Patients with multiple sclerosis (MS) respond differently to apheresis according to the immunopathologic pattern of their MS. In a single-cohort study of 69 patients with MS, about one third of patients with pattern 1 disease and about one half with pattern 2 disease demonstrated functional therapy response to apheresis compared with none of the patients with pattern 3 disease. The findings appear in JAMA Neurology.
Early active demyelinating MS lesions can be classified into three main stable immunopathologic patterns of demyelination that suggest pathogenic heterogeneity. Although patterns 1 and 2 share similar features of demyelination, only pattern 2 lesions are defined by additional antibody and complement deposition along myelin sheaths and present within macrophages. Pattern 3 lesions show a more degenerative character and are defined by oligodendrocytic damage.
For this study, investigators led by Lidia Stork, MD, University Medical Center Göttingen, Germany, recruited 69 patients with early active demyelination who were classified as immunopathologic pattern 1 (n=16), 2 (n=40), or 3 (n=13) on the basis of brain biopsy analysis. Patients were treated for steroid-unresponsive MS relapses with plasma exchange (PLEX) and immunoadsorption (IA).
Dr. Stork and colleagues then assessed treatment response, magnetic resonance imaging (MRI) changes, and Expanded Disability Status Scale (EDSS) scores.
In most demographic and clinical parameters, the three groups showed no significant differences, but pattern 3 patients more frequently showed a clinically isolated syndrome (69%) compared with all three groups (P=0.02). Pattern 2 patients more often had relapsing-remitting disease (65%, P=0.02), and longer disease duration (P=0.07).
After apheresis therapy, functioning improved in pattern 1 and 2 patients, but not in pattern 3. Within 1 month of apheresis, 39% of patients were declared treatment successes, which these researchers defined as moderate or marked therapy response with a functional improvement of deficits.
“This percentage is consistent with published data,” the investigators noted.
Patients with pattern 2 disease had the highest response rate to PLEX/IA (55%). In contrast, 0 of 13 of pattern 3 patients had treatment success (P < 0.001), and 5 of 16 pattern 1 patients experienced improvement (P=0.03 vs pattern 3).
Lesion improvement, defined as lesions becoming smaller and/or showing less gadolinium enhancement, occurred in 39% of patients overall. On MRI, pattern 2 patients demonstrated the most pronounced improvement in lesions, followed by patients with pattern 1 lesions.
Some 56% of patients with pattern 2 disease showed lesion regression compared with only 11% of patients with pattern 3 disease (P=0.03). Finally, 25% of pattern 1 patients showed lesion regression.
The overall rate of response as measured by EDSS was 28%, which was lower than the functional response observed in 39% of patients, the authors pointed out, explaining that the EDSS focuses on the function of the lower extremities “and has a poor sensitivity for disabilities that occur because of involvement of upper extremities or because of cognitive changes.”
The highest EDSS response rate occurred in patients with pattern 2 disease (40%), followed by pattern 1 patients (25%). None of the 13 patients with pattern 3 showed improvements in EDSS. Of the responders, those with pattern 2 lesions showed a median reduction in EDSS of 0.5 points, while responders with pattern 1 lesions showed a median reduction of 1.5 points.
Pattern 1 and pattern 2 disease were positive predictive factors for response to therapy. Therapy with IA compared with PLEX was also predictive of response in patients with pattern 1 and 2 lesions (P=0.01). Pattern 2 patients without brainstem involvement had a high probability of a response to IA.
The study was limited by the low number of patients treated with IA (a total of 10), the authors wrote, “so that further studies are necessary to explore whether IA may even have superior treatment outcomes. Interestingly, IA not only removes antibodies but also other proteins that may be involved in MS pathogenesis.”
In an editorial to accompany the study, Robert J. Fox, MD, from Cleveland Clinic, Cleveland, OH, wrote, “This study is important in providing the first evidence that short-term treatment response is related to pathologic patterns within MS lesions. These observations further support the clinical relevance of MS lesion patterns and suggest that they may be useful in better understanding heterogeneity in treatment response to MS therapies.”
The study also supports apheresis as a short-term treatment for central nervous system demyelination, according to Dr. Fox, who added, “The mechanism by which apheresis disrupts the pathogenesis of acute central nervous system demyelination is not clear, but strong responses across both patterns 1 and 2 suggest that the effect likely crosses multiple immune mechanisms.”