Rituximab and IVIG added to plasma exchange improves the outcome of severe CNS demyelinating attacks: a retrospective study

Abstract

Background:

Plasma exchange (PE) is a therapeutic option for CNS demyelinating attacks unresponsive to corticosteroids, but the potential benefit of adding rituximab and IV immunoglobulins to PE (RTX-IVIG-PE), which has shown its efficacy and safety in other immune-mediated conditions, has not been investigated.

Objective:

We aimed to determine the overall effectiveness of PE in severe demyelinating attacks, identify predictors of response, and compare outcomes between standard PE and RTX-IVIG-PE protocols.

Design:

Retrospective analysis of patients with CNS demyelinating attacks treated with PE between 2012 and 2023 across five Spanish hospitals.

Methods:

Clinical response was measured as an improvement or a complete recovery at discharge and 6 months. Uni- and multivariable logistic regression models were developed to identify predictors of PE response. A logistic regression analysis, after inverse probability of treatment weighting (IPTW), was performed to compare the outcome of attacks treated with standard PE and RTX-IVIG-PE.

Results:

A total of 162 attacks in 150 patients (81 multiple sclerosis; 37 others acquired demyelinating syndromes; 27 neuromyelitis optica spectrum disorder; 5 myelin oligodendrocyte glycoprotein antibody-associated disease; 73% female; median age 43 years (interquartile range 33–52.75)) were analyzed. At discharge, 60% of all attacks showed clinical improvement, and 15% achieved complete recovery. At 6 months, these rates increased to 77% and 31%, respectively. Younger age, lower preattack Expanded Disability Status Scale, and treatment with RTX-IVIG-PE were independent predictors of complete recovery at 6 months. IPTW analysis showed that attacks treated with RTX-IVIG-PE (33) were associated with improvement (adjusted odds ratio (aOR) 5.4, p < 0.001) and complete recovery (aOR 4.55, p < 0.001) at 6 months compared to those treated with standard PE (129), without significant differences in the adverse event profile between the two protocols.

Conclusion:

PE improves the outcome of steroid-refractory CNS demyelinating attacks, and the addition of rituximab and IVIG to PE may increase the likelihood of long-term recovery.

Plain language summary

Improving recovery after severe inflammatory attacks of the brain and spinal cord: how combining plasma exchange with rituximab and immunoglobulins may lead to better long-term outcomes

Severe inflammatory attacks affecting the brain, spinal cord, or optic nerves can cause sudden and serious disability in people with diseases such as multiple sclerosis and related conditions. These attacks are usually treated first with high-dose steroids, but some patients do not improve with this approach. In these situations, a treatment called plasma exchange is often used. Plasma exchange is a procedure that removes harmful antibodies and inflammatory substances from the blood. In this study, we looked at how well plasma exchange worked in people with severe attacks that did not respond to steroids. We also examined whether adding two additional treatments—rituximab (a drug that reduces certain immune cells) and intravenous immunoglobulins (protective antibodies from healthy donors)—could further improve recovery. We reviewed medical records from five hospitals in Spain and included 150 patients who experienced 162 severe attacks between 2012 and 2023. Most patients showed improvement after plasma exchange. About 6 out of 10 patients improved by discharge, and this increased to more than 3 out of 4 patients after six months. Importantly, recovery continued over time, meaning that some patients who did not improve immediately showed benefits months later. Patients who were younger, had less disability before the attack, and received the combined treatment with rituximab and immunoglobulins were more likely to recover fully. Those who received the combined treatment had a higher chance of both improvement and complete recovery six months after the attack compared with those who received plasma exchange alone. Importantly, adding these treatments did not increase the risk of serious side effects or infections. In summary, plasma exchange is an effective treatment for severe inflammatory attacks of the nervous system when steroids fail. Combining plasma exchange with rituximab and immunoglobulins may increase the chances of long-term recovery.

Keywords

demyelinating intravenous immunoglobulins multiple sclerosis neuromyelitis optica plasma exchange rituximab

Introduction

Plasma exchange (PE) is widely used in the management of severe attacks of CNS inflammatory demyelinating diseases. The therapeutic mechanism of PE is primarily based on the rapid extracorporeal removal of plasma autoantibodies, pro-inflammatory mediators, and immune complexes, along with the induction of autoantibody redistribution from the extravascular space.

PE is particularly indicated in cases where patients fail to respond to standard treatment with high-dose methylprednisolone (MTP)^1
–3 and is recommended by the American Academy of Neurology as an adjunctive treatment in steroid-refractory acute attacks (Level B recommendation).⁴ While evidence for response is more robust in multiple sclerosis (MS) attacks, several observational studies have shown a beneficial effect of PE in acute attacks of other demyelinating diseases, such as neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), among others.^5
–8

Clinical predictors of response to PE have been identified, including early initiation of PE and low pre-existing disability.^5,7,9 However, most supporting studies are limited to case reports or single-center experiences and have primarily focused on short-term outcomes.^9
–11 Moreover, the potential benefits of adjunctive treatments such as rituximab for inhibiting the production of antibodies through the removal of B-lymphocytes¹² to enhance the effectiveness of its removal by PE, in neurological conditions remain largely unexplored. In other immune-mediated conditions, such as acute humoral rejection of kidney transplantation,¹³ severe cases of warm autoimmune hemolytic anemia,¹⁴ the removal of the antibodies responsible for the destruction of transfused platelets in cases of platelet transfusion refractoriness,¹⁵ or in cases of autoimmune thrombotic thrombocytopenic purpura, the combination of rituximab and intravenous immunoglobulin (IVIG) replacement with PE was shown to be effective and safe.¹⁶ In these conditions, the strategy is to block the production of the antibodies by rituximab,¹² and after, to perform PE to remove the antibodies in the circulation, since the half-life of IgG in circulation is 23 days.¹⁷ The administration of low doses of IgG between PE shall avoid the hypogammaglobulinemia induced by PE, since not only pathogenic but also protective antibodies are removed, so a humoral immunosuppression is induced.¹⁸ However, other immunomodulatory effects cannot be completely ruled out.¹⁹

As far as we know, this strategy has not been investigated in the setting of inflammatory demyelinating diseases of the CNS.

Objectives

In this study, we aimed to determine the overall outcome of patients with severe attacks of CNS inflammatory demyelinating diseases treated with PE, identify predictors of clinical response, and compare the outcomes of standard PE with that of rituximab and IVIG combined with PE (RTX-IVIG-PE).

Study design

This retrospective observational study included all patients treated with PE for acute attacks of CNS inflammatory demyelinating diseases between January 1, 2012, and November 30, 2023, across five Spanish university hospitals. Inclusion criteria were age ⩾18 years, completion of PE within 90 days of initiating MTP, having received at least one course of high-dose MTP (1 g daily for a minimum of 3 days, administered orally or intravenously) and having undergone between 5 and 10 exchange sessions. Patients were excluded if they did not have a follow-up visit with a neurological examination 6 months after PE. Medical records were reviewed to collect data on patient demographics, disability prior to attack and at PE onset (preattack Expanded Disability Status Scale (EDSS)), previous immunomodulatory or immunosuppressant treatment (disease modifying treatment, DMT), time from MTP initiation to first exchange, PE-related variables, other additional acute immunosuppressive treatments (within 30 days following PE), procedure-related adverse events, and treatment outcomes.

Clinical diagnoses were based on established criteria for MS,²⁰ NMOSD,²¹ and MOGAD.²² Patients not fulfilling any of the above criteria at the last follow-up were classified as having other acquired demyelinating syndrome (OADS).

The study was approved by the ethics committee at Hospital Universitario Ramón y Cajal (code 024/23). Due to its retrospective design, informed consent was deemed unnecessary. This retrospective observational study was designed and reported in accordance with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines.

Methods

Evaluated outcomes

The primary outcomes were improvement and complete recovery, measured at discharge and at 6 months after PE.

Improvement was defined according to any of the following criteria⁷:

a reduction of at least 1.0 point on the EDSS for patients with EDSS ⩽7.5 at PE onset

a reduction of at least 1.5 points for patients with ⩾8.0

for patients experiencing an optic neuritis (ON) attack, an improvement of more than two lines on the visual acuity chart

complete recovery.

Complete recovery was defined as a return to the preattack EDSS score or the presence of only minor residual signs on examination (EDSS ⩽ 1.5).

PE protocols

In all centers, between 1.25 and 1.66 plasma volumes were exchanged every other day, and patients received between 5 and 10 exchanges. The removed plasma volume was replaced with 5% normal serum albumin in all patients.

In one center (Hospital Clínic Barcelona), all patients underwent the RTX-IVIG-PE protocol that included IVIG at a dose of 200 mg/kg after the second, fourth, and sixth PE sessions, along with two doses of 200 mg rituximab—one administered the day before the first exchange, and the second following the last IVIG infusion. In the remaining centers, patients underwent the standard PE protocol.

Statistical analysis

Descriptive analyses were summarized using absolute and relative proportions for categorical variables, while medians with interquartile ranges (IQR) were used for continuous variables. For analytical purposes, the outcome of each attack was considered, as some patients experienced multiple attacks during the study period. Continuous and categorical variables were compared using the Mann-Whitney U test and Fisher’s exact test, respectively, as appropriate.

Univariable and multivariable logistic regression models were used to identify predictors of PE response at discharge and at 6 months. The variables analyzed were age, sex, etiology, type of attack, preattack EDSS, MTP dose, and interval between MTP and PE, EDSS at PE onset, number of PE sessions, type of PE protocol (standard vs RTX-IVIG-PE), and additional acute treatments. Multivariable analysis included age, preattack EDSS, etiology, type of attack, and RTX-IVIG-PE protocol for improvement. Regarding complete recovery, multivariable analysis included age, preattack EDSS, number of exchanges, and RTX-IVIG-PE protocol.

To account for baseline differences between the RTX-IVIG-PE and standard PE groups, an inverse probability of treatment weighting (IPTW) was applied. IPTW is a propensity score-based method designed to reduce confounding in observational studies by mimicking some of the characteristics of a randomized treatment assignment.²³ By weighting individuals according to the inverse probability of receiving the treatment they actually received, IPTW creates a pseudo-population in which baseline covariates are balanced across treatment groups. The propensity model included previous DMT, etiology, EDSS at PE onset, MTP dosage, and number of exchanges as covariates (Supplemental Figure 1). Stabilized weights were used to improve estimation precision for weighted logistic regression models. A sensitivity analysis was carried out excluding recurrent attacks.

All analyses were conducted using RStudio (version 2023.06.0, Posit Software, PBC, Boston). A p-value <0.05 was considered statistically significant.

Results

Clinical characteristics of the CNS demyelinating attacks

A total of 198 attacks in 184 patients with inflammatory demyelinating diseases of the CNS treated with PE were identified. After exclusion of 36 attacks (18%) due to failure to meet inclusion (29) or exclusion (7) criteria, 162 attacks in 150 patients were eligible for assessment (Figure 1, Table 1). Most attacks occurred in women (n = 118, 72.8%), and the median age at the time of PE was 43 years (IQR 33–52.7). Of the 150 patients, 81 had MS (54%), 37 OADS (25%), 19 aquaporine-4 antibodies positive (AQP4+) NMOSD (13%), 8 seronegative NMOSD (5%), and 5 MOGAD (3%). Ten patients (6.7%) experienced more than one attack: seven had AQ4+ NMOSD, two OADS, and one MS. ON (37.7%) and myelitis (29.6%) were the most frequent attack manifestations (Table 1).

Figure 1.

Flow-chart of patients with attacks of demyelinating diseases affecting the central nervous system undergoing PEs.

Table 1.

Demographic, clinical features, and treatment data of 150 patients with 162 attacks undergoing PE.

Characteristics	All attacks (n = 162)	RTX-IVIG-PE (n = 33)	Standard PE (n = 129)	p
Number of patients	150	31	119	1
Patients with 1 attack	140 (93.3%)	29 (93.5%)	111 (93.3%)
Patients with ⩾2 attacks	10 (6.7%)	2 (6.5%)	8 (6.7%)
Age, years	43 (33–52.75)	41 (34–54)	44 (33–52)	0.76
Sex, female	118 (72.8%)	20 (60.6%)	98 (76%)	0.68
Etiology of demyelinating attack				<0.001
MS	82 (50.6%)	6 (18.2%)	76 (58.9%)
OADS^a	39 (24.1%)	16 (48.5%)	23 (17.8%)
AQP4+ NMOSD	28 (17.3%)	7 (21.2%)	21 (16.3%)
Seronegative NMOSD	8 (4.9%)	1 (3%)	7 (5.4%)
MOGAD	5 (3.1%)	3 (9.1%)	2 (1.6%)
Type of attack				0.53
ON	61 (37.7%)	16 (48.5%)	45 (34.9%)
Myelitis	48 (29.6%)	7 (21.2%)	41 (31.8%)
Multifocal	32 (19.8%)	7 (21.2%)	25 (19.4%)
Brainstem/cerebellum	12 (7.4%)	1 (3%)	11 (8.5%)
Pseudotumoral	9 (5.6%)	2 (6.1%)	7 (5.4%)
Patients on DMT	62 (38.2%)	8 (24.2%)	54 (41.0%)	0.008
Anti-CD20	11 (6.8%)	5 (15.6%)	6 (4.7%)
Low-moderate efficacy MS DMT^b	28 (17.3%)	1 (3.1%)	27 (20.9%)
High efficacy MS DMT^b	18 (11.1%)	1 (3.1%)	17 (13.2%)
Other^c	5 (3.1%)	1 (3.1%)	4 (3.2%)
Pre-attack EDSS	0 (0–2.5)	0 (0–1.5)	1 (0–3)	0.18
Patients with EDSS score of 0	84 (51.8%)	21 (63.6%)	63 (48.8%)	0.17
MTP dose given prior to PE, grams	5 (5–6)	5 (3–5)	5 (5–7)	<0.001
Time from MTP to PE, days	11 (6–25.75)	14 (7–21)	11 (6–29)	0.98
EDSS at PE onset	4.5 (3.5–6.5)	5 (4–7)	4 (3.5–6.5)	0.029
Number of exchanges	6 (5–7)	6 (6–6)	7 (5–8)	0.019
Infections after PE^d	6 (3.7%)	2 (6.9%)	4 (3.7%)	0.61

Categorical variables are shown as number (%). Continuous variables are described as median (interquartile range).

Patients with an acute demyelinating attack not meeting any of MS, NMOSD, or MOGAD criteria were classified as having OADS.

Low-moderate efficacy MS DMT included interferon, glatiramer acetate, teriflunomide and fumarates; and high-efficacy treatment included: fingolimod, ponesimod, ozanimod, cladribine, natalizumab, alemtuzumab, rituximab, ocrelizumab, ofatumumab.

Other previous immunomodulators included: azathioprine, methotrexate, steroids, and intravenous immunoglobulins.

Infections occurring within the first 6 months following the initiation of PE were assessed.

p Values that reached statistical significance (p ⩽ 0.05) are highlighted in bold.

AQP4+, aquaporine-4 positive antibodies; DMT, disease modifying treatment; EDSS, expanded disability status scale; MOGAD, myelin oligodendrocyte glycoprotein antibodies associated disease; MS, multiple sclerosis; MTP, methylprednisolone; NMOSD, neuromyelitis optica spectrum disorder; OADS, other acquired demyelinating syndrome; PE, plasma exchanges; RTX-IVIG-PE, Rituximab and IVIG combined with plasma exchange protocol.

At PE onset, all patients were moderately or severely disabled (median EDSS score 4.5, IQR 3.5–6.5). The median interval between MTP initiation and first PE session was 11 days (IQR 6–25.75) and was less than 15 days in 98 attacks (60.5%). This interval did not differ significantly between diagnostic subgroups (p = 0.1). Standard PE was used in 129 attacks and RTX-IVIG-PE in 33 attacks. Median time to complete the standard PE protocol was 14 (10–16) days, while for RTX-IVIG-PE was 13 days (12–13) (p = 0.34). A total of 31 attacks (19.1%) required additional acute treatment after PE, without differences between standard PE (23/129, 18%) and RTX-IVIG-PE (8/33, 24%), (p = 0.19): additional cycles of MTP in 17 attacks, cyclophosphamide in 8, standard courses of IVIG in 2, and other therapies in 4. At 6 months after PE, most patients (73.4%) were on DMT, 57.6% of those treated with RTX-IVIG-PE, and 77.4% of those treated with the standard PE (p = 0.028; Supplemental Table 1).

Outcome results and predictors of response to PE

At discharge (median of 14 days (IQR 10–21) after PE onset), improvement was observed in 97 attacks (60%), and at 6 months in 125 (77%; p < 0.001), while complete recovery was observed in 24 (15%) and 50 (31%) attacks, respectively (p < 0.001). No new relapses were observed during the 6-month follow-up period.

Univariable analyses of factors associated with improvement and complete recovery are provided in Supplemental Tables 1 and 2. In brief, younger age was associated with higher odds of improvement and complete recovery both at discharge and at 6 months. The diagnosis of OADS at PE onset, nonbrainstem or multifocal attack, and a lower EDSS score prior to attack were associated with a higher chance of improvement at discharge. Treatment with RTX-IGIV-PE was associated with higher odds of achieving a complete recovery (odds ratio (OR) 2.6 (95% confidence interval (CI): 1.2–5.8), p = 0.02) and a trend toward improvement (OR 3.6 (95% CI: 1.2–15.6), p = 0.05) at 6 months.

In multivariable analysis, younger age was independently associated with improvement at 6 months (Figure 2(a) and (b)) and with complete recovery at discharge and 6 months; preattack EDSS score was associated with complete recovery at both discharge and 6 months; and the use of RTX-IVIG-PE with a higher likelihood of complete recovery at 6 months (adjusted odds ratio (aOR) 2.7, p = 0.025) (Figure 3(a) and (b)).

Figure 2.

Predictive factors of improvement following PE in central nervous system demyelinating attacks (multivariable analysis). Odds ratios and 95% confidence intervals from multivariable logistic regression models for clinical improvement at discharge (a) and at 6 months (b).

Figure 3.

Predictive factors of complete recovery following PE in central nervous system demyelinating attacks (multivariable analysis). Odds ratios and 95% confidence intervals from multivariable logistic regression models for complete recovery at discharge (a) and at 6-month follow-up (b).

Impact of RTX-IVIG-PE on the outcome

Clinical and demographic characteristics of the attacks that underwent standard PE or RTX-IVIG-PE are shown in Table 1. At 6 months, the rate of improvement was higher for attacks treated with RTX-IVIG-PE than with standard PE (91% vs 74%, p = 0.037), and the same for complete recovery (49% vs 27%, p = 0.02; Figure 4).

Figure 4.

Proportion of patients with improvement and complete recovery in the RTX-IVIG-PE and standard PE groups.

Logistic regression analysis after adjustment for IPTW of attacks treated with standard PE or RTX-IVIG-PE showed that RTX-IVIG-PE was associated with improvement at 6 months (OR 5.4, (95% CI: 2.3–15.85), p < 0.001) and complete recovery at discharge (OR 3.1 (95% CI: 1.6–6.25), p < 0.001) and at 6 months (OR 4.55 (95% CI: 2.6–8.1), p < 0.001; Supplemental Table 4). There were no differences in improvement at discharge.

Sensitivity analysis excluding participants with recurrent attacks displayed similar results: improvement at 6 months (OR 5.1, (95% CI: 2.1–15.45), p = 0.001) and complete recovery at discharge (OR 2.4 (95% CI: 1.2–5.1), p = 0.02) and at 6 months (OR 4.25 (95% CI: 2.4–7.8), p < 0.001).

Safety

Infection rates 6 months after treatment were similar for attacks treated with RTX-IVIG-PE than with standard PE (6.9% vs 3.9%, p = 0.61; Table 1). All infections were mild and included urinary tract infections, phlebitis, and fever of unknown origin, and none required hospitalization. A serious adverse event occurred in two patients treated with standard PE: deep vein thrombosis and retroperitoneal hematoma.

Discussion

In this study, we analyzed the outcomes of 162 attacks in 150 patients with CNS demyelinating syndromes who were unresponsive to high-dose corticosteroids and underwent PE. Our findings indicate that PE is a highly effective therapy in the short term (median 14 days), leading to improvement and complete recovery in 60% and 15% of attacks, respectively, with these rates increasing over the long term to 77% and 31% at 6 months. The latter is important because it means that 43% of the attacks that did not respond early to PE did so at 6 months.

The finding of progressive recovery over several months after PE is not new^7,9,24,25 but the study, with a large number of attacks assessed, confirms the usefulness of PE across the spectrum of severe CNS inflammatory demyelinating diseases, and provides important information on functional neurological outcomes after discharge, a relevant aspect when informing patients and their relatives about expected recovery.

Multivariable analysis showed that several factors were associated with both short- and long-term recovery and should be considered in future studies. Age was the most consistent predictor of both improvement and complete recovery, and each additional year of age was associated with a 5% reduction in the odds of complete recovery. Unlike some studies,^9,26 but in line with others,^7,8 we did not identify sex as a significant determinant of response to PE. However, the favorable outcome in patients with less disability and a lower preattack EDSS score has been less reported and likely reflects more efficient repair mechanisms.⁵ The trend toward better response in patients diagnosed with OADS is consistent with this finding, as these are patients with early-stage demyelinating diseases in whom a definitive diagnosis has not yet been established due to limited follow-up.

Our findings challenge prior research, which identified early initiation of PE as a favorable predictor of response in steroid-refractory CNS demyelinating diseases attacks.^7,8,24 One possible explanation for this discrepancy is the relatively uniform timing of PE initiation in our cohort, with 75% of patients starting treatment within the first 25 days after high-dose steroid administration. In fact, the median time between MTP and PE was only 11 days. This finding supports the importance of timely intervention to improve treatment outcomes.

A key contribution of this multicenter study was the evaluation of the RTX-IVIG-PE protocol in the treatment of severe CNS demyelinating attacks. Attacks treated with RTX-IVIG-PE demonstrated significantly higher rates of improvement and complete recovery, particularly in the long term, compared to those receiving standard PE. Importantly, RTX-IVIG-PE emerged as an independent predictor of a favorable outcome. Given the observational and retrospective nature of the study—and the inherent risk of confounding due to baseline differences between the two treatment groups—an IPTW approach was applied. RTX-IVIG-PE increased the likelihood of attack improvement and complete recovery, compared with standard PE at 6 months. By integrating B-cell depletion and immunoglobulin replacement with PE, the RTX-IVIG-PE protocol may synergistically enhance immune modulation, potentially reducing long-term sequelae. Rituximab depletes B-cells, the precursors of autoantibody production, while IVIG exerts additional effects on autoantibody regulation. The potential benefit of combining rituximab and IVIG with PE has been demonstrated in other conditions and is currently standard therapy, for instance, for ABO-incompatible kidney transplantation, immune thrombotic thrombocytopenic purpura,^16,27 idiopathic pulmonary fibrosis,²⁸ acute antibody-mediated rejection after ABO-compatible kidney transplantation, as well as hematologic disorders.²⁵

The superior outcomes associated with RTX-IVIG-PE are unlikely to be explained by differences in subsequent relapse activity, additional acute treatments, or postrelapse DMT exposure. No new attacks occurred during the 6-month follow-up in either group, the use of other acute therapies did not differ significantly between both therapies, and DMT use was lower in the RTX-IVIG-PE group. Importantly, the superiority of this protocol in terms of complete recovery was already evident at hospital discharge, further supporting a treatment effect that appears independent of subsequent therapeutic differences.

An important finding is that the addition of rituximab and IVIG did not increase the rate of adverse events, supporting the safety and feasibility of this combined approach in clinical practice. These findings contribute to the growing body of evidence supporting multimodal therapeutic strategies to improve outcomes in patients with severe and disabling neurological disorders.

This study has some limitations, including its retrospective design, the underrepresentation of certain conditions such as MOGAD, the lack of information on the timing of DMT initiation after each attack, and the fact that the RTX-IVIG-PE therapy was administered at a single center, warranting cautious interpretation of the results. Furthermore, while the IPTW approaches help minimize baseline imbalances, prospective randomized trials are needed to confirm the observed benefits and refine predictive models.

Conclusion

In conclusion, our study confirms the effectiveness of PE in the treatment of severe attacks of demyelinating CNS diseases and introduces its combination with rituximab and IVIG as a promising approach that may improve outcomes. By providing both clinical and predictive insights, our findings pave the way for more personalized treatment strategies and underscore the need for further research to validate and expand these observations.

Supplemental Material

sj-docx-1-tan-10.1177_17562864261440665 – Supplemental material for Rituximab and IVIG added to plasma exchange improves the outcome of severe CNS demyelinating attacks: a retrospective study

Supplemental material, sj-docx-1-tan-10.1177_17562864261440665 for Rituximab and IVIG added to plasma exchange improves the outcome of severe CNS demyelinating attacks: a retrospective study by Juan Luis Chico-Garcia, Moisés Morales de la Prida, Almudena Boix Lago, José Manuel García-Domínguez, María Sepúlveda, Eugenia Martínez-Hernández, Mar Guasp, Elianet Fonseca, Alberto Calvi, María Teresa Alba-Isasi, Blanca Albertí, Joan Cid, Miquel Lozano, Paola Charry, Fernando Rodríguez-Jorge, Raquel Sainz-Amo, Susana Sainz de la Maza, Enric Monreal, Luisa Maria Villar, Jaime Masjuan, Gabriel Valero-López, Jorge Millán-Pascual, Juan Pablo Cuello, Michael Palacios, Ariadna Gifreu Fraixinó, María Luisa Martínez-Gins, Gary Álvarez Bravo, José E. Meca-Lallana, Lucienne Costa-Frossard, Yolanda Blanco, Jose Maria Cabrera-Maqueda, Albert Saiz and Sara Llufriu in Therapeutic Advances in Neurological Disorders

Supplemental Material

sj-docx-2-tan-10.1177_17562864261440665 – Supplemental material for Rituximab and IVIG added to plasma exchange improves the outcome of severe CNS demyelinating attacks: a retrospective study

Supplemental material, sj-docx-2-tan-10.1177_17562864261440665 for Rituximab and IVIG added to plasma exchange improves the outcome of severe CNS demyelinating attacks: a retrospective study by Juan Luis Chico-Garcia, Moisés Morales de la Prida, Almudena Boix Lago, José Manuel García-Domínguez, María Sepúlveda, Eugenia Martínez-Hernández, Mar Guasp, Elianet Fonseca, Alberto Calvi, María Teresa Alba-Isasi, Blanca Albertí, Joan Cid, Miquel Lozano, Paola Charry, Fernando Rodríguez-Jorge, Raquel Sainz-Amo, Susana Sainz de la Maza, Enric Monreal, Luisa Maria Villar, Jaime Masjuan, Gabriel Valero-López, Jorge Millán-Pascual, Juan Pablo Cuello, Michael Palacios, Ariadna Gifreu Fraixinó, María Luisa Martínez-Gins, Gary Álvarez Bravo, José E. Meca-Lallana, Lucienne Costa-Frossard, Yolanda Blanco, Jose Maria Cabrera-Maqueda, Albert Saiz and Sara Llufriu in Therapeutic Advances in Neurological Disorders

Footnotes

Acknowledgements

None.

Declarations

ORCID iDs

Juan Luis Chico-Garcia

Moisés Morales de la Prida

María Sepúlveda

Eugenia Martínez-Hernández

Elianet Fonseca

Alberto Calvi

María Teresa Alba-Isasi

Miquel Lozano

Paola Charry

Fernando Rodríguez-Jorge

Susana Sainz de la Maza

Enric Monreal

Luisa Maria Villar

Jaime Masjuan

Juan Pablo Cuello

Michael Palacios

Ariadna Gifreu Fraixinó

Gary Álvarez Bravo

José E. Meca-Lallana

Lucienne Costa-Frossard

Yolanda Blanco

Jose Maria Cabrera-Maqueda

Albert Saiz

Sara Llufriu

Supplemental material

Supplemental material for this article is available online.

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