Non-adherence and discontinuation rate for oral and parenteral methotrexate: A retrospective-cohort study in 8,952 patients with psoriatic arthritis

Abstract

Background and aims Treatment options for PsA, following non-steroidal anti-inflammatory drugs (NSAIDs), include conventional synthetic disease modifying anti-rheumatic drugs (csDMARDS), particularly methotrexate (MTX). The present study was performed to determine the non-adherence and discontinuation rates of different methotrexate (MTX) formulations in psoriatic arthritis (PsA). Approach and results We performed a retrospective-cohort study on patients with PsA identified by disease-specific code in the administrative-health-databases of a Northern Italian region (Lombardy) between 2004 and 2015. Subjects were defined as non-adherent if less than 80% of the prescribed MTX dose was taken based on the time between each prescription. Discontinuation rates were calculated using the time between the first and the last MTX prescription over an observation period of 120 months. Among 8952 patients with PsA, 33% were treated with MTX (mean dosage 10 mg/week ± 2.5 mg standard deviation), more frequently (59%) in its parenteral formulation at a 10 mg weekly dosage (35%). Oral glucocorticoids were prescribed to 21% of patients, while non-steroidal anti-inflammatory drugs to 45%. Approximately 37% of patients with PsA were defined as non-adherent to MTX, with the oral formulation associated with an increased risk of non-adherence (hazard ratio 2.08, 95% confidence interval 1.84–2.35, p < 0.001) compared with parenteral 10–15 mg weekly doses. Oral MTX was discontinued in 52% of cases without a significantly increased risk of discontinuation compared to parenteral formulations which, at higher dosages, had a more favorable retention rate. Conclusion Oral MTX formulation is associated with a 2-fold risk of non-adherence compared to MTX parenteral route in PsA.

An Overview on Causes of Nonadherence in the Treatment of Rheumatoid Arthritis: Its Effect on Mortality and Ways to Improve Adherence

“…Route of administration is another obstacle to adherence. Oral MTX formulation is associated with two times increased risk of non-adherence compared to the parenteral route [ 22 ]. In a study conducted, the non-adherence to MTX treatment was observed in 38% of patients (n=1108) with oral MTX with a high risk of non-adherence (Hazard ratio-HR 2.11, 95% confidence interval-CI 1.87-2.39, p < 0.001) [ 22 ].…”

“…Oral MTX formulation is associated with two times increased risk of non-adherence compared to the parenteral route [ 22 ]. In a study conducted, the non-adherence to MTX treatment was observed in 38% of patients (n=1108) with oral MTX with a high risk of non-adherence (Hazard ratio-HR 2.11, 95% confidence interval-CI 1.87-2.39, p < 0.001) [ 22 ]. For parenteral route of administration of MTX with doses of 7.5,10, and 15 mg weekly doses, there had been lower risk of non-adherence (HR 0.79, 95% CI 0.63-0.99, p = 0.038; HR 0.62, 95% CI 0.55-0.71, p < 0.001; HR 0.7, 95% CI 0.58-0.85, p < 0.001, respectively) [ 22 ].…”

“…In a study conducted, the non-adherence to MTX treatment was observed in 38% of patients (n=1108) with oral MTX with a high risk of non-adherence (Hazard ratio-HR 2.11, 95% confidence interval-CI 1.87-2.39, p < 0.001) [ 22 ]. For parenteral route of administration of MTX with doses of 7.5,10, and 15 mg weekly doses, there had been lower risk of non-adherence (HR 0.79, 95% CI 0.63-0.99, p = 0.038; HR 0.62, 95% CI 0.55-0.71, p < 0.001; HR 0.7, 95% CI 0.58-0.85, p < 0.001, respectively) [ 22 ]. In another study involving 207 patients, switching from oral to subcutaneous route increased the proportion of remission from 22.8% to 52.9% [ 23 ].…”

International Survey to Evaluate Current Options for Subcutaneous Injection of Methotrexate (MTX) and a New Button-Free MTX Autoinjector

“… 15 The non-adherence rate for MTX in Italian patients with psoriatic arthritis was 38% (1108 of 2952 patients) with a twofold increase in non-adherence for oral versus parenteral MTX. 16 In part, this may be due to more gastrointestinal events with oral versus subcutaneous MTX. 2 Concerns about side effects may result in an active avoidance of taking the medication, also named as conscious non-adherence, whereas unconscious, non-intentional poor adherence can be caused by insufficient patient motivation, drug regimen misunderstanding, forgetfulness, needle phobia, and problems with drug administration due to reduced hand capabilities or complex handling.…”