Patients with musculoskeletal pain and ACPA positivity: most progress to arthritis, but not always RA

Long-term outcomes of patients presenting with musculoskeletal pain and baseline anti-citrullinated protein antibodies (ACPA) found that 60% eventually progressed to clinical arthritis. However, rheumatoid arthritis (RA) was not the inevitable outcome: 28% of this at-risk population received alternative diagnoses.

“ACPA-positive individuals with musculoskeletal symptoms but no clinical arthritis represent a management challenge to rheumatologists, and identifying prognostic factors is critically important,” Dr Simon �
hammar (Linköping University, Sweden) stated [1]. Over 128 months, a prospective study followed Swedish patients without arthritis who tested positive for ACPA and had musculoskeletal pain. Patients enrolled between 2010 and 2013 were followed for the development of clinical arthritis in ≥1 joint as the primary outcome. Additional outcomes included fulfilling ACR/EULAR classification criteria for RA.

The cohort consisted of 82 patients with a mean age of 52 at baseline. Furthermore, 81% were women, 29% were rheumatoid factor (RF) positive, and the ACPA levels were categorised as high in 61% and low in 39% of cases.

During the follow-up period, survival curves demonstrated a gradual and ongoing transition to arthritis. “The median time to develop arthritis was 16 months,” Dr �
hammar stated. At the 10-year clinical assessment, 40 out of the 66 (60%) patients who completed the study had developed arthritis. While all of them fulfilled the ACR/EULAR criteria for RA, 28% ultimately received other diagnoses: transient arthritis without the need for disease-modifying anti-rheumatic drug (DMARD) treatment (13%), osteoarthritis (8%), and psoriatic arthritis (7%).

A multivariate model identified ACPA levels (P<0.001) and RF levels (P=0.020) as significant predictors of long-term progression to arthritis. “Other factors, such as the shared epitope, symptom duration, tender joint count, or C-reactive protein levels, were not predictive of arthritis development,” Dr �
hammar informed. He concluded by noting that a future analysis of this cohort will include radiographic data to refine the risk further.

1. �
   hammar S, et Results of a 10-year prospective follow-up of patients with musculoskeletal pain and anti-citrullinated protein antibodies - not every arthritis is rheumatoid arthritis, despite criteria fulfilment. OP0110, EULAR 2025, 11–14 June, Barcelona, Spain.

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Posted on 8 August 2025