AB0333 CLINICAL AND ULTRASONOGRAPHIC RESPONSE TO SUBCUTANEOUS METHOTREXATE IN EARLY RHEUMATOID ARTHRITIS. PRELIMINARY RESULTS.
Authors: L. R. Caballero Motta, A. M. Anzola Alfaro, L. A. Torrens Cid, C. Y. Soleto, B. Serrano Benavente, I. Janta, J. Molina Collada, C. Gonzalez, I. Monteagudo, J. M. Alvaro Gracia, J. C. Nieto
Journal: Annals of the Rheumatic Diseases (2020)

Background: Metotrexate (MTX) is usually the first line therapy for Rheumatoid Arthritis (RA) because of its favorable efficacy-toxicity ratio. However the exact mechanism and treatment response time in both a clinical and ultrasonographic setting are still uncertain. Objectives: To describe the clinical and ultrasound response to MTX during the first 6 months of treatment in early RA patients who started subcutaneous methotrexate as the first disease-modifying drug (DMARD). Methods: Ongoing prospective cohort of patients with early RA (ACR-EULAR 2010 criteria), over 18 years and starting MTX-SC. 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 (delta value of -1.2 in DAS28 scores). Joints explored with ultrasound were elbows and wrists (radio-carpal and inter-carpal joint) counted as a single joint, 1st-5th metacarpophalangeal (MCF), proximal interphalangeal (IFP), knees, tibio-talar and subtalar joints and 2nd-5th metatarsophalangeal (MTF) joints. Bone erosions were evaluated in 2nd and 5th MCF, styloid, distal ulna and 5th MTF. Synovitis was graduated semi-quantitatively from 0 to 3 (OMERACT) and calculated on B mode and Doppler. Results: 35 patients were included (mean age 61.2 years, 65.7% women) with a median of 0.8 (+/-8) months delay to diagnosis. 34 patients (97.1%) started 15mg MTX-SC/weekly. A higher DAS28esr was found in baseline data for the group that had a response by month 1 (DAS28esr baseline 5.5 vs 4.2 p=0.01), no other significant differences were found. During the first month, a significant response was achieved in 13 (41%) patients and remission in 11 (35%) (Table 1). 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 it by month 1. A difference in MTX dose (month1 14.8 vs month6 17.1 p=0.003) was found between month 1 and 6, with no differences in disease activity. In the ultrasonographic baseline data; 8 patients (22.9%) had erosions, with a mean of 2,75 erosions/patient (22 of the 280 locations). During the follow up the global rating lowered, with no differences in B mode but significant differences in Doppler at the 6 month mark (Table 2). As 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. Table 2. Ultrasound synovitis global rating. Baseline Month 1 P Value EULAR response 0 13 (41) 0.00005 MTX Dose mg (SD) 14.8 (+/-0.8) 14.8 (+/-1.6) 1 Prednisone Dose mg(SD) 5.9 (+/-6.5) 2.9 (+/-3) 0.02 DAS28crp (SD) 4.3 (+/-1.5) 3,4 (+/-1.4) 0.02 DAS28esr (SD) (4.8 (+/-1.5) 3.7 (+/-1.4) 0.006 Remission (DAS28&lt;1.2) 3(9.6) 11(35.5) 0.04 Table 1. Baseline characteristics of the patients with RA (n=102). Baseline N=35 1 month N=31 3 months N=25 6 months N=17 B Mode: Median (interquartile range) 8 (3.5-12) 8 (3-12.5) 6 (4-11) 5 (2-11) p 0,16 Doppler Mode : Median (interquartile range) 2 (0.5-6) 2 (0-6) 2 (0-6) 0 (0-2) p 0,005 Conclusion: In this cohort half of the patients that responded to treatment had achieved this by month 1. A higher baseline inflammatory profile was related to the response. Little difference is found between month 1 and 6 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 requiring longer to completely suppress inflammatory activity. References: [1]Braun, J. et al. Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of methotrexate in patients with active rheumatoid arthritis. Arthritis Rheum 2008 Disclosure of Interests: Liz R. Caballero Motta: None declared, Ana Melissa Anzola Alfaro: None declared, Luis A Torrens Cid: None declared, Christian Y Soleto: None declared, Belén Serrano Benavente: None declared, Iustina Janta: None declared, Juan Molina Collada: None declared, Carlos Gonzalez Consultant of: Gilead, Janssen, Novartis,, Speakers bureau: Abbvie, Celgene, Gilead, Janssen, Novartis, Pfizer, Roche, Indalecio Monteagudo: None declared, Jose Maria Alvaro Gracia: None declared, Juan Carlos Nieto Speakers bureau: Pfizer, Abbvie, MSD, Novartis, Janssen, Lilly, Nordic Pharma, BMS, Gebro, FAES Farma, Roche, Sanofi