Tolerability and Patient/Physician Satisfaction with Subcutaneously Administered Methotrexate Provided in Two Formulations of Different Drug Concentrations in Patients with Rheumatoid Arthritis~!2010-01-14~!2010-02-08~!2010-03-18~!

Abstract

Objectives:To determine preference, satisfaction, usability and local tolerability by patients, physicians and study nurses of two subcutaneously administered methotrexate (MTX) formulations of different concentrations.Methods:This was an open-label, comparative, within-patient controlled, multicentre study of 132 patients with rheumatoid arthritis (RA). MTX treatment consisted of 20 mg/week administered as a medium-concentration formulation (MC) (2.0 ml of 10 mg/ml solution in prefilled syringe; separate needle) compared to a novel high-concentration formulation (HC) (0.4 ml of 50 mg/ml in prefilled syringe; pre-attached needle). Each treatment was given for three weeks. Questionnaires and visual analogue scales were used to measure outcomes.Results:At the end of the study, 93% of the patients preferred HC over MC as further treatment. Overall assessment of HC was “good” or “very good” in 90.6% vs 34.4% in MC-treated patients. Physician’s and patients global assessment of syringe usability showed highly statistically significant differences (P < 0.0001) in favour of HC. Overall assessment by study nurses’ and investigators’ was “good” (18.8%) or “very good” (81.2%) for HC and “good” in 31.3% or “very good” in 12.5% for MC, and no preference in 50%. Local tolerability improved slightly also with HC.Conclusions:The total smaller volume of administered drug and the improved usability of a pre-attached needle in combination with a smaller prefilled syringe resulted in preference of the patients of HC over MC. The slightly improved local tolerability may also have added to this preference. This assessment was confirmed by similar assessments made by healthcare professionals.Eudra-CT number: 2007-003591-19.

Pharmacokinetic profile of methotrexate in psoriatic skin via the oral or subcutaneous route using dermal microdialysis showing higher methotrexate bioavailability in psoriasis plaques than in non‐lesional skin

“…MTX was compared in several clinical trials. The outcome suggested that the s.c. route is superior regarding clinical efficacy, tolerability and AUC or drug levels when ≥15 mg MTX is applied …”

“…The outcome suggested that the s.c. route is superior regarding clinical efficacy, tolerability and AUC or drug levels when ≥15 mg MTX is applied. 3,29,30 A metaanalysis recommended the most efficient therapy starting with an oral dose of 15 mg/week, to increase in 5 mg steps to 30 mg as a maximum dose and/or to switch to the subcutaneous application when therapy fails. 2 Since the bioavailability of MTX in psoriasis plaques was higher in all patients compared to the unaffected skin and also reached significantly higher drug levels the practical aspect consequence is that it might be better to start with a lower dose of MTX such as 5 or 7.5 mg per week and then wait longer until the full efficacy for the treatment of psoriasis is reached rather than increasing the dose too early given the huge individual differences in MTX metabolism based on a different pharmacogenetic background 4,26,27,31 preventing unnecessary toxicity for patients' unaffected skin or mucosa.…”

Methotrexate: New Therapeutic Approaches

“…Greater familiarity with subcutaneous injections among dermatology patients will undoubtedly contribute to this increased use, as will the introduction of higher-concentration formulations (50 mg/mL) in prefilled syringes, as these offer greater tolerability and convenience 53 and are preferred to the 10-mg/mL formulations by the majority of patients treated with 20 mg per week. 54 Single-dose formulations also have environmental and safety benefits as they eliminate the need to handle and discard unused portions of vials or syringes. 55…”

Preference, satisfaction and usability of subcutaneously administered methotrexate for rheumatoid arthritis or psoriatic arthritis: results of a postmarketing surveillance study with a high-concentration formulation

“…Two MTX formulations for SC use were tested in an open-label, comparative, within-patient controlled, multicenter study in 132 patients with RA [Müller-Ladner et al 2010]. MTX treatment consisted of 20 mg/week administered as a medium-concentration formulation (2.0 ml of 10 mg/ml solution in prefilled syringe; separate needle) which was compared to a novel high-concentration formulation (0.4 ml of 50 mg/ml in prefilled syringe; pre-attached needle).…”