MRI predictors of early conversion to clinically definite MS in the CHAMPS placebo group

Simon, Jack H.; O’Connor, Paul; Fleming, Piers; Gray, T A; Jacobs, Lawrence; Miller, Chris; Munschauer, Frederick E.; Kinkel, R. Philip; Bolibrush, D.; Cohen, Joel L.; Freedman, M. S.; Webb, Ute H.; Rabinowicz, H.; Metz, Luanne M.; Patry, David G.; Yeung, Michael; Peters, Stevany L.; Hashimoto, S. A.; Morrison, W.; Oger, Joél; Panitch, Hillel S.; Costello, Kathleen; Bever, Christopher; Stuart, William H.; Court, D.; Stuart, David; Tornatore, Carlo; Bartlett, David L.; Richert, John R.; Duquette, Pierre; Dubois, Reuben S.; Bernier, George M.; Scott, Thomas F.; Pappert, L.; Brillman, Judith C.; Felton, Warren L.; Anderson, T.; Astruc, J.; Rose, James C.; Kline, J. A.; Burns, J. B.; Murray, Thomas J.; Weldon, P.; Bhan, Virender; Maxner, Charles; Wall, Margaret J.; Vining, Lynn; Grabowski, T.; Apatoff, Brian R.; Orapello, C.; Friedman, Jan M.; Galetta, Steven; Pfohl, D.; Liu, G.; Rice, G; Bental, Tamir; Mandalfino, P.; Eggenberger, Eric; Snider, Denis P.; Kaufman, Dimitri; Guarnaccia, Joseph; Lesser, Robert L.; Goldstein, J.; Reiss, Moshe; Carter, E.; Glista, Glen G.; Rolak, Loren A.; Scheller, Lukas; Jacobson, Daniel M.; Warner, Judith E. A.; Goodman, Andrew; Petrie, Mary; Mattson, David H.; Karlin, Kirill; Wallin, Andreas; Stefoski, Dusan; Brod, Staley A.; Cerretta, E.; Wolinsky, Jerry S.; Arnold, Douglas L.; Arnoutelis, R.; Durcan, Lorraine; Kupersmith, Mark J.; Cappolino, L.; Herbert, Joseph; Rosenberg, J.; McHugh, Deaglan Joseph; Blumenfeld, Andrew; Smith, Clayton A.; Kuder, D.; Hamilton, Stephanie; Thurston, Stephen; McGee, Jeanie; O'Bannon, John M.; Kaufman, Michael D.; Butler, M.; Putnam, Samuel; Ramohan, K.; Siffort, A.

doi:10.1212/wnl.59.7.998

Cited by 85 publications

(44 citation statements)

References 29 publications

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“…14 In those who demonstrated two or more Gdenhancing lesions at baseline, 52% developed CDMS by 18 months and 84% had either developed CDMS or exhibited temporal dissemination of disease activity on MRI after 18 months. 43 By contrast, in patients with fewer than two enhancing lesions at baseline, only 24% developed CDMS at 18 months (class I evidence). In this study, 60% of the placebo patients not meeting MRI (a) criteria (see table 3) went on to develop temporal dissemination of disease activity by either experiencing another exacerbation or developing new MRI lesions.…”

Section: Relationship Of Baseline Gd Enhancement and Subsequent Mri Fmentioning

confidence: 99%

The utility of MRI in suspected MS [RETIRED]

et al. 2003

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Abstract-Advancements in imaging technologies and newly evolving treatments offer the promise of more effective management strategies for MS. Until recently, confirmation of the diagnosis of MS has generally required the demonstration of clinical activity that is disseminated in both time and space. Nevertheless, with the advent of MRI techniques, occult disease activity can be demonstrated in 50 to 80% of patients at the time of the first clinical presentation. Prospective studies have shown that the presence of such lesions predicts future conversion to clinically definite (CD) MS. Indeed, in a young to middle-aged adult with a clinically isolated syndrome (CIS), once alternative diagnoses are excluded at baseline, the finding of three or more white matter lesions on a T2-weighted MRI scan (especially if one of these lesions is located in the periventricular region) is a very sensitive predictor (Ͼ80%) of the subsequent development of CDMS within the next 7 to 10 years. Moreover, the presence of two or more gadolinium (Gd)-enhancing lesions at baseline and the appearance of either new T2 lesions or new Gd enhancement on follow-up scans are also highly predictive of the subsequent development of CDMS in the near term. By contrast, normal results on MRI at the time of clinical presentation makes the future development of CDMS considerably less likely.

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Section: Relationship Of Baseline Gd Enhancement and Subsequent Mri Fmentioning

confidence: 99%

The utility of MRI in suspected MS [RETIRED]

et al. 2003

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“…Patients experiencing a CIS with rapid complete recovery, a low T2 lesion burden (<3 lesions), no evidence of brain atrophy, and an older age at CIS onset (>38 years) may elect to monitor their condition before initiation of therapy, with the knowledge that there are no truly low-risk groups identified with any certainty by these clinical and MRI criteria. 18 Overall, it is reassuring that all three intervention trials reviewed here consistently demonstrate the benefits of early use of IFNβ in delaying conversion to CDMS. However, in the absence of head-to-head studies in this population, and because the IFNβ formulations cannot be readily differentiated based on their clinical or neurologic efficacies in the ETOMS, CHAMPS, and BEN-EFIT studies, the choice of treatment may be based on efficacy of IFNβ, particularly over the short term.…”

Section: Champsmentioning

confidence: 59%

“…This effect remained after controlling for baseline MRI characteristics and syndrome type. 18 Several natural history studies have suggested that optic neuritis at CIS onset may signify a form of MS with a better prognosis compared with other syndromes. [24][25][26] However, among patients with abnormal cranial MRI studies and monosymptomatic presentation at CIS onset, syndrome type appears to have little effect on disease course.…”

Section: Results From Phase 3 Studies Of Ifnβ In Patients With a Cismentioning

confidence: 99%

“…28 Relapse rates during the early course of the disease may be predictive of the rate of development of both measurable disability and progressive disease. 2,5,[16][17][18]28,29 However, natural history studies demonstrate that the The CHAMPS study had a planned duration of 3 years, and the efficacy of IM IFNβ-1a once weekly for up to 3 years was published in the primary report. 23 However, the present article focuses on the 2-year efficacy results published recently 32 to allow comparative discussion of the findings from the BENEFIT and ETOMS studies, which included double-blinded followup periods of 2 years.…”

Section: Results From Phase 3 Studies Of Ifnβ In Patients With a Cismentioning

confidence: 99%

“…For example, as discussed previously, younger age, the presence of Gd+ lesions at the time of a CIS, and the number of T2 lesions in patients with an abnormal cranial MRI scan are significantly associated with a higher rate of conversion to CDMS. 2,18,20,32 As a result, patients with these characteristics at onset should be encouraged to initiate treatment early and be monitored closely for treatment efficacy. Patients experiencing a CIS with rapid complete recovery, a low T2 lesion burden (<3 lesions), no evidence of brain atrophy, and an older age at CIS onset (>38 years) may elect to monitor their condition before initiation of therapy, with the knowledge that there are no truly low-risk groups identified with any certainty by these clinical and MRI criteria.…”

Section: Champsmentioning

confidence: 99%

See 2 more Smart Citations

The Efficacy of Interferon Beta in Delaying Conversion to Clinically Definite Multiple Sclerosis

Kremenchutzky¹,

Kinkel²

2010

International Journal of MS Care

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More than half of patients with a clinically isolated syndrome (CIS) develop clinically definite multiple sclerosis (CDMS). Patients at high risk for CDMS often present with asymptomatic lesions characteristic of CDMS on magnetic resonance imaging scans, although an absence of asymptomatic lesions is not atypical. Phase 3 studies of interferon beta in patients with a CIS suggest that this treatment can delay conversion to CDMS and reduce the risk of new asymptomatic white matter lesions. We reviewed phase 3 studies (CHAMPS, BENEFIT, and ETOMS) and post hoc analyses assessing the efficacy of interferon beta in delaying CDMS in patients with a CIS. The evidence supports early initiation of treatment. Int J MS Care. 2010;12:42-50. Multiple sclerosis (MS) is a chronic, demyelinating disorder of the central nervous system (CNS), with evidence of both inflammatory and neurodegenerative pathogenic features. A clinically isolated syndrome (CIS) such as acute monocular optic neuritis, partial transverse myelitis, or acute brainstem syndrome can be the first indication of MS, 1 and approximately 50% of patients who develop a CIS are eventually diagnosed with clinically definite MS (CDMS). 2Studies demonstrate that 80% of MS cases begin with a relapsing-remitting (RR) course 3 characterized by subacute development of neurologic symptoms and findings (relapses), followed by a recovery period of weeks to months. Despite significant recovery in the majority of cases, relapses appear to be the major cause of increases in sustained disability, with approximately 28% of patients with RRMS experiencing a 1-point or greater increase on the Expanded Disability Status Scale 4 (EDSS) following each relapse recovery. 5,6 The median time to reach a fixed EDSS score of 6.0-a disability milestone almost always associated with a secondary progressive (SP) phase of the disease-is 15 to 28 years. 3,7,8 In the course of MS, progression of disability is accompanied by accumulation of CNS abnormalities (including contrast-enhancing lesions, T2 lesions, T1 "black holes," and brain atrophy) and eventual loss of tissue caused by inflammation and axonal injury.9 It has been reported that inflammatory lesion activity in early relapsing MS, as detected by serial monthly magnetic resonance imaging (MRI) studies, may be ten times more frequent than clinical relapses and signals an ongoing pathologic process.9 Widespread inflammationindependent axonal damage has also been demonstrated in patients with a CIS.10 Although inflammatory demyelination is reversible, chronic demyelination and axonal degeneration are irreversible and result in progressive neurologic disability. 11This article reviews the rationale for early treatment of MS, assesses the available clinical evidence for the efficacy of interferon beta (IFNβ) therapy in slowing the development of MS in patients with a CIS, 12-15 and identifies the types of patients who may benefit the most from early treatment. Early Prognostic Factors of Disease Activity and DisabilityThe clinical course of MS v...

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