Volume 117, Issue 2, Pages 400-407 (August 1999) Low-dose methotrexate is ineffective in primary biliary cirrhosis: Long-term results of a placebo-controlled trial  Mark T. Hendrickse, Elizabeth Rigney, Mustapha H. Giaffer, Irshad Soomro, David R. Triger, James C.E. Underwood, Dermot Gleeson  Gastroenterology  Volume 117, Issue 2, Pages 400-407 (August 1999) DOI: 10.1053/gast.1999.0029900400

1 Fig. 1. Serum laboratory values (mean ± SEM) in MTX group (▿) and placebo group (●). Numbers of patients at each time are shown above or below error bars. The mean of all on-treatment values in each patient is shown on the right, including those taken at time points not shown in the main figure. *P < 0.05; **P < 0.02; ***P < 0.01 by ANCOVA. (A) Alkaline phosphatase. The decrease in both groups over the first year is partly artifactual, a result of the use of a different method for calculation of alkaline phosphatase as of April 1992 (1 year after the trial started). (B) γ-Glutamyltransferase. (C) IgM. (D) ALT. Mean on-treatment ALT value refers to values at or after 24 months in the trial. Mean on-treatment ALT levels before 24 months in the trial did not differ between groups (94 + 9 μmol/L placebo vs. 84 + 7 μmol/L MTX). Gastroenterology 1999 117, 400-407DOI: (10.1053/gast.1999.0029900400)

1 Fig. 1. Serum laboratory values (mean ± SEM) in MTX group (▿) and placebo group (●). Numbers of patients at each time are shown above or below error bars. The mean of all on-treatment values in each patient is shown on the right, including those taken at time points not shown in the main figure. *P < 0.05; **P < 0.02; ***P < 0.01 by ANCOVA. (A) Alkaline phosphatase. The decrease in both groups over the first year is partly artifactual, a result of the use of a different method for calculation of alkaline phosphatase as of April 1992 (1 year after the trial started). (B) γ-Glutamyltransferase. (C) IgM. (D) ALT. Mean on-treatment ALT value refers to values at or after 24 months in the trial. Mean on-treatment ALT levels before 24 months in the trial did not differ between groups (94 + 9 μmol/L placebo vs. 84 + 7 μmol/L MTX). Gastroenterology 1999 117, 400-407DOI: (10.1053/gast.1999.0029900400)

1 Fig. 1. Serum laboratory values (mean ± SEM) in MTX group (▿) and placebo group (●). Numbers of patients at each time are shown above or below error bars. The mean of all on-treatment values in each patient is shown on the right, including those taken at time points not shown in the main figure. *P < 0.05; **P < 0.02; ***P < 0.01 by ANCOVA. (A) Alkaline phosphatase. The decrease in both groups over the first year is partly artifactual, a result of the use of a different method for calculation of alkaline phosphatase as of April 1992 (1 year after the trial started). (B) γ-Glutamyltransferase. (C) IgM. (D) ALT. Mean on-treatment ALT value refers to values at or after 24 months in the trial. Mean on-treatment ALT levels before 24 months in the trial did not differ between groups (94 + 9 μmol/L placebo vs. 84 + 7 μmol/L MTX). Gastroenterology 1999 117, 400-407DOI: (10.1053/gast.1999.0029900400)

1 Fig. 1. Serum laboratory values (mean ± SEM) in MTX group (▿) and placebo group (●). Numbers of patients at each time are shown above or below error bars. The mean of all on-treatment values in each patient is shown on the right, including those taken at time points not shown in the main figure. *P < 0.05; **P < 0.02; ***P < 0.01 by ANCOVA. (A) Alkaline phosphatase. The decrease in both groups over the first year is partly artifactual, a result of the use of a different method for calculation of alkaline phosphatase as of April 1992 (1 year after the trial started). (B) γ-Glutamyltransferase. (C) IgM. (D) ALT. Mean on-treatment ALT value refers to values at or after 24 months in the trial. Mean on-treatment ALT levels before 24 months in the trial did not differ between groups (94 + 9 μmol/L placebo vs. 84 + 7 μmol/L MTX). Gastroenterology 1999 117, 400-407DOI: (10.1053/gast.1999.0029900400)

2 Fig. 2. (A) Serum bilirubin level and (B) Mayo score in MTX (▿) and placebo (●) groups. (Mean + SEM, numbers above or below error bars; “intention-to-treat” analysis, i.e., subsequent values included after withdrawal from trial). The number of patients in whom the Mayo score was calculated was lower than the total number of patients at each time point because prothrombin time (necessary for this calculation) was not determined routinely during follow-up after trial withdrawal. Final values (before death or transplantation) are included at subsequent time points in patients dying of or undergoing liver transplantation for liver disease. The final follow-up value in each patient before death, transplantation, or October 1997 is shown on the right. Gastroenterology 1999 117, 400-407DOI: (10.1053/gast.1999.0029900400)

2 Fig. 2. (A) Serum bilirubin level and (B) Mayo score in MTX (▿) and placebo (●) groups. (Mean + SEM, numbers above or below error bars; “intention-to-treat” analysis, i.e., subsequent values included after withdrawal from trial). The number of patients in whom the Mayo score was calculated was lower than the total number of patients at each time point because prothrombin time (necessary for this calculation) was not determined routinely during follow-up after trial withdrawal. Final values (before death or transplantation) are included at subsequent time points in patients dying of or undergoing liver transplantation for liver disease. The final follow-up value in each patient before death, transplantation, or October 1997 is shown on the right. Gastroenterology 1999 117, 400-407DOI: (10.1053/gast.1999.0029900400)

3 Fig. 3. Rates of death from or liver transplantation for liver disease during or after the trial in MTX (—) and placebo (–––) groups. Numbers of patients “at risk” are given below. For MTX vs. placebo groups; χ2 = 1.71 (not significant) by log-rank test. Gastroenterology 1999 117, 400-407DOI: (10.1053/gast.1999.0029900400)