Faculty Bibliography

OBJECTIVE:Evaluate the efficacy and safety of guselkumab, an interleukin-23p19-subunit inhibitor, in participants with active psoriatic arthritis (PsA) and inadequate response (inadequate efficacy and/or intolerance) to one prior tumor necrosis factor inhibitor (TNFi-IR). METHODS:In SOLSTICE (phase 3b, randomized, multicenter, double-blind, placebo-controlled study), enrolled adults with active PsA (≥3 swollen joints;≥3 tender joints; C-reactive protein ≥0.3 mg/dL) and inadequate response to one prior TNFi were randomized to guselkumab 100mg every 4 weeks (Q4W); guselkumab 100mg at Weeks 0 and 4, then Q8W; or placebo➔guselkumab Q4W at Week24. The primary endpoint was ≥20% improvement in American College of Rheumatology criteria (ACR20) at Week24. Secondary endpoints included ACR50; ACR70; Investigator's Global Assessment of psoriasis (IGA) of 0/1 with ≥2-grade improvement; ≥90% improvement in Psoriasis Area and Severity Index (PASI 90); and minimal disease activity (MDA) at Week24 and were analyzed by intention-to-treat. RESULTS:Analyses included 451 randomized participants (Q4W N=150; Q8W N=151; placebo N=150). At Week24, significantly greater proportions of guselkumab Q4W/Q8W-treated vs placebo-treated participants, respectively, achieved ACR20 (primary endpoint: 58.6%/62.2% vs 34.8%), ACR50 (31.4%/32.1% vs 12.2%), ACR70 (17.5%/17.3% vs 2.0%), IGA 0/1 response (50.0%/57.3% vs 17.4%, PASI 90 (49.4%/45.5% vs 12.0%), and MDA (18.8%/23.9% vs 5.4%) (all p<0.001). Through Week24, 46.7%, 53.6%, and 48.3% of participants receiving Q4W, Q8W, and placebo, respectively, had ≥1 adverse event. One death occurred (myocardial infarction). CONCLUSION/CONCLUSIONS:Comparable efficacy was observed with both guselkumab regimens in TNFi-IR participants with active PsA; safety findings were consistent with the known profile of guselkumab in patients with psoriatic disease.

OBJECTIVES/OBJECTIVE:Although genetic risk factors, such as HLA-DRB1 alleles, contribute to the pathogenesis of rheumatoid arthritis (RA), the concordance rate in monozygotic (MZ) twins is low, suggesting that other factors are involved in disease development. Further, the relative contribution of nongenetic elements in identical twins has not been characterised. Here, we aimed to characterise host and microbial biomarkers of RA by studying MZ twins discordant for disease using a multiomics approach. METHODS:Eight pairs of MZ twins discordant for RA (N = 16) were enrolled in the United States (US). The gut microbiome was assessed using shotgun metagenomic sequencing. Autoantibodies, cytokines, and plasma proteins were measured in both plasma and faeces. Levels of short-chain fatty acids (SCFAs) from serum and faeces were quantified using gas chromatography mass spectrometry (GC-MS). Metagenomic data from a UK twin registry (TwinsUK) (N = 14) were used to validate findings in the US population. RESULTS:Although microbiome diversity and composition did not differ between twins, we observed a significant decrease in the SCFA-producing bacteria Blautia faecis and significantly lower concentrations of faecal butyrate and propionate in affected RA twins in the US. TwinsUK showed a similar reduction in the SCFA-producers Gemmiger formicilis and Faecalicatena fissicatena, as well as bacterial SCFA metabolism pathways. CONCLUSIONS:Multiomics biomarkers differentiate MZ twins discordant for RA. Faecal butyrate and propionate, as well as SCFA-producing bacteria, were decreased in affected twins. We found a similar decrease in SCFA-producing taxa in affected twins in a geographically distinct cohort in the UK. Our results suggest that, if further validated in larger cohorts, multiomics approaches may improve our understanding of RA pathogenesis and, potentially, contribute to more accurate diagnostics and coadjuvant therapies.

INTRODUCTION/BACKGROUND:An abnormal composition of gut bacteria along with alterations in microbial metabolites and reduced gut barrier integrity has been associated with the pathogenesis of chronic autoimmune and inflammatory rheumatic diseases (AIRDs). The aim of the systematic review, for which this protocol is presented, is to evaluate the clinical benefits and potential harms of therapies targeting the intestinal microbiota and/or gut barrier function in AIRDs to inform clinical practice and future research. METHODS AND ANALYSIS/METHODS:This protocol used the reporting guidelines from the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol. We will search Embase (Ovid), Medline (Ovid) and the Cochrane Library (Central) for reports of randomised controlled trials of patients diagnosed with an AIRD. Eligible interventions are therapies targeting the intestinal microbiota and/or gut barrier function including probiotics, synbiotics, faecal microbiota transplantation, live biotherapeutic products and antibiotics with the intent to modify disease activity in AIRDs. The primary outcome of the evidence synthesis will be based on the primary endpoint of each trial. Secondary efficacy outcomes will be evaluated and selected from the existing core domain sets of the individual diseases and include the following domains: disease control, patient global assessment, physician global assessment, health-related quality of life, fatigue, pain and inflammation. Harms will include the total number of withdrawals, withdrawals due to adverse events, number of patients with serious adverse events, disease flares and deaths. A meta-analysis will be performed for each outcome domain separately. Depending on the type of outcome, the quantitative synthesis will encompass both ORs and standardised mean differences with corresponding 95% CIs. ETHICS AND DISSEMINATION/BACKGROUND:No ethics approval will be needed for this systematic review. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to disseminate the study results through a peer-reviewed publication. PROSPERO REGISTRATION NUMBER/UNASSIGNED:CRD42025644244.

Obesity constitutes a substantial burden in psoriatic disease that affects approximately half of patients. Importantly, increased adiposity and psoriatic disease are strongly linked, with obesity functioning as both a possible trigger and a disease modifier. Obesity predisposes individuals to develop psoriasis and is likely to drive, at least partially, the progression from psoriasis to psoriatic arthritis. For people with psoriasis or psoriatic arthritis, obesity is associated with lower rates of remission and poorer responses to treatment. Several mechanisms probably underlie this relationship, including systemic and local pro-inflammatory properties of adipose tissue, increased biomechanical stress on joints and entheses, gut dysbiosis and synergistic effects of osteoarthritis. Notably, weight loss can improve both psoriatic disease course and response to therapy; however, current approaches (such as dietary interventions or bariatric surgery) are difficult to implement. Glucagon-like peptide-1-based therapies are an effective strategy for weight loss in psoriatic disease and might even have additive disease-modifying effects to conventional immunomodulators. Although often overlooked, weight loss intervention and obesity management should be included as an integral part of psoriatic disease treatment algorithms.

IMPORTANCE/UNASSIGNED:Achieving good disease control in psoriatic arthritis (PsA) remains a major challenge. Combining multiple systemic immunomodulatory therapies has been shown to be beneficial in other immune-mediated diseases with reasonable safety profiles, but data on the current use and safety of combination targeted therapy among individuals with PsA are limited. OBJECTIVE/UNASSIGNED:To evaluate the use and safety of combination targeted therapies among adults with PsA. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Data from the IBM MarketScan Commercial Claims Database from January 2015 to December 2024 were used to describe use patterns and perform safety analyses. Data were analyzed from April 2024 to June 2025. A validated claims algorithm was used to identify adults with PsA, who were separated into a standard therapy control cohort that was matched 2:1 with the combination targeted therapy cohort. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Descriptive analysis of the use of combination targeted therapies. The safety analysis included a comparison of frequencies of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes for serious or opportunistic infections requiring an inpatient level of care. Relative risks (RRs) were calculated before and after propensity score matching. RESULTS/UNASSIGNED:Among 82 399 individuals identified with PsA, 542 individuals (median [IQR] age, 52.5 [44.0-59.0] years; 341 female individuals [62.9%]) were receiving combination targeted therapy for 3 consecutive months and 200 (median [IQR] age, 55.0 [45.0-61.0] years; 114 female individuals [57.0%]) were receiving combination therapy for 6 consecutive months. The 2 most common combinations used were a tumor necrosis factor inhibitor with apremilast (34%-37%) and an interleukin 17 inhibitor with apremilast (27%-29%). The serious infection incidence rate among patients receiving combination targeted therapy ranged from 7.38 to 15.00 events per 1000 patients; the opportunistic infection incidence rate ranged from 0 to 1.85 events per 1000 patients. Patients receiving combination targeted therapy did not have a significantly increased risk of serious infection (propensity score-matched 3-month and 6-month RRs, 0.53 [95% CI, 0.17-1.63] and 1.50 [95% CI, 0.34-6.65], respectively) or opportunistic infection (adjusted 3-month and 6-month RRs, 1.00 [95% CI, 0.09-11.02] and not applicable, respectively) across all analyses. CONCLUSIONS AND RELEVANCE/UNASSIGNED:The results of this cohort study suggest that among commercially insured adults with PsA, around 1% of individuals were receiving combination targeted therapy. The most common combinations used different biologics with apremilast. This study found no significant difference between the incidence of serious bacterial and opportunistic infections requiring hospitalization compared with standard therapy, suggesting that combination targeted therapy may not be associated with significantly increased infection risk, but further larger studies are needed.

IMPORTANCE/UNASSIGNED:Defining on-treatment remission in plaque psoriasis is important for benchmarking patient responses to therapies. This also helps to facilitate shared understanding, align treatment expectations, and enable more effective psoriasis management. OBJECTIVE/UNASSIGNED:To establish a consensus-based definition of on-treatment remission for plaque psoriasis through a multistage Delphi initiative. EVIDENCE REVIEW/UNASSIGNED:The Remission Workgroup from the medical board and scientific advisory board of the National Psoriasis Foundation engaged various stakeholders, both US based and international, to participate in the consensus process. Following a working group meeting to determine the overall consensus approach, a systematic review of remission definitions in the current literature was performed. This review helped to inform the content of consensus materials. The consensus effort involved 2 stages: pre-Delphi interviews and surveys to inform the Delphi questions, followed by a Delphi exercise with physicians to define on-treatment remission for plaque psoriasis. Outcome measures considered included body surface area (BSA), Investigator Global Assessment (IGA), the product of the Physician Global Assessment and body surface area (PGA × BSA), and Psoriasis Area and Severity Index (PASI) score at various cutoff levels and time points. FINDINGS/UNASSIGNED:The consensus process involved 92 stakeholders, including dermatologists, rheumatologists, researchers, patients, payers, and life sciences professionals. In the pre-Delphi interviews and surveys, patients emphasized that on-treatment remission meant the absence of psoriasis signs and symptoms while recieving therapy. Payers expressed that defining remission is important for long-term treatment coverage. Following the Delphi exercise and discussion with participating physicians specializing in psoriatic disease management, on-treatment remission in plaque psoriasis was defined as patients maintaining a BSA of 0% or IGA of 0 for at least 6 months while on treatment. CONCLUSIONS AND RELEVANCE/UNASSIGNED:Through a Delphi consensus process, on-treatment remission for plaque psoriasis was defined as patients maintaining a BSA involvement of 0% or IGA of 0 for at least 6 months while on treatment. This clear and standardized benchmark is applicable to both research and practice settings.

BACKGROUND/UNASSIGNED:In order to apply current treatment recommendations for psoriatic arthritis (PsA), a complete assessment of psoriatic disease domains must be completed by the clinician. This includes a musculoskeletal examination (including tender and swollen joints, dactylitis, enthesitis, and axial disease) as well as skin and nail examination. Documentation in the clinician's note serves as a proxy for disease assessment. OBJECTIVE/UNASSIGNED:To explore differences in documentation of psoriatic domains between PsA specialist and general rheumatologists at 2 academic centers. METHODS/UNASSIGNED:We identified PsA patients seen by either general rheumatologists or by PsA combined clinic specialist providers at 2 established PPACMAN (Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network) sites. Records were assessed for the presence (and extent) of documentation for musculoskeletal and cutaneous PsA domains. We also examined accuracy of ICD coded diagnoses to understand the extent to which discrete data from the electronic medical record can be used to evaluate completeness of assessment. RESULTS/UNASSIGNED:< 0.001). Additionally, PsA specialists more consistently coded for both psoriasis (PsO) and PsA. CONCLUSIONS/UNASSIGNED:In this multicenter, retrospective study, compared to generalists, PsA combined-clinic specialist providers more thoroughly documented both musculoskeletal and cutaneous psoriatic disease domains and ICD coding of PsO for patients, highlighting gaps in assessment and documentation. These findings underscore the need for improved training in psoriatic disease assessment and simplified modalities for documentation.

BACKGROUND:Psoriatic arthritis (PsA) is a multi-domain, inflammatory disease impacting joints, soft tissues, and skin; tumor necrosis factor inhibitors (TNFi) are typically the first biologic following inadequate response (IR) to conventional therapies. Although guidance is lacking on therapy selection after initial TNFi failure, data suggest TNFi-IR PsA patients may benefit from switching to a different mechanism of action (MOA) vs. cycling to another TNFi. Guselkumab is a fully human monoclonal antibody targeting the interleukin-23p19 subunit. Emphasizing practicality and applicability to routine clinical practice, EVOLUTION will pragmatically evaluate whether switching to guselkumab is more effective than cycling to a second TNFi (subcutaneous [SC] golimumab) in TNFi-IR PsA patients. METHODS:The multicenter, longitudinal, prospective, observational Psoriatic Arthritis Research Consortium study guided eligibility criteria, outcome measures, and sample size estimates. Adults seen in clinical practice with active PsA (≥ 1 swollen joint) while receiving TNFi treatment will be eligible. Participants will be randomized (1:1:1) to guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at Week 0, Week 4, and Q8W; or SC golimumab 50 mg Q4W (no washout period). The novel primary composite endpoint is achievement of clinical Disease Activity in Psoriatic Arthritis (cDAPSA) low disease activity (≤ 13) and an Investigator's Global Assessment (IGA) of psoriasis score of 0/1 (scale: 0-4) at Month12. Secondary endpoints include cDAPSA + IGA 0/1 at Month 6; achievement of minimal disease activity, resolution of enthesitis and dactylitis (among patients affected at baseline) at Months 6/12; and mean changes at Months 6/12 in the 12-item PsA Impact of Disease, Dermatology Life Quality Index, Patient-Reported Outcomes Measurements Information System fatigue and depression questionnaires, and Bath Ankylosing Spondylitis Disease Activity Index (patients with physician-determined axial disease). The target sample size is 150 participants (50/treatment group); all analyses are considered exploratory. DISCUSSION/CONCLUSIONS:EVOLUTION will employ a pragmatic approach, including a novel primary endpoint relevant to clinical practice, to assess whether switching to an alternate MOA biologic with guselkumab is more effective than cycling to a second TNFi among TNFi-IR PsA patients. TRIAL REGISTRATION/BACKGROUND:This trial was registered at ClinicalTrials.gov, NCT05669833, on 3 January 2023, https://www. CLINICALTRIALS/RESULTS:gov/study/NCT05669833?term=%20NCT05669833&rank=1.

OBJECTIVES/OBJECTIVE:Despite significant therapeutic advances in psoriatic arthritis (PsA), many patients do not achieve remission and cycle through multiple biologic (b)- or targeted synthetic (ts)- DMARDs. Identifying the underlying reasons for repetitive therapeutic failure remains a knowledge gap. Here we describe prescribing patterns and characteristics of PsA patients with multi-b/tsDMARD failure at the NYU Psoriatic Arthritis Center. METHODS:Nine hundred sixty PsA patients were enrolled in an observational, longitudinal registry. Demographics, medical history, medication use, and psoriatic disease phenotype were collected. Multi-b/tsDMARD failure was defined as requiring ≥ 4 b/tsDMARDs. RESULTS:Seven hundred twenty-five patients (75%) used ≥ 1 b/tsDMARD during their disease course. The initial b/tsDMARDs prescribed were predominately anti-TNF agents. 166 (17%) patients had multi-b/tsDMARD failure. Compared to those requiring 1 b/tsDMARD, female sex (OR 2.3; 95%CI 1.4-3.8), axial disease (OR 2.1; 95% CI 1.2-3.6), depression (OR 2.0; 95%CI 1.1-3.7), and obesity (OR 1.7; 95%CI 1.0-2.8) were risk factors for multi-b/tsDMARD failure disease after adjustment for age, disease duration, sex, depression, smoking, obesity, and skin severity. Patients with multi-b/tsDMARD failure PsA also had increased disease activity at their clinical visit (i.e., swollen joint count, p = 0.005). CONCLUSION/CONCLUSIONS:In this cohort, 17% patients with PsA experienced multi-b/tsDMARD failure. These patients were more likely to be female, obese, and have higher rates of axial involvement and depression, along with higher active disease activity. This highlights the inflammatory and non-inflammatory drivers of multiple therapeutic failures, underscoring the need for precision medicine strategies and potential non-pharmacologic adjuvant therapies for patients with PsA to improve outcomes and quality of life.