Examining the potential direct cardiovascular benefit of tumor-necrosis factor inhibitor in rheumatoid arthritis: Natural and controlled direct effect analyses.

BACKGROUND/PURPOSE: Tumor necrosis factor inhibitors (TNFi) may have a direct benefit on cardiovascular (CV) disease beyond reducing rheumatoid arthritis (RA) disease activity measured by the Clinical Disease Activity Index (CDAI). METHODS: We compared TNFi initiators and methotrexate (MTX) monotherapy initiators from the CorEvitas RA registry. Two approaches to the "direct effect" of TNFi beyond CDAI were used. In the natural direct effect (NDE) analysis, the potential CV benefit of TNFi was partitioned into NDE and the natural indirect effect (NIE) mediated by CDAI during the first 6 months. We also estimated the controlled direct effects (CDE), corresponding to the direct benefit of TNFi when CDAI trajectories were hypothetically equalized between the initiators of TNFi and MTX monotherapy at a constant value. Estimates were given on the hazard ratio scale. RESULTS: We identified 5764 initiators of TNFi and 3588 initiators of MTX monotherapy. TNFi initiators were younger (58 vs. 64 years) with a shorter disease duration. Our total effect estimates (TNFi vs. MTX [reference]) were protective in direction (0.76-0.91). The NDE estimate was 0.76 [95% confidence interval (CI) 0.59, 0.98], whereas the NIE estimate was 1.00 [95%CI 1.00, 1.00]. In the CDE analyses accounting for longitudinal CDAI, the CDE estimates was 1.27 [95%CI 0.60, 2.69]. CONCLUSIONS: We could not convincingly demonstrate a direct benefit of TNFi outside its impact on CDAI. At present, the emphasis should be on the stringent control of RA disease activity, a known important CV risk factor, regardless of medication choice.

Accuracy of administrative claims prescription fill data to estimate glucocorticoid use and dose in patients with rheumatoid arthritis.

PURPOSE: To assess accuracy of administrative claims prescription fill-based estimates of glucocorticoid use and dose, and approximate bias from glucocorticoid exposure misclassification. METHODS: We identified adults with rheumatoid arthritis with linked Medicare and CorEvitas registry data. An algorithm identifying glucocorticoid use and average dose over 90 days from Medicare prescription fills was compared to physician-reported measures from a CorEvitas visit during the same period, using weighted kappa to compare doses (none, ≤5 mg, 5-10 mg, >10 mg/day). A deterministic sensitivity analysis examined the effect of exposure misclassification on estimated glucocorticoid-associated infection risk from a prior study. RESULTS: We identified 621 observations among 494 patients. Prescription fills identified glucocorticoid use in 41.9% of observations versus 31.1% identified by CorEvitas physician-report. For glucocorticoid use (yes/no), prescription fills had sensitivity 88.1% (95% CI 82.7-92.3), specificity 79.0% (74.8-82.7), PPV 65.4% (59.3-71.2), NPV 93.6% (90.6-95.9), and 81.8% agreement with CorEvitas, with kappa 0.61 (moderate to substantial agreement). There was 89.5% agreement between prescription fills and physician-reported doses, with weighted kappa 0.56 (moderate agreement). Applying these results to a prior Medicare study evaluating glucocorticoid-associated infection risk [risk ratio 1.44 (95% CI 1.41-1.48)] led to an externally adjusted risk ratio of 1.74 when accounting for exposure misclassification, representing -17% bias in infection risk estimate. CONCLUSIONS: This study supports the use of claims data to estimate glucocorticoid use and dose, but investigators should account for exposure misclassification, which may lead to underestimates of glucocorticoid risks. Our results could be applied to adjust risk estimates in other studies that use prescription fills to estimate glucocorticoid use.

Disease activity and patient-reported outcomes in patients with rheumatoid arthritis and Sjögren's syndrome enrolled in a large observational US registry.

The objective of this study was to compare rheumatoid arthritis (RA) disease activity and patient-reported outcomes (PROs) in a national sample of patients with RA with/without Sjögren's syndrome (SS). Adults with RA from a large observational US registry (Corrona RA) with known SS status between 22 April 2010 and 31 July 2018 and a visit 12 (± 3) months after index date were identified (n = 36,256/52,757). SS status: determined from a yes/no variable reported at enrolment into the Corrona RA registry and follow-up visits. Index date: date that SS status was recorded (yes/no). Patients received biologic or targeted synthetic disease-modifying antirheumatic drugs as part of standard care. Patients with RA only were followed for ≥ 12 months to confirm the absence of SS. Patients were frequency- and propensity-score matched (PSM) 1:1 and stratified by disease duration and treatment response-associated variables, respectively. Clinical Disease Activity Index (CDAI) and PROs 12 months after index visit were compared in patients with and without SS. Baseline characteristics in 283 pairs of PSM patients were balanced. Mean change in CDAI score was numerically lower in patients with RA and SS than patients with RA only (8.8 vs 9.3). Reductions in PROs of pain, fatigue and stiffness were two- to threefold lower for patients with RA and SS versus RA only. Reductions in RA disease activity and RA-related PROs were lower in patients with RA and SS versus those with RA only. Our data indicate that SS adds to treatment challenges; physicians may wish to consider SS status when managing patients with RA.

Gout, Hyperuricaemia and Crystal-Associated Disease Network (G-CAN) consensus statement regarding labels and definitions of disease states of gout.

OBJECTIVE: There is a lack of standardisation in the terminology used to describe gout. The aim of this project was to develop a consensus statement describing the recommended nomenclature for disease states of gout. METHODS: A content analysis of gout-related articles from rheumatology and general internal medicine journals published over a 5-year period identified potential disease states and the labels commonly assigned to them. Based on these findings, experts in gout were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach agreement on disease state labels and definitions. RESULTS: The content analysis identified 13 unique disease states and a total of 63 unique labels. The Delphi exercise (n=76 respondents) and face-to-face meeting (n=35 attendees) established consensus agreement for eight disease state labels and definitions. The agreed labels were as follows: 'asymptomatic hyperuricaemia', 'asymptomatic monosodium urate crystal deposition', 'asymptomatic hyperuricaemia with monosodium urate crystal deposition', 'gout', 'tophaceous gout', 'erosive gout', 'first gout flare' and 'recurrent gout flares'. There was consensus agreement that the label 'gout' should be restricted to current or prior clinically evident disease caused by monosodium urate crystal deposition (gout flare, chronic gouty arthritis or subcutaneous tophus). CONCLUSION: Consensus agreement has been established for the labels and definitions of eight gout disease states, including 'gout' itself. The Gout, Hyperuricaemia and Crystal-Associated Disease Network recommends the use of these labels when describing disease states of gout in research and clinical practice.

Sex differences in gout characteristics: tailoring care for women and men.

BACKGROUND: To characterize the differences between women and men with gout. METHODS: We analyzed a US national cohort of gout patients cared for by rheumatologists. RESULTS: Compared with the 1012 men with gout, women with gout (n = 262) were older (71 vs. 61 years, p < 0.001) and had a greater burden of comorbid conditions (p < 0.001 for hypertension, diabetes, renal disease and obesity). Risk factors for gout differed with women more often taking diuretics (p < 0.001), while men more frequently had dietary triggers (p < 0.05). CONCLUSIONS: The profiles of women and men with gout are markedly different, suggesting a need to tailor treatment recommendations.

Preoperative Pain and Function: Profiles of Patients Selected for Total Knee Arthroplasty.

BACKGROUND: Total knee arthroplasty (TKA) is an effective treatment to relieve pain and restore function in patients with advanced knee osteoarthritis. TKA utilization is growing rapidly, and the appropriateness of current TKA use is of great interest. We examined patient-reported preoperative pain and function profiles to understand symptom severity at the time of TKA decision. METHODS: Data were from the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement. We included patients undergoing primary, unilateral TKAs between 2011 and 2014 for osteoarthritis and had data on the Knee Injury and Osteoarthritis Outcome Score (KOOS) pain and Short-Form 36-item Physical Component Summary (PCS) score. We compared patient profiles across groupings by symptoms: (1) little pain and high function (KOOS ≥70, PCS ≥40); (2) little pain but poor function (KOOS ≥70, PCS <40); (3) high pain but high function (KOOS <70, PCS ≥40); and (4) high pain and poor function (KOOS <70, PCS <40). RESULTS: Of 6936 patients, 77% had high pain and poor function (group 4), 19% had high pain "or" poor function (groups 2-3), and 5% had little pain and high function before TKA (group 1). In group 1, 86% were constantly aware of their knee problem, 48% reported pain daily yet 5% experienced severe or extreme pain on stairs, and 1% pain in bed. Over half had a lot of limitations in vigorous activities. Compared with group 4, group 1 were older, less obese, more educated, and included more men and people reporting being healthy, less disabled, and happy (P < .05 for all). CONCLUSION: Most patients undergoing TKAs had significant pain and/or poor function. Our results provide critical information given the current debate of potentially inappropriate TKA utilization in the United States.

Overcoming adherence issues and other barriers to optimal care in gout.

PURPOSE OF REVIEW: This review presents research published over the last year examining use of urate-lowering therapy (ULT) as well as trends over time in adherence to this class of agents. Additionally, it explores factors associated with nonadherence to ULTs for chronic gout and interventions to improve chronic gout management. RECENT FINDINGS: New literature suggests prescriptions of ULTs for prevalent and incident gout patients remains lower than expected based on the burden of the disease in the population. Overall ULT adherence remains suboptimal, in part related to inadequate patient education and copayment costs; although one study demonstrated improvement in adherence over a 15-year study period. Finally, interventions that include patient education and medication titration based on laboratory results successfully lowered serum urate levels to less than 6 mg/dl in the majority of patients. SUMMARY: Gout remains a prevalent disease that is poorly managed despite effective treatments. Recent research suggests that ULTs are underutilized and even when prescribed are not well adhered to. Patient-centered interventions that focus on education about pharmacologic therapy and lifestyle modifications with medication titration have resulted in a greater proportion of patients achieving recommended serum urate levels.

The comparative effectiveness of abatacept versus anti-tumour necrosis factor switching for rheumatoid arthritis patients previously treated with an anti-tumour necrosis factor.

OBJECTIVE: We compared the effectiveness of abatacept (ABA) versus a subsequent anti-tumour necrosis factor inhibitor (anti-TNF) in rheumatoid arthritis (RA) patients with prior anti-TNF use. METHODS: We identified RA patients from a large observational US cohort (2/1/2000-8/7/2011) who had discontinued at least one anti-TNF and initiated either ABA or a subsequent anti-TNF. Using propensity score (PS) matching (n:1 match), effectiveness was measured at 6 and 12 months after initiation based on mean change in Clinical Disease Activity Index (CDAI), modified American College of Rheumatology (mACR) 20, 50 and 70 responses, modified Health Assessment Questionnaire (mHAQ) and CDAI remission in adjusted regression models. RESULTS: The PS-matched groups included 431 ABA and 746 anti-TNF users at 6 months and 311 ABA and 493 anti-TNF users at 12 months. In adjusted analyses comparing response following treatment with ABA and anti-TNF, the difference in weighted mean change in CDAI (range 6-8) at 6 months (0.46, 95% CI -0.82 to 1.73) and 12 months was similar (-1.64, 95% CI -3.47 to 0.19). The mACR20 responses were similar at 6 (28-32%, p=0.73) and 12 months (35-37%, p=0.48) as were the mACR50 and mACR70 (12 months: 20-22%, p=0.25 and 10-12%, p=0.49, respectively). Meaningful change in mHAQ was similar at 6 and 12 months (30-33%, p=0.41 and 29-30%, p=0.39, respectively) as was CDAI remission rates (9-10%, p=0.42 and 12-13%, p=0.91, respectively). CONCLUSIONS: RA patients with prior anti-TNF exposures had similar outcomes if they switched to a new anti-TNF as compared with initiation of ABA.

A description of patient- and rheumatologist-reported depression symptoms in an American rheumatoid arthritis registry population.

OBJECTIVES: Depression is a common and important comorbidity in patients with rheumatoid arthritis (RA). The study aim was to describe rates of depressive symptoms and their associations with RA disease activity using measures reported from patients and rheumatologists. METHODS: The Consortium of Rheumatology Researchers of North America (CORRONA) registry is an observational cohort with data on more than 33,000 RA patients. Using depression symptom measures reported separately by patients and rheumatologists, lifetime prevalence, 12-month prevalence, and annualised incidence rates (IR) were estimated. Additionally, cross-sectional associations between RA disease and a history of depressive symptoms were examined. RESULTS: Lifetime prevalence estimates of 26.5% and 12.9% were reported by patients and rheumatologists, respectively. The 12-month prevalence rates reported by CORRONA patients and rheumatologists were 11.7% and 1.0%, respectively. The annualised IR from the self-reported depressive symptom measure was approximately 7.8 per 100 patient-years, compared to 0.4 per 100 patient-years reported by their rheumatologists. Increased disease activity at study entry was associated with a higher probability of reporting a history of depressive symptoms. CONCLUSIONS: RA patients have a high likelihood of experiencing symptoms of depression, while treating rheumatologists under-report them and disease estimates based on their reports were much lower when compared to healthy individuals. Thus, estimates of prevalence and the impact of these symptoms need to be interpreted based on the source of the diagnosis. Collectively, the findings of this study suggest that depressive symptoms are an important comorbidity that practicing rheumatologists should be aware of during clinical encounters.

The rheumatoid arthritis treat-to-target trial: a cluster randomized trial within the Corrona rheumatology network.

BACKGROUND: The treat-to-target (T2T) approach to the care of patients with rheumatoid arthritis involves using validated metrics to measure disease activity, frequent follow-up visits for patients with moderate to high disease activity, and escalation of therapy when patients have inadequate therapeutic response as assessed by standard disease activity scores. The study described is a newly launched cluster-randomized behavioral intervention to assess the feasibility and effectiveness of the T2T approach in US rheumatology practices. It is designed to identify patient and provider barriers to implementing T2T management. This initial paper focuses on the novel study design and methods created to provide these insights. METHODS/DESIGN: This trial cluster-randomizes rheumatology practices from the existing Corrona network of private and academic sites rather than patients within sites or individual investigators to provide either T2T or usual care (UC) for qualified patients who meet the 2010 revised American College of Rheumatology criteria for the diagnosis of rheumatoid arthritis and have moderate to high disease activity. Specific medication choices are left to the investigator and patient, rather than being specified in the protocol. Enrollment is expected to be completed by the end of 2013, with 30 practices randomized and enrolling a minimum of 530 patients. During the 12-month follow-up, visits are mandated as frequently as monthly in patients with active disease in the T2T group and every 3 months for the UC group. Safety data are collected at each visit. The coprimary endpoints include a comparison of the proportion of patients achieving low disease activity in the T2T and UC groups and assessment of the feasibility of implementing T2T in rheumatology practices, specifically assessment of the rates of treatment acceleration, frequency of visits, time to next visit conditional on disease activity, and probability of acceleration conditional on disease activity in the 2 groups. DISCUSSION: This cluster-randomized behavioral intervention study will provide valuable insights on the outcomes and feasibility of employing a T2T treatment approach in clinical practice in the United States. TRIAL REGISTRATION: NCT01407419.

Disparities in burden of disease in patients with rheumatoid arthritis across racial and ethnic groups.

To examine racial/ethnic differences in rheumatoid arthritis (RA) disease burden and change in clinical outcomes over time. We included CorEvitas Rheumatoid Arthritis Registry patients from two time periods (2013-2015 and 2018-2020). Clinical Disease Activity Index (CDAI) (as a continuous measure and as a dichotomous measure) and the Health Assessment Questionnaire-Disability Index (HAQ-DI) were assessed at each visit. Marginal means and their corresponding 95% confidence interval (CI) by race/ethnicity were estimated for each outcome using adjusted mixed effects linear and logistic regression models. Overall and pairwise tests were conducted to detect differences between race/ethnicity groups. Of 9,363 eligible patients (8,142 White, 527 Black, 545 Hispanic, 149 Asian), most (76%-85%) were female. At Visit 1, the mean disease duration ranged from 9.8-11.8 years. Estimated CDAI was significantly higher for Hispanics compared to Whites at Visit 1 (11.1 vs. 9.9; pairwise P = 0.033) and Visit 2 (9.2 vs. 8.0, pairwise P = 0.005). Disease activity improved over the 5-year study period among all race/ethnicity groups, though Hispanics improved less than Whites. Disease activity improved over the 5-year period across all racial/ethnicity groups, and disparities between racial/ethnicity groups in disease activity and functional status did persist over time, suggesting that further effort is needed to understand the drivers of these discrepancies to close this race/ethnicity gap. Key Points • Disease activity improved over the 5-year period across all racial and ethnic groups. • Disparities between racial and ethnic groups in disease activity and functional status did persist over time, suggesting that further effort is needed to understand the drivers of these discrepancies and close this racial gap.

Effectiveness of bDMARDs in ankylosing spondylitis patients by biologic use: experience from the CorEvitas PsA/SpA Registry.

OBJECTIVE: To describe bDMARD initiators by biologic experience among ankylosing spondylitis (AS) patients and change in disease activity and patient-reported outcomes (PROs) in real-world US patients. METHODS: We included patients ≥18 years with AS based on physician diagnosis enrolled between 3/2013 and 11/2019 in the CorEvitas Psoriatic Arthritis (PSA)/Spondyloarthritis Registry (NCT02530268). Patients concurrently diagnosed with PSA were excluded. Baseline (bDMARD initiation) demographics, comorbidities, disease characteristics, treatment, and PROs were collected. Response rates and changes in disease activity and PROs between baseline and 6- and 12- month follow-up visits were calculated. RESULTS: Of the 489 AS patients in the PsA/SpA Registry, 254 AS (52.0%) patients initiated a bDMARD at enrollment or during follow-up (total initiations: AS = 313). Of the 313 AS initiations, 179 (57.2%) had a 6-month follow-up, 122 (39.0%) had a 12-month follow-up, and 94 (30.0%) had a 6- and 12-month follow-up visit. For those AS initiators with a 6-month follow-up, the mean age was 49.1 years, 44.4% were female, and 70.4%, 47.5%, 96.1%, and 46.9% had never used cDMARDs, TNFis, non-TNFis, and bDMARDs, respectively. Of these 179 AS initiators, 20.1% and 14.0% achieved ASAS20/40, respectively. Further, only 34% achieved low disease activity (ASDAS <2.1). When stratified by biologic-naivete and biologic-experience, the ASAS 20/40 achievement rates were 26.2% and 14.7%, and 21.4% and 7.4%, respectively, for this cohort. CONCLUSION: Although AS patients initiate bDMARDs, many do not achieve optimal treatment responses. Future research is needed to investigate the aspects associated with inadequate improvement and treatment response to bDMARDs.

Comparative effectiveness of abatacept versus TNF inhibitors in rheumatoid arthritis patients who are ACPA and shared epitope positive.

BACKGROUND: The HLA-DRB1 shared epitope (SE) is a risk factor for the development of rheumatoid arthritis (RA) and the production of anti-citrullinated protein antibodies (ACPAs) in RA patients. Our objective was to examine the real-world effectiveness of abatacept versus tumor necrosis factor inhibitors (TNFi) in patients with RA who were SE and anti-cyclic citrullinated peptide antibody (anti-CCP3) positive. METHODS: Abatacept or TNFi initiators who were SE + and anti-CCP3+ (> 20 U/mL) at or prior to treatment and had moderate or high CDAI score (> 10) at initiation were identified. The primary outcome was mean change in CDAI score over six months. Analyses were conducted in propensity score (PS)-trimmed and -matched populations overall and a biologic-experienced subgroup. Mixed-effects models were used. RESULTS: In the overall PS-trimmed (abatacept, n = 170; TNFi, n = 157) and PS-matched cohorts (abatacept, n = 111; TNFi, n = 111), there were numerically greater improvements in mean change in CDAI between abatacept and TNFi but were not statistically significant. Similar trends were seen for biologic-experienced patients, except that statistical significance was reached for mean change in CDAI in the PS-trimmed cohort (abatacept, 12.22 [95% confidence interval (95%CI) 10.13 to 14.31]; TNFi, 9.28 [95%CI 7.08 to 11.48]; p = 0.045). CONCLUSION: In this real world cohort, there were numerical improvements in efficacy outcomes with abatacept over TNFi in patients with RA who were SE + and ACPA+, similar to results from a clinical trial population The only statistically significant finding after adjusting for covariates was greater improvement in CDAI with abatacept versus TNFi in the bio-experienced PS-trimmed cohort..

Heart failure risk among patients with rheumatoid arthritis starting a TNF antagonist.

BACKGROUND: While heart failure (HF) is associated with elevations in tumor necrosis factor (TNF)α, several trials of TNF antagonists showed no benefit and possibly worsening of disease in those with known severe HF. We studied the risk of new or recurrent HF among a group of patients receiving these agents to treat rheumatoid arthritis (RA). METHODS: We used data from four different US healthcare programmes. Subjects with RA receiving methotrexate were eligible to enter the study cohort if they added or switched to a TNF antagonist or another non-biological disease modifying antirheumatic drug (nbDMARD). These groups were compared in Cox regression models stratified by propensity score decile and adjusted for oral glucocorticoid dosage, prior HF hospitalisations, and the use of loop diuretics. RESULTS: We compared 8656 new users of a nbDMARD with 11 587 new users of a TNF antagonist with similar baseline covariates. The HR for the TNF antagonists compared with nbDMARD was 0.85 (95% CI 0.63 to 1.14). The HR was also not elevated in subjects with a history of HF. But, it was elevated prior to 2002 (HR 2.17, 95% CI 0.45 to 10.50, test for interaction p=0.036). Oral glucocorticoids were associated with a dose-related gradient of HF risk: compared with no use, 1≤5 mg HR 1.30 (95% CI 0.91 to 1.85), ≥5 mg HR 1.54 (95% CI 1.09 to 2.19). CONCLUSIONS: TNF antagonists were not associated with a risk of HF hospital admissions compared with nbDMARDs in this RA population.

The temporal relationship between depression and rheumatoid arthritis disease activity, treatment persistence and response: a systematic review.

OBJECTIVE: To determine whether depression has a temporal association with RA disease activity, treatment persistence and response to therapy. METHODS: We performed a systematic review encompassing an electronic database search of all published literature since the availability of biologic response modifiers (beginning in 1998) investigating the impact of depression on downstream RA disease progression and treatment. RESULTS: Only seven articles that evaluated temporal relationships between depression and RA outcomes comprising disease activity, treatment persistence and response to therapy, were included in the review. Results from these studies suggest that depression may exacerbate pain and disease activity and decrease the efficacy of pharmacological (i.e. biologic and non-biologic DMARDs) and some non-pharmacological (e.g. cognitive behavioural therapy) RA treatments. CONCLUSION: Given the available evidence, depression probably has a temporal influence on RA disease progression and treatment. However, it is unclear whether these observed effects are due to a response tendency on patient-reported outcomes created from negative cognitive perceptions, immunologically mediated processes that increase inflammation or behavioural changes that lead to decreased physical activity and a greater sensitivity to pain.

Primary care providers' knowledge, beliefs and treatment practices for gout: results of a physician questionnaire.

OBJECTIVE: We sought to examine primary care providers' gout knowledge and reported treatment patterns in comparison with current treatment recommendations. METHODS: We conducted a national survey of a random sample of US primary care physicians to assess their treatment of acute, intercritical and tophaceous gout using published European and American gout treatment recommendations and guidelines as a gold standard. RESULTS: There were 838 respondents (response rate of 41%), most of whom worked in private practice (63%) with >16 years experience (52%). Inappropriate dosing of medications in the setting of renal disease and lack of prophylaxis when initiating urate-lowering therapy (ULT) accounted for much of the lack of compliance with treatment recommendations. Specifically for acute podagra, 53% reported avoidance of anti-inflammatory drugs in the setting of renal insufficiency, use of colchicine at a dose of ≤2.4 mg/day and no initiation of a ULT during an acute attack. For intercritical gout in the setting of renal disease, 3% would provide care consistent with the recommendations, including initiating a ULT at the appropriate dose with dosing titration to a serum urate level of ≤6 mg/dl and providing prophylaxis. For tophaceous gout, 17% reported care consistent with the recommendations, including ULT use with dosing titration to a serum urate level of ≤6 mg/dl and prophylaxis. CONCLUSION: Only half of primary care providers reported optimal treatment practices for the management of acute gout and <20% for intercritical or tophaceous gout, suggesting that care deficiencies are common.

Prescribing practices in a US cohort of rheumatoid arthritis patients before and after publication of the American College of Rheumatology treatment recommendations.

OBJECTIVE: To examine prescribing practices in the use of biologic and nonbiologic disease-modifying antirheumatic drugs (DMARDs) to treat patients with rheumatoid arthritis (RA), before and after publication of the American College of Rheumatology (ACR) treatment recommendations. METHODS: Biologics-naive RA patients under the care of a rheumatologist in the US were identified from the Consortium of Rheumatology Researchers of North America registry. Patients were included if their visits occurred prior to and/or at least 6 months after publication of the ACR treatment recommendations (time periods of February 2002-June 2008 versus December 2008-December 2009). The population was divided into 2 mutually exclusive cohorts: 1) methotrexate (MTX) monotherapy users, and 2) multiple nonbiologic DMARD users. Initiation or dose escalation of biologic and nonbiologic DMARDs in response to active disease was assessed cross-sectionally and longitudinally in comparison to the ACR recommendations. The impact of the publication of the ACR recommendations on treatment practices was assessed using logistic regression, stratified by disease activity and adjusted for clustering of physicians and geographic region. RESULTS: After 1 visit, 24-37% of patients receiving MTX monotherapy who had moderate disease activity and a poor prognosis or high disease activity received care consistent with the ACR recommendations; after 2 visits, 34-56% of the MTX monotherapy group received care consistent with the recommendations. In the patients receiving multiple nonbiologic DMARDs, 31-47% of those with moderate or high disease activity received care consistent with the recommendations after 1 visit, and 43-51% received such care after 2 visits. Publication of the recommendations did not significantly change treatment patterns for those with active disease. CONCLUSION: Substantial numbers of RA patients with active disease did not receive care consistent with the current ACR treatment recommendations. Innovative approaches to improve care are necessary.

Validity of diagnostic codes and prevalence of psoriasis and psoriatic arthritis in a managed care population, 1996-2009.

BACKGROUND: Few population-based studies have reported the prevalence of psoriatic disease. OBJECTIVE: We validated computerized diagnoses to estimate the prevalence of psoriasis and psoriatic arthritis. METHOD: We identified adults with ≥1 ICD-9 diagnosis codes of 696.0 (psoriatic arthritis) or 696.1 (psoriasis) in clinical encounter data during 1996-2009 and used chart review to confirm the diagnoses in random samples of patients. We then used the best performing case-finding algorithms to estimate the point prevalence of psoriasis and psoriatic arthritis. RESULTS: The number of persons with a diagnosis for psoriasis (ICD-9 code 696.1) was 87 827. Chart review of a random sample of 101 cases with at least one dermatologist-rendered psoriasis code revealed a positive predictive value (PPV) of 90% (95% CI, 83-95) with sensitivity of 88% (95% CI, 80-93). Psoriatic arthritis (code 696.0) was recorded for 5187 patients, with the best performing algorithm requiring ≥2 diagnoses recorded by a rheumatologist or ≥1 diagnosis recorded by a rheumatologist together with ≥1 psoriasis diagnoses recorded by a dermatologist; the PPV was 80% (95% CI, 70-88) with sensitivity 73% (95% CI, 63-82). Among KPNC adults, the point prevalence of psoriasis, with or without psoriatic arthritis, was 939 (95% CI, 765-1142) per 100 000, and the overall prevalence of psoriatic arthritis, with or without psoriasis, was 68 (95% CI, 54-84) per 100 000. CONCLUSION: Within an integrated health care delivery system, the use of computerized diagnoses rendered by relevant disease specialists is a valid method for identifying individuals with psoriatic disease.

Association between anti-TNF-α therapy and interstitial lung disease.

BACKGROUND: Anti-tumor necrosis factor-α (TNF-α) agents have been hypothesized to increase the risk of interstitial lung disease (ILD), including its most severe manifestation, pulmonary fibrosis. METHODS: We conducted a cohort study among autoimmune disease patients who were members of Kaiser Permanente Northern California, 1998-2007. We obtained therapies from pharmacy data and diagnoses of ILD from review of X-ray and computed tomography reports. We compared new users of anti-TNF-α agents to new users of non-biologic therapies using Cox proportional hazards analysis to adjust for baseline propensity scores and time-varying use of glucocorticoids. We also made head-to-head comparisons between anti-TNF-α agents. RESULTS: Among the 8417 persons included in the analysis, 38 (0.4%) received a diagnostic code for ILD by the end of follow-up, including 23 of 4200 (0.5%) who used anti-TNF-α during study follow-up, and 15 of 5423 (0.3%) who used only non-biologic therapies. The age-standardized and gender-standardized incidence rate of ILD, per 100 person-years, was 0.21 [95% confidence interval (CI) 0-0.43] for rheumatoid arthritis and appreciably lower for other autoimmune diseases. Compared with the use of non-biologic therapies, use of anti-TNF-α therapy was not associated with a diagnosis of ILD among patients with rheumatoid arthritis (adjusted hazard ratio, 1.03; 95%CI 0.51-2.07), nor did head-to-head comparisons across anti-TNF-α agents suggest important differences in risk, although the number of cases available for analysis was limited. CONCLUSION: The study provides evidence that compared with non-biologic therapies, anti-TNF-α therapy does not increase the occurrence of ILD among patients with autoimmune diseases and informs research design of future safety studies of ILD.

Comparative Effectiveness of Abatacept vs. Tofacitinib in Rheumatoid Arthritis Patients who are CCP.

INTRODUCTION: Currently there is limited data to drive clinical decision making regarding  the choice of biologic/targeted synthetic disease-modifying antirheumatic drugs (DMARD); thus, head-to-head comparisons are needed to help guide prescribing. In recent years, significant advancements have helped clarify the mechanistic basis of the clinical associations of autoantibodies in rheumatoid arthritis (RA). This study evaluated the effectiveness of abatacept versus tofacitinib in anti-cyclic citrullinated peptide (CCP+) patients with rheumatoid arthritis (RA). METHODS: CorEvitas (formerly known as CORRONA) Registry patients aged ≥ 18 years, who were CCP+ before initiating abatacept or tofacitinib (December 2012 onwards through October 2019), had 6-month follow-up data (baseline and 6-month Clinical Disease Activity Index [CDAI]), and were not in remission at index were included. Patients were frequency matched 1:1 by prior biologic use before propensity score matching (PSM). Primary (mean change [D] in CDAI) and secondary outcomes 6 months after index were compared using mixed-effects models adjusted for variables that remained unbalanced after PSM. RESULTS: Following PSM, most baseline characteristics for 291 patient pairs were well balanced between treatments, although fewer patients initiating abatacept versus tofacitinib received prior non-TNFi biologic DMARDs, and patients initiating abatacept versus tofacitinib had a higher physician global assessment score, patient-reported fatigue, and modified Health Assessment Questionnaire (mHAQ). In adjusted analyses, there were no significant differences in mean [D] from baseline in CDAI at 6 months with abatacept versus tofacitinib (P = 0.936). Patients naïve for b/tsDMARDs initiating abatacept had a numerically greater mean [D] in CDAI at 6 months versus tofacitinib, although this difference was not statistically significant (P = 0.662). There were no significant differences for any secondary outcomes. CONCLUSIONS: In adjusted analyses, CCP+ patients with RA initiating treatment with abatacept versus tofacitinib did not show a statistically significant difference in reducing disease activity or improving patient-reported outcomes.