Rheumatoid Arthritis: Swinkels HL

Welsing PM, Landewé RB, van Riel PL, Boers M, van Gestel AM, van der Linden S, Swinkels HL, van der Heijde DM. · University Medical Center Nijmegen, Nijmegen, The Netherlands. · Arthritis Rheum. · Pubmed #15248205 links to  free full text

Abstract: OBJECTIVE: Radiologic progression in rheumatoid arthritis (RA) is considered the consequence of persistent inflammatory activity. To determine whether a change in disease activity is related to a change in radiologic progression in individual patients, we investigated the longitudinal relationship between inflammatory disease activity and subsequent radiologic progression. METHODS: The databases of the University Medical Center Nijmegen (UMCN) cohort and the Maastricht Combination Therapy in RA (COBRA) followup study cohort were analyzed. The UMCN cohort included 185 patients with early RA who were followed up for up to 9 years. Patients were assessed every 3 months for disease activity and every 3 years for radiologic damage. The COBRA cohort included 152 patients with early RA who were followed up for up to 6 years. Patients were assessed at least every year for disease activity and every 12 months for radiologic damage. Disease activity was assessed with the Disease Activity Score (DAS) (original DAS in the UMCN cohort, DAS28 in the COBRA cohort). Radiologic damage was measured by the Sharp/van der Heijde score in both cohorts. Data were analyzed with longitudinal regression analysis (generalized estimating equations [GEE]), using autoregression for longitudinal associations and radiologic damage as the dependent variable. Time, time(2) baseline predictors for radiologic progression and their interactions with time, as well as DAS/DAS28 (actual values or interval means and interval SDs of the means) were subsequently modeled as explanatory variables. RESULTS: Data analyzed by GEE showed a decrease in radiologic progression over time (regression coefficient for time(2) -1.0 [95% confidence interval -1.4, -0.6] in the UMCN cohort and -0.4 [95% confidence interval -0.8, 0.0] in the COBRA cohort). After adjustment for time effects and baseline predictors of radiologic progression and their interactions with time, a positive longitudinal relationship was indicated by autoregressive GEE between the mean interval DAS and radiologic progression in the UMCN cohort (regression coefficient 5.4 [95% confidence interval 2.1, 8.6]), and between the DAS28 and radiologic progression in the COBRA cohort (regression coefficient 1.4 [95% confidence interval 0.8, 2.0]). In the UMCN cohort, the SD of the mean interval DAS was independently longitudinally related to the radiologic progression over the same periods (regression coefficient 20.2 [95% confidence interval 7.2, 33.3]). In both cohorts, the longitudinal relationships between (fluctuations in) disease activity and radiologic progression were found selectively in rheumatoid factor (RF)-positive patients. CONCLUSION: Radiologic progression is not linear in individual patients. Fluctuations in disease activity are directly related to changes in radiologic progression, which supports the hypothesis that disease activity causes radiologic damage. This relationship might only exist in RF-positive patients.

Swinkels HL, Laan RF, van 't Hof MA, van der Heijde DM, de Vries N, van Riel PL. · Department of Rheumatology, University Medical Centre Nijmegen, The Netherlands. · Semin Arthritis Rheum. · Pubmed #11740798 No free full text.

Abstract: BACKGROUND AND OBJECTIVES: In rheumatoid arthritis, joint radiography is still the most frequently used instrument to assess the progression of joint damage. Unfortunately, the poor quality of the radiographic scoring methods available has a negative impact on the power in clinical trials. This study focuses on the influence of the following 4 factors on radiographic scores according to van der Heijde's modification of the Sharp method: intraobserver variation, interobserver variation, follow-up time, and number of measurement occasions within a patient series. METHODS: One hundred and seventy-two patients in the early stages of rheumatoid arthritis were followed up. During the first 3 years, radiographs of the hands and feet were taken twice yearly and scored by 3 observers. The scoring process was repeated after an additional 3-year period. Correlation coefficients and differences between observers were calculated to define variability. The influence of the 4 factors on variability was studied. RESULTS: One observer assigned a significantly higher score than the other 2, who had been trained together. Interobserver variability decreased as follow-up time increased. Interobserver correlation coefficients became higher, with smaller differences between observers for progression scores than for absolute scores. Increasing the number of measurements within a patient series led to higher scores. Intraobserver correlation coefficients were high, and a training effect occurred when the time between measurements was 1 year, resulting in lower scores. CONCLUSIONS: This study demonstrates that, and shows how, the investigated factors influence the variability of the modified Sharp method. It is extremely important to take interobserver variation into account when designing protocols for multicenter clinical trials. A progression scoring method is recommended for studies assessing radiographic damage or clinical trials.

Welsing PM, van Gestel AM, Swinkels HL, Kiemeney LA, van Riel PL. · Department of Rheumatology, University Medical Center Nijmegen, The Netherlands. · Arthritis Rheum. · Pubmed #11592361 links to  free full text

Abstract: OBJECTIVE: To investigate the relationship between functional capacity, disease activity, and joint destruction over the course of rheumatoid arthritis (RA). METHODS: The followup data on 378 patients with early RA (duration <1 year), included in an open, prospective study since 1985 at the Department of Rheumatology of the University Medical Center Nijmegen, were used. Functional capacity, disease activity, and joint destruction were assessed using the Health Assessment Questionnaire disability index (HAQ DI), the Disease Activity Score (DAS), and a modification of the sharp radiographic damage score, respectively. Multiple linear regression was used to model the data collected at 0, 3, 6, and 9 years after study start, to investigate which variables influenced functional capacity during the disease course. A general linear mixed model for longitudinal data, which included the variables identified as significant in the multiple linear regression models and several interaction terms between the variables, was run. RESULTS: On average, the functional capacity of the patients, as measured by the HAQ DI, worsened over the course of the disease after an initial improvement. After an initial reduction in the extent of disease activity, the mean DAS remained more or less stable over the course of the disease. The mean modified sharp joint damage score worsened over the course of the disease, with a slower progression rate later in the disease. In the multiple linear regression at 0, 3, and 6 years after study start, disease activity was found to be an important factor influencing functional capacity, and at 6 and 9 years, joint damage had an important effect on functional capacity. Furthermore, at 6 and 9 years, there was an interaction effect of joint destruction with disease activity. In the general linear mixed model, disease activity, joint damage, and an interaction effect of disease activity and joint damage were the main factors explaining functional capacity. CONCLUSION: The effect of disease activity and joint destruction on functional capacity changes over the course of the disease. In early RA, functional capacity is most associated with disease activity, and in late disease, with joint damage.

Kuiper S, van Gestel AM, Swinkels HL, de Boo TM, da Silva JA, van Riel PL. · Department of Rheumatology, University Medical Center Nijmegen, The Netherlands. · J Rheumatol. · Pubmed #11508583 No free full text.

Abstract: OBJECTIVE: To investigate the influences of the menopausal state, sex, and age on the course and outcome of rheumatoid arthritis (RA). METHODS: A cohort of patients with early RA (209 female, 123 male) was studied. Sex, age, and menopausal state at baseline, and disease activity, radiographic joint destruction, and physical disability during 6 years of followup were assessed. RESULTS: The Disease Activity Score (DAS) was significantly higher in female compared to male patients at any time point except at the time of inclusion. This was mainly due to postmenopausal patients. Radiographic joint destruction (RJD) was significantly worse in female patients compared to males at the time of inclusion. Postmenopausal patients had significantly higher RJD than premenopausal patients at the time of inclusion and 3 years thereafter. Older male patients showed worse RJD than younger male patients at all time points measured. Physical disability was significantly worse in female compared to male patients, as well as in postmenopausal compared to premenopausal patients, and older male compared to younger male patients. Stepwise regression analysis revealed that at 3 years higher age and female sex were the best predictors for a worse DAS. Higher age and the interaction term between menopausal state and age best predicted higher RJD. Higher age and the interaction term between menopausal state and age best predicted Health Assessment Questionnaire (HAQ) score. CONCLUSION: Higher age at presentation of RA leads to a more severe disease course in terms of DAS, RJD, and HAQ. Although female sex has a deteriorating effect on the DAS, the menopausal state is responsible for the major part of the differences in outcome between men and women. Postmenopausal state in early RA influences future disability and damage, especially in older patients.

Kroot EJ, van Gestel AM, Swinkels HL, Albers MM, van de Putte LB, van Riel PL. · Department of Rheumatology, University Medical Center, Nijmegen, The Netherlands. · J Rheumatol. · Pubmed #11469455 No free full text.

Abstract: OBJECTIVE: To study the presence of chronic coexisting diseases in patients with rheumatoid arthritis (RA) and its effect on RA treatment, disease course, and outcome during the first years of the disease. METHODS: From January 1985 to December 1990, 186 patients with recent onset RA were enrolled in a prospective longitudinal study. Between January 1991 and November 1992 patients were interviewed on the basis of a comorbidity questionnaire. For analysis the diseases were coded according to the International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) medical diagnoses. Disease activity during the period of followup was measured by the Disease Activity Score. Outcome in terms of physical disability (Health Assessment Questionnaire) and radiological damage (Sharp's modified version) over 3 and 6 year periods was determined. RESULTS: In the group of 186 patients, with mean disease duration of 4.3 years at January 1991, 50 patients (27%) reported at least one chronic coexisting disease. The most frequently reported coexisting diseases were of cardiovascular (29%), respiratory (18%), or dermatological (11%) origin. For the major part (66%) chronic coexisting diseases were already present before onset of RA. No statistically significant differences in use of disease modifying antirheumatic drugs or corticosteroids were observed between RA patients with and without chronic coexisting diseases. No statistically significant differences were found in disease activity or in outcome in terms of physical disability and radiological damage over 3 and 6 year periods between the 2 groups with RA. CONCLUSION: The results showed that about 27% of patients with RA in this inception cohort had at least one chronic coexisting disease. Treatment, disease course, and outcome did not differ between patients with and without chronic coexisting diseases during the first years of the disease.

Radstake TR, Barrera P, Albers MJ, Swinkels HL, van de Putte LB, van Riel PL, Anonymous00237. · Department of Rheumatology, University Medical Center St. Radboud, Nijmegen, The Netherlands. · J Rheumatol. · Pubmed #11361223 No free full text.

Abstract: OBJECTIVE: To investigate whether there is evidence for genetic anticipation in rheumatoid arthritis (RA) in Europe. METHODS: Cross sectional comparison of data from all affected parent-offspring pairs identified among (1) the RA population attending our department and (2) a large cohort of families from RA probands with both parents alive recruited by the European Consortium on RA families (ECRAF) for association studies. Longitudinal comparison between probands with and without parental RA. We used prospectively collected data on disease activity, therapies, and radiological outcomes from our Dutch inception cohort of patients with early RA during the first 6 years of followup. RESULTS: From a total of 683 Dutch and 170 European patients we identified 28 Dutch and 21 European parent-offspring pairs with RA. Probands with parental RA had an earlier disease onset compared with affected parents (Dutch p < 0.002, European p < 0.0001). In Dutch patients, the prevalence of HLA-DR4, DR4 double dose, and shared epitope (SE) double dose was slightly higher in probands with parental RA than in those without [odds ratios (95% CI) 2.0 (0.7-5.8), 2.79 (0.8-9.4), and 2.12 (0.6-8.7), respectively]. The same was true for European probands concerning SE double dose [OR (95% CI) 1.76 (0.6-8.7)]. No other relevant differences in demographic or clinical indices were found between probands with affected parents and those without. Disease course (Disease Activity Score) and therapies used during the first 6 years of followup were similar in Dutch patients with and without parental RA. Radiological damage at baseline was lower in the former group and this difference persisted after 3 and 6 years. CONCLUSION: Our data suggest that genetic anticipation in RA does occur in terms of an earlier disease onset in the offspring. Despite a slightly higher prevalence of HLA alleles encoding for the SE, probands with confirmed parental RA had no worse outcome than those without.

Radstake TR, Barrera P, Albers JM, Swinkels HL, van de Putte LB, van Riel PL. · Department of Rheumatology, University Hospital, Nijmegen, The Netherlands. · Rheumatology (Oxford). · Pubmed #10788534 links to  free full text

Abstract: OBJECTIVES: To study potential differences in demographic, process and outcome variables between familial and sporadic rheumatoid arthritis (RA) in an early RA inception cohort. METHODS: In 1998, we ascertained the familial status of all collaborative patients in a large early RA inception cohort at our department. Familial RA was defined by the presence of at least two siblings fulfilling the American College of Rheumatology criteria for RA. Baseline demographic data and prospectively recorded disease activity variables, therapies and radiological damage during the first 6 yr of disease were included in the analysis. A regression analysis was performed to assess whether familial clustering is a prognostic factor. RESULTS: We identified 142 patients with sporadic and 36 with familial RA. The most striking difference between these groups was the larger sibship size in multicase families (8.2 +/- 2.5 vs 5. 5 +/- 2.8; P < 0.0001). Age at onset was similar in both groups, although males with familiar RA were younger at disease onset than those with sporadic RA (median 50 vs 57 yr; P=0.03). No differences were found in gender, presence of rheumatoid factor (RF), antinuclear factor and HLA-DR typing or in disease activity, interventions and outcome over 6 yr of follow-up. Early radiological damage and disease activity, but not familial history of RA were prognostic for X-ray damage. CONCLUSION: We show that sibship size is the only relevant risk factor for familial RA. No differences in genotypic and phenotypic characteristics, disease severity or radiological damage were observed among familial and sporadic RA. Familial history of RA is not a poor prognostic factor. This prospective study confirms previous cross-sectional findings in the Dutch population.