Mean platelet volume in patients with rheumatoid arthritis: the effect of anti-TNF-alpha therapy

A number of mediators are involved in the inflammatory processes that affect joints and vascular wall of patients with rheumatoid arthritis (RA). Tumour necrosis factor alpha (TNFa) is one such mediator, and it is widely regarded as an important target for anti-rheumatic treatment. Most recent studies show that anti-TNFa medication suppresses inflammation and reduces overall activity of RA. The aim of the current study was to investigate changes of mean platelet volume (MPV) in response to the 3-month anti-TNFa therapy in RA. Twenty-one RA patients without established cardiovascular disease were recruited for anti-TNFa therapy and underwent thorough clinical and laboratory evaluation at baseline, 2 weeks, and 12 weeks. Anti-TNFa therapy resulted in a significant (p = 0.01) increase in MPV over the duration of the study (7.7 ± 0.9, 7.8 ± 1.1, and 8.4 ± 1.1 fL at baseline, 2 weeks, and 12 weeks, respectively). The results of the study expand perspectives of the use of MPV in conditions associated with high-grade inflammation, particularly RA, for monitoring anti-inflammatory treatment. More prospective studies with large numbers of patients are warranted to ascertain associations of high and low values of MPV with diverse markers of inflammation and vascular pathology.     

Influence of anti-TNF-alpha infliximab therapy on adhesion molecules associated with atherogenesis in patients with rheumatoid arthritis

OBJECTIVE: Chronic systemic inflammation plays a pivotal role in the development of atherosclerosis in rheumatoid arthritis (RA). Soluble (s) adhesion molecules were found significantly increased in RA patients with active disease. Since increased levels of some adhesion molecules were closely linked to the development of endothelial dysfunction and atherosclerosis and administration of anti-TNF-alpha-infliximab resulted in a rapid and dramatic improvement of endothelial function in long-term infliximab treated RA patients, we assessed whether infusion of the chimeric anti-TNF-alpha infliximab might also yield a rapid and favorable effect on serum levels of soluble adhesion molecules in RA patients periodically treated with this drug because of severe disease. METHODS: We recruited patients with RA refractory to conventional therapy seen over a period of 2 months at Hospital Xeral-Calde, Lugo, Spain, who were on periodical treatment with infliximab for at least 14 weeks. Blood samples for determination of sICAM-1, sICAM-3, sVCAM-1, sE-selectin, and sP-selectin levels by ELISA were taken immediately before and after infliximab infusion.RESULTS: Thirty-four RA patients (25 women; mean age: 55.4 years; mean DAS28: 4.27) fulfilled the inclusion criteria. Following infliximab infusion a reduction of the overall mean values of the five adhesion molecules was observed. However, when a Wilcoxon signed-rank test was used, only significant differences for sICAM-3 and sP-selectin were observed. In this regard, sICAM-3 and sP-selectin levels fell in 26 (77%) and 28 (82%) of the 34 patients. CONCLUSION: Our study confirms a rapid and beneficial effect of infliximab infusion on expression of some adhesion molecules in RA patients treated periodically with this anti-TNF-alpha monoclonal antibody because of severe disease.     

Pulmonary infections in patients with rheumatoid arthritis]

We studied 149 rheumatoid arthritis (RA) patients (mean age 68.0 years; 68 men, 81 women) with pulmonary infections. The mean age at the onset of RA and the duration of RA was 57.2 +/- 15.2 years and 10.9 +/- 11.5 years, respectively. Pulmonary infections included nontuberculous mycobacteriosis in 59 patients (Mycobacterium avium complex infection, 50 cases : Mycobacterium kansasii infection, 4 cases; others, 5 cases), pneumonia in 46 patients, pulmonary tuberculosis in 28 patients, pulmonary aspergillosis in 12 patients, pulmonary cryptococcosis in 5 patients, Pneumocystis jiroveci pneumonia in 5 patients, lung abscess in 9 patients, exacerbation of bronchiectasis in 7 patients, and empyema in 4 patients. One hundred percent of patients with exacerbation of bronchiectasis, 91.7% of patients with pulmonary aspergillosis, 87% of patients with pneumonia, and 81.4% of patients with nontuberculous mycobacteriosis had underlying lung diseases. The pulmonary infections during therapy with steroids were pulmonary tuberculosis (78.6%), pneumonia (65.2%), and pulmonary aspergillosis (58.3%), while the pulmonary infections during methotrexate treatment were Pneumocystis jiroveci pneumonia (80%), pulmonary cryptococcosis (40%), and pulmonary tuberculosis (28.6%). Pulmonary infections in RA patients who were taking TNFalpha inhibitors included 1 patient each with nontuberculous mycobacteriosis, pneumonia, pulmonary tuberculosis, and Pneumocystis jiroveci pneumonia. Among the RA patients with lung abscess, malignancy was noted in 55.6%, and diabetes mellitus in 22.2%. Pseudomonas aeruginosa was the second-most-common cause of pneumonia and cause of all exacerbations of bronchiectasis. As well as immunosuppressive medications (steroids, methotrexate, TNFalpha inhibitors) and systemic comorbid diseases, underlying lung diseases could be one of the risk factor for pulmonary infections in patients with RA. The dominant risk factor for each pulmonary infection in patients with RA might be different.     

Urinary tract infections in patients with rheumatoid arthritis

Co-morbidity from rheumatoid arthritis (RA) has recently focussed on outcomes of cardiovascular and pulmonary disease, but serious infections are an increasingly well-recognised complication of RA. Recent work has demonstrated how the incidence of pneumonia can be reduced in RA, but little attention has been paid to the incidence of urinary tract infection (UTI) in RA or to the associated co-morbidity. The aim of this study was to describe the incidence of UTI leading to hospitalisation in a large cohort of patients with RA and investigate which factors contributed to this. This study assessed all patients with RA hospitalised over a 12-month period with a discharge diagnosis including UTI. Patients were identified through a PAS records search in a single large centre. Historical case controls without RA matched for age and gender were identified from the literature. Clinical notes were manually examined by two observers. We recorded: age, gender, duration of RA, number of UTI, all RA therapy, co-morbidity, results of urine and blood cultures with antimicrobial sensitivities, readmission rates, treatment and outcome. We calculated the relative risk (RR) of developing UTI in patients with RA and the factors influencing this. From a population of 2,200 RA patients, the overall annual incidence of hospitalisation with UTI amongst RA patients was 2.09 %, as against 0.97 and 0.91 % for two control groups (RR?=?2.16 and 2.29). Most patients (90 %) were female, and the group mean age was 76 years. The use of long-term oral steroids as sole therapy was associated with a RR of 6.8 for UTI (p?=?0.002) while failure to take disease-modifying anti-rheumatic drugs (DMARDs) was associated with a similar RR of 6.7 (p?=?0.001). Positive cultures for Escherichia coli were found in 51 % of RA patients. Relevant co-morbidities included permanent catheters, vaginal prolapse, cancer and diabetes. Recurrence of UTI within a year was common. RA was associated with a higher-than-expected incidence of UTI, particularly among older females. This was associated with the use of long-term oral steroids and the absence of DMARDs. Other factors included female gender, greater age and long disease duration. We recommend avoidance of long-term oral steroids but consideration of low-dose prophylactic antibiotics in those patients with recurrent UTI.     

Detection of tuberculosis by extensive screening in a patient with rheumatoid arthritis prior to anti-TNF-alpha therapy

SIR, TNF- blocking agents have seen increasing use in the treatmentof systemic inflammatory diseases such as rheumatoid arthritis(RA). An association of anti-TNF- agents with the occurrenceof mycobacterial infections (MTBI), with a high proportion ofextrapulmonary and disseminated cases, has been noted [1, 2].The article by Horsburgh [3] highlights the public health consequencesof MTBI in     

Safety of anti-TNF-alpha therapy in rheumatoid arthritis and spondylarthropathies with concurrent B or C chronic hepatitis

OBJECTIVE: To assess the safety of anti-tumour necrosis factor (TNF)-alpha therapy in patients with rheumatoid arthritis (RA) or spondylarthropathies (SA) and concurrent chronic hepatitis B or C. METHODS: Records concerning 480 outpatients attending the Rheumatology Department of the University Hospital of Nice (France) for RA or SA were retrospectively reviewed for the duration of disease, treatment, serological status and biological data. RESULTS: Six relevant cases were identified: two of RA with chronic hepatitis B; one of SA with chronic hepatitis B and three of RA with chronic hepatitis C. Five patients had received etanercept and one infliximab; two had been given adalimumab after an unsuccessful trial of etanercept. Patients with concurrent chronic hepatitis B were also given lamivudine. In none of the cases had changes in serum aminotransferases or viral load been reported. CONCLUSION: The use of anti-TNF-alpha therapy (plus lamivudine in the presence of concurrent underlying hepatitis B viral infection) appeared to be safe in that it had no effect on serum aminotransferases and/or viral load. However, repeated monitoring is necessary throughout the treatment period.     

Dose escalation of the anti-TNF-alpha agents in patients with rheumatoid arthritis. A systematic review

OBJECTIVE: To estimate the proportion of rheumatoid arthritis (RA) patients on anti-tumour necrosis factor (anti-TNF) who require dose escalation. METHODS: Systematic review of the scientific literature. Infliximab, etanercept and adalimumab studies in RA were considered. Primary outcome was the proportion of patients requiring dose escalation. American College Rheumatology (ACR) and Disease activity score (DAS) responses post-escalation were assessed when available. RESULTS: From 1801 references, 16 studies with 8510 patients were included. Of all the infliximab patients, 53.7% underwent dose escalation. Fourty-four per cent of the infliximab patients experienced dose increase and 8.3%, frequency increase. The ACR20 response to dose escalation ranged from 27 to 36% and DAS28 improved from 5.2 to 4.5 in one study and from 4.1 to 3.7 in another. Of the etanercept patients, 17.5% experienced a dose increase but changes on the mean dose were not statistically significant. CONCLUSIONS: Dose escalation is common in patients treated with infliximab, and less frequent with etanercept. In a proportion of patients, the dose escalation seems effective. The design and evidence level of the available studies limit the strength of the conclusions.     

Guideline for anti-TNF-alpha therapy in psoriatic arthritis

Rigour of developmentLiterature review Level of evidence Updating Guidelines for anti-TNF- therapy in adults with psoriatic arthritisTreatment algorithm for psoriatic arthritis (Fig. 1) Standard therapy