Disability Outcome Measures in Phase III Clinical Trials in Multiple Sclerosis

CNS Drugs, Год журнала: 2018, Номер 32(6), С. 543 - 558

Опубликована: Июнь 1, 2018

Accumulating neurological disability has a substantial impact on the lives of patients with multiple sclerosis (MS). As well as established Expanded Disability Status Scale (EDSS), several other outcome measures are now available for assessing progression in MS. This review extends findings previous analysis relapsing-remitting MS (RRMS) trials published up to 2012, determine whether there been shift used assess phase III clinical RRMS and progressive Forty relevant were identified (RRMS, n = 16; MS, 18; other/mixed phenotypes, 6). Sustained EDSS worsening, particularly over 3 months, was included an endpoint almost all trials. Other disability-related endpoints Multiple Sclerosis Functional Composite z-score scores physical component summary Impact Medical Outcomes Study Short-Form (36-item) Health Survey. Tests manual dexterity, ambulation, vision cognition also employed, some trials, composite used. However, no obvious trend choice time. worsening short time periods continues be most widely measure pivotal despite its well-recognised limitations. A new tool set is needed use that detects benefit potential treatments slow (or reverse) disability.

Язык: Английский

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Macular ganglion cell–inner plexiform layer thinning as a biomarker of disability progression in relapsing multiple sclerosis

Multiple Sclerosis Journal, Год журнала: 2020, Номер 27(5), С. 684 - 694

Опубликована: Июль 2, 2020

Background: Macular ganglion cell–inner plexiform layer (mGCIPL) is an emerging biomarker of neuroaxonal degeneration in multiple sclerosis (MS). Objective: We aimed to determine cut-off values mGCIPL thinning for discriminating between progressing and stable patients relapsing (RMS). Methods: This a 3-year prospective longitudinal study on 183 RMS with annual optical coherence tomography. Best possible baseline loss macular (aLmGCIPL) clinically (physical progression or cognitive decline) from were defined by receiver operating characteristics analysis tested using multivariate regression models. Results: Baseline thickness <77 µm was associated increased risk (hazard ratio: 2.7, 95% confidence interval (CI): 1.5–4.7, p < 0.001) disability progression. An aLmGCIPL ⩾1 accurately identified (87% sensitivity at 90% specificity) strong predictor clinical (odds 18.3, CI: 8.8–50.3). Conclusion: present evidence that cross-sectionally measured annualized rates are able identify high accuracy.

Язык: Английский

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Evolution of clinical trials in multiple sclerosis

Therapeutic Advances in Neurological Disorders, Год журнала: 2019, Номер 12

Опубликована: Янв. 1, 2019

Clinical trials have advanced the treatment of multiple sclerosis (MS) by demonstrating safety and efficacy disease-modifying therapies (DMTs). This review discusses major changes to MS clinical in era DMTs. As options for continue increase, patients modern present earlier with milder disease compared historic populations. While placebo-controlled some questions may still be relevant, DMT relapsing-remitting (RRMS) are no longer ethical. The replacement placebo arm an active comparator raised cost requiring larger sample sizes detect on-study effects. Efforts improve trial efficiency RRMS focused on exploring adaptive designs relying sensitive magnetic resonance imaging measures activity. In progressive forms (PMS), lack outcome that can used shorter-term delayed development effective treatments. Recent shifting focus advancing PMS has identified paraclinical measurements improved potential, testing agents neuroprotection remyelination is progress.

Язык: Английский

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Long-term efficacy and safety of alemtuzumab in patients with RRMS: 12-year follow-up of CAMMS223

Journal of Neurology, Год журнала: 2020, Номер 267(11), С. 3343 - 3353

Опубликована: Июнь 24, 2020

Abstract Background In the phase 2 CAMMS223 trial (NCT00050778), alemtuzumab significantly improved clinical and MRI outcomes versus subcutaneous interferon beta-1a over 3 years in treatment-naive patients with relapsing–remitting MS. Here, we assess efficacy safety of 12 who enrolled CAMMS03409 extension (NCT00930553), available follow-up through subsequent TOPAZ (NCT02255656). Methods CAMMS223, received courses (12 mg/day; baseline: 5 days; months later: days); 22% a third course. open-label, nonrandomized extensions, could receive as-needed additional or other disease-modifying therapies. Results Of 108 alemtuzumab-treated 60 entered extension; 33% total courses, 73% no more than Year 12. Over years, annualized relapse rate was 0.09, 71% had stable Expanded Disability Status Scale scores, 69% were free 6-month confirmed disability worsening. 12, disease activity. Cumulatively throughout extensions (Years 7–12), 34% evidence Adverse event (AE) incidence declined Infusion-associated reactions peaked at first course thereafter. Cumulative thyroid AE 50%; one immune thrombocytopenia occurred, there autoimmune nephropathy cases. Conclusions Alemtuzumab maintained patients, receiving three courses. The profile this cohort consistent trials.

Язык: Английский

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Digital Endpoints: Definition, Benefits, and Current Barriers in Accelerating Development and Adoption

Digital Biomarkers, Год журнала: 2021, Номер 5(3), С. 216 - 223

Опубликована: Сен. 13, 2021

The assessment of health and disease requires a set criteria to define status progression. These measures are referred as “endpoints.” A “digital endpoint” is defined by its use sensor-generated data often collected outside clinical setting such in patient’s free-living environment. Applicable sensors exist an array devices can be applied diverse contexts. For example, smartphone’s microphone might used diagnose or predict mild cognitive impairment due Alzheimer’s wrist-worn activity monitor (such those found smartwatches) may measure drug’s effect on the nocturnal patients with sickle cell disease. Digital endpoints generating considerable excitement because they permit more authentic experience, reveal formerly untold realities burden, cut drug discovery costs half. However, before these benefits realized, effort must not only technical creation digital but also environment that allows for their development application. future rests meaningful interdisciplinary collaboration, sufficient evidence realize promise, ecosystem which vast quantities generate analyzed. fundamental nature care changing. With coronavirus 2019 serving catalyst, there has been rapid expansion home models, telehealth, remote patient monitoring. increasing adoption health-care innovations will expedite requirement characterization current tools rely upon direct interaction thus fit purpose administered remotely. ubiquity relatively inexpensive sensors, positioned drive this consequential change. It therefore surprising regulators, physicians, researchers, consultants have each offered novel tools. we further describe later, broad require cooperative effort. In article, present analysis state endpoints. We attempt unify perspectives parties involved deployment conclude interdependent list challenges collaboratively addressed widely adopted.

Язык: Английский

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