A new study challenged the prevailing assumption that all patients with rheumatoid arthritis may experience a detectable presymptomatic phase. Researchers at Leiden University Medical Center observed that only a subset of patients exhibited a pre–rheumatoid arthritis phase, emphasizing the variability in disease progression.

In the study, published in RMD Open, the researchers analyzed 699 patients with rheumatoid arthritis (RA) diagnosed between 2012 and 2022. Using K-means clustering, they identified four patient clusters, with only two clusters (55% of the study population) showing significant numbers of patients with a preceding clinically suspect arthralgia phase.

Patients with an identifiable pre-RA phase were predominantly younger (mean age = 49 to 55 years), female, and anticitrullinated protein antibody (ACPA)-positive. They experienced gradual symptom onset and prolonged symptom duration prior to diagnosis. Conversely, those without a detectable pre-RA phase were older (mean age = 69 years), predominantly male, and ACPA-negative, with acute symptom onset and shorter prediagnosis durations.

Notably, the patients without a pre-RA phase achieved sustained disease-modifying anti-rheumatic drug (DMARD)-free remission more frequently (hazard ratio = 0.51, 95% confidence interval = 0.37–0.68) and required biological DMARDs less often (9% vs 19% to 20%). This finding underscored how preventive strategies targeting presymptomatic phases may benefit only specific subgroups.

The researchers highlighted limitations, including potential underrecognition of pre-RA symptoms and short symptom durations in certain clusters. The study's comprehensive data collection and long-term follow-up (median 5.3 years) provided robust insights into disease progression.

The authors declared no competing interests.