The combination of ursodeoxycholic acid and methotrexate for primary biliary cirrhosis is not better than ursodeoxycholic acid alone

González-Koch, Alvaro; Brahm, Javier; Antezana, C; Smok, G; Cumsille, Miguel A.

doi:10.1016/s0168-8278(97)80294-2

Cited by 54 publications

(28 citation statements)

References 22 publications

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“…11,12,21,22 In general, the number of patients assessed was too few, and the duration of therapy too short to provide adequate insight into the long-term effects of such treatment.…”

Section: Discussionmentioning

confidence: 99%

Methotrexate (MTX) Plus Ursodeoxycholic Acid (UDCA) in the Treatment of Primary Biliary Cirrhosis * #

et al. 2005

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This placebo-controlled, randomized, multicenter trial compared the effects of MTX plus UDCA to UDCA alone on the course of primary biliary cirrhosis (PBC). Two hundred and sixty five AMA positive patients without ascites, variceal bleeding, or encephalopathy; a serum bilirubin less than 3 mg/dL; serum albumin 3 g/dL or greater, who had taken UDCA 15 mg/kg daily for at least 6 months, were stratified by Ludwig's histological staging and then randomized to MTX 15 mg/m 2 body surface area (maximum dose 20 mg) once a week while continuing on UDCA. The median time from randomization to closure of the study was 7.6 years (range: 4.6-8.8 years). Treatment failure was defined as death without liver transplantation; transplantation; variceal bleeding; development of ascites, encephalopathy, or varices; a doubling of serum bilirubin to 2.5 mg/dL or greater; a fall in serum albumin to 2.5 g/dL or less; histological progression by at least two stages or to cirrhosis. Patients were continued on treatment despite failure of treatment, unless transplantation ensued, drug toxicity necessitated withdrawal, or the patient developed a cancer. There were no significant differences in these parameters nor to the time of development of treatment failures observed for patients taking UDCA plus MTX, or UDCA plus placebo. The trial was conducted with a stopping rule, and was stopped early by the National Institutes of Health at the advice of our Data Safety Monitoring Board for reasons of futility. In conclusion, methotrexate when added to UDCA for a median period of 7.6 years had no effect on the course of PBC treated with UDCA alone. Supplementary material for this article can be found on the HEPATOLOGY website (http://www.interscience. wiley.com/jpages/0270-9139/suppmat/index.html).

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“…11,12,21,22 In general, the number of patients assessed was too few, and the duration of therapy too short to provide adequate insight into the long-term effects of such treatment.…”

Section: Discussionmentioning

confidence: 99%

Methotrexate (MTX) Plus Ursodeoxycholic Acid (UDCA) in the Treatment of Primary Biliary Cirrhosis * #

et al. 2005

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“…A subset of patients who have persistent abnormalities under UDCA may progress toward cirrhosis and thus may require adjuvant therapy. So far, three classes of drugs have been tested in combination with UDCA: colchicine, [13][14][15][16] methotrexate, [17][18][19][20] and corticosteroids. [21][22][23][24] Briefly, 1) the benefit of colchicine appeared to be marginal or absent in UDCA-treated patients;…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance of Serum Bilirubin Levels Under Ursodeoxycholic Acid Therapy in Patients With Primary Biliary Cirrhosis

Bonnand

et al. 1999

Hepatology

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We determined whether the normalization of serum bilirubin level (SBL) induced by ursodeoxycholic acid (UDCA) therapy was associated with an improved clinical outcome in patients with primary biliary cirrhosis (PBC). We estimated the prognostic values of SBL measured after 6 months of UDCA treatment for survival free of orthotopic liver transplantation (OLT). We used a database of 548 patients with PBC followed in three trials of UDCA. Among UDCA-treated patients, we compared survival free of OLT in patients with normalized SBL (I17 mol/L) with those who had persistently elevated SBL. Difference in survival was tested between UDCA-treated patients whose SBL normalized with treatment and placebo patients who had normal baseline SBL. We evaluated, in each treatment group, the prognostic value of 6-month SBL. Survival was estimated using the Kaplan-Meier method and compared by the Cox model. Survival free of OLT was significantly longer in patients who had normalized SBL (P F .0001; relative risk [RR]: 3.7, UDCA group). Survival free of OLT was not significantly different between UDCA patients with normalized SBL and placebo patients with a normal baseline SBL (P ‫؍‬ .69). For several cutoffs of 6-month SBL, RRs of OLT or death were similar in UDCA-treated and placebo patients: the RR of OLT or death associated with a 6-month SBL more than 30 mol/L was 6.0 for UDCA and 5.7 for placebo groups. In conclusion, normalization of SBL during therapy is associated with improved clinical outcome. SBL under UDCA therapy is a prognostic factor in PBC. SBL under UDCA therapy should be interpreted as in untreated patients. (HEPATOLOGY 1999;29:39-43.)

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“…After preliminary encouraging data coming from a pilot study [13], others reported disappointing results. The beneficial effects of MTX in the treatment of PBC, alone or in combination with UDCA, could not be confirmed by randomized clinical trials performed by other groups [7,14,15]. It should be noted, however, that substantial sideeffects were not observed in these studies, probably due also to low doses [7].…”

mentioning

confidence: 71%

Methotrexate for Primary Biliary Cirrhosis: Who Is to Be Trusted?

Selmi

Podda

2010

Dig Dis Sci

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The combination of ursodeoxycholic acid and methotrexate for primary biliary cirrhosis is not better than ursodeoxycholic acid alone

Cited by 54 publications

References 22 publications

Methotrexate (MTX) Plus Ursodeoxycholic Acid (UDCA) in the Treatment of Primary Biliary Cirrhosis * #

Methotrexate (MTX) Plus Ursodeoxycholic Acid (UDCA) in the Treatment of Primary Biliary Cirrhosis * #

Clinical Significance of Serum Bilirubin Levels Under Ursodeoxycholic Acid Therapy in Patients With Primary Biliary Cirrhosis

Methotrexate for Primary Biliary Cirrhosis: Who Is to Be Trusted?

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