Title: Pharmacotherapy for Primary Biliary Cholangitis: An Assessment of Medication
Candidacy and Rates of Treatment
Version: 1 Date: 10 Oct 2023
Reviewer's report:
In this study, Nicholas MacDonald and colleagues, aimed to characterize usage rates
of Ursodeoxycholic acid  (UDCA) and second-line therapies among patients with PBC.
Overall, 495 PBC patients included. The authors reported that 95% of patients were taking
ursodeoxycholic acid, with 67% of them having disease well-controlled under UDCA
monotherapy. Of interest, only 8% of PBC patients were taking obeticholic acid (either as
combination or monotherapy) but only 3% would benefit from the addition of a second line
therapy but had not yet been offered medication.Moreover, 3% of patients were not on any
medication.
The study has clinical interest as it provides real-world data of first- and second-line treatments
of PBC patients. However, some points need further informations and should be addressed.
-Study population: the authors report that: -95% of all patients had been prescribed UDCA.
While 14% of all patients were determined to be an appropriate candidate for OCA, only 8% of
all patients were taking the medication - 7% were taking OCA in combination with UDCA and
1% were using OCA as monotherapy due to intolerance of UDCA. Likewise, 3% of patients
were on combination therapy with UDCA and a fibrate,  and only 3% of patients were not on
any medication for management of their PBC. In total, 18% of all patients studied had at least
one contraindication to OCA (Child-Pugh class B or C cirrhosis, known portal hypertension,
and/or any history of liver decompensation).
Could the authors describe in details indications and contraindication for UDCA therapy and
dosage used?
Why 24 PBC patients were not taking UDCA? why 5 of them were prescribed OCA, 3 other
montherapya (which one?), and 16 no therapy?
-OCA treated patients: it is well-known that the most frequent adverse event OCA-related is
pruritus. Could the authors provide the safety profile of OCA therapy?
-How the authors could explain the significant discrepancy between literature data describing a
30% rate of unsatisfactory response to UDCA in contrast with their findings?
-Althought the study has a potential interest in describing real-world PBC scenario, to
improve the clinical impact of the study, the authors should also describe (if available)
and discuss the previously identified prognostic factors associated to outcome and UDCA
treatment response rate in PBC, in particular: 1) clinical features at diagnosis since fatigue
and pruritus at diagnosis has been associated to worse prognosis and lower treatment
response rate as previously demonstrated (doi: 10.1111/liv.12560. Epub 2014 Apr 23). This
should be discussed; 2) rate of PBC patients who were anti-gp210 positive since this serum
autoantibody marker is associated to a worse prognosis as previously reported (doi: 10.1586/
erm.11.82; doi: 10.1111/j.1365-2036.2006.03172.x); could the authors exclude in their patients
a condition of autoimmune hepatitis/PBC overlap syndrome (according to previously described
criteria in doi: 10.1038/ajg.2009.126) that could impact of UDCA treatment response?; were
patients regularly followed-up also with surrogate measurement of liver fibrosis such as
liver stiffness measurement as recommended? (DOI: 10.1097/MOG.0000000000000909; doi:
10.1080/00365521.2021.1928277.).
-Could the authors describe (if any) the extrahepatic autoimmune disorders found in their
patients since PBC is frequently associated to other autoimmune disorders (thyroiditis, celiac
disease,  scleroderma, sjogren etc).
Title: Pharmacotherapy for Primary Biliary Cholangitis: An Assessment of Medication
Candidacy and Rates of Treatment
Version: 1 Date: 10 Oct 2023
Reviewer's report:
In this study, Nicholas MacDonald and colleagues, aimed to characterize usage rates
of Ursodeoxycholic acid  (UDCA) and second-line therapies among patients with PBC.
Overall, 495 PBC patients included. The authors reported that 95% of patients were taking
ursodeoxycholic acid, with 67% of them having disease well-controlled under UDCA
monotherapy. Of interest, only 8% of PBC patients were taking obeticholic acid (either as
combination or monotherapy) but only 3% would benefit from the addition of a second line
therapy but had not yet been offered medication.Moreover, 3% of patients were not on any
medication.
The study has clinical interest as it provides real-world data of first- and second-line treatments
of PBC patients. However, some points need further informations and should be addressed.
-Study population: the authors report that: -95% of all patients had been prescribed UDCA.
While 14% of all patients were determined to be an appropriate candidate for OCA, only 8% of
all patients were taking the medication - 7% were taking OCA in combination with UDCA and
1% were using OCA as monotherapy due to intolerance of UDCA. Likewise, 3% of patients
were on combination therapy with UDCA and a fibrate,  and only 3% of patients were not on
any medication for management of their PBC. In total, 18% of all patients studied had at least
one contraindication to OCA (Child-Pugh class B or C cirrhosis, known portal hypertension,
and/or any history of liver decompensation).
Could the authors describe in details indications and contraindication for UDCA therapy and
dosage used?
Why 24 PBC patients were not taking UDCA? why 5 of them were prescribed OCA, 3 other
montherapya (which one?), and 16 no therapy?
-OCA treated patients: it is well-known that the most frequent adverse event OCA-related is
pruritus. Could the authors provide the safety profile of OCA therapy?
-How the authors could explain the significant discrepancy between literature data describing a
30% rate of unsatisfactory response to UDCA in contrast with their findings?
-Althought the study has a potential interest in describing real-world PBC scenario, to
improve the clinical impact of the study, the authors should also describe (if available)
and discuss the previously identified prognostic factors associated to outcome and UDCA
treatment response rate in PBC, in particular: 1) clinical features at diagnosis since fatigue
and pruritus at diagnosis has been associated to worse prognosis and lower treatment
response rate as previously demonstrated (doi: 10.1111/liv.12560. Epub 2014 Apr 23). This
should be discussed; 2) rate of PBC patients who were anti-gp210 positive since this serum
autoantibody marker is associated to a worse prognosis as previously reported (doi: 10.1586/
erm.11.82; doi: 10.1111/j.1365-2036.2006.03172.x); could the authors exclude in their patients
a condition of autoimmune hepatitis/PBC overlap syndrome (according to previously described
criteria in doi: 10.1038/ajg.2009.126) that could impact of UDCA treatment response?; were
patients regularly followed-up also with surrogate measurement of liver fibrosis such as
liver stiffness measurement as recommended? (DOI: 10.1097/MOG.0000000000000909; doi:
10.1080/00365521.2021.1928277.).
-Could the authors describe (if any) the extrahepatic autoimmune disorders found in their
patients since PBC is frequently associated to other autoimmune disorders (thyroiditis, celiac
disease,  scleroderma, sjogren etc).
Please review this paper.
user
Title: Pharmacotherapy for Primary Biliary Cholangitis: An Assessment of Medication
Candidacy and Rates of Treatment
Version: 1 Date: 10 Oct 2023
Reviewer's report:
In this study, Nicholas MacDonald and colleagues, aimed to characterize usage rates
of Ursodeoxycholic acid  (UDCA) and second-line therapies among patients with PBC.
Overall, 495 PBC patients included. The authors reported that 95% of patients were taking
ursodeoxycholic acid, with 67% of them having disease well-controlled under UDCA
monotherapy. Of interest, only 8% of PBC patients were taking obeticholic acid (either as
combination or monotherapy) but only 3% would benefit from the addition of a second line
therapy but had not yet been offered medication.Moreover, 3% of patients were not on any
medication.
The study has clinical interest as it provides real-world data of first- and second-line treatments
of PBC patients. However, some points need further informations and should be addressed.
-Study population: the authors report that: -95% of all patients had been prescribed UDCA.
While 14% of all patients were determined to be an appropriate candidate for OCA, only 8% of
all patients were taking the medication - 7% were taking OCA in combination with UDCA and
1% were using OCA as monotherapy due to intolerance of UDCA. Likewise, 3% of patients
were on combination therapy with UDCA and a fibrate,  and only 3% of patients were not on
any medication for management of their PBC. In total, 18% of all patients studied had at least
one contraindication to OCA (Child-Pugh class B or C cirrhosis, known portal hypertension,
and/or any history of liver decompensation).
Could the authors describe in details indications and contraindication for UDCA therapy and
dosage used?
Why 24 PBC patients were not taking UDCA? why 5 of them were prescribed OCA, 3 other
montherapya (which one?), and 16 no therapy?
-OCA treated patients: it is well-known that the most frequent adverse event OCA-related is
pruritus. Could the authors provide the safety profile of OCA therapy?
-How the authors could explain the significant discrepancy between literature data describing a
30% rate of unsatisfactory response to UDCA in contrast with their findings?
-Althought the study has a potential interest in describing real-world PBC scenario, to
improve the clinical impact of the study, the authors should also describe (if available)
and discuss the previously identified prognostic factors associated to outcome and UDCA
treatment response rate in PBC, in particular: 1) clinical features at diagnosis since fatigue
and pruritus at diagnosis has been associated to worse prognosis and lower treatment
response rate as previously demonstrated (doi: 10.1111/liv.12560. Epub 2014 Apr 23). This
should be discussed; 2) rate of PBC patients who were anti-gp210 positive since this serum
autoantibody marker is associated to a worse prognosis as previously reported (doi: 10.1586/
erm.11.82; doi: 10.1111/j.1365-2036.2006.03172.x); could the authors exclude in their patients
a condition of autoimmune hepatitis/PBC overlap syndrome (according to previously described
criteria in doi: 10.1038/ajg.2009.126) that could impact of UDCA treatment response?; were
patients regularly followed-up also with surrogate measurement of liver fibrosis such as
liver stiffness measurement as recommended? (DOI: 10.1097/MOG.0000000000000909; doi:
10.1080/00365521.2021.1928277.).
-Could the authors describe (if any) the extrahepatic autoimmune disorders found in their
patients since PBC is frequently associated to other autoimmune disorders (thyroiditis, celiac
disease,  scleroderma, sjogren etc).
assistant