Defining a standard set of health outcomes for patients with relapsing-remitting multiple sclerosis.

BACKGROUND: Standardizing health outcomes is challenging in clinical management, but it also holds the potential for creating a healthcare system that is both more effective and efficient. The aim of the present study is to define a standardized set of health outcomes for managing Relapsing-Remitting Multiple Sclerosis (RRMS). METHODS: The project was led and coordinated by a multidisciplinary scientific committee (SC), which included a literature review, a patient-focused group, three nominal group meetings, and two SC meetings. RESULTS: 36 outcome variables were included in the standard set: 24 clinical (including weight, smoking habit, comorbidities, disability, mobility, diagnosis of secondary progressive multiple sclerosis, relapsed-related variables, radiological variables, cognitive status and disease-related symptoms), nine treatment-related (pharmacological and non-pharmacological information), and 3 related to the impact of RRMS on the patient's life (quality of life, pregnancy desire, work-related difficulties). In addition, experts also agreed to collect 10 case-mix variables that may affect but cannot be controlled as part of the management of the condition: 4 sociodemographic (age, sex, race, and employment status) and 6 clinical (height, date of diagnosis and first episode, serological status, early symptoms, and number of relapses pre-diagnosis). CONCLUSION: The information provided through the present standard set of outcome variables can improve the management of RRMS and promote patient-centred quality care.

Best practices in phase III clinical trials on DMTs for multiple sclerosis: a systematic analysis and appraisal of published trials.

BACKGROUND: Great advances have been made in the field of multiple sclerosis (MS) therapy due to the publication of numerous randomised clinical trials (RCTs). In this study, we carried out a critical appraisal of phase III RCTs of disease-modifying therapies (DMTs) for MS published after 2010, intending to identify critical areas of improvement. METHODS: We performed a systematic search of published RCTs on MS from January 2010 until December 2021. RCTs were assessed using an ad-hoc tool. This tool was developed based on existing generic methodological instruments and MS-specific guidelines and methodological papers. It included 14 items grouped in 5 domains: methodological quality, adequacy and measurement of outcomes, adverse event reporting, applicability and relevance of results, and transparency and conflict of interest. RESULTS: We identified 31 phase III RCTs. Most of them were fully compliant in terms of sample size (87%), randomisation (68%), blinding (61%), participant selection (68%), adverse event reporting (84%) and clinical relevance (52%). Only a few were compliant in terms of participant description (6%), comparison (42%), attrition bias (26%), adequacy of outcome measures (26%), applicability (23%), transparency (36%) and conflict of interest (6%). None were compliant in terms of analysis and reporting of outcomes. The most common limitations related to the absence of comorbidity data, unjustified use of placebo, inadequacy of outcomes design and absence of protocol and/or prospective registration. CONCLUSIONS: RCTs for DMTs in MS have relevant and frequent limitations. These should be addressed to enhance their quality, transparency and external validity.

Effectiveness and Safety of Teriflunomide in Relapsing-Remitting Multiple Sclerosis and Improvements in Quality of Life: Results from the Real-World TERICARE Study.

INTRODUCTION: Teriflunomide is a once-daily oral immunomodulator approved for relapsing forms of multiple sclerosis (MS) or relapsing-remitting multiple sclerosis (RRMS; depending on the local label), based on extensive evidence from clinical trials and a real-world setting on efficacy, tolerability and patient-reported benefits. The TERICARE study assessed the impact of teriflunomide treatment over 2 years on health-related quality of life (HRQoL) and some of the most common and disabling symptoms of MS, such as fatigue and depression. METHODS: This prospective observational study in Spain included RRMS patients treated with teriflunomide for ≤ 4 weeks. The following patient-reported outcomes (PROs) were collected at baseline and every 6 months for 2 years: the 29-item Multiple Sclerosis Impact Scale version 2 (MSIS-29), the 21-item Modified Fatigue Impact Scale (MFIS-21), the Beck Depression Inventory (BDI-II), the Short Form (SF)-Qualiveen and the Treatment Satisfaction Questionnaire for Medication v1.4 (TSQM). Annualised relapse rate (ARR), disability progression according to the Expanded Disability Status Scale (EDSS), and no evidence of disease activity (NEDA-3) were also assessed. RESULTS: A total of 325 patients were analysed. Patients had a mean (SD) age of 43.2 years (10.4), a mean baseline EDSS score of 1.75 (1.5), a mean number of relapses in the past 2 years of 1.5 (0.7), and 64% had received prior disease-modifying therapy (DMT). Patients showed significant improvements in the psychological domain of MSIS-29 from 35.9 (26.6) at baseline to 29.4 (25.5) at 18 months (p = 0.004) and 29.0 (24.6) at 24 months (p = 0.002). Levels of fatigue and depression were also reduced. After 2 years of treatment with teriflunomide, ARR was reduced to 0.17 (95% CI 0.14-0.21) from the baseline of 0.42 (95% CI 0.38-0.48), representing a 60.1% reduction. Mean EDSS scores remained stable during the study, and 79.9% of patients showed no disability progression. 54.7% of patients achieved NEDA-3 in the first 12 months, which increased to 61.4% during months 12-24. Patients reported increased satisfaction with treatment over the course of the study, regardless of whether they were DMT naive or not. CONCLUSION: Teriflunomide improves psychological aspects of HRQoL and maintains low levels of fatigue and depression. Treatment with teriflunomide over 2 years is effective in reducing ARR and disability progression.

Disease modifying therapy switching in relapsing multiple sclerosis: A Delphi consensus of the demyelinating expert group of the Spanish society of neurology.

BACKGROUND: The increase in available disease modifying therapies (DMTs) for multiple sclerosis has led to greater emphasis on improving treatment sequencing paradigms. This article summarises the opinions from a panel of 25 experts on treatment switching approaches in relapsing multiple sclerosis (RMS). METHODS: A modified Delphi consensus process was carried out to develop clinically relevant statements for aiding treatment decisions in patients with RMS between the 16th January and the 9th October 2019. A sub-group of two experts (core group) carried out an extensive review of the literature and formulated 106 statements for the expert panel to evaluate. RESULTS: From a total number of 106 statements that were submitted to the expert panel for critical evaluation, consensus (at least 80% of the panelists agreed) was reached on 99 of them. These statements cover treatment objectives, reasons for DMT switching, suboptimal response criteria, strategies for treatment change and washout periods. CONCLUSION: The agreed statements provide up-to-date guidance on DMT sequencing for optimal patient management.

SARS-CoV-2 Infection in Multiple Sclerosis: Results of the Spanish Neurology Society Registry.

OBJECTIVE: To understand COVID-19 characteristics in people with multiple sclerosis (MS) and identify high-risk individuals due to their immunocompromised state resulting from the use of disease-modifying treatments. METHODS: Retrospective and multicenter registry in patients with MS with suspected or confirmed COVID-19 diagnosis and available disease course (mild = ambulatory; severe = hospitalization; and critical = intensive care unit/death). Cases were analyzed for associations between MS characteristics and COVID-19 course and for identifying risk factors for a fatal outcome. RESULTS: Of the 326 patients analyzed, 120 were cases confirmed by real-time PCR, 34 by a serologic test, and 205 were suspected. Sixty-nine patients (21.3%) developed severe infection, 10 (3%) critical, and 7 (2.1%) died. Ambulatory patients were higher in relapsing MS forms, treated with injectables and oral first-line agents, whereas more severe cases were observed in patients on pulsed immunosuppressors and critical cases among patients with no therapy. Severe and critical infections were more likely to affect older males with comorbidities, with progressive MS forms, a longer disease course, and higher disability. Fifteen of 33 patients treated with rituximab were hospitalized. Four deceased patients have progressive MS, 5 were not receiving MS therapy, and 2 were treated (natalizumab and rituximab). Multivariate analysis showed age (OR 1.09, 95% CI, 1.04-1.17) as the only independent risk factor for a fatal outcome. CONCLUSIONS: This study has not demonstrated the presumed critical role of MS therapy in the course of COVID-19 but evidenced that people with MS with advanced age and disease, in progressive course, and those who are more disabled have a higher probability of severe and even fatal disease.

[Management of complications related to intraduodenal infusion of levodopa/carbidopa in patients with Parkinson's disease]. / Manejo de las complicaciones relacionadas con la infusion intraduodenal de levodopa/carbidopa en pacientes con enfermedad de Parkinson.

Continuous infusion of intraduodenal levodopa/carbidopa is an effective treatment that improves the motor complications and the quality of life of patients in the advanced stages of Parkinson's disease. However, it is not free of complications. These may present in the post-operative period following surgery (gastrostomy) or in the long-term during the follow-up period and can be related with the medication (levodopa/carbidopa), the stoma, the gastrostomy or the device (pump, enteral tube, parts of the FREKA system). The aim of this review is to report on the management of the complications that can be observed in patients with advanced Parkinson's disease treated with continuous infusion of intraduodenal levodopa/carbidopa.

TITLE: Manejo de las complicaciones relacionadas con la infusion intraduodenal de levodopa/carbidopa en pacientes con enfermedad de Parkinson.La infusion continua de levodopa/carbidopa intraduodenal es un tratamiento eficaz que mejora las complicaciones motoras y la calidad de vida de los pacientes con enfermedad de Parkinson avanzada. Sin embargo, no esta exento de complicaciones. Estas pueden presentarse en el postoperatorio de la cirugia (gastrostomia) o a largo plazo durante el seguimiento, y pueden estar relacionadas con la medicacion (levodopa/carbidopa), el estoma, la gastrostomia o el dispositivo (bomba, sonda enteral, piezas del sistema FREKA). El objetivo de la presente revision es describir el manejo de las complicaciones que pueden presentar los pacientes con enfermedad de Parkinson avanzada tratados con infusion continua de levodopa/carbidopa intraduodenal.

[Pain in Parkinson's disease: prevalence, characteristics, associated factors, and relation with other non motor symptoms, quality of life, autonomy, and caregiver burden]. / Dolor en la enfermedad de Parkinson: prevalencia, características, factores asociados y relación con otros síntomas no motores, calidad de vida, autonomía y sobrecarga del cuidador.

INTRODUCTION: Pain is one of the most common non motor symptoms in patients with Parkinson's disease (PD). However, it is underrecognized. We examine the prevalence of pain, characteristics, associated factors, and relation with quality of life and autonomy in a consecutive series of PD patients. PATIENTS AND METHODS: Pain was identified according to International Association for the Study of Pain. Brief Pain Inventory and Medical Outcomes Study 36-Item Short Form were used. RESULTS: Of the 159 patients (72.31 ± 8.83 years; 51.3% female), 115 (72.3%) presented pain. Of these, 51.3% reported pain onset before PD-diagnosis, 27.8% two or more pain types, and 53% PD-related pain. Musculoskeletal (74.8%) and radicular-neuropathic (24.3%) were the types of pain most frequent. The 37.4% of the patients with pain did not received analgesic treatment. Depression was an independent predictor of pain (OR = 7.82; 95% CI = 1.151-53.183; p = 0.035). Pain was an independent predictor of worst quality of life (PDQ-39; regression coefficient: 25.53; standard error: 11.852; 95% CI = 1.48-49.57; p = 0.03) and lower autonomy (Schwab and England; regression coefficient: -13.85; standard error: 6.327; 95% CI = -26.58 to -1.2; p = 0.034). CONCLUSIONS: Pain is very frequent in PD patients. It is associated with depression, and predicts a worst quality of life and lower autonomy for the patient.