Influence of Efgartigimod on Curative Efficacy and Inflammation Factors of Patients with Long Segmental Myelitis

Summary

Efgartigimod has demonstrated significant efficacy and safety in patients with long-segment myelitis. Efgartigimod reduced serum levels of IL-6, IL-41, and IL-10 in LETM patients. The levels of these cytokines correlated with EDSS scores, suggesting their potential utility as biomarkers for predicting disease severity and treatment response in long-segment myelitis.

Abstract

The paper aims to evaluate the efficacy and impact of efgartigimod on clinical outcomes and inflammatory markers in patients with antibody-negative long-segment myelitis (LETM).This retrospective study enrolled 47 patients diagnosed with antibody-negative LETM, including 36 in the control group who received methylprednisolone alone and 11 in the observation group who received a combination of efgartigimod and methylprednisolone. Comparisons of the expanded disability status scale (EDSS), clinical frailty scale (CFS), and Health Survey Short Form-36 (SF-36) scores between the two groups were conducted. Concentrations of interleukin-6 (IL-6), IL-10, and IL-41 were detected using enzyme-linked immunosorbent assay (ELISA), and their correlations with EDSS scores were also evaluated. The potential predictors of therapeutic efficacy were identified using univariate and multivariate logistic regression analyses.Efgartigimod significantly reduced EDSS and CFS scores after 1 month of treatment, with the observation group demonstrating greater improvements than the control group. Efgartigimod improved the quality of life as assessed by the SF-36, with significant increases in physical functioning (PF) and vitality (VT) scores in the observation group (p < 0.05). Efgartigimod decreased serum cytokine (IL-41, IL-10, and IL-6) levels and EDSS scores at the time of treatment (p < 0.05). Serum cytokine levels were positively correlated with EDSS scores. The group (treatment strategy) and length of the involved segment were predictive factors of drug efficacy.Efgartigimod demonstrated significant efficacy and safety for the treatment of LETM. Efgartigimod lowered serum concentrations of IL-6, IL-41, and IL-10 in LETM patients. The levels of IL-6, IL-41, and IL-10 correlated with EDSS scores, indicating their potential as predictive biomarkers for disease severity and treatment efficacy in LETM.

Introduction

Long-segmental myelitis (LETM) is a rare but severe central nervous system disorder, typically defined by the involvement of three or more contiguous spinal cord segments, leading to motor, sensory, and autonomic dysfunction¹. Clinically, LETM is frequently associated with neuromyelitis optica spectrum disorder (NMOSD), which is primarily mediated by aquaporin-4 (AQP4) antibodies². However, a subset of LETM patients lacks detectable AQP4, myelin oligodendrocyte glycoprotein (MOG), or glial fibrillary acidic protein (GFAP) antibodies in serum, a condition termed antibody-negative LETM³. Intravenous meprednisone therapy is a conventional treatment for LETM⁴. However, its clinical utility is substantially limited due to the significant side effects associated with meprednisone^5,6. The etiology and pathogenesis of antibody-negative LETM remain unclear, with no established treatment guidelines leading to a relatively poor prognosis.

Currently, the management of antibody-negative LETM primarily depends on empirical therapies, including glucocorticoids, intravenous immunoglobulin (IVIG), and plasma exchange^7,8. However, the effectiveness of these treatments varies from person to person and can be accompanied by significant adverse effects^9,10. Given the absence of identified pathogenic antibodies, traditional immunosuppressive therapies offer limited efficacy in antibody-negative LETM, highlighting the urgent need for novel therapeutic strategies¹¹.

Efgartigimod, a novel human IgG1 antibody fragment, binds to the neonatal Fc receptor (FcRn), thereby blocking IgG-FcRn interactions, facilitating IgG degradation, and reducing serum levels of pathogenic IgG antibodies^12,13. Efgartigimod is currently approved for the treatment of patients with acetylcholine receptor (AChR) antibody-positive myasthenia gravis (gMG). Its efficacy in patients with gMG has been validated in several studies, showing good safety and tolerability^14,15. Studies have reported that combination therapy with efgartigimod and corticosteroids significantly improves spasticity, bladder function, and quality of life in patients with myelopathy^16,17. However, evidence regarding the efficacy of efgartigimod in the treatment of long-segment transverse myelitis (LETM) remains limited, warranting further clinical investigation.

Considering the potential presence of unidentified pathogenic IgG-mediated immune dysfunction in antibody-negative LETM, efgartigimod may offer a promising therapeutic option by reducing serum IgG levels. However, there are currently no data on the use of efgartigimod in patients with antibody-negative LETM. This study aimed to evaluate the efficacy and safety of efgartigimod in antibody-negative LETM and provide novel insights and evidence for its therapeutic use.

Protocol

The research protocol was approved by the Ethics Committee of The Second Affiliated Hospital, Zhejiang University School of Medicine (No. 2025-0581). All experiments and procedures were performed according to the Declaration of Helsinki (as revised in 2013). This retrospective study included 47 patients hospitalized for LETM at the Second Affiliated Hospital, Zhejiang University School of Medicine. This study has obtained informed consent from all participants. This retrospective cohort study included all eligible patients. A post hoc power analysis was conducted to assess the adequacy of the sample size. The results showed that with the current sample size, the observed effect size was 1.213515, and the achieved power (1-β err prob) was 0.9659161, which exceeds the conventional threshold of 0.8. Thus, the sample size meets statistical requirements.

Patient recruitment

Inclusion criteria: Include patients who were suffering from acute attacks, have complete clinical data, whose serum tested negative for MOG, AQP4, and GFAP antibodies, and whose affected segments were more than or equal to three¹⁸. Exclusion criteria: Exclude patients who experienced other diseases that may cause disability, and patients who had accepted efgartigimod at the acute onset¹⁸. Patient information collection: Demographics, including age, sex, disease duration, and the length of the involved spinal segments, were recorded.

Treatment and clinical evaluation

Group patients according to their respective treatment regimens. Patients were divided into two groups: the efgartigimod treatment group (n = 11) and the conventional treatment group (n = 36). In the efgartigimod group, patients were treated with 400 mg efgartigimod administration for 2 weeks, along with intravenous infusion of 1,000 mg methylprednisolone mixed with 500 mL of 10% glucose solution, administered over a 2-week treatment period¹⁶. In the traditional treatment group, patients were treated with intravenous infusion of 1,000 mg methylprednisolone mixed with 500 mL of 10% glucose solution administered over a 2-week treatment period¹⁹.

Clinical assessment parameters of the patients

Disability of patients was evaluated with a series of indices, including the expanded disability status scale (EDSS) and the clinical frailty scale (CFS)^20,21. Quality of life of the patients was assessed with the Health Survey Short Form-36 (SF-36), including physical functioning (PF), mental health (MH), pain (PA), general health (GH), vitality (VT), social functioning (SF), role-emotional (RE), and role-physical (RP)²².

Measurement of interleukin-6 (IL-6), IL-10, and IL-41

Fasting blood samples were collected in the morning. Serum was isolated from blood by 10 min centrifugation at 1,000 x g and stored at -80 °C for subsequent analysis. The storage duration for all the samples ranged from 6 to 48 months.

Serum levels of IL-6, IL-10, and IL-41 were measured using enzyme-linked immunosorbent assay (ELISA) kits, following the manufacturer's instructions (Table of Materials). Equilibrate all reagents from the ELISA kit to room temperature for 20 min prior to the assay. Standard, sample, and blank wells were used. 50 µL of standard solution at different concentrations (0-100 pg/mL) was added into the standard wells, 50 µL of the serum sample was added into the sample wells, and 50 µL of sample diluent was added to the blank wells. A wash buffer was prepared by diluting the concentrated washing solution with double-distilled water at a ratio of 1:24. The prepared buffer was used on the same day to ensure optimal washing efficiency.

Calculated the working solution volume based on experimental requirements (100 µL per well). At 15 min before use, centrifuged the 100x concentrated biotinylated antibody at 7,150 x g for 1 min and diluted with biotinylated antibody dilution buffer at a ratio of 1:99 to achieve a 1x working concentration. Used the prepared working solution immediately to maintain its activity. The HRP conjugate consisted of HRP-conjugated streptavidin. Calculated the required volume based on experimental requirements (100 µL per well), with an additional 100-200 µL prepared to ensure a sufficient quantity. At 15 min before use, centrifuged the 100x concentrated HRP conjugate at 11,173 x g for 1 min and then diluted with HRP conjugate dilution buffer at a ratio of 1:99 to achieve a 1x working concentration. Used the prepared working solution immediately to preserve its activity.

Prepared standard wells (100 µL of diluted standard), blank wells (100 µL of standard and sample dilution buffer), and sample wells (100 µL of diluted test sample) accordingly. After the solutions were added, seal the plate with a membrane and incubate at room temperature for 1.5 h. After incubation, remove the liquid in the wells without washing. Then, 100 µL of biotinylated antibody working solution was added to each well. Seal the plate and incubate at 37 °C for 1 h to facilitate binding of the biotinylated antibody to the antigen-antibody complexes. Following incubation, remove the liquid in the wells and blot the plate dry on clean absorbent paper. Fill each well with 350 µL of wash buffer and allow it to stand for 1 min. After removing the liquid, blot the plate dry again on absorbent paper. Repeated this washing procedure 4x.

After washing, add 100 µL of enzyme conjugate working solution to each well. Seal the plate and incubate at 37 °C for 30 min to allow thorough binding between the HRP conjugate and the biotinylated antibody. After incubation, remove the liquid completely from the wells and blot the plate dry on clean absorbent paper. Repeat the washing procedure described above 5x to thoroughly remove the unbound enzyme conjugates and minimize nonspecific reactions. After washing, add 90 µL of the substrate solution to each well. Seal the plate and incubate at 37 °C in the dark for approximately 15 min. Preheated the microplate reader for 15 min to ensure detection accuracy. After incubation, 50 µL of stop solution was added to each well to terminate color development and enzymatic reaction. After the reaction was terminated, the optical density (OD) at 450 nm of each well was immediately measured, and the results were recorded using a microplate reader for subsequent data analysis and calculation.

Statistical analysis

Statistical analysis was performed on SPSS 27.0 and GraphPad Prism 8.4.3. Independent samples t-test and χ2 test were used to compare baseline data between the two groups. Paired sample t-test or Wilcoxon test was used to compare clinical scores and life quality scores before and after treatment. Additionally, levels of serum IL-6, IL-10, and IL-41 were compared before and after treatment using a paired sample t-test. A comparison between the two groups was performed using an independent samples t-test. Pearson correlation coefficient was used to measure the correlation between levels of inflammation factors and EDSS. Differences were considered statistically significant at p < 0.05.

Results

A total of 47 patients were enrolled in this study across two cohorts. As shown in Table 1, there were no significant differences between the two groups in terms of age (p=0.414), sex (p=0.880), disease duration (p=0.144), and length of the involved spinal segments (p=0.945).

We evaluated the clinical efficacy of the two groups using the EDSS and CFS scores (Table 2). There were no significant differences in EDSS and CFS scores between the two groups before tr...

Discussion

LETM frequently manifests as paralysis, limb weakness, urinary dysfunction, and other neurological symptoms²³. Methylprednisolone is the main clinical drug for the treatment of LETM and has a long history^24,25. However, there are some patients who do not respond²⁶. Efgartigimod is a reliable drug for the treatment of myasthenia gravis by reducing pathogenic IgG^27,...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
efgartigimod	Vetter Pharma-Fertigung GmbH & Co. KG, Germany	SJ20230008
ElaBoX Human Interleukin-10 Detection Kit	Solarbio, Beijing, China	SEKH-0018
ElaBoX Human Interleukin-6 Detection Kit	Solarbio, Beijing, China	SEKH-0014
GraphPad Prism 8	Graphpad, San Diego, CA, USA
Human IL-4 ELISA Kit	Thermo Fisher Scientific, Waltham, MA, USA	BMS225-2
IBM Corporation's SPSS 26.0	SPSS, Chicago, Illinois, USA
methylprednisolone	PFIZER SA,Bruxelles,Belgium	H20130302
Multiskan FC Enzyme-Linked Immunosorbent Assay (ELISA) Reader	Thermo Fisher Scientific, Waltham, MA, USA	1410101