Efficacy of the anti-IL-6 receptor antibody tocilizumab in neuromyelitis optica: a pilot study

Manabu Araki, Takako Matsuoka, Katsuichi Miyamoto, Susumu Kusunoki, Tomoko Okamoto, Miho Murata, Sachiko Miyake, Toshimasa Aranami, Takashi Yamamura, Manabu Araki, Takako Matsuoka, Katsuichi Miyamoto, Susumu Kusunoki, Tomoko Okamoto, Miho Murata, Sachiko Miyake, Toshimasa Aranami, Takashi Yamamura

Abstract

Objective: To evaluate the safety and efficacy of a humanized anti-interleukin-6 receptor antibody, tocilizumab (TCZ), in patients with neuromyelitis optica (NMO).

Methods: Seven patients with anti-aquaporin-4 antibody (AQP4-Ab)-positive NMO or NMO spectrum disorders were recruited on the basis of their limited responsiveness to their current treatment. They were given a monthly injection of TCZ (8 mg/kg) with their current therapy for a year. We evaluated the annualized relapse rate, the Expanded Disability Status Scale score, and numerical rating scales for neurogenic pain and fatigue. Serum levels of anti-AQP4-Ab were measured with AQP4-transfected cells.

Results: Six females and one male with NMO were enrolled. After a year of TCZ treatment, the annualized relapse rate decreased from 2.9 ± 1.1 to 0.4 ± 0.8 (p < 0.005). The Expanded Disability Status Scale score, neuropathic pain, and general fatigue also declined significantly. The ameliorating effects on intractable pain exceeded expectations.

Conclusion: Interleukin-6 receptor blockade is a promising therapeutic option for NMO.

Classification of evidence: This study provides Class IV evidence that in patients with NMO, TCZ reduces relapse rate, neuropathic pain, and fatigue.

Figures

Figure 1. Clinical course of the patients…
Figure 1. Clinical course of the patients before and after tocilizumab treatment
The zero on the x-axis represents the first administration of tocilizumab (TCZ). Dark gray bars: exacerbations of myelitis or optic neuritis (EMON); downward arrow: TCZ treatment; black X: IV methylprednisolone (IVMP); white X: oral betamethasone pulse (OBP) therapy; black triangle: plasma exchange (PLEX); white triangle: IV immunoglobulin (IVIg). After receiving 12 injections, all patients continued treatment with TCZ by entering an extension study that evaluates the long-term safety and efficacy of TCZ. We showed the clinical status after completion of the 1-year study to indicate the continuation of remission.
Figure 2. Effects of tocilizumab on clinical…
Figure 2. Effects of tocilizumab on clinical and immunologic parameters
(A) Annualized relapse rate (ARR) before and after tocilizumab (TCZ) treatment. (B) Expanded Disability Status Scale (EDSS) score during the 1-year study period. Pain severity (numerical rating scale [NRS]) (C) and fatigue severity (D) scores before, 6 months after, and 12 months after the start of TCZ treatment. The dots and I bars indicate means ± SEM. We analyzed only data obtained during the first year of TCZ treatment. (E) The alterations in the serum anti–aquaporin-4 antibody (AQP4-Ab) were evaluated by the relative ratio of the mean fluorescence intensity (MFI), which was based on the MFI before TCZ treatment. Serum anti-AQP4-Ab detection assay was performed as described previously, with minor modifications. In brief, optimally diluted serum was added to human AQP4-expressing Chinese hamster ovary (CHO) cells. CHO cell-bound anti-AQP4-Ab was detected using fluorescein isothiocyanate–anti-human immunoglobulin G antibody by flow cytometry. For comparison, the MFI of each sample was divided by the MFI of the sample before the start of TCZ treatment.

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Source: PubMed

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