Jaap Fransen

2013 Classification Criteria for Systemic Sclerosis: An American College of Rheumatology/European League Against Rheumatism Collaborative Initiative

OBJECTIVE The 1980 American College of Rheumatology (ACR) classification criteria for systemic sclerosis (SSc) lack sensitivity for early SSc and limited cutaneous SSc. The present work, by a joint committee of the ACR and the European League Against Rheumatism (EULAR), was undertaken for the purpose of developing new classification criteria for SSc. METHODS Using consensus methods, 23 candidate items were arranged in a multicriteria additive point system with a threshold to classify cases as SSc. The classification system was reduced by clustering items and simplifying weights. The system was tested by 1) determining specificity and sensitivity in SSc cases and controls with scleroderma-like disorders, and 2) validating against the combined view of a group of experts on a set of cases with or without SSc. RESULTS It was determined that skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for the patient to be classified as having SSc; if that is not present, 7 additive items apply, with varying weights for each: skin thickening of the fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynauds phenomenon, and SSc-related autoantibodies. Sensitivity and specificity in the validation sample were, respectively, 0.91 and 0.92 for the new classification criteria and 0.75 and 0.72 for the 1980 ACR classification criteria. All selected cases were classified in accordance with consensus-based expert opinion. All cases classified as SSc according to the 1980 ACR criteria were classified as SSc with the new criteria, and several additional cases were now considered to be SSc. CONCLUSION The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria for SSc and should allow for more patients to be classified correctly as having the disease.

2013 classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative

Objective The 1980 American College of Rheumatology (ACR) classification criteria for systemic sclerosis (SSc) lack sensitivity for early SSc and limited cutaneous SSc. The present work, by a joint committee of the ACR and the European League Against Rheumatism (EULAR), was undertaken for the purpose of developing new classification criteria for SSc. Methods Using consensus methods, 23 candidate items were arranged in a multicriteria additive point system with a threshold to classify cases as SSc. The classification system was reduced by clustering items and simplifying weights. The system was tested by (1) determining specificity and sensitivity in SSc cases and controls with scleroderma-like disorders, and (2) validating against the combined view of a group of experts on a set of cases with or without SSc. Results It was determined that skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for the patient to be classified as having SSc; if that is not present, seven additive items apply, with varying weights for each: skin thickening of the fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynauds phenomenon, and SSc-related autoantibodies. Sensitivity and specificity in the validation sample were, respectively, 0.91 and 0.92 for the new classification criteria and 0.75 and 0.72 for the 1980 ACR classification criteria. All selected cases were classified in accordance with consensus-based expert opinion. All cases classified as SSc according to the 1980 ACR criteria were classified as SSc with the new criteria, and several additional cases were now considered to be SSc. Conclusions The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria for SSc and should allow for more patients to be classified correctly as having the disease.

Physical Exercise in Cancer Patients During and After Medical Treatment: A Systematic Review of Randomized and Controlled Clinical Trials

PURPOSE To systematically review the methodologic quality of, and summarize the evidence from trials examining the effectiveness of physical exercise in improving the level of physical functioning and psychological well-being of cancer patients during and after medical treatment. METHODS Thirty-four randomized clinical trials (RCTs) and controlled clinical trials were identified, reviewed for substantive results, and assessed for methodologic quality. RESULTS Four of 34 trials met all (seven of seven) methodologic criteria on the Delphi criteria list. Failure to conceal the sequencing of treatment allocation before patient recruitment, failure to blind the outcome assessor, and failure to employ an intention-to-treat analysis strategy were the most prevalent methodologic shortcomings. Various exercise modalities have been applied, differing in content, frequency, intensity, and duration. Positive results have been observed for a diverse set of outcomes, including physiologic measures, objective performance indicators, self-reported functioning and symptoms, psychological well-being, and overall health-related quality of life. CONCLUSION The trials reviewed were of moderate methodologic quality. Together they suggest that cancer patients may benefit from physical exercise both during and after treatment. However, the specific beneficial effects of physical exercise may vary as a function of the stage of disease, the nature of the medical treatment, and the current lifestyle of the patient. Future RCTs should use larger samples, use appropriate comparison groups to rule out the possibility of an attention-placebo effect, use a comparable set of outcome measures, pay greater attention to issues of motivation and adherence of patients participating in exercise programs, and examine the effect of exercise on cancer survival.

Defining minimal disease activity in psoriatic arthritis: a proposed objective target for treatment

Objective: To create minimal disease activity (MDA) criteria for psoriatic arthritis (PsA). With recent therapeutic advances, this is now a goal for treatment and may represent a measure to compare therapies. It defines a satisfactory state of disease activity rather than a change, and encompasses all aspects of the disease. Methods: 40 patient profiles were sampled from an observational PsA database. Sixty experts in PsA classified these as in MDA or not. A consensus of ⩾70% was accepted, identifying 13 profiles in MDA. Summary statistics created possible cut-off points for the definition. Considering the number of measures that must be met, 35 candidate definitions were created and tested using receiver operating characteristic curves (ROC) for sensitivity and specificity. Results: Four candidate definitions showed high area under the curve values on ROC testing. Definitions with high outlying values were excluded as they were not considered to represent MDA. Aiming for high specificity to reduce false positives resulted in a preference for the following definition: “A patient is classified as achieving MDA when meeting 5 of the 7 following criteria: tender joint count ⩽1; swollen joint count ⩽1; Psoriasis Activity and Severity Index ⩽1 or body surface area ⩽3; patient pain visual analogue score (VAS) ⩽15; patient global disease activity VAS ⩽20; health assessment questionnaire ⩽0.5; tender entheseal points ⩽1”. Conclusion: This study provides the first definition of a “state” of MDA in PsA and defines a target for treatment. It must now be validated in other populations and tested in clinical trials.

The efficacy of anti‐TNF in rheumatoid arthritis, a comparison between randomised controlled trials and clinical practice

Background: Randomised controlled trials (RCTs) evaluating the efficacy of antagonists to tumour necrosis factor α (TNFα) showed high response percentages in the groups treated with active drugs. Objective: To compare the efficacy of anti-TNF treatments for rheumatoid arthritis (RA) patients in RCTs and in daily clinical practice, with an emphasis on the efficacy for patients eligible and not eligible for RCTs of anti-TNF treatments. Methods: First, randomised placebo-controlled trials written in English for etanercept, infliximab and adalimumab for patients with RA were selected by a systematic review. Second, the DREAM (Dutch Rheumatoid Arthritis Monitoring) register with patients starting for the first time on one of the TNF-blocking agents was used. Patient characteristics, doses of medication and co-medication as well as the ACR20 response percentages were compared between RCTs and DREAM data, stratified for trial eligibility. Results: In 10 of 11 comparisons, the ACR20 response percentages were lower in daily clinical practice than in the RCT active drug group, which was significant in five of 11 comparisons. Only 34–79% of DREAM patients fulfilled the selection criteria for disease activity in the several RCTs examined. DREAM patients eligible for RCTs had higher response percentages than ineligible DREAM patients. ACR20 response percentages of eligible DREAM patients were comparable with the ACR20 response percentages of the RCT active drug group in 10 of 11 comparisons. Conclusion: The efficacy of TNF-blocking agents in RCTs exceeded the efficacy of these drugs in clinical practice. However, in clinical practice more patients with lower disease activity were treated with TNF-blocking agents compared with those treated in RCTs. For daily practice patients who were eligible for RCTs, responses were more similar to responses reached in RCTs.

The development of candidate composite disease activity and responder indices for psoriatic arthritis (GRACE project)

Objective To develop new composite disease activity indices for psoriatic arthritis (PsA). Methods Data from routine clinic visits at multiple centres were collected in a systematic manner. Data included all domains identified as important in randomised controlled trials in PsA. Decisions to change treatment were used as surrogates for high disease activity. New indices were developed by multiple linear regression (psoriatic arthritis disease activity score: PASDAS) and empirically, utilising physician-defined cut-offs for disease activity (arithmetic mean of desirability functions: AMDF). These were compared with existing composite measures: Composite Psoriatic arthritis Disease Activity Index (CPDAI), Disease Activity for PSoriatic Arthritis (DAPSA), and Disease Activity Score for rheumatoid arthritis (DAS28). Results 161/503 (32%) subjects had treatment changes. Although all measures performed well, compared with existing indices, PASDAS was better able to discriminate between high and low disease activity (area under receiver operating curves (ROC)) curve with 95% CI: PASDAS 0.773 (0.723, 0.822); AMDF 0.730 (0.680, 0.780); CPDAI 0.719 (0.668, 0.770); DAPSA 0.710 (0.654, 0.766); DAS28 0.736 (0.680, 0.792). All measures were able to discriminate between disease activity states in patients with oligoarthritis, although area under the receiver operating curves (AUC) were generally smaller. In patients with severe skin disease (psoriasis area and severity index >10) both nonparametric and AUC curve statistics were nonsignificant for all measures. Conclusions Two new composite measures to assess disease activity in PsA have been developed. Further testing in other datasets, including comparison with existing measures, is required to validate these instruments.

Performance of response criteria for assessing peripheral arthritis in patients with psoriatic arthritis: analysis of data from randomised controlled trials of two tumour necrosis factor inhibitors

Background: In recent clinical trials in patients with psoriatic arthritis (PsA), the response criteria and disease activity measures that have been used were those developed for rheumatoid arthritis. However, these have not yet been validated in PsA. Objective: To compare the responsiveness and discriminative capacity of the psoriatic arthritis response criteria (PsARC), American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response criteria and the Disease Activity Score (DAS) and core-set measures in patients with PsA and peripheral arthritis, using the data from two randomised placebo-controlled trials of tumour necrosis factor inhibitors. Methods: In an infliximab trial, 104 patients with active PsA were randomised to receive placebo or infliximab for 16 weeks. In an etanercept trial, 60 patients with active PsA were randomised to receive placebo or etanercept for 12 weeks. Data from baseline and the end of the intervention phase were used from each study. Responsiveness was assessed using the standardised response mean and effect size. Capacity to discriminate between the active drug and placebo was assessed using t values or a χ2 test. Measures were ranked in order of their t value or χ2 value. Results: The EULAR criteria performed better in discriminating the active drug from placebo than the ACR20 improvement criteria, which in turn performed better than the PsARC. It was also found that the pooled indices (DAS and DAS28) were generally more responsive, and performed better in discriminating active drug from placebo, than the single core-set measures. Conclusion: Response criteria and pooled indices developed for rheumatoid arthritis are useful for the assessment of arthritis in PsA clinical trials.

Physical and psychosocial correlates of severe fatigue in rheumatoid arthritis

OBJECTIVES Fatigue is a frequently experienced and patient-relevant complaint in RA. Disease activity, anaemia and pain are regarded as disease-related factors that may lead to fatigue in RA. However, psychosocial factors may also play a role in maintaining severe fatigue. The objectives of this study were to determine the prevalence of severe fatigue in RA patients, to study patient perceptions of fatigue and to determine which disease-related factors and psychosocial factors are independently associated with fatigue severity. METHODS For this study consecutive RA outpatients were enrolled (n = 228). The patients filled out questionnaires regarding fatigue using the Checklist Individual Strength (CIS), including psychosocial factors, pain and disability. The clinical data that were collected included ESR, CRP, haemoglobin level and 28-joint disease activity score (DAS-28). Chunk-wise backward linear regression was used for analysis. RESULTS Severe fatigue (CIS > or = 35) was experienced by 42% of the RA patients, and they perceived their fatigue as frustrating or exhausting. The severely fatigued RA patients scored worse on all measured psychosocial items, compared with patients without severe fatigue. Pain severity, role functioning, depressive mood, self-efficacy on fatigue, worrying, helplessness and non-restorative sleep were the factors most strongly associated with fatigue level. CONCLUSIONS A considerable proportion of RA patients had severe fatigue, with fatigue levels similar to chronic fatigue syndrome. Fatigue in RA was related to pain and functioning, not inflammation, as disease-related factors and to several psychosocial factors including coping and cognitions concerning fatigue.

The Disease Activity Score and the EULAR Response Criteria

The Disease Activity Score (DAS), its modified version the DAS28, and the DAS-based European League Against Rheumatism (EULAR) response criteria are well-known measures of disease activity in rheumatoid arthritis (RA). The DAS is a clinical index of RA disease activity that combines information from swollen joints, tender joints, the acute phase response, and general health. The EULAR response criteria classify individual patients as non-, moderate, or good responders, depending on the extent of change and the level of disease activity reached. The DAS, DAS28, and EULAR response criteria have been validated extensively. For daily practice, it has been shown that a tight control strategy, including measurement of disease activity using the DAS and planned adjustment of antirheumatic medication, is an effective strategy for RA. This article summarizes the development and validation of the DAS and DAS28 and their use in clinical trials and practice for the clinician.

Performance of four current risk algorithms in predicting cardiovascular events in patients with early rheumatoid arthritis

Objective This study was undertaken to assess the predictive ability of 4 established cardiovascular (CV) risk models for the 10-year risk of fatal and non-fatal CV diseases in European patients with rheumatoid arthritis. Methods Prospectively collected data from the Nijmegen early rheumatoid arthritis (RA) inception cohort was used. Discriminatory ability for CV risk prediction was estimated by the area under the receiver operating characteristic curve. Calibration was assessed by comparing the observed versus expected number of events using Hosmer-Lemeshov tests and calibration plots. Sensitivity and specificity were calculated for the cut-off values of 10% and 20% predicted risk. Results Areas under the receiver operating characteristic curve were 0.78–0.80, indicating moderate to good discrimination between patients with and without a CV event. The CV risk models Systematic Coronary Risk Evaluation (SCORE), Framingham risk score (FRS) and Reynolds risk score (RRS) primarily underestimated CV risk at low and middle observed risk levels, and mostly overestimated CV risk at higher observed risk levels. The QRisk II primarily overestimated observed CV risk. For the 10% and 20% cut-off values used as indicators for CV preventive treatment, sensitivity ranged from 68–87% and 40–65%, respectively and specificity ranged from 55–76% and 77–88%, respectively. Depending on the model, up to 32% of observed CV events occurred in patients with RA who were classified as low risk (<10%) for CV disease. Conclusions Established risk models generally underestimate (Systematic Coronary Risk Evaluation score, Framingham Risk Score, Reynolds risk score) or overestimate (QRisk II) CV risk in patients with RA.