Synovial lymphoid neogenesis does not define a specific clinical rheumatoid arthritis phenotype.

OBJECTIVE: To investigate the relationship between lymphoid neogenesis in the synovium of patients with rheumatoid arthritis (RA) and characteristics of inflammation and disease severity. METHODS: Arthroscopic synovial biopsy was performed in 103 patients with active RA (Disease Activity Score 28-joint assessment >or=3.2) who had not received treatment with biologic agents. Sections were stained and assessed by digital image analysis. Lymphocyte aggregates were counted and graded for size (1-3). Synovial lymphoid neogenesis was defined as the presence of grade 2 or 3 aggregates and subclassified based on the presence of follicular dendritic cells (FDCs). RESULTS: Lymphoid neogenesis was present in 31% of the RA synovial tissues, whereas an additional 25% contained only grade 1 aggregates. FDCs were present in 28% of the samples with lymphoid neogenesis, corresponding to 8% of the total RA cohort. Histologically, synovia with lymphoid neogenesis showed increased infiltration by T and B lymphocytes, plasma cells, and macrophages, and increased expression of tumor necrosis factor alpha and lymphotoxin beta compared with samples without lymphoid neogenesis. Patients with lymphoid neogenesis also had higher C-reactive protein levels, erythrocyte sedimentation rates, and leukocyte and thrombocyte counts, but exhibited no increase in the severity of clinical signs and symptoms. Of importance, there was no relationship between the presence of lymphoid neogenesis and IgM rheumatoid factor or anti-citrullinated protein antibodies. The presence of lymphocyte aggregates with FDCs did not define a specific clinical phenotype compared with lymphocyte aggregates without FDCs. CONCLUSION: These findings indicate that synovial lymphoid neogenesis is associated with more severe synovial and systemic inflammation, but this is not confined to a specific clinical subset of RA.

Poor and good health outcomes in rheumatoid arthritis: the role of comorbidity.

OBJECTIVE: To assess the predictive value of selected sociodemographic characteristics, rheumatoid arthritis (RA)-specific clinical factors, and comorbidity with respect to patient-reported health outcomes, i.e., pain, disability, and health-related quality of life, among patients with RA. METHODS: Data were collected between 1997 and 2002 among 882 patients with RA of varying disease duration using questionnaires and clinical examinations. Health outcomes were evaluated over 5 years as a function of disease duration by means of random intercept linear regression. Then we selected the 10% of patients with the poorest and best health outcomes during the 5 years of followup compared to others with equal disease duration. Separate multivariate logistic regression analyses were conducted to identify factors associated with poor and good outcomes. RESULTS: Sociodemographic characteristics seemed to be less important in the prediction of health outcomes. After RA-specific clinical factors, comorbidity appeared to be a major predictive factor for health outcomes. In particular, psychological comorbidity, i.e., depressive symptomatology, was a consistent predictive factor with respect to all health outcomes. CONCLUSION: Assessment of comorbidity needs to be incorporated into the management of RA in order to prevent poor outcomes and to adapt therapies to the specific situation of individual patients. Periodic routine screening for and monitoring of somatic and psychological comorbidity should be included in clinical practice.

Course of patient-reported health outcomes in rheumatoid arthritis: comparison of longitudinal and cross-sectional approaches.

OBJECTIVE: To describe health outcomes reported by patients with rheumatoid arthritis (RA), i.e., pain, disability and health-related quality of life, as a function of disease duration in a longitudinal approach, and to compare the course of patient-reported health outcomes by a longitudinal versus a cross-sectional approach. METHODS: Data were collected with 4 series of questionnaires between 1997 and 2002 among patients with RA (maximum number = 882) of varying disease duration. The course of patient-reported health outcomes as a function of disease duration was evaluated using both longitudinal data and cross-sectional data of the first series. RESULTS: The course of RA shows a different pattern for various health outcomes. We observed similar trends in health outcomes in this large patient sample using the longitudinal and the cross-sectional approach. CONCLUSION: Although longterm consequences of RA are preferably assessed in longer duration followup studies, cross-sectional studies, including patients with a broad range of disease durations, seem to provide fairly reliable estimates of the course of health outcomes.

Quality of rheumatoid arthritis care: the patient's perspective.

OBJECTIVE: To identify health care aspects of inadequate quality in rheumatoid arthritis (RA) care from the perspective of patients, and to study to what extent patients' perspectives on quality of care are associated with patient characteristics. DESIGN: Cross-sectional questionnaire survey performed in 1999. SETTING: Secondary and tertiary rheumatology outpatient clinics. STUDY PARTICIPANTS: A random sample (n = 683) of patients diagnosed with rheumatoid arthritis according to the 1987 revised American College of Rheumatology criteria. Patients varied widely with respect to age (mean 61.5 years) and disease duration (mean 10.7 years). MAIN OUTCOME MEASURES: Using the method of the QUOTE-questionnaire, patients' were asked to rate the importance to them of 29 aspects of care, and to rate the performance of five different health care providers [i.e. rheumatologist, general practitioner (GP), physiotherapist, home nurse, and formal home help] relating to these aspects. To identify aspects of inadequate quality, patients' performance ratings were weighted by importance ratings within each health care service. Inadequate performance on an extremely important aspect was found to be a more serious quality problem than an inadequate performance on an aspect that was less important to patients. Using regression analyses, the association between patients' quality ratings and patient characteristics was assessed. RESULTS: Several aspects of inadequate quality were identified, namely in the field of knowledge of rheumatism and particularly for GPs, physiotherapists, home nurses, and formal home help, and in the field of information on medication and treatment for rheumatologists and GPs. Furthermore, for the majority of the importance and performance ratings, we found no association with patient-related characteristics. CONCLUSIONS: Our study demonstrated that the quality of care could be improved further from the perspective of patients. These findings may be used for making health care more responsive to patients' needs.

Comorbidity in patients with rheumatoid arthritis: effect on health-related quality of life.

OBJECTIVE: To describe the extent of somatic comorbid conditions in patients with rheumatoid arthritis (RA) and to assess the influence of comorbidity on health-related quality of life (HRQOL). METHODS: A 2-year followup study on health and HRQOL was conducted among 679 patients with RA with varying disease duration. Data were collected by means of questionnaires and clinical examinations at baseline and at 2-year followup. Comorbidity was measured by a self-administered questionnaire including 17 chronic diseases. HRQOL was assessed with the RAND-36. The effect of incident comorbid conditions on HRQOL was investigated with linear regression analyses. RESULTS: At least one comorbid condition was reported at baseline by 56% of patients. Significant differences in prevalence rates with the Dutch population were found. The effect of comorbidity on HRQOL depended on both the type of comorbid condition and the dimension of HRQOL. Gastrointestinal (GI) diseases, cancer, dizziness with falling (and less severe chronic pulmonary disease and heart complaints) resulted in significant adverse changes in HRQOL. For the other conditions under study no influence could be detected. CONCLUSION: Our results indicate that measuring comorbidity by a summary count, assuming an overall equally large effect of each comorbid condition, may not reveal the real effect. With respect to clinical practice, our results emphasize the relevance for health care providers to be aware of specific comorbid conditions exposing patients with RA at risk for additional impairment of HRQOL, and to be aware of interactions with RA that may be unique.

Impact of fatigue on health-related quality of life in rheumatoid arthritis.

OBJECTIVE: To multidimensionally assess fatigue in rheumatoid arthritis (RA) and to evaluate the impact of fatigue on health-related quality of life (HRQOL). METHODS: The study was conducted in 1999 among 490 RA patients with varying disease duration. Fatigue was measured with the Multidimensional Fatigue Inventory (MFI-20) and HRQOL with a validated Dutch version of the RAND 36-Item Health Survey. We evaluated the impact of fatigue on HRQOL by multiple linear regression analyses taking into account RA-related pain and depressive symptoms. RESULTS: Different aspects of fatigue selectively explained different dimensions of HRQOL. The MFI-20 was entered last to the linear regression models, resulting in an additional increase of explained variance of 1% (mental health) to 14% (vitality). CONCLUSION: The multidimensional portrayal of RA-related fatigue can be used to develop intervention strategies targeted to specific aspects of fatigue. Fatigue, supplementary to RA-related pain and depressive symptoms, appears to be a feasible and treatable target in the clinical management of RA to increase HRQOL.

Unmet demands for health care among patients with rheumatoid arthritis: indications for underuse?

OBJECTIVE: To assess the prevalence of unmet health care demands among rheumatoid arthritis (RA) patients, and to determine if these unmet demands indicate underuse. METHODS: A total of 679 patients with RA participated in a questionnaire survey and clinical examination. Unmet health care demands and health care use were assessed for orthopedic care, allied health care, home care, and psychosocial care. Indications for underuse were determined by comparing health outcomes of patients with unmet health care demands and of health care users. RESULTS: Of the 679 patients, 28.7% had an unmet demand for 1 of the 4 services: 13.4% for allied health care, 9.7% for orthopedic care, 9.4% for home care, and 6.2% for psychosocial care. Underuse of allied health care, home care and psychosocial care was observed. CONCLUSION: Unmet demands for health care are frequent among RA patients. Most unmet demands indicate underuse. Health care professionals should therefore be more responsive to the demands of patients.

Impact of socioeconomic status on the course of rheumatoid arthritis and on related use of health care services.

OBJECTIVE: To quantify the impact of socioeconomic status (SES) among patients with rheumatoid arthritis on 1) health outcomes and related health care utilization in relation to disease duration and 2) changes in health outcomes and related health care utilization over a 2-year period. METHODS: A questionnaire survey was conducted among 878 patients with rheumatoid arthritis (RA), varying in disease duration from 0 to more than 15 years. To determine the impact of SES on the health outcomes and health care use, patients were compared within and between 3 disease duration groups. Additionally, longitudinal changes in health outcomes and health care use were assessed with a followup questionnaire sent out 2 years later. RESULTS: Patients with low SES have worse disease activity, physical health, mental health, and quality of life than patients with high SES. These differences, however, decreased over time. Regarding health care use, we found that patients with low SES made considerably less use of allied health care than patients with high SES. CONCLUSION: Efforts should be undertaken in health care to alleviate the health disadvantages of RA patients in lower socioeconomic groups. In particular, the access to allied health care could be improved.

Selection bias due to non-response in a health survey among patients with rheumatoid arthritis.

BACKGROUND: Non-response may lead to bias in health(care) outcomes. METHODS: We compared respondents (n = 334) to a questionnaire survey among patients with rheumatoid arthritis with non-respondents (n = 68) and determined predictors of (non-)response. The bias in prevalence estimates of health characteristics and health care use was quantified. RESULTS: Self-reported pain and health care utilization were the most important predictors of (non-)response with respondents experiencing pain more often and more often using specific health care services. Bias concerned especially an underestimation of 'never having pain' (60%) and 'no contact with health care services' (51%). CONCLUSION: More insight into the phenomenon of non-response is important to assess disease burden and health care burden more precisely.

Alefacept treatment in psoriatic arthritis: reduction of the effector T cell population in peripheral blood and synovial tissue is associated with improvement of clinical signs of arthritis.

OBJECTIVE: To investigate whether alefacept (a fully human lymphocyte function-associated antigen 3 [LFA-3]/IgG1 fusion protein that blocks the LFA-3/CD2 interaction) is able to reduce the signs and symptoms of joint inflammation in patients with active psoriatic arthritis (PsA). METHODS: Eleven patients with active PsA were treated with alefacept for 12 weeks in an open-label and explorative study. Clinical joint assessment and laboratory assessments were performed at baseline and after 4, 9, 12, and 16 weeks of treatment. Serial synovial tissue (ST) biopsy specimens from an inflamed index joint (knee, ankle, wrist, or metacarpophalangeal joint) were obtained by arthroscopy at baseline and after 4 and 12 weeks of treatment. RESULTS: At the completion of treatment, 6 of 11 patients (55%) fulfilled the Disease Activity Score (DAS) response criteria. Nine patients (82%) fulfilled the DAS response criteria at any point during the study. There was a statistically significant reduction in CD4+ lymphocytes (P < 0.05), CD8+ lymphocytes (P = 0.05), and CD68+ macrophages (P < 0.02) in the ST after 12 weeks of treatment compared with baseline. The ST and peripheral blood of those patients fulfilling the DAS response criteria contained more CD45RO+ cells at baseline and displayed a significant reduction in these cells compared with nonresponding patients. CONCLUSION: The changes in ST, together with the improvement in clinical joint scores, after treatment with alefacept support the hypothesis that T cell activation plays an important role in this chronic inflammatory disease. Furthermore, since alefacept, a T cell-specific agent, led to decreased macrophage infiltration, the data indicate that T cells are highly involved in synovial inflammation in PsA.