PT  - JOURNAL ARTICLE
AU  - Pellkofer, H.L.
AU  - Krumbholz, M.
AU  - Berthele, A.
AU  - Hemmer, B.
AU  - Gerdes, L.A.
AU  - Havla, J.
AU  - Bittner, R.
AU  - Canis, M.
AU  - Meinl, E.
AU  - Hohlfeld, R.
AU  - Kuempfel, T.
TI  - Long-term follow-up of patients with neuromyelitis optica after repeated therapy with rituximab
AID  - 10.1212/WNL.0b013e3182152881
DP  - 2011 Apr 12
TA  - Neurology
PG  - 1310--1315
VI  - 76
IP  - 15
4099  - http://n.neurology.org/content/76/15/1310.short
4100  - http://n.neurology.org/content/76/15/1310.full
SO  - Neurology2011 Apr 12; 76
AB  - Background: Neuromyelitis optica (NMO) is a severe autoimmune disease targeting optic nerves and spinal cord. The monoclonal anti-CD20 B-cell antibody rituximab is an emerging therapeutic option in NMO. However, neither long-term efficacy or safety of rituximab, nor the correlation between B-cell counts, B-cell fostering cytokines, aquaporin-4 antibodies (AQP4-ab), and disease activity in NMO, have been investigated prospectively. Methods: We performed a prospective long-term cohort study of 10 patients with NMO who were treated up to 5 times with rituximab as a second-line therapy. Clinical examinations, B-cell counts, and serum concentrations of BAFF (B-cell activating factor of the TNF family; also called TNFSF13b), APRIL (a proliferation-inducing ligand; also called TNFSF13), AQP4-ab, and immunoglobulin levels were measured every 3 months. Results: Repeated treatment with rituximab led to sustained clinical stabilization in most patients with NMO. Disease activity correlated with B-cell depletion, but not clearly with AQP4-ab or levels of APRIL. BAFF levels increased after application of rituximab and indicated persisting efficacy of the drug but did not correlate with disease activity. Overall, rituximab was well-tolerated even after up to 5 consecutive treatment courses; however, we observed several severe adverse reactions. Conclusion: Our data indicate that long-term therapy with rituximab is effective in NMO as a second-line therapy and has an acceptable safety profile. Retreatment with rituximab should be applied before reappearance of circulating B cells. Classification of evidence: This study provides Class IV evidence that repeated doses of rituximab result in stabilization in most patients.