Simone L. Gorter

Current evidence for the management of rheumatoid arthritis with glucocorticoids: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis

Glucocorticoids (GCs) rapidly reduce disease activity in early and advanced rheumatoid arthritis (RA). This systematic review on behalf of the task force on recommendations for the management of RA addresses the efficacy of GCs in RA. A literature search was performed in Medline, Embase, the Cochrane database, and the ACR/EULAR abstracts 2007 and 2008 on a set of questions relating to the use of GCs in RA. Eleven publications (including three Cochrane reviews comprising 33 trials) that met the criteria for detailed assessment were found. Robust evidence that GCs are effective as bridging therapy was obtained. The addition of GCs, to either standard synthetic disease-modifying antirheumatic drug (DMARD) monotherapy or combinations of synthetic DMARDs, yields clinical benefits and inhibition of radiographic progression that may extend over many years. In early RA, the addition of low-dose GCs (<7.5 mg/day) to DMARDs leads to a reduction in radiographic progression; in longstanding RA, GCs (up to 15 mg/day) improve disease activity. There is some evidence that appropriate timing of GC administration may result in less morning stiffness. Only indirect information was found on the best tapering strategy, supporting the general view that GCs should be tapered slowly in order to avoid clinical relapses. GCs are effective in relieving signs and symptoms and inhibiting radiographic progression, either as monotherapy or in combination with synthetic DMARD monotherapy or combination therapy.

Factors Associated With Treatment Response to Etanercept in Juvenile Idiopathic Arthritis

CONTEXT Since the introduction of biologic therapies, the pharmacological treatment approach for juvenile idiopathic arthritis (JIA) has changed substantially, with achievement of inactive disease as a realistic goal. OBJECTIVE To determine the response to therapy after initiation of etanercept therapy among patients with JIA and to examine the association between baseline factors and response to etanercept treatment. DESIGN, SETTING, AND PATIENTS The Arthritis and Biologicals in Children Register, an ongoing prospective observational study since 1999, includes all Dutch JIA patients who used biologic agents. All biologically naive patients who started etanercept before October 2009 were included, with follow-up data to January 2011. Among the 262 patients, 185 (71%) were female, 46 (18%) had systemic-onset, and the median age at initiation of etanercept treatment was 12.4 years. MAIN OUTCOME MEASURES Excellent response (inactive disease or discontinuation earlier due to disease remission), intermediate response (more than 50% improvement from baseline, but no inactive disease), and poor response (less than 50% improvement from baseline or discontinuation earlier due to ineffectiveness or intolerance) evaluated 15 months after initiation of etanercept. RESULTS At 15 months after treatment initiation, 85 patients (32%) were considered excellent responders; 92 (36%), intermediate responders; and 85 (32%), poor responders. Compared with an intermediate or poor response, an excellent response was associated with lower baseline disability score (range, 0-3 points, with 0 being the best score; adjusted odds ratio [OR] per point increase, 0.49; 95% CI, 0.33-0.74); fewer disease-modifying antirheumatic drugs (DMARD) (including methotrexate) used before initiating etanercept (adjusted OR per DMARD used, 0.64; 95% CI, 0.43-0.95), and younger age at onset (adjusted OR per year increase, 0.92; 95% CI, 0.84-0.99). Compared with an intermediate or excellent response, a poor response was associated with systemic JIA (adjusted OR systemic vs nonsystemic categories, 2.92; 95% CI, 1.26-6.80), and female sex (adjusted OR female vs male, 2.16; 95% CI, 1.12-4.18). Within the first 15 months of etanercept treatment, 119 patients experienced 1 or more infectious, noninfectious, or serious adverse events, including 37 among those with an excellent response, 36 with an intermediate response, and 46 with a poor response. Within the first 15 months of treatment, 61 patients discontinued etanercept treatment, including 4 with an excellent response, 0 with an intermediate response, and 57 with a poor response. In a secondary analysis of 262 patients with a median follow-up of 35.6 months after initiation of etanercept, a range of 37% to 49% of patients reached inactive disease. The mean adherence to etanercept was 49.2 months (95% CI, 46.4-52.0) for patients with an excellent response after 15 months, 47.5 months (95% CI, 44.9-50.1) for patients with an intermediate response, and 17.4 months (95% CI, 13.6-21.2) for patients with a poor response. CONCLUSIONS Among patients with JIA who initiated treatment with etanercept, one-third achieved an excellent response, one-third an intermediate response, and one-third a poor response to therapy. Achievement of an excellent response was associated with low baseline disability scores, DMARDs used before initiating etanercept, and younger age at onset of JIA. Achievement of a poor treatment response was associated with systemic JIA and female sex.

Unannounced standardised patients in real practice: a systematic literature review.

Background No attempt has been made to give a systematic overview of the innovative use of unannounced or incognito standardised patients.

Tumor necrosis factor-blocking agents for children with enthesitis-related arthritis--data from the dutch arthritis and biologicals in children register, 1999-2010

Objective. To evaluate the effectiveness and safety of biological agents in children with enthesitis-related arthritis (ERA). Methods. All patients with ERA in whom a biological agent was initiated between 1999 and 2010 were selected from the Dutch Arthritis and Biologicals in Children (ABC) register. In this ongoing multicenter observational register, data on the course of the disease and medication use are retrieved prospectively at the start of the biological agent, after 3 months, and yearly thereafter. Inactive disease was assessed in accordance with the Wallace criteria. Results. Twenty-two patients with ERA started taking 1 or more biological agents: 20 took etanercept, 2 took adalimumab (1 switched from etanercept to adalimumab), and 2 took infliximab (1 switched from etanercept to infliximab). Characteristics: 77% were male, 77% had enthesitis, 68% were HLA-B27-positive. The median age of onset was 10.4 (IQR 9.4–12.0) years; median followup from the start of the biological agent was 1.2 (IQR 0.5–2.4) years. Intention-to-treat analysis shows that inactive disease was achieved in 7 of 22 patients (32%) after 3 months, 5 of 13 patients (38%) after 15 months, and 5 of 8 patients (63%) after 27 months of treatment. Two patients discontinued etanercept because of ineffectiveness, and switched to adalimumab (inactive disease achieved) or infliximab (decline in joints with arthritis after 3 months of treatment). One patient discontinued etanercept because of remission, but had flare and restarted treatment, with good clinical response. No serious adverse events occurred. Conclusion. Tumor necrosis factor (TNF)-blocking agents seem effective and safe for patients with ERA that was previously unresponsive to 1 or more DMARD. However, a sustained disease-free state could not be achieved, and none discontinued TNF-blocking agents successfully.

Psoriatic arthritis: performance of rheumatologists in daily practice

Objectives: To assess, using standardised patients (SPs), how rheumatologists diagnose psoriatic arthritis, whether the diagnostic efficiency is influenced by specific characteristics of the rheumatologists, and to study the relationship with costs. Methods: Twenty three rheumatologists were each visited by one of two SPs (one male, one female) presenting as a patient with psoriatic arthritis. SPs remained incognito for all meetings for the duration of the study. Immediately after the encounter, SPs completed case-specific checklists on the medical content of the encounter. Information on ordered laboratory and imaging tests was obtained from each hospital. Results: Fourteen rheumatologists diagnosed psoriatic arthritis correctly. They inspected the skin for psoriatic lesions more often than those rheumatologists who established other diagnoses. Rheumatologists diagnosing psoriatic arthritis spent more on additional laboratory and imaging investigations. These were carried out after the diagnosis to confirm it and to record the extent and severity of the disease. No differences in type of practice, number of outpatients seen each week, working experience, or sex were found between rheumatologists who made the correct diagnosis and those who made other diagnoses. The correct diagnosis was more often missed by rheumatologists who saw the male SP, who presented with clear distal interphalangeal DIP joint arthritis only, causing confusion with osteoarthritis of the DIP joints. Conclusion: There is a considerable amount of variation in the delivery of care among rheumatologists who see an SP with psoriatic arthritis. Rheumatologists focusing too much on the most prominent features (DIP joint arthritis) sometimes seem to forget “the hidden (skin) symptoms”.

Effects of the Live Attenuated Measles-Mumps-Rubella Booster Vaccination on Disease Activity in Patients With Juvenile Idiopathic Arthritis: A Randomized Trial

IMPORTANCE The immunogenicity and the effects of live attenuated measles-mumps-rubella (MMR) vaccination on disease activity in patients with juvenile idiopathic arthritis (JIA) are matters of concern, especially in patients treated with immunocompromising therapies. OBJECTIVES To assess whether MMR booster vaccination affects disease activity and to describe MMR booster immunogenicity in patients with JIA. DESIGN, SETTING, AND PARTICIPANTS Randomized, multicenter, open-label clinical equivalence trial including 137 patients with JIA aged 4 to 9 years who were recruited from 5 academic hospitals in The Netherlands between May 2008 and July 2011. INTERVENTION Patients were randomly assigned to receive MMR booster vaccination (n=68) or no vaccination (control group; n=69). Among patients taking biologics, these treatments were discontinued at 5 times their half-lives prior to vaccination. MAIN OUTCOMES AND MEASURES Disease activity as measured by the Juvenile Arthritis Disease Activity Score (JADAS-27), ranging from 0 (no activity) to 57 (high activity). Disease activity in the year following randomization was compared between revaccinated patients and controls using a linear mixed model. A difference in JADAS-27 of 2.0 was the equivalence margin. Primary immunogenicity outcomes were seroprotection rates and MMR-specific antibody concentrations at 3 and 12 months. RESULTS Of 137 randomized patients, 131 were analyzed in the modified intention-to-treat analysis, including 60 using methotrexate and 15 using biologics. Disease activity during complete follow-up did not differ between 63 revaccinated patients (JADAS-27, 2.8; 95% CI, 2.1-3.5) and 68 controls (JADAS-27, 2.4; 95% CI, 1.7-3.1), with a difference of 0.4 (95% CI, -0.5 to 1.2), within the equivalence margin of 2.0. At 12 months, seroprotection rates were higher in revaccinated patients vs controls (measles, 100% vs 92% [95% CI, 84%-99%]; mumps, 97% [95% CI, 95%-100%] vs 81% [95% CI, 72%-93%]; and rubella, 100% vs 94% [95% CI, 86%-100%], respectively), as were antibody concentrations against measles (1.63 vs 0.78 IU/mL; P = .03), mumps (168 vs 104 RU/mL; P = .03), and rubella (69 vs 45 IU/mL; P = .01). Methotrexate and biologics did not affect humoral responses, but low patient numbers precluded definite conclusions. CONCLUSION AND RELEVANCE Among children with JIA who had undergone primary immunization, MMR booster vaccination compared with no booster did not result in worse JIA disease activity and was immunogenic. Larger studies are needed to assess MMR effects in patients using biologic agents. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00731965.

Effects of the Live Attenuated Measles-Mumps-Rubella Booster Vaccination on Disease Activity in Patients With Juvenile Idiopathic Arthritis

IMPORTANCE The immunogenicity and the effects of live attenuated measles-mumps-rubella (MMR) vaccination on disease activity in patients with juvenile idiopathic arthritis (JIA) are matters of concern, especially in patients treated with immunocompromising therapies. OBJECTIVES To assess whether MMR booster vaccination affects disease activity and to describe MMR booster immunogenicity in patients with JIA. DESIGN, SETTING, AND PARTICIPANTS Randomized, multicenter, open-label clinical equivalence trial including 137 patients with JIA aged 4 to 9 years who were recruited from 5 academic hospitals in The Netherlands between May 2008 and July 2011. INTERVENTION Patients were randomly assigned to receive MMR booster vaccination (n=68) or no vaccination (control group; n=69). Among patients taking biologics, these treatments were discontinued at 5 times their half-lives prior to vaccination. MAIN OUTCOMES AND MEASURES Disease activity as measured by the Juvenile Arthritis Disease Activity Score (JADAS-27), ranging from 0 (no activity) to 57 (high activity). Disease activity in the year following randomization was compared between revaccinated patients and controls using a linear mixed model. A difference in JADAS-27 of 2.0 was the equivalence margin. Primary immunogenicity outcomes were seroprotection rates and MMR-specific antibody concentrations at 3 and 12 months. RESULTS Of 137 randomized patients, 131 were analyzed in the modified intention-to-treat analysis, including 60 using methotrexate and 15 using biologics. Disease activity during complete follow-up did not differ between 63 revaccinated patients (JADAS-27, 2.8; 95% CI, 2.1-3.5) and 68 controls (JADAS-27, 2.4; 95% CI, 1.7-3.1), with a difference of 0.4 (95% CI, -0.5 to 1.2), within the equivalence margin of 2.0. At 12 months, seroprotection rates were higher in revaccinated patients vs controls (measles, 100% vs 92% [95% CI, 84%-99%]; mumps, 97% [95% CI, 95%-100%] vs 81% [95% CI, 72%-93%]; and rubella, 100% vs 94% [95% CI, 86%-100%], respectively), as were antibody concentrations against measles (1.63 vs 0.78 IU/mL; P = .03), mumps (168 vs 104 RU/mL; P = .03), and rubella (69 vs 45 IU/mL; P = .01). Methotrexate and biologics did not affect humoral responses, but low patient numbers precluded definite conclusions. CONCLUSION AND RELEVANCE Among children with JIA who had undergone primary immunization, MMR booster vaccination compared with no booster did not result in worse JIA disease activity and was immunogenic. Larger studies are needed to assess MMR effects in patients using biologic agents. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00731965.

Approaches to professional behaviour assessment: tools in the professionalism toolbox.

There is general agreement that professionalism and professional behaviour should be (formatively and summatively) assessed, but consensus on how this should be done is still lacking. After discussing some of the remaining issues and questions regarding professionalism assessment, this article discusses the importance of qualitative comments to the assessment of professional behaviour, focuses on the currently most frequently used tools, as well as stresses the need for triangulation (combining) of these tools.

Reproducibility of clinical performance assessment in practice using incognito standardized patients

Background  The reproducibility of authentic assessment methods has been investigated for objective structured clinical examinations (OSCEs) and video assessment in general practice, but not for assessment with incognito standardized patients.

Trends in prescription of biological agents and outcomes of juvenile idiopathic arthritis: results of the Dutch national Arthritis and Biologics in Children Register

Background Treatment of juvenile idiopathic arthritis (JIA) has changed dramatically since the introduction of biological agents in 1999. Objective To evaluate trends in prescription patterns of biological agents and the subsequent outcome of JIA. Methods The Arthritis and Biologics in Children register (multicentre prospective observational study) aimed to include all consecutive patients with JIA in the Netherlands who had started biological agents since 1999. Patients were divided according to year of introduction of first biological agent. Patient characteristics at introduction of the first biological agent and its effectiveness were analysed over 12 years. Results 335 patients with non-systemic JIA and 86 patients with systemic JIA started a biological agent between 1999 and 2010. Etanercept remained the most often prescribed biological agent for non-systemic JIA; anakinra became first choice for systemic JIA. The use of systemic glucocorticoids and synthetic disease-modifying antirheumatic drugs before biological agents decreased. During these 12 years of observation, biological agents were prescribed earlier in the disease course and to patients with lower baseline JADAS (Juvenile Arthritis Disease Activity Score) disease activity. All baseline disease activity parameters were lowered in patients with non-systemic JIA. In systemic JIA, prescription patterns changed towards very early introduction of biological agents (median 0.4 years of disease duration) in patients with a low number of joints with active arthritis and high erythrocyte sedimentation rates. These changes for both systemic and non-systemic JIA resulted in more patients with inactive disease after 3 and 15 months of treatment. Conclusions Biological agents are increasingly prescribed, earlier in the disease and in patients with JIA with lower disease activity. These changes are accompanied by better short-term disease outcomes.