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.

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.

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: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.

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.

Rheumatoid arthritis is a chronic systemic immune-mediated disease caused by genetic and environmental factors. It is often characterized by the generation of autoantibodies that lead to synovial inflammation and eventual multi-joint destruction. A growing number of studies have shown significant differences in the gut microbiota composition of rheumatoid arthritis (RA) patients compared to healthy controls. Environmental factors, and changes in diet and nutrition are thought to play a role in developing this dysbiosis. This review aims to summarize the current knowledge of intestinal dysbiosis, the role of nutritional factors, and its implications in the pathogenesis of rheumatoid arthritis and autoimmunity. The future direction focuses on developing microbiome manipulation therapeutics for RA disease management.

OBJECTIVE:To evaluate secukinumab 300 mg and 150 mg vs placebo in a US-only population of biologic-naive patients with psoriatic arthritis (PsA). METHODS:CHOICE was a randomized, double-blind, controlled trial conducted in the United States. Biologic-naive patients with PsA and psoriasis were randomized 2:2:1 to secukinumab 300 mg (n = 103), secukinumab 150 mg (n = 103), or placebo (n = 52). The primary objective was to show superiority of secukinumab 300 mg vs placebo in ACR20 response at week 16. Additional objectives included the effect of secukinumab on dactylitis, enthesitis, psoriasis, and safety. RESULTS:= .0011). Secukinumab 300 mg also led to greater ACR50/70 responses and improvements in other variables vs placebo. Responses were generally sustained over time. Patients with inadequate response to secukinumab 150 mg at weeks 16, 28, or 40 who received dose escalation to 300 mg experienced improved clinical response after uptitration. The most common adverse events were upper respiratory tract infections and diarrhea. No inflammatory bowel disease was reported or new safety signals observed. CONCLUSION/CONCLUSIONS:Secukinumab 300 mg led to rapid and significant improvements over placebo in symptoms of PsA in this heavier population of US-only biologic-naive patients. Findings were consistent with previous studies and suggest that secukinumab 300 mg is a safe and efficacious first-line biologic treatment for patients with PsA.