Background/Purpose: Primary Sjögren’s syndrome (pSjS) is characterized by chronic inflammation of the lacrimal and salivary glands, as well as frequent extraglandular involvement and increased risk of B cell lymphoma. Several lines of evidence implicate the lymphotoxin (LT) pathway in the pathogenesis of this disease. Baminercept inhibits the LT pathway, which is important in lymphoid tissue organization and chronic inflammation. This study tests the clinical efficacy and safety of baminercept in pSjS.

Methods: We randomized subjects in a 2:1 ratio to receive 24 weekly subcutaneous injections of baminercept 100 mg or placebo. Eligible subjects met the 2002 American-European Consensus Group classification criteria for pSjS, had a pilocarpine-stimulated whole salivary flow (SWSF) of ≥ 0.1 mL/min, and had ≥ 1 systemic manifestations. The primary endpoint was the change in SWSF between baseline and week 24. Secondary endpoints included the safety of baminercept and the changes in unstimulated whole salivary flow (UWSF), Schirmer-I-test, ocular staining, fatigue, joint pain, overall dryness, and the EULAR SjS Disease Activity Index (ESSDAI). Subjects that received at least one dose of study medication constituted the modified intent-to-treat (mITT) population. Subjects were followed for 48 weeks. 

Results: Only 52 of the planned 72 subjects were enrolled due to study drug expiration. Of the 52 eligible subjects, 33 and 19 subjects were randomized to the baminercept and placebo treatment groups, respectively. Ten of the 52 (19%) participants withdrew from treatment (adverse event, 4; subject decision 3; > 4 missed doses, 1; investigator decision, 1; other, 1). In the mITT population (n=52), we found no difference between the baminercept and placebo groups in the change in SWSF (adjusted mean: -0.01 vs. 0.06 mL/min; p=0.37). However, the ESSDAI improved significantly more in the baminercept than the placebo group (adjusted mean change: -1.6 vs. -0.25; p=0.043). In addition, there were no significant differences between treatment groups in the change in UWSF, Schirmer-I-test, ocular staining, fatigue, joint pain, and overall dryness. Lymphocyte numbers increased during baminercept treatment compared to the placebo group (p < 0.0001), an expected effect of baminercept on cellular trafficking. Baminercept treatment was not associated with any significant changes in the serum levels of CXCL13, LIGHT, IP10, and BAFF. Seven subjects had a serious adverse event (SAE), including 2 subjects (baminercept group) with grade 3 hepatic injury who recovered without sequela. Transaminase abnormalities (>ULN) occurred more frequently in the baminercept group (10 subjects [30%], 15 events) than the placebo group (3 subjects [16%], 5 events), including the 2 subjects with SAEs who had grade 3 abnormalities; the remainder had grade 1 elevations.

Conclusion: Baminercept therapy was no more effective than placebo for increasing salivary flow or reducing ocular dryness, and was accompanied by an imbalance in transaminase elevations and 2 cases of reversible grade 3 hepatic injury. The finding that baminercept therapy was associated with improvement in the ESSDAI warrants further study.

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ACR Meeting Abstracts - http://acrabstracts.org/abstract/the-clinical-efficacy-and-safety-of-baminercept-a-lymphotoxin-beta-receptor-fusion-protein-in-primary-sjogrens-syndrome-results-from-a-randomized-double-blind-placebo-controlled-phase-ii-trial/