MTX-intolerance? Consider JAKi as monotherapy

About one third of RA patients are intolerant to MTX, and as a result receive target therapies as monotherapy. Clinical studies show that without the added MTX, TNF-inhibitors are not as effective. For these patients a JAKi may be the better choice.

JAKis has proven highly effective in RA in large phase 3 studies. When it comes to managing pain, function (HAQ) and fatigue, JAKis such as filgotinib have proven to be significantly more effective than TNF-inhibitors (1-3). Another advantage with JAKis is that the efficacy is consistent with or without the added MTX. 

Almost one of three are intolerant to MTX

A large proportion (app 30%) of RA patients are intolerant to MTX and receive target therapies as monotherapy (2). Filgotinib has proven effective in this patient population (4). On the other hand, TNFi’s, repeatedly, have proven to be lesser effective in this population, as well as having significant more tolerability issues compared to RA patients treated with concomitant MTX (4,5). Direct evidence from a single trial also shows that filgotinib compared to adalimumab was more effective and had fewer serious adverse events in this monotherapy population (6). Moreover, IL-6i agents which also have proven effective in monotherapy RA patients seems to depend on seropositivity and high CRP-level to perform effectively (7), where as JAK-inhibitors do not have these limitations.

In conclusion: when faced with a patient that is intolerant to MTX, but is a good fit for JAKis, this may be the better therapeutic choice.







5. Arthritis & Rheum 2006; 54: 26-37

6. Fleischmann R, Cutolo M, Genovese MC, Lee EB, Kanik KS, Sadis S, Connell CA, Gruben D, Krishnaswami S, Wallenstein G, Wilkinson BE, Zwillich SH.Arthritis Rheum. 2012 Mar;64(3):617-29