Genetically Proxied Interleukin-13 Inhibition Is Associated With Risk of Psoriatic Disease: A Mendelian Randomization Study.

OBJECTIVE: Inhibitors of the interleukin 13 (IL-13) pathway, such as dupilumab, are licensed for atopic dermatitis and asthma. Adverse events resembling psoriatic disease after dupilumab initiation have been reported, but evidence is limited to case reports with uncertain causality. We aimed to investigate whether genetically mimicked IL-13 inhibition (IL-13i) is associated with risk of psoriatic arthritis (PsA) and psoriasis. METHODS: We instrumented IL-13i using a protein-coding variant in the IL13 gene, rs20541, that is associated with circulating eosinophil count (biomarker of IL-13i) at genome-wide significance in a study of 563,946 individuals. Outcome genetic data were taken from studies of PsA, psoriasis, and related spondyloarthritis traits in up to 10,588 cases and 209,287 controls. Colocalization analysis was performed to examine genetic confounding. We additionally used circulating IgE as a biomarker to test whether associations were replicated, both in the test and in an independent genetic dataset. We also replicated analyses using individual-level data from the UK Biobank. RESULTS: Genetically proxied IL-13i was associated with increased risk of PsA (odds ratio [OR] 37.39; 95% confidence interval [95% CI] 11.52-121.34; P = 1.64 × 10-9) and psoriasis (OR 20.08; 95% CI 4.38-92.01; P = 1.12 × 10-4). No consistent associations were found for Crohn disease, ulcerative colitis, ankylosing spondylitis, or iritis. Colocalization showed no strong evidence of genetic confounding for psoriatic disease. Results were replicated using circulating IgE for the exposure, using independent outcome data and using individual-level data. CONCLUSION: We provide supportive genetic evidence that IL-13i is linked to increased risk of PsA and psoriasis. Physicians prescribing IL-13 inhibitors should be vigilant for these adverse events.

10-year multimorbidity patterns among people with and without rheumatic and musculoskeletal diseases: an observational cohort study using linked electronic health records from Wales, UK.

OBJECTIVES: To compare the patterns of multimorbidity between people with and without rheumatic and musculoskeletal diseases (RMDs) and to describe how these patterns change by age and sex over time, between 2010 and 2019. PARTICIPANTS: 103 426 people with RMDs and 2.9 million comparators registered in 395 Wales general practices (GPs). Each patient with an RMD aged 0-100 years between January 2010 and December 2019 registered in Clinical Practice Research Welsh practices was matched with up to five comparators without an RMD, based on age, gender and GP code. PRIMARY OUTCOME MEASURES: The prevalence of 29 Elixhauser-defined comorbidities in people with RMDs and comparators categorised by age, gender and GP practices. Conditional logistic regression models were fitted to calculate differences (OR, 95% CI) in associations with comorbidities between cohorts. RESULTS: The most prevalent comorbidities were cardiovascular risk factors, hypertension and diabetes. Having an RMD diagnosis was associated with a significantly higher odds for many conditions including deficiency anaemia (OR 1.39, 95% CI (1.32 to 1.46)), hypothyroidism (OR 1.34, 95% CI (1.19 to 1.50)), pulmonary circulation disorders (OR 1.39, 95% CI 1.12 to 1.73) diabetes (OR 1.17, 95% CI (1.11 to 1.23)) and fluid and electrolyte disorders (OR 1.27, 95% CI (1.17 to 1.38)). RMDs have a higher proportion of multimorbidity (two or more conditions in addition to the RMD) compared with non-RMD group (81% and 73%, respectively in 2019) and the mean number of comorbidities was higher in women from the age of 25 and 50 in men than in non-RMDs group. CONCLUSION: People with RMDs are approximately 1.5 times as likely to have multimorbidity as the general population and provide a high-risk group for targeted intervention studies. The individuals with RMDs experience a greater load of coexisting health conditions, which tend to manifest at earlier ages. This phenomenon is particularly pronounced among women. Additionally, there is an under-reporting of comorbidities in individuals with RMDs.

Population Pharmacokinetic Analysis and Simulation of Alternative Dosing Regimens for Biosimilars to Adalimumab and Etanercept in Patients with Rheumatoid Arthritis.

Efficacy to biologics in rheumatoid arthritis (RA) patients is variable and is likely influenced by each patient's circulating drug levels. Using modelling and simulation, the aim of this study was to investigate whether adalimumab and etanercept biosimilar dosing intervals can be altered to achieve therapeutic drug levels at a faster/similar time compared to the recommended interval. RA patients starting subcutaneous Amgevita or Benepali (adalimumab and etanercept biosimilars, respectively) were recruited and underwent sparse serum sampling for drug concentrations. Drug levels were measured using commercially available kits. Pharmacokinetic data were analysed using a population approach (popPK) and potential covariates were investigated in models. Models were compared using goodness-of-fit criteria. Final models were selected and used to simulate alternative dosing intervals. Ten RA patients starting the adalimumab biosimilar and six patients starting the etanercept biosimilar were recruited. One-compartment PK models were used to describe the popPK models for both drugs; no significant covariates were found. Typical individual parameter estimates were used to simulate altered dosing intervals for both drugs. A simulation of dosing the etanercept biosimilar at a lower rate of every 10 days reached steady-state concentrations earlier than the usual dosing rate of every 7 days. Simulations of altered dosing intervals could form the basis for future personalised dosing studies, potentially saving costs whilst increasing efficacy.

Factors facilitating and hindering South Asian immigrant adults from engaging in exercise and physical activity - a qualitative systematic review.

BACKGROUND: Exercise and physical activity are key components of management in patients with rheumatic musculoskeletal diseases (RMD), but people of the South Asian communities have a lower level of engagement with these activities compared to their Caucasian counterparts. The aim of this qualitative systematic review was to determine the barriers and facilitators of exercise and physical activity in South Asian communities who have migrated and live in western countries, particularly in those who have RMD. METHODS: Qualitative studies, published in English between 1999 and 2021 and including evaluation of barriers and/or facilitators to exercise or physical activity behaviour in people of South Asian adult communities who have migrated and/or lived in western countries were identified from Embase, MEDLINE, CINAHL, PsycINFO, Google Scholar and manual searches. The studies were appraised using the CASP checklist. Inductive thematic synthesis was used to identify common and global themes. RESULTS: A total of 32 studies that discussed barriers and facilitators of physical activity in South Asian communities who have migrated and lived in western countries were used for this review but there were no studies identified that focussed specifically on those with RMD. Following appraisal of the reporting of the studies, 30 studies were included in the pooling of the results. The facilitators and barriers to physical activities were broadly categorized into 'extrinsic' and 'intrinsic' factors. Extrinsic factors such as 'opportunity' included environmental factors such as weather and safety; socioeconomic factors such as education, language and literacy, and support in the form of social, psychological and resources. Intrinsic factors included cultural factors, such as life stages and family influence, beliefs and knowledge, which impacted attitudes and skills. CONCLUSIONS: This review has synthesised evidence of barriers or facilitators and identified potentially modifiable factors influencing physical activity and exercise engagement, which could form the basis of evidence-based interventions to promote participation in healthy behaviour change. Provision of a safe, comfortable and culturally acceptable environment together with culturally-aligned cognitive strategies to facilitate acquisition of exercise-efficacy skills could help engagement. REGISTRATION: The systematic review was registered on PROSPERO, registration no. 289,235.

Overcoming provider barriers to therapeutic drug monitoring of tumour necrosis factor inhibitors for rheumatoid arthritis: a qualitative analysis.

Objective: Therapeutic drug monitoring (TDM) of tumour necrosis factor-α inhibitors (TNFi), by measuring drug levels and/or anti-drug antibodies, is being considered by various international bodies to improve patient health outcomes and the value of care for people with rheumatoid arthritis. Rheumatology care providers may perceive barriers to adopting TNFi TDM within their own clinical practice, limiting the potential for patients and health care systems to benefit. This study aimed to explore the barriers perceived by rheumatologists that may reduce their uptake of TNFi TDM for rheumatoid arthritis. Method: Semi-structured one-to-one telephone interviews were performed with a convenience sample of senior rheumatologists with experience of managing people with rheumatoid arthritis. The interviews explored the rheumatologists' understanding of TDM and their beliefs about how it can be integrated into their own routine practice. Interviews were audio recorded, transcribed verbatim and anonymized. Transcripts were coded inductively and barriers to using TNFi TDM were identified by thematic framework analysis. Result: A sample of eleven senior rheumatologists were interviewed. The rheumatologists described five barriers to adopting TNFi TDM in routine practice: (i) observing clinical need; (ii) understanding how testing can improve practice; (iii) insufficient clinical evidence; (iv) insufficient resources to pay for testing; and (v) insufficient capability to deliver testing. Conclusion: Barriers to adopting TNFi TDM in routine care settings will restrict the ability for patients to benefit from effective monitoring strategies as they begin to emerge. Strategies to overcome these barriers are suggested which will require a coordinated response from stakeholders across health care systems.

Barriers and enablers to engagement in exercise and physical activity in non-English speaking South Asian people with chronic musculoskeletal disease.

BACKGROUND: Exercise and physical activity (EPA) are recommended for people with chronic musculoskeletal disease; however, lower levels of engagement with EPA has been consistently reported in people from the South Asian community across a range of diseases. As language can pose a significant barrier in healthcare, this study aimed to understand the enablers and barriers to the acceptance of EPA among non-English speaking South Asian people who attended rheumatology clinics. METHODS: 12 non-English speaking individuals from the South Asian community who had chronic musculoskeletal disease with significant pain scores were interviewed via telephone or face-to-face in their spoken languages. The audio recordings of the interviews were translated into English and transcribed verbatim. Data was analysed using thematic analysis implemented in the NVivo 12 Pro software program. RESULTS: The mean age was 52 years (9 women and 2 men). One main theme was identified: 'Enablers and barriers to exercise and physical activity'. Enablers to EPA were having knowledge about the benefits of EPA, being given resources in a language that they understood, and supportive environments such as having access to community facilities for those who could not undertake EPA in their houses. Barriers included physical health such as pain and fatigue, lack of time, difficulties with transportation to exercise venues, dislike of group exercises and lack of understanding of what and how to do exercise and be physically active. Participants' beliefs about EPA and whether they impacted their physical health seemed to influence whether they were undertaken or not. There was a perception that their culture shaped their compatriots' beliefs about EPA, and it was not normal practice for people from their country of birth to engage in it. CONCLUSIONS: This is the first qualitative study to explore the barriers and enablers to engagement in EPA in non-English speaking South Asian people with chronic musculoskeletal disease. Modifiable factors such as addressing the level of knowledge on the benefits of EPA in the management of chronic joint and muscle pain; aiding the development of the skills required to exercise safely and confidently despite chronic pain and providing information and services in the native language could promote the EPA engagement of non-English speaking South Asian individuals with chronic musculoskeletal disease. The findings may inform improvements within clinical services to promote the benefits, impact and self-efficacy of engagement with EPA as part of chronic musculoskeletal disease management. ETHICS APPROVAL: The West Midlands-Edgbaston Research Ethics Committee (reference:20/WM/0305).

Psoriatic arthritis: the role of self-reported non-adherence, non-trough drug levels, immunogenicity and conventional synthetic DMARD co-therapy in adalimumab and etanercept response.

Objective: The aim of this study was to assess the relationship between self-reported non-adherence, non-trough drug levels, immunogenicity and conventional synthetic DMARD (csDMARD) co-therapy in TNF inhibitor (TNF-i) drug response in PsA. Methods: Serum samples and adherence questionnaires were collected at baseline, 3, 6 and 12 months for PsA patients prescribed TNF-i. Non-trough adalimumab (ADL) and etanercept (ETN) drug levels were measured at 3 and 6 months using commercially available ELISAs. Clinical response was assessed using PsA response criteria (PsARC) and change in 28-joint DAS (ΔDAS28) between baseline and 3, 6 and 12 months. Results: In 244 PsA patients (52.5% ADL and 47.5% ETN), self-reported non-adherence was associated with PsARC non-response over 12 months using generalized estimating equation (GEE) modelling (P = 0.037). However, there was no significant difference between non-trough ADL or ETN drug levels based on self-reported non-adherence. Higher ETN levels at 3 months were associated with PsARC response at 3 (P = 0.015), 6 (P = 0.037) and 12 months (P = 0.015) and over 12 months using GEE modelling (P = 0.026). Increased ADL drug levels at 3 months were associated with greater ΔDAS28 at 3 months (P = 0.019). ADL anti-drug antibody-positive status was significantly associated with lower 3- and 6-month ADL levels (P < 0.001) and ΔDAS28 and PsARC response at 3, 6 and 12 months. Meanwhile, MTX co-therapy was associated with a reduction in immunogenicity at 3 and 6 months (P = 0.008 and P = 0.024). Conclusion: Although both were associated with reduced response, the objectively measured non-trough drug levels showed more significant associations with drug response than self-reported non-adherence measures.

Expression quantitative trait loci analysis in rheumatoid arthritis identifies tissue specific variants associated with severity and outcome.

OBJECTIVE: Genome-wide association studies have successfully identified more than 100 loci associated with susceptibility to rheumatoid arthritis (RA). However, our understanding of the functional effects of genetic variants in causing RA and their effects on disease severity and response to treatment remains limited. METHODS: In this study, we conducted expression quantitative trait locus (eQTL) analysis to dissect the link between genetic variants and gene expression comparing the disease tissue against blood using RNA-Sequencing of synovial biopsies (n=85) and blood samples (n=51) from treatment-naïve patients with RA from the Pathobiology of Early Arthritis Cohort. RESULTS: This identified 898 eQTL genes in synovium and genes loci in blood, with 232 genes in common to both synovium and blood, although notably many eQTL were tissue specific. Examining the HLA region, we uncovered a specific eQTL at HLA-DPB2 with the critical triad of single-nucleotide polymorphisms (SNPs) rs3128921 driving synovial HLA-DPB2 expression, and both rs3128921 and HLA-DPB2 gene expression correlating with clinical severity and increasing probability of the lympho-myeloid pathotype. CONCLUSIONS: This analysis highlights the need to explore functional consequences of genetic associations in disease tissue. HLA-DPB2 SNP rs3128921 could potentially be used to stratify patients to more aggressive treatment immediately at diagnosis.

A proteomics study of rheumatoid arthritis patients on etanercept identifies putative biomarkers associated with clinical outcome measures.

OBJECTIVES: Biologic DMARDs (bDMARDs) are widely used in patients with RA, but response to bDMARDs is heterogeneous. The objective of this work was to identify pretreatment proteomic biomarkers associated with RA clinical outcome measures in patients starting bDMARDs. METHODS: Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) was used to generate spectral maps of sera from patients with RA before and after 3 months of treatment with the bDMARD etanercept. Protein levels were regressed against RA clinical outcome measures, i.e. 28-joint DAS (DAS28) and its subcomponents and DAS28 <2.6 (i.e. remission). The proteins with the strongest evidence for association were analysed in an independent, replication dataset. Finally, subnetwork analysis was carried out using the Disease Module Detection algorithm and biological plausibility of identified proteins was assessed by enrichment analysis. RESULTS: A total of 180 patients with RA were included in the discovery dataset and 58 in the validation dataset from a UK-based prospective multicentre study. Ten individual proteins were found to be significantly associated with RA clinical outcome measures. The association of T-complex protein 1 subunit η with DAS28 remission was replicated in an independent cohort. Subnetwork analysis of the 10 proteins from the regression analysis identified the ontological theme, with the strongest associations being with acute phase and acute inflammatory responses. CONCLUSION: This longitudinal study of 180 patients with RA commencing etanercept has identified several putative protein biomarkers of treatment response to this drug, one of which was replicated in an independent cohort.

Socioeconomic deprivation is associated with reduced response and lower treatment persistence with TNF inhibitors in rheumatoid arthritis.

OBJECTIVE: To investigate the association between socioeconomic deprivation and outcomes following TNF inhibitor (TNFi) treatment. METHODS: Individuals commencing their first TNFi in the British Society for Rheumatology Biologics Register for RA (BSRBR-RA) and Biologics in RA Genetics and Genomics Study Syndicate (BRAGGSS) cohort were included. Socioeconomic deprivation was proxied using the Index of Multiple Deprivation and categorized as 20% most deprived, middle 40% or 40% least deprived. DAS28-derived outcomes at 6 months (BSRBR-RA) and 3 months (BRAGGSS) were compared using regression models with the least deprived as referent. Risks of all-cause and cause-specific drug discontinuation were compared using Cox models in the BSRBR-RA. Additional analyses adjusted for lifestyle factors (e.g. smoking, BMI) as potential mediators. RESULTS: 16 085 individuals in the BSRBR-RA were included (mean age 56 years, 76% female), of whom 18%, 41% and 41% were in the most, middle and least deprived groups, respectively. Of 3459 included in BRAGGSS (mean age 57, 77% female), proportions were 22%, 36% and 41%, respectively. The most deprived group had 0.3-unit higher 6-month DAS28 (95% CI 0.22, 0.37) and were less likely to achieve low disease activity (odds ratio [OR] 0.76; 95% CI 0.68, 0.84) in unadjusted models. Results were similar for 3-month DAS28 (ß = 0.23; 95% CI 0.11, 0.36) and low disease activity (OR 0.77; 95% CI 0.63, 0.94). The most deprived were more likely to discontinue treatment (hazard ratio 1.18; 95% CI 1.12, 1.25), driven by ineffectiveness rather than adverse events. Adjusted estimates were generally attenuated. CONCLUSION: Socioeconomic deprivation is associated with reduced response to TNFi. Improvements in determinants of health other than lifestyle factors are needed to address socioeconomic inequities.

Non-trough serum drug levels of adalimumab and etanercept are associated with response in patients with psoriatic arthritis.

OBJECTIVES: Up to 40% of psoriatic arthritis (PsA) patients experience first-line Tumour Necrosis Factor inhibitors (TNF-i) failure. Lower serum drug levels (SDL) have been associated with lower response in autoimmune conditions. This study aimed to: (i) establish the relationship between adalimumab (ADL) and etanercept (ETN) SDL and 3-month response; and (ii) identify optimal non-trough SDL thresholds in PsA. METHODS: PsA patients commencing ADL or ETN were recruited to the UK observational study OUTPASS. Patients were seen pre-TNF-i and at 3 months when response was measured, and non-trough serum samples collected. Response was defined according to the PsARC or EULAR criteria. Descriptive statistics and concentration-effect curves established differences in SDL based on response. Receiver operating characteristics and regression identified optimal SDL thresholds. RESULTS: PsA ETN (n = 97) PsARC and EULAR good responders had significantly higher 3-month SDL compared with non-responders (p= 0.006 and p= 0.020 respectively). Non-trough 3-month ETN SDL discriminated PsARC responders from non-responders (AUC = 0.70), with a threshold of 1.8 µg/ml being 63% specific and 69% sensitive. EULAR good and non-/moderate responders were discriminated with an AUC of 0.65 with a threshold of 2.0 µg/ml being 57% specific and 69% sensitive. ADL prescribed (n = 104) EULAR good responders had significantly higher 3-month SDL (p= 0.049). Non-trough 3-month ADL SDL discriminated EULAR good and non-/moderate responders (AUC = 0.63) with a threshold of 3.6 µg/ml being 48% specific and 81% sensitive. CONCLUSION: Higher 3-month SDL were detected in responders. Interventions to optimise SDL may improve treatment response earlier. This study suggests 3-month SDL thresholds which may be useful in clinical practice to optimise treatment response.

Using Polygenic Risk Scores to Aid Diagnosis of Patients With Early Inflammatory Arthritis: Results From the Norfolk Arthritis Register.

OBJECTIVE: There is growing evidence that genetic data are of benefit in the rheumatology outpatient setting by aiding early diagnosis. A genetic probability tool (G-PROB) has been developed to aid diagnosis has not yet been tested in a real-world setting. Our aim was to assess whether G-PROB could aid diagnosis in the rheumatology outpatient setting using data from the Norfolk Arthritis Register (NOAR), a prospective observational cohort of patients presenting with early inflammatory arthritis. METHODS: Genotypes and clinician diagnoses were obtained from patients from NOAR. Six G-probabilities (0%-100%) were created for each patient based on known disease-associated odds ratios of published genetic risk variants, each corresponding to one disease of rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, spondyloarthropathy, gout, or "other diseases." Performance of the G-probabilities compared with clinician diagnosis was assessed. RESULTS: We tested G-PROB on 1,047 patients. Calibration of G-probabilities with clinician diagnosis was high, with regression coefficients of 1.047, where 1.00 is ideal. G-probabilities discriminated clinician diagnosis with pooled areas under the curve (95% confidence interval) of 0.85 (0.84-0.86). G-probabilities <5% corresponded to a negative predictive value of 96.0%, for which it was possible to suggest >2 unlikely diseases for 94% of patients and >3 for 53.7% of patients. G-probabilities >50% corresponded to a positive predictive value of 70.4%. In 55.7% of patients, the disease with the highest G-probability corresponded to clinician diagnosis. CONCLUSION: G-PROB converts complex genetic information into meaningful and interpretable conditional probabilities, which may be especially helpful at eliminating unlikely diagnoses in the rheumatology outpatient setting.

Application of clinical and molecular profiling data to improve patient outcomes in psoriatic arthritis.

Achieving a good outcome for a person with Psoriatic Arthritis (PsA) is made difficult by late diagnosis, heterogenous clinical disease expression and in many cases, failure to adequately suppress inflammatory disease features. Single-centre studies have certainly contributed to our understanding of disease pathogenesis, but to adequately address the major areas of unmet need, multi-partner, collaborative research programmes are now required. HIPPOCRATES is a 5-year, Innovative Medicines Initiative (IMI) programme which includes 17 European academic centres experienced in PsA research, 5 pharmaceutical industry partners, 3 small-/medium-sized industry partners and 2 patient-representative organizations. In this review, the ambitious programme of work to be undertaken by HIPPOCRATES is outlined and common approaches and challenges are identified. It is expected that, when completed, the results will ultimately allow for changes in the approaches to diagnosing, managing and treating PsA allowing for better short-term and long-term outcomes.

Improving outcomes in Psoriatic Arthritis Psoriatic Arthritis (PsA) is a form of arthritis which is found in approximately 30% of people who have the skin condition, Psoriasis. Frequently debilitating and progressive, achieving a good outcome for a person with PsA is made difficult by late diagnosis, disease clinical features and in many cases, failure to adequately control features of inflammation. Research studies from individual centres have certainly contributed to our understanding of why people develop PsA but to adequately address the major areas of unmet need, multi-centre, collaborative research programmes are now required. HIPPOCRATES is a 5-year, Innovative Medicines Initiative (IMI) programme which includes 17 European academic centres experienced in PsA research, 5 pharmaceutical industry partners, 3 small-/medium-sized industry partners and 2 patient representative organisations (see appendix). In this review, the ambitious programme of work to be undertaken by HIPPOCRATES is outlined and common approaches and challenges are identified. The participation of patient research partners in all stages of the work of HIPPOCRATES is highlighted. It is expected that, when completed, the results will ultimately allow for changes in the approaches to diagnosing, managing and treating PsA allowing for improvements in short-term and long-term outcomes.

Utility of Musculoskeletal Ultrasound in Psoriatic Arthritis.

PURPOSE: Psoriatic arthritis (PsA) is a chronic autoimmune disease that causes a variety of musculoskeletal abnormalities. Musculoskeletal ultrasound in PsA is becoming increasingly popular, both in clinical practice and research. This narrative reviews recent literature on the utility of ultrasound in PsA. METHODS: A search of PubMed was used to identify publications written in English, with titles containing the term psoriatic arthritis and either ultrasound, ultrasonography, or sonographic. A total of 178 publications were identified; those that were not relevant (n = 59), were not original research (n = 45), or that had small (<30) sample sizes (n = 34) were excluded, leaving 40 studies for review of the use of ultrasound in various aspects of PsA. Publications with similar findings were grouped into seven domains: (1) the use of ultrasound findings compared to clinical assessment; (2) the use of ultrasound in the assessment of enthesitis; (3) the use of ultrasound in the assessment of nails; (4) the use of ultrasound as a screening tool in patients with psoriasis at risk for PsA; (5) the use of ultrasound in differentiating PsA from other similar conditions; (6) the use of ultrasound as a measure of disease activity; and (7) the use of ultrasound compared to MRI. FINDINGS: In recent studies, ultrasound measures of inflammation tended to agree with objective clinical findings of disease, such as swollen joint counts, while being less influenced by subjective measures, such as pain. Ultrasound has utility in the assessment of enthesitis and psoriatic nail disease in PsA, and as an overall measure of disease activity. Ultrasound-based outcomes measures have been used in observational studies and in clinical trials involving PsA, and may have utility as a measure of treatment response. The findings from recent studies suggest that ultrasound may have utility in improving the accuracy and precision of screening programs designed to identify subclinical PsA in cohorts of patients with psoriasis; however, cost-efficacy remains to be determined. Beyond screening, ultrasound may have utility in the diagnosis of PsA in patients with suspected inflammatory arthritis, and ultrasound measures of inflammation agree with MRI measures of inflammation, meaning that incorporating ultrasound into clinical practice might help to overcome the barriers associated with MRI. IMPLICATIONS: As ultrasound technology continues to advance, and associated costs decrease, it is likely that ultrasound will become more integrated into the clinical journeys of patients with PsA.

Genetic Studies Investigating Susceptibility to Psoriatic Arthritis: A Narrative Review.

PURPOSE: Approximately 30% of patients with psoriasis will develop psoriatic arthritis (PsA), leading to a decreased quality of life for the patient caused by increasing disability and additional health complications. The identification of risk factors for the development of PsA would facilitate the development of risk prediction models in which patients with psoriasis at high risk of developing PsA could be targeted in a stratified medicine approach, enabling early intervention and treatment. PsA is known to have a genetic contribution to susceptibility, and the identification of genetic risk factors that differentiate PsA from cutaneous-only psoriasis is a key area of research. This narrative review summarizes the discovery of genetic risk factors and, with the aid of a primer on risk prediction models, discusses their potential role for the classification of PsA risk and diagnosis. METHODS: All relevant research articles were identified through searches of the PubMed database for literature published up until December 2022. Search terms included psoriatic arthritis, genetic susceptibility, genetic association, genome-wide association study, GWAS, prediction, and polygenic risk score. FINDINGS: The current literature reveals considerable overlap between the genetic susceptibility loci for PsA and psoriasis. Several PsA-specific genetic risk factors have been reported, and most notably these implicate the HLA-B and IL23R genes. Efforts to include genetic risk factors in prediction models for the development of PsA have reported good discrimination. IMPLICATIONS: Key messages emerging from this narrative are as follows: the limited number of PsA-specific susceptibility loci reported to date suggest larger studies are required, facilitated by international collaboration, to achieve the power to detect further genetic factors; the early promising results for genetic-based risk prediction require further validation in independent datasets; and risk prediction models combining clinical and genetic risk factors have yet to be explored.