Faculty Bibliography

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

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)

Objective: To develop an evidence-based guideline for the pharmacologic and nonpharmacologic treatment of psoriatic arthritis (PsA), as a collaboration between the American College of Rheumatology (ACR) and the National Psoriasis Foundation (NPF). Method(s): We identified critical outcomes in PsA and clinically relevant PICO (population/intervention/comparator/outcomes) questions. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available pharmacologic and nonpharmacologic therapies for PsA. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of the evidence. A voting panel, including rheumatologists, dermatologists, other health professionals, and patients, achieved consensus on the direction and the strength of the recommendations. Result(s): The guideline covers the management of active PsA in patients who are treatment-naive and those who continue to have active PsA despite treatment, and addresses the use of oral small molecules, tumor necrosis factor inhibitors, interleukin-12/23 inhibitors (IL-12/23i), IL-17 inhibitors, CTLA4-Ig (abatacept), and a JAK inhibitor (tofacitinib). We also developed recommendations for psoriatic spondylitis, predominant enthesitis, and treatment in the presence of concomitant inflammatory bowel disease, diabetes, or serious infections. We formulated recommendations for a treat-to-target strategy, vaccinations, and nonpharmacologic therapies. Six percent of the recommendations were strong and 94% conditional, indicating the importance of active discussion between the health care provider and the patient to choose the optimal treatment. Conclusion(s): The 2018 ACR/NPF PsA guideline serves as a tool for health care providers and patients in the selection of appropriate therapy in common clinical scenarios. Best treatment decisions consider each individual patient situation. The guideline is not meant to be proscriptive and should not be used to limit treatment options for patients with PsA.

OBJECTIVE:To develop an evidence-based guideline for the pharmacologic and nonpharmacologic treatment of psoriatic arthritis (PsA), as a collaboration between the American College of Rheumatology (ACR) and the National Psoriasis Foundation (NPF). METHODS:We identified critical outcomes in PsA and clinically relevant PICO (population/intervention/comparator/outcomes) questions. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available pharmacologic and nonpharmacologic therapies for PsA. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of the evidence. A voting panel, including rheumatologists, dermatologists, other health professionals, and patients, achieved consensus on the direction and the strength of the recommendations. RESULTS:The guideline covers the management of active PsA in patients who are treatment-naive and those who continue to have active PsA despite treatment, and addresses the use of oral small molecules, tumor necrosis factor inhibitors, interleukin-12/23 inhibitors (IL-12/23i), IL-17 inhibitors, CTLA4-Ig (abatacept), and a JAK inhibitor (tofacitinib). We also developed recommendations for psoriatic spondylitis, predominant enthesitis, and treatment in the presence of concomitant inflammatory bowel disease, diabetes, or serious infections. We formulated recommendations for a treat-to-target strategy, vaccinations, and nonpharmacologic therapies. Six percent of the recommendations were strong and 94% conditional, indicating the importance of active discussion between the health care provider and the patient to choose the optimal treatment. CONCLUSION/CONCLUSIONS:The 2018 ACR/NPF PsA guideline serves as a tool for health care providers and patients in the selection of appropriate therapy in common clinical scenarios. Best treatment decisions consider each individual patient situation. The guideline is not meant to be proscriptive and should not be used to limit treatment options for patients with PsA.

OBJECTIVE:To develop an evidence-based guideline for the pharmacologic and nonpharmacologic treatment of psoriatic arthritis (PsA), as a collaboration between the American College of Rheumatology (ACR) and the National Psoriasis Foundation (NPF). METHODS:We identified critical outcomes in PsA and clinically relevant PICO (population/intervention/comparator/outcomes) questions. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available pharmacologic and nonpharmacologic therapies for PsA. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of the evidence. A voting panel, including rheumatologists, dermatologists, other health professionals, and patients, achieved consensus on the direction and the strength of the recommendations. RESULTS:The guideline covers the management of active PsA in patients who are treatment-naive and those who continue to have active PsA despite treatment, and addresses the use of oral small molecules, tumor necrosis factor inhibitors, interleukin-12/23 inhibitors (IL-12/23i), IL-17 inhibitors, CTLA4-Ig (abatacept), and a JAK inhibitor (tofacitinib). We also developed recommendations for psoriatic spondylitis, predominant enthesitis, and treatment in the presence of concomitant inflammatory bowel disease, diabetes, or serious infections. We formulated recommendations for a treat-to-target strategy, vaccinations, and nonpharmacologic therapies. Six percent of the recommendations were strong and 94% conditional, indicating the importance of active discussion between the health care provider and the patient to choose the optimal treatment. CONCLUSION/CONCLUSIONS:The 2018 ACR/NPF PsA guideline serves as a tool for health care providers and patients in the selection of appropriate therapy in common clinical scenarios. Best treatment decisions consider each individual patient situation. The guideline is not meant to be proscriptive and should not be used to limit treatment options for patients with PsA.

PURPOSE OF REVIEW/OBJECTIVE:Despite a robust therapeutic landscape, significant gaps exist in the quality of care of psoriatic disease. Thus, an improved understanding of the challenges in providing quality care and the implementation of effective strategies to overcome them is needed. In this review, we summarize the burden of psoriatic disease, discuss the challenges in the care of psoriatic patients, and outline how combined dermatology-rheumatology clinics bridge many of these gaps. RECENT FINDINGS/RESULTS:Multiple challenges are faced in providing high-quality care to patients with psoriasis and psoriatic arthritis from the pre-diagnosis phase of disease to the follow-up period. Challenges are mainly driven by lack of education of patients and healthcare providers, inefficient communication between specialists, lack of a holistic approach to patients, and limitations of available therapies. The Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN) is working on demonstrating the effectiveness of combined dermatology-rheumatology clinics in addressing some of these challenges. Recent findings show that combined clinic models may improve quality of care by raising awareness of psoriatic disease, fostering educational activities for both patients and physicians, and allowing for comprehensive evaluation and management of patients through improved communications between disciplines. Psoriasis and psoriatic arthritis are complex diseases that often require an interdisciplinary approach. Thus, combined dermatology-rheumatology clinics and local-regional partnerships are potentially effective in improving quality of care in psoriatic disease.

Background/Purpose: Psoriatic Arthritis (PsA) affects up to 30% patients with psoriasis and is characterized by wide spread synovio-entheseal inflammation. Physiologically, the human gut microbiota metabolizes dietary fiber into shortchain fatty acids (FA)- which exert anti-inflammatory effects by increasing activity of regulatory T cells (Tregs).Moreover, we have previously shown decreased abundance of Akkermansia and Ruminococcus and concomitant decrease in mediumchain FA (MCFA) levels in stool of PsA patients. We therefore hypothesized that FA supplementation may have favorable effects on gut microbiome and lead to increase in tolerance, potentially serving as therapeutic target in psoriatic disease.
Method(s): Wild type (WT)animals were fed SCFA-rich diet for 14 days followed by 16S rRNA sequencing and microbiota analysis of pellet specimens.We then evaluated effects ofMCFA-rich diet in healthy subjects. Peripheral blood and stool samples were collected at days 0, 7 and 14 for 16s rRNA sequencing and FACS. Finally, we conducted a small, prospective, proof-ofprinciple study in new-onset, drug-naive psoriatic disease patients (with or without PsA). Each participant received MCFA (1 gm 4 times a day for 6 weeks). Clinical history was obtained at baseline. Skin and joint exam were performed at baseline and follow up. Serum and stool samples were collected at baseline, weeks 3, and 6 for 16S rRNA sequencing and FACS, respectively. Wilcoxon signed-rank test was used to compare differences in Tregs before and after MCFA-rich administration.
Result(s): SCFA rich diet in WT mice led to statistically significant perturbations in gut bacterial composition 14 days into intervention, with a dramatic increase in commensals (Fig 1A; p<0.001), most notably in Akkermansia(Fig 1B). MCFA administration to healthy subjects (n=7) also led to significant changes in community structure (Fig 2A; p=0.03) and associated increases in circulating Treg cells (Fig 2B; p<0.001). These findings were also observed in psoriatic disease patients (n=4) showing a significant alteration in specific taxa, including Actinobacteria (Fig 2 C; p<0.05) and Mollicutes (p=0.09) and concomitant increase in circulatory Treg cells (Fig 2D)
Conclusion(s): In both health and psoriatic disease, MCFA supplementation is associated with distinct changes in human gut microbiota composition and peripheral Treg cells. These findings rationalize the need for a larger placebo controlled, prospective trial to study the effects of MCFA in patients with psoriasis and PsA as a potential therapy alone or in combination with DMARDs. (Figure Presented)

Background/Purpose: The microbiome serves a number of important functions, including modulation of the immune system and protection from pathogenic microorganisms1. Many autoimmune diseases have been associated with intestinal microbial dysbiosis1. Recent studies have also demonstrated that microbiota can affect the lifetime, bioavailability and efficacy of drugs2. Conversely, even drugs designed to specifically target human cells have been associated with changes in microbial composition3. To date, most research has focused on bacterial microorganisms and little is known about the role that fungal microorganisms (the mycobiome) play, including their interactions with bacteria. In this study, we characterized the ecological effects of biologic therapies on the intestinal mycobiome.
Method(s): Fecal samples were collected from SpA patients pre- and post-treatment with either tumor necrosis factor inhibitors (TNFi; n=15) or secukinumab (n=14), an anti-IL-17A monoclonal antibody (IL-17i). Subjects treated with TNFi were naive to biologic therapy, whereas those treated with secukinumab previously failed or had incomplete response to TNFi. Samples underwent DNA extraction, amplification, and gene sequencing of the ITS1 region conserved in fungi. In parallel, gene sequencing of the 16S rRNA gene region conserved in bacteria was also performed. Sequences were analyzed with R and Quantitative Insights into Microbial Ecology (QIIME).
Result(s): ITS fungal data reveled that, on average, subjects treated with TNFi and IL-17i did not have major differences in overall microbial alpha or beta diversity pre- and post-treatment. However, there were dramatic shifts in the relative abundance of specific taxa, such as Candida albicans, which were more prominent in the IL-17i cohort compared to the TNFi cohort (p=0.04). The IL-17i cohort also demonstrated similar changes in certain 16S bacterial taxa, including Clostridia (p=0.02) and Clostridiales (p=0.02).
Conclusion(s): We characterized, for the first time, the effects of two biologic therapies on human intestinal fungal and bacterial microbiota composition. Treatment with biologics, particularly IL-17i, leads to a gut microbial dysbiosis characterized by significant changes in abundance of C. albicans and Clostridia in a subgroup of SpA patients. This is in line with the known increased risk of candidiasis seen with IL-17i, and may at least partially explain the potential link between IL-17 blockade, intestinal dysbiosis, and the subclinical and clinical gut inflammation observed in some patients treated with these molecules. Further studies to understand the downstream effects of these perturbations may allow for the development of precision medicine approaches in PsA and SpA

Background/Purpose: The Psoriatic Arthritis Impact of Disease (PsAID) questionnaire is a patient reported measure of disease impact. The 12-item questionnaire has many advantages including demonstrated validity, reliability, responsiveness and discrimination. However, few studies have examined the use of individual items as surrogates for important patient reported outcomes. For example, we were interested in whether the single PsAID fatigue item could be used in place of the 13 item FACIT-F instrument. Likewise, the pain, function, depression, and anxiety items could be used in place of additional questionnaires if the items correlated well with validated instruments both in cross-sectional and longitudinal settings. The objective of this study was to examine the longitudinal construct validity of the individual PSAID items for pain, fatigue, function, depression and anxiety.
Method(s): Patients with PsA were enrolled in the Psoriatic Arthritis Research Consortium (PARC) between 2015- 2017. PARC is a longitudinal observational cohort at four institutions: University of Pennsylvania, Cleveland Clinic, New York University, and University of Utah. Two of these institutions (Utah and Penn) administered the PSAID. Patient characteristics at the first/baseline visit were descriptively reported. The correlations were calculated among individual PSAID items with similar constructs (e.g., 'tired' item with FACIT-F, BASDAI tired item, etc.) at baseline using Spearman's correlation coefficients. The change scores (e.g., score at visit 1 - score at visit 0) and the correlation among change scores between the individual items and related constructs were also calculated.
Result(s): PSAID data were available from 862 visits; 302 patients completed at least one PSAID and 208 patients completed PSAIDs at >=2 visits. Most patients were in low disease activity (mean 66/68 swollen and tender joint counts were 2.6 and 5.3, respectively). At baseline, the mean PsAID9 and PsAID12 scores were 3.39 (SD2.45) and 3.22 (2.40) respectively. The individual PsAID items were moderately correlated (rho= 0.5-0.8) with similar constructs at baseline. However, aside from the moderate to strong correlation between the PsAID pain question with the RAPID3 pain question (rho=0.71), change scores were only slightly correlated with like instruments (rho = 0.2-0.45, Table).
Conclusion(s): The individual PsAID items did not correlate well with change in similar constructs over time. This may be due to the attribution of each symptom to PsA in the PSAID questionnaire. The assessed PsAID items cannot be used as close substitutes for the validated questionnaires with which they were compared

At the 2017 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members received updates on several ongoing educational and research efforts. Among them were updates on GRAPPA's continued education efforts; GRAPPA's continued research efforts, including the Biomarker Project, a collaborative research effort to identify and study biomarkers of joint damage; treatment recommendations, including recommendations and core principles related to biosimilars; efforts to update GRAPPA's Website and to create a GRAPPA smart-phone application (app); and the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network.