- 1Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland.
- 2Graduate School for Health Sciences, University of Bern, 3012, Bern, Switzerland.
- 3Department of Rheumatology and Immunology, Bern University Hospital, University of Bern, Switzerland.
Background: The majority of patients with autoimmune hepatitis (AIH) achieve complete remission with established treatment regiments. In patients with intolerance or insufficient response to these drugs, the remaining options are limited and novel treatment approaches necessary. In primary biliary cholangitis (PBC), ursodeoxycholic acid (UDCA) and fibrates have improved prognosis dramatically, but there remains a proportion of patients with refractory disease.In patients with refractory AIH and/or PBC, we used a novel treatment strategy with the anti-B cell activating factor, belimumab. The first three patients had concomitant Sjögren's disease. The connecting element between all three diseases is B cell activation, including elevated levels of the B cell activating factor (BAFF). Furthermore, belimumab has been shown to be beneficial in Sjögren's disease.
Aims and methods: To retrospectively investigate treatment response in six patients with AIH or PBC with or without concomitant Sjögren's disease treated with the anti-BAFF therapy belimumab at the University Hospital in Bern, Switzerland.
Results: In all three patients with AIH, belimumab improved disease control and helped by-pass or reduce problematic side effects from corticosteroids and calcineurin inhibitors. In PBC patients (n = 3), there was no clear improvement of liver function tests, despite reduction or normalization of IgM. All patients with concomitant Sjögren's disease (n = 3) had an improvement of sicca symptoms and two out of three patients experienced an initially marked reduction in fatigue, which lessened over time.
Conclusions: Belimumab may be a promising treatment option for patients with AIH and further investigations are needed. In PBC however, response was not convincing. The effects on sicca symptoms and fatigue were encouraging.
Keywords: AIH, autoimmune hepatitis; ALT, alanine aminotransferase; AMA, anti-mitochondrial antibodies; ANA, anti-nuclear antibodies; AP, alkaline phosphatase; APS, anti-phospholipid-antibody syndrome; AZA, azathioprine; Autoimmune hepatitis; Autoimmune liver disease; BDN, budesonide; Belimumab; CI, calcineurin inhibitor; CyA, cyclosporine A; INR, international normalized ratio; IgG, immunoglobulin G; IgM, immunoglobulin M; LC 1, liver cytosol 1 antibodies; LKM-1, liver-kidney-microsomal antibodies; MMF, mycophenolate mofetil; MRCP, magnetic resonance cholangiopancreatography; NA, not applicable; NRH, nodular regenerative hyperplasia; PBC, primary biliary cholangitis; PDN, prednisolone; PLA2R, anti-phospholipase 2 receptor antibody; PSC, primary sclerosing cholangitis; Primary biliary cholangitis; RF, rheumatoid factor; SLA, soluble liver antigen antibodies; SLE, systemic lupus erythematosus; SMA, smooth-muscle cell antibodies; SS-A, SS-A (Ro) antibodies; SS-B, SS-B (La) antibodies; Sjögren's disease; TNFi, tumor necrosis factor inhibitor; UDCA, ursodeoxycholic acid; ULN, upper limit of normal; disease-modifying anti-rheumatic drugs, DMARDs.