Comparison of Care Provided in Practices With Nurse Practitioners and Physician Assistants Versus Subspecialist Physicians Only: A Cohort Study of Rheumatoid Arthritis.

OBJECTIVE: The Affordable Care Act proposes wider use of nurse practitioners (NPs) and physician assistants (PAs), but little is known about outcomes of care provided by them in medical specialties. We compared the outcomes of care for patients with rheumatoid arthritis (RA) seen in practices with NPs or PAs and rheumatologists versus practices with rheumatologists only. METHODS: We enrolled 7 rheumatology practices in the US (4 with NPs or PAs and 3 without). RA disease activity (categorized as in remission, low, moderate, or high, using standardized measures) was abstracted from medical records from the most recent 2 years. We performed a repeated-measures analysis using generalized linear regression to compare disease activity for visits to practices with NPs or PAs versus rheumatologist-only practices, adjusting for disease duration, serologic status, RA treatments, and disease activity measures. RESULTS: Records from 301 patients, representing 1,982 visits, were reviewed. The patients' mean age was 61 years and 77% were female. In the primary adjusted analysis, patients seen in practices with NPs or PAs were less likely to have higher disease activity (odds ratio 0.32, 95% confidence interval 0.17-0.60; P = 0.004) than those seen in rheumatologist-only practices. However, there were no differences in the change in disease activity. CONCLUSION: Patients seen in practices with NPs or PAs had lower RA disease activity over 2 years compared to those seen in rheumatologist-only practices; no differences were observed in the change in disease activity between visits either within or between the different types of provider practice.

Roles of nurse practitioners and physician assistants in rheumatology practices in the US.

OBJECTIVE: A recent workforce study of rheumatology in the US suggests that during the next several decades, the demand for rheumatology services will outstrip the supply of rheumatologists. Midlevel providers such as nurse practitioners and physician assistants may be able to alleviate projected shortages. METHODS: We administered a nationwide survey of midlevel providers during 2012. Invitations with the survey were sent with one followup reminder. The survey contained questions regarding demographics, training, level of practice independence, responsibilities, drug prescribing, use of objective outcome measures, and knowledge and use of treat-to-target (TTT) strategies. RESULTS: The invitation was sent to 482 eligible midlevel providers via e-mail and 90 via US mail. We received a total of 174 responses (30%). The mean age was 46 years and 83% were women. Nearly 75% had ≤10 years of experience and 53% had received formal training in rheumatology. Almost two-thirds reported having their own panel of patients. The top 3 practice responsibilities described were performing patient education (99%), adjusting medication doses (98%), and conducting physical examinations (97%). More than 90% felt very or somewhat comfortable diagnosing rheumatoid arthritis (RA) and a similar percentage prescribed disease-modifying antirheumatic drugs. Three-quarters reported using disease activity measures for RA and 56% reported that their practices used TTT strategies. CONCLUSION: Most respondents reported that they had substantial patient care responsibilities, used disease activity measures for RA, and incorporated TTT in their practice. These data suggest midlevel providers may help to reduce shortages in the rheumatology workforce and conform with recommendations to employ TTT strategies in RA treatment.

Comparative cancer risk associated with methotrexate, other non-biologic and biologic disease-modifying anti-rheumatic drugs.

OBJECTIVE: There is little information comparing the potential risk of cancer across conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). Methotrexate has not been the focus of most contemporary pharmacoepidemiologic studies of cancer. METHODS: We conducted a comparative effectiveness study with cancer as the outcome. A large observational cohort of RA was followed up from 2001 to 2010. Reports of any cancer prompted a confirmation process that included adjudication of the primary cancer records. We used a propensity score (PS) with relevant covariates and cohort trimming to improve the balance between DMARD cohorts. Cox proportional hazard regression models were constructed to estimate the risk of cancer with various DMARDs, all compared with methotrexate. RESULTS: We identified 6806 DMARD courses for analysis (1566 methotrexate; 904 nbDMARDs; 3761 TNF antagonists; 408 abatacept; and 167 rituximab). Non-biologic DMARDs (HR 0.17, 95% CI 0.05-0.65) and TNF antagonists (HR 0.29, 95% CI 0.05-0.65) were associated with a reduced adjusted risk of cancer compared with methotrexate. Abatacept (HR 1.55, 95% CI 0.40-5.97) and rituximab (HR 0.42, 95% CI 0.07-2.60) were similar in risk of cancer with methotrexate. These results were robust to sensitivity analyses. After controlling for DMARD exposures, risk factors for cancer included male gender, age, and alcohol consumption. CONCLUSIONS: Cancer risk was elevated for methotrexate users compared with nbDMARDs and TNF antagonists.

Association of discoid lupus erythematosus with other clinical manifestations among patients with systemic lupus erythematosus.

BACKGROUND: Cutaneous discoid lupus erythematosus (DLE) among patients with systemic lupus erythematosus (SLE) may be associated with less severe disease and with low frequency of nephritis and end-stage renal disease (ESRD). OBJECTIVE: We sought to investigate associations between confirmed DLE and other SLE manifestations, adjusting for confounders. METHODS: We identified patients with rheumatologist confirmation, according to 1997 American College of Rheumatology (ACR) SLE classification criteria, more than 2 visits, longer than 3 months of follow-up, and documented year of SLE diagnosis. DLE was confirmed by a dermatologist, supported by histopathology and images. SLE manifestations, medications, and serologies were collected. Multivariable-adjusted logistic regression analyses tested for associations between DLE and each of the ACR SLE criteria, and ESRD. RESULTS: A total of 1043 patients with SLE (117 with DLE and 926 without DLE) were included in the study. After multivariable adjustment, DLE in SLE was significantly associated with photosensitivity (odds ratio [OR] 1.63), leukopenia (OR 1.55), and anti-Smith antibodies (OR 2.41). DLE was significantly associated with reduced risks of arthritis (OR 0.49) and pleuritis (OR 0.56). We found no significant associations between DLE and nephritis or ESRD. LIMITATIONS: Cross-sectional data collection with risk of data not captured from visits outside system was a limitation. CONCLUSIONS: In our SLE cohort, DLE was confirmed by a dermatologist and we adjusted for possible confounding by medication use, in particular hydroxychloroquine. We found increased risks of photosensitivity, leukopenia, and anti-Smith antibodies and decreased risks of pleuritis and arthritis in patients with SLE and DLE. DLE was not related to anti-double-stranded DNA antibodies, lupus nephritis, or ESRD. These findings have implications for prognosis among patients with SLE.

Rheumatoid arthritis decision making: many information sources but not all rated as useful.

BACKGROUND: Patients who make high-quality medical decisions are more likely to have better health outcomes. One of the central components to a high-quality decision is the well-informed manner in which it is made. However, there has been little research studying patient behaviors regarding how they seek information about treatments for rheumatoid arthritis (RA). METHODS: We conducted a pilot study surveying beneficiaries of a health plan who had 2 or more visits coded for RA. Of 799 invited subjects, 101 (13%) completed interviews. Participants answered a questionnaire regarding sources of RA treatment information and their usefulness, sociodemographic items, and scales regarding their attitudes toward providers and medicines. Outcomes of interest included the average number of sources described (range, 0-10) and the usefulness for each source (1 "not useful" and 4 "extremely useful"). RESULTS: Methotrexate was the most widely used medication reported. The mean (SD) number of information sources used was 5.0 (2.1). Participants rated the information they used with a mean (SD) score of 2.8 (0.7). We found no strong patient correlates of these outcomes when compared with the aforementioned domains. Of the 98% of the total sample who referred to a rheumatologist for information, 87% rated the source as extremely useful. The Internet was the most frequently used nonprovider source, with 63% of subjects reporting use, and a mean (SD) usefulness rating of 3.0 (1.03). CONCLUSIONS: In this pilot study, participants used many sources of information regarding treatment decisions for RA. Ninety-eight percent of the participants used rheumatologists as a source and found them extremely useful. Of the nonprovider sources, the Internet was most common, and 40% found it very useful.

Tumour necrosis factor antagonist use and associated risk reduction of cardiovascular events among patients with rheumatoid arthritis.

OBJECTIVE: To examine the association of cardiovascular events with tumour necrosis factor (TNF) α antagonist use compared with non-biological disease-modifying antirheumatic drug (DMARD) utilisation in patients with rheumatoid arthritis (RA). METHODS: The study population included 10 156 patients enrolled in the Consortium of Rheumatology Researchers of North America RA registry. Three study cohorts were defined based on three mutually exclusive drug use categories, including TNF antagonists, methotrexate and other non-biological DMARDs. HR were calculated adjusting for cardiovascular risk factors, RA disease characteristics and prednisone use. The primary study outcome was a composite of non-fatal myocardial infarction (MI), transient ischaemic attack (TIA) or stroke and cardiovascular-related death. RESULTS: There were 88 cardiovascular events, including 26 MI, 45 TIA/strokes and 17 cardiovascular-related deaths. After adjusting for age, gender, cardiovascular risk factors and RA disease characteristics, patients using a TNF antagonist experienced a reduced risk of the primary composite cardiovascular endpoint (HR 0.39, 95% CI 0.19 to 0.82) compared with users of non-biological DMARDs. Methotrexate was not associated with a reduced risk (HR 0.94, 95% CI 0.49 to 1.80). Prednisone use was associated with a dose-dependent increased risk (p=0.04). The risk reduction associated with TNF antagonists was also observed for non-fatal cardiovascular events (HR 0.35, 95% CI 0.16 to 0.74). CONCLUSION: TNF antagonist use was associated with a reduced risk of cardiovascular events in patients with RA.

Explaining the cardiovascular risk associated with rheumatoid arthritis: traditional risk factors versus markers of rheumatoid arthritis severity.

BACKGROUND: Cardiovascular (CV) disease has a major impact on patients with rheumatoid arthritis (RA), however, the relative contributions of traditional CV risk factors and markers of RA severity are unclear. The authors examined the relative importance of traditional CV risk factors and RA markers in predicting CV events. METHODS: A prospective longitudinal cohort study was conducted in the setting of the CORRONA registry in the USA. Baseline data from subjects with RA enrolled in the CORRONA registry were examined to determine predictors of CV outcomes, including myocardial infarction, stroke or transient ischemic attack. Possible predictors were of two types: traditional CV risk factors and markers of RA severity. The discriminatory value of these variables was assessed by calculating the area under the receiver operating characteristic curve (c-statistic) in logistic regression. The authors then assessed the incidence rate for CV events among subjects with an increasing number of traditional CV risk factors and/or RA severity markers. RESULTS: The cohort consisted of 10 156 patients with RA followed for a median of 22 months. The authors observed 76 primary CV events during follow-up for a composite event rate of 3.98 (95% CI 3.08 to 4.88) per 1000 patient-years. The c-statistic improved from 0.57 for models with only CV risk factors to 0.67 for models with CV risk factors plus age and gender. The c-statistic improved further to 0.71 when markers of RA severity were also added. The incidence rate for CV events was 0 (95% CI 0 to 5.98) for persons without any CV risk factors or markers of RA severity, while in the group with two or more CV risk factors and three or more markers of RA severity the incidence was 7.47 (95% CI 4.21 to 10.73) per 1000 person-years. CONCLUSIONS: Traditional CV risk factors and markers of RA severity both contribute to models predicting CV events. Increasing numbers of both types of factors are associated with greater risk.

The design and synthesis of novel orally active inhibitors of AP-1 and NF-kappaB mediated transcriptional activation. SAR of in vitro and in vivo studies.

We have developed novel orally active quinazoline analogues as inhibitors of AP-1 and NF-kappaB mediated transcriptional activation. Among the derivatives prepared, 1-[2-(2-thienyl)quinazolin-4-ylamino]-3-methyl-3-pyrroline-2,5-dione (10) showed significant activity in an adjuvant-induced arthritis rat model by reducing the swelling by 65% in the non-injected foot. The synthesis, structure-activity relationship, and in vivo activity are described.