Faculty Bibliography

To assess the impact of allopurinol on diabetes in a retrospective cohort of Veterans' Affairs patients with gout.The New York Harbor VA computerized patient record system was searched to identify patients with an ICD-9 code for gout meeting at least 4 modified 1977 American Rheumatology Association gout diagnostic criteria. Patients were divided into subgroups based on >30 continuous days of allopurinol, versus no allopurinol. New diagnoses of diabetes, defined according to American Diabetes Association diagnostic criteria or clinical documentation explicitly stating a new diagnosis of diabetes, were identified during an observation period from January 1, 2000 through December 31, 2015.Six hundred six gout patients used allopurinol >30 continuous days, and 478 patients never used allopurinol. Over an average 7.9 ± 4.8 years of follow-up, there was no significant difference in diabetes incidence between the allopurinol and non-allopurinol groups (11.7/1000 person-years vs 10.0/1000 person-years, P = .27). A lower diabetes incidence in the longest versus shortest quartiles of allopurinol use (6.3 per 1000 person-years vs 19.4 per 1000 person-years, P<.0001) was attributable to longer duration of medical follow-up.In this study, allopurinol use was not associated with decreased diabetes incidence. Prospective studies may further elucidate the relationship between hyperuricemia, gout, xanthine oxidase activity, and diabetes, and the potential impact of gout treatments on diabetes incidence.

OBJECTIVE:To assess longterm safety in a US cohort of patients with rheumatoid arthritis (RA) treated with adalimumab (ADA) in real-world clinical care settings. METHODS:This observational study analyzed the longterm incidence of safety outcomes among patients with RA initiating ADA, using data from the Corrona RA registry. Patients were adults (≥ 18 yrs) who initiated ADA treatment between January 2008 and June 2017, and who had at least 1 followup visit. RESULTS:In total, 2798 ADA initiators were available for analysis, with a mean age of 54.5 years, 77% female, and mean disease duration of 8.3 years. Nearly half (48%) were biologic-naive, and 9% were using prednisone ≥ 10 mg at ADA initiation. The incidence rates per 100 person-years for serious infections, congestive heart failure requiring hospitalization, malignancy (excluding nonmelanoma skin cancer), and all-cause mortality were 1.86, 0.15, 0.64, and 0.33, respectively. The incidence of serious infections was higher in the first year of therapy (3.44, 95% CI 2.45-4.84) than in subsequent years, while other measured adverse effects did not vary substantially by duration of exposure. The median time to ADA discontinuation was 11 months, while the median time to first serious infection among those experiencing a serious infection event was 12 months. CONCLUSION/CONCLUSIONS:Analysis of longterm data from this prospective real-world registry demonstrated a safety profile consistent with previous studies in patients with RA. This analysis did not identify any new safety signals associated with ADA treatment and provides guidance for physicians prescribing ADA for extended periods.

OBJECTIVE:To identify the extent to which opioid prescribing rates for patients with rheumatoid arthritis (RA) varied in the U.S. and to determine the implications of baseline opioid prescribing rates on future probability of chronic opioid use. METHODS:We identified patients with RA from physicians who contributed ≥10 patients within the first 12 months of participation in the Consortium of Rheumatology Researchers of North America (Corrona) RA registry. Baseline opioid prescribing rate was calculated by dividing the number of patients with RA reporting opioid use during the first 12 months by the number of patients with RA providing data that year. To estimate odds ratios (ORs) for chronic opioid use, we used generalized linear mixed models. RESULTS:The percent of patients who reported chronic opioid use during the follow-up period was 7.0% (163/2322) in the very low (referent) intensity prescribing group compared to 6.8% (153/2254) in the low intensity prescribing group, 12.5% (294/2352) in the moderate prescribing group, and 12.7% (307/2409) in the high prescribing group. The OR (95% confidence interval) for chronic opioid use after the baseline period was 1.16 (0.79 to 1.70) for patients of low prescribing physicians, 1.89 (1.27 to 2.82) for patients of moderate prescribing physicians, and 2.01 (1.43 to 2.83) for patients of high prescribing physicians, compared to very low prescribing physicians. CONCLUSIONS:Rates of opioid prescriptions varied widely. Baseline opioid prescribing rates were a strong predictor of whether a patient would become a chronic opioid user in the future, after controlling for patient characteristics.

INTRODUCTION/BACKGROUND:Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) are three common inflammatory rheumatic diseases that can lead to deformities and joint destruction. Few studies have compared disease burden across patients with these diseases. The objective of this study was to compare disease burden in patients with RA, PsA, or axSpA in routine US clinical practice. METHODS:or Fisher's exact tests for categorical variables. RESULTS:A total of 11,350 patients with RA, 2003 with PsA, and 495 with axSpA were included. Patients with RA had shorter mean symptom and disease duration (9.4 and 7.6 years, respectively) than those with PsA (11.2 and 8.4 years) or axSpA (16.7 and 9.8 years). Patients with PsA had lower mean physician global assessment (18.6 vs. 27.3), higher patient global assessment (43.2 vs. 36.9), comparable pain (38.9 vs. 39.5), and lower fatigue (41.1 vs. 43.4) scores than those with RA. Patients with axSpA had comparable mean physician global assessment (25.5 vs. 27.3) and higher patient global assessment (50.2 vs. 36.9), pain (46.1 vs. 39.5), and fatigue (48.3 vs. 43.4) scores than those with RA. CONCLUSIONS:Disease burden in patients with PsA or axSpA was comparable to or greater than that in patients with RA on the basis of common patient-reported outcome measures but appeared lower when assessed using RA disease activity measures, suggesting that disease-specific approaches to care are needed to optimize disease management. FUNDING/BACKGROUND:This study was sponsored by Corrona, LLC, and financial support was provided by Novartis. The Rapid Service Fee was funded by Novartis. Plain language summary available for this article.

BACKGROUND:The goal of this study is to use comprehensive molecular profiling to characterize clinical response to anti-TNF therapy in a real-world setting and identify reproducible markers differentiating good responders and non-responders in rheumatoid arthritis (RA). METHODS:Whole-blood mRNA, plasma proteins, and glycopeptides were measured in two cohorts of biologic-naïve RA patients (n = 40 and n = 36) from the Corrona CERTAIN (Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory coNditions) registry at baseline and after 3 months of anti-TNF treatment. Response to treatment was categorized by EULAR criteria. A cell type-specific data analysis was conducted to evaluate the involvement of the most common immune cell sub-populations. Findings concordant between the two cohorts were further assessed for reproducibility using selected NCBI-GEO datasets and clinical laboratory measurements available in the CERTAIN database. RESULTS:A treatment-related signature suggesting a reduction in neutrophils, independent of the status of response, was indicated by a high level of correlation (ρ = 0.62; p < 0.01) between the two cohorts. A baseline, response signature of increased innate cell types in responders compared to increased adaptive cell types in non-responders was identified in both cohorts. This result was further assessed by applying the cell type-specific analysis to five other publicly available RA datasets. Evaluation of the neutrophil-to-lymphocyte ratio at baseline in the remaining patients (n = 1962) from the CERTAIN database confirmed the observation (odds ratio of good/moderate response = 1.20 [95% CI = 1.03-1.41, p = 0.02]). CONCLUSION/CONCLUSIONS:Differences in innate/adaptive immune cell type composition at baseline may be a major contributor to response to anti-TNF treatment within the first 3 months of therapy.

Background/Purpose : Real-world evidence (RWE) is key to understanding post-approval long-term safety of medications. Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. A prospective observational 5-year study, embedded within the US Corrona RA registry, was initiated to evaluate the safety of tofacitinib after US Food and Drug Administration approval on Nov 6, 2012. The objective of this analysis was to compare 5-year incidence rates (IRs) of malignancy and mortality in patients (pts) initiating tofacitinib vs biologic (b)DMARDs using US Corrona RA registry cohorts. Methods : This prospective, observational 5-year study derived from the ongoing US Corrona RA registry routinely collects structured safety data on serious adverse events (AEs) and AEs of interest from investigators. IRs (no. of events/100 pt-years [PY]) of total cancer (excluding non-melanoma skin cancer [NMSC]), NMSC, and death were compared using propensity score (PS) methods to adjust for non-random treatment assignment among RA pts who newly initiated tofacitinib (US approved dose 5 mg twice daily) or a bDMARD regardless of dose/schedule between Nov 6, 2012 and July 31, 2018 (follow-up through Jan 31, 2019). Sufficient malignancy and mortality events occurred to provide 80% power to detect a hazard ratio (HR) of 2.0. Baseline variables with standardized difference > 0.10 between cohorts and a priori selected covariates (gender, age, line of therapy, history of AE of interest) were used to derive PS-trimmed (primary analysis) and PS-matched populations (ratio: max. 4 bDMARD:1 tofacitinib; caliper= 0.05). Analyses used a 'once exposed, always exposed' approach following patients from therapy initiation until an AE of interest, loss to follow-up, or end of data collection period, whichever came first; follow-up continued if a patient discontinued or switched therapy. Multivariable-adjusted Cox regression was used to estimate HRs of first events between cohorts. Results : In total, 1999 tofacitinib (4505.62 PY) and 6354 bDMARD (16670.84 PY) initiators were included. Following PS trimming, analyses for total cancer excluding NMSC, NMSC, and death, respectively, included 1420/1419/1419 tofacitinib initiators, and 4820/4820/4821 bDMARD initiators. Of tofacitinib and bDMARD initiators, respectively, 88% and 59% had prior bDMARD use. IRs of all three outcomes were similar in both cohorts; the adjusted HR (95% confi-dence interval [CI]) was 1.04 (0.68, 1.61) for total cancer excluding NMSC, 1.02 (0.69, 1.50) for NMSC, and 1.0 (0.62, 1.63) for death (Figure 1). Similar results were observed in PS-matched populations. Conclusion : To our knowledge, this is the first comparative RWE for tofacitinib and bDMARDs to use PS-trimmed/ matched analyses to adjust for channeling/prescribing patterns. RA pts initiating tofacitinib or bDMARDs had similar rates of total cancer excluding NMSC, NMSC, and death

This study described treatment patterns in a psoriatic arthritis (PsA) patient registry for new or ongoing tumor necrosis factor inhibitor (TNFi) monotherapy, conventional synthetic disease-modifying antirheumatic drug (csDMARD) monotherapy, or TNFi/csDMARD combination therapy. This retrospective analysis included adults with PsA who enrolled in the Corrona PsA/spondyloarthritis registry between March 21, 2013 (registry initiation), and January 31, 2017, and received an approved TNFi and/or csDMARD as "existing use" starting before registry entry or "initiated use" starting on/after registry entry. Therapy persistence was defined as index therapy use for ≥ 12 months without a treatment gap of ≥ 30 days. Among the evaluable patients with existing TNFi monotherapy (n = 251), csDMARD monotherapy (n = 225), and combination therapy (n = 214), 93, 87, and 87% were persistent for ≥ 12 months, and another 6, 5, and 5%, respectively, had no change with < 12 months of follow-up after first use. Among evaluable patients who initiated use of TNFi monotherapy (n = 26), csDMARD monotherapy (n = 35), and combination therapy (n = 15), 50, 43, and 53% were persistent for ≥ 12 months, and another 27, 20, and 20%, respectively, had no change with < 12 months of follow-up after first use. After initiation of index therapy, most changes (19-27% of patients) were discontinuation; 4-13% switched biologic therapy during follow-up. The results of this analysis of real-world treatment patterns in a PsA patient registry suggest that nonpersistence for TNFi monotherapy, csDMARD monotherapy, or TNFi/csDMARD combination therapy occurs more commonly after initiation of therapy than in patients with existing therapy. Trial registration: NCT02530268.

OBJECTIVE:To examine predictors of remission among patients with psoriatic arthritis (PsA) initiating a tumor necrosis factor (TNF) inhibitor. METHODS:Patients with PsA enrolled in the Corrona Registry between 2005 and 2013 were followed from initiation of a TNF inhibitor (TNFi; etanercept, adalimumab, infliximab, certolizumab, or golimumab) to the visit closest to 12 months. Additional inclusion criteria included 3 tender or 3 swollen joints. Outcomes of interest were Clinical Disease Activity Index (CDAI) ≤ 2.8 (remission), low disease activity (LDA; CDAI ≤ 10), change in the modified Health Assessment Questionnaire (mHAQ) ≥ 0.35 and achievement of mHAQ < 0.30. Predictors were measured on or before TNFi initiation. Covariates significant in univariable logistic regression models and ≤ 5% missing values were included in a multivariable model and removed individually until all remaining variables were significant (p < 0.05). RESULTS:Among 1832 TNFi initiations, 774 initiations (624 patients) met inclusion criteria. Median age at initiation was 52 years [interquartile range (IQR) 44-60], 56% were female, median PsA duration was 4 years (IQR 2-11), and median CDAI at baseline was 20 (IQR 14.5-28). Remission was achieved by 14% and LDA (or remission) by 37%. Achieving remission was positively associated with college education (OR 1.88, 95% CI 1.11-3.19) but negatively associated with female sex (0.62, 95% CI 0.40-0.97), obese body mass index (0.51, 95% CI 0.32-0.81), hypertension (0.55, 95% CI 0.32-0.95), previous biologic use (0.41, 95% CI 0.26-0.65), and baseline pain (0.80 per 10 mm visual analog scale, 95% CI 0.73-0.87). Predictors for LDA, mHAQ < 0.30, and mHAQ change were similar. CONCLUSION/CONCLUSIONS:Few patients with PsA in a US-based registry achieved remission by CDAI criteria. Female sex, obesity, comorbidities, and education influence achievement of remission on a TNFi.

BACKGROUND:Despite increasing awareness of the disease, rates of undiagnosed psoriatic arthritis (PsA) are high in patients with psoriasis (PsO). The validated Psoriasis Epidemiology Screening Tool (PEST) is a 5-item questionnaire developed to help identify PsA at an early stage. OBJECTIVES/OBJECTIVE:To assess the risk of possible undiagnosed PsA among patients with PsO and characterize patients based on PEST scores. METHODS:This study included all patients enrolled in the Corrona Psoriasis Registry with data on all 5 PEST questions. Demographics, clinical characteristics, and patient-reported outcomes were compared in Corrona Psoriasis Registry patients with PEST scores ≥ 3 and < 3 using t-tests for continuous variables and chi-squared tests for categorical variables; scores ≥ 3 may indicate PsA. RESULTS:Of 1516 patients with PsO, 904 did not have dermatologist-reported PsA; 112 of these 904 patients (12.4%) scored ≥ 3 and were significantly older, female, less likely to be working, and had higher BMI than patients with scores < 3. They also had significantly longer PsO duration, were more likely to have nail PsO, and had worse health status, pain, fatigue, Dermatology Life Quality Index, and activity impairment. CONCLUSIONS:Improved PsA screening is needed in patients with PsO because the validated PEST identified over one-tenth of registry patients who were not noted to have PsA as having scores ≥ 3, who could have had undiagnosed PsA. Appropriate, earlier care is important because these patients were more likely to have nail PsO, worse health-related quality of life, and worse activity impairment.

OBJECTIVES/OBJECTIVE:The opioid epidemic is a major public health concern. However, little is known about opioid use among rheumatoid arthritis (RA) patients. We examined trends in chronic opioid use in RA patients from 2002-2015 and identified clinical predictors. METHODS:RA patients were identified from the Corrona registry. Opioid use was ascertained from surveys obtained at clinical visits, as often as every 3 months. Chronic opioid use was defined as any opioid use reported during ≥2 consecutive study visits. Annual prevalence of chronic opioid use was calculated among 33,739 RA patients with data on opioid use from ≥2 visits. Among the 26,288 individuals who were not taking opioids at baseline, Cox proportional hazards models identified associations between patient characteristics and incident chronic opioid use. RESULTS:Chronic opioid use increased from 7.4% in 2002 to 16.9% in 2015. Severe pain (HR 2.53, 95% CI 2.19-2.92) and antidepressant use (HR 1.79, 95% CI 1.64-1.92) were associated with increased risk for chronic opioid use. High disease activity (HR 1.55, 95% CI 1.30-1.84) and high disability (HR 1.45, 95% CI 1.27-1.65) were also associated with chronic opioid use, whereas Asian race (HR 0.49, 95% CI 0.36-0.68) was associated with decreased risk for chronic opioid use. CONCLUSION/CONCLUSIONS:Among RA patients, chronic opioid use doubled from 2002 to 2015. Pain and antidepressant use were the strongest predictors of chronic opioid use. To curb the rise in chronic opioid use, strategies for stringent control of RA disease activity and management of pain and depression should be research priorities.