RESUMEN

Progressive gait impairment is common among aging adults. Remote phenotyping of gait during daily living has the potential to quantify gait alterations and evaluate the effects of interventions that may prevent disability in the aging population. Here, we developed ElderNet, a self-supervised learning model for gait detection from wrist-worn accelerometer data. Validation involved two diverse cohorts, including over 1000 participants without gait labels, as well as 83 participants with labeled data: older adults with Parkinson's disease, proximal femoral fracture, chronic obstructive pulmonary disease, congestive heart failure, and healthy adults. ElderNet presented high accuracy (96.43 ± 2.27), specificity (98.87 ± 2.15), recall (82.32 ± 11.37), precision (86.69 ± 17.61), and F1 score (82.92 ± 13.39). The suggested method yielded superior performance compared to two state-of-the-art gait detection algorithms, with improved accuracy and F1 score (p < 0.05). In an initial evaluation of construct validity, ElderNet identified differences in estimated daily walking durations across cohorts with different clinical characteristics, such as mobility disability (p < 0.001) and parkinsonism (p < 0.001). The proposed self-supervised method has the potential to serve as a valuable tool for remote phenotyping of gait function during daily living in aging adults, even among those with gait impairments.

Asunto(s)

RESUMEN

Background: The brain reserve hypothesis posits that larger maximal lifetime brain growth (MLBG) may confer protection against physical disability in multiple sclerosis (MS). Larger MLBG as a proxy for brain reserve, has been associated with reduced progression of physical disability in patients with early MS; however, it is unknown whether this association remains once in the secondary progressive phase of MS (SPMS). Our aim was to assess whether larger MLBG is associated with decreased physical disability progression in SPMS. Methods: We conducted a post hoc analysis of participants in the MS-Secondary Progressive Multi-Arm Randomisation Trial (NCT01910259), a multicentre randomised placebo-controlled trial of the neuroprotective potential of three agents in SPMS. Physical disability was measured by Expanded Disability Status Scale (EDSS), 9-hole peg test (9HPT) and 25-foot timed walk test (T25FW) at baseline, 48 and 96 weeks. MLBG was estimated by baseline intracranial volume (ICV). Multivariable time-varying Cox regression models were used to investigate the association between MLBG and physical disability progression. Results: 383 participants (mean age 54.5 years, 298 female) were followed up over 96 weeks. Median baseline EDSS was 6.0 (range 4.0-6.5). Adjusted for covariates, larger MLBG was associated with a reduced risk of EDSS progression (HR 0.84,95% CI:0.72 to 0.99;p=0.04). MLBG was not independently associated with time to progression as measured by 9HPT or T25FW. Conclusion: Larger MLBG is independently associated with physical disability progression over 96 weeks as measured by EDSS in SPMS. This suggests that MLBG as a proxy for brain reserve may continue to confer protection against disability when in the secondary progression phase of MS. Trail registration number: NCT01910259.

RESUMEN

Autologous hematopoietic stem cell transplantation (HSCT) is associated with 5-year treatment-free remissions in approximately 80% of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who failed or were dependent on intravenous immunoglobulin and or plasmapheresis. Autologous HSCT was associated with significant improvement in strength, independent ambulation, quality of life, nerve conduction velocity, and compound muscle action potential amplitude. The results of HSCT are dependent on proper patient selection, i.e., the right diagnosis and the right stage of the disease. An important caveat is that a significant number of patients with a CIDP diagnostic label are found upon further workup have a peripheral neuropathy of another etiology. Patients undergoing HSCT for CIDP should be reevaluated before HSCT to confirm the diagnosis and those who fail HSCT should be reevaluated for a diagnosis other than CIDP.

Asunto(s)

RESUMEN

Autologous hematopoietic stem cell transplantation (AHSCT) is a therapeutic procedure for autoimmune diseases which suppresses inflammation and resets the immune system, thereby halting disease activity and disability progression in treatment-resistant patients. This chapter reviews existing guidelines and health economic evaluations of AHSCT for multiple sclerosis (MS) and presents a cost-utility analysis from the UK NHS and personal social services perspective comparing AHSCT with disease-modifying therapies (DMTs) in patients with highly active relapsing-remitting MS (RRMS) based on the only published randomized controlled trial, "MIST," in this population. Over a 5-year time horizon, AHSCT was dominant (more effective and less costly) over the DMTs in MIST. At a threshold of £20,000 per QALY, there was a 100% probability that AHSCT was cost-effective. This result is explained by the high ongoing costs of DMTs compared with the up-front cost of AHSCT, combined with the high effectiveness of AHSCT. When compared with natalizumab, the result did not change; AHSCT remained dominant. These results support current guideline recommendations regarding AHSCT for highly active RRMS. The cost-effectiveness of AHSCT in progressive and aggressive MS and other immune-mediated neurologic diseases remains uncertain due to a lack of health economic analyses, reflecting the limited clinical evidence base.

Asunto(s)

RESUMEN

Autologous hematopoietic stem cell transplantation (AHSCT) is emerging as a potent treatment for highly active relapsing remitting multiple sclerosis (RRMS), potentially surpassing the efficacy of traditional disease-modifying therapies (DMTs). Phase II and III randomized controlled trials (RCTs) have demonstrated AHSCT's superiority in reducing relapse rates and delaying disability progression compared to standard DMTs. Despite the evolution of treatment guidelines, questions persist regarding patient selection criteria and optimal conditioning regimens. Notably, ongoing clinical trials in the United Kingdom, the United States, Italy, and Norway aim to address these uncertainties by evaluating the safety, efficacy, and long-term outcomes of AHSCT vs. high efficacy DMTs in both DMT-experienced and treatment-naïve patients with active RRMS or aggressive multiple sclerosis (MS). These trials promise to provide valuable insights into the positioning of AHSCT within the treatment landscape of MS.

Asunto(s)

RESUMEN

Despite the use of 'high efficacy' disease-modifying therapies, disease activity and clinical progression of different immune-mediated neurological diseases continue for some patients, resulting in accumulating disability, deteriorating social and mental health, and high economic cost to patients and society. Although autologous hematopoietic stem cell transplant is an effective treatment modality, it is an intensive chemotherapy-based therapy with a range of short- and long-term side-effects. Chimeric antigen receptor T-cell therapy (CAR-T) has revolutionized the treatment of B-cell and other hematological malignancies, conferring long-term remission for otherwise refractory diseases. However, the toxicity of this treatment, particularly cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, and the complexity of production necessitate the need for a high level of specialization at treating centers. Early-phase trials of CAR-T therapies in immune-mediated B cell driven conditions, such as systemic lupus erythematosus, neuromyelitis optica spectrum disorder and myasthenia gravis, have shown dramatic clinical response with few adverse events. Based on the common physiopathology, CAR-T therapy in other immune-mediated neurological disease, including multiple sclerosis, chronic inflammatory polyradiculopathy, autoimmune encephalitis, and stiff person syndrome, might be an effective option for patients, avoiding the need for long-term immunosuppressant medications. It may prove to be a more selective immunoablative approach than autologous hematopoietic stem cell transplant, with potentially increased efficacy and lower adverse events. In this review, we present the state of the art and future directions of the use of CAR-T in such conditions. ANN NEUROL 2024;96:441-452.

Asunto(s)

RESUMEN

Background: Over the last 3 decades, hematopoietic stem cell transplantation (HSCT) has been successfully used to treat severe and refractory autoimmune diseases (AIDs). A multidisciplinary appraisal of potential benefits and risks by disease and transplant specialists is essential to determine individual suitability for HSCT. Objective: Our aim was to observe that patient-reported outcomes (PROs) and health-related quality of life instruments can capture the unique patient perspective on disease burden and impact of treatment. Methods: Herein, we describe the basis and complexity of end points measuring patient-reported perceptions of efficacy and tolerability used in clinical practice and trials for patients with AIDs undergoing autologous HSCT. Results: PRO measures and patient-reported experience measures are key tools to evaluate the impact and extent of disease burden for patients affected by AIDs. For formal scientific assessment, it is essential that validated general instruments are used, whereas adaptations have resulted in disease-specific instruments that may help guide tailored interventions. An additional approach relates to qualitative evaluations, from carefully structured qualitative research to informal narratives, as patient stories. The patients' subjectively reported responses to HSCT may be influenced by their preprocedure expectations and investment in the HSCT journey. Conclusions: The complexity of AIDs advocates for individualized and multidisciplinary approach to positively affect the patient journey. PROs and health-related quality of life need to be collected using validated instruments in clinical practice and trials to enable robustness of data and to ensure the impact of the intervention is comprehensively assessed, addressing the main questions and needs of the involved stakeholders.

RESUMEN

BACKGROUND: Wrist-worn inertial sensors are used in digital health for evaluating mobility in real-world environments. Preceding the estimation of spatiotemporal gait parameters within long-term recordings, gait detection is an important step to identify regions of interest where gait occurs, which requires robust algorithms due to the complexity of arm movements. While algorithms exist for other sensor positions, a comparative validation of algorithms applied to the wrist position on real-world data sets across different disease populations is missing. Furthermore, gait detection performance differences between the wrist and lower back position have not yet been explored but could yield valuable information regarding sensor position choice in clinical studies. OBJECTIVE: The aim of this study was to validate gait sequence (GS) detection algorithms developed for the wrist position against reference data acquired in a real-world context. In addition, this study aimed to compare the performance of algorithms applied to the wrist position to those applied to lower back-worn inertial sensors. METHODS: Participants with Parkinson disease, multiple sclerosis, proximal femoral fracture (hip fracture recovery), chronic obstructive pulmonary disease, and congestive heart failure and healthy older adults (N=83) were monitored for 2.5 hours in the real-world using inertial sensors on the wrist, lower back, and feet including pressure insoles and infrared distance sensors as reference. In total, 10 algorithms for wrist-based gait detection were validated against a multisensor reference system and compared to gait detection performance using lower back-worn inertial sensors. RESULTS: The best-performing GS detection algorithm for the wrist showed a mean (per disease group) sensitivity ranging between 0.55 (SD 0.29) and 0.81 (SD 0.09) and a mean (per disease group) specificity ranging between 0.95 (SD 0.06) and 0.98 (SD 0.02). The mean relative absolute error of estimated walking time ranged between 8.9% (SD 7.1%) and 32.7% (SD 19.2%) per disease group for this algorithm as compared to the reference system. Gait detection performance from the best algorithm applied to the wrist inertial sensors was lower than for the best algorithms applied to the lower back, which yielded mean sensitivity between 0.71 (SD 0.12) and 0.91 (SD 0.04), mean specificity between 0.96 (SD 0.03) and 0.99 (SD 0.01), and a mean relative absolute error of estimated walking time between 6.3% (SD 5.4%) and 23.5% (SD 13%). Performance was lower in disease groups with major gait impairments (eg, patients recovering from hip fracture) and for patients using bilateral walking aids. CONCLUSIONS: Algorithms applied to the wrist position can detect GSs with high performance in real-world environments. Those periods of interest in real-world recordings can facilitate gait parameter extraction and allow the quantification of gait duration distribution in everyday life. Our findings allow taking informed decisions on alternative positions for gait recording in clinical studies and public health. TRIAL REGISTRATION: ISRCTN Registry 12246987; https://www.isrctn.com/ISRCTN12246987. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2021-050785.

RESUMEN

Progressive gait impairment is common in aging adults. Remote phenotyping of gait during daily living has the potential to quantify gait alterations and evaluate the effects of interventions that may prevent disability in the aging population. Here, we developed ElderNet, a self-supervised learning model for gait detection from wrist-worn accelerometer data. Validation involved two diverse cohorts, including over 1,000 participants without gait labels, as well as 83 participants with labeled data: older adults with Parkinson's disease, proximal femoral fracture, chronic obstructive pulmonary disease, congestive heart failure, and healthy adults. ElderNet presented high accuracy (96.43 ± 2.27), specificity (98.87 ± 2.15), recall (82.32 ± 11.37), precision (86.69 ± 17.61), and F1 score (82.92 ± 13.39). The suggested method yielded superior performance compared to two state-of-the-art gait detection algorithms, with improved accuracy and F1 score (p < 0.05). In an initial evaluation of construct validity, ElderNet identified differences in estimated daily walking durations across cohorts with different clinical characteristics, such as mobility disability (p < 0.001) and parkinsonism (p < 0.001). The proposed self-supervised gait detection method has the potential to serve as a valuable tool for remote phenotyping of gait function during daily living in aging adults.

RESUMEN

BACKGROUND: Natalizumab was not shown to modify disability in progressive multiple sclerosis (MS). This matched observational study compared the effectiveness of autologous haematopoietic stem cell transplantation (AHSCT) with natalizumab in progressive MS. METHODS: Patients with primary/secondary progressive MS from seven AHSCT MS centres and the MSBase registry, treated with AHSCT or natalizumab, were matched on a propensity score derived from sex, age, Expanded Disability Status Scale (EDSS), number of relapses 12/24 months before baseline, time from MS onset, the most effective prior therapy and country. The pairwise-censored groups were compared on hazards of 6-month confirmed EDSS worsening and improvement, relapses and annualised relapse rates (ARRs), using Andersen-Gill proportional hazards models and conditional negative binomial model. RESULTS: 39 patients treated with AHSCT (37 with secondary progressive MS, mean age 37 years, EDSS 5.7, 28% with recent disability progression, ARR 0.54 during the preceding year) were matched with 65 patients treated with natalizumab. The study found no evidence for difference in hazards of confirmed EDSS worsening (HR 1.49, 95% CI 0.70 to 3.14) and improvement (HR 1.50, 95% CI 0.22 to 10.29) between AHSCT and natalizumab over up to 4 years. The relapse activity was also similar while treated with AHSCT and natalizumab (ARR: mean±SD 0.08±0.28 vs 0.08±0.25; HR 1.05, 95% CI 0.39 to 2.82). In the AHSCT group, 3 patients experienced febrile neutropenia during mobilisation, 9 patients experienced serum sickness, 6 patients required intensive care unit admission and 36 patients experienced complications after discharge. No treatment-related deaths were reported. CONCLUSION: This study does not support the use of AHSCT to control disability in progressive MS with advanced disability and low relapse activity.

Asunto(s)

RESUMEN

Autoimmune diseases (ADs) are characterized by loss of immune tolerance, high chronicity, with substantial morbidity and mortality, despite conventional immunosuppression (IS) or targeted disease modifying therapies (DMTs), which usually require repeated administration. Recently, novel cellular therapies (CT), including mesenchymal stromal cells (MSC), Chimeric Antigen Receptors T cells (CART) and regulatory T cells (Tregs), have been successfully adopted in ADs. An international expert panel of the European Society for Blood and Marrow Transplantation and the International Society for the Cell and Gene Therapy, reviewed all available evidence, based on the current literature and expert practices, on use of MSC, CART and Tregs, in AD patients with rheumatological, neurological, and gastroenterological indications. Expert-based consensus and recommendations for best practice and quality of patient care were developed to support clinicians, scientists, and their multidisciplinary teams, as well as patients and care providers and will be regularly updated.

RESUMEN

INTRODUCTION: Autologous haematopoietic stem cell transplantation (aHSCT) is increasingly used as treatment for patients with active multiple sclerosis (MS), typically after failure of disease-modifying therapies (DMTs). A recent phase III trial, 'Multiple Sclerosis International Stem Cell Transplant, MIST', showed that aHSCT resulted in prolonged time to disability progression compared with DMTs in patients with relapsing remitting MS (RRMS). However, the MIST trial did not include many of the current high-efficacy DMTs (alemtuzumab, ocrelizumab, ofatumumab or cladribine) in use in the UK within the control arm, which are now offered to patients with rapidly evolving severe MS (RES-MS) who are treatment naïve. There remain, therefore, unanswered questions about the relative efficacy and safety of aHSCT over these high-efficacy DMTs in these patient groups. The StarMS trial (Autologous Stem Cell Transplantation versus Alemtuzumab, Ocrelizumab, Ofatumumab or Cladribine in Relapsing Remitting Multiple Sclerosis) will assess the efficacy, safety and long-term impact of aHSCT compared with high-efficacy DMTs in patients with highly active RRMS despite the use of standard DMTs or in patients with treatment naïve RES-MS. METHODS AND ANALYSIS: StarMS is a multicentre parallel-group rater-blinded randomised controlled trial with two arms. A total of 198 participants will be recruited from 19 regional neurology secondary care centres in the UK. Participants will be randomly allocated to the aHSCT arm or DMT arm in a 1:1 ratio. Participants will remain in the study for 2 years with follow-up visits at 3, 6, 9, 12, 18 and 24 months postrandomisation. The primary outcome is the proportion of patients who achieve 'no evidence of disease activity' during the 2-year postrandomisation follow-up period in an intention to treat analysis. Secondary outcomes include efficacy, safety, cost-effectiveness and immune reconstitution of aHSCT and the four high-efficacy DMTs. ETHICS AND DISSEMINATION: The study was approved by the Yorkshire and Humber-Leeds West Research Ethics Committee (20/YH/0061). Participants will provide written informed consent prior to any study specific procedures. The study results will be submitted to a peer-reviewed journal and abstracts will be submitted to relevant national and international conferences. TRIAL REGISTRATION NUMBER: ISRCTN88667898.

Asunto(s)

RESUMEN

This study aimed to validate a wearable device's walking speed estimation pipeline, considering complexity, speed, and walking bout duration. The goal was to provide recommendations on the use of wearable devices for real-world mobility analysis. Participants with Parkinson's Disease, Multiple Sclerosis, Proximal Femoral Fracture, Chronic Obstructive Pulmonary Disease, Congestive Heart Failure, and healthy older adults (n = 97) were monitored in the laboratory and the real-world (2.5 h), using a lower back wearable device. Two walking speed estimation pipelines were validated across 4408/1298 (2.5 h/laboratory) detected walking bouts, compared to 4620/1365 bouts detected by a multi-sensor reference system. In the laboratory, the mean absolute error (MAE) and mean relative error (MRE) for walking speed estimation ranged from 0.06 to 0.12 m/s and - 2.1 to 14.4%, with ICCs (Intraclass correlation coefficients) between good (0.79) and excellent (0.91). Real-world MAE ranged from 0.09 to 0.13, MARE from 1.3 to 22.7%, with ICCs indicating moderate (0.57) to good (0.88) agreement. Lower errors were observed for cohorts without major gait impairments, less complex tasks, and longer walking bouts. The analytical pipelines demonstrated moderate to good accuracy in estimating walking speed. Accuracy depended on confounding factors, emphasizing the need for robust technical validation before clinical application.Trial registration: ISRCTN - 12246987.

Asunto(s)

RESUMEN

BACKGROUND AND AIMS: In people with relapsing-remitting multiple sclerosis (pwRRMS), data from studies on non-pharmacological factors which may influence relapse risk, other than age, are inconsistent. There is a reduced risk of relapses with increasing age, but little is known about other trajectories in real-world MS care. METHODS: We studied longitudinal questionnaire data from 3885 pwRRMS, covering smoking, comorbidities, disease-modifying therapy (DMT), and patient-reported outcome measures, as well as relapses during the past year. We undertook Rasch analysis, group-based trajectory modelling, and multilevel negative binomial regression. RESULTS: The regression cohort of 6285 data sets from pwRRMS over time showed that being a current smoker was associated with 43.9% greater relapse risk; having 3 or more comorbidities increased risk and increasing age reduced risk. Those diagnosed within the last 2 years showed two distinct trajectories, both reducing in relapse frequency but 25.8% started with a higher rate and took 4 years to reduce to the rate of the second group. In the cohort with at least three data points completed, there were three groups: 73.7% followed a low stable relapse rate, 21.6% started from a higher rate and decreased, and 4.7% had an increasing then decreasing pattern. These different trajectory groups showed significant differences in fatigue, neuropathic pain, disability, health status, quality of life, self-efficacy, and DMT use. CONCLUSIONS: These results provide additional evidence for supporting pwRRMS to stop smoking and underline the importance of timely DMT decisions and treatment initiation soon after diagnosis with RRMS.

Asunto(s)

RESUMEN

Introduction: The clinical assessment of mobility, and walking specifically, is still mainly based on functional tests that lack ecological validity. Thanks to inertial measurement units (IMUs), gait analysis is shifting to unsupervised monitoring in naturalistic and unconstrained settings. However, the extraction of clinically relevant gait parameters from IMU data often depends on heuristics-based algorithms that rely on empirically determined thresholds. These were mainly validated on small cohorts in supervised settings. Methods: Here, a deep learning (DL) algorithm was developed and validated for gait event detection in a heterogeneous population of different mobility-limiting disease cohorts and a cohort of healthy adults. Participants wore pressure insoles and IMUs on both feet for 2.5 h in their habitual environment. The raw accelerometer and gyroscope data from both feet were used as input to a deep convolutional neural network, while reference timings for gait events were based on the combined IMU and pressure insoles data. Results and discussion: The results showed a high-detection performance for initial contacts (ICs) (recall: 98%, precision: 96%) and final contacts (FCs) (recall: 99%, precision: 94%) and a maximum median time error of -0.02 s for ICs and 0.03 s for FCs. Subsequently derived temporal gait parameters were in good agreement with a pressure insoles-based reference with a maximum mean difference of 0.07, -0.07, and <0.01 s for stance, swing, and stride time, respectively. Thus, the DL algorithm is considered successful in detecting gait events in ecologically valid environments across different mobility-limiting diseases.

RESUMEN

Background: We developed a 29-item Questionnaire, Long-term Unmet Needs in MS (LUN-MS) to identify the unmet needs of people with multiple sclerosis (pwMS). Objective: To assess acceptability, test-retest reliability, internal consistency, and validity of the LUN-MS. Methods: Participants completed the LUN-MS and MSIS-29 twice, four weeks apart. Acceptability was assessed by looking at the response rate in each time point. Reliability was calculated by comparing the response during the two time points using Cohen's weighted kappa. Using principal component analysis, the dimensionality of the questionnaire's items was reduced, to five domains and the internal consistency of each domain was assessed using Cronbach's alpha. Concurrent validity was tested by comparing the total LUN-MS score against MSIS-29 and EQ-5D-3L using Pearson's product-moment correlation coefficient. Results: Among 88 participants, rate of completion at time points-1 and 2 was 96 and 80% respectively. Test-retest reliability for individual items was between fair to near-perfect (weighted Cohen's kappa 0.39-0.81). The unmet needs could be divided into five internally consistent domains (Cronbach's alpha 0.83-0.74): neuropsychological, ambulation, physical, interpersonal relationship and informational. Concurrent validity with MSIS-29 (r = 0.705, P < .001) and EQ-5D-3L (r = 0.617, P < .001) were good. Conclusion: LUN-MS is a reliable, valid, and acceptable tool to identify the unmet needs of pwMS.

RESUMEN

INTRODUCTION: Reliable measurement of disability in multiple sclerosis (MS) using a comprehensive, patient self-reported scale, such as the World Health Organization Disability Assessment Schedule (WHODAS) 2.0, would be of clinical and research benefit. METHODS: In the Trajectories of Outcome in Neurological Conditions-MS study, WHODAS 2.0 (WHODAS-36 items for working, WHODAS-32 items if not working, WHODAS-12 items short-form) was examined using Rasch analysis in 5809 people with MS. RESULTS: The 36- and 32-item parallel forms, and the cognitive and physical domains, showed reliability consistent with individual or group use. The 12-item short-form is valid for group use only. Interval level measurement for parametric statistics can be derived from all three scales which showed medium to strong effect sizes for discrimination across characteristics such as age, subtype, and disease duration. Smallest detectable difference for each scale was < 6 on the standardised metric of 0-100 so < 6% of the total range. There was no substantial differential item functioning (DIF) by age, gender, education, working full/part-time, or disease duration; the finding of no DIF for time or sample supports the use of WHODAS 2.0 for longitudinal studies, with the 36- and 32-item versions and the physical and cognitive domains valid for individual patient follow-up. CONCLUSIONS: Disability in MS can be comprehensively measured at interval level by the WHODAS 2.0, and validly monitored over time. Routine use of this self-reported measure in clinical and research practice would give valuable information on the trajectories of disability of individuals and groups.

Asunto(s)

RESUMEN

Importance: Autologous hematopoietic stem cell transplant (AHSCT) is available for treatment of highly active multiple sclerosis (MS). Objective: To compare the effectiveness of AHSCT vs fingolimod, natalizumab, and ocrelizumab in relapsing-remitting MS by emulating pairwise trials. Design, Setting, and Participants: This comparative treatment effectiveness study included 6 specialist MS centers with AHSCT programs and international MSBase registry between 2006 and 2021. The study included patients with relapsing-remitting MS treated with AHSCT, fingolimod, natalizumab, or ocrelizumab with 2 or more years study follow-up including 2 or more disability assessments. Patients were matched on a propensity score derived from clinical and demographic characteristics. Exposure: AHSCT vs fingolimod, natalizumab, or ocrelizumab. Main outcomes: Pairwise-censored groups were compared on annualized relapse rates (ARR) and freedom from relapses and 6-month confirmed Expanded Disability Status Scale (EDSS) score worsening and improvement. Results: Of 4915 individuals, 167 were treated with AHSCT; 2558, fingolimod; 1490, natalizumab; and 700, ocrelizumab. The prematch AHSCT cohort was younger and with greater disability than the fingolimod, natalizumab, and ocrelizumab cohorts; the matched groups were closely aligned. The proportion of women ranged from 65% to 70%, and the mean (SD) age ranged from 35.3 (9.4) to 37.1 (10.6) years. The mean (SD) disease duration ranged from 7.9 (5.6) to 8.7 (5.4) years, EDSS score ranged from 3.5 (1.6) to 3.9 (1.9), and frequency of relapses ranged from 0.77 (0.94) to 0.86 (0.89) in the preceding year. Compared with the fingolimod group (769 [30.0%]), AHSCT (144 [86.2%]) was associated with fewer relapses (ARR: mean [SD], 0.09 [0.30] vs 0.20 [0.44]), similar risk of disability worsening (hazard ratio [HR], 1.70; 95% CI, 0.91-3.17), and higher chance of disability improvement (HR, 2.70; 95% CI, 1.71-4.26) over 5 years. Compared with natalizumab (730 [49.0%]), AHSCT (146 [87.4%]) was associated with marginally lower ARR (mean [SD], 0.08 [0.31] vs 0.10 [0.34]), similar risk of disability worsening (HR, 1.06; 95% CI, 0.54-2.09), and higher chance of disability improvement (HR, 2.68; 95% CI, 1.72-4.18) over 5 years. AHSCT (110 [65.9%]) and ocrelizumab (343 [49.0%]) were associated with similar ARR (mean [SD], 0.09 [0.34] vs 0.06 [0.32]), disability worsening (HR, 1.77; 95% CI, 0.61-5.08), and disability improvement (HR, 1.37; 95% CI, 0.66-2.82) over 3 years. AHSCT-related mortality occurred in 1 of 159 patients (0.6%). Conclusion: In this study, the association of AHSCT with preventing relapses and facilitating recovery from disability was considerably superior to fingolimod and marginally superior to natalizumab. This study did not find evidence for difference in the effectiveness of AHSCT and ocrelizumab over a shorter available follow-up time.

Asunto(s)