Biomedical subjects

Elena Massarotti

Publications and source records attributed to Elena Massarotti.

5 recordsLinked to original sources

PubMed2005

Regulation of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis: contrasting effects of HLA-DR3 and the shared epitope alleles.

OBJECTIVE: To examine the association between HLA-DRB1 alleles and the production of anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) autoantibodies in patients with rheumatoid arthritis (RA). METHODS: We studied 1,723 Caucasian RA patients enrolled in the North American Rheumatoid Arthritis Consortium (NARAC) family cohort and the Study of New Onset Rheumatoid Arthritis (SONORA) cohort. All patients were tested for anti-CCP antibodies (by enzyme-linked immunosorbent assay), RF (by nephelometry), and HLA-DR genotype (by polymerase chain reaction and sequence-specific oligonucleotide hybridization). RESULTS: When controlled for the presence of RF, anti-CCP positivity was strongly associated with the HLA-DRB1 shared epitope (SE). In RF+ patients, the presence of the SE was very significantly associated with anti-CCP positivity, with an odds ratio (OR) of 5.8 and a 95% confidence interval (95% CI) of 4.1-8.3. This relationship was also seen in RF- patients (OR 3.1 [95% CI 1.8-5.3]). In contrast, RF positivity was not significantly associated with presence of the SE independently of anti-CCP antibodies. Strikingly, HLA-DRB1*03 was strongly associated with reduced anti-CCP titers, even after controlling for the presence of the SE and restricting the analysis to anti-CCP+ patients. HLA-DR3 was also associated with anti-CCP- RA in our population. CONCLUSION: The HLA-DRB1 SE is strongly associated with the production of anti-CCP antibodies, but not RF. In contrast, HLA-DR3 alleles are associated with anti-CCP- disease and with lower levels of anti-CCP antibodies, even when controlling for the SE. These data emphasize the complexity of the genetic effects of the major histocompatibility complex on the RA phenotype.

Adult↗

PubMed2005

Rheumatoid arthritis: an overview of new and emerging therapies.

Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic autoimmune disorder characterized by symmetric inflammation of synovial joints leading to progressive erosion of cartilage and bone. The aim of treatment is to mitigate joint destruction, preserve function, and prevent disability. The American College of Rheumatology guidelines for the treatment of RA recommend that newly diagnosed patients with RA begin treatment with disease-modifying antirheumatic drugs (DMARDs) within 3 months of diagnosis. Methotrexate remains the most commonly prescribed DMARD and is the standard by which recent new and emerging therapies are measured. Increasing knowledge regarding the immunologic basis of RA and advances in biotechnology have resulted in new, targeted biological therapies against proinflammatory cytokines that have dramatically changed the treatment paradigm and outcomes of patients with RA. This article reviews the pharmacological rationale underlying RA therapy, with a focus on currently available biological therapies and new therapies in development.

Abatacept↗

PubMed2005

Rituximab.

Rituximab is a chimeric monoclonal antibody that targets the CD20 molecule on the B-cell surface. It is the first antibody of its kind to be licensed for the treatment of non-Hodgkin's lymphoma. Rituximab was found to be effective, well-tolerated and has a good safety profile, though its precise cellular effects are still not well understood. Rituximab has been shown to be of therapeutic benefit in various autoimmune diseases in which B lymphocytes play a role. This article summarizes the current literature regarding the use of rituximab in lymphoma, rheumatoid arthritis, systemic lupus erythematosus and other selected autoimmune diseases.

Antibodies, Monoclonal↗

PubMed2005

Frequency, predictors, and economic impact of upward dose adjustment of infliximab in managed care patients with rheumatoid arthritis.

OBJECTIVE: To examine dosing patterns and costs among rheumatoid arthritis (RA) patients newly treated with infliximab in a large national health care claims database. METHODS: Using data from a proprietary database of pharmacy and medical claims for 75 U.S. health plans, RA patients newly treated with infliximab between June 2000 and June 2002 were selected and assigned an .index date. based on the first infusion. A pretreatment period of 6 months was created; patients were also followed for a minimum of 6 months after the initial infusion. Follow-up was allowed to vary beyond this minimum 6 months in order to preserve all available patient data. A maintenance number of infliximab vials was determined as of the second infusion; patients with 1 subsequent increase in vials used or 2 intervals between infusions of <49 days were considered to have had an upward dose adjustment. Differences (i.e., between those with upward dose adjustment and those with no upward dose) in patient characteristics were examined using descriptive statistics. In addition, time to upward dose adjustment and factors influencing its likelihood were analyzed using Kaplan-Meier and Cox proportional hazards techniques. Finally, differences in RA-related and unrelated costs (medication, outpatient, inpatient, and total, expressed in 2003 dollars) were examined using Wilcoxon rank-sum tests and were also stratified by a number of patient characteristics found to differ between the 2 groups. RESULTS: A total of 1,236 patients met all study entry criteria and were included in these analyses. One or more upward dose adjustments were experienced by 61.7% (N=762) of patients during an average of 15 months of follow-up (median =13 months, range=6 to 31 months). The majority (63.3%) of upward dose adjustments were due to increases in the number of billed vials. Median time to upward dose adjustment was 254 days and declined steadily based on year of initiation (from 330 days in 2000 to 224 days in 2002). Factors significantly influencing upward dose adjustment included pretreatment use of leflunomide, comorbid Crohn.s disease, and pretreatment liver function testing. During followup, patients in the upward dose adjustment group used a mean (SD) of 30.28 (20.90) vials of infliximab, compared with 15.90 (14.28) among those not adjusting dose (P<0.001). Annualized (i.e., standardized to a 365-day rate) RA-related costs were higher by more than 50% among patients with upward dose adjustment (SD $22,283 [$20,517] versus $14,425 [$10,828] for those without upward dose adjustment; P<0.001); differences were driven almost entirely by the costs of infliximab itself ($16,336 [$9,490] versus $9,573 [$6,790], P<0.001). CONCLUSIONS: In a cohort of managed care members with RA, upward dose adjustment with infliximab was frequent and appeared to occur earlier in the drug therapy in 2002 compared with 2000. Upward dose adjustment was associated with significant increases in drug treatment costs; therefore, payers and providers should consider the impact of current dosing trends when monitoring the use of biologics for autoimmune diseases.

Adult↗

PubMed2002

The Work Limitations Questionnaire's validity and reliability among patients with osteoarthritis.

The 25-item Work Limitations Questionnaire (WLQ) was recently developed to measure health-related decrements in ability to perform job roles among employed individuals. Research has demonstrated its validity and reliability in several populations. We assessed the WLQ's performance when administered to patients with osteoarthritis (OA), which is a leading cause of work disability and productivity loss. We recruited a representative sample of 230 employed, confirmed OA patients and a comparison group of 37 healthy employed controls. Subjects completed a mail survey. In tests of the WLQ's scale internal reliability, the questionnaire met all established criteria. Additionally, in construct validity tests, the WLQ correctly detected OA vs. control group differences, and correlated significantly with arthritis pain, stiffness, and functional limitation, and self-reported work productivity. The WLQ is an accurate and reliable source of information for assessing the work impact of OA.

Adult↗