Belimumab in Autoimmune Liver Diseases with associated Sjögren’s Syndrome

Background: Autoimmune hepatitis (AIH) is an auto-inflammatory disease of the liver with, if untreated, a high mortality rate. About 75% of patients are responsive to synthetic disease modifying drugs (sDMARD). Primary biliary cholangitis (PBC) is an inflammatory disease of small and medium sized bile ducts. Despite standard treatments (ursodeoxycholic acid (UDCA), fibrates and obeticholic acid (OCA)), a significant proportion of patients has progressive disease. Twenty percent of PBC patients have Sjogren’s syndrome (SjS). PBC has many features in common with SjS: epidemiology, epithelitis, well-characterized autoantibodies and a poor response to immunosuppressive treatments. Hypothesis: Based on the increased B cell-activating factor (BAFF) levels in AIH, PBC and SjS patients and the similarities between PBC and SjS, we hypothesized that belimumab is effective in AIH and PBC. Methods: Retrospective analysis of treatment responses to belimumab in three female patients with AIH and/or PBC with moderate to advanced liver fibrosis and concomitant SjS. Patient 1: 52y, with AIH, PBC and SjS. Indication: active AIH with intolerance to previous treatments (AZA, MMF, rituximab); belimumab since 01/20. Patient 2: 72y, with PBC and SjS. Indication: refractory PBC despite UDCA and fibrates (OCA declinedby health insurance); belimumab since 11/20. Patient 3: 54y, with PBC (with ductopenia), SjS and erosive rheumatoid arthritis (RA). RA responding insufficiently to all commonly used sDMARDs and biologicals. She was on low dose steroids, HCQ and etanercept. Her PBC was active despite UDCA and fibrates (OCA not tolerated). Indication: refractory PBC; belimumab since 11/20. We discontinued etanercept, when belimumab was started. Results: Patient 1: Remission of AIH under belimumab. Patient 2: Remission of PBC after 6 months of belimumab. Patient 3: Stable cholestasis parameters. Improvement of slightly elevated transaminases and almost normalization of IgM. Improvement of sicca symptoms in all patients. Two patients had a transient improvement in fatigue. RA in patient 3 remained on a level of moderate disease activity. Conclusions: These preliminary findings suggest belimumab as a promising treatment option in AIH and PBC, with so far no safety concerns. Our study shows how the basket of autoimmune diseases can guide us to evaluate new drug candidates in a more efficient way and highlights the strengths of a tight collaboration between hepatology and rheumatology.