medwireNews: Temporary methotrexate treatment in patients with arthralgia may delay the onset of clinical rheumatoid arthritis (RA) and reduce disease burden, researchers have found.
However, methotrexate treatment failed to prevent the development of clinical arthritis, reported Doortje Krijbolder (Leiden University Medical Center, the Netherlands), who presented the findings at the EULAR 2022 Congress in Copenhagen, Denmark.
Despite this, Krijbolder said the study provides the “first evidence for disease modification when intervening in pre-RA.”
She noted that the focus on identifying the “critical period for disease modification” has shifted from the 2 years after RA diagnosis, for which there is strong evidence, to earlier disease stages, including undifferentiated arthritis and arthralgia, to look at sustained disease modification.
Two trials performed in arthralgia to date have failed to find that therapeutic intervention prevents RA, but “this could depend on the chosen treatment or selected outcomes,” said Krijbolder.
The TREAT EARLIER proof-of-concept trial involved 236 adults who had arthralgia that was clinically suspected to progress to RA as well as subclinical joint inflammation identified on magnetic resonance imaging (MRI). They were randomly assigned to receive a single intramuscular glucocorticoid 120 mg injection followed by a 1-year course of methotrexate of up to 25 mg/week or placebo.
The 119 patients treated with methotrexate were no less likely to develop persistent clinical arthritis, defined as fulfilling the 2010 RA criteria or involving at least two joints for at least 2 weeks, at 2 years than the 117 patients receiving placebo, at rates of 80% and 82%, respectively.
But Krijbolder said their results did show a delay in the onset of persistent clinical arthritis in two prespecified subgroups of high-risk patients: those with a positive predictive value (PPV) of at least 70%, and those positive for anti-citrullinated protein antibodies.
The proportion of patients developing arthritis earlier on was smaller among those in the treatment group than the placebo group, with a statistically significant difference between the two groups at 6 and 12 months in those with a PPV of at least 70%. But during the second year “this difference disappears,” indicating a delay but no prevention, said Krijbolder.
There was also a reduction in disease burden in the overall study population that was significantly greater with methotrexate treatment, as seen by a significantly greater reduction in joint pain, morning stiffness, functional impairment on the HAQ scale, and presenteeism at work that persisted over the entire 2 years and was evident across all subgroups. And there was a similar treatment effect on MRI-detected joint inflammation.
Krijbolder commented that it “may seem counterintuitive that on the one hand we found a delay in arthritis development at most, but no prevention, and on the other hand we did find a sustained treatment effect in MRI-detected joint inflammation and related symptoms and impairment.”
To explain this, the researchers performed a post-hoc analysis in high-risk participants stratified according to whether or not they progressed to clinical arthritis.
The results showed that “both progressors and nonprogressors are benefiting from this treatment,” said Krijbolder.
“Participants who did not progress to arthritis almost had a complete relief of pain and nearly returned to the normal range of MRI-detected inflammation that can be found in symptom-free controls,” she noted.
“Participants who did progress, whether early or later during follow-up, had clearly less pain and less MRI-detected inflammation if they were in the treatment group.”
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