Objectives: To describe the clinical and ultrasound response to methotrexate (MTX) during the first 6 months of treatment in early Rheumatoid Arthritis (RA) patients who started subcutaneous methotrexate (MTX-SC) as the first disease-modifying drug (DMARD).

Methods: Ongoing prospective cohort of patients with early RA according to ACR-EULAR 2010 criteria, over 18 years and starting MTX-SC by their treating rheumatologist. Patients had a clinical and ultrasonographic evaluation at baseline, 1, 3 and 6 months. We collected demographic data, C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], rheumatoid factor [FR], anti-citrullinated protein antibody [ACPA]), inflammatory activity indexes (DAS28esr and DAS28crp) and EULAR’s response to treatment (defined as a delta value of -1.2 in DAS28 scores). The ultrasonographic examination was performed in joints, tendons and bone erosions locations bilaterally. The joints explored were elbows and wrist (radio-carpal and inter-carpal joint) counted as a single joint, 1^st to 5^th metacarpophalangeal (MCF), proximal interphalangeal (IFP), knees, tibio-talar and subtalar joints and from the 2^nd to the 5^th metatarsophalangeal (MTF) joints. Bone erosions were evaluated in the 2^nd and 5^th MCF, styloid and distal ulna and the 5^th MTF. Synovitis and tenosynovitis were graduated semi-quantitatively from 0 to 3 following OMERACT. Total synovitis was calculated on B mode and Doppler mode.

Results: 35 patients were included (mean age 61.2 years, 65.7% women) with a mean of 0.3 (± 8) months delay between symptoms and diagnosis. 34 patients (97.1%) started 15 mg per week of MTX-SC. A slightly higher DAS28esr was found in baseline data for one group (Table 1). After the first month, a significant response was achieved in 13 (41%) patients and remission in 11 (35%) (Table 2). 17 patients have 6^th month data. 11 (64.7%) have achieved EULAR response compared to baseline (p = 0.0005) out of which 7 (54.5%) had already reached EULAR response by month 1. No significant differences were found between month 1 and 6 in disease activity; only a slight difference in MTX dose (month1 14.8 vs month 6 17.1, p = 0.003). Comparing the ultrasonographic baseline data; 8 patients (22.9%) already had erosions, with a mean of 2.75 erosions per patient (22 of the 280 possible locations). During the follow up the global rating lowered, with no differences in B mode, but with significant differences in Doppler mode at the 6 month mark (Table 3). At the cut of this report, 10 patients (28.5%) had stopped MTX treatment due to lack on response or adverse effects and 8 (22.9%) are waiting 6^th month evaluation.

Conclusions: MTX is usually first treatment of RA. In this cohort, we found that half the patients that responded to treatment had achieved this by month 1. A higher inflammatory profile made response more likely. It seems little difference is found between month 1 and 6 of treatment on clinical data, however ultrasonographic results suggest that at least 6 months are needed for Doppler improvement. Perhaps MTX has a faster effect over joint pain and lowers DAS28 scores, however it requires longer to completely suppress inflammatory activity.