defining suboptimal response to ms treatment: mri outcome
TRANSCRIPT
![Page 1: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/1.jpg)
Tony Traboulsee, MD (Neurology) University of British Columbia
CMSC June 5th, 2004Toronto, Ontario
Defining suboptimal response to MS treatment: MRI outcome
![Page 2: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/2.jpg)
Disclosure
I have received honoraria from the Consortium of MS Centers and from all the major
pharmaceutical companies currently involved in MS clinical trials of DMTs.
![Page 3: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/3.jpg)
1984MRI detects clinically
silent lesions.
Its role in monitoring individual patients is
unknown.
0.15 Tesla MRI, UBC
![Page 4: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/4.jpg)
What is the value of MRI in monitoring MS patients?
1. Does MRI predict if a patient will have clinical relapses?
3. Does MRI predict clinical disability?
5. Does MRI predict treatment response?
7. Is the clinical MRI data reliable?
Dr. T. Traboulsee, UBC MS/MRI Research Group
![Page 5: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/5.jpg)
What is the value of MRI in monitoring MS patients?
1. Does MRI predict if a patient will have clinical relapses?
3. Does MRI predict clinical disability?
5. Does MRI predict treatment response?
7. Is the clinical MRI data reliable?
Dr. T. Traboulsee, UBC MS/MRI Research Group
![Page 6: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/6.jpg)
Bashir analog model for assessing the effectiveness of therapeutic strategies
Reproduced without permission from International Journal of MS Care 2002 (suppl):1-7
![Page 7: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/7.jpg)
Freedman analog model for assessing the effectiveness of MS therapies.
Reproduced without permission from Canadian Journal of Neurological Sciences 2004; 31(2)
![Page 8: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/8.jpg)
Why do any test in medicine?
To monitor the disease course.To predict clinical outcome.To modify therapy.
Dr. T. Traboulsee, UBC MS/MRI Research Group
![Page 9: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/9.jpg)
Freedman analog model for assessing the effectiveness of MS therapies.
Reproduced without permission from Canadian Journal of Neurological Sciences 2004; 31(2)
![Page 10: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/10.jpg)
Reproduced without permission from Canadian Journal of Neurological Sciences 2004; 31(2)
![Page 11: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/11.jpg)
What is the value of MRI in monitoring MS patients?
Dr. T. Traboulsee, UBC MS/MRI Research Group
![Page 12: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/12.jpg)
Does a single MRI Predict Relapses?
• MRI abnormalities in CIS predict CDMS (Brex 14 year natural history cohort NEJM 2003)
• Gad activity predicts higher rate of conversion from CIS to CDMS (CHAMPS)
Dr. T. Traboulsee, UBC MS/MRI Research Group
![Page 13: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/13.jpg)
Does a single MRI Predict Relapses?
An initial MRI with no gad lesions would
predict 1.3 relapses in the next year.
An initial MRI with 10 gad lesions would
predict 1.6 relapses in the next year.
Kappos Meta Analysis of 307 patients, Lancet 1999
Dr. T. Traboulsee, UBC MS/MRI Research Group
![Page 14: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/14.jpg)
Do Serial MRI Predict Relapses?
• PPV 0.2 when using monthly gad activity on MRI predicting relapse at 6 months (Koziol AJNR 2002)
• R = 0.25 for monthly MRI gad activity correlating with relapses (Rovaris AJNR 2003)
• The relative risk of having a relapse at 1 or 2 years was slightly increased (RR 1.13) by the presence of gad lesions with 6 monthly scans (Kappos Lancet 1999)
Dr. T. Traboulsee, UBC MS/MRI Research Group
![Page 15: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/15.jpg)
What is the value of MRI in monitoring MS patients?
1. Does MRI predict if a patient will have clinical relapses?
• Does MRI predict clinical disability?
• Does MRI predict treatment response?
• Is the clinical MRI data reliable?
Dr. T. Traboulsee, UBC MS/MRI Research Group
![Page 16: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/16.jpg)
Does a single MRI Predict Disability?
CIS patients with larger number and volume of T2 lesions tend to have greater disability at 14 years (Brex NEJM 2002)
There was no relationship between gad enhancing lesions at baseline and EDSS at 2 years. (Kappos Meta Analysis, Lancet 1999)
Dr. T. Traboulsee, UBC MS/MRI Research Group
![Page 17: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/17.jpg)
Do serial MRI Predict Disability?
New T2 activity weakly correlated with relapses (r=0.2) but not with disability at 5 years .
Change in BOD weakly correlated with relapses (r=0.2) and with EDSS (r=0.3)
Paty, IFNB RRMS study, 115 Placebo patients followed with annual MRI for 5 years
![Page 18: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/18.jpg)
Do serial MRI Predict Disability?
New T2 activity weakly predicts disability at 2-3 years of follow-up (r=0.13, p=0.02).
Filippi et al, pooled data of 281 MS patients, Neurology 1995
![Page 19: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/19.jpg)
Do serial MRI Predict Disability?
The most active patients on MRI have a worse prognosis than the less active ones.
However, there is so much overlap between groups that one cannot yet predict prognosis for individual patients.
Paty, AAN 1992
![Page 20: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/20.jpg)
What is the value of MRI in monitoring MS patients?
1. Does MRI predict if a patient will have clinical relapses?
• Does MRI predict clinical disability?
• Does MRI predict treatment response?
• Is the clinical MRI data reliable?
Dr. T. Traboulsee, UBC MS/MRI Research Group
![Page 21: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/21.jpg)
Does MRI predict Treatment Success?Observations from RRMS:
Studies have shown up to a 90% suppression of new gadolinium enhancement lesions.
These studies also showed no net accumulation of total T2 lesion load.
However, the clinical impact on relapses is only modest (33% reduction), and the long term impact on clinical disability remains controversial.
![Page 22: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/22.jpg)
-300
-200
-100
0
100
200
300
400
500
0 1 2
Time (years)
Placebo1.6mIU8 mIU
Change from
Baseline in MRI Area
Pivotal IFN beta 1b RRMS studyPivotal IFN beta 1b RRMS studyT2 BOD is suppressed compared to placeboT2 BOD is suppressed compared to placebo
![Page 23: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/23.jpg)
IFN Beta-1a: IFN Beta-1a: % Change of BOD from Baseline % Change of BOD from Baseline Population DistributionPopulation Distribution
00
1010
2020
3030
-40-40 -20-20 00 2020 4040 6060 8080 100100 120120 140140 160160 180180 200200
% o
f pa
tien
ts%
of
pati
ents
% change in BOD from baseline% change in BOD from baseline
PlaceboPlacebo
Rebif 44 TIWRebif 44 TIW
GOOD MRI GOOD MRI OutcomeOutcome POOR MRI OutcomePOOR MRI Outcome
![Page 24: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/24.jpg)
Does MRI predict Treatment Success?Observations from SPMS:
Studies have shown similar suppression of new inflammatory MRI activity and on T2 BOD as seen in RRMS.
However, there is no consistent clinical impact on disability.
![Page 25: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/25.jpg)
What is the value of MRI in monitoring MS patients?
1. Does MRI predict if a patient will have clinical relapses?
• Does MRI predict clinical disability?
• Does MRI predict treatment response?
• Is the clinical MRI data reliable?
Dr. T. Traboulsee, UBC MS/MRI Research Group
![Page 26: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/26.jpg)
CMSC MRI Protocol
If a follow-up MRI is to be done, it should be performed by the standardized MRI protocol.
Dr. A. Traboulsee and the CMSC work group
![Page 27: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/27.jpg)
Total Lesion Frequency and EDSS
12 24 36 48
Months
Nu
mb
er
of
Gd
en
ha
nci
ng
le
sio
ns
10
8
6
4
2
5
4
3
2
ED
SS
Kindly provided by Joe Frank, NIH
![Page 28: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/28.jpg)
Why do any test in medicine?
To monitor the disease course.To predict clinical outcome.To modify therapy.
Dr. T. Traboulsee, UBC MS/MRI Research Group
![Page 29: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/29.jpg)
How can this be applied to individual patients?
Dr. T. Traboulsee, UBC MS/MRI Research Group
There is so much overlap between groups that one cannot yet predict prognosis for individual patients.
Paty, AAN 1992
![Page 30: Defining Suboptimal Response to MS Treatment: MRI Outcome](https://reader034.vdocuments.site/reader034/viewer/2022052601/5595a80f1a28ab524f8b4594/html5/thumbnails/30.jpg)
Conclusion
Treat the patient, not the test.
Dr. T. Traboulsee, UBC MS/MRI Research Group.