IL-6 Inhibitor Tocilizumab Effective in Treating NMOSD, Meta-Analysis Suggests

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A recent meta-analysis on tocilizumab in neuromyelitis optica spectrum disorder (NMOSD) emphasized its effectiveness in reducing relapse rates and improving patient function, with patient-specific factors influencing outcomes.

Xingchao Geng, director of the National Center for Safety Evaluation of Drugs in China

Xingchao Geng

Data from a recently published meta-analysis of studies assessing tocilizumab found the therapy to be effective in reducing the frequency of relapses and improving patient function among those with neuromyelitis optica spectrum disorder (NMOSD). The effectiveness of the IL-6 inhibitor in reducing relapse rates was related to multiple factors such as gender, race, and dosage level.1

After searching MEDLINE, PubMed, Embase, and the Cochrane Library, investigators included 9 articles comprising 153 patients in the systematic review and meta-analysis. At the outset of treatment, the average age of all patient was 44.1 (range, 23-62) years, with most patients seropositive (84.3%). Among those in the cohort, dosages of tocilizumab 8 mg/kg every 4 weeks were the most commonly used. After initiating therapy, findings showed a mean reduction of –0.81 (95% CI, –1.04 to –0.58) in Expanded Disability Status Scale (EDSS) scores, with moderate heterogeneity detected (I2 = 45.0%).

Senior investigator Xingchao Geng, director of the National Center for Safety Evaluation of Drugs in China, and colleagues documented a mean reduction of –1.34 (95% CI, –1.60 to –1.09) in annualized relapse ratio (ARR) after tocilizumab therapy. No significant correlation was detected between the outcome (ARR change) and variables such as age at onset (95% CI, –0.0086 to 0.1023; P = .105), aquaporin-4 immunoglobulin serostatus (95% CI, –0.0191 to 0.0242; P = .815), follow-up time (95% CI, –0.0645 to 0.0350; P = .562), and disease duration (95% CI, –0.2079 to 0.2690; P = .802).

Clinical Takeaways

  1. Tocilizumab reduces relapse rates and improves function in NMOSD patients, with efficacy influenced by demographics and dosages.
  2. Tocilizumab, an IL-6 inhibitor, may be a valuable treatment option for NMOSD, though adverse events occur.
  3. Patient-specific factors, such as gender and ethnicity, influence the efficacy of tocilizumab in NMOSD management.

IL-6 is a key cytokine in the pathogenesis of NMOSD, and the level of IL-6 in the sera and cerebrospinal fluid of patients with the disease is significantly increased. In a subgroup of 39 patients, several factors played a role into clinical outcomes. Firstly, patients who were positive for AQP4-IgG demonstrated significant reductions in ARR (n = 31; P <.001) and an improvement in patient disability (n = 24; P <.05) whereas those who were seronegative did not show the same positive effects. Additionally, females on treatment responded better to tocilizumab better than males (n = 35; 2.82 [±0.41] vs n = 4; 0.25 [±0.25]; P <.01).

READ MORE: Patients With NMOSD Who Switch From Rituximab to Eculizumab Report Fewer Comorbidities and Hospitalizations

The effectiveness of the therapy was also higher in African patients than in those of Asian descent (n = 6; 3.28 [±0.42] vs n = 8; 2.51 [±0.38]; P <.05) and Caucasians (n = 6; 3.28 [±0.42] vs n = 24; 2.09 [±0.36]; P <.05). The dosage had an impact too, as an 8 mg/kg dose administered every 4 weeks was considered more effective than a dose of 6 mg/kg every 4 weeks (n = 20; 2.56 [±0.42] vs n = 4; 0.97 [±0.51]; P <.05). A dose of 162 mg/kg administered every 1-2 weeks was more effective than a dose of 6 mg/kg every 4 weeks (n = 11; 2.49 [±0.36] vs n = 4; 0.97 [±0.51]; P <.05). Despite this, the effectiveness of tocilizumab in improving EDSS score among patients with NMOSD was not related to the patient’s gender, ethnicity, and dose.

In terms of safety, about two-third (66%) of patients treated with tocilizumab experienced adverse events (AEs). Cases of hepatoxicitiy, recorded in 27.7% (n = 28) of the cohort, were the most common AE, followed by urinary tract infection (26.7%; n = 27) and upper respiratory infections (21.8%; n = 22). Some patients experienced elevated cholesterol levels (11.9%), anemia (12.9%), and other AEs like intestinal obstruction, headache, fatigue, and nausea. The serious AEs included cellulitis (n = 1), hemorrhage (n = 1), and death (n = 1), although the patient’s death was not considered treatment-related.

"IL-6 may promote plasma cell survival, stimulate the production of antibodies against AQP4, disrupt the integrity and functionality of the blood-brain barrier, and enhance proinflammatory T lymphocyte differentiation and activation in the pathophysiology of NMOSD,” the study authors wrote.1 "As a result, IL-6 inhibition is thought to be an effective way to improve disease severity."

REFERENCE
1. Wang Y, Zhao M, Yao M, et al. Tocilizumab treatment in neuromyelitis optica spectrum disorders: updated meta-analysis of efficacy and safety. Mult Scler & Relat Disor. 2023;80:105062. doi:10.1016/j.msard.2023.105062
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