# Which arthralgia patients benefit most in reduction of subclinical joint inflammation by methotrexate treatment: results from the TREAT EARLIER trial

## TL;DR

The study found that arthralgia patients with higher subclinical joint inflammation, especially tenosynovitis and osteitis, responded best to methotrexate treatment.

## Contribution

Identified subclinical inflammation markers that predict methotrexate response in arthralgia patients.

## Key findings

- 44 of 115 patients (38%) showed MRI-defined treatment response to methotrexate.
- Patients with ≥2 sites of tenosynovitis or a combination of osteitis and tenosynovitis had high predictive values for response.
- Treatment response was linked to improved pain and physical functioning.

## Abstract

The TREAT EARLIER trial showed in clinically suspect arthralgia (CSA) that methotrexate induced reductions in subclinical inflammation and related disease burden during the year of treatment, which was sustained thereafter. We studied whether the treatment response defined at the level of subclinical joint inflammation was present in all treated CSA patients and, if not, what characterises the subgroup of responders.

CSA patients with subclinical inflammation were randomised to receive an intramuscular glucocorticoid injection and a 1-year course of methotrexate. Treatment response was defined as a reduction of MRI-detected synovitis, tenosynovitis or osteitis levels beyond the smallest detectable change at 12 months. Baseline clinical and imaging characteristics were studied in relation to treatment response. Predictive values were determined.

44 of 115 (38%) treated patients had an MRI-defined treatment response. These patients also significantly improved in pain and physical functioning (−22 Visual Analogue Scale pain, −0.29 Health Assessment Questionnaire). Baseline clinical variables were not independently associated with this response, in contrast to the severity of subclinical joint inflammation. Tenosynovitis and osteitis levels in particular were predictive. Patients with ≥2 sites with tenosynovitis or a combination of osteitis and tenosynovitis (with ≥1 of these features at ≥2 sites) had high positive predictive values (PPV 77%, 79%). PPVs were similar in ACPA-positive and ACPA-negative patients at increased risk for rheumatoid arthritis (RA).

CSA patients with subclinical inflammation who responded best to methotrexate during the first year were identified by increased levels of subclinical inflammation at diagnosis, primarily due to multiple sites of tenosynovitis with/without osteitis. These data may contribute to personalised medicine for arthralgia at risk for RA.