AB0495 Subcutaneous Methotrexate Safety in RA Patients (Remarca Trial Materials)

Abstract

BackgroundMethotrexate (MT) – is one of most preferable disease modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients.ObjectivesAim – prospective study of harm caused by subcutaneous MT to achieve target RA activity and inflammation control (within REMARCA trial protocol).Methods237 RA patients (with RA duration ≤6 mo (very early RA) – 101, >6 mo – 136) were administered subcutaneous MT (SC MT) as DMARD starting at 10 mg/week with further rapid dose increment up to 20–30 mg/week. All ITT (who received at least I MT injection) population was evaluated. Patients were monitored with monthly routine clinical, lab and instrumental examination, all adverse drug reactions (ADRs) were documented in a special standardized form by a physician. MT discontinuations (for up to 3 weeks, i.e. with total medication washout) and withdrawals were also registered. Randomly assigned 60 patients were filling questionnaires in order to better evaluate SC MT tolerability and patient's willingness to inject the drug continuously.ResultsMT–associated ADRs were registered in 49 (21%) patients: in 30 (61%) with very early RA and in 19 (39%) with RA >6 mo. Most common ADRs: increase of aminotransferases levels (ALT; 5,1%), (AST; 4,2%), nausea – 3,4%; post-dosing reactions (dizziness, BP increase) – 2,5%; alopecia – 2,1%; rash – 1,7%; injection site skin reactions in situ – 1,3%; infections requiring antibiotics or antiviral drugs, – 1,3%; leukopenia – 1,3%; less common: diarrhea – 0,8%; metallic taste in the mouth – 0,4%; remote from injection site soft tissue abscess/infiltrate – 0,4%. In 4,2% patients both MT-related and non-related ADRs led to SC drug withdrawal: rash (2,1%), post-dosing reactions (0,8%), nausea (0,4%), elevated transaminases (0,4%), leukopenia (0,4%). In these patients ADRs were not related RA duration.Only in 1% of patients SC MT was intolerable, while other patients classified SC MT as comfortable (42%) or tolerable (57%). 88% of responders were in favor of SC MT long-term use, the rest were either not willing (12%) or have not yet made their mind (1%).ConclusionsADRs associated with SC MT were registered in one of every 5 patients and led to withdrawal from SC MT in 4,2% RA patients. In 11% SC MT was discontinued due to ADRs, bat later restarted again. Obtained results allow to discuss the usefullnes of SC MT before administration of GEBA. This study has also established RA patients' compliance with continuous use of SC MT.Disclosure of InterestNone declared