AB0486 Subcutaneous methotrexate discontinuation in patients with rheumatoid arthritis
Authors: G. Gridneva, Y. Muraviev
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Safety of methotrexate (MT) therapy remains the most important issue of early rheumatoid arthritis (RA) therapy. <h3>Objectives</h3> A prospective evaluation of most common causes of MT discontinuation in RA patients with disease duration &lt;3 years. <h3>Methods</h3> An open 1 year study included 106 patients with active RA meeting ACR/EULAR 2010 or ACR 1987 (DAS28 &gt;3,2) criteria, naïve to subcutaneous (SC) MT. All pts were administered SC MT, starting with 10–15 mg/week dose, and following 5 mg up-titration each 1–2 weeks (to max 30 mg/week) until achieving the target (remission or minimum disease activity) or emergence of adverse reactions (AR). Pts' monthly monitoring procedures included physical examination, blood analysis and biochemistry panel. T. Woodworth et al. inventory was used to assess the severity of ARs, and Naranjo scale was used to assess casual relationship of MT with an AR. <h3>Results</h3> Totally 12 (11%) MT discontinuations for the period of &gt;3 weeks were analysed. Permanent discontinuation occured in 9 pts (8%), and temporary (from 4 weeks to 4 months)—in 3 (3%). 83% of all cases of withdrawal took place during the first 3 months. in 3 patients MT was discontinuated because of an AR and inefficiency. Combination of drug failure with AR was the reason for permanent SC MT discontinuation in 3 pts. The causes led to SC MT discontinuation were: skin reactions in 3 pts(25%), "after-dose reactions"—in 2 (17%), allergic rash—in 2 (17%), diarrhoea—in 2 (17%), elevated liver enzymes—in 3 (25%), leukopenia – in 1 (8%), breast abscess—in 1 (8%). Some patients manifested multiple ARs. Two ARs (17%) were serious (grade 4 severity). Grade 3 ARs were documented in 4 cases (30%), Grade 2 ARs – in 4, and Grade 1 (mild) ARs – in 2 (17%) pts. Skin lesions became the underlying cause for SC MT discontinuation, such as active dermatitis (n=1) and lichenoid skin reaction (n=1). Totally 12 (11%) MT discontinuations for the period of &gt;3 weeks were analysed. Permanent discontinuation occured in 9 pts (8%), and temporary (from 4 weeks to 4 months)—in 3 (3%). 83% of all cases of withdrawal took place during the first 3 months. in 3 patients MT was discontinuated because of an AR and inefficiency. Combination of drug failure with AR was the reason for permanent SC MT discontinuation in 3 pts. The causes led to SC MT discontinuation were: skin reactions in 3 pts(25%), "after-dose reactions"—in 2 (17%), allergic rash—in 2 (17%), diarrhoea—in 2 (17%), elevated liver enzymes—in 3 (25%), leukopenia – in 1 (8%), breast abscess—in 1 (8%). Some patients manifested multiple ARs. Two ARs (17%) were serious (grade 4 severity). Grade 3 ARs were documented in 4 cases (30%), Grade 2 ARs – in 4, and Grade 1 (mild) ARs – in 2 (17%) pts. Skin lesions became the underlying cause for SC MT discontinuation, such as active dermatitis (n=1) and lichenoid skin reaction (n=1). <h3>Conclusions</h3> Skin reactions were the most common cause for SC MT discontinuation. Therapeutic failure as the leading cause for drug discontinuation was not documented in a single patient. <h3>References</h3> [1] Standardizing assessment and reporting of adverse effects in rheumatology clinical trials II: the Rheumatology Common Toxicity Criteria v.2.0. [2] Thasia Woodworth, Daniel E Furst, Rieke Alten, Clifton Bingham, David Yocum, Victor Sloan, Wayne Tsuji, Randall Stevens, James Fries, James Witter, Kent Johnson, Marissa Lassere, Peter Brooks. The Journal of RheumatologyJun 2007;34(6):1401–1. <h3>Disclosure of Interest</h3> None declared