Evaluation of the use of high-efficacy treatments (HETs) in patients with relapsing-remitting multiple sclerosis in Argentina.

BACKGROUND: Disease-modifying therapies (DMTs) in multiple sclerosis (MS) can be classified according to the efficacy in which they prevent inflammatory activity. To date, there are limited data regarding the use of high-efficacy treatments (HETs) in Latin America (LATAM). We aimed to analyze the use of HETs in Argentina, focusing on the clinical and sociodemographic characteristics of the patients who use these treatments and the changes in the trend of use over the years. METHODS: A retrospective cohort study was done using the Argentina MS patient registry, RelevarEM. Patients diagnosed with relapsing-remitting MS (RRMS) according to validated diagnostic criteria and under treatment with natalizumab, alemtuzumab, cladribine, rituximab or ocrelizumab were included. RESULTS: Out of 2450 RRMS patients under a DMT, 462 (19%) were on HETs. One third of those patients (35%) received HETs as the first treatment. The most frequent reason for switching to HETs was treatment failure to previous DMT (77%). The time from MS diagnosis to the first HET in treatment-naive patients was less than one year (IQR: 0-1 year) and in treatment-experienced patients it was 5 years (IQR: 3-9 years). Between 2015 and 2017 (P1), 729 patients included in RelevarEM started a new treatment, of which 85 (11.65%) were HETs. Between 2018 and 2020 (P2), 961 patients included in RelevarEM started a new treatment, of which 284 (29.55%) were HETs. When comparing P2 with P1, a significant increase in the use of HETs was observed (p < 0.01). The most frequently used HETs were alemtuzumab (50.59%) in P1, and cladribine (45.20%) in P2. CONCLUSION: The demographic and clinical characteristics of patients under HET in Argentina were identified. Based on a real-world setting, we found a significant trend towards and a rapid increase in the use of HETs in clinical practice in patients with RRMS.

Achieving no evidence of disease activity-3 in highly active multiple sclerosis patients treated with cladribine and monoclonal antibodies.

Background: We aimed to determine the proportion of highly active multiple sclerosis patients under high-efficacy therapies (HETs) achieve no evidence of disease activity-3 (NEDA-3) at 1 and 2 years, and to identify factors associated with failing to meet no evidence of disease activity 3 at 2 years. Methods: This retrospective cohort study based on Argentina Multiple Sclerosis patient registry (RelevarEM), includes highly active multiple sclerosis patients who received HETs. Results: In total, 254 (78.51%) achieved NEDA-3 at year 1 and 220 (68.12%) achieved NEDA-3 at year 2. Patients who achieved NEDA-3 at 2 years had a shorter duration of multiple sclerosis (p < 0.01) and a shorter time between first treatment and current treatment (p = 0.01). Early high-efficacy strategy patients reached NEDA-3 more frequently (p < 0.01). Being a naïve patient (odds ratio: 3.78, 95% confidence interval 1.50-9.86, p < 0.01) was an independent predictor to reach NEDA-3 at 2 years. No association was found between type of HETs and NEDA-3 at 2 years when adjusted for potential confounders (odds ratio: 1.73; 95% confidence interval 0.51-6.06, p 0.57). Conclusion: We found a high proportion of patients who achieved NEDA-3 at 1 and 2 years. Early high-efficacy strategy patients had a higher probability of achieving NEDA-3 at 2 years.

Evaluation of adherence to treatment in patients with multiple sclerosis from Latin America.

INTRODUCTION AND AIM: Several factors have been associated with poor adherence to disease-modifying drugs (DMD). The aim of this study is to evaluate the adherence to DMD in people with multiple sclerosis (PwMS) in Argentina and Ecuador. METHODS: A cross-sectional study was performed. The study was carried out between June 2020 and October 2020, and 303 PwMS treated with DMD were included. Patients undergoing immune reconstitution treatments were excluded. Two definitions of DMD adherence were previously determined. Adherence to MS treatments was assessed using the multiple sclerosis treatment adherence questionnaire (MS-TAQ). The logistic regression model was used to evaluate factors related to adherence, and p < 0.05 was considered significant. RESULT: The mean age at study entry for patients was 40.7 ± 11.2 years, 207 (68.3%) were female, and the mean EDSS score was 2.2 ± 1.9. The overall adherence in our sample was 78.1% (79.7% in Argentina and 76% Ecuador, p = 0.23). Patients using infusion therapies significantly more often belonged to the adherent group (p = 0.042). Sharing decision-making (OR = 3.4, 95% CI: 1.7-6.9, p = 0.01), lower EDSS (OR = 0.8, 95% IC: 0.6-0.9, p = 0.004), and lower treatment duration (OR = 0.8, 95% IC: 0.6-0.9, p = 0.001) were independent predictors of adherence in our multivariate model. CONCLUSION: We found a prevalence of non-adherence similar to that previously reported. Furthermore, new factors associated with lower adherence were identified.

[A safe use of medications in Primary Care, in COVID-19 pandemic as well]. / Uso seguro de los medicamentos en Atención Primaria, también en época de pandemia de la COVID-19.

The third Global Patient Safety Challenge, Medication Without Harm, was launched in 2017 by the World Health Organization with the goal of reducing the already well-known severe preventable medication-related harm by 50% over the next 5 years. Nothing suggested that, two years later, the world would suffer a terrible pandemic, which has been a much greater challenge than the aforementioned one and that would put it to test from the first stages of the medication use process. The rapid pace imposed by the pandemic has created new risks in the use of medication in those affected by COVID-19 and in the population due to organizational changes in the provision of health care in health services. Therefore, prudent prescribing is becoming more important than ever in health systems. This article aims to analyze the main risks produced during the pandemic period and offer Primary Care professionals an update and a reminder of the main aspects related to the safety use of medications.

Aggressive multiple sclerosis in Argentina: Data from the nationwide registry RelevarEM.

The objectives of the present study were to describe the frequency of aggressive multiple sclerosis (aMS) as well as to compare clinical and radiological characteristics in aMS and non-aMS patients included in RelevarEM (NCT03375177). METHODS: The eligible study population and cohort selection included adult-onset patients (≥18 years) with definite MS. AMS were defined as those reaching confirmed EDSS ≥ 6 within 5 years from symptom onset. Confirmation was achieved when a subsequent EDSS ≥ 6 was recorded at least six months later but within 5 years of the first clinical presentation. AMS and non-aMS were compared using the χ2 test for categorical and the Mann-Whitney for continuous variables at MS onset and multivariable analysis was performed using forward stepwise logistic regression with baseline characteristics at disease onset. RESULTS: A total of 2158 patients with MS were included: 74 aMS and 2084 non-aMS. The prevalence of aMS in our cohort was 3.4% (95%CI 2.7-4.2). AMS were more likely to be male (p = 0.003), older at MS onset (p < 0.001), have primary progressive MS (PPMS) phenotype (p = 0.03), multifocal presentation (p < 0.001), and spinal cord as well as infratentorial lesions at MRI during disease onset (p = 0.004 and p = 0.002, respectively). CONCLUSION: 3.4% of our patient population could be considered aMS. Men, patients older at symptom onset, multifocal presentation, PPMS phenotype, and spinal cord as well as brainstem lesions on MRI at clinical presentation all had higher odds of having aMS.

Usage trend of oral drugs for multiple sclerosis patients in Argentina.

INTRODUCTION: Over the past decade, numerous disease modifying drugs (DMDs) for relapsing- remitting multiple sclerosis (RRMS) have been approved in Argentina. The use of oral DMDs (oDMDs) has increased in recent years, although real-life data in our region is limited. We aimed to describe the tendency in the use of oDMDs (as first treatment option or after switch) in relationship with their approval in Argentina. METHODS: A retrospective study in a cohort of MS patients from five Argentinian MS centers was conducted. Regarding the availability of different oDMDs in Argentina, we define three periods (P1-3): P1: 2012 - 2014; P2: 2015 - 2017 and P3: 2018 - 2020. An analysis was performed comparing between these three periods to assess the tendency for oDMDs use over time. RESULT: The most frequently prescribed treatment as first DMD was: interferon beta 1a (40%) in P1, fingolimod (37.3%) in P2 and also fingolimod (35%) in P3. We found an increase in the use of oDMTs as initial treatment over time (P1: 17.7%, P2: 63.9% and P3: 65.0%; Chi-square = 41.9 p <0.01). We also found a tendency to increase the use of oDMTs after a first switch (P1: 45.5%, P2: 60.1% and P3 78.3%). Multivariate analysis showed that disease evolution (OR=1.06, p=0.04), and year of treatment initiation (OR=1.01 p<0.01) were independently associated with choice of oDMTs. CONCLUSION: This study identified an increasing tendency for the use of oDMDs as initial treatment of RMS in relationship with their approval in Argentina.

Absence of latitudinal gradient in oligoclonal bands prevalence in Argentina.

BACKGROUND: Like MS prevalence, oligoclonal bands (OCB) frequency seems to follow a latitudinal gradient. Argentina is extensive, latitude-wise, and previous studies have not found an MS prevalence latitudinal gradient. Our aim is to describe OCB prevalence in MS, clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS) patients included in the Argentinean MS and NMOSD registry (RelevarEM) and to investigate if it follows a latitudinal gradient. METHODS: For each province, an average latitude was calculated, and OCB frequency was investigated. Multivariate logistical regression analysis and linear correlation were performed. Statistical analysis was repeated after excluding patients from centers using isoelectric focusing (IEF) in less than 95% of patients (CwIEF<95). RESULTS: We included 2866 patients. OCB where positive in 73.9% of patients. No association or correlation were found between OCB and latitude of residence, even after excluding patients from (CwIEF<95). CONCLUSION: OCB positivity does not follow a latitudinal gradient in Argentina. Also, OCB positivity is lower than described in other world regions.

Perceived fatigue in multiple sclerosis: The importance of highlighting its impact on quality of life, social network and cognition.

OBJECTIVES: To study the relationship between perceived fatigue and heath related quality of life (HRQoL), social support and cognition in an Argentinean population of patients with MS (PwMS). PATIENTS AND METHODS: 128 PwMS were studied, 75 women (58 %). Mean age: 40 ±â€¯10.49 years-old, education: 14 ±â€¯3.04, Expanded Disability Status Scale (EDSS): 2.43 ±â€¯1.87, evolution: 10.07 ±â€¯7.23 years. INSTRUMENTS: Fatigue Severity Scale (FSS); EDSS; Beck's Depression Inventory II (BDI-II); International Quality of Life questionnaire (MusiQoL); Medical Outcomes Study Social Support Survey (MOS); BICAMS Battery, 7/24 Spatial Recall Test, Paced Auditory Serial Task (PASAT-3), Word list generation task (WLG). RESULTS: Sixty-six patients (51.6 %) presented fatigue. Significant differences were found between fatigued and non-fatigued patients in EDSS and BDI II (p < 0.001). Fatigue was associated with age, EDSS and BDI II (p < 0.05). When analyzing differences in HRQoL between fatigued and non-fatigued patients statistically significant differences were found in MusiQol (p < 0.05). FSS proved to be an independent predictor of HRQoL (typified ß =-0.612 and -0.287, p < 0.05). Fatigued patients had fewer friends in their social support network (p = 0.031) and worse performance in PASAT. FSS was established as an independent predictor of PASAT (ß = -0.280, p = 0.009) CONCLUSION: Fatigue is one of the most common symptoms in Multiple Sclerosis (MS) and has a great impact on patients daily life. This study highlights the importance of studying fatigue and treating it properly, since otherwise, it contributes to the dysfunction of patients daily life with psychological and social consequences.

Clinical and demographic characteristics of primary progressive multiple sclerosis in Argentina: Argentinean registry cohort study (RelevarEM).

BACKGROUND: Primary progressive multiple sclerosis (PPMS) is an infrequent clinical form of multiple sclerosis (MS). Scarce information is available about PPMS in Latin America. The aim of this work is to describe the clinical and demographic characteristics of PPMS patients in Argentina. MATERIAL AND METHODS: RelevarEM is a longitudinal, strictly observational registry in Argentina. Clinical and epidemiological data from PPMS patients were described. RESULTS: There were 144 cases of PPMS. They represented 7% of MS patients. The mean age was 44.1 years. The female:male ratio was 1.08. The mean Expanded Disability Status Scale (EDSS) score was 5.5 and the mean disease evolution time was 10.6 years. Oligoclonal bands were found in 72.9%. At the time of diagnosis, magnetic resonance imaging showed spinal cord lesions in 82.6% and contrast-enhancing brain lesions in 18.1% of patients. Almost one third of patients were treated with a disease-modifying drug, and ocrelizumab was the most frequently used (55.8%). CONCLUSIONS: PPMS is an infrequent subtype of MS and its recognition is of the highest importance as it has its own evolution, treatment, and prognosis. The importance of our research resides in providing local data and contributing to a better understanding of PPMS and its treatment in Latin America.

Consensus recommendations for family planning and pregnancy in multiple sclerosis in argentina.

BACKGROUND: Multiple sclerosis (MS) is the most common chronic immune-mediated neurological disorder in young adults, more frequently found in women than in men. Therefore, pregnancy-related issues have become an object of concern for MS professionals and patients. The aim of this work was to review the existing data to develop the first Argentine consensus for family planning and pregnancy in MS patients. METHODS: A panel of expert neurologists from Argentina engaged in the diagnosis and care of MS patients met both virtually and in person during 2019 to carry out a consensus recommendation for family planning and pregnancy in MS. To achieve consensus, the procedure of the "formal consensus-RAND/UCLA method" was used. RESULTS: Recommendations were established based on published evidence and expert opinion focusing on pre-pregnancy counseling, pregnancy, and postpartum issues. CONCLUSION: The recommendations of these consensus guidelines are intended to optimize the management and treatment of MS patients during their reproductive age in Argentina.

Multiple sclerosis and neuromyelitis optica spectrum disorders in Argentina: comparing baseline data from the Argentinean MS Registry (RelevarEM).

The objective of this study was to describe and compare the baseline epidemiological data of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) patients included in RelevarEM (Clinical Trials registry number NCT03375177). METHODS: RelevarEM is a longitudinal, strictly observational MS and NMOSD registry in Argentina. Epidemiological and comorbidity data from MS and NMOSD patients were described and compared. For comorbidities, the Charlson comorbidity index (CCI) was used to calculate the burden at entry. CCI was stratified in 0 and ≥ 1 and described for the entire cohort. RESULTS: A total of 1588 and 75 MS and NMOSD patients (respectively) were included. For MS patients, the mean age was 42 ± 7 years, female sex 65.3%, mean EDSS 2, and mean disease duration 8 ± 6 years. In NMOSD, the mean age was 40 ± 7 years, female sex 78.7%, mean disease duration 5 ± 3.5 years, and mean EDSS 2.5. The most frequent MS phenotype was RRMS in 82.4%. In MS, the CCI was 0 in 85.8.2% while ≥ 1 was in 14.2% of patients. Regarding phenotype stratification, CCI ≥ 1 was 3.9% in CIS, 13.5% in RRMS, 28.7% in SPMS, and 17.4% in PPMS (p < 0.001 between groups). In NMOSD, the CCI was 0 in 64% while ≥ 1 was in 36%. The MS/NMOSD ratio found was 21/1. CONCLUSIONS: This is the first analysis of the longitudinal Argentinean registry of MS and NMOSD describing and comparing conditions that contributes to provide reliable real-world data in the country.

Changes in the Multiple Sclerosis Treatment Paradigm. What Do We Do Now and What Were We Doing Before?

BACKGROUND AND PURPOSE: The number of disease-modifying drugs (DMDs) available for treating relapsing-remitting multiple sclerosis is increasing. Numerous drugs have been approved since 2010 in South America, which has increased the complexity of the treatment algorithm. The aim of this study was to determine the changes in multiple sclerosis treatments relative to the underlying causes and the availability of new DMDs in Argentina. METHODS: A descriptive retrospective study was carried out on a group of 59 patients diagnosed with RRMS who use more than one DMD. RESULTS: The first treatment switch occurred before 2010 in 27% of the patients and after 2010 in the other 73%. Efficacy was the main reason for switching during both periods. A second treatment switch was required in 25% of the patients, with this occurring after 2010 in 86.6% of them. Interferon was the most-used drug before 2010 and fingolimod was the most-used drug thereafter. CONCLUSIONS: We have identified that the tendency for treatment changes has increased following the arrival of new drugs. Efficacy has been the main cause of these changes.

Drug assessment by a Pharmacy and Therapeutics committee: from drug selection criteria to use in clinical practice.

BACKGROUND: In Spain, hospital medicines are assessed and selected by local Pharmacy and Therapeutics committees (PTCs). Of all the drugs assessed, cancer drugs are particularly important because of their budgetary impact and the sometimes arguable added value with respect to existing alternatives. This study analyzed the PTC drug selection process and the main objective was to evaluate the degree of compliance of prescriptions for oncology drugs with their criteria for use. METHODS: This was a retrospective observational study (May 2007 to April 2010) of PTC-assessed drugs. The variables measured to describe the committee's activity were number of drugs assessed per year and number of drugs included in any of these settings: without restrictions, with criteria for use, and not included in formulary. These drugs were also analyzed by therapeutic group. To assess the degree of compliance of prescriptions, a score was calculated to determine whether prescriptions for bevacizumab, cetuximab, trastuzumab, and bortezomib were issued in accordance with PTC drug use criteria. RESULTS: The PTC received requests for inclusion of 40 drugs, of which 32 were included in the hospital formulary (80.0%). Criteria for use were established for 28 (87.5%) of the drugs included. In total, 293 patients were treated with the four cancer drugs in eight different therapeutic indications. The average prescription compliance scores were as follows: bevacizumab, 83% for metastatic colorectal cancer, 100% for metastatic breast cancer, and 82.3% for non-small-cell lung cancer; cetuximab, 62.0% for colorectal cancer and 50% for head and neck cancer; trastuzumab, 95.1% for early breast cancer and 82.4% for metastatic breast cancer; and bortezomib, 63.7% for multiple myeloma. CONCLUSION: The degree of compliance with criteria for use of cancer drugs was reasonably high. PTC functions need to be changed so that they can carry out more innovative tasks, such as monitoring conditions for drug use.