AB0486 Subcutaneous methotrexate discontinuation in patients with rheumatoid arthritis

Abstract

BackgroundSafety of methotrexate (MT) therapy remains the most important issue of early rheumatoid arthritis (RA) therapy.ObjectivesA prospective evaluation of most common causes of MT discontinuation in RA patients with disease duration <3 years.MethodsAn open 1 year study included 106 patients with active RA meeting ACR/EULAR 2010 or ACR 1987 (DAS28 >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.ResultsTotally 12 (11%) MT discontinuations for the period of >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 >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).ConclusionsSkin 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.References[1...

Methotrexate injection site reactions: Case report and literature review

“…1,6,7 Rare adverse events reported with the subcutaneous administration of MTX have included hypocellular marrow, cutaneous ulcers, dermatitis, and lichenoid skin reactions, none of which were specific to injection sites. 8,9 Injection site reactions are extremely rare among patients utilizing subcutaneous MTX. Among 101 patients with rheumatoid arthritis utilizing MTX autoinjectors for subcutaneous administration, no injection site reactions were reported.…”