Clinical Efficacy and Safety of Baminercept, a Lymphotoxin β Receptor Fusion Protein, in Primary Sjögren's Syndrome: Results From a Phase II Randomized, Double-Blind, Placebo-Controlled Trial

Arthritis Rheumatol. 2018 Sep;70(9):1470-1480. doi: 10.1002/art.40513. Epub 2018 Jul 18.


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.

Trial registration: NCT01552681.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • B-Lymphocytes / drug effects
  • Chemokine CXCL13 / blood
  • Double-Blind Method
  • Female
  • Humans
  • Lymphotoxin beta Receptor / immunology
  • Male
  • Middle Aged
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / therapeutic use*
  • Sjogren's Syndrome / blood
  • Sjogren's Syndrome / drug therapy*
  • Sjogren's Syndrome / immunology
  • T-Lymphocytes / drug effects
  • Treatment Outcome


  • CXCL13 protein, human
  • Chemokine CXCL13
  • LTBR protein, human
  • Lymphotoxin beta Receptor
  • Recombinant Fusion Proteins
  • baminercept

Associated data