Intravenous immunoglobulin for maintenance treatment of multifocal motor neuropathy: A multi-center, open-label, 52-week phase 3 trial

Satoshi Kuwabara, Sonoko Misawa, Masahiro Mori, Yuta Iwai, Kazuhide Ochi, Hidekazu Suzuki, Hiroyuki Nodera, Akira Tamaoka, Masahiro Iijima, Tatsushi Toda, Hiroo Yoshikawa, Takashi Kanda, Ko Sakamoto, Susumu Kusunoki, Gen Sobue, Ryuji Kaji, Glovenin-I MMN Study Group, Satoshi Kuwabara, Masahiro Mori, Sonoko Misawa, Yuta Iwai, Kazuhide Ochi, Susumu Kusunoki, Hidekazu Suzuki, Ryuji Kaji, Hiroyuki Nodera, N Matsui, Akira Tamaoka, A Ishi, Gen Sobue, Masahiro Iijima, Tatsushi Toda, K Sekiguchi, Hiroo Yoshikawa, A Yamamoto, Takashi Kanda, T Maeda, M Tahara, M Nakagawa, T Mizuno, Satoshi Kuwabara, Sonoko Misawa, Masahiro Mori, Yuta Iwai, Kazuhide Ochi, Hidekazu Suzuki, Hiroyuki Nodera, Akira Tamaoka, Masahiro Iijima, Tatsushi Toda, Hiroo Yoshikawa, Takashi Kanda, Ko Sakamoto, Susumu Kusunoki, Gen Sobue, Ryuji Kaji, Glovenin-I MMN Study Group, Satoshi Kuwabara, Masahiro Mori, Sonoko Misawa, Yuta Iwai, Kazuhide Ochi, Susumu Kusunoki, Hidekazu Suzuki, Ryuji Kaji, Hiroyuki Nodera, N Matsui, Akira Tamaoka, A Ishi, Gen Sobue, Masahiro Iijima, Tatsushi Toda, K Sekiguchi, Hiroo Yoshikawa, A Yamamoto, Takashi Kanda, T Maeda, M Tahara, M Nakagawa, T Mizuno

Abstract

Intravenous immunoglobulin (IVIg) therapy is currently the only established treatment in patients with multifocal motor neuropathy (MMN), and many patients have an IVIg-dependent fluctuation. We aimed to investigate the efficacy and safety of every 3 week IVIg (1.0 g/kg) for 52 weeks. This study was an open-label phase 3 clinical trial, enrolling 13 MMN patients. After an induction IVIg therapy (0.4 g/kg/d for 5 consecutive days), maintenance dose (1.0 g/kg) was given every 3 weeks for 52 weeks. The major outcome measures were the Medical Research Council (MRC) sum score and hand-grip strength at week 52. This trial is registered with ClinicalTrials.gov, number NCT01827072. At week 52, 11 of the 13 patients completed the study, and all 11 had a sustained improvement. The mean (SD) MRC sum score was 85.6 (8.7) at the baseline, and 90.6 (12.8) at week 52. The mean grip strength was 39.2 (30.0) kPa at the baseline and 45.2 (32.8) kPa at week 52. Two patients dropped out because of adverse event (dysphagia) and decision of an investigator, respectively. Three patients developed coronary spasm, dysphagia, or inguinal herniation, reported as the serious adverse events, but considered not related with the study drug. The other adverse effects were mild and resolved by the end of the study period. Our results show that maintenance treatment with 1.0 g/kg IVIg every 3 week is safe and efficacious for MMN patients up to 52 weeks. Further studies are required to investigate optimal dose and duration of maintenance IVIg for MMN.

Keywords: clinical trial; efficacy; intravenous immunoglobulin; multifocal motor neuropathy; safety.

Conflict of interest statement

S.K., S.K., G.S., and R.K. have received consultancy fees, lecture fees, and travel expenses on the steering committee from Nihon Pharmaceutical Co., Ltd. G.S. have received lecture fees from Takeda Pharmaceutical Co., Ltd and Mitsubishi Tanabe Pharma Corporation. T.K. has received lecture fees from Japan Blood Products Organization. K.S. is employee of Nihon Pharmaceutical Co., Ltd. All other authors declare that they have no conflict of interest.

© 2018 The Authors. Journal of the Peripheral Nervous System published by Wiley Periodicals, Inc. on behalf of Peripheral Nerve Society.

Figures

Figure 1
Figure 1
Study design and trial profile
Figure 2
Figure 2
Transition diagram of symptoms in multifocal motor neuropathy (MMN). (A) Medical Research Council (MRC) sum score, (B) hand‐grip strength of dominant hand, (C) Guy's Neurological Disability Scale (GNDS) sum score. The visit interval was every 3 weeks in maintenance period. Error bars represent SEM

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