Implicit and explicit attitudes towards disease-modifying antirheumatic drugs as possible target for improving medication adherence.

OBJECTIVE: This study aims to explore the contribution of implicit attitudes and associations towards conventional disease-modifying antirheumatic drugs (cDMARDs), alongside explicit measures, on medication-taking behaviour and clinical outcomes in adult patients with rheumatoid arthritis (RA). METHODS: In this observational study, implicit attitudes (positive-negative) and health-related associations (health-sickness) were measured with Single Category Implicit Association Tests, whereas explicit outcomes were measured with a bipolar evaluative adjective scale and the Beliefs about Medicines Questionnaire Specific. The primary outcome of this study was medication-taking behaviour subjectively measured by self-report (i.e. validated Compliance Questionnaire on Rheumatology) and objectively measured with electronic drug monitors over a 3 month period. Spearman rank correlations were used to describe correlations between implicit and explicit outcomes. Nested linear regression models were used to assess the additional value of implicit measures over explicit measures and patient-, clinical-, and treatment-related characteristics. RESULTS: Of the 1659 initially-invited patients, 254 patients with RA agreed to participate in this study. Implicit attitudes correlated significantly with necessity-concerns differential (NCD) scores (ρ = 0.13, P = 0.05) and disease activity scores (ρ = -0.17, P = 0.04), whereas implicit health-related associations correlated significantly with mean scores for explicitly reported health-related associations (ρ = 0.18, P = 0.004). Significant differences in age, number of DMARDs, biologic DMARD use, NCD-scores, and self-reported correct dosing were found between the four attitudinal profiles. Nested linear regression models revealed no additional value of implicit measures in explaining self-reported medication-taking behaviour and clinical outcomes, over and above all other variables. CONCLUSION: Implicit attitudes and associations had no additional value in explaining medication-taking behaviour and clinical outcomes over and above often used explicitly measured characteristics, attitudes and outcomes in the studied population. Only age and NCD scores contributed significantly when the dependent variable was correct dosing measured with self-report.

Effect of Aerobic Exercise Training on Fatigue in Rheumatoid Arthritis: A Meta-Analysis.

OBJECTIVE: Rheumatoid arthritis (RA) fatigue is not being well-managed currently, and evidence of effective interventions is limited. Aerobic exercise may provide benefit to treat fatigue in RA. Therefore, the purpose of this meta-analysis is to analyze the effect of aerobic land-based exercise on fatigue in RA. METHODS: A literature search was conducted using PubMed, Cochrane Library, Embase, and trial registers to identify randomized controlled trials (RCTs) with a supervised land-based aerobic exercise program performed with an intensity between 50% and 90% of maximal heart rate, of at least 15 minutes' duration, performed at least 2 times a week, and lasting for a time period of at least 4 consecutive weeks. Risk of bias was assessed using the Cochrane tool. A meta-analysis of fatigue outcomes was performed by calculating the standardized mean difference (SMD) using a random-effects model. RESULTS: Five RCTs were included. None of the trials selected patients with RA for having fatigue. Risk of bias was low in 3 RCTs and unclear in 2. Land-based aerobic exercise programs had a positive effect on fatigue in RA compared to no exercise at 12 weeks, SMD -0.31 (95% confidence interval [95% CI] -0.55, -0.06). At 24 weeks, the effect of aerobic land-based exercise was smaller and not statistically significant: SMD -0.15 (95% CI -0.33, 0.02). CONCLUSION: There is evidence with low risk of bias that an aerobic exercise program is effective in reducing fatigue among patients with RA, especially in the short term; however, effects are small. To substantiate the evidence, RCTs should be performed in patients with RA selected for having fatigue.

Septic arthritis caused by Legionella dumoffii in a patient with systemic lupus erythematosus-like disease.

We describe a patient with systemic lupus erythematosus (SLE)-like disease on immunosuppressive treatment who developed septic arthritis of the knee involving Legionella dumoffii. Cultures initially remained negative. A broad-range 16S PCR using synovial fluid revealed L. dumoffii rRNA genes, a finding that was subsequently confirmed by positive Legionella culture results.

Titration of infliximab treatment in rheumatoid arthritis patients based on response patterns.

OBJECTIVES: To observe the course of the disease activity in rheumatoid arthritis (RA) patients treated with the standard infliximab dosing regimen and to adjust treatment guided by the pattern of disease activity. METHODS: All RA patients starting infliximab treatment were included and observed for at least 37 weeks. At infusion 4 (week 14), European League Against Rheumatism response was assessed. In moderate responders the dose was unchanged and the disease activity was carefully observed. In case of stable disease activity, the dose was increased at infusion 5 (week 22). In case of a temporary response the interval was reduced. Paired t-testing was applied to the disease activity score with 28-joint counts (DAS28) at week 22 and study endpoint. RESULTS: A total of 76 patients were included. Response after 14 weeks: good 22 (29%) patients, moderate 26 (34%) patients, and non-response in 21 patients. Seven patients (9%) dropped out before week 14 due to adverse events (5) or patients' initiative (2). In patients with moderate response, the following disease course between infusion 4 and 5 was observed: improvement to good response 6, temporary response 6, stable disease activity 6, drop out 8. In moderate responders, interval reduction and dose increase resulted in a decrease in mean DAS28 from 5.1 to 3.6 [P = 0.005, mean interval 5.6 weeks, mean infliximab dose 4.8 mg/kg/8 week (endpoint)] and from 4.1 to 3.6 [P = 0.04, mean infliximab dose 7.3 mg/kg/8 week (endpoint)], respectively. CONCLUSION: Three different patterns of disease activity were observed in moderate responders after 14 weeks of infliximab treatment, i.e. further improvement, no change in disease activity or a temporary response. Both interval reduction and dose increase significantly reduced disease activity, however, with different mean infliximab dosages. In good responders the response was often sustained over follow-up, whereas non-responders showed modest or no improvement despite dose adjustments.

Observational study on efficacy, safety, and drug survival of anakinra in rheumatoid arthritis patients in clinical practice.

BACKGROUND: The efficacy and safety of anakinra, a recombinant human interleukin 1 (IL1) receptor antagonist used in rheumatoid arthritis, has been documented in five randomised controlled studies. However, long term post-marketing efficacy data are lacking. OBJECTIVE: To evaluate the efficacy, safety, and drug survival of anakinra in clinical practice. METHODS: All patients with rheumatoid arthritis who started anakinra in six hospitals between May 2002 and February 2004 were included in a two year prospective, in part retrospective, cohort study. Efficacy was assessed using the 28 joint disease activity score (DAS28) and the EULAR response criteria. Safety was evaluated using the common toxicity criteria. Drug survival and prognostic factors were analysed using Kaplan-Meier and Cox proportional hazard analyses. RESULTS: After three months, 55% of the patients (n = 146) showed a response (43% moderate, 12% good). A subset of patients continuing anakinra after 18 months had a sustained clinical response compared with patients who switched to other disease modifying antirheumatic drug treatment (DAS28 improvement, 2.46 v 1.79). Drug survival was 78%, 54%, and 14% after three, six, and 24 months, respectively. The reason for discontinuation was lack of efficacy in 78% and adverse events in 22%. Except for higher drug survival in women (odds ratio = 0.51, 95% confidence interval, 0.27 to 0.97), no prognostic factors were found. Adverse events were reported 206 times in 111 patients, the most common being injection site reactions (36%). Serious adverse events occurred in 12% of the patients, with one classified as related. CONCLUSIONS: The short term efficacy and safety profile of anakinra are comparable to those found in randomised clinical studies. However, the drug survival of anakinra after two years is low, mostly because of lack of efficacy.

The influence of previous and concomitant leflunomide on the efficacy and safety of infliximab therapy in patients with rheumatoid arthritis; a longitudinal observational study.

OBJECTIVE: To investigate the influence of previous and concomitant leflunomide on the efficacy and safety of infliximab therapy in rheumatoid arthritis (RA) and to compare it to infliximab in combination with other disease-modifying anti-rheumatic drugs. METHODS: RA patients starting infliximab therapy were prospectively followed from January 2000. Every 3 months data were collected regarding disease activity (DAS28), adverse events and treatment changes. In the primary analyses all patients were classified into a leflunomide group (LEF group) if they had used leflunomide during infliximab therapy or within 6 months prior to starting infliximab therapy, the latter because of the long half-life of leflunomide. All other patients were considered as controls (non-LEF group). Secondary drug survival analyses were performed with the LEF group consisting only of patients on active leflunomide at the start of infliximab (active LEF group). RESULTS: A total of 162 RA patients started infliximab therapy (57 in the LEF group, 105 in the non-LEF group). No statistically significant differences in baseline characteristics were observed between the groups. Maximum follow-up time was 46 months for both groups. No differences in drug survival, disease activity or adverse events were observed between the groups. In both groups an increase in patients positive for antinuclear antibodies (ANA) was seen. ANA positivity at start did not predict DAS28 or the occurrence of adverse events. Secondary drug survival analyses showed no differences between the active LEF group and the non-LEF group. CONCLUSION: The results indicate that the administration of infliximab after or simultaneously with leflunomide is safe and efficacious in RA patients.

Survival during treatment with tumour necrosis factor blocking agents in rheumatoid arthritis.

Tumour necrosis factor (TNF) blocking agents are an important advance in the clinical treatment of rheumatoid arthritis (RA). They were introduced into clinical practice while limited safety information was available. This means that intensive monitoring is needed early in the life cycle of these new drugs. Setting up large cohort studies to monitor efficacy, safety, and tolerability in long term use of these so-called biological agents will provide information about the consequences of using TNF blocking agents in chronic rheumatic disease like RA. Currently, a Dutch multicentre registry on biological agents in RA is being set up. This study aimed at investigating the efficacy and toxicity of TNF blocking agents in patients with RA at one participating academic centre by a drug survival analysis. Since 1997 230 patients with RA at the centre have been treated with TNF blocking agents for the first time (94 with adalimumab, 120 with infliximab, and 16 with etanercept). No differences in drug survival between the three TNF blocking agents were found despite the diversity in selection and patient numbers. Adverse events which occurred, leading to discontinuation, were similar to those from previous reports.