TY - JOUR
T1 - Clinical Efficacy and Safety of Baminercept, a Lymphotoxin β Receptor Fusion Protein, in Primary Sjögren's Syndrome
T2 - Results From a Phase II Randomized, Double-Blind, Placebo-Controlled Trial
AU - the Autoimmunity Centers of Excellence
AU - St.Clair, E. William
AU - Baer, Alan N.
AU - Wei, Chungwen
AU - Noaiseh, Ghaith
AU - Parke, Anne
AU - Coca, Andreea
AU - Utset, Tammy O.
AU - Genovese, Mark C.
AU - Wallace, Daniel J.
AU - McNamara, James
AU - Boyle, Karen
AU - Keyes-Elstein, Lynette
AU - Browning, Jeffrey L.
AU - Franchimont, Nathalie
AU - Smith, Kira
AU - Guthridge, Joel M.
AU - Sanz, Ignacio
AU - James, Judith A.
N1 - Publisher Copyright:
© 2018, American College of Rheumatology
PY - 2018/9
Y1 - 2018/9
N2 - Objective: To evaluate the clinical efficacy and safety of baminercept, a lymphotoxin β receptor IgG fusion protein (LTβR-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 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.
AB - Objective: To evaluate the clinical efficacy and safety of baminercept, a lymphotoxin β receptor IgG fusion protein (LTβR-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 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.
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U2 - 10.1002/art.40513
DO - 10.1002/art.40513
M3 - Article
C2 - 29604186
AN - SCOPUS:85050358146
SN - 2326-5191
VL - 70
SP - 1470
EP - 1480
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
IS - 9
ER -