Abstract:
:Primary biliary cholangitis (PBC) is a classic autoimmune disease in which humoral, cytotoxic, and innate immune responses have been implicated with the specific targeting of a mitochondrial antigen. The mainstay of treatment remains the bile acid ursodeoxycholic acid (UDCA). Corticosteroids may have some benefits, but to date, clinical trials of biologics targeting B cells and IL-12/23 have not shown any efficacy. Because activated T cells target the intrahepatic bile ducts in PBC and pre-clinical models suggested that blocking CD80/CD86 with CTLA-4 Ig might have therapeutic benefit in PBC, we performed an open-label trial to determine if CTLA-4 Ig (abatacept) is safe and potentially efficacious in PBC patients with an incomplete response to UDCA. PBC patients with an alkaline phosphatase (ALP) > 1.67 × the upper limit of normal after 6 months on UDCA treatment or who were intolerant of UDCA received abatacept 125 mg s.q. weekly for 24 weeks. The co-primary endpoint was ALP normalization or a >40% reduction from baseline. Among 16 subjects enrolled and who received at least 1 dose of abatacept, 1 (6.3%) met the co-primary endpoint. Absolute and percent changes in ALP [median (95% CI)] were +2.8 U/L (-90.9-96.6) and -0.28% (-21.1-15.5), respectively. No significant changes were observed in ALP, ALT, total bilirubin, albumin, immunoglobulins, or liver stiffness. Abatacept treatment decreased several non-terminally differentiated CD4+ but not CD8+ T cell populations, including decreases in CD4+ CCR5+ (p = 0.02) and CD4+ PD1+ (p = 0.03) lymphocytes. In contrast there were increases in CD4+ CCR7+ lymphocytes (p = 0.034). Treatment emergent adverse events occurred in 4 subjects. Abatacept was well tolerated in this population of PBC patients but like other biologics in PBC was ineffective in achieving biochemical responses associated with improved clinical outcomes.
journal_name
J Autoimmunjournal_title
Journal of autoimmunityauthors
Bowlus CL,Yang GX,Liu CH,Johnson CR,Dhaliwal SS,Frank D,Levy C,Peters MG,Vierling JM,Gershwin MEdoi
10.1016/j.jaut.2019.04.005subject
Has Abstractpub_date
2019-07-01 00:00:00pages
26-34eissn
0896-8411issn
1095-9157pii
S0896-8411(19)30086-1journal_volume
101pub_type
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journal_title:Journal of autoimmunity
pub_type: 杂志文章
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journal_title:Journal of autoimmunity
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journal_title:Journal of autoimmunity
pub_type: 杂志文章
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journal_title:Journal of autoimmunity
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更新日期:2000-06-01 00:00:00
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pub_type: 杂志文章
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journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
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journal_title:Journal of autoimmunity
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journal_title:Journal of autoimmunity
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