Contributions
Abstract: P1266
Type: Poster
Abstract Category: Therapy - disease modifying - Tools for detecting therapeutic response
Purpose: We have previously shown that permeability of the blood-brain barrier, measured as the transfer constant Ktrans (ml/100g/min) by dynamic contrast-enhanced MRI (DCE-MRI) is linked to the degree of inflammation in MS patients, and thus could provide a quantitative measure of the current level of disease activity (Cramer, SP 2014 and 2015). Many efficacious treatment options have emerged in recent years, however detecting an unfavourable treatment response remains a challenge due to lack of quantitative methods. This study aimed to investigate whether Ktrans measured in the normal appearing white (NAWM) and grey matter (NAGM) can predict early inadequate response to second-line treatment (Fingolimod or Natalizumab, at the time of study initiation).
Methods: Sixty relapsing remitting MS patients were included in the study protocol consisting of a DCE-MRI at baseline (pre-treatment), and again three and six months post-treatment. Of these, thirty-four patients initiated second-line treatment for clinical reasons and completed the study protocol. Treatment effect after one year was assessed according to the international No Evidence of Disease Activity (NEDA) criteria by an experienced MS clinician, blinded to the DCE-MRI results.
Results: Baseline Ktrans in NAWM was inversely correlated with increasing baseline treatment intensity (categorical variable: (a) no treatment, (b) interferon-beta/glatiramer acetate or (c) prednisolone treatment after relapse within the last month) and positively correlated with 2) presence of relapse within three months (linear regression, model r2=0.35, p=0.0001). There was no effect of time in the linear regression analysis. We observed a significantly higher average Ktrans in the treatment period in both NAWM and NAGM (Student´s t-test; p=0.01 and p=0.007, respectively), in the patients who did not have NEDA (equal to high disease activity despite treatment; n=15 out of 34). A logistic regression analysis showed that average Ktrans in the treatment period in both NAWM and NAGM predicted NEDA at one year (r2=0.27, p=0.04 and r2=0.33, p=0.03, respectively).
Conclusions: Here, for the first time we show that permeability of the blood-brain barrier measured by DCE-MRI holds important clinical information, which could be highly useful in clinical management of MS patients. Being able to detect early inadequate treatment response could potentially save MS patients from both relapses, and side-effects of an inefficacious treatment.
Disclosure:
SP Cramer has received speaking honoraria from Genzyme and research support from the The Danish Council for Independent Research, The Danish Multiple Sclerosis association, Rigshospitalets Research Fund and Biogen Idec.
HJ Simonsen: nothing to disclose.
J Frederiksen has served on scientific advisory boards for and received funding for travel related to these activities as well as honoraria from Biogen Idec, Merck Serono, Sanofi-Aventis, Teva, Novartis and Almirall. Dr. Frederiksen has received speaker honoraria from Biogen Idec, Merck Serono and Teva. She has served as advisor on preclinical development for Takeda.
HBW Larsson has received research support from the The Danish Council for Independent Research, The Danish Multiple Sclerosis association, Rigshospitalets Research Fund and Biogen Idec.
Abstract: P1266
Type: Poster
Abstract Category: Therapy - disease modifying - Tools for detecting therapeutic response
Purpose: We have previously shown that permeability of the blood-brain barrier, measured as the transfer constant Ktrans (ml/100g/min) by dynamic contrast-enhanced MRI (DCE-MRI) is linked to the degree of inflammation in MS patients, and thus could provide a quantitative measure of the current level of disease activity (Cramer, SP 2014 and 2015). Many efficacious treatment options have emerged in recent years, however detecting an unfavourable treatment response remains a challenge due to lack of quantitative methods. This study aimed to investigate whether Ktrans measured in the normal appearing white (NAWM) and grey matter (NAGM) can predict early inadequate response to second-line treatment (Fingolimod or Natalizumab, at the time of study initiation).
Methods: Sixty relapsing remitting MS patients were included in the study protocol consisting of a DCE-MRI at baseline (pre-treatment), and again three and six months post-treatment. Of these, thirty-four patients initiated second-line treatment for clinical reasons and completed the study protocol. Treatment effect after one year was assessed according to the international No Evidence of Disease Activity (NEDA) criteria by an experienced MS clinician, blinded to the DCE-MRI results.
Results: Baseline Ktrans in NAWM was inversely correlated with increasing baseline treatment intensity (categorical variable: (a) no treatment, (b) interferon-beta/glatiramer acetate or (c) prednisolone treatment after relapse within the last month) and positively correlated with 2) presence of relapse within three months (linear regression, model r2=0.35, p=0.0001). There was no effect of time in the linear regression analysis. We observed a significantly higher average Ktrans in the treatment period in both NAWM and NAGM (Student´s t-test; p=0.01 and p=0.007, respectively), in the patients who did not have NEDA (equal to high disease activity despite treatment; n=15 out of 34). A logistic regression analysis showed that average Ktrans in the treatment period in both NAWM and NAGM predicted NEDA at one year (r2=0.27, p=0.04 and r2=0.33, p=0.03, respectively).
Conclusions: Here, for the first time we show that permeability of the blood-brain barrier measured by DCE-MRI holds important clinical information, which could be highly useful in clinical management of MS patients. Being able to detect early inadequate treatment response could potentially save MS patients from both relapses, and side-effects of an inefficacious treatment.
Disclosure:
SP Cramer has received speaking honoraria from Genzyme and research support from the The Danish Council for Independent Research, The Danish Multiple Sclerosis association, Rigshospitalets Research Fund and Biogen Idec.
HJ Simonsen: nothing to disclose.
J Frederiksen has served on scientific advisory boards for and received funding for travel related to these activities as well as honoraria from Biogen Idec, Merck Serono, Sanofi-Aventis, Teva, Novartis and Almirall. Dr. Frederiksen has received speaker honoraria from Biogen Idec, Merck Serono and Teva. She has served as advisor on preclinical development for Takeda.
HBW Larsson has received research support from the The Danish Council for Independent Research, The Danish Multiple Sclerosis association, Rigshospitalets Research Fund and Biogen Idec.