Methotrexate Reduces TNF Inhibitor Withdrawal Rates in Seropositive Rheumatoid Arthritis

methotrexate syringe
Study authors evaluated whether methotrexate reduced withdrawal rates of anti-tumor necrosis factor therapy in patients with rheumatoid arthritis who were seropositive and seronegative.

In patients with seropositive rheumatoid arthritis (RA), methotrexate may reduce withdrawal rates of tumor necrosis factor inhibitors (TNFis) due to ineffectiveness, according to a letter published in Annals of the Rheumatic Diseases.

The objective of the current analysis was to determine whether methotrexate can reduce anti-TNF therapy withdrawal due to ineffectiveness in patients with seropositive and seronegative RA.

Using retrospective, real-world data from a single center, treatment durations of adalimumab or etanercept were analyzed among 301 patients with RA. Rates of anti-TNF therapy withdrawal due to ineffectiveness were determined in patients who received anti-TNF therapy only, compared with those who received concomitant methotrexate and anti-TNF therapy.

During 5 years of follow-up, 52 withdrawals for adverse events and 10 withdrawals for other reasons were recorded.

Treatment discontinuation for ineffectiveness was more common in seropositive than seronegative patients with RA receiving only anti-TNF therapy (P =.002). Rates of anti-TNF therapy withdrawal for ineffectiveness were significantly lower among seropositive patients receiving concomitant methotrexate and anti-TNF therapy compared with those not receiving methotrexate. However, in the relatively small group of seronegative patients, withdrawal rates were significantly higher with methotrexate. The findings were confirmed in a separate validation cohort of 534 patients from 2 other hospitals.

Concomitant sulfasalazine, hydroxychloroquine, or number of concomitant disease-modifying antirheumatic drugs were not associated with withdrawal due to ineffectiveness, regardless of seropositivity.

Cox regression analyses revealed several risk factors for ineffectiveness of anti-TNF therapy, including seropositive status (hazard ratio [HR], 6.17; P =.012), methotrexate use (HR, 4.47; P =.049), and their interaction (HR, 0.12; P =.007).

“These results support the coprescription of [methotrexate] for patients with RA on adalimumab or etanercept but only for seropositive patients,” the study authors concluded.


Greenwood M, Shipa M, Yeoh SA, Roussou E, Mukerjee D, Ehrenstein MR. Methotrexate reduces withdrawal rates of TNF inhibitors due to ineffectiveness in rheumatoid arthritis but only in patients who are seropositive. Annals of the Rheumatic Diseases. Letter. 2020;79:1516-1517.