ABSTRACT
BACKGROUND: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS). OBJECTIVE: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion. METHODS: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUCτ) and maximum plasma concentration (Cmax) for Weeks 8-12. B-cell depletion and safety/tolerability were assessed. RESULTS: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUCτ, 487.7 vs 474.1 h × µg/mL (ratio 1.03); Cmax, 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated. CONCLUSION: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion.
Subject(s)
Multiple Sclerosis , Antibodies, Monoclonal , Antibodies, Monoclonal, Humanized/adverse effects , Humans , Injections, Subcutaneous , Multiple Sclerosis/chemically inducedABSTRACT
BACKGROUND: In this pooled, post hoc analysis of a phase 2 trial and the phase 3 TEMSO, TOWER, and TENERE clinical trials, long-term efficacy and safety of teriflunomide were assessed in subgroups of patients with relapsing multiple sclerosis (MS) defined by prior treatment status. METHODS: Patients were classified according to their prior treatment status in the core and core plus extension periods. In the core period, patients were grouped according to treatment status at the start of the study: treatment naive (no prior disease-modifying therapy [DMT] or DMT > 2 years prior to randomization), previously treated with another DMT (DMT > 6 to ≤24 months prior to randomization), and recently treated with another DMT (DMT ≤6 months prior to randomization). In the core plus extension period, patients were re-baselined to the time of starting teriflunomide 14 mg and grouped according to prior treatment status at that time point. Efficacy endpoints included annualized relapse rate (ARR), probability of confirmed disability worsening (CDW) over 12 weeks, and Expanded Disability Status Scale (EDSS) score. The incidence of adverse events was also assessed. RESULTS: Most frequently received prior DMTs at baseline were glatiramer acetate and interferon beta-1a across treatment groups. Teriflunomide 14 mg significantly reduced ARR versus placebo in the core period, regardless of prior treatment status. In the core and extension periods, adjusted ARRs were low (0.193-0.284) in patients treated with teriflunomide 14 mg across all subgroups. Probability of CDW by Year 4 was similar across subgroups; by Year 5, the percentage of patients with 12-week CDW was similar in treatment-naive patients and patients recently treated with another DMT (33.9 and 33.7%, respectively). EDSS scores were stable over time in all prior-treatment subgroups. There were no new or unexpected safety signals. Limitations include selective bias due to patient attrition, variability in subgroup size, and lack of magnetic resonance imaging outcomes. CONCLUSIONS: The efficacy and safety of teriflunomide 14 mg was similar in all patients with relapsing MS, regardless of prior treatment history. TRIAL REGISTRATION: Phase 2 trial core: NCT01487096 ; Phase 2 trial extension: NCT00228163 ; TEMSO core: NCT00134563 ; TEMSO extension: NCT00803049 ; TOWER: NCT00751881 ; TENERE: NCT00883337 .
Subject(s)
Crotonates/therapeutic use , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Toluidines/therapeutic use , Treatment Outcome , Adult , Female , Follow-Up Studies , Humans , Hydroxybutyrates , Male , Middle Aged , Nitriles , TimeABSTRACT
INTRODUCTION: The risk of SARS-CoV-2 infection or severe coronavirus disease 2019 (COVID-19) has been shown to increase in patients with multiple sclerosis (MS). Vaccination is recommended in this patient population, and the effect of disease-modifying treatments (DMTs) on response to vaccination should be considered. METHODS: This prospective, observational, cross-sectional study investigated humoral response after COVID-19 vaccination as well as possible predictors for response in patients with MS and other neuroinflammatory diseases who received DMTs in routine clinical practice in Spain. Responses were compared versus those seen in healthy controls. RESULTS: After vaccination against COVID-19, most patients with MS developed an immune response comparable to that of healthy individuals. However, approximately half of patients receiving a sphingosine-1-phosphate modulator (SP1-M, fingolimod or siponimod) or a B-cell-depleting agent (aCD20, ocrelizumab or rituximab) did not develop protective antibodies, although patients receiving other DMTs had humoral immune responses comparable to healthy controls. Lymphocyte count was not associated with reduced humoral response in patients receiving an SP1-M or aCD20, whereas, in patients receiving an aCD20 or SP1-M, older age was associated with lower anti-SARS-CoV-2 spike protein immunoglobulin G antibody levels. CONCLUSIONS: Treatment with aCD20 or SP1-M therapies appears to be associated with a lower humoral response to vaccines against SARS-CoV-2. Vaccination prior to initiation of these DMTs should be recommended whenever possible.
ABSTRACT
BACKGROUND: People with secondary progressive multiple sclerosis (pwSPMS) experience increasing disability, which impacts negatively on their health-related quality of life (HRQoL). Our aims were to assess the impact of secondary progressive multiple sclerosis (SPMS) on functional status and HRQoL and describe the clinical profile in this population. METHODS: DISCOVER is an observational, cross-sectional, multicenter study with retrospective data collection in real-world clinical practice in Spain. Sociodemographic and clinical variables, functional and cognitive scales, patient-reported outcomes (PROs), and direct healthcare, and non-healthcare and indirect costs were collected. RESULTS: A total of 297 evaluable pwSPMS with a EDSS score between 3-6.5 participated: 62.3 % were female and 18.9 % had active SPMS. At the study visit, 77 % of them presented an Expanded Disability Scale Score (EDSS) of 6-6.5. Nearly 40 % did not receive any disease-modifying treatment. Regarding the working situation, 61.6 % were inactive due to disability. PROs: 99.3 % showed mobility impairment in EuroQoL-5 Dimensions-5 Levels, and about 60 % reported physical impact on the Multiple Sclerosis Impact Scale-29. Fatigue was present in 76.1 %, and almost 40 % reported anxiety or depression. The Symbol Digit Modalities Test was used to assess cognitive impairment; 80 % of the patients were below the mean score. Participants who presented relapses two years before and had high EDSS scores had a more negative impact on HRQoL. PwSPMS with a negative impact on HRQoL presented a higher cost burden, primarily due to indirect costs. CONCLUSIONS: PwSPMS experience a negative impact on their HRQoL, with a high physical impact, fatigue, cognitive impairment, and a high burden of indirect costs.
ABSTRACT
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.
ABSTRACT
BACKGROUND: Pregnancy planning in women with highly active multiple sclerosis (HAMS) who need a high-efficacy disease-modifying therapy (heDMT) currently requires a careful risk-benefit evaluation. This includes minimizing fetal drug toxicity and preventing MS reactivation. We describe our experience with natalizumab in women with HAMS and unplanned pregnancy by implementing a clinical practice protocol (NAP-30) designed to maintain the effectiveness of natalizumab during pregnancy, reduce fetal exposure and prevent complications. METHODS: This was an observational retrospective study including women with HAMS on active treatment with natalizumab who became unexpectedly pregnant in the period 2018-2021 and continued this treatment during pregnancy according to the NAP-30 protocol. MS clinical and radiological variables were analyzed before and during pregnancy and in the postpartum period, along with maternal and fetal toxicity during pregnancy and safety findings in newborns. We also describe the NAP-30 protocol, which includes the use of a bridging dose to adjust and maintain natalizumab infusions every 6 weeks during pregnancy up to week 30 and scheduled delivery at week 40. RESULTS: Six women (one in her first gestation) with a median age of 31.5 years at the onset of pregnancy (min-max: 24-37 years) were included. All were negative for anti-John Cunningham virus (JCV) antibodies and were on treatment with intravenous natalizumab 300 mg every 4 weeks. At the time of conception, three patients had received 12, 17 and 53 infusions of natalizumab, respectively, while for the remaining three patients natalizumab was their first DMT (two patients had received 6 infusions and one patient had received 3 infusions of natalizumab). All six patients received 6 doses of natalizumab during pregnancy according to the NAP-30 protocol. After delivery, all six patients restarted natalizumab every 4 weeks (median: 3 days; range: 2-4 days). No patients had relapses during pregnancy or at 6 months postpartum, nor did they develop any general health or laboratory abnormalities. The MRI scan performed at 4-6 months postpartum showed no new T2 lesions or gadolinium-enhancing lesions. No miscarriages or threatened miscarriages were reported. One of the patients underwent elective preterm delivery at week 35 after mild-to-moderate anemia was detected by fetal Doppler scan. The newborn had low birth weight (2080 g) and mild anemia, which resolved within two months with oral iron supplementation. The other infants were born with normal birth weight and showed no blood count abnormalities. After a median follow-up of 10 months, all six babies showed normal development with no complications detected. CONCLUSIONS: Based on our experience, the implementation of the NAP-30 protocol in women with HAMS and unplanned pregnancy undergoing treatment with natalizumab allows the continuation of natalizumab during pregnancy, with a very favorable clinical and radiological effectiveness and maternal-fetal safety profile during pregnancy and postpartum. Both in pregnancy with HAMS and in general, and particularly for successful implementation of the NAP-30 protocol, obstetric support and monitoring is essential for adequate pregnancy management.
Subject(s)
Multiple Sclerosis , Adult , Female , Gadolinium/therapeutic use , Humans , Immunologic Factors/adverse effects , Infant , Infant, Newborn , Iron , Multiple Sclerosis/drug therapy , Natalizumab/adverse effects , Observational Studies as Topic , Pregnancy , Retrospective StudiesABSTRACT
Background: Early identification of the transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive MS (SPMS) can be challenging for clinicians, as diagnostic criteria for SPMS are primarily based on physical disability and a holistic interpretation. Objective: To establish a consensus on patient monitoring to identify promptly disease progression and the most useful clinical and paraclinical variables for early identification of disease progression in MS. Methods: A RAND/UCLA Appropriateness Method was used to establish the level of agreement among a panel of 15 medical experts in MS. Eighty-three items were circulated to the experts for confidential rating of the grade of agreement and recommendation. Consensus was defined when ≥66% agreement or disagreement was achieved. Results: Consensus was reached in 72 out of 83 items (86.7%). The items addressed frequency of follow-up visits, definition of progression, identification of clinical, cognitive, and radiological assessments as variables of suspected or confirmed SPMS diagnosis, the need for more accurate assessment tools, and the use of promising molecular and imaging biomarkers to predict disease progression and/or diagnose SPMS. Conclusion: Consensus achieved on these topics could guide neurologists to identify earlier disease progression and to plan targeted clinical and therapeutic interventions during the earliest stages of SPMS.
ABSTRACT
INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is associated with a reduced health-related quality of life (HRQoL). The purpose of this study was to describe the impact of NMOSD on HRQoL from the patients' perspective and its relationship with other disease factors. METHODS: An observational, cross-sectional study was conducted at 13 neuroimmunology clinics in Spain. Patients with NMOSD diagnosis (2015 Wingerchuk criteria) were included. The 29-item Multiple Sclerosis Impact Scale (MSIS-29) was used to assess the HRQoL. Different questionnaires were used to measure symptom severity, stigma, mood disorders, pain, fatigue, and difficulties in the workplace. Factors that impact HRQoL were identified by Spearman's correlation and multivariate linear regression analysis. RESULTS: Seventy-one patients were included (mean age 47.4 ± 14.9 years, 80.3% female, mean time since disease onset 9.9 ± 8.1 years). The median Expanded Disability Status Scale score was 3.0 (1.5-4.5). The mean (± SD) physical and psychological MSIS-29 sub-scores were 41.9 ± 16.8 and 20.9 ± 8.3, respectively. Fatigue and body pain were the most prevalent symptoms. Depressive symptoms were found in 44.3% (n = 31) of patients. The physical MSIS-29 dimension showed the highest correlation with symptom severity (ρ = 0.85584, p < 0.0001), whereas the highest correlations for psychological MSIS-29 dimension were pain, MSIS-29 physical dimension, and depression (ρ = 0.76487, 0.72779, 0.71380; p < 0.0001, respectively). Pain was a predictor of both dimensions of MSIS-29. CONCLUSION: Fatigue, pain, and depressive symptoms are frequent problems among patients with NMOSD, impacting on their quality of life. Assessment of patient-oriented outcomes may be useful to achieve a holistic approach, allowing early specific interventions.
ABSTRACT
Background: The frequency of cognitive impairment (CI) reported in neuromyelitis optica spectrum disorder (NMOSD) is highly variable, and its relationship with demographic and clinical characteristics is poorly understood. We aimed to describe the cognitive profile of NMOSD patients, and to analyse the cognitive differences according to their serostatus; furthermore, we aimed to assess the relationship between cognition, demographic and clinical characteristics, and other aspects linked to health-related quality of life (HRQoL). Methods: This cross-sectional study included 41 patients (median age, 44 years; 85% women) from 13 Spanish centres. Demographic and clinical characteristics were collected along with a cognitive z-score (Rao's Battery) and HRQoL patient-centred measures, and their relationship was explored using linear regression. We used the Akaike information criterion to model which characteristics were associated with cognition. Results: Fourteen patients (34%) had CI, and the most affected cognitive domain was visual memory. Cognition was similar in AQP4-IgG-positive and -negative patients. Gender, mood, fatigue, satisfaction with life, and perception of stigma were associated with cognitive performance (adjusted R2 = 0.396, p < 0.001). Conclusions: The results highlight the presence of CI and its impact on HRQoL in NMOSD patients. Cognitive and psychological assessments may be crucial to achieve a holistic approach in patient care.
ABSTRACT
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.
Subject(s)
Multiple Sclerosis , Neurology , Consensus , Delphi Technique , HumansABSTRACT
BACKGROUND: The assessment of self-reported outcomes in neuromyelitis optica spectrum disorder (NMOSD) is limited by the lack of validated disease-specific measures. The SymptoMScreen (SyMS) is a patient-reported questionnaire for measuring symptom severity in different domains affected by multiple sclerosis (MS), but has not been thoroughly evaluated in NMOSD. The aim of this study was to assess the psychometric properties of the SyMS in a sample of patients with NMOSD. METHODS: A non-interventional, cross-sectional study in adult subjects with NMOSD (Wingerchuk 2015 criteria) was conducted at 13 neuroimmunology clinics applying the SyMS. A non-parametric item response theory procedure, Mokken analysis, was performed to assess the underlying dimensional structure and scalability of items and overall questionnaire. All analyses were performed with R (v4.0.3) using the mokken library. RESULTS: A total of 70 patients were studied (mean age: 47.5 ± 15 years, 80% female, mean Expanded Disability Status Scale score: 3.0 [interquartile range 1.5, 4.5]). Symptom severity was low (median SyMS score: 19.0 [interquartile range 10.0, 32.0]). The SyMS showed a robust internal reliability (Cronbach's alpha: 0.90 [95% confidence interval 0.86, 0.93]) and behaved as a unidimensional scale with all items showing scalability coefficients > 0.30. The overall SyMS scalability was 0.45 conforming to a medium scale according to Mokken's criteria. Fatigue and body pain were the domains with the highest scalability coefficients. The SyMS was associated with disability (rho: 0.586), and physical and psychological quality of life (rho: 0.856 and 0.696, respectively). CONCLUSIONS: The SyMS shows appropriate psychometric characteristics and may constitute a valuable and easy-to-implement option to measure symptom severity in patients with NMOSD.
Subject(s)
Neuromyelitis Optica , Psychometrics , Adult , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Quality of Life , Reproducibility of ResultsABSTRACT
BACKGROUND: Perception of stigma was associated with low self-esteem, psychological problems, and decreased health-seeking behavior among patients with different neurological disorders. The purpose of this study was to assess stigmatization and its impact in patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: A non-interventional study was conducted at thirteen neuroimmunology clinics in Spain. Patients with a diagnosis of NMOSD (2015 Wingerchuk criteria) were included. The 8-item Stigma Scale for Chronic Illness (SSCI-8), the Expanded Disability Status Scale (EDSS), the 29-item Multiple Sclerosis Impact Scale (MSIS-29), the Beck Depression Inventory-Fast Screen (BDI-FS), the MOS Pain Effects Scale (MOS-PES) and the Fatigue Impact Scale for Daily Use (D-FIS) were used to assess the perception of stigma, disability, quality of life, mood, pain, and fatigue, respectively. Associations between outcome measures were analyzed using Spearman's rank correlation. RESULTS: Seventy-one patients were studied (mean age: 47.4 years ± 14.9, 81.7% female, mean time since disease onset: 9.9 years ± 8.1). The median EDSS score was 3.0 (interquartile range 1.5, 4.5). Stigma prevalence was 61.4% (n=43). Thirty-one patients (43.6%) had depression. The SSCI-8 score showed a significant correlation with both physical (rho=0.576, p<0.0001) and psychological (rho=0.608, p<0.0001) MSIS-29 scales scores, EDSS score (rho=0.349, p=0.0033), BDI-FS score (rho= 0.613, p<0.0001), MOS-PES score (rho= 0.457, p<0.0001), and D-FIS score (rho=0.556, p<0.0001). CONCLUSION: Stigma is a common phenomenon affecting over 6 out of 10 patients with NMOSD. Understanding stigma may be useful to develop educational strategies improving NMOSD knowledge.
ABSTRACT
The advent of cellular reprogramming technology converting somatic cells into induced pluripotent stem cells (iPSCs) has revolutionized our understandings of neurodegenerative diseases that are otherwise hard to access and model. Multiple Sclerosis (MS) is a chronic demyelinating, inflammatory disease of central nervous system eventually causing neuronal death and accompanied disabilities. Here, we report the generation of several relapsing-remitting MS (RRMS) and primary progressive MS (PPMS) iPSC lines from MS patients along with their age matched healthy controls from peripheral blood mononuclear cells (PBMC). These patient specific iPSC lines displayed characteristic embryonic stem cell (ESC) morphology and exhibited pluripotency marker expression. Moreover, these MS iPSC lines were successfully differentiated into neural progenitor cells (NPC) after subjecting to neural induction. Furthermore, we identified the elevated expression of cellular senescence hallmarks in RRMS and PPMS neural progenitors unveiling a novel drug target avenue of MS pathophysiology. Thus, our study altogether offers both RRMS and PPMS iPSC cellular models as a good tool for better understanding of MS pathologies and drug testing.
Subject(s)
Induced Pluripotent Stem Cells , Multiple Sclerosis, Chronic Progressive , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Humans , Leukocytes, MononuclearABSTRACT
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.
Subject(s)
COVID-19/physiopathology , Immunocompromised Host , Immunosuppressive Agents/administration & dosage , Multiple Sclerosis, Chronic Progressive/drug therapy , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Registries , Severity of Illness Index , Adult , Age Factors , COVID-19/epidemiology , Comorbidity , Female , Humans , Immunosuppressive Agents/adverse effects , Male , Middle Aged , Multiple Sclerosis, Chronic Progressive/epidemiology , Multiple Sclerosis, Relapsing-Remitting/epidemiology , Neurology , Retrospective Studies , Risk Factors , Sex Factors , Societies, Medical , SpainABSTRACT
BACKGROUND: Natalizumab (NTZ) is a disease-modifying treatment (DMT) in multiple sclerosis (MS) whose discontinuation can produce a "rebound effect", consisting of severe clinical deterioration and/or evidence of disease reactivation on magnetic resonance imaging (MRI). OBJECTIVE: To analyze the efficacy of two treatment schedules with intravenous methylprednisolone (IVMP) administered during the washout period of natalizumab (i.e., before starting another DMT) in preventing the rebound phenomenon. METHODS: Five-year retrospective study of NTZ withdrawals after at least 24 uninterrupted doses. Two IVMP schedules were tested. In schedule 1 (3-month washout), 1, 2, and 3 g of IVMP were administered on the first, second, and third month respectively. In schedule 2 (2-month washout), 1 and 2 g of IVMP were administered on the first and second month respectively. A new DMT was started 10 days after the end of each schedule. Rebound was defined as at least one clinical relapse plus rebound activity on MRI (>5 gadolinium-enhanced lesions and a number of new/T2-enhanced and/or gadolinium-enhanced lesions greater than before initiation of NTZ) during washout or at 6 months after new DMT initiation (6M-DMT). Clinical and MRI evaluations were performed at 3, 6, 12, and 24 months after initiation of the new DMT. RESULTS: Fifty patients (68% women) were included, with a mean (SD) age of 37.76 (10.88) years and pre-NTZ annualized relapse rate (ARR) of 1.78 (1.04). During NTZ therapy, mean Expanded Disability Status Scale (EDSS) score was 3.7 (1.73) and ARR was 0.23 (0.39). The ARR (mean of both schedules) was 0.1 (0.71) during washout and 0.32 (0.84) at 6M-DMT. Rebound was observed in 10% of cases (n = 5), with no significant clinical or radiological differences (p>0.05) between the two IVMP schedules. Rebound was observed in younger patients and was associated with new MRI lesions and higher ARR at 3M-DMT and 6M-DMT respectively, with no difference in EDSS after 2 years of follow-up. Neither the ARR before NTZ initiation nor the choice of new DMT after NTZ discontinuation was associated with development of rebound effect. CONCLUSIONS: Both IVMP schedules were well tolerated during NTZ washout and rebound was observed in only 10% of cases. In our experience, administration of IVMP during NTZ washout could reduce the possibility of a rebound effect.
Subject(s)
Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Adult , Female , Humans , Magnetic Resonance Imaging , Male , Methylprednisolone , Multiple Sclerosis/diagnostic imaging , Multiple Sclerosis/drug therapy , Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Natalizumab/adverse effects , Retrospective StudiesABSTRACT
BACKGROUND: The demographics and management of patients with multiple sclerosis (MS) differ across geographical regions, but it is unclear whether/how these differences affect treatment outcomes. The aim of this post-hoc analysis was to assess teriflunomide use and patient-reported outcomes in the United States (US) and the rest of the world (ROW) in the phase 4 Teri-PRO study (NCT01895335). METHODS: In the phase 4, real-world, Teri-PRO study, patients with relapsing forms of MS received teriflunomide for 48 weeks according to local labeling. The primary endpoint was treatment satisfaction measured using the Treatment Satisfaction Questionnaire for Medication Version 1.4 (TSQM 1.4). Secondary endpoints included scores on the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Performance Scale (MSPS), and Patient-Determined Disease Steps (PDDS), and occurrence of adverse events. Primary and secondary endpoints were assessed at baseline and Week 48. An exploratory subgroup analysis assessed PROs in the black patient population. RESULTS: The US and ROW groups included 545 and 455 patients, respectively. The mean age of patients in the ROW group was lower, they had a shorter mean time since first symptoms of MS, and had lower mean EDSS scores at baseline, compared with the US group (all p < 0.0001). Black patients made up 9% of US patients vs 0.2% of ROW patients. TSQM global satisfaction scores and effectiveness, side effects, and convenience subscale scores were significantly improved from baseline to Week 48 (all p < 0.0001). Disability measures were stable from baseline to Week 48 for both groups, despite different baseline level scores between the two groups. The overall proportion of patients who experienced an AE was similar across both groups. Fewer patients in the US group vs the ROW group reported hair thinning (16.1% vs 31.2%). Black patients showed comparable baseline demographics and disease characteristics and similar change over time in PROs compared with the overall US group. CONCLUSION: Patient differences observed at baseline between the US and ROW groups suggest variation in teriflunomide prescribing practices in the real-world Teri-PRO study. Improvement in treatment satisfaction and stability of disability measures were comparable between patients in the US and ROW. This suggests that teriflunomide was effective despite differences in baseline demographics and possible cultural and management differences between these geographical regions.
Subject(s)
Crotonates/therapeutic use , Immunologic Factors/therapeutic use , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Toluidines/therapeutic use , Adult , Female , Humans , Hydroxybutyrates , Male , Middle Aged , Nitriles , Patient Reported Outcome Measures , Prospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Patient-reported outcomes (PROs) can assist clinicians in understanding the impact of disease-modifying therapy (DMT) on the daily lives of patients with multiple sclerosis (MS). With an increased number of DMTs becoming available, patients are now switching treatments more frequently in clinical practice. The effects of switching DMTs on a patient's daily life and their disease course may be reflected in PROs. The global, multicenter, open-label, phase 4 Teri-PRO study (NCT01895335), which was conducted in routine clinical practice, previously showed statistically and clinically significant increases in patient-reported treatment satisfaction in patients switching to teriflunomide from other DMTs. The impact of switching to teriflunomide from other DMTs on treatment satisfaction and a range of additional PROs was also evaluated. METHODS: Patients with relapsing forms of MS (Nâ¯=â¯1000) received teriflunomide for 48 weeks per local labeling. Outcomes assessed in this analysis included treatment satisfaction (as measured by Treatment Satisfaction Questionnaire for Medication [Version 1.4]), disability worsening (as measured using the Expanded Disability Status Scale [EDSS] score, the Patient-Determined Disease Steps scale, and the Multiple Sclerosis Performance Scale), cognition (as measured using the Symbol Digit Modalities Test [SDMT]), treated relapses, quality of life (as measured by the Multiple Sclerosis International Quality of Life [MusiQoL] questionnaire and the Stern Leisure Activity Scale), and safety/tolerability over the course of the study in the subgroup of patients switching to teriflunomide from another DMT (n = 594). RESULTS: Patients reported significant improvements in treatment satisfaction scores following the switch to teriflunomide regardless of the reason for treating with teriflunomide (Global Satisfaction, disease worsening: baseline, 46.0, Week 48, 65.1; convenience: baseline, 57.4, Week 48, 72.4; intolerance: baseline, 50.9, Week 48, 71.1; side effects: baseline, 49.7, Week 48, 67.2; P < 0.0001 in all comparisons). These patients also showed improvement or stability in PROs evaluating disability worsening, cognition, and quality of life (EDSS: baseline, 3.1, Week 48, 3.0; SDMT: baseline, 0.975, Week 48, 0.978; MusiQoL: baseline, 67.5, Week 48, 69.5). The safety and tolerability profile of teriflunomide was consistent with that observed in other teriflunomide clinical trials. CONCLUSION: This analysis of the Teri-PRO study demonstrates the value of switching to teriflunomide from other DMTs in a real-world, clinical practice setting. The high levels of treatment satisfaction associated with teriflunomide in Teri-PRO may lead to improved adherence and thus improved outcomes.
Subject(s)
Crotonates/pharmacology , Drug Substitution , Immunologic Factors/pharmacology , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Patient Reported Outcome Measures , Patient Satisfaction , Toluidines/pharmacology , Adult , Crotonates/administration & dosage , Crotonates/adverse effects , Female , Humans , Hydroxybutyrates , Immunologic Factors/administration & dosage , Immunologic Factors/adverse effects , Male , Middle Aged , Nitriles , Prospective Studies , Toluidines/administration & dosage , Toluidines/adverse effectsABSTRACT
BACKGROUND: Patient-reported outcomes (PROs) provide clinicians with further understanding of the impact of treatment on patients' daily lives. In addition, real-world studies, which employ broader inclusion criteria than randomized trials, may help to inform prescribing decisions when selecting a disease-modifying therapy (DMT) to treat relapsing forms of MS (RMS). We sought to use PROs to determine patient treatment satisfaction and other treatment outcomes, and report safety and tolerability associated with teriflunomide, in the global, phase 4 Teri-PRO study (NCT01895335). METHODS: Patients with RMS (N = 1000) received teriflunomide for 48 weeks per local labeling. The primary endpoint was Global Satisfaction with teriflunomide treatment measured by the Treatment Satisfaction Questionnaire for Medication (TSQM, V1.4). Secondary endpoints included TSQM scores at Week (W)48 vs baseline in patients switching to teriflunomide from other DMTs ('switchers'), additional PROs, and safety. RESULTS: Mean TSQM Global Satisfaction score at W48 was high (68.2). Switchers reported significant improvements across all four TSQM domains at W48 vs baseline (all p < 0.0001). Adverse events were consistent with teriflunomide clinical trials. CONCLUSION: Patients reported high treatment satisfaction with teriflunomide, with switchers also reporting improved treatment satisfaction vs baseline. High treatment satisfaction in patients with RMS may lead to improved adherence, and hence treatment outcomes.
Subject(s)
Crotonates/therapeutic use , Immunologic Factors/therapeutic use , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Patient Reported Outcome Measures , Toluidines/therapeutic use , Crotonates/adverse effects , Disability Evaluation , Drug Substitution , Female , Humans , Hydroxybutyrates , Immunologic Factors/adverse effects , Kaplan-Meier Estimate , Male , Middle Aged , Multiple Sclerosis, Relapsing-Remitting/psychology , Nitriles , Patient Satisfaction , Prospective Studies , Quality of Life , Surveys and Questionnaires , Toluidines/adverse effects , Treatment OutcomeABSTRACT
61-year-old woman with Neuromyelitis optica (NMO) diagnosis treated with rituximab was referred to our hospital with severe hypovolemic shock and anasarca. The laboratory findings showed marked hemoconcentration and a decrease in total serum protein. She developed a multiple organ failure and died three hours later. We diagnosed the patient as having capillary leak syndrome (CLS). CLS is a very rare condition caused by unexplained episodic capillary hyperpermeability, which can be idiopathic or secondary to some conditions like infection, malignant disease and some drugs like monoclonal antibodies. We reported the first CLS case in NMO patient treated with rituximab.
Subject(s)
Capillary Leak Syndrome/etiology , Immunologic Factors/adverse effects , Neuromyelitis Optica/drug therapy , Rituximab/adverse effects , Capillary Leak Syndrome/diagnosis , Capillary Leak Syndrome/metabolism , Capillary Leak Syndrome/therapy , Diagnosis, Differential , Fatal Outcome , Female , Humans , Immunologic Factors/therapeutic use , Middle Aged , Rituximab/therapeutic useABSTRACT
Objetivo: El objetivo del presente estudio fue evaluar la Calidad de Vida Relacionada con la salud (CVRS) en personas con Esclerosis Múltiple (EM) mediante el cuestionario MSQOL-54 y analizar su relación con la salud de las personas cuidadoras principales a través del cuestionario GHQ-12 y un cuestionario de salud física autopercibida. Metodología: Se evaluó a 115 personas con diagnóstico de EM y a 79 personas cuidadoras principales. Resultados: Los resultados obtenidos señalan la significativa afectación de la CVRS de las personas con EM y su relación con la salud de las personas cuidadoras principales. Se encontraron relaciones significativas entre la salud física y mental de la persona con EM y un mayor número de enfermedades, peor salud mental y menor autopercepción de salud en la persona cuidadora. Conclusiones: Los resultados obtenidos señalan la significativa afectación de la CVRS de las personas con EM y su relación directa con la salud de las personas cuidadoras principales. (AU)