Faculty Bibliography

In individuals with inflammatory bowel disease (IBD), extraintestinal manifestations (EIMs) represent a significant burden of illness, with reported prevalence rates of up to 50%.¹ Of the various types of EIMs, the most commonly involved organ system is the musculoskeletal system.

Whereas the cellular and molecular features of human inflammatory skin diseases are well characterized, their tissue context and systemic impact remain poorly understood. We thus profiled human psoriasis (PsO) as a prototypic immune-mediated condition with a high predilection for extracutaneous involvement. Spatial transcriptomics (ST) analyses of 25 healthy, active lesion, and clinically uninvolved skin biopsies and integration with public single-cell transcriptomics data revealed marked differences in immune microniches between healthy and inflamed skin. Tissue-scale cartography further identified core disease features across all active lesions, including the emergence of an inflamed suprabasal epidermal state and the presence of B lymphocytes in lesional skin. Both lesional and distal nonlesional samples were stratified by skin disease severity and not by the presence of systemic disease. This segregation was driven by macrophage-, fibroblast-, and lymphatic-enriched spatial regions with gene signatures associated with metabolic dysfunction. Together, these findings suggest that mild and severe forms of PsO have distinct molecular features and that severe PsO may profoundly alter the cellular and metabolic composition of distal unaffected skin sites. In addition, our study provides a valuable resource for the research community to study spatial gene organization of healthy and inflamed human skin.

OBJECTIVES/OBJECTIVE:To investigate the cutaneous microbiome spanning the entire psoriatic disease spectrum, and to evaluate distinguishing features of psoriasis (PsO) and psoriatic arthritis (PsA). METHODS:Skin swabs were collected from upper and lower extremities of healthy individuals and patients with PsO and PsA. Psoriatic patients contributed both lesional (L) and contralateral non-lesional (NL) samples. Microbiota were analysed using 16S rRNA sequencing. RESULTS:was higher in NL PsA samples compared with NL PsO samples (p<0.05), potentially serving as a biomarker for disease progression. CONCLUSIONS:These findings show differences in diversity, bacterial composition and microbe-microbe interactions between healthy and psoriatic skin, both L and NL. We further identified bacterial biomarkers that differentiate disease phenotypes, which could potentially aid in predicting the transition from PsO to PsA.

OBJECTIVE:Recent large-scale randomised trials demonstrate that immunomodulators reduce cardiovascular (CV) events among the general population. However, it is uncertain whether these effects apply to rheumatoid arthritis (RA) and if certain treatment strategies in RA reduce CV risk to a greater extent. METHODS:F-fluorodeoxyglucose-positron emission tomography/CT scans were assessed for change in arterial inflammation, an index of CV risk, measured as an arterial target-to-background ratio (TBR) in the carotid arteries and aorta. RESULTS:115 patients completed the protocol. The two treatment groups were well balanced with a median age of 58 years, 71% women, 57% seropositive and a baseline disease activity score in 28 joints of 4.8 (IQR 4.0, 5.6). Baseline TBR was similar across the two groups. Significant TBR reductions were observed in both groups-ΔTNFi: -0.24 (SD=0.51), Δtriple therapy: -0.19 (SD=0.51)-without difference between groups (difference in Δs: -0.02, 95% CI -0.19 to 0.15, p=0.79). While disease activity was significantly reduced across both treatment groups, there was no association with change in TBR (β=0.04, 95% CI -0.03 to 0.10). CONCLUSION:We found that addition of either a TNFi or triple therapy resulted in clinically important improvements in vascular inflammation. However, the addition of a TNFi did not reduce arterial inflammation more than triple therapy. TRIAL REGISTRATION NUMBER:NCT02374021.

INTRODUCTION:Psoriatic arthritis (PsA) is a complex, immune-mediated disease associated with skin psoriasis that, if left untreated, can lead to joint destruction. Up to 30% of patients with psoriasis progress to PsA. In most cases, psoriasis precedes synovio-entheseal inflammation by an average of 5-7 years, providing a unique opportunity for early and potentially preventive intervention in a susceptible and identifiable population. Guselkumab is an effective IL-23p19 inhibitor Food and Drug Administration (FDA-approved for treatment of moderate-to-severe psoriasis and PsA. The Preventing Arthritis in a Multicentre Psoriasis At-Risk cohort (PAMPA) study aims to evaluate the efficacy of guselkumab in preventing PsA and decreasing musculoskeletal power Doppler ultrasound (PDUS) abnormalities in a population of patients with psoriasis who are at-increased risk for PsA progression. METHODS AND ANALYSIS:The PAMPA study is a multicentre, randomised, double-blind, placebo-controlled, interventional, preventive trial comparing PDUS involvement and conversion to PsA in patients with psoriasis at-increased risk for progression treated with guselkumab compared with non-biological standard of care. The study includes a screening period, a double-blind treatment period (24 weeks) and an open-label follow-up period (72 weeks). At baseline, 200 subjects will be randomised (1:1) to receive either guselkumab 100 mg (arm 1) or placebo switching to guselkumab 100 mg starting at week 24 (arm 2). Arm 3 will follow 150 at-risk psoriasis patients who decline biological therapy and randomisation. Changes from baseline in the PDUS score at week 24 and the difference in proportion of patients transitioning to PsA at 96 weeks will be examined as the coprimary endpoints. ETHICS AND DISSEMINATION:Ethics approval for this study was granted by the coordinating centre's (NYU School of Medicine) Institutional Review Board (IRB). Each participating site received approval through their own IRBs. The findings will be shared in peer-reviewed articles and scientific conference presentations. TRIAL REGISTRATION NUMBER:NCT05004727.

OBJECTIVES/OBJECTIVE:Autoantibody seroconversion has been extensively studied in the context of COVID-19 infection but data regarding post-vaccination autoantibody production is lacking. Here we aimed to determine the incidence of common autoantibody formation following mRNA COVID-19 vaccines in patients with inflammatory arthritis (IA) and in healthy controls. METHODS:Autoantibody seroconversion was measured by serum ELISA in a longitudinal cohort of IA participants and healthy controls before and after COVID-19 mRNA-based immunization. RESULTS:Overall, there was a significantly lower incidence of ANA seroconversion in participants who did not contract COVID-19 prior to vaccination compared with those who been previously infected (7.4% vs 24.1%, p= 0.014). Incidence of de novo anti-cyclic citrullinated protein (CCP) seroconversion in all participants was low at 4.9%. Autoantibody levels were typically of low titer, transient, and not associated with increase in IA flares. CONCLUSIONS:In both health and inflammatory arthritis, the risk of autoantibody seroconversion is lower following mRNA-based immunization than following natural SARS-CoV-2 infection. Importantly, seroconversion does not correlate with self-reported IA disease flare risk, further supporting the encouragement of mRNA-based COVID-19 immunization in the IA population.

CASE:This case describes a 45-year-old man with documented history of untreated bilateral lower extremity psoriasis of equal severity who sustained a closed left tibial-fibular shaft fracture. After operative fixation with an intramedullary nail under a regional nerve block, the left lower extremity circumferential psoriatic plaque resolved throughout 1 year of follow-up with persistence of the contralateral limb disease. CONCLUSION:This case describes a rare outcome for a patient with bilateral leg psoriasis who experienced resolution of psoriatic plaques on the operated leg only after surgery. It is unknown which process: injury, anesthetic, surgery, or fracture healing mediated this unique finding.

Background/Purpose: Despite significant heterogeneity in psoriatic arthritis (PsA), randomized controlled trials (RCTs) generally enroll a homogenous subgroup of PsA patients (polyarticular similar to rheumatoid arthritis). In clinical practice, however, majority of patients have oligoarticular disease, often making it difficult to observe meaningful changes. To improve our understanding of how therapies work in the "real world" and among understudied patient subgroups, trials in real world environments are crucial. Before conducting pragmatic studies in PsA, however, it is necessary to define the appropriate outcome measures including patient-reported outcomes (PROs). The objectives of this study were to determine the responsiveness to therapy and minimally clinically important improvement (MCII) for PROs in PsA and to examine the impact of baseline disease activity on the ability to demonstrate change.
Method(s): A longitudinal cohort study was performed within the PsA Research Consortium (PARC). Patients completed PROs including the Routine Assessment of Patient Index Data, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the PsA Impact of Disease questionnaire, and three PRO Measure Information System (PROMIS) instruments (global 10a, depression 8a, and fatigue 8a). Mean change in the scores between visits and standardized response means (SRMs) were calculated. The MCII was calculated as the mean change in score among patients who reported minimal improvement. SRMs and MCIIs were compared among subgroups with moderate to highly active PsA (>=3 swollen and >=3 tender joint counts based on 66-and 68-joint counts respectively) and those with less active PsA (< 3 swollen and < 3 tender joint counts). This cut-off is used as an inclusion criterion in most PsA RCTs.
Result(s): Among 171 patients, 266 therapy courses were included. Mean age was 51 (SD 13.8), 53% were female, and mean body mass index (BMI) was 29.9 (SD 6.5). At baseline, the mean swollen and tender joint counts were 3 and 6, respectively. Therapies initiated included a tumor necrosis factor inhibitor (N=145), interleukin 17 inhibitor (N=55), other biologic or JAK inhibitor (N=14), or an oral small molecule (N=96). SRMs (Figure 1) and MCII for all measures (Table 1 & 2) were small to moderate though greater among those with higher baseline disease activity. BASDAI had the best SRM overall and for less active PsA. cDAPSA and PsAID performed better and comparable to BASDAI respectively in the moderate to highly active PsA subgroup. SRMs were similar among those initiating a biologic therapy compared to those initiating any therapy.
Conclusion(s): SRMs and MCII were relatively small in this real-world population, particularly among those with lower disease activity at baseline. The PsAID and cDAPSA measures performed better in those with higher disease activity compared to Figure 1. Standard Response Means of different measures tested in PARC. Abbreviations: PARC: Psoriatic Arthritis Research Consortium; TNFi: tumor necrosis factor inhibitor; IL17i: interleukin-17 inhibitor; HAQDI: Health Assessment Questionnaire Disability Index; MD global: physician's global assessment; Pt: patient; SJC: swollen joint count; TJC: tender joint count; BASDAI: Bath Ankylosing Spondylitis Disease Activity Index; PSAID: Psoriatic Arthritis Impact of Disease; cDAPSA: clinical Disease Activity of Psoriatic Arthritis; MDHAQ: Multidimensional Health Assessment Questionnaire; PROMIS: Patient-Reported Outcomes Measurement Information System Global Short Form; PROMIS10 MH: Patient-Reported Outcomes Measurement Information System Global Short Form Mental Health; PROMIS10 PH: Patient-Reported Outcomes Measurement Information System Global Short Form Physical Health; RAPID3: Routine Assessment of Patient Index Data. those with lower disease activity. In future pragmatic trials, selection of measures should take into account the projected baseline disease activity of patients enrolled