A Canadian Study Assessing the Utility of the Treatment Optimization Recommendations in Multiple Sclerosis (CanTOR)
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|ClinicalTrials.gov Identifier: NCT01142583|
Recruitment Status : Completed
First Posted : June 11, 2010
Last Update Posted : March 18, 2014
The Canadian Multiple Sclerosis Working Group (CMSWG) has developed practical recommendations on how neurologists can assess the status of subjects on disease modifying drugs (DMDs) and decide when it may be necessary to modify treatment in order to optimize outcomes. These recommendations are based on relapses, disease progression as measured by the Expanded Disability Status Scale (EDSS) or EDSS progression, and magnetic resonance imaging (MRI) outcomes. The CMSWG agreed to compare post-treatment relapse rates and severity to baseline rates and severity in each individual subject. The recommended minimum baseline reference time frame needed to assess relapse rate was 2 years prior to treatment initiation. The objective and prospective relapse data should be ideally collected during this reference period. The CMSWG recommended that the following should be taken into consideration when assessing relapse severity: the effect of the relapse on activities of daily living (ADL), the type and number of systems involved (i.e., relapses that are polysymptomatic or that affect the cerebellar/motor systems tend to be more severe), and whether or not a course of corticosteroids was required. The CMSWG also recommended that, prior to considering treatment modification on the basis of progression in disability, progression should be confirmed at 6 months.
The CMSWG's Treatment Optimization Recommendations (TORs) have been retrospectively applied to the 4 year data set from the PRISMS study. Applying the model to subjects after their first year on therapy allowed for accurate prediction of continued disease activity in the form of relapses in the majority of subjects who actually experienced ongoing attacks. The model was less effective in predicting disability progression, but this may well have been due to the low numbers of subjects on treatment progressing over the study period. This observational study used the TOR model to identify subjects as either candidates for therapy optimization or as candidates to maintain current therapy. All subjects were then followed prospectively until re- assessment will be done with this model.
|Condition or disease|
|Multiple Sclerosis, Relapsing-Remitting|
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Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS) and is one of the most common causes of neurological disability in young adults. The neuropathology of the disease is marked by accumulation of leukocytes in the CNS, oligodendrocyte loss, demyelination, axonal atrophy, and neuronal loss. Clinically it is characterized by multi-focal recurrent attacks of neurological symptoms and signs with variable recovery and eventually, the majority of subjects develop a progressive clinical course of MS. The exact cause of MS is unknown, although an autoimmune process has been implicated. Genetic susceptibility plays a role in disease initiation but unidentified environmental factors may also be involved. Three clinical forms of MS are recognized: primary progressive multiple sclerosis (PPMS), secondary progressive multiple sclerosis (SPMS) and RRMS. Primary progressive subjects are characterized by slow and steady accumulation of neurological deficits from onset without superimposed attacks. Subjects with RRMS have exacerbations or relapses with subsequent variable recovery (remission). Secondary progressive multiple sclerosis is characterized by the steady accumulation of significant and persistent neurological deficit with or without superimposed relapses.
In approximately 90% of subjects, the first presentation of MS is an acute, usually reversible episode of CNS dysfunction, referred to as Clinically Isolated Syndrome (CIS). With the advent of MRI, it has become possible to reasonably predict the clinical course of CIS subjects presenting with abnormal MRI findings. The first 5 year follow up study of CIS subjects presenting with abnormal MRI demonstrated a trend for those with more lesions to develop clinically definite MS (CDMS) more frequently, with 92% of those with 4-10 T2 lesions developing CDMS compared to 67% of those with 2-3 T2 lesions. It is also well established that the vast majority of CIS subjects continue to experience ongoing demyelinating disease activity, as evidenced by MRI, even in the absence of a clinical conversion to CDMS.
The introduction of the disease modifying drugs (DMDs) for MS has had a significant impact on the management of those living with this disease. These DMDs are the first agents that have been shown to alter the natural course of relapsing MS. Although there is evidence that the DMDs significantly reduce disease activity, these agents are not "cures" for MS. Thus, many subjects with MS continue to experience disease activity, in spite of treatment with DMDs, including continued relapses, progressive impairment, and ongoing accumulation of MRI disease burden.
- To assess if application of the TOR influences clinicians' decisions regarding DMD treatment in the Canadian clinic setting
- To evaluate the perceived utility of the TOR in the DMD treatment decision making process in the Canadian clinic setting
- To determine the proportion of subjects meeting a medium or high level of concern according to the TOR in the Canadian Clinic setting.
This was a non-interventional, open-label, observational, multicentric, phase IV study. Subjects were assessed according to the TOR on two occasions over a prospective 12 month observation period. All subjects were assessed according to the TOR at baseline. Subjects were subsequently assessed according to the TOR either at a time-point within the 12-month period when treatment modification is being considered for reasons other than intolerance or at the end of the 12-month observational period. Treatment decisions after each TOR assessment was noted, and perceptions on the utility of the TOR in the decision making process was captured. Additional feedback on the TOR was collected at the end of the observational period through a separate evaluation questionnaire. The assessments that were carried out at baseline and subsequent visits included EDSS history/current status, relapse history/current status, MRI history/current status, cognitive history/current status (if done) and neutralizing antibody (NAb) history/current status (if done).
|Study Type :||Observational|
|Actual Enrollment :||192 participants|
|Official Title:||Canadian Assessment of the Utility of the Treatment Optimization Recommendations in Multiple Sclerosis|
|Study Start Date :||July 2006|
|Actual Primary Completion Date :||August 2009|
|Actual Study Completion Date :||August 2009|
- Assessment of history or current status of Expanded Disability Status Score (EDSS) [ Time Frame: Baseline to 12 month TOR assessment ]
- Assessment of history or current relapse status [ Time Frame: Baseline to 12 month TOR assessment ]
- Assessment of history or current magnetic resonance imaging (MRI) status [ Time Frame: Baseline to 12 month TOR assessment ]
- Assessment of history or current cognitive status [ Time Frame: Baseline to 12 month TOR assessment ]
- Assessment of history or current status of neutralizing antibodies (NAb) [ Time Frame: Baseline to 12 month TOR assessment ]
- Treatment Optimization Recommendation Questionnaire [ Time Frame: At the end of the 12 months observational period. ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01142583
|Study Director:||Medical Responsible||EMD Serono a division of EMD Canada Inc., an affiliate of Merck KGaA, Darmstadt, Germany|