Continue the Methotrexate, Leave the Cannoli Save

Placebo responses are to be expected in rheumatoid arthritis (RA) clinical trials, but are such placebo responses affected by continuing background DMARDs like methotrexate (MTX) even though there was an inadequate response (IR) to MTX? 

A post hoc analysis of placebo-treated patients in two RCTs (GO-AFTER and SIRROUND-T) looked at MTX-IR patients who either continued or stopped MTx with randomization to placebo (PBO) or the active study drug.  The primary outcomes were the ACR 20%/50%/70% response rates and Clinical Disease Activity Index (CDAI) low disease activity (LDA; ie, CDAI ≤10) responses. 

A total of 398 MTX-IR patients went on to receive placebo, 285 continued MTX and 113 had no background DMARD. By week 16, ACR20 responses were higher in the PBO + MTX group (25.3%) compared to PBO without MTX (12.4%) (p=0.005). Similarly, continuing MTX lead to higher PBO responses as measured by ACR50 (8.4% vs. 0.9%; p=0.003), ACR70 (2.8% vs. 0%; p=0.112) and CDAI-LDA (8.8% vs.1.8%; p=0.013).

These data suggest that despite an insufficient response to MTX, it may be prudent to continue MTX and add on a new DMARD or biologic in RA patients.

(Editors note: for those confused by the "playful" title here, it's a reference to the famous line from the movie, "The Godfather" that says "Leave the Gun, Take the Cannoli".  The point of this article (and the line from the movie) is to be sure about what you take and leave behind.  Don't leave the MTX behind!)