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Clinical Efficacy and Safety of Baminercept, a Lymphotoxin β Receptor Fusion Protein, in Primary Sjögren's Syndrome

2018; Wiley; Volume: 70; Issue: 9 Linguagem: Inglês

10.1002/art.40513

2326-5205

E. William St. Clair, Alan N. Baer, Chungwen Wei, Ghaith Noaiseh, A. L. Parke, Andreea Coca, Tammy O. Utset, Mark C. Genovese, Daniel J. Wallace, James McNamara, Karen Boyle, Lynette Keyes‐Elstein, Jeffrey L. Browning, Nathalie Franchimont, Kira Smith, Joel M. Guthridge, Igñacio Sanz, Judith A. James,

Ocular Surface and Contact Lens

Objective To evaluate the clinical efficacy and safety of baminercept, a lymphotoxin β receptor IgG fusion protein ( LT βR‐Ig), for the treatment of primary Sjögren'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 Sjögren'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 CXCL 13 and significant changes in the number of circulating B and T cells, consistent with its known inhibitory effects on LT βR 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 LT βR signaling.