Tacrolimus is effective for neuromyelitis optica spectrum disorders with or without anti-AQP4 antibody

Background: Neuromyelitis optica spectrum disorders (NMOSD) are a group of inflammatory central nervous system disorders characterized by optic neuritis, transverse myelitis, and anti-aquaporin 4 (AQP4) antibody production. However, it has recently been shown that some cases of typical NMOSD can be anti-AQP4 antibody-negative as well. In this study, we retrospectively investigated the disorder relapse-suppressing effect of tacrolimus (TAC) when combined with prednisolone (PSL) in anti-AQP4 antibody-positive and -negative NMOSD cases.

Methods: Subjects were NMOSD outpatients treated at our hospital in August 2016 who fulfilled the 2015 International Panel for NMO Diagnosis criteria and whose medical history before visiting our department was known; anti-myelin oligodendrocyte glycoprotein antibody-positive cases were excluded. We retrospectively investigated the annualized relapse rate (ARR) before and after combined TAC and PSL treatment in 50 NMOSD cases who had been using TAC with PSL for at least 1 year and whom we were also able to observe.

Results: There were 42 anti-AQP4 antibody-positive cases and 8 negative cases. Observation periods of the anti-AQP4 antibody-positive cases were 1.1 years before TAC and 5.1 years after TAC. ARR before TAC was 1.0 and 0.08 after TAC, indicating a relapse-suppression rate of 92% (p < 0.001) and clear improvement. In the anti-AQP4 antibody-negative group, the observation period was 5.6 years before and 4.1 years after TAC. ARR before TAC was 0.5 and 0.07 after TAC. The relapse-suppression rate was 86% (p < 0.05), which was obviously as effective as in the anti-AQP4 antibody-positive group. PSL dose in the anti-AQP4 antibody-positive group was 15.0 mg/day at the start of TAC and was reduced to 6.3 mg/day after 2 years (p < 0.001). The Expanded Disability Status Scale (EDSS) score decreased from 4.5 at the start of TAC to 2.0 after 2 years in the anti-AQP4 antibody-positive group (p < 0.05), which was a clear improvement.

Conclusion: Combined use of TAC with PSL clearly suppressed relapse of both anti-AQP4 antibody-positive and -negative NMOSD. In the anti-AQP4 antibody-positive group, both PSL dose and EDSS score decreased compared with the dose at the start of the study.