Is there a direct relationship between serum level of methotrexate and clinical efficacy and tolerability? (Annals of the Rheumatic Diseases)

We have read with interest the article by Schiff et al1 comparing oral with subcutaneous administration of methotrexate (MTX). The authors, as one would have predicted, have shown that there is higher bioavailability of subcutaneous MTX compared with oral administration.2–4 We are somewhat confused, however, with the interpretation of some of the data. First, Figure 1 in the article clearly shows that there is an increase in area under the curve (AUC) of MTX with an increase in dose of subcutaneous MTX up to 25 mg. The authors state that with an oral dose of MTX, the AUC plateaus at 15 mg. Yet, in figure 1, it appears there is an increase in AUC of oral MTX 15 mg from approximately 1850 ng.h/mL to approximately 2000 ng.h/mL with 20 mg of oral MTX. The recommended dose of MTX is between 7.5 and 25 mg a week with many clinical...