Contributions
Abstract: P741
Type: Poster
Abstract Category: Therapy - disease modifying - Tools for detecting therapeutic response
Apheresis therapies include plasma exchange (PLEX) and immunoadsorption (IA), second line therapies to treat steroid unresponsive multiple sclerosis (MS) relapses that show a comparable response rate of 40 - 90%. Early active MS lesions can be classified into three main, intraindividually stable immunopathological patterns of demyelination (IP I-III), which suggests pathogenic heterogeneity and may also predict therapy response to PLEX/IA. A prior study of 19 patients showed that patients with an IP II, characterized by immunoglobulin and complement deposition, responded to PLEX treatment in contrast to patients with IPs I and III who had no treatment effects.
We aimed to evaluate the PLEX/IA response for MS relapses in relation to histopathologically defined IPs in a larger cohort of 69 patients.
For this we retrospectively analyzed the efficacy of PLEX/IA in patients with early active demyelinating MS lesions classified into IPs I-III, diagnosed in brain biopsies taken for differential diagnostic purposes. Primary outcome was a functional improvement of the neurological deficit occurring with the relapse. MRI and expanded disability status scale (EDSS) changes were used as secondary outcome parameters.
Clinical records of 69 patients (IP I - 16, IP II - 40, IP III - 13) were assessed. The highest response rate to PLEX/IA was 55% (22/40 patients) observed among IP II patients compared to no improvement found in patients with IP III (0/13; p< 0.001). However, one third of IP I patients also benefited from therapy (5/16 patients, IP I vs IP III p=0.03). Radiological assessment showed a decreasing lesion size or less contrast enhancement in 56% of patients with an IP II, 25% with an IP I and 11% with an IP III. Responders showed a reduction in the mean EDSS one month after PLEX/IA of 1.0 in IP II and of 0.7 in IP I patients. Brain stem involvement was found to be a negative predictive factor for therapy response. The highest predicted probability of clinical improvement after PLEX/IA was thus found in patients with an IP II who had no brainstem involvement (78%).
In conclusion, we confirmed that the therapy response to apheresis treatment is related to histopathologically defined IPs. Importantly, patients with both patterns I and II improved clinically after apheresis treatment; however, those patients with signs of a humoral immune response profited most from therapy. No clinical improvement was observed in patients with an IP III.
Disclosure:
L. Stork: nothing to disclose
D. Ellenberger: nothing to disclose
T. Beißbarth: nothing to disclose
T. Friede reports personal fees for consultance (including DMCs) from Novartis, Biogen, AstraZeneca, Bayer, Janssen, SGS, and Pharmalog outside the submitted work.
C. Lucchinetti reports grants from Biogen, Sanofi, Novartis, NMSS outside the submitted work.
W. Brück has received honoraria for lectures by Bayer Vital, Biogen, Merck Serono, Teva Pharma, Genzyme, Sanofi-Aventis and Novartis and is a member of scientific advisory boards for Teva Pharma, Biogen, Novartis and Genzyme. He received funding for research projects by Teva Pharma, Biogen, Novartis and Genzyme. Dr Brück serves on the editorial boards of Neuropathology and Applied Neurobiology, Multiple Sclerosis International and Therapeutic Advances in Neurological Disorders.
I. Metz reports grants from German Ministry for Education and Research (BMBF "German Competence Network Multiple Sclerosis (KKNMS), Pattern MS/NMO), grants from BiogenIdec as well as personal fees from BiogenIdec, Bayer Healthcare, TEVA, Serono and Novartis outside the submitted work.
Abstract: P741
Type: Poster
Abstract Category: Therapy - disease modifying - Tools for detecting therapeutic response
Apheresis therapies include plasma exchange (PLEX) and immunoadsorption (IA), second line therapies to treat steroid unresponsive multiple sclerosis (MS) relapses that show a comparable response rate of 40 - 90%. Early active MS lesions can be classified into three main, intraindividually stable immunopathological patterns of demyelination (IP I-III), which suggests pathogenic heterogeneity and may also predict therapy response to PLEX/IA. A prior study of 19 patients showed that patients with an IP II, characterized by immunoglobulin and complement deposition, responded to PLEX treatment in contrast to patients with IPs I and III who had no treatment effects.
We aimed to evaluate the PLEX/IA response for MS relapses in relation to histopathologically defined IPs in a larger cohort of 69 patients.
For this we retrospectively analyzed the efficacy of PLEX/IA in patients with early active demyelinating MS lesions classified into IPs I-III, diagnosed in brain biopsies taken for differential diagnostic purposes. Primary outcome was a functional improvement of the neurological deficit occurring with the relapse. MRI and expanded disability status scale (EDSS) changes were used as secondary outcome parameters.
Clinical records of 69 patients (IP I - 16, IP II - 40, IP III - 13) were assessed. The highest response rate to PLEX/IA was 55% (22/40 patients) observed among IP II patients compared to no improvement found in patients with IP III (0/13; p< 0.001). However, one third of IP I patients also benefited from therapy (5/16 patients, IP I vs IP III p=0.03). Radiological assessment showed a decreasing lesion size or less contrast enhancement in 56% of patients with an IP II, 25% with an IP I and 11% with an IP III. Responders showed a reduction in the mean EDSS one month after PLEX/IA of 1.0 in IP II and of 0.7 in IP I patients. Brain stem involvement was found to be a negative predictive factor for therapy response. The highest predicted probability of clinical improvement after PLEX/IA was thus found in patients with an IP II who had no brainstem involvement (78%).
In conclusion, we confirmed that the therapy response to apheresis treatment is related to histopathologically defined IPs. Importantly, patients with both patterns I and II improved clinically after apheresis treatment; however, those patients with signs of a humoral immune response profited most from therapy. No clinical improvement was observed in patients with an IP III.
Disclosure:
L. Stork: nothing to disclose
D. Ellenberger: nothing to disclose
T. Beißbarth: nothing to disclose
T. Friede reports personal fees for consultance (including DMCs) from Novartis, Biogen, AstraZeneca, Bayer, Janssen, SGS, and Pharmalog outside the submitted work.
C. Lucchinetti reports grants from Biogen, Sanofi, Novartis, NMSS outside the submitted work.
W. Brück has received honoraria for lectures by Bayer Vital, Biogen, Merck Serono, Teva Pharma, Genzyme, Sanofi-Aventis and Novartis and is a member of scientific advisory boards for Teva Pharma, Biogen, Novartis and Genzyme. He received funding for research projects by Teva Pharma, Biogen, Novartis and Genzyme. Dr Brück serves on the editorial boards of Neuropathology and Applied Neurobiology, Multiple Sclerosis International and Therapeutic Advances in Neurological Disorders.
I. Metz reports grants from German Ministry for Education and Research (BMBF "German Competence Network Multiple Sclerosis (KKNMS), Pattern MS/NMO), grants from BiogenIdec as well as personal fees from BiogenIdec, Bayer Healthcare, TEVA, Serono and Novartis outside the submitted work.