Obeticholic Acid for Primary Biliary Cholangitis
Abstract
:1. Introduction
2. Pharmacological Actions of OCA
3. Pre-Registration Studies
4. Real-World Data on OCA
5. Combined Therapy with OCA and Fibrates
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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NCT Number [Ref] | Type of Study | Therapeutic Scheme | Population | Outcome | Adverse Events |
---|---|---|---|---|---|
NCT00570765 [31] | Phase II study, 3-month randomized, double-blind, placebo-controlled, parallel group phase, followed by a long-term safety extension (LTSE) | OCA monotherapy (10 or 50 mg) | 60 PBC patients (18–70 years) | ALP reduction at both dosages after a 3-month treatment. Improvement of GGT, ALT, conjugated bilirubin, IgG | Pruritus (placebo 35%, OCA 10 70%, 94% OCA 50 |
NCT01473524 [32,33] | Phase III study, international 12-month randomized, double-blind (DB), placebo-controlled, parallel group phase, followed by a long-term safety extension (LTSE) phase of up to 5 years | OCA 5 mg (6 months) up to 10 mg or 10 mg vs. placebo | 217 patients (≥18 years) | ALP reduction only after 12-month treatment with combination Reduction in total and direct bilirubin | Pruritus (56% in the 5–10% group and 68% in the 10 mg group vs. 38% placebo |
NCT03253276 [38] | Early phase I, double-blind placebo-controlled crossover study | OCA vs. placebo | 8 PBC patients | OCA reduced the time hepatocytes are exposed to potentially cytotoxic bile acids. | 1 patient dropped for pruritus |
NCT00550862 [39] | Phase II, randomized, double-blind study | OCA (10, 25, 50 mg) plus UDCA combination | 165 patients (18–75 years) | Significant reduction in ALP, γ-GT, and ALT compared with placebo, in patients with PBC experiencing an inadequate response to UDCA | 13% discontinuation for pruritus |
NCT Number | Type of Study | Therapeutic Scheme | Estimated Enrollment | Primary Endpoints |
---|---|---|---|---|
NCT05450887 | Randomized, double-blind, multicenter, placebo-controlled phase III clinical trial | OCA (5 mg titrated to 10 mg) ± UDCA vs. placebo ± UDCA (13~15 mg/kg/day) | 156 PBC patients (18–75 years) | Percentage of PBC patients reaching ALP < 1.67× Upper Limit of Normal, and ALP decrease ≥ 15% from baseline, and total bilirubin ≤ ULN after 12-month treatment |
NCT03703076 | Post-authorization non-interventional observational, multi-site study | OCA (5 or 10 mg) | 150 patients | Response to Ocaliva® after 12-month treatment (monotherapy or combination) assessed by Paris II response criteria |
NCT05293938 | Retrospective study | OCA (5 or 10 mg) and UDCA | 2544 participants | Time to the first occurrence of the composite endpoint of all-cause death, liver transplant, or hospitalization for hepatic decompensation after 67 months |
NCT05292872 (HEROES PBC) | Retrospective study | OCA (5 or 10 mg) and UDCA | 3156 participants | Time to the first occurrence of all-cause death, liver transplant, or hospitalization for hepatic decompensation after 67 months |
NCT05239468 | Phase IIa, double-blind, randomized, active-controlled, parallel group study | Bezafibrate 100 or 200 mg, OCA 5 mg, Bezafibrate placebo, OCA placebo | 60 patients | ALP change after 12 weeks vs. baseline |
NCT04594694 | Phase II, double-blind, randomized, parallel group study | Bezafibrate 200 or 400 mg, OCA mg, Bezafibrate placebos, OCA placebo | 75 patients | ALP change after 12 weeks vs. baseline |
NCT04076527 | Prospective, multicenter cohort study | OCA vs. UDCA | 1200 patients | Construction of a systematic registry to describe the characteristics and the recent state of usual clinical care of the respective population |
NCT04956328 | Multicenter, randomized, double-blind trial | OCA (5 to 10 mg) + UDCA, or placebo + UDCA | 120 patients | Percentage of PBC patients reaching ALP < 1.67× ULN, and ALP decrease ≥ 15% from baseline, and total bilirubin ≤ ULN after 48week-treatment |
Author | Country | N. of Patients | Inclusion Criteria | % of Cirrhosis | % of pts with AIH/PBC Overlap | % of Response According to POISE |
---|---|---|---|---|---|---|
Roberts | Canada | 64 | Hepatologist’s discretion | 23.7 | 6.3 | 18 |
Gomez | Spain/Portugal | 120 | Lack of response to Paris II criteria | 21.7 | 10 | 29.5 |
D’Amato | Italy | 191 | ALP > 1.5 UNL | 32 | 15 | 51.9 |
Outcome | Baseline Dual | Baseline Triple | Last Follow-Up Triple |
---|---|---|---|
ALP (xULN) | 2.5 | 1.8 | 1.1 |
Normal ALP (%) | 0.7 | 10.3 | 47.4 |
Absence of pruritus | 41.1 | 51.8 | 66.1 |
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Floreani, A.; Gabbia, D.; De Martin, S. Obeticholic Acid for Primary Biliary Cholangitis. Biomedicines 2022, 10, 2464. https://doi.org/10.3390/biomedicines10102464
Floreani A, Gabbia D, De Martin S. Obeticholic Acid for Primary Biliary Cholangitis. Biomedicines. 2022; 10(10):2464. https://doi.org/10.3390/biomedicines10102464
Chicago/Turabian StyleFloreani, Annarosa, Daniela Gabbia, and Sara De Martin. 2022. "Obeticholic Acid for Primary Biliary Cholangitis" Biomedicines 10, no. 10: 2464. https://doi.org/10.3390/biomedicines10102464
APA StyleFloreani, A., Gabbia, D., & De Martin, S. (2022). Obeticholic Acid for Primary Biliary Cholangitis. Biomedicines, 10(10), 2464. https://doi.org/10.3390/biomedicines10102464