TREAT EARLIER - Methotrexate in Clinically Suspect Arthralgia Patients Save

Lancet Rheumatology has published the results of the TREAT EARLIER trial, showing the prevention of rheumatoid arthritis may be enhanced by risk stratification, particularly in anti-citrullinated protein antibody (ACPA)-negative people with clinically suspect arthralgia. 

 

The TREAT EARLIER trial, a double-blind, placebo-controlled, proof-of-concept trial wherein adults with arthralgia and subclinical joint inflammation (by imaging) were randomized (1:1) to active treatment (methotrexate weekly) or placebo for 1 year, after a single intramuscular glucocorticoid injection (120 mg of methylprednisolone).  This report represents data after 4 years of follow-up. 

Participants were stratified via a prediction model into low risk, increased risk, and high risk of developing persistent inflammatory arthritis. The primary outcome was development of rheumatoid arthritis RA).

 

A total of 236 people with clinically suspect arthralgia were enrolled and included in the intention-to-treat analysis; 217 (92%) completed 4-year follow-up. Serologies revealed that 182 (77%) were ACPA-negative and 54 (23%) were ACPA-positive. 

 

The key finding was that a MTX benefit in CSA patients was mainly seen in the ACPA negative individuals. In the 182 ACPA-negative participants, 66 (36%) were predicted to be at increased risk (by Leiden criteria), and 116 (64%) were predicted to be at low risk. Of the 66 ACPA-negative participants predicted to be at increased risk, Only 3 (9%) on MTX developed RA compared with 9 (29%) on placebo group (hazard ratio 0.27, 95% CI 0.07–0.99; p=0·034). Of the 116 ACPA-negative participants predicted to be at low risk, there was no difference in RA outcomes between those on MTX (8%) vs. placebo (10%) (HR 0.79, 0.22–2.80; p=0·71). 

 

In the 54 ACPA-positive participants, 24 (44%) were predicted to be at high risk, 30 (56%) at increased risk, and none at low risk. After 4 years, RA developed in 21% on MTX (initially) vs 23% on placebo. 

 

A 1-year course of MTX also benefitted subclinical joint inflammation, physical functioning, and grip strength in ACPA-negative participants at increased risk of RA, but not in those with low risk.

 

MTX treatment of clinically suspect arthralgia patients only seemed to benefit those who were ACPA-negative, suggesting a role for risk stratification when considering how to RA in those with clinically suspect arthralgia.