Estudios primarios relacionados a este tópico

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Estudio primario

No clasificado

Oral Methotrexate in split dose weekly versus oral or parenteral Methotrexate once weekly in Rheumatoid Arthritis: a short-term study.

Revista International journal of rheumatic diseases
Año 2018
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OBJECTIVE: To investigate whether methotrexate (MTX) administered orally to rheumatoid arthritis (RA) patients in split doses at 2-3 days' interval, would result in equal or better efficacy, tolerability and compliance, without increasing toxicity compared to single weekly dose given orally or parenterally. MATERIALS AND METHODS: One hundred and thirty-five patients fulfilling the American College of Rheumatology (ACR) 2010 criteria for RA, on 7.5 mg of MTX weekly orally, with the Simplified Disease Activity Index (SDAI) > 11 were enrolled for a 24-week period. Patients were randomly divided into three groups and were given MTX: Group 1 7.5 mg twice or thrice weekly orally, Group 2 15 mg or 22.5 mg in a single dose weekly orally and Group 3 15 mg or 22.5 mg in a single dose weekly as an intramuscular injection. The primary outcomes were low disease activity (LDA) and mean change in SDAI at week 24, whereas secondary outcomes included remission, adverse events and compliance. RESULTS: At week 24, adherence to treatment was maximum in Group 1, 69% (P = 0.09). In intention-to-treat analysis at 24 weeks, Group 1, 49%, Group 2, 36% and Group 3, 47% achieved LDA (P = 0.4). There was significant difference in mean change in SDAI at week 24 from baseline (P = 0.008) among the groups. Group 3 patients were more uncomfortable with the mode of administration of MTX (P = 0.003). There was no significant difference in adverse events. CONCLUSION: Oral split doses of MTX are better than an oral single dose and similar to parenteral MTX in terms of efficacy.

Estudio primario

No clasificado

Oral to subcutaneous methotrexate dose-conversion strategy in the treatment of rheumatoid arthritis.

Autores Schiff MH , Sadowski P
Revista Rheumatology international
Año 2017
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Both the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) guidelines recommend the use of methotrexate (MTX) for the treatment of rheumatoid arthritis (RA) when there is no contraindication. While MTX is the foundation of RA therapy (Singh et al. in Arthritis Care Res 64:625-639,2012), absorption saturation compromises its oral bioavailability (BA). Differences in the relative BA of oral versus subcutaneous (SC) MTX demonstrate the need for guidance on successful dose-conversion strategies. This study was designed to compare MTX PK profiles as a result of MTX administration via three different treatment administrations: oral, SC MTX administered via an auto-injector (MTXAI) into the abdomen (MTXAIab) and into the thigh (MTXAIth). In this paper, we establish a dose-conversion method based on the BA of MTX from oral and SC administration. SC administration provided higher exposure of MTX than the same dose given orally. Unlike the exposure limitations of oral MTX, dose-proportional exposure was seen with SC MTX.

Estudio primario

No clasificado

The comparative effectiveness of oral versus subcutaneous methotrexate for the treatment of early rheumatoid arthritis.

Revista Annals of the rheumatic diseases
Año 2016
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Este artículo está incluido en 2 Revisiones sistemáticas Revisiones sistemáticas (2 referencias)

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OBJECTIVE: To determine the comparative effectiveness of oral versus subcutaneous methotrexate (MTX) as initial therapy for patients with early rheumatoid arthritis (ERA). METHODS: Patients with ERA (symptoms ≤1 year) initiating MTX therapy were included from a multicentre, prospective cohort study. We compared the effectiveness between starting with oral versus subcutaneous MTX over the first year. Longitudinal multivariable models, adjusted for potential baseline and time-varying confounders, were used to compare treatment changes due to inefficacy or toxicity and treatment efficacy (Disease Activity Score-28 (DAS-28), DAS-28 remission and Health Assessment Questionnaire-Disability Index (HAQ-DI)). RESULTS: 666 patients were included (417 oral MTX, 249 subcutaneous MTX). Patients prescribed subcutaneous MTX were prescribed a higher dose of MTX (mean dose over first three months 22.3 mg vs 17.2 mg/week). At 1 year, 49% of patients initially treated with subcutaneous MTX had changed treatment compared with 77% treated with oral MTX. After adjusting for potential confounders, subcutaneous MTX was associated with a lower rate of treatment failure ((HR (95% CI) 0.55 (0.39 to 0.79)). Most treatment failures were due to inefficacy with no difference in failure due to toxicity. In multivariable models, subcutaneous MTX was also associated with lower average DAS-28 scores (mean difference (-0.38 (95% CI -0.64 to -0.10)) and a small difference in DAS-28 remission (OR 1.2 (95% CI 1.1 to 1.3)). There was no significant difference in sustained remission or HAQ-DI (p values 0.43 and 0.75). CONCLUSIONS: Initial treatment with subcutaneous MTX was associated with lower rates of treatment changes, no difference in toxicity and some improvements in disease control versus oral MTX over the first year in patients with ERA.

Estudio primario

No clasificado

Subcutaneous administration of methotrexate with a prefilled autoinjector pen results in a higher relative bioavailability compared with oral administration of methotrexate.

Autores Pichlmeier U , Heuer KU
Revista Clinical and experimental rheumatology
Año 2014
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OBJECTIVES: Methotrexate (MTX) is recognised as the cornerstone of treatment for rheumatoid arthritis. For some patients, oral MTX demonstrates variable bioavailability, especially at higher doses. Such concerns may be mitigated by subcutaneous (SC) MTX administration. This study investigated the relative bioavailability, safety, and tolerability of MTX administered either by SC injection with a prefilled autoinjector pen (MTX pen) or orally. METHODS: This single-centre, open-label, randomised, 2-period, 2-sequence, single-dose, crossover study enrolled healthy subjects aged 18 to 55 years into 1 of 4 dose groups (7.5 mg, 15 mg, 22.5 mg, and 30 mg), where they received a single dose of SC MTX and of the oral MTX tablets. Blood samples were collected from subjects predose and at prespecified time points postdose for pharmacokinetic analyses. Adverse events (AEs) were recorded to assess differences in safety and tolerability. RESULTS: Bioavailability, as measured by maximum plasma concentrations (Cmax) and area under the plasma-concentration curves (AUC0-t), was generally higher with the SC MTX pen compared with oral administration for all dose groups. AUC0-t ratios increased with ascending doses; Cmax ratios did not increase. A total of 80 AEs were reported in 35/62 subjects; none were severe. Differences in the safety profiles were related to the route of administration. Single administrations with the MTX pen were well tolerated at the injection site. CONCLUSIONS: Single-dose administration with the SC MTX pen resulted in a higher relative bioavailability compared with oral administration. SC MTX pen administration was associated with fewer gastrointestinal AEs than oral MTX.

Estudio primario

No clasificado

Factors associated with methotrexate dosing and therapeutic decisions in veterans with rheumatoid arthritis.

Autores Ng B , Chu A
Revista Clinical rheumatology
Año 2014
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The purpose of this study is to explore patient factors associated with differences in methotrexate (MTX) dosing and to compare patient factors and MTX-dosing patterns between those who remained on MTX monotherapy and those who were switched or had additional therapy. A retrospective cohort of 7,017 patients with newly diagnosed rheumatoid arthritis (RA) was identified in the United States Department of Veterans Affairs administrative databases between 1 October 1999 and 30 September 2009. Regression analyses were used to study the association of MTX start and maximum dose attained with various patient characteristics and compare differences between groups who had therapeutic change (having switched to or added another anti-rheumatic agent or having steroids increased by 2.5 mg of prednisone or equivalent) with those remaining on MTX monotherapy. Abnormal serum creatinine (>1.5 mg/dL) was associated lower start and peak MTX doses (p < 0.01). Older RA patients were less likely to attain peak MTX dose of 15 mg or more (p < 0.01). Males and patients 75 and older (compared with <45) had lower risk of therapeutic change (hazard ratio, [HR] 0.80, 95 % confidence interval [CI] 0.72-0.90, and HR 0.42, 95% CI 0.42-0.36-0.50, respectively). Patients who attained higher peak MTX dose had lower risk of therapeutic change compared with those dosed at less than 15 mg/week (HR 0.85, 95% CI 0.77-0.92 for 15 to <20 and HR 0.79, 95% CI 0.72-0.86 for 20 or more). Injectable MTX use conferred lower risk of therapeutic change (HR 0.64, 95% CI 0.52-0.78). Two thirds did not attain a maximum MTX dose of 20 mg/week or more before therapeutic change occurred. Older age and renal insufficiency were barriers to the use of higher MTX maximum dosages. Use of injectable MTX and higher maximum MTX dose were independently associated with higher likelihood to remain on MTX monotherapy. Further studies are needed to explore targeted interventions that may optimize MTX dosing to improve success rates of MTX monotherapy.

Estudio primario

No clasificado

Head-to-head, randomised, crossover study of oral versus subcutaneous methotrexate in patients with rheumatoid arthritis: drug-exposure limitations of oral methotrexate at doses ≥15 mg may be overcome with subcutaneous administration.

Revista Annals of the rheumatic diseases
Año 2014
Enlaces Pubmed DOI PubMed Central

Este artículo está incluido en 3 Revisiones sistemáticas Revisiones sistemáticas (3 referencias)

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OBJECTIVE: To compare the relative bioavailability, safety and tolerability of oral methotrexate (MTX) and subcutaneous (SC) MTX administered via an auto-injector (MTXAI) in patients with rheumatoid arthritis (RA). METHODS: In this randomised, multicenter, open-label, three-way crossover study, patients ≥18 years with adult RA undergoing treatment with MTX for ≥3 months were assigned to receive MTX 10, 15, 20 and 25 mg weekly in a random sequence of three treatments: oral, SC into the abdomen and SC into the thigh. For 24 h after administration of each treatment, blood samples were collected for pharmacokinetic analysis and injection sites were assessed. RESULTS: Forty-seven patients completed the study. Systemic exposure of oral MTX plateaued at doses ≥15 mg/week. In contrast, SC MTX demonstrated a linear increase in systemic exposure that was greater than oral MTX at each dose. No unexpected AEs were noted for either formulation. CONCLUSIONS: Unlike oral MTX, the systemic exposure of SC MTX did not plateau over the doses studied, particularly at doses ≥15 mg/week. In this study, higher systemic MTX exposure was not associated with increases in AEs. Patients with an inadequate clinical response to oral MTX may benefit from higher drug exposure by switching to SC MTX. TRIAL REGISTRATION NUMBER: NCT01618968.

Estudio primario

No clasificado

Is subcutaneous methotrexate is better than oral methotrexate in the treatment of rheumatoid arthritis?

Autores Borman P , Demir G , Okumus M
Revista Ann Rheumat J
Año 2014

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Estudio primario

No clasificado

Comparative efficacy of subcutaneous versus oral methotrexate in active rheumatoid arthritis.

Revista Mymensingh medical journal : MMJ
Año 2013
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Este artículo está incluido en 3 Revisiones sistemáticas Revisiones sistemáticas (3 referencias)

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This prospective study was conducted in rheumatology clinic under the department of medicine of Bangabandhu Sheikh Mujib Medical University from December 2004 to December 2005 to asses the efficacy, safety and compliance of subcutaneous methotrexate (MTX) in active rheumatoid arthritis (RA) patients. A total of 92 active rheumatoid arthritis patients according to American College of Rheumatology (ACR) criteria were recruited for the trial for six months. Among them 46 cases belonged to injectable MTX group and 46 cases belonged to oral MTX group. Mean±SD age of patients was 45.54±12.42 vs. 44.63±13.99 years in subcutaneous group and oral group respectively. In the subcutaneous group 41 were female and 5 male; in the oral group 34 were female and 12 male. Mean duration of the disease was 49.74 months in subcutaneous group and 49 months in oral group. RA test was positive in 35 cases in both groups whereas Rose Waaler test was positive in 19 patients in subcutaneous group and 14 patients in oral group. At 24 week, response rate of ACR 20 was significantly higher in subcutaneous MTX than oral MTX group (93% vs. 80%, p=0.02). Similarly ACR 50 response was significantly higher in subcutaneous MTX than in oral group (89% vs. 72%, p=0.03). ACR 70 response was not significantly higher in SCMTX group then oral group (11% vs. 9 %, p=0.72). Adverse effects were relatively less in subcutaneous MTX and most common side effects were nausea (37% vs. 63%), vomiting (11% vs. 30%), dyspepsia (29% vs. 48%), dizziness (4l% vs. 52%) and alopecia (72% vs. 85%). The results of the study demonstrated that subcutaneous MTX was significantly more effective than oral MTX at the same dosage in active Rheumatoid arthritis patients with no increase in side effects.

Estudio primario

No clasificado

Effects of changing from oral to subcutaneous methotrexate on red blood cell methotrexate polyglutamate concentrations and disease activity in patients with rheumatoid arthritis.

Revista The Journal of rheumatology
Año 2011
Enlaces Pubmed DOI www.cochranelibrary.com

Este artículo está incluido en 1 Revisión sistemática Revisiones sistemáticas (1 referencia)

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OBJECTIVE: To determine the effects of changing from oral to subcutaneous (SC) methotrexate (MTX) in patients with rheumatoid arthritis (RA) on red blood cell MTX polyglutamate (RBC MTXGlu(n)) concentrations, disease activity, and adverse effects. METHODS: Thirty patients were changed from oral to SC MTX. Trough RBC MTXGlu(n) concentrations were measured for 24 weeks and concentrations fitted to a first-order accumulation model. Disease activity was assessed by 28-joint Disease Activity Score (DAS28). RESULTS: MTXGlu(3), MTXGlu(4), and MTXGlu(5) concentrations, but not MTXGlu(1) and MTXGlu(2), increased significantly over 24 weeks, reaching 90% of new steady-state concentrations by about 40 weeks. A decrease in DAS28 was associated with increased RBC MTXGlu(5) (p = 0.035) and RBC MTXGlu(3-5) (p = 0.032). No change in adverse effect frequency occurred. CONCLUSION: Changing to SC MTX results in increased long-chain MTXGlu(n). However, it takes at least 6 months for RBC steady-state concentrations to be achieved. Increased long-chain MTXGlu(n) concentrations were significantly associated with reduced disease activity.

Estudio primario

No clasificado

When should we use parenteral methotrexate?

Revista Clinical rheumatology
Año 2010
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Oral methotrexate is the benchmark against which other disease-modifying anti rheumatic drugs are measured. The use of parenteral methotrexate for those failing to tolerate or respond to oral therapy is accepted, but indications for its use and its place in the therapeutic ladder have not been fully investigated. We assessed the use of parenteral methotrexate (MTX) in our rheumatoid arthritis (RA) population and compared the characteristics of these patients to a matched group of those on oral therapy. We compared response rates to each approach using DAS 28 scores, ESR and visual analogue scales. Inferences on costs of parenteral therapy were made and predictors of response defined. We found that 10% of our total RA patient population were on parenteral methotrexate, having failed to tolerate or respond to oral therapy. Seventy-five percent of these met the criteria for the use of anti-tumour necrosis factor (TNF) agents. Overall response rates were equivalent to those obtained by responders to oral MTX. Patients on parenteral therapy were younger and were more likely to have extreme values of body mass index (BMI) than those on oral therapy. The approach was economically viable, although many patients unnecessarily attended hospital to receive their injections. We advocate consideration of parenteral MTX in all RA patients unresponsive to oral therapy prior to treatment with anti-TNF therapy. Response to parenteral therapy can be predicted by low BMI (below 22 kg/m(2)), possibly as a result of malabsorption, or by high BMI (over 30) as a result of gastrointestinal intolerance. A mechanism to deliver this option through self-administration in the community should be encouraged.