Melanie J. Harrison

Real-world utilization of DMARDs and biologics in rheumatoid arthritis: the RADIUS (Rheumatoid Arthritis Disease- Modifying Anti-Rheumatic Drug Intervention and Utilization Study) study

ABSTRACT Objective: Rheumatoid Arthritis (RA) Disease-Modifying Anti-Rheumatic Drug (DMARD) Intervention and Utilization Study (RADIUS) is a unique, real-world, prospective, 5-year, observational study of over 10 000 patients with RA. RADIUS provides a snapshot of use patterns, effectiveness, and safety of DMARDs, biologics, and combination therapies used to manage RA in clinical practice. Research design and methods: Patients with RA requiring a new DMARD or biologic (addition or switch) were eligible for the RADIUS study. Two separate patient cohorts were enrolled; RADIUS 1 patients initiated any new therapy at entry, and RADIUS 2 patients initiated etanercept at entry. Patient demographics and disease activity measures were collected at study entry, and baseline characteristics were summarized for various subgroups. Effectiveness, safety, and patterns of use will be tracked for therapies utilized during the 5‐year study. Results: RADIUS 1 enrolled 4959 patients, and RADIUS 2 enrolled 5102 patients, mostly at community private practices (88%). In RADIUS 1, most patients initiated methotrexate (MTX) monotherapy, followed by MTX in combination with a biologic (e.g. infliximab plus MTX) or other DMARD. In RADIUS 2, most patients initiated etanercept in combination with MTX, followed by etanercept monotherapy. When a new therapy was required, physicians tended to add another therapy versus switching therapies. Patients initiating a biologic had a longer duration of RA and more severe disease compared with patients initiating non-biologic therapy. Conclusions: These real-world data provide evidence of the prescribing practices of rheumatologists in 2001–2003. Future analyses will allow evidence-based comparisons of the long-term safety and effectiveness of DMARDs, biologics, and combination therapies to assist physicians in clinical decision-making.

Results of intervention for lupus patients with self-perceived cognitive difficulties.

The authors developed an 8-week psychoeducational group intervention for patients with systemic lupus erythematosus (SLE) who reported cognitive dysfunction but were not globally impaired on neuropsychological testing. Results of a nonrandomized, uncontrolled pilot study of this program in 17 women with SLE suggest that metamemory and memory self-efficacy improve after participation. One hundred percent retention throughout the study further suggests that patients with SLE are willing and capable of successfully completing the program.

Infliximab treatment shifts the balance between stimulatory and inhibitory Fcγ receptor type II isoforms on neutrophils in patients with rheumatoid arthritis

OBJECTIVE Human neutrophils express both activating and inhibitory Fcgamma receptors (FcgammaR), and their relative expression determines the inflammatory response to immune complexes. Tumor necrosis factor alpha (TNFalpha) up-regulates the expression of stimulatory FcgammaRIIa on neutrophils in vitro, and amplifies immune complex-induced activation of neutrophils in vivo. This study was undertaken to determine whether TNFalpha blockade in patients with rheumatoid arthritis (RA) alters the balance of activating FcgammaR and inhibitory FcgammaR and thereby decreases inflammation. METHODS We used fluorescence-activated cell sorting and Western blotting to examine FcgammaR expression on neutrophils in 24 patients with RA, preceding their first infusion of infliximab and immediately prior to >or=3 subsequent infusions. RESULTS In 13 of 24 patients (54.2%), there was a decrease in the expression of the predominant activating FcgammaR, FcgammaRIIa, after treatment with infliximab, an effect that persisted over >or=3 months of treatment. Although prior to initiation of infliximab therapy the inhibitory FcgammaR, FcgammaRIIb, was undetectable in neutrophils from 23 of 24 patients with RA, FcgammaRIIb protein was detected by Western blotting in 9 patients (37.5%) at the time of the third infliximab infusion. The induction of inhibitory FcgammaRIIb was always associated with decreased levels of FcgammaRIIa, and improvement following infliximab therapy, measured using the Health Assessment Questionnaire, was significantly associated with down-regulation of FcgammaRIIa. CONCLUSION Our findings indicate that TNFalpha inhibition may reduce inflammation in patients with RA by restoring the balance of activating and inhibitory FcgammaR and thereby raising the threshold for immune complex-mediated activation of neutrophils.

The importance of visual function in the quality of life of children with uveitis

BACKGROUND Studies of quality of life (QOL) in children with juvenile idiopathic arthritis (JIA) have focused on changes in musculoskeletal function secondary to arthritis. The role of visual functionality as a result of JIA-associated uveitis and its complications has not been examined. We evaluated the individual impact of physical and visual disability on QOL in children with and without uveitis. METHODS We administered patient-based questionnaires that measured visual function, physical function, and overall QOL to 27 children with JIA or idiopathic uveitis. Demographic data, assessed joint involvement, and reviewed medical records were recorded. Groups with and without uveitis were compared for differences in arthritis and uveitis disease characteristics with use of the Wilcoxon-Mann-Whitney, chi2, and Fisher exact tests. Associations between physical or visual function, and overall QOL were measured with use of Pearsons correlation coefficient. RESULTS Of 27 patients, 85.2% had had arthritis and 51.9% had had uveitis. The group without uveitis had increased morning stiffness (p = 0.036). Patients with uveitis reported more eye redness (p = 0.033) and photophobia (p = 0.013) than those without uveitis. We observed moderate associations between overall QOL and visual function in the uveitis group (r = -0.579) and overall QOL and physical function in the nonuveitis group (r = -0.562). CONCLUSIONS This study demonstrates that visual impairment is an important component of QOL in children with uveitis. It suggests that QOL studies should incorporate both visual and physical function measures in their analyses, especially because many children with JIA also suffer from uveitis and visual impairment.

Physical function assessment tools in pediatric rheumatology

Pediatric rheumatic diseases with predominant musculoskeletal involvement such as juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis(JDM) can cause considerable physical functional impairment and significantly affect the childrens quality of life (QOL). Physical function, QOL, health-related QOL (HRQOL) and health status are personal constructs used as outcomes to estimate the impact of these diseases and often used as proxies for each other. The chronic, fluctuating nature of these diseases differs within and between patients, and complicates the measurement of these outcomes. In children, their growing needs and expectations, limited use of age-specific questionnaires, and the use of proxy respondents further influences this evaluation. This article will briefly review the different constructs inclusive of and related to physical function, and the scales used for measuring them. An understanding of these instruments will enable assessment of functional outcome in clinical studies of children with rheumatic diseases, measure the impact of the disease and treatments on their lives, and guide us in formulating appropriate interventions.

Cognitive dysfunction in neuropsychiatric systemic lupus erythematosus.

Neuropsychiatric syndromes associated with systemic lupus erythematosus are common, but diverse in etiology and presentation. Cognitive dysfunction is prevalent among these syndromes, but exhibit a significant degree of heterogeneity both within and between patient variability. Earlier studies of SLE-associated cognitive dysfunction addressed its identification and description. Common associations were repeatedly acknowledged, including concomitant or past neuropsychiatric disease, use of corticosteroids, disease activity, emotional disturbance, and antiphospholipid antibodies. The past several years have focused more on elucidating the relative strengths of various risk associations, patterns of cognitive abnormalities, both cross-sectionally and longitudinally (ie, clinical course), and novel means to identify cognitive impairment, both functionally and biologically.