OP-8 SECOND LINE THERAPY IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS AND INADECUATE RESPONSE: ARE WE CHOOSING THE RIGHT TARGET POPULATION FOR CLINICALS TRIALS?

Conflict of interest

No

Introduction and Objectives

Identification of primary biliary cholangitis (PBC) patients who could benefit from second line therapy is uncertain. Most trials rely on 12 month UDCA response assessed by POISE criteria.

Evaluate eligible patients and identify epidemiological-clinical and histological findings that may adversely influence response.

Patients / Materials and Methods

Among 614 patients with established diagnosis of PBC (Jan/16 and Dec/23) 279 were unable to normalize alkaline phosphatase (ALP) and BT after 12 months of UDCA. 107/279 (38.3 %) fulfilled elegibility criteria for second line trials (ALP >1.67, bilirubin <2 and non significant portal hypertension) were analyzed. Fibrosis, bile duct loss, cholangitic and hepatitis activity were obtained in 92/107 patients (Scheuer and Nakanuma scores). All samples were stained with cytokeratin 7. Elastography was done in all patients.

Results and Discussion

Characteristics of patients who fulfilled POISE criteria are described in Table 1. Mean MELD was higher in cirrhotic (9.0vs7.1, p<.001) and correlated with liver events (9.6vs7.0, p<.001). 43/92 patients had moderate-severe ductopenia in histological samples, and it was significantly more frequent in <45 years (66%vs32%, p.008). Moderate-severe portal inflammation with interface hepatitis and lobular spilling was observed in 52/92 samples (56.5%), irrespective of age and correlated with fibrosis. ALP was significantly higher in patients with ductopenia (437.9±207.8vs319.2±162.0, p.01). Elastography correlated with cirrhosis and liver events (10.4vs22.9, p<0.001) but not with inflammation or ductopenia.

Conclusions

A significant proportion of patients unresponsive to UDCA were not eligible for second line trials. Poise criteria eligibility was associated with the presence of ductopenia and advanced fibrosis, particularly in young patients. The presence of moderate to severe portal inflammation is suggestive of ongoing disease activity. Elastography and MELD score correlate with cirrhosis and development of liver events. These findings suggest that we are selecting for second line trials a significant proportion of patients with adverse findings for response. Adverse histological findings might suggest early second line intervention.

Baseline characteristics	Patients (n=92)
Age, mean (years)	55.9 (± 11.8)
Female, num (%)	93 (22.4)
< 45 years, num (%)	22 (22.4%)
Associated autoimmune disease, num (%)	16 (17.3)
Pruritus, num (%)	51 (55.1)
ALP, mean (UI/L)	366.7 (± 192.5)
GGT, mean (UI/L)	366.6 (± 326.2)
ALT, mean (UI/L)	64.7 (± 43.6)
TB, mean (mg/dL)	1.7 (± 4.6)
Elastography >9.6 kPa, num (%)	42 (50%)
MELD score, mean	7.4 (± 1.8)
Cirrhotic, num (%)	17 (16)
Moderate to severe portal inflammation with interface hepatitis and lobular spilling, num (%)	52 (56.5)
AMA, num (%)	80 (86)
Sp100, num (%)	9 (9.7)
GP210, num (%)	8 (8.6)
Under UDCA treatment, num (%)	89 (96.7)

Abbreviations: ALP: alkaline phosfatase, gGT: gamma-glutamyl-transferase, ALT: alanine-transferase, TB: total bilirrubine, AMA: anti-mitochondrial antibody, UDCA ursodeoxycholic acid.

Characteristics of non responders patients