60-85). Prevalence among the native Spanish population was 82.0 per 100,000 (95% CI=68-98). Considering prevalence by sex, it was 118.1 per 100,000 (95% CI: 95-146) in the female native Spanish population, and 45.4 per 100,000 (95% CI: 31-64) in the male native Spanish population. The prevalence in the native Spanish population in this district was calculated by sex and age (grouped by decades). A peak was observed among women aged between 20 and 29 years: 234.2 per 100,000 inhabitants (95% CI: 151-361). CONCLUSION: Our results suggest that the population in this healthcare district presents a risk of MS similar to that recently reported in other regions of Spain, which is higher than in previous decades.