Abstract
The introduction of obeticholic acid (OCA) and the emerging evidence on the efficacy of fibrates and other PPAR-agonists have shifted the treatment paradigm for primary biliary cholangitis (PBC) away from the UDCA-only approach. This expanded drug armamentarium has increased the complexity of disease management, resulting in heterogeneous and diverse PBC practices worldwide. We aimed to define who are the patients offered second line treatment and what is the dynamic of add-on, switches or stop of second line treatment across the Globe.
We conducted a retrospective, international, multicentric cohort study involving PBC patients who began second-line treatment with either fibric acid derivatives (fibrates) or OCA in 40 tertiary centres across Europe, Japan, South America, and North America. We collected clinical, biochemical, and treatment data at diagnosis and at the initiation of second-line treatment. Adverse effects and treatment changes during follow-up were also recorded.
We accrued data on 1,831 patients, 917 initiated on OCA (901 already on UDCA) and 868 on fibrates (863 on UDCA). Among these, 635 patients started on bezafibrate and 233 on fenofibrate. 276 of the patients on Bezafibrate were from 18 centres with restricted access to OCA, in Japan, Argentina and Netherlands. Only 17 patients began bezafibrate and OCA simultaneously. The sex distribution did not differ significantly between the fibrate and OCA groups (female: 87.9% vs 88.9%, p=0.570). Baseline mean ALT, ALP, GGT, and bilirubin (ratios to the upper limit of normal) were 1.47 (±1.29) vs 1.63 (±1.58) (p=0.100), 2.64 (±1.55) vs 2.43 (±2.47) (p=0.070), 5.39 (±4.20) vs 5.06 (±4.79) (p=0.453), and 0.98 (±0.94) vs 0.98 (±0.64) (p=0.986), respectively. Baseline cirrhosis was more frequent in OCA patients (28.3.0%, n=216; vs 19.5%, n=83, p=0.01). Most cirrhotic patients on OCA were Child A (97.7%) compared with 64% on fibrates. The median time from UDCA initiation to second-line treatment was longer for OCA patients (70.7 (28-132) months vs 53 (15-123) months, p< 0.001). During follow-up, 96 OCA patients added a fibrate, while 22 fibrate patients added OCA. OCA was discontinued by 302 patients (33%), primarily due to pruritus (33%). 128 of them switched to fibrates. Fibrates were discontinued by 182 patients (21%) due to increased transaminases (18%) or worsening renal function (10%); 39 switched to OCA. The median time before adding a third medication or switching treatments was 23.5 (12.0-39.8) months for OCA and 27.0 (12.5-53.0) months for fibrates.
The management of PBC involves dynamic adjustments to second-line treatments. The high rates of treatment discontinuation and changes highlight the need for better tools to allocate second-line treatments more effectively. Additionally, these data suggest that second-line treatments should be offered earlier in the disease course to optimize management strategies.