Leflunomide increases the risk of early healing complications in patients with rheumatoid arthritis undergoing elective orthopedic surgery

The aim of this object is to study whether treatment with biological or leflunomide increases the risk of wound-healing complications after elective orthopedic surgery. Between March 2002 and September 2003, 201 patients participated in this study with the following inclusion criteria: (a) Rheumatoid arthritis (RA) or psoriatic arthritis (psA), (b) therapy with: MTX, leflunomide, etanercept, infliximab, adalimumab, anakinra, (c) undergoing elective orthopedic surgery. The incidence of early postoperative wound-healing complications was compared among the different groups. In comparison with patients who received MTX therapy (n = 59), the risk of postoperative wound-healing complications in patients undergoing leflunomide therapy (n = 32) was significantly higher: 13.6% in the MTX group, 40.6% in the leflunomide group (P = 0.01). It is recommended that leflunomide medication for patients with RA undergoing elective orthopedic surgical procedure is interrupted preoperatively to reduce the risk of early wound-healing complications or infections.     

Lack of increase in postoperative complications with low-dose methotrexate therapy in patients with rheumatoid arthritis undergoing elective orthopedic surgery

To determine the potential contribution of intermittent low-dose methotrexate (MTX) treatment (2–8 mg/week) to postoperative complications, we studied 122 patients with rheumatoid arthritis (RA) who had 201 surgical procedures. The patients with treatment with MTX were allocated to two groups: those who continued MTX (group A, 77 procedures) and those who discontinued MTX more than 1 week (group B, 21 procedures). The patients who had no treatment with MTX were allocated to group C (103 procedures). The incidence of postoperative infection, poor wound healing, and flare-up of RA was compared between the three groups. Postoperative infection occurred in 3.9%, 4.8%, and 3.9% in groups A, B, and C, respectively. Poor wound healing was experienced in 1.3%, 9.5%, and 7.8% in groups A, B, and C, respectively. At 4 weeks postoperatively, 3.9%, 14.3%, and 6.8% of flares were seen in groups A, B, and C, respectively. No significant difference was found in the patients with or without perioperative use of MTX. From these results, it is unlikely that continuation of intermittent low-dose MTX treatment increases the risk of postoperative complications in patients with RA. Continued treatment with MTX during perioperative period could suppress disease flares, especially in severe RA patients.     

Lack of increase in postoperative complications with low-dose methotrexate therapy in patients with rheumatoid arthritis undergoing elective orthopedic surgery

Abstract

To determine the potential contribution of intermittent low-dose methotrexate (MTX) treatment (2–8mg/week) to postoperative complications, we studied 122 patients with rheumatoid arthritis (RA) who had 201 surgical procedures. The patients with treatment with MTX were allocated to two groups: those who continued MTX (group A, 77 procedures) and those who discontinued MTX more than 1 week (group B, 21 procedures). The patients who had no treatment with MTX were allocated to group C (103 procedures). The incidence of postoperative infection, poor wound healing, and flare-up of RA was compared between the three groups. Postoperative infection occurred in 3.9%, 4.8%, and 3.9% in groups A, B, and C, respectively. Poor wound healing was experienced in 1.3%, 9.5%, and 7.8% in groups A, B, and C, respectively. At 4 weeks postoperatively, 3.9%, 14.3%, and 6.8% of flares were seen in groups A, B, and C, respectively. No significant difference was found in the patients with or without perioperative use of MTX. From these results, it is unlikely that continuation of intermittent low-dose MTX treatment increases the risk of postoperative complications in patients with RA. Continued treatment with MTX during perioperative period could suppress disease flares, especially in severe RA patients.     

Perioperative complications in elective surgery in patients with rheumatoid arthritis treated with biologics

Abstract

We retrospectively investigated the influence of biological agents on delayed wound healing and the occurrence of postoperative surgical site infection (SSI) in patients after surgery for rheumatoid arthritis. The patients were divided into two groups—those with and without treatment with biological agents (276 and 278 joints, respectively)—and adverse events (delay in wound healing and SSI) were investigated. Wound healing was delayed in 11.4% of total knee arthroplasty (TKA) operations, 16.7% of total ankle arthroplasty operations, and 9.7% of foot surgeries in the treatment group, and in 5.5% of TKA operations, 12.5% of total elbow arthroplasty operations, and 5.7% of foot surgeries in the non-treatment group. The difference in the incidence of delayed wound healing between the two groups was not statistically significant. In the treatment group, postoperative superficial and deep infection developed in one and two joints, respectively. In the non-treatment group, superficial infection developed in one joint. There was no statistically significant difference between the two groups. These findings suggest that the use of biological agents may not affect the incidence of postoperative adverse events related to wound healing and SSI.     

Perioperative complications in elective surgery in patients with rheumatoid arthritis treated with biologics

We retrospectively investigated the influence of biological agents on delayed wound healing and the occurrence of postoperative surgical site infection (SSI) in patients after surgery for rheumatoid arthritis. The patients were divided into two groups—those with and without treatment with biological agents (276 and 278 joints, respectively)—and adverse events (delay in wound healing and SSI) were investigated. Wound healing was delayed in 11.4% of total knee arthroplasty (TKA) operations, 16.7% of total ankle arthroplasty operations, and 9.7% of foot surgeries in the treatment group, and in 5.5% of TKA operations, 12.5% of total elbow arthroplasty operations, and 5.7% of foot surgeries in the non-treatment group. The difference in the incidence of delayed wound healing between the two groups was not statistically significant. In the treatment group, postoperative superficial and deep infection developed in one and two joints, respectively. In the non-treatment group, superficial infection developed in one joint. There was no statistically significant difference between the two groups. These findings suggest that the use of biological agents may not affect the incidence of postoperative adverse events related to wound healing and SSI.     

Anaesthesiological problems in patients with rheumatoid arthritis undergoing orthopaedic surgeries

The article presents anaesthesiological problems in patients with rheumatoid arthritis (RA) scheduled for orthopaedic surgeries. Organ changes due to RA and related treatment were taken into account. The anaesthetic techniques used for patients with RA underwent orthopaedic procedures were presented.     

Methotrexate pharmacokinetics in patients with rheumatoid arthritis

Few studies have evaluated the pharmacokinetics of low dose oral methotrexate (MTX) therapy. MTX pharmacokinetics were studied in 10 patients with classic rheumatoid arthritis (RA) after a single 7.5 mg oral dose. MTX was rapidly absorbed. Peak concentrations varied considerably, ranging from 0.31-0.72 microM. Measurable drug concentration was found in all patients at 24 h after the dose. CL/F-MTX = 145 +/- 52 ml/min/1.73 m2 and elimination half-life was 4.5 +/- 0.89 h. Oral MTX given as a single weekly dose has predictable pharmacokinetics. Further studies to examine what relationship exists, if any, with efficacy and toxicity of MTX in RA must be undertaken.     

Functional testing of tranexamic acid effects in patients undergoing elective orthopaedic surgery

Tranexamic acid (TXA) can reduce blood loss and transfusion rates in orthopaedic surgery. In this regard, a new viscoelastometric test (TPA-test, ClotPro), enables the monitoring of TXA effects. This prospective observational study evaluated and correlated TXA plasma concentrations (cTXA) following intravenous and oral administration in patients undergoing elective orthopaedic surgery with lysis variables of TPA-test. Blood samples of 42 patients were evaluated before TXA application and 2, 6, 12, 24 and 48 h afterwards. TPA-test was used to determine lysis time (LT) as well as maximum lysis (ML) and cTXA was measured using Ultra-High-Performance-Liquid-Chromatography/Mass-Spectrometry. Data are presented as median (min–max). LT_TPA-test and ML_TPA-test correlated with cTXA (r?=?0.9456/r?=?0.5362; p?<?0.0001). 2 h after intravenous TXA administration all samples showed complete lysis inhibition (LT_TPA-test prolongation: T1: 217 s (161–529) vs. T2: 4500 s (4500–4500);p?<?0.0001), whereas after oral application high intraindividual variability was observed as some samples showed only moderate changes in LT_TPA-test (T1: 236 s (180–360) vs. T2: 4500 s (460–4500); p?<?0.0001). Nevertheless, statistically LT_TPA-test did not differ between groups. ML_TPA-test differed 2 h after application (i.v.: 9.0% (5–14) vs. oral: 31% (8–97); p?=?0.0081). In 17/21 samples after oral and 0/21 samples after intravenous administration cTXA was?<?10 µg ml^?1 2 h after application. TPA-test correlated with cTXA. ML_TPA-test differed between intravenous and oral application 2 h after application. Most patients with oral application had TXA plasma concentration?<?10 µg ml^?1. The duration of action did not differ between intravenous and oral application. Additional studies evaluating clinical outcomes and side-effects based on individualized TXA prophylaxis/therapy are required.

     

Methotrexate effects in patients with rheumatoid arthritis with cardiovascular comorbidity

Methotrexate, an antirheumatic drug that may increase serum homocysteine, significantly increases mortality in patients with rheumatoid arthritis and cardiovascular comorbidity.     

Should methotrexate be discontinued before elective orthopedic surgery in patients with rheumatoid arthritis?

To determine if methotrexate (MTX) contributes to early postoperative complications, we studied 38 patients with rheumatoid arthritis (RA) who underwent elective orthopedic surgery. There were 4 complications of prosthetic joint infection or wound dehiscence or infection among 19 procedures performed on patients who continued MTX until less than 4 weeks before surgery, compared to no complications among 34 procedures performed on patients who discontinued MTX 4 weeks before surgery or who were taking no remittive agent for 3 months before surgery (p less than 0.03, Fisher's exact, 2-tailed). No demographic, clinical, laboratory, nutritional, or intraoperative differences between the 2 groups were apparent, suggesting that MTX may play a role in early postoperative complications in patients with RA. A larger, prospective trial to study this issue is warranted.     

Methotrexate in refractory rheumatoid arthritis

Summary Fourteen patients with severe rheumatoid arthritis refractory to hydroxychloroquine, gold-thioglucose, D-penicillamine and azathioprine completed a 6-month open study with oral methotrexate (2.5 to 5 mg every 12 hours, three doses weekly). Twelve of them were followed up for 12 months. Compared with pretreatment values, there was a significant reduction in duration of morning stiffness (p<0.01), in the number of tender or painful joints (p<0.02), number of swollen joints (p<0.01), visual analog scale, patient's assessment of joint discomfort and overall well-being (p 0.01) after 2, 6 and 12 months. Likewise there was an improvement in the erythrocyte sedimentation rate (p<0.001) C-reactive protein (p<0.01) and the levels of IgG, IgM and IgA (p<0.01). Two patients were withdrawn from the study, one for severe diarrhoea and one because of a depression. Adverse reactions during methotrexate therapy included nausea (5/16) and transaminase elevation (4/16). We conclude that this pilot study provides evidence that a weekly low dose of methotrexate is effective in the short-term treatment for patients with rheumatoid arthritis, refractory to hydroxychloroquine, auriothioglucose, D-penicillamine and azathioprine.     

Methotrexate inhibits interleukin-6 production in patients with juvenile rheumatoid arthritis

OBJECTIVES: Methotrexate (MTX) is one of the most widely used disease-modifying antirheumatoid drugs in the treatment of juvenile rheumatoid arthritis (JRA). We studied its effect on the production of two proinflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFalpha), by peripheral blood cells in patients with JRA. METHODS: Interleukin-6 and TNFalpha levels were measured at 0 and 4 weeks in whole blood cultures with and without lipopolysaccharide (LPS) stimulation in 19 children treated with MTX (10 mg/m(2 )per week) or placebo. Ten healthy individuals were included as healthy controls. RESULTS: Spontaneous production of IL-6 and TNFalpha by peripheral blood cells of patients with JRA was higher than in healthy controls ( P<0.01). However, IL-6 and TNFalpha production after LPS stimulation was similar in healthy controls and patients. The two groups of patients, i.e., those treated with placebo and those treated with MTX, had similar spontaneous and induced IL-6 and TNFalpha production. At 4 weeks, the drop in spontaneous IL-6 and TNFalpha production was no different in the two groups, but LPS-stimulated IL-6 production was significantly lower in the MTX-treated group than the placebo group ( P<0.05). CONCLUSION: Methotrexate reduces the production of IL-6 by activated cells, and this may be responsible for its anti-inflammatory property.