A randomized crossover trial to assess therapeutic efficacy and cost reduction of acid ursodeoxycholic manufactured by the university hospital for the treatment of primary biliary cholangitis

Abstract

Background: Health care costs are growing faster than the rest of the global economy, according to the World Health Organization (WHO). Countries' health expenditures include paying for general medicine, diagnostic procedures, hospitalizations and surgeries, as well as medications and prescribed treatment. Primary biliary cholangitis (PBC) is a rare autoimmune liver disease and the first line available treatment is ursodeoxycholic acid (UDCA), however, direct and indirect treatment costs are expensive. Main aim of this trial was to assess if the therapeutic efficacy of UDCA manufactured by the university hospital is equivalent to that of standard UDCA and treatment cost reduction in patients with PBC.

Methods: It is a prospective, interventional, randomized, and crossover study in patients diagnosed with PBC. UDCA 300 mg tablets and capsules were developed and manufactured by the university hospital. Thirty patients under treatment with standard UDCA, in stable doses were randomized in sequence A and B, 15 patients in each arm. The groups were treated for 12 weeks and after, the UDCA formulation was changed, following for another 12 weeks of continuous therapy (tablets and capsules / capsules and tablets). Laboratory tests were performed at time T0 (beginning of treatment), T1 (at the 12 week-therapy, before the crossing-over) and T2 (end of treatment). The evaluation was done by comparing the hepatic parameters ALP, GGT, ALT, AST and total bilirubin, also considering the adverse events. The comparison of costs was based on price of the manufactured UDCA and standard UDCA price of the hospital.

Results: Hospital reduced 66.1% the PBC treatment costs using manufactured UDCA. There were no differences in the biochemical parameters between sequence (A and B) and tablets or capsules of UDCA formulations applied in the treatment of PBC.

Conclusions: The study showed that there was no significant difference between manufactured UDCA (capsule and tablet) and standard UDCA. Hospital reduced the PBC treatment costs using the manufactured UDCA by the university hospital.

Trial registration: ClinicalTrials.gov: NCT03489889 retrospectively registered on January 12th, 2018; Ethics Committee approved the study (ID: 1.790.088) on October 25th, 2016.

Keywords: Capsules; Health care costs; Hospital; Primary biliary cholangitis; Tablets; Ursodeoxycholic acid.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1

CONSORT diagram of patients’ recruitment and analysis. Study design and randomization: Thirty patients under treatment with commercial UDCA, in stable doses were randomized in groups A and B, 15 patients in each arm. The groups were treated for 12 weeks and after, the UDCA formulation was changed, following for another 12 weeks of continuous therapy (tablets and capsules / capsules and tablets). Laboratory tests were performed at time T0 (beginning of treatment), T1 (at the 12 week-therapy, before the crossing-over) and T2 (end of treatment)

Fig. 2

The patients’ preference of study medication. Fifteen patients (15/30) did not express a preference for one of the formulations but 30% (9/30) preferred UDCA tablets and 20% (6/30) capsule

Fig. 3

Adverse events. Most patients did not have AE 55.88% (19/34). The majority of adverse events were with capsule 29.41% (10/34) resulted more AE compared with tablets. No patient of sequence B had AE using UDCA tablets while sequence A had adverse event in UDCA tablets and capsules 5.88% (2/34). The discontinuation due to adverse event occurred in 5.88% (2/34) of patients in the sequence B. Legend: AE = adverse events