Use Of Subcutaneous Methotrexate Research Articles

Potential Benefits of the Self-Administration of Subcutaneous Methotrexate with Autoinjector Devices for Patients: A Review.

The role of patient adherence in improving the efficacy of any treatment is widely accepted, as well as its impact in optimizing the use of healthcare resources and associated costs. Adherence is particularly affected in chronic conditions, such as rheumatoid arthritis (RA), requiring long-term therapies and a commitment of the patient to manage his/her disease. Methotrexate (MTX) is one of the mainstays of treatment for several immune-mediated inflammatory joint and skin diseases, especially RA. The use of parenteral MTX, particularly when administered as a subcutaneous (SC) injection, has recently raised a great interest to overcome the limitations of oral MTX. For addressing this issue, new optimized self-injection systems have been developed to improve the ease of use of SC MTX. Increasing evidence shows how patients tend to opt for autoinjectors over prefilled syringes or conventional syringes in terms of easiness of use, preference and satisfaction, regardless of whether the treatment is a biologic or MTX. Additionally, positive views and beliefs of patients about treatment may contribute to increasing expectations of effectiveness and treatment adherence. Similarly, the implementation of prefilled pens in clinical practice might be a way to facilitate and simplify the self-injection of SC MTX delivery, optimizing adherence and treatment outcomes as a consequence. This article aimed to review the available literature data on the use of MTX autoinjectors and their impact on treatment adherence and patients’ perceptions.

The use of subcutaneous methotrexate from various manufacturers in real clinical practice: a comparative study

Background: Methotrexate is the main synthetic disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and other immunoinflammatory conditions. In the recent years, the subcutaneous form of methotrexate (SC MTX), particularly as ready-to-use syringes, has been increasingly used worldwide. Currently, several generics of SC MTX from different manufacturers are available. In literature we could not find any publications on the comparison of SC MTX generics.Aim: To evaluate the possibility to effectively use various SC MTXs for the treatment of RA and PsA in real clinical practice. Materials and methods: Patients older than 18 years old with a diagnosis of RA by ACR 1987 or ACR / EULAR 2010 criteria or diagnosis of PsA by CASPAR criteria with indications for SC MTX were included in this open-label 6-month observational study “Therapy of Rheumatoid Arthritis with Methotrexate in the Subcutaneous Form in Clinical Practice (TRAMPLIN)”. TRAMPLIN included two study periods: 1) a retrospective study of the safety of SC MTX from various manufacturers in clinical practice, according to patients' medical records; 632 patients (67.2% female, 32.8% male) on SC MTX were identified, and the number of adverse reactions recorded in the documentation (spontaneous reports) was determined; 2) a prospective study of the treatment duration and the reasons for the withdrawal of SC MTX from different manufacturers, which included 69 patients with RA and PsA. SC MTXs from three manufacturers were used in this study, namely Metoject (Medac GmbH, Germany); Métortrites (S.C. Rompharm Company S.R.L., Romania); Methotrexat Ebewe (Sandoz Pharmaceuticals D.D., Slovenia).Results: In the retrospective part of the study very few adverse events (AEs) were registered, which were related to SC MTX in the physician's opinion (41 patients, or 6.5%). Their incidence was higher in methotrexate-naïve patients. In the prospective part of the study at 3 months after the start of SC MTX therapy, 25 patients (36.2%) changed the treatment regimen (switched between the study drugs or to oral methotrexate). The main reasons for switching (20.3%) were “non-medical” events in the outpatients. AEs ranked second as a reason for the drug withdrawal (14.5%), irrespective of the manufacturer. At 6 month of the study, 38% patients were treated with Metoject, 30% with Methotrexat Ebewe, 28% with Métortrites, and 4% of patients switched to oral methotrexate.Conclusion: This first Russian study of SC MTX generics from three different manufacturers confirmed a good SC MTX safety profile in a large clinical sample and showed good retention rates for therapy: by the end of the observation, 96% of the patients with available follow-up data remained on SC MTX. All three SC MTXs from different manufacturers were compatible in terms of safety, tolerability, and drug survival.

Using subcutaneous methotrexate to prolong duration of methotrexate therapy in rheumatoid arthritis.

Our study aims to determine whether the use of subcutaneous methotrexate (SC MTX) is associated with prolonged MTX use and lower incidence of hepatotoxicity in rheumatoid arthritis (RA) patients on MTX monotherapy and multiple drug therapy. We conducted a retrospective cohort study using national databases of a large hospital system. Subjects had been diagnosed with RA and treated with MTX between September 30, 1999, and October 1, 2009. Outcomes of interest were the amount of time on MTX monotherapy or multiple disease-modifying anti-rheumatic drug (DMARD) therapy before addition of additional DMARDs or biologic agents, respectively. We conducted Cox regressions and Kaplan-Meier curves for association between SC MTX use and length of time before therapeutic change. We conducted chi-square tests for association between SC MTX use and elevated liver function tests (LFT). MTX monotherapy: SC MTX was associated with a significantly lower likelihood of therapeutic change (HR 0.64, 95% CI 0.52-0.78). Multiple DMARD therapy: SC MTX was not associated with a lower risk of adding a biologic (HR 1.13, 95% CI 0.97-1.31). Liver enzymes: There was no significant association between use of SC MTX and decreased frequency of abnormal LFTs [p=0.09 for alanine aminotransferase (ALT), p=0.924 for aspartate aminotransferase (AST)]. Use of SC MTX is associated with longer duration of MTX monotherapy before addition of other DMARDs/biologic agents in RA patients. Use of SC MTX is not associated with significantly longer duration of multiple DMARD therapy before addition of biologic agents. Use of oral MTX is not significantly associated with increased frequency of elevated LFTs.

Underuse of Methotrexate in the Treatment of Rheumatoid Arthritis: A National Analysis of Prescribing Practices in the US.

Methotrexate (MTX) is the anchor drug in the treatment of rheumatoid arthritis (RA) due to its effectiveness, tolerability, and cost. This study examines MTX prescribing practices in the US from 2009 to 2014. Symphony Health Solutions, which covers 274 million patients in the US, was used to identify patients diagnosed with RA who were naive to MTX in 2009 and 2012. Data were collected, including medication use and doses, demographics, and medical comorbidities. Of the patients who had 5-year followup data available, oral MTX was started in 35,640 in 2009, and 44% continued taking this dose during the followup. Of the 20,041 patients who changed therapy during the study period, 87% had the addition of or switched to a biologic agent, while 13% were changed from oral to subcutaneous (SC) MTX. The mean oral dose prior to the start of a biologic agent was 15.3 ± 5 mg/week. A comparison of 2009 with 2012 showed a modest increase in the mean dose of oral MTX from 15.3 mg/week to 15.9 mg/week, as well as a small but statistically significant (P < 0.0001) increase in the use of SC MTX after failure of oral MTX from 13% to 16% of patients. MTX is underutilized in the treatment of RA with suboptimal dosing, inadequate duration of therapy, and failure to use SC administration. The comparison of MTX use between the 2009 and the 2012 cohorts demonstrates only a marginal increase in the dose of oral MTX and the use of SC MTX.

Non-adherence to disease-modifying antirheumatic drugs is associated with higher disease activity in early arthritis patients in the first year of the disease.

IntroductionNon-adherence to disease-modifying antirheumatic drugs (DMARDs) hampers the targets of rheumatoid arthritis (RA) treatment, obtaining low disease activity and decreasing radiological progression. This study investigates if, and to what extent, non-adherence to treatment would lead to a higher 28-joint count disease activity score (DAS28) in the first year after diagnosis.MethodsAdult patients from an ongoing cohort study on treatment adherence were selected if they fulfilled the EULAR/ACR2010 criteria for RA, and were to start with their first DMARDs. Clinical variables were assessed at baseline and every 3 months. Non-adherence was continuously electronically measured and was defined as the proportion of days with a negative difference between expected and observed openings of the medication container out of the 3-month period before DAS28 measurement. Generalized linear mixed models were used to investigate whether the DAS28 related to non-adherence. Covariates included were age, sex, baseline DAS28, rheumatoid factor positivity, anti-cyclic citrullinated peptide antibodies (ACPA) positivity, anxiety, depression, weeks of treatment, number of DMARDs used, education level, use of subcutaneous methotrexate and biological use.ResultsOne hundred and twenty patients met the inclusion criteria for RA. During the study period 17 patients became lost to follow-up. There was a decline in adherence over time for all DMARDs except for prednisone. Non-adherence is a predictor of disease activity in the first 6 months of therapy, adjusted for weeks of treatment, baseline DAS28, and baseline anxiety.ConclusionsNon-adherence relates to disease activity. Therefore, interventions towards enhancing adherence can improve disease outcome.

Subcutaneous methotrexate for symptomatic control of severe recalcitrant psoriasis: safety, efficacy, and patient acceptability.

BackgroundAlthough oral methotrexate is an effective first-line traditional systemic therapy for psoriasis, the use of the subcutaneous form of methotrexate for the treatment of psoriasis has not been fully established.ObjectiveThis study is a literature review of the research related to the safety, efficacy, and patient acceptability of subcutaneous methotrexate for its application in the treatment of severe recalcitrant psoriasis.MethodsSystematic literature searches were conducted of the PubMed, Ovid, and ClinicalTrials.gov databases.ResultsOnly three relevant sources of literature were found studying subcutaneous methotrexate specifically in the context of psoriasis. Of these, only one clinical trial was found to directly study the use of subcutaneous methotrexate in psoriasis patients; however, results of this study have not been published. The other two literature sources involved a cost-effectiveness analysis and a literature review for subcutaneous methotrexate. Otrexup™ and Rasuvo™ are two particular single-use auto-injector modalities of subcutaneous methotrexate that are approved by the US Food and Drug Administration. The equivalents of Rasuvo available in countries outside of the USA are advertised as Metoject® or Metex®. Much more research has been conducted on the use of subcutaneous methotrexate in rheumatoid arthritis patients.ConclusionThere is a lack of original evidence-based studies evaluating the use of subcutaneous methotrexate specifically for the treatment of psoriasis. Based on the more extensively researched data on the safety, efficacy, and patient acceptability of subcutaneous methotrexate in rheumatoid arthritis patients, its application for the treatment of moderate-to-severe psoriasis is promising. More evidence-based studies on psoriasis subjects are needed to explore the practical application of subcutaneous methotrexate as a treatment option for severe recalcitrant psoriasis.

Procedural pain and patient-reported side effects with weekly injections of subcutaneous methotrexate in children with rheumatic disorders.

BackgroundDespite the widespread use of subcutaneous methotrexate in treating pediatric rheumatic disorders, the amount of pain associated with the injections has not been quantified. Our study aims 1) to quantify the amount of pain associated with subcutaneous injections of methotrexate, 2) to explore predictors of pain, 3) to determine the frequency of patient-reported clinical adverse effects of methotrexate, and 4) identify coping strategies of patients and caregivers.MethodsPatients aged 4–17 years with rheumatologic diseases who were receiving weekly subcutaneous methotrexate injections for at least 4 weeks were invited to participate in this prospective cohort study. They were trained to use the Faces Pain Scale – Revised (FPS-R) and Faces, Legs, Arms, Cry, Consolability (FLACC) tools to rate pain associated with the injections. All patients underwent focused interviews exploring their experiences with methotrexate injections.ResultsForty-one patients consented to the study. The mean age was 11.2 years (SD = 3.9 years) and 68% were female. Most patients were diagnosed with JIA (73%). Mean duration of methotrexate therapy was 2.5 years (SD = 2.1 yrs). All but one of the patients used methotrexate 25 mg/ml solution for injection in 1 cc or 3 cc syringe with 30 gauge ½” needle. Median amount of pain was 2/10 on the FPS-R and 1/10 on the FLACC. Higher intensity of pain was significantly associated with presence of side effects (p = 0.004), but not duration of therapy (p = 0.20) or age (p = 0.24). Most participants (61%) experienced at least one adverse effect; nausea (56%) and vomiting (34%) were the most common symptoms reported. Patients and caregivers reported using ice (34%), comfort positions (51%), rewards (49%), reassurance (54%), distraction (51%), and analgesic medications (22%) to cope with the injections.ConclusionSubcutaneous injections of methotrexate are associated with a mild amount of pain. Presence of side effects may amplify the amount of perceived pain. Clinicians can apply this knowledge when counseling patients and family members about methotrexate therapy.

New autoinjector technology for the delivery of subcutaneous methotrexate in the treatment of rheumatoid arthritis

Methotrexate (MTX) is the cornerstone of treatment for rheumatoid arthritis (RA), and is widely used both as first-line therapy and as an important component of long-term therapy. Although subcutaneous MTX is typically delivered orally, parenteral administration offers benefits with respect to tolerability and systemic exposure, and may be an underutilized treatment option. The RA patient population presents specific challenges for safe and accurate administration of parenteral therapies, because of common symptoms of joint pain and limited manual dexterity. These challenges may contribute to the low incidence of parenteral MTX administration. A novel MTX autoinjector (MTXAI) was recently introduced, which is designed to facilitate subcutaneous MTX self-administration among patients with RA. Here we review the development and utility of the MTXAI in the treatment of RA, and discuss how this technology may facilitate the use of subcutaneous MTX.

Ms Hassanzadeh, et al reply

To the Editor: We thank Dr. Kapoor for his interest1 in our recent article on the use of subcutaneous methotrexate (MTX)2. He lists the rare side effects of this drug but fails to point out … Address correspondence to Dr. R. Hassanzadeh, University of Glasgow – Medical School, Wolfson Medical School Building, University Avenue, Glasgow G12 8QQ, UK. E-mail: royahmr{at}googlemail.com