Clinical Efficacy and Safety of Baminercept, a Lymphotoxin β Receptor Fusion Protein, in Primary Sjögren's Syndrome
| Autor: | Ghaith Noaiseh, Tammy O. Utset, St Clair Ew, Andreea Coca, Smith K, Daniel J. Wallace, Alan N. Baer, James McNamara, Mark C. Genovese, Joel M. Guthridge, Nathalie Franchimont, Iñaki Sanz, Lynette Keyes-Elstein, Karen D. Boyle, Ann L. Parke, Jeffrey L. Browning, Chungwen Wei, Judith A. James |
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| Rok vydání: | 2018 |
| Předmět: |
030203 arthritis & rheumatology
0301 basic medicine medicine.medical_specialty business.industry T cell Immunology Placebo-controlled study medicine.disease Placebo Gastroenterology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Lymphotoxin Rheumatology Multicenter trial Internal medicine medicine Clinical endpoint Immunology and Allergy Adverse effect business Rheumatism |
| Zdroj: | Arthritis & Rheumatology. 70:1470-1480 |
| ISSN: | 2326-5191 |
| DOI: | 10.1002/art.40513 |
| Popis: | OBJECTIVE To evaluate the clinical efficacy and safety of baminercept, a lymphotoxin β receptor IgG fusion protein (LTβR-Ig), for the treatment of primary Sjogren's syndrome (SS), and to explore the possible mechanisms of action of this treatment. METHODS In this multicenter trial, 52 patients with primary SS were randomized in a 2:1 ratio to receive subcutaneous injections of 100 mg of baminercept every week for 24 weeks or matching placebo. The primary end point was the change between screening and week 24 in the stimulated whole salivary flow (SWSF) rate. Secondary end points included the European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI), as well as measurements of select chemokines and cytokines and enumeration of peripheral blood B and T cell subsets. RESULTS The change from baseline to week 24 in the SWSF rate was not significantly different between the baminercept and placebo treatment groups (baseline-adjusted mean change -0.01 versus 0.07 ml/minute; P = 0.332). The change in the ESSDAI during treatment was also not significantly different between the treatment groups (baseline-adjusted mean change -1.23 versus -0.15; P = 0.104). Although the incidence of adverse events was similar between the treatment groups, baminercept therapy was associated with a higher incidence of liver toxicity, including 2 serious adverse events. Baminercept also produced a significant decrease in plasma levels of CXCL13 and significant changes in the number of circulating B and T cells, consistent with its known inhibitory effects on LTβR signaling. CONCLUSION In this trial, treatment with baminercept failed to significantly improve glandular and extraglandular disease in patients with primary SS, despite evidence from mechanistic studies showing that it blocks LTβR signaling. |
| Databáze: | OpenAIRE |
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