Faculty Bibliography

The concept of psoriatic arthritis (PsA) prevention is gaining increased interest owing to the physical limitation, poor quality of life and low remission rates that are achieved with current therapies for PsA. The psoriasis-to-PsA transition offers a unique opportunity to identify individuals at increased risk of developing PsA and to implement preventive strategies. However, identifying individuals at increased risk of developing PsA is challenging as there is no consensus on how this population should be defined. This Consensus Statement puts forward recommended terminology from the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN) for defining specific subgroups of individuals during the preclinical and early clinical phases of PsA to be used in research studies. Following a three-round Delphi process, consensus was reached for three terms and definitions: 'increased risk for PsA', 'psoriasis with asymptomatic synovio-entheseal imaging abnormalities' and 'psoriasis with musculoskeletal symptoms not explained by other diagnosis'. These terms and their definitions will enable improved identification and standardization of study populations in clinical research. In the future, as increasing evidence emerges regarding the molecular and clinical features of the psoriasis-to-PsA continuum, these terms and definitions will be further refined and updated.

Background/Purpose: Remission (REM), and at times low disease activity (LDA), are treatment targets in psoriatic arthritis (PsA) that can vary with different provider-assessed measures and patient perception of clinical response. This can lead to treatment dilemmas and patient dissatisfaction. In this study we examined the relationship between LDA and REM in PsA patients using commonly accepted disease activity measures and their relationship to PROs as measured by the Patient- Reported Outcomes Measurement Information System (PROMIS) Global Health questionnaire and Routine Assessment of Patient Index Data 3 (RAPID3).
Method(s): A cross-sectional study was performed within the Psoriatic Arthritis Research Consortium between 2016-2019 comparing MDA/VLDA, CDAI, and DAPSA scores with PROs. PROMIS Global Health (GH) physical and mental health subscores and PROMIS Fatigue (all expressed as Tscores) were compared between groups using t-tests. RAPID3 was compared using Chi-Squared test or Fisher's exact test, when appropriate. Correlations between MDA/VLDA, CDAI, and DAPSA scores and PROMIS domains were calculated using Spearman's rank correlation. Boxplots and scatterplots were used to present the results graphically. All tests are twosided, with an alpha level of 0.05 using SAS software (Version 9.4; Cary, NC).
Result(s): 227 patients (52.2% female, average age 52.7+/-14 years) were included. 72 patients were in MDA and 28 in VLDA; 84 in CDAI LDA and 23 in CDAI REM; 84 in DAPSA LDA and 50 in DAPSA REM. Patients meeting VLDA, CDAI REM and DAPSA REM had significantly higher PROMIS GH physical and mental T-scores (reflecting better outcomes) and better Fatigue T-scores compared to MDA, CDAI and DAPSA LDA (Figure 1, p<0.001). There was a correlation between MDA/VLDA, CDAI, and DAPSA scores and PROMIS GH physical and mental health and Fatigue domains; correlation was strongest for PROMIS GH physical health domain across all three disease activity measures (Figure 2, MDA r=0.69, CDAI r=-0.65, DAPSA r= -0.68). Majority of patients achieving VLDA, CDAI REM, or DAPSA REM had RAPID3 scores indicating low severity or remission, while >50% of patients in MDA/LDA reported moderate to severe impairment (Table 2, p<0.001).
Conclusion(s): PROMIS and RAPID3 measures successfully differentiated between low disease activity and remission as measured by disease activity measures MDA/VLDA, CDAI, and DAPSA. PROMIS measures correlated with all three disease activity measures, with strongest correlation for PROMIS GH physical health domain. These data contribute to the construct validity of using additional PRO measures such as PROMIS and RAPID3 for use in clinical practice

OBJECTIVE:To examine the construct validity of Routine Assessment of Patient Index Data (RAPID3) and Psoriatic Arthritis Impact of Disease (PSAID) in patients with psoriatic arthritis (PsA). In examining construct validity, we also addressed scores among subgroups with severe psoriasis, polyarticular disease, enthesitis and dactylitis and evaluated influences of sociodemographic factors and comorbidities (contextual factors) on these patient-reported outcomes (PROs). METHODS:Patients with PsA were enrolled in the Psoriatic Arthritis Research Consortium (PARC) between 2014-2016. PARC is a longitudinal observational cohort study conducted at four United States institutions. In this cross-sectional study, construct validity was assessed by examining Spearman's correlation coefficients for RAPID3 and PSAID with physician-reported disease activity measures and other PROs (e.g., Short Form 12 (SF12-PCS/-MCS), Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue). Contextual factors and disease subgroups were assessed in multivariable linear regression models with RAPID3 or PSAID12 as outcomes of interest and the hypothesized contextual factors as covariates. RESULTS:Among 401 patients enrolled in PARC, 347 completed RAPID3 or PSAID12. Of these, most were Caucasian females with a mean age of 51.74 (SD 14.02). RAPID3 and PSAID were highly correlated (r=0.90). These measures were also correlated with the SF12-PCS (r=-0.67) and FACIT-Fatigue (r=-0.77). Important contextual factors and disease subgroups included enthesitis, joint counts, education, insurance type, and depression. CONCLUSION/CONCLUSIONS:RAPID3 and PSAID12 have excellent construct validity in PsA and are strongly correlated despite differing items. Contextual factors (i.e., the presence of depression and obesity) should be considered when interpreting raw scores of the RAPID3 and PSAID12.

OBJECTIVE:The purpose of our study was to determine the cost-effectiveness of radiography and MRI-based imaging strategies for the initial diagnosis of sacroiliitis in a hypothetical population with suspected axial spondyloarthritis. MATERIALS AND METHODS/METHODS:A decision analytic model from the health care system perspective for patients with inflammatory back pain suggestive of axial spondyloarthritis was used to evaluate the incremental cost-effectiveness of 3 imaging strategies for the sacroiliac joints over a 3-year horizon: radiography, MRI, and radiography followed by MRI. Comprehensive literature search and expert opinion provided input data on cost, probability, and utility estimates. The primary effectiveness outcome was quality-adjusted life-years (QALYs), with a willingness-to-pay threshold set to $100,000/QALY gained (2018 American dollars). RESULTS:Radiography was the least costly strategy ($46,220). Radiography followed by MRI was the most effective strategy over a 3-year course (2.64 QALYs). Radiography was the most cost-effective strategy. MRI-based and radiography followed by MRI-based strategies were not found to be cost-effective imaging options for this patient population. Radiography remained the most cost-effective strategy over all willingness-to-pay thresholds up to $100,000. CONCLUSION/CONCLUSIONS:Radiography is the most cost-effective imaging strategy for the initial diagnosis of sacroiliitis in patients with inflammatory back pain suspicious for axial spondyloarthritis.

Background/Purpose: For psoriatic arthritis (PsA), several different composite instruments are available to define low disease activity (LDA) and remission (REM) targets for treatment. Patient-reported outcomes (PROs) may also be useful in assessing disease activity and may be more practical than composite indices in some settings. In this study, we examined the ability of PROs to differentiate between states of low disease activity and remission treatment targets (LDA and REM), using composite indices as the reference standards.
Method(s): This cross-sectional study was performed with the Psoriatic Arthritis Research Consortium between 2016-2019. PROs included Patient-Reported Outcomes Measurement Information System [PROMIS] instruments, EULAR Psoriatic Arthritis Impact of Disease [PSAID12], and Routine Assessment of Patient Index Data 3 [RAPID3]). Participants (pts) were classified as LDA if they fulfilled composite index criteria for Minimal Disease Activity (MDA), Clinical Disease Activity Index (CDAI)-LDA, or Disease Activity in Psoriatic Arthritis (cDAPSA)-LDA and REM if they fulfilled composite index criteria for Very Low Disease Activity (VLDA), CDAI-REM, or cDAPSA-REM. PROs were evaluated by determining 1) score differences between pts in LDA vs. REM, 2) correlations with composite indices scores, and 3) percentages of pts in LDA and REM who fulfilled PRO criteria for low disease states (in PROs with previously established low disease state criteria). PROs were compared between groups using t-tests or Wilcoxon rank sum test, depending on their distributions. The categorical versions of RAPID3 and PSAID12 were compared between groups using Chi-Squared test or Fisher's exact test, when appropriate. Correlations were calculated with Spearman's rank correlation. Data was analyzed using R software (Version 3.5; Vienna, Austria).
Result(s): 227 PsA pts were included (52.2% female, average age 52.7+/-14 years). Compared to pts in LDA, pts in REM had significantly more favorable PROMIS Physical, PROMIS Mental, PROMIS Fatigue, and PSAID12 scores (Figure 1). Correlations were strong between the composite indices and PROMIS GH physical health (r=0.65- 0.69) and between the composite indices and PSAID12 (r=-0.77- 0.79) (Figure 2). RAPID3 Low Severity and Near-Remission were reported by >98% of patients in REM, but only up to 54% of patients in LDA (Table 1). PSAID12 Patient AccepTable State occurred more frequently in pts in DAPSA-REM than pts in DAPSA-LDA (Table 1).
Conclusion(s): PROMIS and PSAID12 instruments correlated well with composite indices and differentiated between states of LDA vs REM. RAPID3 Near-Remission may be the most rigorous PRO criteria (including only the lowest states of disease activity), while PSAID Patient AccepTable State may identify a broader range of low states of disease activity. These data contribute to the construct validity of using PROs to measure low states of disease activity that may be considered for additional treatment targets in PsA

The Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN) was established to optimize the clinical care of patients with psoriatic disease through multidisciplinary collaboration, education, and innovative research. This article is a report of the 2018 PPACMAN Annual Meeting held in New York City, on December 8, 2018. At this meeting, attendees discussed the benefits and challenges of combined dermatology/rheumatology clinics and PPACMAN ongoing project updates. In addition, collaborators participated in breakout sessions and plenary voting dedicated to achieving consensus on terminology for preclinical psoriatic arthritis studies, one of PPACMAN's main areas of interest. The data obtained from this voting exercise were used to draft a formal Delphi survey that is currently underway.
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OBJECTIVE:To characterize the ecological effects of biologic therapies on the gut bacterial and fungal microbiome of psoriatic arthritis (PsA)/spondyloarthritis (SpA) patients. METHODS:Fecal samples from PsA/SpA patients pre- and post-treatment with tumor necrosis factor inhibitors (TNFi; n=15) or an anti-interleukin (IL)-17A monoclonal antibody inhibitor (IL-17i; n=14) underwent sequencing (16S, ITS and shotgun metagenomics) and computational microbiome analysis. Fecal levels of fatty acid metabolites and cytokines/proteins implicated in PsA/SpA pathogenesis or intestinal inflammation were correlated with sequence data. Additionally, ileal biopsies obtained from SpA patients who developed clinically overt Crohn's disease (CD) after treatment with IL-17i (n=5) were analyzed for expression of IL-23/Th-17 related cytokines, IL-25/IL-17E-producing cells and type-2 innate lymphoid cells (ILC2s). RESULTS:There were significant shifts in abundance of specific taxa after treatment with IL-17i compared to TNFi, particularly Clostridiales (p=0.016) and Candida albicans (p=0.041). These subclinical alterations correlated with changes in bacterial community co-occurrence, metabolic pathways, IL-23/Th17-related cytokines and various fatty acids. Ileal biopsies showed that clinically overt CD was associated with expansion of IL-25/IL-17E-producing tuft cells and ILC2s (p<0.05) compared to pre-IL-17i treatment levels. CONCLUSION/CONCLUSIONS:In a subgroup of SpA patients, the initiation of IL-17A blockade correlated with features of subclinical gut inflammation and intestinal dysbiosis of certain bacterial and fungal taxa, most notably C. albicans. Further, IL-17i-related CD was associated with overexpression of IL-25/IL-17E-producing tuft cells and ILC2s. These results may help to explain the potential link between inhibition of a specific IL-17 pathway and the (sub)clinical gut inflammation observed in SpA.

Background/Purpose : Patient-reported outcomes (PROs) are an important part of clinical decision making and are frequently used in combination with objective measures of disease activity and physicians' clinical assessment to help guide treatment decisions. Discrepancies between PROs and clinical measures of disease activity can lead to over-treated or under-treated disease and patient dissatisfaction. We sought to examine the correlation between minimal disease activity (MDA) with PROs as measured by the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health (GH) questionnaire, and assess the effect of demographics, psoriatic arthritis related comorbidities, and number of comorbidities on PROMIS GH and MDA status. Methods : A cross-sectional study was performed within Psoriatic Arthritis Research Consortium (PARC), a cohort of adult psoriatic arthritis patients meeting CASPAR criteria enrolled between 2016-2019. PARC is a longitudinal observational cohort study conducted at four institutions in the United States. The mean differences of PROMIS Physical, Mental and Fatigue T-scores between patients in MDA compared to those not in MDA were compared using the two sample t-tests. Correlations between MDA scores (0-7 criteria met) and PROMIS Physical, Mental and Fatigue T-scores were calculated using Spearman rank correlation. Higher T-scores on PROMIS measures mean 'more' of that concept for PROMIS Physical and Mental domains. Logistic regression model was used to evaluate contribution of additional covariates on MDA, including age, gender, hypertension, dyslipidemia, BMI, diabetes, smoking and number of comorbidities (Table 2). The odds ratios and 95% confidence intervals were presented. Multiple imputation was performed to impute missing data points. Data analysis was performed in SAS software (Version 9.4; Cary, NC). Results : 235 patients (50% female, mean age 51+/-13.9) were included. 129 were in MDA and 106 were not in MDA. Patients in MDA had significantly higher PROMIS Physical, Mental and improved Fatigue T-scores compared to non-MDA patients (Table 1; p< 0.001). There was a positive correlation between MDA scores and PROMIS scores in Physical and Mental domains; correlation was strongest for PROMIS Physical T-score (Figure 1; r=0.65, p< 0.001). There was a moderate correlation between MDA and PROMIS Fatigue T-score (Figure 1; r=-0.51, p< 0.001). In the univariate analysis, there was a statistically significant association between hypertension and number of comorbidities with MDA status (Table 2). However, this effect was not observed in the multivariate analysis. Conclusion : Achieving MDA was associated with a positive effect on patients' physical, mental and fatigue domains, irrespective of their demographics or PsA comorbidities. However, patients with a greater number of comorbidities were less likely to be in MDA. In this study, the PROMIS Physical domain had a higher correlation with MDA scores compared to the Mental domain and PROMIS Fatigue. PROMIS measures may be a useful tool in assessing disease activity from the patient's perspective. (Table Presented)

Background/Purpose : Psoriatic arthritis (PsA) is a heterogenous inflammatory disease affecting skin, joints, and other domains. While psychiatric diseases (i.e., depression and anxiety) are known comorbidities, little is known about their impact on disease severity and patient reported outcomes (PROs). The objective of this study was to characterize the prevalence of psychiatric comorbidities in an academic combined psoriasis-psoriatic arthritis center and determine their impact on PsA clinical and patient derived outcomes. Methods : Consecutive adult patients meeting CASPAR criteria for PsA (n=436) were prospectively recruited at the NYU Psoriatic Arthritis Center. All data was collected from clinical visits utilizing a standardized EPIC template. Depression was defined by established diagnosis and/or use of anti-depressant medications. Objective measures of disease severity included swollen and tender joint counts (SJC/TJC) and PROs including RAPID3 scores. Data was analyzed using statistical software R. Results : Our cohort was comprised of 436 patients: 54% male, mean age of 47 years, and mostly Caucasians (74.1%). Within our population, 19.5% had depression, 15.6% had anxiety, and 4.8% had ADHD (Table 1). Of those with depression, 71% were on anti-depressive medication. At the initial visit, patients with PsA and depression were more likely to be on medication(s) for PsA (80% vs 65%, p=.01) and had a trend towards higher rates of biologic use (47.5% vs 40.4%, p=.126). Those with depression had a similar TJC to their non-depressed counterparts, but had a trend towards fewer swollen joints and concomitant higher RAPID3 scores (Table 2). When analyzing repeated outcome measures over subsequent visits, individuals with depression were similarly more likely to have a higher TJC, a lower SJC, and a higher RAPID3 score (although only RAPID3 was found to be statistically significant, p=.004). Importantly, these findings persisted when analyzing participants that were matched with propensity scores to adjust for age, sex, comorbidities, and medication use. In addition to joint activity, psoriasis activity measured by body surface area (BSA) was lower in those who were depressed (1.4% vs 3.03%, p=.001) and these differences were maintained over subsequent visits. Conclusion : Our results expand on prior reports of significantly elevated rates of depression in PsA. Notably, individuals with depression were more likely to be on medication(s) for their PsA, had fewer swollen joints, and a lower BSA but, paradoxically reported higher RAPID3 scores. This discrepancy is likely a manifestation of how depression could affect the way patients experience their PsA despite apparent improvement in skin and joint symptoms. Depression should, therefore, be considered a critical comorbidity when addressing PsA care in routine visits. Further work is needed to understand whether modulation of psychiatric comorbidities can lead to improved PsA outcomes