2. Academic Validation
  3. 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

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.
E William St Clair 1,  Alan N Baer 2,  Chungwen Wei 3,  Ghaith Noaiseh 4,  Anne Parke 5,  Andreea Coca 6,  Tammy O Utset 7,  Mark C Genovese 8,  Daniel J Wallace 9,  James McNamara 10,  Karen Boyle 11,  Lynette Keyes-Elstein 11,  Jeffrey L Browning 12,  Nathalie Franchimont 13,  Kira Smith 14,  Joel M Guthridge 15,  Ignacio Sanz 3,  Judith A James 15,  Autoimmunity Centers of Excellence
Affiliations

Affiliations

  • 1 Duke University School of Medicine, Durham, North Carolina.
  • 2 Johns Hopkins University, Baltimore, Maryland.
  • 3 Ignacio Sanz, Emory University, Atlanta, Georgia.
  • 4 UPMC Presbyterian, Pittsburgh, Pennsylvania.
  • 5 Saint Francis Medical Group, Hartford, Connecticut.
  • 6 University of Rochester, Rochester, New York.
  • 7 University of Chicago, Chicago, Illinois.
  • 8 Stanford University, Palo Alto, California.
  • 9 Cedars-Sinai Medical Center, Los Angeles, California.
  • 10 National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland.
  • 11 Rho, Inc., Chapel Hill, North Carolina.
  • 12 Boston University School of Medicine, Boston, Massachusetts.
  • 13 Biogen, Inc., Cambridge, Massachusetts.
  • 14 Emory Healthcare, Atlanta, Georgia.
  • 15 Oklahoma Medical Research Foundation, Oklahoma City.
PMID: 29604186 DOI: 10.1002/art.40513
Abstract

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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