The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
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
Open accessAbstract
Objective: To assess the safety of interleukin‐6 receptor inhibition and to collect preliminary data on the clinical and immunologic efficacy of tocilizumab in patients with systemic lupus erythematosus (SLE). Methods: In an open‐label phase I dosage‐escalation study, 16 patients with mild‐to‐moderate disease activity were assigned to receive 1 of 3 doses of tocilizumab given intravenously every other week for 12 weeks (total of 7 infusions): 2 mg/kg in 4 patients, 4 mg/kg in 6 patients, or 8 mg/kg in 6 patients. Patients were then monitored for an additional 8 weeks. Results: The infusions were well tolerated. Tocilizumab treatment led to dosage‐related decreases in the absolute neutrophil count, with a median decrease of 38% in the 4 mg/kg dosage group and 56% in the 8 mg/kg dosage group. Neutrophil counts returned to normal after cessation of treatment. One patient was withdrawn from the study because of neutropenia. Infections occurred in 11 patients; none was associated with neutropenia. Disease activity showed significant improvement, with a decrease of ≥4 points in the modified Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index score in 8 of the 15 evaluable patients. Arthritis improved in all 7 patients who had arthritis at baseline and resolved in 4 of them. Levels of anti–double‐stranded DNA antibodies decreased by a median of 47% in patients in the 4 mg/kg and 8 mg/kg dosage groups, with a 7.8% decrease in their IgG levels. These changes, together with a significant decrease in the frequency of circulating plasma cells, suggest a specific effect of tocilizumab on autoantibody‐producing cells. Conclusion: Although neutropenia may limit the maximum dosage of tocilizumab in patients with SLE, the observed clinical and serologic responses are promising and warrant further studies to establish the optimal dosing regimen and efficacy.
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Treg cell-based therapies: challenges and perspectives
Raffin, C., Vo, L. T., & Bluestone, J. A. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0232-6 · Cited by 720
Translating IL-6 biology into effective treatments
Choy, E. H., De Benedetti, F., Takeuchi, T., Hashizume, M., John, M. R., & Kishimoto, T. (2020) · Nature Reviews Rheumatology · doi:10.1038/s41584-020-0419-z · Cited by 668
Interleukin-6: designing specific therapeutics for a complex cytokine
Garbers, C., Heink, S., Korn, T., & Rose-John, S. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.45 · Cited by 643
Immunopathogenic mechanisms of systemic autoimmune disease
Wahren-Herlenius, M., & Dörner, T. (2013) · The Lancet · doi:10.1016/s0140-6736(13)60954-x · Cited by 593
Pathogenesis of Human Systemic Lupus Erythematosus: A Cellular Perspective
Moulton, V. R., Suarez-Fueyo, A., Meidan, E., Li, H., Mizui, M., & Tsokos, G. C. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.05.006 · Cited by 469
Metadata
- Authors
- Illei, G. G., Shirota, Y., Yarboro, C. H., Daruwalla, J., Tackey, E., Takada, K., Fleisher, T., Balow, J. E., & Lipsky, P. E.
- Venue
- Arthritis & Rheumatism
- Publisher
- Wiley
- Published
- 2010-01-28
- Volume
- 62
- Issue
- 2
- Pages
- 542-552
- ISSN
- 0004-3591 (ISSN-L)
- 1529-0131
- OpenAlex
- W2043298079
- Cited by
- 507
- References
- 25
- FWCI
- 33.73
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Illei, G. G., Shirota, Y., Yarboro, C. H., Daruwalla, J., Tackey, E., Takada, K., Fleisher, T., Balow, J. E., & Lipsky, P. E. (2010). 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. Arthritis & Rheumatism. https://doi.org/10.1002/art.27221
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