Lowering Expectations: Glucocorticoid Tapering Among Veterans With Rheumatoid Arthritis Achieving Low Disease Activity on Stable Biologic Therapy.

OBJECTIVE: In the Steroid EliMination In Rheumatoid Arthritis (SEMIRA) trial, 65% of patients with rheumatoid arthritis (RA) in low disease activity (LDA) on stable biologic therapy successfully tapered glucocorticoids. We aimed to evaluate real-world rates of glucocorticoid tapering among similar patients in the Veterans Affairs Rheumatoid Arthritis registry. METHODS: Within a multicenter, prospective RA cohort, we used registry data and linked pharmacy claims from 2003 to 2021 to identify chronic prednisone users achieving LDA after initiating a new biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD). We defined the index date as first LDA occurring 60 to 180 days after b/tsDMARD initiation. The primary outcome of successful tapering, assessed at day 180 after LDA, required a 30-day averaged prednisone dose both less than or equal to 5mg/day and at least 50% lower than at the index date. The secondary outcome was discontinuation, defined as a prednisone dose of 0 mg/day at days 180 through 210. We used univariate statistics to compare patient characteristics by fulfillment of the primary outcome. RESULTS: We evaluated 100 b/tsDMARD courses among 95 patients. Fifty-four courses resulted in successful tapering; 33 resulted in discontinuation. Positive rheumatoid factor, higher erythrocyte sedimentation rate, more background DMARDs, shorter time from b/tsDMARD initiation to LDA, and higher glucocorticoid dose 30 days before LDA were associated with greater likelihood of successful tapering. CONCLUSION: In a real-world RA cohort of chronic glucocorticoid users in LDA, half successfully tapered and a third discontinued prednisone within 6 months of initiating a new b/tsDMARD. Claims-based algorithms of glucocorticoid tapering and discontinuation may be useful to evaluate predictors of tapering in administrative data sets.

Vehicle Control as a Measure of Real-World Driving Performance in Patients With Rheumatoid Arthritis.

OBJECTIVE: To quantify vehicle control as a metric of automobile driving performance in patients with rheumatoid arthritis (RA). METHODS: Naturalistic driving assessments were completed in patients with active RA and controls without disease. Data were collected using in-car, sensor-based instrumentation installed in the participants' own vehicles to observe typical driving habits. RA disease status, disease activity, and functional status were associated with vehicle control (lateral [steering] and longitudinal [braking/accelerating] acceleration variability) using mixed-effect linear regression models stratified by road type (defined by roadway speed limit). RESULTS: Across 1,292 driving hours, RA drivers (n = 33) demonstrated differences in vehicle control compared to controls (n = 23), with evidence of significant statistical interaction between disease status and road type (P < 0.001). On residential roads, participants with RA demonstrated overall lower braking/accelerating variability than controls (P ≤ 0.004) and, when disease activity was low, lower steering variability (P = 0.03). On interstates/highways, RA was associated with increased steering variability among those with moderate/high Clinical Disease Activity Index scores (P = 0.04). In models limited to RA, increases in disease activity and physical disability over 12 weeks of observation were associated with a significant increase in braking/accelerating variability on interstate/highways (both P < 0.05). CONCLUSION: Using novel naturalistic assessments, we linked RA and worsening RA disease severity with aberrant vehicle control. These findings support the need for further research to map these observed patterns in vehicle control to metrics of driver risk and, in turn, to link patterns of real-world driving behavior to diagnosis and disease activity.

Cause-Specific Mortality in Patients With Gout in the US Veterans Health Administration: A Matched Cohort Study.

OBJECTIVE: To compare all-cause and cause-specific mortality risk between patients with gout and patients without gout in the Veteran's Health Administration (VHA). METHODS: We performed a matched cohort study, identifying patients with gout in the VHA from January 1999 to September 2015 based on the presence of ≥2 International Classification of Diseases, Ninth Revision codes for gout (274.X). Gout patients were matched up to 1:10 on birth year, sex, and year of VHA enrollment with patients without gout and followed until death or end of study (December 2017). Cause of death was obtained from the National Death Index. Associations of gout with all-cause and cause-specific mortality were examined using multivariable Cox regression. RESULTS: Gout (n = 559,243) and matched non-gout controls (n = 5,428,760) had a mean age of 67 years and were 99% male. There were 246,291 deaths over 4,250,371 patient-years in gout patients and 2,000,000 deaths over 40,441,353 patient-years of follow-up in controls. After matching, gout patients had an increased risk of death (hazard ratio [HR] 1.09 [95% confidence interval (95% CI) 1.08-1.09]), which was no longer present after adjusting for comorbidities (HR 0.98 [95% CI 0.97-0.98]). The strongest association of gout with cause-specific mortality was observed with genitourinary conditions (HR 1.50 [95% CI 1.47-1.54]). Gout patients were at lower risk of death related to neurologic (e.g., Alzheimer's disease and Parkinson's disease) (HR 0.63 [95% CI 0.62-0.65]) and mental health (HR 0.66 [95% CI 0.65-0.68]) conditions. CONCLUSION: A higher risk of death among gout patients in the VHA was related to comorbidity burden. While deaths attributable to neurologic and mental health conditions were less frequent among gout patients, genitourinary conditions were the most overrepresented causes of death.

Coadministration of Immunosuppressant Treatments With Pegloticase in the Context of Solid-Organ Transplantation and Gout: A Case Report.

Refractory gout can be treated with infusions of pegloticase, which metabolizes uric acid into a product readily excreted in urine. Antidrug antibodies often develop, leading to reduced efficacy and potential infusion reactions. The concomitant administration of immunosuppressive agents has been suggested as a means of mitigating the effects of drug-related immunogenicity, rendering treatment more tolerable, and resulting in better outcomes. This report presents cases of 2 patients with tophaceous gout, each having previously undergone a solid-organ transplant, each taking immunosuppressants to prevent organ rejection, and each successfully treated with pegloticase. Although data from randomized controlled studies are needed, these cases suggest that it may be beneficial to coadminister an immunosuppressive medication to extend drug persistence with pegloticase in the management of refractory gout. This approach could allow patients to receive long-term treatment, resulting in improved patient outcomes.

Comparison of Rates of Lower Extremity Amputation in Patients With and Without Gout in the US Department of Veterans Affairs Health System.

Importance: Cardiometabolic and other risk factors could render patients with gout more likely to undergo lower extremity amputation (LEA). Objective: To examine the rate of and factors associated with LEA in patients with gout. Design, Setting, and Participants: In this matched cohort study using national administrative data, multivariable Cox proportional hazards regression models were used to examine the associations of gout with LEA. In analyses limited to patients with gout, attributes of serum urate control and treatment with urate-lowering therapy were examined as factors associated with LEA. This study included patients who used US Department of Veterans Affairs services from January 1, 2000, to July 31, 2015. Patients with gout were identified using diagnostic codes and matched with up to 10 controls by age, sex, and year of benefit enrollment. Data analysis was performed from January 26, 2021, to September 3, 2021. Exposures: Gout classification served as the primary independent variable of interest. In analyses limited to patients with gout, factors associated with serum urate control and urate-lowering therapy were examined. Main Outcomes and Measures: Overall LEA, as well as toe, transmetatarsal, below-the-knee, and above-the-knee amputation. Results: This cohort study included 5 924 918 patients, 556 521 with gout (mean [SD] age, 67 [12] years; 550 963 (99.0%) male; 88 853 [16.0%] Black non-Hispanic; 16 981 [4.3%] Hispanic/Latinx; 345 818 [62.1%] White non-Hispanic; 80 929 [14.5%] with race and ethnicity data missing; and 23 940 [4.3%] classified as other) and 5 368 397 without gout (mean [SD] age, 67 [12] years; 5 314 344 [99.0%] male; 558 464 [10.4%] Black non-Hispanic; 204 291 [3.0%] Hispanic/Latinx; 3 188 504 [59.4%] White non-Hispanic; 1 257 739 [23.4%)] with race and ethnicity data missing; and 159 399 [3.0%] classified as other). Compared with patients without gout, patients with gout were more likely to undergo amputation, an increased rate that remained after adjustment (adjusted hazard ratio, 1.20; 95% CI, 1.16-1.24) and was highest for below-the-knee amputation (adjusted hazard ratio, 1.59; 95% CI, 1.39-1.81). In those with gout, poor serum urate control (mean >7 mg/dL during the preceding year) was associated with a 25% to 37% increase in the rate of amputation. In contrast, treatment with urate-lowering therapy was not associated with the LEA rate. Conclusions and Relevance: In this matched cohort study, patients with gout were more likely to undergo LEA. This increase was independent of other comorbidities that have been associated with amputation, including diabetes and peripheral vascular disease. Serum urate control was independently associated with the LEA rate, suggesting the possibility that lower extremity amputation may be preventable in some patients.

Incidence, Prevalence, and Burden of Gout in the Veterans Health Administration.

OBJECTIVE: To determine the prevalence, incidence, and burden of gout in the Veterans Health Administration (VHA) from 2005 to 2014. METHODS: We used national VHA data from January 1999 to December 2014 to determine the annual incidence and prevalence of gout in the VHA. Gout burden to the VHA was determined by the proportion of patients with an encounter related to gout. Rates of urate-lowering therapy (ULT) and opiate use were determined annually. Characteristics of those with and without gout were compared using 2014 data. RESULTS: From 2005 to 2014, gout prevalence in the VHA increased from 4.2% to 5.8%, while disease incidence ranged from 5.8 to 7.4 cases per 1,000 patient-years. Gout prevalence was highest among men, older patients, and non-Hispanic black patients. During 2014, 4.0% of all inpatient or outpatient encounters and 1.3% of hospitalizations were gout related. Administration of ULT remained stable over the 10-year period, with 46% of gout patients receiving ULT in 2014. In contrast, 16.4% of prevalent gout patients were receiving a weak opioid in 2014, nearly doubling the prescription rate of weak opioids in 2005, while the use of stronger opioids did not change significantly over this period. Patients with gout had greater comorbidity and health care utilization than patients without gout. CONCLUSION: The burden posed by gout in the VHA is considerable and increased between 2005 and 2014. While the use of ULT has remained stable, the use of opioid therapy has increased among patients with gout.

Associations between an expanded autoantibody profile and treatment responses to biologic therapies in patients with rheumatoid arthritis.

BACKGROUND: Although biologics represent a major advance in rheumatoid arthritis (RA), many patients fail to achieve adequate responses to these agents. We examined whether combined positivity to three well-characterized autoantibodies predicts treatment response among RA patients initiating biologics. METHODS: The study included biologic-naïve patients initiating anti-TNF treatment, biologic-exposed patients switching to rituximab or tocilizumab, and patients (biologic naïve or exposed) initiating abatacept. Rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP) antibody, and IgG antibodies to malondialdehyde-acetaldehyde (MAA) were measured using banked enrollment serum. The relationship between the number of autoantibodies positive (0-3) and treatment response (absolute improvement in 28-joint Disease Activity Score [DAS28-CRP] or improvement > 1.2) at 6 months was examined using multivariable linear and logistic regression. RESULTS: Of 1,229 patients initiating biologics, 79% were women; 89% were Caucasian. The number of baseline RA-related autoantibodies positive was associated with improved treatment response in a dose-dependent fashion. Compared to patients seronegative for all autoantibodies, adjusting for covariates, those positive for all three were more than twice (OR 2.35; 95% CI 1.57-3.51) as likely to achieve DAS28 improvement > 1.2 units. Associations of autoantibody positivity with biologic treatment response were strongest for anti-CCP antibody, persisted in analyses limited to biologic naïve patients, and did not appear to differ markedly among different agents examined. CONCLUSION: An expanded autoantibody profile appears to significantly predict RA treatment response to biologic treatment in a dose-dependent fashion. Incorporating these serologic profiles with additional biomarkers or other informative patient characteristics could provide an opportunity to personalize RA management.