Tocilizumab in systemic lupus erythematosus: Data on safety, preliminary efficacy, and impact on circulating plasma cells from an open-label phase I dosage-escalation study

Abstract

OBJECTIVE: To assess the safety of interleukin-6 receptor inhibition and to collect preliminary data on clinical and immunologic efficacy of tocilizumab in patients with systemic lupus erythematosus (SLE). METHODS: In an open label, dose-escalating, Phase I study, 16 patients with mild to moderate disease activity were treated bi-weekly for 12 weeks with one of three doses (2 mg/kg [n=4], 4 mg/kg [n=6], 8 mg/kg [n=6]) of tocilizumab and followed for 8 additional weeks. RESULTS: The infusions were well tolerated. Tocilizumab led to dose-related decreases in absolute neutrophil count with a median decrease of 38% in the 4 mg/kg and 56% in the 8 mg/kg dose groups. Neutrophil counts returned to normal after cessation of treatment. One subject was withdrawn because of neutropenia. Infections occurred in 11 patients; none was associated with neutropenia. Disease activity showed a significant improvement with 8/15 evaluable patients having a decrease of 4 or more points in the modified SELENA-SLEDAI score. Arthritis improved in all seven patients with arthritis at baseline and resolved in four. Anti-dsDNA antibody levels decreased by a median 47% in the 4 and 8 mg/kg dose groups compared to a 7.8% decrease in IgG levels. These changes together with a significant decrease in circulating plasma cells suggest a specific effect of tocilizumab on autoantibody producing cells. CONCLUSION: Although neutropenia may limit the maximum dose of tocilizumab in SLE, the observed clinical and serological response data are promising and warrant further studies to establish the optimal dosing regimen and efficacy