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Intravenous immunoglobulin treatment for steroid-resistant optic neuritis: a multicenter, double-blind, randomized, controlled phase III study

  • Clinical Investigation
  • Published:
Japanese Journal of Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

To evaluate the efficacy and safety of intravenous “freeze-dried sulfonated human normal immunoglobulin (GGS)” in patients with steroid-resistant optic neuritis (ON).

Study design

Multicenter, prospective, double-blind, parallel-group, randomized controlled trial.

Methods

Patients with steroid-resistant acute ON were randomly assigned to receive either intravenous GGS (GGS group) or intravenous methylprednisolone (steroid pulse [SP] group). Visual acuity (logarithm of the minimum angle of resolution [logMAR]), mean deviation (MD) value of the Humphrey Field Analyzer, and critical flicker fusion frequency were measured as efficacy endpoints; adverse events (AEs) were assessed as the safety endpoint.

Results

Thirty-two patients (16 patients/group) received the study drugs. The primary endpoint, change in logMAR at week 2 compared to baseline, showed no statistically significant intergroup difference. However, compared with the SP group, change in the GGS group was increasingly indicative of visual improvement, with least squares mean difference of > 0.3 logMAR. On post-hoc analyses, the percentage of patients in the GGS and SP groups with improvement by ≥ 0.3 logMAR at week 2 were 75.0% and 31.3%, respectively. Changes in MD values at week 2 compared to baseline were 9.258  ±  8.296 (mean ± standard deviation) dB and 3.175  ±  6.167 dB in the GGS and SP groups, respectively. These results showed statistically significant intergroup differences (visual acuity improvement, P = 0.032; change in MD values, P = 0.030). No clinically significant AEs were observed.

Conclusion

Our results suggest that intravenous immunoglobulin could be a safe and efficacious therapeutic option for prompt treatment of steroid-resistant acute ON. Trial registration: JapicCTI-132080.

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Acknowledgements

Teijin Pharma Limited, the sponsor, provided funding for this study, determined the study design, and prepared the clinical study protocol. It also collected and analyzed the data and supported the writing of this report. The investigational and the control drugs used in this study were provided to Teijin Pharma Limited by Chemo-Sero-Therapeutic Research Institute (now, KM Biologics Co., Ltd.). We are deeply grateful to Dr. Yusaku Nakamura (Chairman, Department of Neurology, Sakai City Medical Center) for the central review of head/spinal cord MRI data. We also thank all investigators and the patients who participated in this study.

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Authors and Affiliations

  1. Department of Ophthalmology, Hyogo College of Medicine, Nishinomiya, Japan

    Osamu Mimura & Akiko Kimura

  2. Department of Orthoptics and Visual Science, School of Allied Health Sciences, Kitasato University, Sagamihara, Japan

    Hitoshi Ishikawa

  3. Department of Ophthalmology, Tokyo Medical University, Shinjuku, Japan

    Takeshi Kezuka

  4. Department of Ophthalmology, The Jikei University School of Medicine, Minato, Japan

    Keigo Shikishima

  5. Department of Ophthalmology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan

    Tone Suzuki

  6. Division of Ophthalmology, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan

    Makoto Nakamura

  7. Department of Ophthalmology, University of Miyazaki, Miyazaki, Japan

    Hideki Chuman

  8. Inoue Eye Hospital, Chiyoda, Japan

    Kenji Inoue & Akiko Yamagami

  9. Pharmaceutical Development Administration Department, Teijin Pharma Limited, Chiyoda, Japan

    Maki Mihoya

  10. Department of Ophthalmology, Kindai University Faculty of Medicine, Osakasayama, Japan

    Yuzo Nakao

Authors
  1. Osamu Mimura
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  2. Hitoshi Ishikawa
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Corresponding author

Correspondence to Osamu Mimura.

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Conflicts of interest

O. Mimura, Grant (Teijin), Lecture fee (Santen, Senju, Otsuka, Pfizer, Alcon, GSK); H. Ishikawa, Grant (Teijin), Grant-in-aid for Scientific Research from Ministry of Health, Labor and Welfare 2015–2017 (Research Project on Intractable Diseases Policy); T. Kezuka, Grant, Financial support (Teijin), Financial support (AbbVie, Alcon, Cosmic Corp, Eisai, Kowa, Mitsubishi Tanabe, Santen, Senju), Non-Financial support (Cosmic Corp); K. Shikishima, Grant (Teijin), Honorarium for Speaker (Santen, Senju, Johnson & Johnson, Chugai, Cosmic Corp), T. Suzuki, Grant (Teijin); M. Nakamura, Grant (Teijin); H. Chuman, Grant (Teijin); K. Inoue, Grant (Teijin), Grant, Research support, Lecture fee, Writing assistance, Consultant fee (Santen), Research support (Alcon), Lecture fee (Otsuka), Grant, Research support, Lecture fee, Consultant fee (Senju), Lecture fee, Consultant fee (Kowa), Grant, Research support, Lecture fee (Allergan), Lecture fee (Novartis, Wakamoto), Research support (IQVIA, Mayo Corp, Lilly); A. Kimura, Grant (Teijin); A. Yamagami, Grant (Teijin); M. Mihoya, Employee (Teijin), Y. Nakao, Grant (Teijin).

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Mimura, O., Ishikawa, H., Kezuka, T. et al. Intravenous immunoglobulin treatment for steroid-resistant optic neuritis: a multicenter, double-blind, randomized, controlled phase III study. Jpn J Ophthalmol 65, 122–132 (2021). https://doi.org/10.1007/s10384-020-00790-9

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  • DOI: https://doi.org/10.1007/s10384-020-00790-9

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