We were not disheartened by our efforts in the PUMPS trial which did not show a positive effect of methotrexate on the course of PBC treated with UDCA alone. We were impressed, however, that it will take many patients, adequately controlled, and followed for many years if a positive effect of any therapy is to be demonstrated when the endpoints are complications of liver disease, transplant-free survival, and overall survival.
We agree with Professor Jones and the other members of the Liver Research Group at Newcastle that improving the Quality of Life (QOL) even while not extending it is a very important objective of therapy, particularly in PBC. Parenthetically, we did assess QOL using a diary that carefully examined an incapacitation index and pruritus, and found no differences in the groups treated with methotrexate and UDCA or with UDCA alone.
Our “pessimism” is based more on the numbers of patients it will take to demonstrate therapeutic effects on complications of liver diseases other than QOL. Hopefully, it may take many fewer subjects to show meaningful improvement in QOL.