Primary studies included in this broad synthesis

loading
20 articles (21 Referencias) Revertir Estudificar

Hilo de publicación

CAMERA 1 (Computer Assisted Management in Early Rheumatoid Arthritis)

Este hilo de publicación incluye 4 referencias

Estudio primario

No clasificado

Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of methotrexate in patients with active rheumatoid arthritis: results of a six-month, multicenter, randomized, double-blind, controlled, phase IV trial.

Revista Arthritis and rheumatism
Año 2008
Enlaces Pubmed DOI

Este artículo está incluido en 6 Revisiones sistemáticas Revisiones sistemáticas (6 referencias) 2 Síntesis amplias Síntesis amplias (2 referencias)

Cargando información sobre las referencias
OBJECTIVE: To compare the efficacy and safety of subcutaneous (SC) versus oral administration of methotrexate (MTX) in patients with active rheumatoid arthritis (RA). METHODS: MTX-naive patients with active RA (Disease Activity Score in 28 joints >or= 4) were eligible for the study if they had not previously taken biologic agents and had not taken disease-modifying antirheumatic drugs for 2 weeks prior to randomization. Patients were randomly assigned to receive 15 mg/week of MTX either orally (2 7.5-mg tablets plus a dummy prefilled syringe; n=187 patients) or SC (prefilled syringe containing 10 mg/ml plus 2 dummy tablets; n=188 patients) for 24 weeks. At week 16, patients who did not meet the American College of Rheumatology criteria for 20% improvement (ACR20) were switched from 15 mg of oral MTX to 15 mg of SC MTX and from 15 mg of SC MTX to 20 mg of SC MTX for the remaining 8 weeks, still in a blinded manner. The primary outcome was an ACR20 response at 24 weeks. RESULTS: At week 24, significantly more patients treated with SC MTX than with oral MTX showed ACR20 (78% versus 70%) and ACR70 (41% versus 33%) responses. Patients with a disease duration >or= 12 months had even higher ACR20 response rates (89% for SC administration and 63% for oral). In 52 of the ACR20 nonresponders (14%), treatment was switched at week 16. Changing from oral to SC MTX and from 15 mg to 20 mg of SC MTX resulted in 30% and 23% ACR20 response rates, respectively, in these patients. MTX was well tolerated. The rate of adverse events was similar in all groups. CONCLUSION: This 6-month prospective, randomized, controlled trial is the first to examine oral versus SC administration of MTX. We found that SC administration was significantly more effective than oral administration of the same MTX dosage. There was no difference in tolerability.

Estudio primario

No clasificado

Methotrexate in rheumatoid arthritis, starting dose and dose escalation regimens

Autores Jassim IAH , Al-Allaf A , Newton P
Revista Ann Rheum Dis
Año 2007

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

Cargando información sobre las referencias

Hilo de publicación

BeSt (Behandel-Strategieën [“treatment strategies”])

Este hilo de publicación incluye 35 referencias

Estudio primario

No clasificado

Bioavailability of higher dose methotrexate comparing oral and subcutaneous administration in patients with rheumatoid arthritis.

Revista The Journal of rheumatology
Año 2004
Enlaces Pubmed

Este artículo está incluido en 1 Síntesis amplia Síntesis amplias (1 referencia) 3 Revisiones sistemáticas Revisiones sistemáticas (3 referencias)

Cargando información sobre las referencias
OBJECTIVE: To determine the bioavailability of higher oral doses of methotrexate (MTX) in adult patients with rheumatoid arthritis (RA). METHODS: A pharmacokinetic analysis was performed in 15 patients with RA taking a stable dose of MTX (> or = 25 mg weekly). Separated by 2 weeks, a pharmacokinetic analysis was performed in each patient after oral and subcutaneous administration of the same dose of MTX. MTX serum concentrations were measured by a fluorescence polarization immunoassay. Pharmacokinetic analysis was performed with an iterative 2-stage Bayesian population procedure, obtaining population and individual pharmacokinetic parameters. RESULTS: The median MTX dose was 30 mg weekly (range 25-40 mg). A 2-compartment model best described the serum MTX concentration versus time curves. The mean bioavailability after oral MTX was 0.64 (range 0.21-0.96) compared to subcutaneous administration. There was a statistically significant difference in the bioavailability of the 2 administration regimens. CONCLUSION: Bioavailability of a higher oral dose of MTX in adult patients with RA is highly variable, and on average two-thirds that of the subcutaneous administration. To improve efficacy of MTX at dosages of 25 mg weekly or more, a change to parenteral administration should be considered.

Estudio primario

No clasificado

Better efficacy of methotrexate given by intramuscular injection than orally in patients with rheumatoid arthritis.

Autores Wegrzyn J , Adeleine P , Miossec P
Revista Annals of the rheumatic diseases
Año 2004
Enlaces Pubmed DOI PubMed Central

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

Cargando información sobre las referencias
OBJECTIVE: To compare the clinical efficacy of methotrexate and tolerance to the drug in patients with rheumatoid arthritis who were switched from intramuscular to oral administration because of a shortage of the intramuscular preparation. METHODS: 143 patients were switched from intramuscular to oral methotrexate. Of these, 47 were switched back to the intramuscular form. A multiple choice questionnaire was sent by mail to evaluate clinical and biological criteria of efficacy and tolerance. RESULTS: When methotrexate was first switched from intramuscular to oral administration, increased disease activity, exacerbation of morning pain and hand stiffness, duration of morning stiffness, increased joint pain, and increased joint swelling were observed. There was a greater frequency of gastrointestinal symptoms, but without a significant increase in liver abnormalities. When intramuscular methotrexate became available again, 47 of the 143 patients were switched back and were followed for at least three months. On average, disease manifestations were improved and side effects reduced by the switch. CONCLUSIONS: Methotrexate given intramuscularly had improved clinical efficacy with fewer side effects than given orally. Intramuscular methotrexate administration should be considered when rheumatoid arthritis remains active in spite of high dose oral methotrexate.

Estudio primario

No clasificado

Benefit of very early referral and very early therapy with disease-modifying anti-rheumatic drugs in patients with early rheumatoid arthritis.

Revista Rheumatology (Oxford, England)
Año 2004
Enlaces Pubmed DOI

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

Cargando información sobre las referencias
OBJECTIVE: Delay of disease-modifying anti-rheumatic drug (DMARD) therapy is a major contributing factor for poor outcome in rheumatoid arthritis (RA). Although early therapy has been shown to be particularly effective, there is still uncertainty about the optimal time point of DMARD introduction. We wanted to test if a therapeutic window of opportunity may exist within the first few months of the disease. METHODS: In this case-control parallel-group study, 20 very early RA (VERA) patients with median disease duration of 3 months were age and gender matched to a group of 20 late early RA (LERA) patients with median disease duration of 12 months until first DMARD initiation. Follow-up time was 36 months. Primary outcome measures were the disease activity score (DAS28) and radiological joint destruction using the Larsen method. RESULTS: Already after 3 months of DMARD therapy we found a significant difference of improvement in favour of the VERA patients in the DAS28. This trend continued over the study period. At study end the DAS28 showed an improvement of 2.8+/-1.5 in the VERA vs 1.7+/-1.2 in the LERA group (P(c)<0.05). The Larsen scores showed a statistically significant retardation of progression in the VERA compared with the LERA. CONCLUSION: Our results indicate that there is a window of opportunity for highly successful treatment of RA in the first year, and especially within the first 3 months of therapy. Thus, early diagnosis and therapy may be the crucial step in achieving optimal control of disease progression and prognosis in RA.

Hilo de publicación

TICORA (Tight Control of Rheumatoid Arthritis)

Este hilo de publicación incluye 1 referencias

Estudio primario

No clasificado

The role of subcutaneous administration of methotrexate in children with juvenile idiopathic arthritis who have failed oral methotrexate.

Revista The Journal of rheumatology
Año 2004
Enlaces Pubmed

Este artículo está incluido en 1 Síntesis amplia Síntesis amplias (1 referencia)

Cargando información sobre las referencias
OBJECTIVE: To describe the outcome of patients with juvenile idiopathic arthritis (JIA) treated with subcutaneous (Sc) methotrexate (MTX) after failing oral MTX (either because of inefficacy or toxicity) in a clinic population. METHODS: The study cohort was identified from our clinical database, and consisted of 61 children with JIA treated with MTX between 1988-2001. All patients fulfilled International League Against Rheumatism (ILAR) criteria for JIA and had disease duration of >/= 6 months and 3 or more active joints before institution of MTX. All patients had a core set of outcome variables assessed at baseline and at 3 months after achieving both maximum oral and SC MTX. Outcome variables included physician global assessment of disease activity, number of active joints, number of joints with limited range of motion, duration of early morning stiffness, and erythrocyte sedimentation rate (ESR). Improvement was defined as at least 30% improvement from baseline in 3 of 5 variables in the core set, with no more than one of the remaining variables worsening by more than 30%. RESULTS: A total of 61 patients, 43 females and 18 males with JIA were studied. The disease subtypes were systemic 8, polyarticular 25 (12 rheumatoid factor positive), oligoarticular 14, enthesitis related arthritis 5, and unclassified 4. Thirty-one patients were switched to SC MTX, 13 of whom had not improved, and 18 who had improved, but had nausea (11) or insufficient clinical improvement (7). After 3 months of SC MTX treatment, 76% of patients were classified as improved and 23% as not improved. Toxicity on SC MTX was less than on oral MTX. CONCLUSION: Our results suggest that for patients failing oral MTX either because of inefficacy or toxicity, the use of SC MTX has a high likelihood of success with more than 70% of patients achieving clinically significant improvement, without clinically significant toxicity.

Estudio primario

No clasificado

Dose escalation of parenteral methotrexate in active rheumatoid arthritis that has been unresponsive to conventional doses of methotrexate: a randomized, controlled trial.

Revista Arthritis and rheumatism
Año 2004
Enlaces Pubmed DOI
Cargando información sobre las referencias
OBJECTIVE: To examine whether dose escalation of intramuscular (IM) methotrexate (MTX) up to 45 mg/week improves disease control in patients who have active rheumatoid arthritis (RA) despite receiving conventional doses (15 mg/week) of IM MTX, and to obtain preliminary data on patient tolerability and adverse effects of higher doses of IM MTX. METHODS: Patients >18 years of age who had active RA, defined as a European League Against Rheumatism (EULAR) Disease Activity Score in 28 joints (DAS28) of >3.2, and who had received 15-20 mg/week of oral MTX for at least 2 months were switched (week 0) to 15 mg/week of IM MTX for 6 weeks. Patients whose DAS28 remained >3.2 at both week 4 and week 6 were randomized, in a double-blind manner, either to continue to receive 15 mg/week IM MTX with monthly placebo escalation or to receive escalating doses of IM MTX monthly up to 45 mg/week. The dose of MTX or placebo was escalated every 4 weeks if the DAS28 was >2.5. Safety assessments and determination of the DAS28 were performed every 2 weeks and monthly, respectively. Disease activity parameters from the American College of Rheumatology (ACR) core disease activity set and health status as recorded on the Medical Outcomes Study Short-Form 12 were determined at baseline (week 0) and final assessment (week 22). The primary outcome was the percentage of patients in each group achieving a target DAS28 of <3.2. Secondary outcomes comprised the percentage of patients whose DAS28 improved by >1.2, the percentage of patients achieving a 20% improvement in the ACR core disease activity measures (ACR20), and the percentage of patients achieving a good response, a moderate response, or no response in accordance with the EULAR response criteria. RESULTS: Sixty-four patients were eligible for entry and were switched from oral MTX to 15 mg/week IM MTX. At baseline, the mean +/- SD DAS28 was 5.6 +/- 0.88; after 6 weeks of IM MTX, the DAS28 had improved by a mean of 0.42 (95% confidence interval [95% CI] 0.15-0.69). At 6 weeks, 54 patients still had a DAS28 of >3.2 and were therefore eligible for randomization. By 22 weeks, 1 patient (3.7%) in each group achieved the primary outcome of a DAS28 <3.2 (95% CI for the difference between the groups -15% to +15%). Five patients (18.5%) in each group showed an improvement of >1.2 in the DAS28 (95% CI for the difference between the groups -18% to +18%). One patient (3.7%) in each group achieved an ACR20 response, but none achieved a good response as defined by the EULAR response criteria. One patient in each group had a serious adverse reaction; minor adverse reactions were more frequently reported in the dose escalation group. CONCLUSION: Switching from oral to parenteral MTX 15 mg/week results in a minor improvement in disease control. For patients with active RA receiving 15 mg/week IM MTX, increasing the dose up to 45 mg/week does not improve disease control. Higher doses of IM MTX were generally well tolerated and not associated with an increase in serious adverse reactions to the drug.