Association of Cardiovascular Outcomes with Low-Dose Glucocorticoid Use in Patients with Rheumatoid Arthritis.

OBJECTIVE: Many guidelines recommend limiting glucocorticoids in patients with rheumatoid arthritis (RA), but 40% of patients remain on glucocorticoids long-term. We evaluated the cardiovascular risk of long-term glucocorticoid use by studying patients on stable disease modifying anti-rheumatic drugs (DMARDs). METHODS: Using two claims databases, we identified patients with RA on stable DMARD therapy for >180 days. Proportional hazards models with inverse probability weights and clustering to account multiple observations were used to estimate the effect of glucocorticoid dose on composite cardiovascular outcomes (stroke or myocardial infarction). RESULTS: There were 135,583 patients in Medicare and 39,272 in Optum's de-identified Clinformatics® Data Mart (CDM) database. Medicare and CDM patients had an incidence of 1.3 and 0.8 composite cardiovascular outcomes per 100 person-years, respectively. In the older, comorbid Medicare cohort, glucocorticoids were associated with a dose-dependent increase in composite cardiovascular outcomes in adjusted models with predicted 1-year incidence of 1.4% (95% CI 1.2-1.6) for ≤5mg, 1.6% (1.4-1.9) for >5-10mg, and 1.8% (1.2-2.5) for >10mg versus 1.1% (95% CI 1.1-1.2) among patients using no glucocorticoids. There was no significant association among the CDM cohort. However, in the subgroup of younger patients with RA and higher cardiovascular risk, glucocorticoids were associated with a dose-dependent increase in composite cardiovascular outcomes. CONCLUSION: Among older, more comorbid and younger, higher cardiovascular risk patients with RA on stable DMARD therapy, glucocorticoids were associated with a dose-dependent increased risk of myocardial infarction and stroke, even at doses ≤5mg/d. By contrast, no association was noted among younger, healthier patients with RA.

Primary Care Appointment Completion Rates and Telemedicine Utilization Among Black and Non-Black Patients from 2019 to 2020.

Objective: To understand how differences in primary care appointment completion rates between Black and non-Black patients changed in 2020 within the context of the COVID-19 pandemic and when telemedicine utilization peaked. Materials and Methods: We conducted a retrospective cohort study using the electronic health record from January 1 to December 31, 2020, among all adults scheduled for a primary care appointment within a large academic medical center. We used mixed-effects logistic regression to estimate adjusted appointment completion rates for Black patients compared with those for non-Black patients in 2020 as compared with those in 2019 within four time periods: (1) prepandemic (January 1, 2020, to March 12, 2020), (2) shutdown (March 13, 2020, to June 3, 2020), (3) reopening (June 4, 2020, to September 30, 2020), and (4) second wave (October 1, 2020, to December 31, 2020). Results: Across 1,947,399 appointments, differences in appointment completion rates between Black and non-Black patients improved in all time periods: +1.4 percentage points prepandemic (95% confidence interval [CI]: +0.8 to +2.0), +11.7 percentage points during shutdown (95% CI: +11.0 to +12.3), +8.2 percentage points during reopening (95% CI: +7.8 to +8.7), and +7.1 percentage points during second wave (95% CI: +6.4 to +7.8) (all p-values <0.001). The types of conditions managed by primary care shifted during the shutdown period, but the remainder of 2020 mirrored those from 2019. Discussion: Racial differences in appointment completion rates narrowed significantly in 2020 even as the mix of disease conditions began to mirror patterns observed in 2019. Conclusions and Relevance: Telemedicine may be an important tool for improving access to primary care for Black patients. These findings should be key considerations as regulators and payors determine telemedicine's future.

Physical activity measured using wearable activity tracking devices associated with gout flares.

OBJECTIVE: To determine the feasibility and validity of using wearable activity trackers to test associations between gout flares with physical activity and sleep. METHODS: Participants with physician-diagnosed gout, hyperuricemia (≥ 6.8 mg/dl), current smartphone use, and ≥ 2 self-reported flares in the previous 6 months were enrolled. Physical activity, heart rate, and sleep data were obtained from wearable activity trackers (Fitbit Charge HR2). Daily compliance was defined by the availability of sufficiently complete activity data at least 80% of the day. Associations of weekly gout flares with sleep and activity were measured by comparing flare-related values to average sleep and steps per day. We used mixed linear models to account for repeated observations. RESULTS: Forty-four participants enrolled; 33 met the criteria for minimal wear time and flare reporting, with activity tracker data available for 60.5% of all total study days. Mean ± SD age was 48.8 ± 14.9 years; 85% were men; 15% were black; 88% were on allopurinol or febuxostat, and 30% reported ≥ 6 flares in the prior 6 months. Activity trackers captured 204 (38%) person-weeks with flares and 340 (62%) person-weeks without flares. Mean ± SD daily step count was significantly lower (p < 0.0001) during weeks with gout flares (5900 ± 4071) than during non-flare periods (6972 ± 5214); sleep however did not differ. CONCLUSION: The pattern of wear in this study illustrates reasonable feasibility of using such devices in future arthritis research. The use of these devices to passively measure changes in physical activity patterns may provide an estimate of gout flare occurrence and duration. TRIAL REGISTRATION: NCT, NCT02855437 . Registered 4 August 2016.

Comparison of an interactive voice response system and smartphone application in the identification of gout flares.

OBJECTIVE: To examine the feasibility, preference, and satisfaction of an interactive voice response (IVR) system versus a customized smartphone application (StudyBuddy) to capture gout flares METHODS: In this 24-week prospective, randomized, crossover, open-label pilot study, 44 gout patients were randomized to IVR vs. StudyBuddy and were crossed over to the other technology after 12 weeks. Flares were reported via weekly (and later daily) scheduled StudyBuddy or IVR queries. Feasibility was ascertained via response rate to scheduled queries. At 12 and 24 weeks, participants completed preference/satisfaction surveys. Preference and satisfaction were assessed using dichotomous or ordinal questions. Sensitivity was assessed by the frequency of flare reporting with each approach. RESULTS: Thirty-eight of 44 participants completed the study. Among completers, feasibility was similar for IVR (81%) and StudyBuddy (80%). Conversely, most (74%) preferred StudyBuddy. Measures of satisfaction (ease of use, preference over in-person clinic visits, and willingness for future use) were similar between the IVR and StudyBuddy; however, more participants deemed the StudyBuddy as convenient (95% vs. 73%, P = 0.01) and less disruptive (97% vs. 82%, P = 0.03). Although the per patient number of weeks in flare was not significantly different (mean 3.4 vs. 2.6 weeks/patient, P = 0.15), the StudyBuddy captured more of the total flare weeks (35%) than IVR (27%, P = 0.02). CONCLUSION: A smartphone application and IVR demonstrated similar feasibility but overall sensitivity to capture gout flares and participant preference were greater for the smartphone application. Participant preference for the smartphone application appeared to relate to perceptions of greater convenience and lower disruption. TRIAL REGISTRATION: NCT, NCT02855437 . Registered 4 August 2016.

Adherence and Outcomes with Urate-Lowering Therapy: A Site-Randomized Trial.

PURPOSE: The purpose of this study was to test a pharmacist-led intervention to improve gout treatment adherence and outcomes. METHODS: We conducted a site-randomized trial (n=1463 patients) comparing a 1-year, pharmacist-led intervention to usual care in patients with gout initiating allopurinol. The intervention was delivered primarily through automated telephone technology. Co-primary outcomes were the proportion of patients adherent (proportion of days covered ≥0.8) and achieving a serum urate <6.0 mg/dl at 1 year. Outcomes were reassessed at year 2. RESULTS: Patients who underwent intervention were more likely than patients of usual care to be adherent (50% vs 37%; odds ratio [OR] 1.68; 95% confidence interval [CI] 1.30, 2.17) and reach serum urate goal (30% vs 15%; OR 2.37; 95% CI 1.83, 3.05). In the second year (1 year after the intervention ended), differences were attenuated, remaining significant for urate goal but not for adherence. The intervention was associated with a 6%-16% lower gout flare rate during year 2, but the differences did not reach statistical significance. CONCLUSIONS: A pharmacist-led intervention incorporating automated telephone technology improved adherence and serum urate goal in patients with gout initiating allopurinol. Although this light-touch, low-tech intervention was efficacious, additional efforts are needed to enhance patient engagement in gout management and ultimately to improve outcomes.

Allopurinol Dose Escalation and Mortality Among Patients With Gout: A National Propensity-Matched Cohort Study.

OBJECTIVE: Observational data suggest that hyperuricemia and gout are associated with increased mortality, while allopurinol use is associated with reduced mortality. In addition, the protective effect of allopurinol may be dose dependent. The aim of the current study was to determine whether allopurinol dose escalation is associated with cause-specific mortality in patients with gout. METHODS: In this 10-year observational, active-comparator study of US Veterans with gout who initiated treatment with allopurinol, propensity score matching, Cox proportional hazards models, and competing risks regression analyses were used to assess differences in cause-specific mortality between patients whose allopurinol dose was escalated (dose escalators) and those whose allopurinol dose was not escalated or was reduced (non-escalators) over a 2-year period. RESULTS: Among the 6,428 dose escalators and 6,428 matched non-escalators, there were 2,867 deaths during the observation period (40.4 deaths per 1,000 person-years). Dose escalators experienced an increase in all-cause mortality (hazard ratio [HR] 1.08, 95% confidence interval [95% CI] 1.01-1.17), with the effect sizes being similar for incidence of cardiovascular-related deaths (HR 1.08, 95% CI 0.97-1.21) and cancer-related deaths (HR 1.06, 95% CI 0.88-1.27), although neither reached statistical significance. Dose escalation to achieve the goal of lowering the serum urate (SU) level to <6.0 mg/dl was infrequent. At 2 years, 10% of dose escalators were receiving a final daily dose of >300 mg and 31% had achieved the SU goal. In a sensitivity analysis limited to dose escalators achieving the SU goal, there was a nonsignificant reduction of 7% in the hazard of cardiovascular-related mortality (HR 0.93, 95% CI 0.76-1.14). CONCLUSION: This is the largest study to date to investigate the effects of allopurinol use on mortality and is the first to use a rigorous active-comparator design. Dose escalation was associated with a small (<10%) increase in all-cause mortality, thus showing that a strategy of allopurinol dose escalation, which in current real-life practice is characterized by limited dose increases, is unlikely to improve the survival of patients with gout.

Allopurinol Medication Adherence as a Mediator of Optimal Outcomes in Gout Management.

BACKGROUND: Patient and provider factors, including allopurinol medication adherence, affect gout treatment outcomes. OBJECTIVES: The aim of this study was to examine associations of patient and provider factors with optimal gout management. METHODS: Linking longitudinal health and pharmacy dispensing records to questionnaire data, we assessed patient and provider factors among 612 patients with gout receiving allopurinol during a recent 1-year period. Associations of patient (medication adherence and patient activation) and provider factors (dose escalation, low-dose initiation, and anti-inflammatory prophylaxis) with serum urate (SU) goal achievement of less than 6.0 mg/dL were examined using multivariable logistic regression. Medication adherence was assessed as a mediator of these factors with goal achievement. RESULTS: A majority of patients (63%) were adherent, whereas a minority received dose escalation (31%). Medication adherence was associated with initiation of daily allopurinol doses of 100 mg/d or less (odds ratio [OR], 1.82; 95% confidence interval [CI], 1.20-2.76). In adjusted models, adherence (OR, 2.35; 95% CI, 1.50-3.68) and dose escalation (OR, 2.48; 95% CI, 2.48-4.25) were strongly associated with SU goal attainment. Low starting allopurinol dose was positively associated with SU goal attainment (OR, 1.11; 95% CI, 1.02-1.20) indirectly through early adherence, but also had a negative direct association with SU goal attainment (OR, 0.21; 95% CI, 0.12-0.37). CONCLUSIONS: Medication adherence and low starting dose combined with dose escalation represent promising targets for future gout quality improvement efforts. Low starting dose is associated with better SU goal attainment through increased medication adherence, but may be beneficial only in settings where appropriate dose escalation is implemented.

Rationale and design of the randomized evaluation of an Ambulatory Care Pharmacist-Led Intervention to Optimize Urate Lowering Pathways (RAmP-UP) Study.

BACKGROUND: Despite the availability of effective therapies, most gout patients achieve suboptimal treatment outcomes. Current best practices suggest gradual dose-escalation of urate lowering therapy and serial serum urate (sUA) measurement to achieve sUA<6.0mg/dl. However, this strategy is not routinely used. Here we present the study design rationale and development for a pharmacist-led intervention to promote sUA goal attainment. METHODS: To overcome barriers in achieving optimal outcomes, we planned and implemented the Randomized Evaluation of an Ambulatory Care Pharmacist-Led Intervention to Optimize Urate Lowering Pathways (RAmP-UP) study. This is a large pragmatic cluster-randomized trial designed to assess a highly automated, pharmacist-led intervention to optimize allopurinol treatment in gout. Ambulatory clinics (n=101) from a large health system were randomized to deliver either the pharmacist-led intervention or usual care to gout patients over the age of 18years newly initiating allopurinol. All participants received educational materials and could opt-out of the study. For intervention sites, pharmacists conducted outreach primarily via an automated telephone interactive voice recognition system. The outreach, guided by a gout care algorithm developed for this study, systematically promoted adherence assessment, facilitated sUA testing, provided education, and adjusted allopurinol dosing. The primary study outcomes are achievement of sUA<6.0mg/dl and treatment adherence determined after one year. With follow-up ongoing, study results will be reported subsequently. CONCLUSION: Ambulatory care pharmacists and automated calling technology represent potentially important, underutilized resources for improving health outcomes for gout patients.

Target Serum Urate: Do Gout Patients Know Their Goal?

OBJECTIVE: To examine gout patients' knowledge of their condition, including the central role of achieving and maintaining the serum urate (SU) goal with the use of urate-lowering therapy (ULT). METHODS: This study of 612 gout patients was conducted at a Veterans Affairs medical center. Gout patients were included based on administrative diagnostic codes and receipt of at least 1 allopurinol prescription over a 1-year period. Questionnaires were mailed to patients and linked to medical records data. The questionnaire included gout-specific knowledge questions, the Patient Activation Measure, and self-reported health outcomes. Knowledge was assessed descriptively. Multivariable logistic regression was used to determine predictors of SU goal knowledge. Associations of knowledge with health outcomes were examined in exploratory analyses. RESULTS: The questionnaire had a 62% response rate. Only 14% of patients knew their SU goal, while the majority answered correctly for the other 5 gout-specific knowledge questions. In adjusted analyses, having a rheumatologist as initial prescriber (odds ratio [OR] 3.0 [95% confidence interval (95% CI) 1.4-6.2]) and knowing all of the other 5 gout-specific knowledge questions (OR 2.1 [95% CI 1.3-3.4]) were associated with greater odds of knowing the SU goal. SU goal knowledge was associated with self-reported global health status, but not with self-reported health-related quality of life or gout-specific health status. CONCLUSION: There is a knowledge deficit regarding the SU treatment goal among gout patients receiving ULT, despite generally high levels of other gout-specific knowledge. SU goal information may be an important and underutilized concept among providers treating gout patients.

Treatment Options for Acute Gout.

Careful consideration of comorbidities and contraindications are important when determining the appropriate treatment of patients with gout.

Performance of self-reported measures for periodontitis in rheumatoid arthritis and osteoarthritis.

BACKGROUND: This study evaluates the performance of self-report against the reference standard of clinically defined periodontitis in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) after accounting for factors associated with periodontitis. METHODS: Six self-report periodontitis questions were evaluated in patients with RA and OA. Questions were validated against a reference standard of severe and moderate-to-severe periodontitis based on full-mouth examination. Multivariable logistic regression was used to evaluate the performance of: 1) self-report alone; 2) age, sex, education, and smoking status; and 3) a combination of the above. Model performance was assessed using the c-statistic. Convergent validity of self-reported "bone loss/deep pockets" and "loose teeth" was assessed; associations of self-report with RA disease characteristics were explored. RESULTS: Self-report performed similarly in RA and OA, with individual question specificity for periodontitis ≥ 68% and sensitivity from 9.8% to 45%. Question-only models yielded c-statistics of 0.66 to 0.72, whereas risk factor-only models yielded c-statistics of 0.74 to 0.79. The highest-performing models incorporated both self-report questions and periodontitis risk factors, with c-statistics ≥ 0.79. Greater radiographic alveolar bone loss was observed among participants reporting "bone loss/deep pockets" (P < 0.001) and "loose teeth" (P < 0.001). Among patients with RA, "loose teeth," but not other self-report items, was associated with rheumatoid factor positivity (P = 0.047) and higher disease activity (P < 0.001). CONCLUSIONS: Patient self-report, when combined with other risk factors, performs well in identifying periodontitis among patients with RA and OA. Self-report questions related to alveolar bone loss exhibit excellent convergent validity in these patient subsets.

Modifiable factors associated with allopurinol adherence and outcomes among patients with gout in an integrated healthcare system.

OBJECTIVE: To identify modifiable patient and provider factors associated with allopurinol adherence and the achievement of a serum urate acid (SUA) goal in gout. METHODS: We identified a retrospective cohort of patients with gout, newly treated with allopurinol. All patient data came from administrative datasets at a large integrated health delivery system. Patients were ≥ 18 years old at time of initial allopurinol dispensing, and had 12 months or more of membership and drug eligibility prior to the index date. Allopurinol adherence was defined as a proportion of days covered ≥ 0.80, evaluated during the first 12 months of observation after the initial dispensing. Multivariable logistic regression was used to examine factors associated with allopurinol nonadherence and attaining an SUA concentration < 6.0 mg/dl. RESULTS: We identified 13,341 patients with gout with incident allopurinol use (mean age 60 yrs, 78% men). Of these, 9581 patients (72%) had SUA measured both at baseline and during followup. Only 3078 patients (32%) attained an SUA target of < 6.0 mg/dl during followup. Potentially modifiable factors associated with treatment adherence and obtaining the SUA goal in the multivariable analysis included concomitant diuretic use, prescriber specialty, and allopurinol dosing practices. Adherent patients were 2.5-fold more likely than nonadherent patients to achieve an SUA < 6.0 mg/dl during observation. CONCLUSION: Among patients with gout initiating allopurinol in our study, 68% did not reach the SUA goal and 57% of patients were nonadherent. Modifiable factors, including allopurinol dose escalation, treatment adherence, rheumatology referral, and concomitant medication use, could be important factors to consider in efforts aimed at optimizing gout treatment outcomes.