The combination of ursodeoxycholic acid and methotrexate for patients with primary biliary cirrhosis

The results of a pilot study

Keith Lindor, E. Rolland Dickson, Roberta A. Jorgensen, Monte L. Anderson, Russell H. Wiesner, Gregory J. Gores, Stephen M. Lange, Steven S. Rossi, Alan F. Hofmann, William P. Baldus

Research output: Contribution to journalArticle

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Abstract

Ursodeoxycholic acid (UDCA) and methotrexate (MIX) have both been proposed as treatments for patients with primary biliary cirrhosis (PBC). It has been suggested that a combination of the two drugs may offer advantages over either used separately. In this pilot study, we sought to evaluate the safety and efficacy of this combination for patients with PBC. Thirty-two patients with antimitochondrial antibody positive PBC were prospectively entered into a pilot study and received UDCA, 13 to 15 mg/kg/d, in conjunction with MTX, 0.25 mg/kg/wk, for a period of 2 years. The results of this treatment were compared with those obtained from 180 patients with PBC studied in a placebo-controlled trial of UDCA alone conducted during the same period. Patients in the pilot study and randomized study were comparable with regard to age, gender, and liver biochemistries. The UDCA/MTX-treated patients were of earlier histologic stage and had a lower mean Mayo risk score. During this period, seven patients in the UDCA/MTX group were withdrawn, four for pulmonary toxicity (two who required hospitalization), and one each with mouth ulcer, extreme fatigue, and hair loss. The use of UDCA/ MTX was not associated with improvement in symptoms. In the patients receiving UDCA/MTX, biochemical changes were comparable to those of patients receiving UDCA alone but superior to those in the placebo group (P < .05). Histological changes were comparable in all groups at 2 years. Cessation of MTX while UDCA was continued led to no deterioration in liver biochemistries. In a 2-year study, the use of MTX in combination with UDCA was associated with substantial toxicity, but with no evidence for symptomatic, biochemical, or histologic improvement over that seen with UDCA alone. The use of MTX in patients with PBC should be confined to patients in prospective trials and not used on an empiric basis.

Original languageEnglish (US)
Pages (from-to)1158-1162
Number of pages5
JournalHepatology
Volume22
Issue number4 PART 1
DOIs
StatePublished - 1995
Externally publishedYes

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Ursodeoxycholic Acid
Biliary Liver Cirrhosis
Methotrexate
Biochemistry
Placebos
Oral Ulcer
Liver
Alopecia
Drug Combinations
Fatigue
Hospitalization

ASJC Scopus subject areas

  • Hepatology

Cite this

Lindor, K., Rolland Dickson, E., Jorgensen, R. A., Anderson, M. L., Wiesner, R. H., Gores, G. J., ... Baldus, W. P. (1995). The combination of ursodeoxycholic acid and methotrexate for patients with primary biliary cirrhosis: The results of a pilot study. Hepatology, 22(4 PART 1), 1158-1162. https://doi.org/10.1016/0270-9139(95)90624-X

The combination of ursodeoxycholic acid and methotrexate for patients with primary biliary cirrhosis : The results of a pilot study. / Lindor, Keith; Rolland Dickson, E.; Jorgensen, Roberta A.; Anderson, Monte L.; Wiesner, Russell H.; Gores, Gregory J.; Lange, Stephen M.; Rossi, Steven S.; Hofmann, Alan F.; Baldus, William P.

In: Hepatology, Vol. 22, No. 4 PART 1, 1995, p. 1158-1162.

Research output: Contribution to journalArticle

Lindor, K, Rolland Dickson, E, Jorgensen, RA, Anderson, ML, Wiesner, RH, Gores, GJ, Lange, SM, Rossi, SS, Hofmann, AF & Baldus, WP 1995, 'The combination of ursodeoxycholic acid and methotrexate for patients with primary biliary cirrhosis: The results of a pilot study', Hepatology, vol. 22, no. 4 PART 1, pp. 1158-1162. https://doi.org/10.1016/0270-9139(95)90624-X
Lindor, Keith ; Rolland Dickson, E. ; Jorgensen, Roberta A. ; Anderson, Monte L. ; Wiesner, Russell H. ; Gores, Gregory J. ; Lange, Stephen M. ; Rossi, Steven S. ; Hofmann, Alan F. ; Baldus, William P. / The combination of ursodeoxycholic acid and methotrexate for patients with primary biliary cirrhosis : The results of a pilot study. In: Hepatology. 1995 ; Vol. 22, No. 4 PART 1. pp. 1158-1162.
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abstract = "Ursodeoxycholic acid (UDCA) and methotrexate (MIX) have both been proposed as treatments for patients with primary biliary cirrhosis (PBC). It has been suggested that a combination of the two drugs may offer advantages over either used separately. In this pilot study, we sought to evaluate the safety and efficacy of this combination for patients with PBC. Thirty-two patients with antimitochondrial antibody positive PBC were prospectively entered into a pilot study and received UDCA, 13 to 15 mg/kg/d, in conjunction with MTX, 0.25 mg/kg/wk, for a period of 2 years. The results of this treatment were compared with those obtained from 180 patients with PBC studied in a placebo-controlled trial of UDCA alone conducted during the same period. Patients in the pilot study and randomized study were comparable with regard to age, gender, and liver biochemistries. The UDCA/MTX-treated patients were of earlier histologic stage and had a lower mean Mayo risk score. During this period, seven patients in the UDCA/MTX group were withdrawn, four for pulmonary toxicity (two who required hospitalization), and one each with mouth ulcer, extreme fatigue, and hair loss. The use of UDCA/ MTX was not associated with improvement in symptoms. In the patients receiving UDCA/MTX, biochemical changes were comparable to those of patients receiving UDCA alone but superior to those in the placebo group (P < .05). Histological changes were comparable in all groups at 2 years. Cessation of MTX while UDCA was continued led to no deterioration in liver biochemistries. In a 2-year study, the use of MTX in combination with UDCA was associated with substantial toxicity, but with no evidence for symptomatic, biochemical, or histologic improvement over that seen with UDCA alone. The use of MTX in patients with PBC should be confined to patients in prospective trials and not used on an empiric basis.",
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N2 - Ursodeoxycholic acid (UDCA) and methotrexate (MIX) have both been proposed as treatments for patients with primary biliary cirrhosis (PBC). It has been suggested that a combination of the two drugs may offer advantages over either used separately. In this pilot study, we sought to evaluate the safety and efficacy of this combination for patients with PBC. Thirty-two patients with antimitochondrial antibody positive PBC were prospectively entered into a pilot study and received UDCA, 13 to 15 mg/kg/d, in conjunction with MTX, 0.25 mg/kg/wk, for a period of 2 years. The results of this treatment were compared with those obtained from 180 patients with PBC studied in a placebo-controlled trial of UDCA alone conducted during the same period. Patients in the pilot study and randomized study were comparable with regard to age, gender, and liver biochemistries. The UDCA/MTX-treated patients were of earlier histologic stage and had a lower mean Mayo risk score. During this period, seven patients in the UDCA/MTX group were withdrawn, four for pulmonary toxicity (two who required hospitalization), and one each with mouth ulcer, extreme fatigue, and hair loss. The use of UDCA/ MTX was not associated with improvement in symptoms. In the patients receiving UDCA/MTX, biochemical changes were comparable to those of patients receiving UDCA alone but superior to those in the placebo group (P < .05). Histological changes were comparable in all groups at 2 years. Cessation of MTX while UDCA was continued led to no deterioration in liver biochemistries. In a 2-year study, the use of MTX in combination with UDCA was associated with substantial toxicity, but with no evidence for symptomatic, biochemical, or histologic improvement over that seen with UDCA alone. The use of MTX in patients with PBC should be confined to patients in prospective trials and not used on an empiric basis.

AB - Ursodeoxycholic acid (UDCA) and methotrexate (MIX) have both been proposed as treatments for patients with primary biliary cirrhosis (PBC). It has been suggested that a combination of the two drugs may offer advantages over either used separately. In this pilot study, we sought to evaluate the safety and efficacy of this combination for patients with PBC. Thirty-two patients with antimitochondrial antibody positive PBC were prospectively entered into a pilot study and received UDCA, 13 to 15 mg/kg/d, in conjunction with MTX, 0.25 mg/kg/wk, for a period of 2 years. The results of this treatment were compared with those obtained from 180 patients with PBC studied in a placebo-controlled trial of UDCA alone conducted during the same period. Patients in the pilot study and randomized study were comparable with regard to age, gender, and liver biochemistries. The UDCA/MTX-treated patients were of earlier histologic stage and had a lower mean Mayo risk score. During this period, seven patients in the UDCA/MTX group were withdrawn, four for pulmonary toxicity (two who required hospitalization), and one each with mouth ulcer, extreme fatigue, and hair loss. The use of UDCA/ MTX was not associated with improvement in symptoms. In the patients receiving UDCA/MTX, biochemical changes were comparable to those of patients receiving UDCA alone but superior to those in the placebo group (P < .05). Histological changes were comparable in all groups at 2 years. Cessation of MTX while UDCA was continued led to no deterioration in liver biochemistries. In a 2-year study, the use of MTX in combination with UDCA was associated with substantial toxicity, but with no evidence for symptomatic, biochemical, or histologic improvement over that seen with UDCA alone. The use of MTX in patients with PBC should be confined to patients in prospective trials and not used on an empiric basis.

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