Rates and predictors of methotrexate-related adverse events in patients with early rheumatoid arthritis: results from a nationwide UK study

Abstract

Objectives To estimate prevalence rates and identify baseline predictors of adverse events (AEs) over the first year of treatment in patients with rheumatoid arthritis (RA) starting methotrexate (MTX). Methods Data came from the UK Rheumatoid Arthritis Medication Study (RAMS), a prospective cohort of patients with RA starting MTX. This analysis included patients aged ≥ 18 years with physician diagnosed RA and symptom duration ≤ two years, who were commencing MTX for the first time. AEs were recorded by interviewing patients at six- and twelve-month follow-up visits. The period prevalence rates of AEs are reported for 0–6 months, 6–12 months, and 0–12 months of follow-up. The associations between baseline characteristics and AEs were assessed using multivariable logistic regression. Results A total of 1069 patients were included in the analysis. Overall, 77.5% experienced at least one AE. The most commonly reported AEs were: gastrointestinal (42.0%), neurological (28.6%), mucocutaneous (26.0%), pulmonary (20.9%), elevated alanine transaminase (18.0%) and haematologic AEs (5.6%). Factors associated with increased odds of AEs were: women vs men (gastrointestinal, mucocutaneous, neurological), and alcohol consumption (nausea, alopecia, mucocutaneous). Older age, higher estimated Glomerular Filtration Rate (eGFR), and alcohol consumption were associated with less reporting of haematologic AEs. Conclusions AEs were common among patients over the first year of MTX, although most were not serious. Knowledge of the rates and factors associated with AEs occurrence are valuable when communicating risks prior to commencing MTX. This can help patients make informed decisions whether to start MTX, potentially increasing adherence to treatment.

Drug survival of methotrexate and predictor factors for discontinuation in psoriasis

“…and Greebe et al 23,25,27,37 . Among adverse events (occurring during therapy with MTX), gastrointestinal events were the most frequent (30.8–42%), followed by hepatotoxicity (15.1–20.2%), mucocutaneous (8.9–26.0%), neurological (5.5–28.6%), pulmonary (2.4–30.7%), and hematological side effects (5.2–5.6%) 38–40 . Similarly, the most frequent adverse events in our patients were hepatotoxicity (14.6%), nausea/emesis (14.1%), renal insufficiency (0.5%), medullary aplasia (1.5%), and pulmonary fibrosis (1.5%).…”

“…In fact, several authors have reported longer drug survival in elderly psoriatic patients, and Sherbini et al found a decreased incidence of AEs in these patients. 26,27,38 Nevertheless, as early as 1989, some authors found that psoriasis in elderly patients could be controlled with a lower dose than the recommended and investigated some of the factors associated with the required dose. 41 Our results also showed that dosage >15 mg for a period of at least 3 months was a positive predictive factor for persistence in therapy and was negatively associated with suspension for both ineffectiveness and adverse events.…”

“…In fact, several authors have reported longer drug survival in elderly psoriatic patients, and Sherbini et al. found a decreased incidence of AEs in these patients 26,27,38 . Nevertheless, as early as 1989, some authors found that psoriasis in elderly patients could be controlled with a lower dose than the recommended and investigated some of the factors associated with the required dose 41 .…”

Fatal low‐dose methotrexate toxicity: A case report and literature review

“…Due to MTX's folate antagonism, highly proliferative tissues such as the bone marrow and GI mucosa are particularly affected. The most common adverse effects include GI symptoms such as nausea, vomiting, diarrhea, mucositis, and mucosal ulcerations 26 . Additionally, patients commonly present with symptoms such as fatigue, dizziness, headache, cough, alopecia, and various types of cutaneous eruptions.…”

Practical issues in the use of levilimab, a novel interleukin-6 receptor inhibitor, in patients with rheumatoid arthritis

“…В недавно опубликованном британском когортном исследовании по крайней мере одно нежелательное явлений было зарегистрировано у 77,5% из 1069 больных ранним РА, которые впервые начали лечение метотрексатом. Чаще всего встречались желудочно-кишечные расстройства (42,0%), неврологические нарушения (28,6%), изменения со стороны кожи и слизистых оболочек (26,0%) и легких (20,9%), повышение активности печеночных аминотрансфераз (18,0%) и гематологические нарушения (5,6%) [25]. Основными побочными эффектами были тошнота (31,2%), утомляемость (29,4%) и головная боль (19,0%).…”