medwireNews: UK researchers have identified characteristics in patients with inflammatory polyarthritis that may make them less likely to respond to oral methotrexate treatment.
The team found that patients who were younger, positive for rheumatoid factor (RF), or had higher baseline disease activity were more likely to stop methotrexate or need the addition of another antirheumatic drug due to its inefficacy.
Reporting in Arthritis Research & Therapy, Suzanne Verstappen, from the University of Manchester, and colleagues suggest: “Such patients may require combination therapy as a first-line treatment.”
Oral methotrexate is the first-line therapy for patients with rheumatoid arthritis (RA), but approximately a quarter of patients discontinue therapy within 12 months, say the researchers.
They studied 431 patients with early inflammatory polyarthritis who were recruited onto the Norfolk Arthritis Register between 2000 and 2008, and who started methotrexate as their first DMARD. In all, 82% of patients remained on methotrexate at 2 years, while 72% were still receiving methotrexate at 5 years.
Overall, 16% of patients reported an adverse event – most commonly gut symptoms – as the reason for discontinuing methotrexate, whereas 33% of the group experienced methotrexate failure due to inefficacy, which was defined as methotrexate cessation due to inefficacy, switching to another DMARD, or the addition of a second DMARD during follow-up.
After adjusting for competing risks, earlier methotrexate failure due to inefficacy was significantly associated with age of disease onset, RF-positivity, and a higher baseline disease activity as assessed by the Disease Activity Score at 28 joints based on C-reactive protein, with subdistribution hazard ratios (sHRs) of 0.97, 1.67, and 1.23, respectively.
Methotrexate cessation due to an adverse event was significantly less likely in patients who were RF positive than those who were RF negative (sHR=0.34).
The researchers note that a fifth of the patients stopped methotrexate as a result of a reported adverse event that could have been identified during routine blood test monitoring and suggest the data support ongoing blood monitoring for patients.
Verstappen et al explain: “Within the past decade there has been a major shift in the treatment paradigm of RA with the aim of achieving low disease activity or remission.”
They add that “[t]his ‘treat to target’ approach incorporates early escalation of [methotrexate] dose and use of combination therapy.”
And the team concludes: “Knowledge of predictors of [methotrexate] failure should enable early identification of individuals who are at increased risk of [methotrexate] inefficacy or adverse events and appropriate adjustment in treatment.”
By Anita Chakraverty
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