Anti cytokine therapy of secondarily-progressing multiple sclerosis (ms)

For treating active forms of secondarily-progressing multiple sclerosis a preliminary clinical trial was performed by two courses: antibody-to-cytokine course (INT, INT and TNF) and cyclosporin А-course (sandimmun). Data of preliminary test of antibodies to cytokines evidence to possibility of performing further clinical trials "antibodies to INT and to TNF (to a lesser degree)" during active forms of progressive MS. Were obtained the results, evidencing to a possible use of sandimmun in constantly progressive forms of secondarily progressing disease, when favourable clinical effect coincided with supression of cytokine IL-2 production and lowering of activeness of immunocytes.

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Digital Technology in Clinical Trials for Multiple Sclerosis: a systematic review. (Preprint)

10.2196/preprints.20670 ◽

2020 ◽

Author(s):

Marcello De Angelis ◽

Luigi Lavorgna ◽

Antonio Carotenuto ◽

Martina Petruzzo ◽

Roberta Lanzillo ◽

...

Keyword(s):

Multiple Sclerosis ◽

Clinical Trial ◽

Clinical Trials ◽

Outcome Measures ◽

Digital Technology ◽

Clinical Trial Design ◽

Motor Rehabilitation ◽

Robot Assisted ◽

Future Directions ◽

Treatment Side Effects

BACKGROUND Clinical trials in multiple sclerosis (MS) have leveraged the use of digital technology to overcome limitations in treatment and disease monitoring. OBJECTIVE To review the use of digital technology in concluded and ongoing MS clinical trials. METHODS In March 2020, we searched for “multiple sclerosis” and “trial” on pubmed.gov and clinicaltrials.gov using “app”, “digital”, “electronic”, “internet” and “mobile” as additional search words, separately. Overall, we included thirty-five studies. RESULTS Digital technology is part of clinical trial interventions to deliver psychotherapy and motor rehabilitation, with exergames, e-training, and robot-assisted exercises. Also, digital technology has become increasingly used to standardise previously existing outcome measures, with automatic acquisitions, reduced inconsistencies, and improved detection of symptoms. Some trials have been developing new patient-centred outcome measures for the detection of symptoms and of treatment side effects and adherence. CONCLUSIONS We will discuss how digital technology has been changing MS clinical trial design, and possible future directions for MS and neurology research.

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The future of multiple sclerosis therapies: redesigning multiple sclerosis clinical trials in a new therapeutic eraa

Multiple Sclerosis Journal ◽

10.1191/1352458505ms1231oa ◽

2005 ◽

Vol 11 (6) ◽

pp. 669-676 ◽

Cited By ~ 17

Author(s):

H F McFarland ◽

S C Reingold

Keyword(s):

Multiple Sclerosis ◽

Clinical Trial ◽

Clinical Trials ◽

Controlled Trial ◽

International Workshop ◽

Regulatory Approval ◽

Ethical Considerations ◽

New Therapies ◽

Clinical Trial Designs ◽

New Strategies

Due to past success in testing and gaining regulatory approval for a variety of therapies in multiple sclerosis (MS), the conduct of future clinical trials has become increasingly problematic. An international workshop has met to discuss the issues facing the MS clinical trial community and to examine possible new strategies for the design of trials. Particular focus has been placed on trials that either avoid the use of a placebo because of ethical considerations or on designs that allow new therapies to be studied more rapidly or with fewer patients than needed in a conventional placebo-controlled trial. The discussions resulting from the workshop should provide a basis for the examination and implementation of innovative clinical trial designs in MS.

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The risk of malignancy is not increased in patients with multiple sclerosis treated with subcutaneous interferon beta-1a: analysis of data from clinical trial and post-marketing surveillance settings

Multiple Sclerosis Journal ◽

10.1177/1352458511403642 ◽

2011 ◽

Vol 17 (4) ◽

pp. 431-440 ◽

Cited By ~ 17

Author(s):

Magnhild Sandberg-Wollheim ◽

Gabrielle Kornmann ◽

Dorina Bischof ◽

Margaretha Stam Moraga ◽

Brian Hennessy ◽

...

Keyword(s):

Multiple Sclerosis ◽

Clinical Trial ◽

Clinical Trials ◽

Safety Data ◽

Data Set ◽

Safety Database ◽

Post Marketing Surveillance ◽

Risk Of Malignancy ◽

Post Marketing ◽

Medical Dictionary

Background: Risks that are potentially associated with long-term therapies should be assessed. Objective: The present analyses were performed to determine the risk of malignancy in patients with multiple sclerosis (MS) receiving subcutaneous (sc) interferon (IFN) beta-1a, using pooled safety data from key clinical trials and data from the Merck Serono Global Drug Safety database. Methods: The standard Medical Dictionary for Regulatory Activities query “malignancies” was used to retrieve relevant cases from each data set. The incidence of malignancies per 1000 patient-years was calculated using the pooled safety data from clinical trials. The reporting rates of malignancy types were calculated for the post-marketing setting based on sales volume. Malignancies were grouped by organ localization and classified as medically confirmed or not medically confirmed according to the source of each report. The number of reported cases of each type was compared with the expected number in the general population. Results: Analysis of pooled safety data from 12 key clinical trials did not show an increased incidence of malignancy per 1000 patient-years with sc IFN beta-1a (4.0; 95% confidence interval (CI): 2.9–5.5) compared with placebo (6.4; 95% CI: 3.3–11.2). Analysis of the database shows that among the medically confirmed cases, reported to expected ratios ranged from 1 : 6 to 1 : 18 for solid tumours and from 1 : 2 to 1 : 9 for lymphohaematopoietic tumours. Conclusion: Safety data from both clinical trial and post-marketing settings suggest that treatment with sc IFN beta-1a does not increase the risk of malignancy in patients with MS.

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Effect of applying inclusion and exclusion criteria of phase III clinical trials to multiple sclerosis patients in routine clinical care

Multiple Sclerosis Journal ◽

10.1177/1352458520985118 ◽

2021 ◽

pp. 135245852098511

Author(s):

Kris Oliver Jalusic ◽

David Ellenberger ◽

Paulus Rommer ◽

Alexander Stahmann ◽

Uwe Zettl ◽

...

Keyword(s):

Multiple Sclerosis ◽

Clinical Trial ◽

Clinical Trials ◽

Clinical Care ◽

Routine Care ◽

Phase Iii ◽

Exclusion Criteria ◽

Phase Iii Clinical Trial ◽

Phase Iii Clinical Trials ◽

Multiple Sclerosis Patients

Background: Newly approved, drug-modifying therapies are associated with still unknown adverse events, although clinical trials leading to approval have strict inclusion and exclusion criteria and analyse safety and efficacy. Objectives: The aim of this study was to analyse the eligibility of multiple sclerosis (MS) patients treated in routine care into the phase III clinical trial of the respective drug. Methods: In total, 3577 MS patients with 4312 therapies were analysed. Patients with primary-progressive MS were excluded. Inclusion and exclusion criteria of phase III clinical trials in relapsing–remitting MS were adopted and subsequently applied. A comparison in clinical and sociodemographic characteristics was made between patient who met the criteria and those who did not. Results: 83% of registered patients would not have been eligible to the respective phase III clinical trial. Relapse was the single most frequent criterion not fulfilled (74.7%), followed by medication history (21.2%). Conclusion: The majority of MS patients treated in routine care would not have met clinical trials criteria. Thus, the efficacy and safety of therapies in clinical trials can differ from those in the real world. Broader phase III inclusion criteria would increase their eligibility and contribute to a better generalizability of the results in clinical trials.

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Digital Technology in Clinical Trials for Multiple Sclerosis: Systematic Review

Journal of Clinical Medicine ◽

10.3390/jcm10112328 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2328

Author(s):

Marcello De Angelis ◽

Luigi Lavorgna ◽

Antonio Carotenuto ◽

Martina Petruzzo ◽

Roberta Lanzillo ◽

...

Keyword(s):

Multiple Sclerosis ◽

Clinical Trial ◽

Clinical Trials ◽

Outcome Measures ◽

Digital Technology ◽

Cognitive Rehabilitation ◽

English Language ◽

Self Assessment ◽

Treatment Delivery ◽

Electronic Recording

Clinical trials in multiple sclerosis (MS) have been including digital technology tools to overcome limitations in treatment delivery and disease monitoring. In March 2020, we conducted a systematic search on pubmed.gov and clinicaltrials.gov databases (with no restrictions) to identify all relevant published and unpublished clinical trials, in English language, including MS patients, in which digital technology was applied. We used “multiple sclerosis” and “clinical trial” as the main search words, and “app”, “digital”, “electronic”, “internet” and “mobile” as additional search words, separately. Digital technology is part of clinical trial interventions to deliver psychotherapy and motor rehabilitation, with exergames, e-training, and robot-assisted exercises. Digital technology has been used to standardise previously existing outcome measures, with automatic acquisitions, reduced inconsistencies, and improved detection of symptoms (e.g., electronic recording of motor performance). Other clinical trials have been using digital technology for monitoring symptoms that would be otherwise difficult to detect (e.g., fatigue, balance), for measuring treatment adherence and side effects, and for self-assessment purposes. Collection of outcome measures is progressively shifting from paper-based on site, to internet-based on site, and, in the future, to internet-based at home, with the detection of clinical and treatment features that would have remained otherwise invisible. Similarly, remote interventions provide new possibilities of motor and cognitive rehabilitation.

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Sharing data from MS clinical trials: Opportunities, challenges, and future directions

Multiple Sclerosis Journal ◽

10.1177/1352458515608005 ◽

2015 ◽

Vol 21 (11) ◽

pp. 1365-1368 ◽

Cited By ~ 2

Author(s):

Timothy Coetzee

Keyword(s):

Multiple Sclerosis ◽

Clinical Trial ◽

Clinical Trials ◽

Clinical Trial Data ◽

Therapeutic Agents ◽

Research Community ◽

Trial Data ◽

Fundamental Question ◽

Future Directions ◽

Phase Ii And Iii

The treatment of people affected by multiple sclerosis, particularly the relapsing forms of the disease, has been transformed by the availability of various therapeutic agents. This landmark progress is due to an enormous foundation of clinical research and, particularly, numerous phase II and III clinical trials. Although the research community has many reasons to take pride in this progress, a fundamental question remains about whether opportunities for additional research are being lost due to inadequate clinical trial data sharing.

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Clinical trial design for progressive MS trials

Multiple Sclerosis Journal ◽

10.1177/1352458517729461 ◽

2017 ◽

Vol 23 (12) ◽

pp. 1642-1648 ◽

Cited By ~ 7

Author(s):

Matteo Pardini ◽

Gary Cutter ◽

Maria Pia Sormani

Keyword(s):

Multiple Sclerosis ◽

Clinical Trial ◽

Clinical Trials ◽

Trial Design ◽

Clinical Trial Design ◽

Progressive Multiple Sclerosis ◽

Phase 2 ◽

The Right ◽

Selection Of Patients ◽

Selection Of

The design of clinical trials is a key aspect to maximizing the possibility to detect a treatment effect. This fact is particularly challenging in progressive multiple sclerosis (PMS) studies due to the uncertainty about the right target and/or outcome in phase-2 studies. The aim of this review is to evaluate the current challenges facing the design of clinical trials for PMS. The selection of patients, the instrumental and clinical outcomes that can be used in PMS trials, and issues in their design will be covered in this report.

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Multiple Sclerosis Clinical Trials: Part 1—Basic Considerations

International Journal of MS Care ◽

10.7224/1537-2073-3.1.6 ◽

2001 ◽

Vol 3 (1) ◽

pp. 6-12

Author(s):

Robert M. Herndon

Keyword(s):

Multiple Sclerosis ◽

Clinical Trial ◽

Clinical Trials ◽

Positive Result ◽

Signs And Symptoms ◽

Relapsing Remitting ◽

Varied Distribution

ABSTRACT Clinical trials in neurology are difficult, complex, usually expensive, and fraught with pitfalls. Clinical trials in multiple sclerosis (MS) are particularly difficult because of the relapsing-remitting nature of the disease, the highly varied distribution of the lesions, and varied signs and symptoms. While the number and quality of MS clinical trials have increased enormously in recent years, they remain controversial and are subject to endless criticism. There is no shortage of individuals willing and eager to criticize clinical trials if they claim a positive result. Conversely, negative trials are rarely published1 and, when they are, they are rarely criticized even though some negative trials are equally deserving of criticism. No trial is perfect, and few scientific endeavors are subject to more rigorous review and criticism than clinical trials. This article—the first in a series—will discuss various aspects of planning, designing, and implementing a clinical trial. (Int J MS Care. 2001; 3(1): 6–12)

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