MTX Group (mtx + group)

Distribution by Scientific Domains

Selected Abstracts

Effect of growth hormone on testicular dysfunction induced by methotrexate in rats

ANDROLOGIA, Issue 2 2009
H. Serati Nouri
Summary Methotrexate (MTX) is a chemotherapeutic agent causing defective oogenesis and spermatogenesis. This study was performed to assess the role of human growth hormone (GH) on testis recovery after treatment with MTX. Forty male Wistar rats were selected and randomly divided into four groups (n = 10): control (vehicle), GH group (0.3 mg kg,1 GH for 28 days, IP), MTX group (MTX 1 mg kg,1 week,1 for 4 weeks, IP) and GH/MTX group (0.3 mg kg,1 GH for 28 day plus 1 mg kg,1 week,1 MTX for 4 weeks, IP). On days 14 and 28, five rats from each group were killed, testes of rats of all groups were removed, spermatozoa were collected from epididymis and then prepared for analysis. MTX caused significant increase in interstitial tissue and capsular thickness and decrease of testicular and body weight (P < 0.05). Moreover, it caused significant decline in seminiferous tubule diameter and epithelium thickness (P < 0.05). There was no obvious change in morphometrical parameters between MTX/GH and control groups. In MTX group, sperm parameters decreased significantly (P < 0.05). Administration of GH plus MTX reduced the effects of MTX on sperm parameters and testosterone concentration. These results suggested that GH had a protective effect on almost all destructive effects caused by MTX in rat testes and thus improved sperm parameters. [source]

Golimumab in patients with active rheumatoid arthritis despite treatment with methotrexate: A randomized, double-blind, placebo-controlled, dose-ranging study,

Jonathan Kay
Objective To assess the efficacy, safety, and pharmacology of subcutaneous administration of golimumab in patients with active rheumatoid arthritis (RA) despite treatment with methotrexate (MTX). Methods Patients were randomly assigned in a double-blinded manner to receive injections of placebo plus MTX or 50 mg or 100 mg golimumab every 2 or 4 weeks plus MTX through week 48. Patients originally assigned to receive injections every 2 weeks had the interval increased to every 4 weeks starting at week 20. The primary end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at week 16. The study was powered to detect a difference in the primary end point when the combined golimumab groups and at least 1 of the individual dose groups were compared with placebo. Results The primary end point was attained. Sixty-one percent of patients in the combined golimumab plus MTX dose groups achieved an ACR20 response at week 16 compared with 37% of patients in the placebo plus MTX group (P = 0.010). In addition, 79% of patients in the group receiving 100 mg golimumab every 2 weeks achieved an ACR20 response (P < 0.001 versus placebo). Through week 20 (after which patients receiving placebo were switched to active infliximab therapy), serious adverse events were reported in 9% of patients in the combined golimumab groups and in 6% of patients in the placebo group. Conclusion Golimumab plus MTX effectively reduces the signs and symptoms of RA and is generally well tolerated in patients with an inadequate response to MTX. [source]

Treatment of early rheumatoid arthritis: A randomized magnetic resonance imaging study comparing the effects of methotrexate alone, methotrexate in combination with infliximab, and methotrexate in combination with intravenous pulse methylprednisolone,

Patrick Durez
Objective To compare the effects of methotrexate (MTX), alone or in combination with intravenous (IV) methylprednisolone (MP) or infliximab, on magnetic resonance imaging (MRI),detected synovitis, bone edema, and erosive changes in patients with early rheumatoid arthritis (RA). Methods Forty-four patients with early RA were randomized to receive MTX alone (MTX group), MTX plus IV MP (IV MP group), or MTX plus infliximab (infliximab group), infused on day 0 and weeks 2, 6, 14, 22, 30, 38, and 46. Gadolinium-enhanced MRI scans of the metacarpophalangeal joints, wrists, and metatarsophalangeal joints were performed at baseline, week 18, and week 52. Results Scores for MRI-detected synovitis and bone edema improved over time in the 3 groups, with significantly lower synovitis scores in the infliximab group compared with the MTX group and significantly lower bone edema scores in the infliximab group compared with the MTX and the IV MP groups. Scores for MRI-detected erosion significantly increased over time in all groups. There were no differences in erosion scores between the MTX group and the other groups. It is of note that patients treated with IV MP showed more significant progression in MRI-detected erosions compared with patients treated with infliximab. At week 22, response rates according to the American College of Rheumatology 20% improvement criteria (ACR20), the ACR50, and the ACR70 were significantly higher in both the IV MP group and the infliximab group compared with the MTX group. At week 52, remission was achieved in 40% of patients in the MTX group and in 70% of patients in the IV MP and infliximab groups. Health Assessment Questionnaire scores improved significantly over time in all groups, with patients receiving IV MP experiencing significantly more improvement compared with patients treated with MTX alone. No severe side effects were observed, except 1 case of MTX-related pneumonitis. Conclusion The combination of MTX and infliximab is superior to MTX alone for reducing MRI-detected signs of synovitis and bone edema in patients with early RA. Progression of MRI-detected erosion was greater in patients treated with MTX plus IV MP compared with that in patients who received MTX plus infliximab. [source]

Efficacy of methotrexate treatment in patients with probable rheumatoid arthritis: A double-blind, randomized, placebo-controlled trial

Henrike van Dongen
Objective To determine whether patients with undifferentiated arthritis (UA; inflammatory, nontraumatic arthritis that cannot be diagnosed using current classification criteria) benefit from treatment with methotrexate (MTX). Methods The PRObable rheumatoid arthritis: Methotrexate versus Placebo Treatment (PROMPT) study was a double-blind, placebo-controlled, randomized, multicenter trial involving 110 patients with UA who fulfilled the American College of Rheumatology (ACR) 1958 criteria for probable RA. Treatment started with MTX (15 mg/week) or placebo tablets, and every 3 months the dosage was increased if the Disease Activity Score was >2.4. After 12 months, the study medication was tapered and discontinued. Patients were followed up for 30 months. When a patient fulfilled the ACR criteria for RA (primary end point), the study medication was changed to MTX. Joint damage was scored on radiographs of the hands and feet. Results In 22 of the 55 patients (40%) in the MTX group, UA progressed to RA compared with 29 of 55 patients (53%) in the placebo group. However, in the MTX group, patients fulfilled the ACR criteria for RA at a later time point than in the placebo group (P = 0.04), and fewer patients showed radiographic progression over 18 months (P = 0.046). Conclusion This study provides evidence for the efficacy of MTX treatment in postponing the diagnosis of RA, as defined by the ACR 1987 criteria, and retarding radiographic joint damage in UA patients. [source]

Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis: Two-year clinical and radiographic results from the TEMPO study, a double-blind, randomized trial

Désirée van der Heijde
Objective To evaluate the efficacy, including radiographic changes, and safety of etanercept and methotrexate (MTX), used in combination and alone, in patients with rheumatoid arthritis (RA) in whom previous treatment with a disease-modifying antirheumatic drug other than MTX had failed. Methods Patients with RA were treated with etanercept (25 mg subcutaneously twice weekly), oral MTX (up to 20 mg weekly), or combination therapy with etanercept plus MTX through a second year, in a double-blinded manner. Clinical response was assessed using American College of Rheumatology (ACR) criteria and the Disease Activity Score (DAS), in a modified intent-to-treat analysis with the last observation carried forward (LOCF) and in a population of completers. Radiographs of the hands, wrists, and forefeet were scored for erosions and joint space narrowing at annual intervals. Results A total of 503 of 686 patients continued into year 2 of the study. During the 2 years, significantly fewer patients receiving combination therapy withdrew from the study (29% of the combination therapy group, 39% of the etanercept group, and 48% of the MTX group). Both the LOCF and the completer analyses yielded similar results. The ACR 20% improvement (ACR20), ACR50, and ACR70 responses and the remission rates (based on a DAS of <1.6) were significantly higher with combination therapy than with either monotherapy (P < 0.01). Similarly, improvement in disability (based on the Health Assessment Questionnaire) was greater with combination therapy (P < 0.01). The combination therapy group showed significantly less radiographic progression than did either group receiving monotherapy (P < 0.05); moreover, radiographic progression was significantly lower in the etanercept group compared with the MTX group (P < 0.05). For the second consecutive year, overall disease progression in the combination therapy group was negative, with the 95% confidence interval less than zero. Adverse events were similar in the 3 treatment groups. Conclusion Etanercept in combination with MTX reduced disease activity, slowed radiographic progression, and improved function more effectively than did either monotherapy over a 2-year period. No increase in toxicity was associated with combination treatment with etanercept plus MTX. [source]

Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate: Results of a twenty-four,week, multicenter, randomized, double-blind, placebo-controlled trial

Stanley Cohen
Objective To evaluate the efficacy and safety of anakinra in combination with methotrexate (MTX) in patients with active rheumatoid arthritis (RA). Methods Patients with moderate-to-severe active RA who were receiving MTX for 6 consecutive months, with stable doses for ,3 months (those with disease duration of >6 months but <12 years) were randomized into 6 groups: placebo or 0.04, 0.1, 0.4, 1.0, or 2.0 mg/kg of anakinra administered in a single, daily, subcutaneous injection. The primary efficacy end point was the proportion of subjects who met the American College of Rheumatology 20% improvement criteria (attained an ACR20 response) at week 12. Results A total of 419 patients were randomized in the study. Patient demographics and disease status were similar in the 6 treatment groups. The ACR20 responses at week 12 in the 5 active treatment plus MTX groups demonstrated a statistically significant (P = 0.001) dose-response relationship compared with the ACR20 response in the placebo plus MTX group. The ACR20 response rate in the anakinra 1.0-mg/kg (46%; P = 0.001) and 2.0-mg/kg (38%; P = 0.007) dose groups was significantly greater than that in the placebo group (19%). The ACR20 responses at 24 weeks were consistent with those at 12 weeks. Similar improvements in anakinra-treated subjects were noted in individual ACR components, erythrocyte sedimentation rate, onset of ACR20 response, sustainability of ACR20 response, and magnitude of ACR response. Anakinra was safe and well tolerated. Injection site reaction was the most frequently noted adverse event, and this led to premature study withdrawal in 7% (1.0-mg/kg group) to 10% (2.0-mg/kg group) of patients receiving higher doses. Conclusion In patients with persistently active RA, the combination of anakinra and MTX was safe and well tolerated and provided significantly greater clinical benefit than MTX alone. [source]

Decrease of adenosine deaminase activity and increase of the lipid peroxidation after acute methotrexate treatment in young rats: protective effects of grape seed extract

F. V. Pinheiro
Abstract The methotrexate (MTX) is an anti-folate used to treat cancer and some inflammatory diseases. The efficacy of MTX is often limited by its severe toxicity. The present study was undertaken to determine whether Grape seed (Cabernet Sauvignon) extract (GSE) could ameliorate the MTX-induced oxidative injury and the effect on adenosine deaminase activity (ADA) in rats. The rats were pretreated with 50,mg/kg of GSE, i.p., prior to MTX administration (10,mg/kg, i.p.) with a second dose given 4,h and a third dose 16,h after MTX administration. Biochemical parameters were investigated 48,h after the last MTX administration. The administration of MTX increased thiobarbituric acid reactive species (TBARS) levels in hippocampus, kidney and liver, whereas induced a significant decreased in the ADA activity in the cerebral cortex, kidney and liver tissues. MTX administration significantly increased the activity of ALT(alanine aminotransferase) and urea levels and decreased uric acid levels in the serum. Urinary uric acid levels decreased in the MTX group when compared to those of the control group. The GSE along with MTX-administration significantly reversed these parameters toward to near normal. These results indicated that GSE could reduce hepatic and nephritic damage induced by MTX-treatment in young rats therefore having free radical scavenging. Copyright © 2009 John Wiley & Sons, Ltd. [source]