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A C Verhoeven

Publications and source records attributed to A C Verhoeven.

17 recordsLinked to original sources
PubMed2003

Influence of glucocorticoids and disease activity on total and high density lipoprotein cholesterol in patients with rheumatoid arthritis.

BACKGROUND: Glucocorticoids induce hypercholesterolaemia, a cardiovascular risk factor, in patients with diseases other than rheumatoid arthritis (RA), but the data in RA are contradictory. OBJECTIVE: To determine the effects of antirheumatic treatment, including prednisolone (combination) therapy on total and high density lipoprotein (HDL) cholesterol levels in RA, taking disease activity into account. METHODS: HDL cholesterol and total cholesterol levels were determined in:(a) established RA (b) two cohorts with early active RA, (c) a previously conducted 56 week trial among patients with early RA comparing the value of intensive combination therapy (that included glucocorticoids) with sulfasalazine alone (COBRA trial). RESULTS: In established RA total cholesterol levels were only slightly raised, irrespective of disease activity. However, HDL cholesterol was significantly higher in patients in remission than in patients with active disease. In contrast, in active early RA at baseline total cholesterol was low normal: between 4.6 and 5.1 mmol/l in the different populations. The level of HDL cholesterol was highly dependent on the duration of storage. In both COBRA groups total cholesterol increased by a mean of 0.6 mmol/l. HDL cholesterol increased by more than 50% after treatment, leading to an improvement of the total cholesterol/HDL ratio (atherogenic index). This increase (and index improvement) was much more rapid in the group receiving combination treatment. A similar pattern was seen in the 2001 cohort with early RA. In all the groups with active disease HDL and total cholesterol levels correlated inversely with disease activity. CONCLUSION: In established, but especially in early RA, disease activity is accompanied by atherogenic lipid levels. This dyslipidaemia can be rapidly reversed by aggressive antirheumatic treatment including glucocorticoids.

Adult↗
PubMed2001

American College of Rheumatology criteria for improvement in rheumatoid arthritis should only be calculated from scores that decrease on improvement.

OBJECTIVE: Change in a patient's condition is expressed as a percentage of the baseline value for a core set of measures in the American College of Rheumatology (ACR) improvement criteria for rheumatoid arthritis (RA), and this is used as the basis to decide whether a patient has improved. The result is dependent on whether the underlying measure has a score that increases or decreases on improvement. We examined the importance of this effect in the application of the ACR improvement criteria. METHODS: Data were obtained from the COBRA trial, in which 155 patients with early active RA had been randomized to receive either combination treatment with step-down prednisolone, methotrexate, and sulfasalazine or sulfasalazine alone. Patient and physician global assessments were recoded to reflect decreasing scores on improvement. The effects of this difference in scoring systems were compared among 3 response criteria levels (20%, 50%, and 70%) that are currently being used to assess improvement in RA clinical trials. RESULTS: Analyses showed that the effects of a decreasing, versus increasing, score on the designation of improvement cannot be ignored, especially at higher percentages of improvement (e.g., 50%, 70%). CONCLUSION: We recommend that percentage improvement in RA be calculated only on scores that decrease on improvement. When necessary, raw data should be recoded before the ACR improvement criteria are applied.

Anti-Inflammatory Agents↗
PubMed2001

Inflammation and damage in an individual joint predict further damage in that joint in patients with early rheumatoid arthritis.

UNLABELLED: OBJECTIVE; Several factors predict joint damage in early rheumatoid arthritis (RA). In the context of a trial in early RA, we studied the relationship between clinical signs in individual joints and their propensity to develop progressive damage. METHODS: The COBRA (Combinatietherapie Bij Reumatoide Artritis) multicenter trial compared the efficacy of prednisolone, methotrexate, and sulfasalazine against sulfasalazine alone in 155 patients with early RA. Two blinded observers interpreted radiographs in sequence (using the Sharp/Van der Heijde scoring system); in each center, one blinded observer performed clinical assessments every 3 months. The current analysis is based on clinical and radiologic data of the individual metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of 135 patients. Conditional stepwise logistic regression analyzed the relationship between damage (progression) and clinical signs at baseline and followup for each of these joints individually in each patient. RESULTS: Combination therapy strongly retarded the progression of damage. Progression was stronger in patients with rheumatoid factor, HLA-DR4, and high levels of disease activity at baseline. At baseline, 6% of the MCP and PIP joints showed damage; after 1 year, disease had progressed in 10% of these joints. Baseline damage, swelling, or pain in a joint independently and strongly predicted the progression of damage in that joint (P < 0.001). Each additional point in the swelling score (range 0-2) tripled the risk for subsequent progression. Each additional point on the Sharp scale (range 0-8 per joint) and each additional point on the pain scale (range 0-3) doubled the risk. The mean pain and swelling scores over the year were even stronger predictors of damage. CONCLUSION: Local expression of early RA disease activity, both at baseline and at 1-year followup, is strongly related to progression of damage in the individual joint.

Adult↗
PubMed2001

Bone turnover, joint damage and bone mineral density in early rheumatoid arthritis treated with combination therapy including high-dose prednisolone.

OBJECTIVES: Exploration of bone metabolism changes at different levels of disease activity, both with and without oral corticosteroid therapy, and prediction of changes in joint damage and bone density from the observed changes in markers of bone turnover. METHODS: Data analysis from a randomized clinical trial with 155 rheumatoid arthritis (RA) patients; median age 50 yr, early and active disease (diagnosis < 2 yr); one group treated with a combination of sulphasalazine (SSZ; 2000 mg/day), methotrexate (MTX; 7.5 mg/week) and prednisolone (initially 60 mg/day, tapered in six weekly steps to 7.5 mg/day), the other group with SSZ alone. Prednisolone and MTX were tapered and stopped after weeks 28 and 40, respectively, while SSZ was continued. Urine and serum samples were collected at baseline and weeks 16, 28, 40 and 56. Measurements of urinary pyridinoline (PYD) and deoxypyridinoline (DPD) and serum alkaline phosphatase (tAP) and osteocalcin (OC) were performed, as well as standard clinimetry and bone densitometry. RESULTS: Over time and in both treatment groups, bone formation and bone resorption markers showed a pattern similar to erythrocyte sedimentation rate (ESR): a significant decrease compared with baseline and a larger decrease with combined treatment at weeks 16 and 28. PYD excretion, tAP, OC, and joint damage scores were significantly lower in the combined treatment group. Changes in bone density (of spine and hips) did not significantly differ between treatment groups. Mainly cumulative ESR explained progression of joint damage. CONCLUSIONS: Prednisolone and disease-modifying anti-rheumatic drug therapy in patients with early and active RA are both independently associated with decreased levels of urinary excretion of bone collagen resorption markers PYD and DPD. Markers of bone formation and resorption closely followed changes in ESR in both treatment groups. Reduced bone resorption together with reduced bone formation-initially at a somewhat faster pace-resulted in less bone turnover and explain the observed (non-significant and partially reversible) extra bone loss in the lumbar spine associated with prednisolone (combined treatment).

Adult↗
PubMed2000

Factors predicting response to treatment in rheumatoid arthritis: the importance of disease duration.

OBJECTIVE: To use individual patient data from rheumatoid arthritis (RA) clinical trials to identify factors that affect the response to treatment as defined by the American College of Rheumatology (ACR) criteria for improvement (the "ACR response"). METHODS: Primary trial data from 14 diverse, randomized, controlled trials of second-line drugs or devices in RA were analyzed. The trials included 11 methotrexate (MTX) trials (5 placebo controlled and 6 comparative, of which 2 were unpublished), 1 combination trial of cyclosporine plus MTX, 1 induction trial of a combination treatment in early RA (the COBRA trial), and 1 placebo-controlled trial of a new device (Prosorba). Both patient factors and disease activity measures (primarily, items from the ACR core criteria set) were available. RESULTS: A total of 1,435 patients (549 in placebo-controlled trials, 886 in comparative trials) were studied. In both active treatment and placebo groups, disease duration had a strong effect on the likelihood of patient response (e.g., with any active treatment, the response rate was 53% for patients with < or =1 year of disease, 43% for 1-2 years' disease duration, 44% for 2-5 years, 38% for 5-10 years, and 35% for > 10 years; P = 0.001). Decreasing response with greater disease duration was seen during treatment with most of the individual active drugs, as well as with placebo. Other factors decreasing the rate of response to treatment included any prior use of a disease-modifying antirheumatic drug (DMARD), higher disease functional class (according to the Steinbrocker criteria), low disease activity (according to patient's global assessment), and female sex. Each ACR core set variable exhibited a diminished response to treatment in patients with long-standing disease. The difference between active treatment and placebo response rates was not affected by disease duration nor by other factors associated with the ACR response. CONCLUSION: RA patients with longer disease duration do not respond as well to treatment compared with patients with early disease, and female sex, prior DMARD use, disease functional class, and disease activity also have effects on the likelihood of patient response to treatment. This has implications for trial interpretation and for the clinical expectations of RA patients.

Antirheumatic Agents↗
PubMed2000

Responsiveness of the core set, response criteria, and utilities in early rheumatoid arthritis.

OBJECTIVE: Validation of responsiveness and discriminative power of the World Health Organisation/International League of Associations for Rheumatology (WHO/ILAR) core set, the American College of Rheumatology (ACR), and European League for Rheumatology (EULAR) criteria for improvement/response, and other single and combined measures (indices) in a trial in patients with early rheumatoid arthritis (RA). METHODS: Ranking of measures by response (standardised response means and effect sizes) and between-group discrimination (unpaired t test and chi(2) values) at two time points in the COBRA study. This study included 155 patients with early RA randomly allocated to two treatment groups with distinct levels of expected response: combined treatment, high response; sulfasalazine treatment, moderate response. RESULTS: At week 16, standardised response means of core set measures ranged between 0.8 and 3.5 for combined treatment and between 0.4 and 1.2 for sulfasalazine treatment (95% confidence interval +/-0.25). Performance of patient oriented measures (for example, pain, global assessment) was best when the questions were focused on the disease. The most responsive single measure was the patient's assessment of change in disease activity, at 3.5. Patient utility, a generic health status measure, was moderately (rating scale) to poorly (standard gamble) responsive. Response means of most indices (combined measures) exceeded 2.0, the simple count of core set measures improved by 20% was most responsive at 4.1. Discrimination performance yielded similar but not identical results: best discrimination between treatment groups was achieved by the EULAR response and ACR improvement criteria (at 20% and other percentage levels), the pooled index, and the disease activity score (DAS), but also by the Health Assessment Questionnaire (HAQ) and grip strength. CONCLUSIONS: Responsiveness and discrimination between levels of response are not identical concepts, and need separate study. The WHO/ILAR core set comprises responsive measures that discriminate well between different levels of response in early RA. However, the performance of patient oriented measures is highly dependent on their format. The excellent performance of indices such as the ACR improvement and EULAR response criteria confirms that they are the preferred primary end point in RA clinical trials.

Adult↗
PubMed2000

Validity of the MACTAR questionnaire as a functional index in a rheumatoid arthritis clinical trial. The McMaster Toronto Arthritis.

OBJECTIVES: The McMaster Toronto Arthritis patient preference questionnaire (MACTAR) is a functional index that measures change in impaired activities selected by each patient in a baseline interview, and change in rheumatoid arthritis (RA) disease activity. In addition, it contains questions on the state of physical, social and emotional function and overall health, and their relation to RA. We evaluated MACTAR's feasibility and validity (content validity, construct validity, and responsiveness). METHODS: A randomized trial of combined treatment in 155 patients with early RA; patients' mean age at baseline was 50 years and median disease duration since diagnosis was 4 months. RESULTS: Feasibility: MACTAR requires trained interviewers. In the trial, interviews took about 15 min. In longer term followup, activities selected at baseline may become less relevant as the pattern of disability changes. Followup from 153 patients (99%) was available. At least 5 impaired activities were identified and ranked by 147 patients (95%); interviewers could follow 99% of these. The scoring system proved complex and required amendments. Content validity: Although its main focus is physical function, the MACTAR also contains generic questions; 75% of the patients named at least one impaired activity from the category "mobility." Only 48% were covered by Health Assessment Questionnaire (HAQ) items. Construct validity: MACTAR scores correlate highly with other functional indices and with measures of disease activity. Responsiveness: At 16 weeks the standardized response mean for the total MACTAR score in the combined-treatment group was excellent, at 2.2. Items that directly address change were even more responsive. CONCLUSION: The MACTAR interview is a valid and highly responsive instrument to assess change in functional ability of patients with early RA with active disease. It provides insight into problems--mainly of physical function--that really matter to patients. For standard clinical trials and clinical care, feasibility of the MACTAR is limited and the simpler HAQ remains the instrument of choice.

Arthritis, Rheumatoid↗
PubMed1999

Validity of area-under-the-curve analysis to summarize effect in rheumatoid arthritis clinical trials.

There is a continuing interest in increasing the statistical efficiency of the analysis of clinically meaningful endpoints in rheumatology. One issue that is attracting increasing attention is whether the conventional practice of only reporting the outcome at the end of the study (EOS) might be replaced or complemented by a longitudinal summary that better reflects the clinical course of the disease. The area under the curve (AUC) is a summary measure that integrates serial assessments of a patient's endpoint over the duration of the study. We evaluated the utility of AUC as a summary measure for the analysis and reporting of two RA trials: (i) methotrexate combined with cyclosporine versus methotrexate and placebo in partial methotrexate responders in relatively late disease, and (ii) prednisone plus methotrexate plus sulfasalazine versus sulfasalazine alone in relatively early disease. We replicated the published results of each trial first using the conventional EOS and then AUC summaries. For each patient, the changes from baseline over time were transformed into a summary measure by calculating AUC using the trapezium rule and then standardizing it by the study duration. Using an approach similar to the index of responsiveness to change, we scaled treatment differences derived from EOS and AUC summary measures by their standard deviation of the control group. This signal-versus-noise ratio captures the treatment discrimination ability of each summary measure. Compared to EOS and within each treatment group, the AUC summary reported smaller effects (i.e., change from baseline) with reduced errors in the estimates. AUC measures preserved discriminant validity in treatment comparisons and reported smaller but more precise treatment effect estimates. In the COBRA trial with rapidly-acting medications, AUC seemed to be more sensitive than EOS to detect treatment difference. With slow acting medications and in relatively late disease patients as in the cyclosporine trial, EOS was more sensitive to detect treatment difference than was AUC. In this setting, AUC, however, still seemed to be more sensitive than EOS for the two responsive-to-change endpoints: tender joint counts and pain by visual analog scale. AUC integrates repeated assessments during the trial duration into summary measures. Compared to EOS, the report of RA trial results using AUC summary provides smaller estimates of treatment effects but with better precision. AUC summary is likely to preserve treatment group discrimination taking into account the appropriate onset and offset of the drug action. Trial reports using AUC summary have smaller effect sizes. For trials with long acting medications and short duration similar to the cyclosporine trial, AUC still preserves treatment discrimination but may not be as sensitive as EOS. The calculations of AUC require some additional work in the analysis of each endpoint.

Antirheumatic Agents↗
PubMed1999

Smallest detectable difference in radiological progression.

Omeract IV started a discussion on the development of radiological response criteria in rheumatoid arthritis (RA). Such criteria depend on the definition of what constitutes the minimum clinically important progression of damage. Because such a definition is currently not available, as a first step we have used the concept of random measurement error to determine what is the smallest detectable difference (SDD) in radiological progression between 2 radiographs of a particular patient. Baseline and 12 month radiographs (hands, wrists, feet) of 52 patients representative of the spectrum of radiological progression were selected from a randomized controlled trial of early rheumatoid arthritis (COBRA study) and were read paired and chronologically by 2 observers using the van der Heijde modified Sharp method (0-448 scale) and another 2 observers using the Scott modified Larsen method (0-200). The measurement error of progression was determined using the metric 95% limits of agreement method of Bland and Altman. In the setting of early RA the SDD is 11 modified Sharp score units and 8 modified Larsen score units if there is an equal distribution of baseline damage and progression in the sample and the mean score of the same trained observers is always used. The SDD is 15.5 modified Sharp score units and 11 modified Larsen score units if there is an equal distribution of baseline damage and progression in the sample and the mean score of any 2 trained observers is used. Other SDD were determined depending on the context of measurement. Although this exercise needs repetition in other settings, the SDD is a useful starting point in the development of radiological response criteria.

Adolescent↗
PubMed1998

Cost-effectiveness and cost-utility of combination therapy in early rheumatoid arthritis: randomized comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone. COBRA Trial Group. Combinatietherapie Bij Reumatoïde Artritis.

OBJECTIVE: Assessment of the cost-effectiveness and cost-utility of early intervention in rheumatoid arthritis (RA) patients, with combined step-down prednisolone, methotrexate and sulphasalazine, compared to sulphasalazine alone. METHODS: Multicentre 56 week randomized double-blind trial with full economic analysis of direct costs and utility analysis with rating scale and standard gamble measurement techniques. RESULTS: The combined-treatment group included 76 patients and the sulphasalazine group 78 patients. The mean total costs per patient in the first 56 weeks of follow-up were $5519 for combined treatment and $6511 for treatment with sulphasalazine alone (P = 0.37). Out-patient care, in-patient care and non-health care each contributed about one-third to the total costs. The combined-treatment group appeared to generate savings in the length of hospital stay for RA, non-protocol drugs and costs of home help, but comparisons were not statistically significant. Protocol drugs and monitoring were slightly more expensive in the combined-treatment group. Clinical, radiographic and functional outcomes significantly favoured combined treatment at week 28 (radiography also at week 56). Utility scores also favoured combined treatment. CONCLUSION: Combined treatment is cost-effective due to enhanced efficacy at lower or equal direct costs.

Adult↗
PubMed1998

Combination therapy in rheumatoid arthritis: updated systematic review.

In a second update of a systematic review, many new developments in the combined drug treatment of rheumatoid arthritis (RA) are highlighted. In early RA patients, step-down bridge therapy that includes corticosteroids leads to much enhanced efficacy at acceptable or low toxicity. The effects on joint damage may be persistent, but the symptomatic effects are probably dependent on continued corticosteroid dosing. In late patients, cyclosporin improves a suboptimal clinical response to methotrexate, and the triple combination of methotrexate, sulphasalazine and hydroxychloroquine appears to be clinically better than the components. Other combinations are either untested, tested at low sample size, or show negative interaction. In view of the low volume of evidence, most studies need confirmation by replication.

Antirheumatic Agents↗
PubMed1997

[Combination therapy in early rheumatoid arthritis: the COBRA study].

The scheme 'Combination therapy in rheumatoid arthritis' (COBRA) in early rheumatoid arthritis (RA) involves administration of not only sulfasalazine but also prednisolone and methotrexate during the first six months. The trial showed that the COBRA scheme over a period of 1.5 years was superior to sulfasalazine alone: less disease activity in the major part of the year of treatment, less articular damage on radiographs, fewer side effects and equal or reduced costs. An 'aggressive' treatment in patients with early RA is indicated, with (re)assessment of the use of corticosteroids.

Anti-Inflammatory Agents↗
PubMed1997

Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis.

BACKGROUND: The value of intensive combination therapy in early rheumatoid arthritis is unproven. In a multicentre, double-blind, randomised trial (COBRA), we compared the combination of sulphasalazine (2 g/day), methotrexate (7.5 mg/week), and prednisolone (initially 60 mg/day, tapered in 6 weekly steps to 7.5 mg/day) with sulphasalazine alone. METHODS: 155 patients with early rheumatoid arthritis (median duration 4 months) were randomly assigned combined treatment (76) or sulphasalazine alone (79). Prednisolone and methotrexate were tapered and stopped after 28 and 40 weeks, respectively. The main outcomes were the pooled index (a weighted change score of five disease activity measures) and the Sharp/Van der Heijde radiographic damage score in hands and feet. Independent health-care professionals assessed the main outcomes without knowledge of treatment allocation. FINDINGS: At week 28, the mean pooled index was 1.4 (95% CI 1.2-1.6) in the combined treatment group and 0.8 (0.6-1.0) in the sulphasalazine group (p < 0.0001). At this time, 55 (72%) and 39 (49%) patients, respectively, were improved according to American College of Rheumatology criteria. The clinical difference between the groups decreased and was no longer significant after prednisolone was stopped, and there were no further changes after methotrexate was stopped. At 28 weeks, the radiographic damage score had increased by a median of 1 (range 0-28) in the combined-therapy group and 4 (0-44) in the sulphasalazine group (p < 0.0001). The increases at week 56 (2 [0-43] vs 6 [0-54], p = 0.004), and at week 80 (4 [0-80] vs 12 [0-72], p = 0.01) were also significant. Further analysis suggests that combined therapy immediately suppressed damage progression, whereas sulphasalazine did so less effectively and with a lag of 6 to 12 months. There were fewer withdrawals in the combined therapy than the sulphasalazine group (6 [8%] vs 23 [29%]), and they occurred later. INTERPRETATION: This combined-therapy regimen offers additional disease control over and above that of sulphasalazine alone that persists for up to a year after corticosteroids are stopped. Although confirmatory studies and long-term follow-up are needed, this approach may prove useful in the treatment of early rheumatoid arthritis.

Adult↗
PubMed1997

Limited bone loss due to corticosteroids; a systematic review of prospective studies in rheumatoid arthritis and other diseases.

OBJECTIVE: To clarify the relation between changes in bone density, the treated disease, and dose of corticosteroids prescribed. METHODS: MEDLINE database (1966-95) and bibliographic searches selected cohorts of patients with rheumatoid arthritis (RA) and non-RA patients, studied by reliable serial bone density measurements. RESULTS: Two randomized controlled trials in early RA found greater lumbar bone loss after corticosteroid treatment (pooled effect size at 6 mo 3.9%; 95% CI: 1.9, 6.0%). The other studies included 66 patients with RA taking mean 7 mg prednisone/day; 371 "untreated" RA patients; and 216 non-RA patients taking mean 20 mg prednisone/day. Lumbar bone mass changed (weighted mean) 0.0% (-0.6, 0.7%) per year in steroid treated RA, -0.6% (-0.9, -0.2%) in untreated RA, and -4.7% (-5.2, -4.3%) in non-RA. Femoral neck changed -3.0% (-4.2, -1.8%), -0.7% (-1.0, -0.3%), and -1.5% (-2.5, -0.4%), respectively. In RA, most bone was lost in the first half year, and in early or uncontrolled disease. CONCLUSION: In patients with RA bone loss is limited, influenced by the interaction of disease characteristics and low dose corticosteroid therapy. In contrast, non-RA patients taking higher doses of corticosteriods may loss clinically relevant amounts of bone (i.e., > 5%) within one year.

Arthritis, Rheumatoid↗
PubMedDate not supplied

Reliability of spot samples for assessment of urinary excretion of pyridinoline in patients with rheumatoid arthritis.

OBJECTIVE: To determine how well a spot urine sample of patients with active rheumatoid arthritis (RA) can predict 24-hour urinary pyridinoline and deoxypyridinoline excretion. METHODS: Urine samples of 11 hospitalized RA patients taken on 2 consecutive days at 8 a.m. and 4 p.m. were compared with samples from 24-hour collections (gold standard). High-performance liquid chromatography was used to measure the collagen crosslink concentrations. RESULTS: Sampling time was the only significant factor (repeated measurement ANOVA). Significant differences were found between morning and 24-hour samples and between morning and afternoon samples, but not between afternoon and 24-hour samples. CONCLUSIONS: Samples collected in the afternoon (4 p.m.) give the best approximation of 24-hour urinary pyridinoline excretion in patients with active rheumatoid arthritis. In longitudinal studies the sampling time should be fixed.

Adult↗