In this retrospective study focused on the effect of TPE on EDSS improvement in patients with a steroid–resistant relapse of RRMS, we observed that 50% patients reached a significant EDSS improvement, 37% of patients remained unchanged in their EDSS, while 13% patients experienced further clinical worsening. Females responded better to the TPE than males in our cohort. We did not observe a significant difference in TPE effectivity according to the severity of baseline EDSS or a total number of TPE procedures.
The ASFA recommends TPE for a treatment of aggressive MS relapse to the category II, meaning that it is accepted as the second–line therapy. The AAN recommends TPE as an adjunctive therapy (level B).12,13 A recent systematic review and meta–analysis16 focused on TPE in RRMS systematically analyzed 14 studies (mostly retrospective) of a different methodological quality and heterogeneity of patient cohorts. These studies differed also in the numbers of patients, TPE protocols (some of them even do not mention their TPE protocols), number of TPE procedures and TPV. Our study focused solely on the patients with RRMS.
Our study analyzed 603 TPEs performed in 155 patients, which represents one of the largest cohorts so far. In all 155 patients, it was their first TPE treatment. The above–mentioned meta–analysis included 398 patients from 14 studies. The six studies were considered to be methodologically similar to our study. 3,18,20−23. Nevertheless, most of the primary studies selected the target neurological deficit (TND) as a primary endpoint20–22, one study used the MSFC18 and one study used the EDSS as an outcome measure23. The EDSS was considered as a secondary outcome in most of the studies18,20,22. In our study, we used the EDSS as a primary outcome, as it still represents the most commonly used clinical scale in MS patients. Since it was evaluated by a certified MS specialist on every follow–up, it allowed us to monitor the EDSS dynamics over time (before corticosteroid treatment, after corticosteroid treatment, before initiation of TPE and after the TPE treatment/at the next clinical follow–up). Even though the TND and MSFC are considered as being more sensitive scales to detect changes in patient clinical status, unfortunately we lacked sufficient data to evaluate these outcomes accordingly.
The data from the meta–analysis suggest the effectivity of TPE between 41–93%, mostly around 76%16. In our cohort, we observed the therapy response (EDSS improvement) in 50 patients. The relatively lower percentage of improvement might be explained by selecting a less sensitive scale for addressing the relapse (EDSS). Considering the number of patients included, methodological background, number of TPEs and major findings, the study by Ehler et al.22 was a very similar to our study. They included MS patients with a history of steroid–intolerance and/or inadequate response to steroids. The study differed in their primary endpoint (TND). A significant therapy response was observed in 72 %patients, which is higher than in 34 %patients who experienced improvement in EDSS in our cohort.
Considering the safety of TPE, even though many adverse events have been described, they are usually preventable and thus rare in occurrence. What we cannot predict is an allergic reaction or technical problems with the set. The occurrence of adverse events in literature ranges between 4 to 26%.16 In our cohort, only 6 of adverse events were reported, most of them accounting for a PIVC failure (3.7 ), followed by a vasovagal reaction (1.8 ) and allergic reactions (0.5 ), and all of them were not considered as severe.
Though commonly used, TPE is not the only way to treat a steroid–refractory MS relapse. The first successful use of immunoadsorption (IA) in MS relapse was described in 2000 by De Andrés et. al24. Since then, several studies have compared IA to TPE as a new, possibly safer and more effective alternative of a second–line therapy in MS. MS patients, who underwent IA, showed a higher response rate after 4 weeks (86.7%) compared to patients treated with the TPE (76.7%). A study by Lipphardt et al. conducted in 2018 did not support these findings and claimed, that IA and TPE seemed to be equally safe and effective in steroid–resistant MS relapse. Further well–designed studies are thus needed. The problem that arises with IA is that in many countries the costs are not covered from the health insurance and thus it limits the use of IA.
Single center and retrospective design of our study represent major limitations. Unmeasured confounders may have affected treatment decisions. Additionally, the EDSS assessment was not blinded, as it was performed by different certified MS specialists (who were not aware about this project at the time of clinical assessment). Another limitation of all the studies included, and ours as well, was that there was no separate control group. Since properly–designed randomized control trials are lacking and most of the published studies suffer from several limitations, treating severe MS relapse still remains a challenge.3,25