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.

Keywords: Adherence; HCQ, hydroxychloroquine; HR, Hazard ratio; IQR, inter-quartile range; LEF, leflunomide; MTX, methotrexate; Methotrexate; NSAIDs, non-steroidal anti-inflammatory drugs; OGC, oral glucocorticoids; Oral; Parenteral; PsA, psoriatic arthritis; PsO, psoriasis; Psoriatic arthritis; Retention rate; SSZ, sulfasalazine; TNF, tumor necrosis factor alpha; list: csDMARDs, conventional synthetic disease modifying anti-rheumatic drugs.

Fig. 1

Kaplan Meier curves showing the proportion (%) of patients still taking MTX at different dosages after 1, 2, 3, and, 4 years. In the associated table the numbers and the percentages of the patients still taking MTX at basal time, after 1, 2, and, 4 years are reported.