Effect of Bimekizumab on Patient-Reported Disease Impact in Patients with Psoriatic Arthritis: 1-Year Results from Two Phase 3 Studies.

OBJECTIVES: To evaluate 1-year bimekizumab efficacy in psoriatic arthritis (PsA) from the patient perspective using the 12-item PsA Impact of Disease (PsAID-12) questionnaire. METHODS: BE OPTIMAL (NCT03895203; biologic disease-modifying antirheumatic drug [bDMARD]-naïve), BE COMPLETE (NCT03896581; inadequate response/intolerance to tumour necrosis factor inhibitors [TNFi-IR]) and BE VITAL (NCT04009499; open-label extension) assessed bimekizumab 160 mg every 4 weeks in patients with PsA. Post hoc analyses of patient-reported disease impact, assessed by the PsAID-12 questionnaire, are reported to 1 year (collected to week 40 in BE COMPLETE). RESULTS: Overall, 1,112 total patients were included (698 bimekizumab, 414 placebo). Rapid improvements observed with bimekizumab treatment at week 4 continued to week 16 and were sustained to 1 year. At 1 year, mean (standard error) change from baseline in PsAID-12 total score was comparable between bimekizumab-randomized patients and patients who switched to bimekizumab at week 16 (bDMARD-naïve bimekizumab -2.3 [0.1], placebo/bimekizumab -2.2 [0.1]; TNFi-IR bimekizumab -|2.5 [0.1], placebo/bimekizumab -2.2 [0.2]). Proportions of bimekizumab-randomized patients achieving clinically meaningful within-patient improvement (≥3-point decrease from baseline) at week 16 were sustained to 1 year (bDMARD-naïve 49.0%; TNFi-IR 48.5%) and were similar for placebo/bimekizumab patients (bDMARD-naïve 44.4%; TNFi-IR 40.6%). Across studies and arms, 35.3% to 47.8% of patients had minimal or no symptom impact at 1 year. Improvements were observed to 1 year across all single-item domains, including pain, fatigue and skin problems. CONCLUSION: Bimekizumab treatment resulted in rapid and sustained clinically meaningful improvements in disease impact up to 1 year in bDMARD-naïve and TNFi-IR patients with PsA.

Multimorbidity in Psoriasis as a Risk Factor for Psoriatic Arthritis: A Population-Based Study.

OBJECTIVES: To examine multimorbidity in psoriasis and its association with the development of PsA. METHODS: A retrospective cohort study was performed using the Rochester Epidemiology Project. Population-based incidence (2000-2009) and prevalence (Jan 1, 2010) cohorts of psoriasis were identified by manual chart review. A cohort of individuals without psoriasis (comparators) were identified (1:1 matched on age, sex, and county). Morbidities were defined using ≥2 Clinical Classification Software codes ≥30 days apart within prior five years. PsA was defined using ClASsification of Psoriatic ARthritis (CASPAR) criteria. χ2 and rank-sum tests were used to compare morbidities, and age-, sex-, and race-adjusted Cox models to examine the association of baseline morbidities in psoriasis with development of PsA. RESULTS: Among 817 incident psoriasis patients, the mean age was 45.2 years with 52.0% females, and 82.0% moderate/severe psoriasis. No multimorbidity differences were found between incident psoriasis patients and comparators. However, in the 1,088 prevalent psoriasis patients, multimorbidity was significantly more common compared with 1,086 comparators (OR : 1.35 and OR : 1.48 for ≥2 and ≥5 morbidities, respectively). Over a median 13.3-year follow-up, 23 patients (cumulative incidence: 2.9% by 15 years) developed PsA. Multimorbidity (≥2 morbidities) was associated with a 3-fold higher risk of developing PsA. CONCLUSION: Multimorbidity was more common in the prevalent but not incident cohort of psoriasis compared with the general population, suggesting patients with psoriasis may experience accelerated development of multimorbidity. Moreover, multimorbidity at psoriasis onset significantly increased the risk of developing PsA, highlighting the importance of monitoring multimorbid psoriasis patients for the development of PsA.

Use of the Bath Ankylosing Spondylitis Disease Activity Index in Patients With Psoriatic Arthritis With and Without Axial Disease.

OBJECTIVE: To evaluate whether the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is a responsive instrument in psoriatic arthritis (PsA) and whether it differentiates between axial and peripheral disease activity in PsA. METHODS: Individuals with PsA initiating therapy in a longitudinal cohort study based in the United States were included. Axial PsA (axPsA), most often also associated with peripheral disease, was defined as fulfillment of the Assessment of Spondyloarthritis international Society axial spondyloarthritis classification criteria or presence of axial disease imaging features. Baseline BASDAI, individual BASDAI items, patient global assessment, patient pain, and Routine Assessment of Patient Index Data 3, and score changes following therapy initiation were descriptively reported. Standardized response means (SRMs) were calculated as the mean change divided by the SD of the change. RESULTS: The mean (SD) baseline BASDAI score at the time of therapy initiation was 5.0 (2.2) among those with axPsA (n = 40) and 4.8 (2.0) among those with peripheral-only disease (n = 79). There was no significant difference in patient-reported outcome scores between the groups. The mean change for BASDAI was similar among axial vs peripheral disease (-0.75 vs -0.83). SRMs were similar across axial vs peripheral disease for BASDAI (-0.37 vs -0.44) and the individual BASDAI items. CONCLUSION: BASDAI has reasonable responsiveness in PsA but does not differentiate between axPsA and peripheral PsA. (ClinicalTrials.gov: NCT03378336).

Which Educational Topics and Smartphone App Functions Are Prioritized by US Patients With Rheumatic and Musculoskeletal Diseases? A Mixed-Methods Study.

OBJECTIVE: We sought to identify (1) what types of information US adults with rheumatic and musculoskeletal diseases (RMD) perceive as most important to know about their disease, and (2) what functions they would use in an RMD-specific smartphone app. METHODS: Nominal groups with patients with RMD were conducted using online tools to generate a list of needed educational topics. Based on nominal group results, a survey with final educational items was administered online, along with questions about desired functions of a smartphone app for RMD and wearable use, to patients within a large community rheumatology practice-based research network and the PatientSpot registry. Chi-square tests and multivariate regression models were used to determine differences in priorities between groups of respondents with rheumatic inflammatory conditions (RICs) and osteoarthritis (OA), and possible associations. RESULTS: At least 80% of respondents considered finding a rheumatologist, understanding tests and medications, and quickly recognizing and communicating symptoms to doctors as extremely important educational topics. The highest-ranked topic for both RIC and OA groups was "knowing when the medication is not working." The app functions that most respondents considered useful were viewing laboratory results, recording symptoms to share with their rheumatology provider, and recording symptoms (eg, pain, fatigue) or disease flares for health tracking over time. Approximately one-third of respondents owned and regularly used a wearable activity tracker. CONCLUSION: People with RMD prioritized information about laboratory test results, medications, and disease and symptom monitoring, which can be used to create educational and digital tools that support patients during their disease journey.

Clinical Validation of Digitally Acquired Clinical Data and Machine Learning Models for Remote Measurement of Psoriasis and Psoriatic Arthritis: A Proof-of-Concept Study.

OBJECTIVE: Psoriatic disease remains underdiagnosed and undertreated. We developed and validated a suite of novel, sensor-based smartphone assessments (Psorcast app) that can be self-administered to measure cutaneous and musculoskeletal signs and symptoms of psoriatic disease. METHODS: Participants with psoriasis (PsO) or psoriatic arthritis (PsA) and healthy controls were recruited between June 5, 2019, and November 10, 2021, at 2 academic medical centers. Concordance and accuracy of digital measures and image-based machine learning models were compared to their analogous clinical measures from trained rheumatologists and dermatologists. RESULTS: Of 104 study participants, 51 (49%) were female and 53 (51%) were male, with a mean age of 42.3 years (SD 12.6). Seventy-nine (76%) participants had PsA, 16 (15.4%) had PsO, and 9 (8.7%) were healthy controls. Digital patient assessment of percent body surface area (BSA) affected with PsO demonstrated very strong concordance (Lin concordance correlation coefficient [CCC] 0.94 [95% CI 0.91-0.96]) with physician-assessed BSA. The in-clinic and remote target plaque physician global assessments showed fair-to-moderate concordance (CCCerythema 0.72 [0.59-0.85]; CCCinduration 0.72 [0.62-0.82]; CCCscaling 0.60 [0.48-0.72]). Machine learning models of hand photos taken by patients accurately identified clinically diagnosed nail PsO with an accuracy of 0.76. The Digital Jar Open assessment categorized physician-assessed upper extremity involvement, considering joint tenderness or enthesitis (AUROC 0.68 [0.47-0.85]). CONCLUSION: The Psorcast digital assessments achieved significant clinical validity, although they require further validation in larger cohorts before use in evidence-based medicine or clinical trial settings. The smartphone software and analysis pipelines from the Psorcast suite are open source and freely available.

The impact of dietary interventions in psoriatic arthritis.

PURPOSE OF REVIEW: Psoriatic arthritis (PsA) is a common form of inflammatory arthritis that affects people with psoriasis. Both psoriasis and PsA are associated with metabolic diseases including obesity, hypertension, hyperlipidaemia, diabetes mellitus, fatty liver disease, and cardiovascular disease including myocardial infarction. Dietary interventions for psoriatic disease have been of great interest, particularly among patients with PsA. RECENT FINDINGS: Herein, we review the evidence for dietary intervention in psoriatic arthritis. To date, weight loss among patients who are obese has the greatest evidence for benefit. We also examine the evidence for fasting, nutrient supplementation, and specific diets as adjunct therapeutic strategies. SUMMARY: While the data do not clearly support a single dietary intervention across the disease, weight loss among those who are obese results in improved PsA disease activity and physical function. Additional studies are needed to better understand the impact of diet on psoriatic arthritis.

Strong site-specific association of pharyngeal cultures with the onset of psoriatic arthritis and psoriasis, regardless of pathogen.

OBJECTIVES: The objective of this study was to evaluate any association between culture site / culture result / pathogen and incident PsA or psoriasis. METHODS: Records of all samples sent for culture from a large population during a 3-year period were linked with nationwide registry data on diagnoses and death over a 15-year period. The main outcomes of interest were incident diagnoses of PsA and psoriasis, defined by International Classification of Diseases (ICD) codes. The effect of culture site, culture result (positive vs negative), and pathogen (Streptococcus vs negative culture) on the risk of developing PsA and psoriasis was calculated using Cox proportional hazards models adjusted for age and gender. RESULTS: A total of 313 235 bacterial cultures from 128 982 individuals were analysed. Comparing individuals with pharyngeal cultures to those with urine cultures, the hazard ratio for incident PsA was 8.78 [95% confidence interval (CI) 3.23, 23.91] and for incident psoriasis it was 8.00 (95% CI 5.28, 12.12). Most of the risk was concentrated in the first 50 days after the culture date. Increased risk was also found when comparing individuals with cultures from the pharynx with those with cultures from the nasopharynx and blood. An association with streptococci was not found, neither in the pharynx nor at any other site. A positive bacterial culture from any site was associated with reduced risk for both PsA and psoriasis. CONCLUSION: There is a strong site-specific association between pharyngeal culture samples and an increased risk of PsA and psoriasis, regardless of the pathogen. This may indicate that the site of infection, rather than the pathogen, is associated with increased risk.

Sleep Problems in Patients With Psoriatic Arthritis: A Systematic Literature Review and Metaanalysis.

OBJECTIVE: The aim of this systematic review and metaanalysis is to summarize evidence regarding the relationship between psoriatic arthritis (PsA) and sleep problems. METHODS: We identified 36 eligible studies-26 cross-sectional, 7 cohort, and 3 interventional studies-in PubMed and Embase. RESULTS: The prevalence of self-reported sleep problems in patients with PsA ranged from 30% to 85%. A metaanalysis of 6 studies that used the Pittsburgh Sleep Quality Index revealed a prevalence of poor sleep quality for patients with PsA of 72.9% (95% CI 63-81.8; I2 = 78%), which was statistically higher than in healthy controls (26.9%, 95% CI 11.7-45.4; I2 = 81%) but not significantly different than in patients with psoriasis (59.8%, 95% CI 46.9-72.1; I2 = 51%). Sleep disturbance was ranked in the top 4 health-related quality of life domains affected by PsA. One study suggested a bidirectional relationship between PsA and obstructive sleep apnea. Predictors of sleep problems included anxiety, pain, erythrocyte sedimentation rate, depression, fatigue, physical function, and tender or swollen joint count. Tumor necrosis factor inhibitors, guselkumab, and filgotinib (a Janus kinase inhibitor) were associated with improved sleep outcomes. CONCLUSION: Poor sleep quality is prevalent in patients with PsA. Objective sleep measures (ie, actigraphy and polysomnography) have not been used in PsA studies, and evidence on the validity of patient-reported sleep measures in PsA is lacking. Future studies should validate self-reported sleep measures in PsA, explore how sleep quality relates to PsA disease activity and symptoms using both objective and subjective sleep measures, assess the efficacy of strategies to manage sleep problems, and assess the effects of such management on symptoms and disease signs in patients with PsA.

Patient Perspectives on Psoriatic Disease Burden: Results from the Global Psoriasis and Beyond Survey.

BACKGROUND: Patients' understanding of the systemic nature of psoriatic disease (PsD) remains insufficiently explored. OBJECTIVES: The objective of this study was to assess patients' understanding of PsD, associated comorbidities, disease burden, and relationships with healthcare professionals (HCPs). METHODS: Psoriasis and Beyond was a cross-sectional, quantitative online survey conducted in patients with a self-reported, physician-given diagnosis of moderate to severe psoriasis (body surface area [BSA] >5% to <10%, affecting sensitive and/or prominent body parts or BSA ≥10%) at its worst, with/without psoriatic arthritis (PsA). Patients were recruited through online panels by the Institut de Publique Sondage d'Opinion Secteur (Ipsos SA) and patient advocacy groups. RESULTS: Overall, 4,978 respondents with psoriasis completed the online survey from 20 countries across Australia, Asia, Europe, and the Americas; 30% of patients also reported having concomitant PsA. Overall, 69% of patients with psoriasis had heard that their disease was part of a systemic disease, and 60% had heard of the term "psoriatic disease." Despite this, recognition of common manifestations and comorbidities associated with PsD was low. Among psoriasis-only patients (n = 3,490), 38% screened positive using the Psoriasis Epidemiology Screening Tool (PEST), indicative of potential PsA. Overall, 48% of patients reported that their disease had a very large to extremely large effect on quality of life (QoL; Dermatology Life Quality Index [DLQI] score, 11-30); only 13% of patients reported no impact of the disease on QoL (DLQI, 0-1). Most patients had experienced stigma and discrimination (82%) and a negative impact on relationships (81%) in their lives. Overall, 59% of patients were not involved in deciding their treatment goals: 58% of all treated patients (n = 4,757) and 64% of treated patients with concomitant PsA (n = 1,409) were satisfied with their current treatment. CONCLUSIONS: These results highlight that patients may not fully understand the systemic nature of their disease, were frequently uninvolved in deciding treatment goals, and were often not satisfied with their current treatment. Increasing patients' participation in their care can facilitate shared decision-making between patients and HCPs, which may result in better treatment adherence and patient outcomes. Furthermore, these data indicate that policies should be implemented to protect against stigma and discrimination, which are commonly experienced by patients with psoriasis.

Does biologic therapy impact the development of PsA among patients with psoriasis?

OBJECTIVE: To examine the association of biologic therapy use for psoriasis with incident psoriatic arthritis (PsA) diagnosis. METHODS: A retrospective cohort study was conducted in the OptumInsights Electronic Health Record Database between 2006 and 2017 among patients with psoriasis between the ages of 16 and 90 initiating a therapy for psoriasis (oral, biologic or phototherapy). The incidence of PsA was calculated within each therapy group. Multivariable Cox models were used to calculate the HR for biologic versus oral or phototherapy using biologics as a time-varying exposure and next in a propensity score-matched cohort. RESULTS: Among 1 93 709 patients with psoriasis without PsA, 14 569 biologic and 20 321 cumulative oral therapy and phototherapy initiations were identified. Mean age was lower among biologic initiators compared with oral/phototherapy initiators (45.9 vs 49.8). The incidence of PsA regardless of therapy exposure was 9.75 per 1000 person-years compared with 77.26 among biologic users, 61.99 among oral therapy users, 26.11 among phototherapy users and 5.85 among those without a prescription for one of the target therapies. Using a multivariable adjustment approach with time-varying exposure, adjusted HR (95% CI) for biologic users was 4.48 (4.23 to 4.75) compared with oral or phototherapy users. After propensity score matching, the HR (95% CI) was 2.14 (2.00 to 2.28). CONCLUSIONS: In this retrospective cohort study, biologic use was associated with the development of PsA among patients with psoriasis. This may be related to confounding by indication and protopathic bias. Prospective studies are needed to address this important question.

Body surface area affected by psoriasis and the risk for psoriatic arthritis: a prospective population-based cohort study.

OBJECTIVE: Increasing psoriasis severity has been associated with comorbidities including cardiovascular disease. The objective of this study was to examine the association of psoriasis severity with the development of PsA. METHODS: A prospective population-based cohort study was performed within The Health Improvement Network, a UK medical record database. Patients aged 25-60 years with a code for psoriasis were randomly selected between 2008 and 2011. Questionnaires were sent to their general practitioners to confirm the diagnosis of psoriasis and provide the patient's approximate body surface area (BSA). Incidence of PsA was calculated by BSA, and Cox proportional hazard ratios were used to examine the risk of developing PsA by BSA category after adjusting for other covariates. RESULTS: Among 10 474 questionnaires sent, 9987 (95%) were returned, 9069 (91%) had confirmed psoriasis, and BSA was provided for 8881 patients: 52% had mild psoriasis, 36% moderate psoriasis and 12% severe psoriasis. The mean age was 46, and 49% were female. Mean follow-up time was 4.2 years (s.d. 2.1); the incidence of PsA was 5.4 cases per 1000 person-years. After adjusting for age and sex, BSA >10% [hazard ratio (HR) 2.01, 95% CI: 1.29, 3.13], BSA 3-10% (HR 1.44, 95% CI: 1.02, 2.03), obesity (HR 1.64, 95% CI: 1.19, 2.26) and depression (HR 1.68, 95% CI: 1.21, 2.33) were associated with incident PsA. CONCLUSIONS: In this large prospective cohort study, BSA assessed by general practitioners was a strong predictor of developing PsA, and obesity and depression were additive risk factors.

Prospective cohort study of psoriatic arthritis risk in patients with psoriasis in a real-world psoriasis registry.

BACKGROUND: The characteristics that predict the onset of psoriatic arthritis (PsA) among patients with psoriasis (PsO) may inform diagnosis and treatment. OBJECTIVE: To develop a model to predict the 2-year risk of developing PsA among patients with PsO. METHODS: This was a prospective cohort study of patients in the CorEvitas Psoriasis Registry without PsA at enrollment and with 24-month follow-up. Unregularized and regularized logistic regression models were developed and tested using descriptive variables to predict dermatologist-identified PsA at 24 months. Model performance was compared using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. RESULTS: A total of 1489 patients were included. Nine unique predictive models were developed and tested. The optimal model, including Psoriasis Epidemiology Screening Tool (PEST), body mass index (BMI), modified Rheumatic Disease Comorbidity Index, work status, alcohol use, and patient-reported fatigue, predicted the onset of PsA within 24 months (AUC = 68.9%, sensitivity = 82.9%, specificity = 48.8%). A parsimonious model including PEST and BMI had similar performance (AUC = 68.8%; sensitivity = 92.7%, specificity = 36.5%). LIMITATIONS: PsA misclassification bias by dermatologists. CONCLUSION: PEST and BMI were important factors in predicting the development of PsA in patients with PsO over 2 years and thereby foundational for future PsA risk model development.

Disease activity, cytokines, chemokines and the risk of incident diabetes in rheumatoid arthritis.

PURPOSE: Rheumatoid arthritis (RA) is associated with a higher risk of diabetes mellitus (DM). Our aim was to determine associations between inflammatory disease activity (including evaluation of specific cytokines and chemokines) and incident DM. METHODS: Participants were adults with physician-confirmed RA from Veteran's Affairs Rheumatoid Arthritis Registry. Disease activity and clinical assessments occur longitudinally as part of clinical care. Thirty cytokines and chemokines were measured in banked serum obtained at the time of enrolment. Cytokine/chemokine values were log-adjusted and standardised (per SD). Incident DM was defined based on validated algorithms using diagnostic codes and medications. Multivariable Cox proportional hazard models evaluated associations between clinical factors and incident DM. Independent associations between cytokines/chemokines and incident DM were assessed adjusting for age, sex, race, smoking, body mass index (BMI) and medication use at baseline. RESULTS: Among 1866 patients with RA without prevalent DM at enrolment, there were 130 incident cases over 9223 person-years of follow-up. High Disease Activity Score (DAS28)-C reactive protein (CRP), obese BMI, older age and male sex were associated with greater risk for incident DM while current smoking and methotrexate use were protective. Patients using methotrexate were at lower risk. Several cytokines/chemokines evaluated were independently associated (per 1 SD) with DM incidence including interleukin(IL)-1, IL-6 and select macrophage-derived cytokines/chemokines (HR range 1.11-1.26). These associations were independent of the DAS28-CRP. CONCLUSIONS: Higher disease activity and elevated levels of cytokines/chemokines are associated with a higher risk of incident DM in patients with RA. Future study may help to determine if targeted treatments in at-risk individuals could prevent the development of DM.

Persistent premature mortality gap in dermatomyositis and polymyositis: a United Kingdom general population-based cohort study.

OBJECTIVE: DM and PM are associated with substantial morbidity and mortality. We aimed to examine recent trends. METHODS: Using The Health Improvement Network, we identified patients with incident DM/PM (defined by ≥1 Read diagnosis code) aged 18-89 years with ≥1 year of continuous enrolment prior to the cohort entry date and up to 10 comparators matched on age, sex and entry year. The cohort was divided in two based on the year of DM/PM diagnosis: the early cohort (1999-2006) and late cohort (2007-2014). We calculated multivariable hazard ratios (HR) for death using a Cox-proportional hazards model and multivariable rate differences (RD) using an additive hazard model. RESULTS: We identified 410 DM cases (mean age: 58 years, 66% female) and 407 PM cases (mean age: 59 years, 61% female). Both DM cohorts had excess mortality compared with the comparison cohorts (71.5 vs 12.9 deaths/1000 person-years [PY] in the early cohort and 49.1 vs 10.4 deaths/1000 PY in the late cohort). The multivariable HRs were 7.51 (95% CI: 4.20, 13.42) in the early cohort and 5.42 (95% CI: 3.11, 9.45) in the late cohort (P-value for interaction = 0.59), and multivariable RDs were 56.2 (95% CI: 31.8, 81.2) in the early cohort and 36.3 (95% CI: 19.6, 53.0) in the late cohort (P-value for interaction = 0.15). A similar trend existed in PM. CONCLUSION: The premature mortality gap in DM/PM has not considerably improved in recent years, highlighting an unmet need for therapeutic improvement.

A comparison of physical function instruments in psoriatic arthritis: HAQ-DI vs MDHAQ vs PROMIS10 global physical health.

OBJECTIVES: Physical function is a core outcome in PsA. We examined the construct validity and responsiveness of three commonly used instruments to assess physical function in PsA: HAQ disability index (HAQ-DI), MultiDimensional HAQ (MDHAQ) and the Patient-Reported Outcomes Measurement Information System (PROMIS®) Global-10. METHODS: Between 2016 and 2019, patients with PsA were enrolled in the Psoriatic Arthritis Research Consortium longitudinal cohort study in the USA. Correlations were calculated at baseline and among change scores using Spearman's correlation coefficient. Standardized response means were calculated. Agreement with the 20% improvement cut-off was used to determine the potential effect of using MDHAQ or the PROMIS Global-10 physical health (GPH) subscore in place of HAQ-DI when assessing the ACR20. RESULTS: A total of 274 patients were included in the analysis. The mean age of patients was 49 years and 51% were male. At baseline, the mean HAQ-DI was 0.6 (s.d. 0.6; range 0-3), the mean MDHAQ was 1.8 (s.d. 1.6; range 0-10) and the mean GPH T-score was 43.4 (s.d. 9.3; range 0-100). All three instruments were strongly correlated at baseline (rho 0.75-0.85). Change scores were moderately correlated (rho 0.42-0.71). Among therapy initiators, the mean change between two visits in HAQ-DI, MDHAQ and GPH was -0.1 (s.d. 0.4), -0.2 (s.d. 1.2) and 2.5 (s.d. 6.1), respectively. The standardized response means were 0.18, 0.16 and 0.41, respectively. CONCLUSION: The three instruments tested are not directly interchangeable but have overall similar levels of responsiveness.

Performance of composite measures used in a trial of etanercept and methotrexate as monotherapy or in combination in psoriatic arthritis.

OBJECTIVES: To examine which composite measures are most sensitive to change when measuring psoriatic arthritis (PsA) disease activity, analyses compared the responsiveness of composite measures used in a 48-week randomized, controlled trial of MTX and etanercept in patients with PsA. METHODS: The trial randomised 851 patients to receive weekly: MTX (20 mg/week), etanercept (50 mg/week) or MTX plus etanercept. Dichotomous composite measures examined included ACR 20/50/70 responses, minimal disease activity (MDA) and very low disease activity (VLDA). Continuous composite measures examined included Disease Activity Score (28 joints) using CRP (DAS28-CRP), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Disease Activity for Psoriatic Arthritis (DAPSA) and Psoriatic Arthritis Disease Activity Score (PASDAS). RESULTS: At week 24, etanercept-treated groups were significantly more effective than MTX monotherapy to achieve ACR 20 (primary end point) and MDA (key secondary end point). When examining score changes from baseline at week 24 across the five continuous composite measures, PASDAS demonstrated relatively greater changes in the etanercept-treated groups compared with MTX monotherapy and had the largest effect size and standardized response. Joint count changes drove overall score changes at week 24 from baseline in all the continuous composite measures except for PASDAS, which was driven by the Physician and Patient Global Assessments. CONCLUSION: PASDAS was the most sensitive continuous composite measure examined with results that mirrored the protocol-defined primary and key secondary outcomes. Composite measures with multiple domains, such as PASDAS, may better quantify change in PsA disease burden. TRAIL REGISTRATION: https://ClinicalTrials.gov, number NCT02376790.

Age-appropriate cancer screening: A cohort study of adults with psoriasis prescribed biologics, adults in the general population, and adults with hypertension.

BACKGROUND: Psoriasis is associated with increased risk of developing and dying from cancer. OBJECTIVE: To evaluate whether psoriasis patients who are prescribed biologics receive the recommended screening for cervical, breast, and colon cancer. METHODS: We conducted a retrospective cohort study using the Optum deidentified Electronic Health Record data set. Incidence rates for cervical, breast, and colon cancer screening were compared between psoriasis patients who were prescribed biologics and 2 matched comparator cohorts: general patient population and patients being managed for hypertension. Multivariable Cox proportional hazards regression was performed to assess for differences in the rates of cancer screening. RESULTS: Compared with those in the general population without psoriasis, psoriasis patients who were prescribed biologics had higher screening rates for cervical cancer (adjusted hazard ratio [aHR] 1.09; 95% confidence interval [CI] 1.02-1.16) and colon cancer (aHR 1.10; 95% CI 1.02-1.18). Compared with those with hypertension, patients with psoriasis who were prescribed biologics had lower screening rates for breast cancer (aHR 0.88; 95% CI 0.83-0.94) and colon cancer (aHR 0.89; 95% CI 0.83-0.95). CONCLUSIONS AND RELEVANCE: Patients with psoriasis who are prescribed biologic therapies may not be receiving adequate age-appropriate cancer screening, especially for breast and colon cancer.

Risk of liver disease in patients with psoriasis, psoriatic arthritis, and rheumatoid arthritis receiving methotrexate: A population-based study.

BACKGROUND: Patients with psoriatic disease may be more susceptible to methotrexate hepatotoxicity than those with rheumatoid arthritis (RA); however, direct evidence supporting this notion is lacking. OBJECTIVE: To compare liver disease risk among patients with psoriasis (PsO), psoriatic arthritis (PsA), or RA receiving methotrexate. METHODS: In a population-based cohort study, Danish individuals with PsO, PsA, or RA receiving methotrexate between 1997 and 2015 were compared according to 4 disease outcomes: mild liver disease, moderate-to-severe liver disease, cirrhosis, and cirrhosis-related hospitalization. RESULTS: Among 5687, 6520, and 28,030 patients with PsO, PsA, and RA, respectively, the incidence rate of any liver disease was greatest for PsO, followed by PsA, and lowest for RA. Compared with patients with RA, patients with PsO were 1.6-3.4 times more likely to develop at least one of the liver disease outcomes, whereas those with PsA were 1.3-1.6 times more likely to develop mild liver disease and cirrhosis after adjusting for demographics, smoking, alcohol use, comorbidities, and methotrexate dose. LIMITATIONS: Confounding due to unmeasured variables, misclassification, and surveillance bias. CONCLUSION: PsO, PsA, and RA differentially influence liver disease risk in the setting of methotrexate use independent of other major risk factors. More conservative monitoring should be considered in patients receiving methotrexate for psoriatic disease, particularly in PsO patients.

Validation of coding algorithms for the identification of herpes zoster among children.

PURPOSE: To examine the validity of International Classification of Diseases, 10th Revision, (ICD-10) code-based algorithms for herpes zoster (HZ) in the electronic medical record (EMR) of a large, integrated pediatric healthcare network and to examine baseline demographics and chronic comorbidities associated with HZ in a representative pediatric population. METHODS: We reviewed the electronic charts of all patients with a single ICD-10 for HZ (B02.xx) as their primary or secondary diagnosis in the EMR of the Children's Hospital of Philadelphia (CHOP) healthcare network from January 2010-March 2019. The positive predictive value (PPV) for a single code for HZ was calculated and alternative algorithms were examined to determine which method resulted in the highest PPV. RESULTS: The PPV for a single ICD-10 code was 91.7% (95% CI 80.8-95.4) for definitive and/or probable cases of HZ and 63.9% (95% CI 53.4%-75.5%) for definitive cases alone. Adding a prescription for an antiviral did not improve the PPV. However, adding a new code for rash entered within 1 week of the HZ code increased the PPV to 100% for definitive and/or probable cases but with substantial loss of sensitivity. A high proportion of children with HZ who required inpatient hospitalization had chronic disease (70%) and were on systemic immunomodulatory therapy (50%). CONCLUSIONS: HZ can be identified with a high PPV in electronic medical records of children using ICD-10 code alone. These findings lay the foundation for future pharmacoepidemiologic research to better understand risk factors for HZ infection.

Simulation-based design of pragmatic trials in psoriatic arthritis using propensity scores.

BACKGROUND/AIMS: Design of clinical trials requires careful decision-making across several dimensions, including endpoints, eligibility criteria, and subgroup enrichment. Clinical trial simulation can be an informative tool in trial design, providing empirical evidence by which to evaluate and compare the results of hypothetical trials with varying designs. We introduce a novel simulation-based approach using observational data to inform the design of a future pragmatic trial. METHODS: We utilize propensity score-adjusted models to simulate hypothetical trials under alternative endpoints and enrollment criteria. We apply our approach to the design of pragmatic trials in psoriatic arthritis, using observational data embedded within the Tight Control of Inflammation in Early Psoriatic Arthritis study to simulate hypothetical open-label trials comparing treatment with tumor necrosis factor-α inhibitors to methotrexate. We first validate our simulations of a trial with traditional enrollment criteria and endpoints against a recently published trial. Next, we compare simulated treatment effects in patient populations defined by traditional and broadened enrollment criteria, where the latter is consistent with a future pragmatic trial. In each trial, we also consider five candidate primary endpoints. RESULTS: Our results highlight how changes in the enrolled population and primary endpoints may qualitatively alter study findings and the ability to detect heterogeneous treatment effects between clinical subgroups. For treatments of interest in the study of psoriatic arthritis, broadened enrollment criteria led to diluted estimated treatment effects. Endpoints with greater responsiveness to treatment compared with a traditionally used endpoint were identified. These considerations, among others, are important for designing a future pragmatic trial aimed at having high external validity with relevance for real-world clinical practice. CONCLUSION: Observational data may be leveraged to inform design decisions in pragmatic trials. Our approach may be generalized to the study of other conditions where existing trial data are limited or do not generalize well to real-world clinical practice, but where observational data are available.