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Objective: It is known that fracture risk is increased in patients with psoriatic arthritis (PsA); however, there is no consensus on the association with osteoporosis. The purpose of this study was to elicit the rate of osteoporosis and the risk factors of osteoporosis in patients with PsA at our institution. Methods: The data in this study were extracted from 163 patients with PsA. Osteoporosis and osteopenia were defined based on the WHO definition. Osteoporosis was also diagnosed when a fragility vertebral compression fracture was observed. Results: The osteoporosis and osteopenia rates for PsA patients were 11.7% and 33.1%, respectively. The rates of osteoporosis and osteopenia in males were particularly high compared to previous reports, at 9.3% and 34.3%, respectively. Trabecular bone score was considered age-appropriate for both males and females. Body mass index and Trabecular bone score were significantly lower in patients with osteoporosis. Conclusions: In patients with PsA, males are at elevated risk of osteoporosis and associated fragility fractures even if they are under 50 years. Body mass index was significantly lower in osteoporotic cases, suggesting the importance of bone mineral density testing and treatment in such cases. [ABSTRACT FROM AUTHOR]

Objective SpA and PsA represent two frequent inflammatory rheumatic disorders characterized by an increased burden on quality of life due to the association of several comorbidities, especially cardiovascular disease (CVD). The estimated prevalence of CVD ranges from 12 to 19% and differs between the two diseases, however, the incidence of CVD is not completely known. We aimed to systematically review the literature and perform a meta-analysis of controlled observational studies to assess the incidence rate of CVD over time in SpA and PsA. Methods We performed a systematic literature review (SLR) of longitudinal studies with a study period of at least 5 years, including SpA/PsA patients and general population. The main outcome was the occurrence of CVD, including ischaemic heart disease, stroke and death from CV causes. We then performed a random-effects model for meta-analysis. Results The SLR included 34 articles, mainly focused on the association between SpA/PsA and CVD. Twenty-four articles were then selected for the meta-analysis. The overall incidence of CVD was increased in PsA [hazard ratio (HR) 1.28 (95% CI 1.15, 1.43)] and in SpA [HR 1.45 (95% CI 1.22, 1.72)] compared with the general population, with consistency across the different types of CVDs. Interestingly the incidence tended to decrease over time in PsA but not in SpA. Conclusion The SLR and meta-analysis confirmed the increased incidence of CVD in both SpA and PsA patients compared with the general population, although the increase seems to be less prominent in PsA than in SpA. Future studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Objectives PsA is the most prevalent coexisting condition associated with psoriasis. Early-stage PsA patients always present unspecific and subtle clinical manifestations causing delayed diagnosis and leading to unfavourable health outcomes. The application of US enables precise identification of inflammatory changes in musculoskeletal structures. Hence, we constructed US models to aid early diagnosis of PsA. Methods This was a cross-sectional study carried out in the Department of Dermatology at West China Hospital (October 2018–April 2021). All participants underwent thorough US examinations. Participants were classified into the under 45 group (18 ≤ age ≤ 45 years) and over 45 (age >45 years) group and then randomly grouped into derivation and test cohort (7:3). Univariable logistic regression, least absolute shrinkage and selection operator, and multivariable logistic regression visualized by nomogram were conducted in order. Receiver operating characteristic (ROC), calibration curve, decision curve analysis (DCA) and clinical impact curve analysis (CICA) were performed for model verification. Results A total of 1256 participants were included, with 767 participants in the under 45 group and 489 in the over 45 group. Eleven and 16 independent ultrasonic variables were finally selected to construct the under 45 and over 45 model with the area under the ROC of 0.83 (95% CI 0.78–0.87) and 0.83 (95% CI 0.78–0.88) in derivation cohort, respectively. The DCA and CICA analyses showed good clinical utility of the two models. Conclusion The implementation of the US models could streamline the diagnostic process for PsA in psoriasis patients, leading to expedited evaluations while maintaining diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Objectives To describe the clinical features and treatment outcomes of children with juvenile psoriatic arthritis (JPsA) and compare the distinct patterns of the disease between early-onset and late-onset age groups. Methods Patients with JPsA followed regularly for at least 6 months between 2010 and 2020 in seven paediatric rheumatology centres in Turkey were included in the study. The demographic features, clinical manifestations, treatment strategies and outcomes of the patients were evaluated retrospectively. Results A total of 87 (46 male/41 female) patients were included in the study. The mean age at diagnosis was 11.9 years (s. d. 4.5). Fifty-seven (65.5%) patients had psoriasis at the time of diagnosis and arthritis preceded psoriasis in 10 (11.5%) patients. Thirty (34.5%) patients had dactylitis, 28 (32.2%) had nail pitting, 36 (41.4%) had involvement of the small joints and 20 (23%) had enthesitis. Sacroiliitis was detected in 11 (12.6%) patients by MRI. ANA was positive in 35 (40.2%) patients. Twelve children (13.8%) were in the early-onset (<5 years) group. Uveitis and ANA positivity were more common in the early-onset group. Active joint counts and activity scores of our patients showed significant improvement at month 6 and at the last control compared with baseline. Conclusion About one-third of patients with JPsA do not have psoriasis at the time of diagnosis. In some patients, no skin lesion is seen during the course of the disease. Children with PsA seem to display two different phenotypes. Younger children have a female predominance, ANA positivity and uveitis, while older children have more axial involvement. [ABSTRACT FROM AUTHOR]

Objective This study was designed to compare thiol/disulfide and ischemia-modified albumin (IMA) levels between psoriatic arthritis (PsA) and healthy controls and evaluate the correlation between these molecules and the disease activity scores used in PsA. Methods A total of 63 PsA patients and 49 healthy volunteers were included in the study. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), modified disease activity score 28 (DAS28), and Bath Ankylosing Spondylitis Functional Index (BASFI) scores were used as disease activity indices for PsA patients. Calculations of native thiol (-SH), disulfide (-SS), and total thiol (-SH+-SS) molecules were made by the automatic spectrophotometric method, and the albumin cobalt binding test was used to measure IMA levels. Results In the PsA group, -SS/-SH and -SS/(-SH+-SS) levels were higher and -SH/(-SH+-SS) levels were lower than in controls. In the linear regression analysis, a significant correlation relationship was detected between DAS28-erythrocyte sedimentation rate (ESR) and -SS/(-SH+-SS) (β = 0.795, CI 95%, 0.196-1.395; P =.010), -SH/(-SH+-SS) (β = -0.475, CI 95%, 0.114-0.836; P =.010) and IMA (β = 3.932, CI 95%, 0.859-7.005; P =.013). Additionally, a significant correlation was detected between IMA and BASDAI and BASFI. Conclusion In PsA, thiol/disulfide homeostasis has shifted in favor of disulfide as an oxidative indicator. Serum thiol/disulfide levels are correlated with PsA disease activity indices. [ABSTRACT FROM AUTHOR]

Objectives To evaluate 1-year bimekizumab efficacy in PsA from the patient perspective using the 12-item PsA Impact of Disease (PsAID-12) questionnaire. Methods BE OPTIMAL (NCT03895203; biologic DMARD [bDMARD]-naïve), BE COMPLETE (NCT03896581; inadequate response/intolerance to TNF inhibitors [TNFi-IR]) and BE VITAL (NCT04009499; open-label extension) assessed bimekizumab 160 mg every 4 weeks in patients with PsA. Post hoc analyses of patient-reported disease impact, assessed by the PsAID-12 questionnaire, are reported to 1 year (collected to Week 40 in BE COMPLETE). Results Overall, 1,112 total patients were included (698 bimekizumab, 414 placebo). Rapid improvements observed with bimekizumab treatment at Week 4 continued to Week 16 and were sustained to 1 year. At 1 year, mean (SE) change from baseline in PsAID-12 total score was comparable between bimekizumab-randomized patients and patients who switched to bimekizumab at Week 16 (bDMARD-naïve bimekizumab –2.3 [0.1], placebo/bimekizumab –2.2 [0.1]; TNFi-IR bimekizumab –2.5 [0.1], placebo/bimekizumab –2.2 [0.2]). Proportions of bimekizumab-randomized patients achieving clinically meaningful within-patient improvement (≥3-point decrease from baseline) at Week 16 were sustained to 1 year (bDMARD-naïve 49.0%; TNFi-IR 48.5%) and were similar for placebo/bimekizumab patients (bDMARD-naïve 44.4%; TNFi-IR 40.6%). Across studies and arms, 35.3% to 47.8% of patients had minimal or no symptom impact at 1 year. Improvements were observed to 1 year across all single-item domains, including pain, fatigue and skin problems. Conclusion Bimekizumab treatment resulted in rapid and sustained clinically meaningful improvements in disease impact up to 1 year in bDMARD-naïve and TNFi-IR patients with PsA. Trial registration BE OPTIMAL: NCT03895203; BE COMPLETE: NCT03896581; BE VITAL: NCT04009499 (ClinicalTrials.gov) [ABSTRACT FROM AUTHOR]

Objective To present the characteristics of patients with potential difficult-to-treat (D2T) PsA. Methods We used data from the Greek multicentre registry of PsA patients. D2T PsA was defined as follows: patients with at least 6 months' disease duration, who have failed to at least one conventional synthetic DMARD and at least two biologic DMARDs/targeted synthetic DMARDs with a different mechanism of action and have either at least moderate disease activity (MODA) defined as DAPSA (Disease Activity index in PSoriatic Arthritis) >14, and/or are not at minimal disease activity (MDA). Demographic and clinical characteristics were compared between D2T and non-D2T PsA patients. In two sensitivity analyses, patients classified as D2T solely according to the MODA or MDA criterion were examined separately. Results Among 467 patients included, 77 (16.5%) were considered D2T and 390 non-D2T PsA. Compared with non-D2T, patients with D2T PsA presented more commonly with extensive psoriasis (P  < 0.0001) and were more likely to have higher BMI (P  = 0.023) and a history of IBD (P  = 0.026). In the MODA and MDA sensitivity analyses, 7.5% and 12.5% of patients were considered D2T, respectively. In both sensitivity analyses, extensive psoriasis was again identified as an independent variable for D2T PsA (P  = 0.001 and P  = 0.008, respectively). Moreover, female gender (P  = 0.034) in the MODA analysis and axial disease (P  = 0.040) in the MDA analysis were independent variables for D2T PsA. Conclusion Despite the availability of therapies, D2T PsA is common in real-life cohorts of patients with PsA and extensive psoriasis. High BMI, female gender, axial disease and history of IBD were also associated with D2T PsA. [ABSTRACT FROM AUTHOR]

Background Early identification, diagnosis and symptom control of psoriatic arthritis (PsA) in patients with psoriasis remain unmet medical needs. Objectives To compare the impact of disease and other characteristics between patients with psoriasis who screened positive for PsA using the Psoriasis Epidemiology Screening Tool (PEST) (screen-positive group) and patients who (i) have PsA (PsA group) or (ii) screened negative for PsA (screen-negative group). Also, to determine the proportion of patients at a patient-acceptable symptom state (PASS) in the screen-positive and PsA groups. Methods This was a cross-sectional analysis of the CorEvitas Psoriasis Registry. We included a convenience sample of patients with psoriasis from the screen-positive and PsA groups who completed the Psoriatic Arthritis Impact of Disease-12 (PsAID12), and a comparator screen-negative group who did not complete the PsAID12. We report descriptive summaries of demographics, comorbidities, psoriasis characteristics, patient-reported outcome measures and the proportion of patients at PASS (i.e. PsAID12 ≤ 4). Results The screen-positive, PsA and screen-negative groups included 369, 70 and 4724 patients, respectively. The screen-positive and PsA groups had a similar impact of disease, demographics, comorbidities and psoriasis characteristics (d < 0.337). Mean PsAID12 scores were 3.1 (SD 2.3) and 3.7 (SD 2.6) in the screen-positive and PsA groups, respectively. Compared with patients who screened negative for PsA, patients who screened positive exhibited higher rates of selected known predictors of PsA such as older age, longer psoriasis duration, nail disease and inverse psoriasis. The proportion of patients at PASS was 56% and 67% for the PsA and screen-positive groups, respectively. Conclusions The similar profiles between screen-positive and PsA groups, in comparison with the screen-negative group, support observations of possible underdiagnosis of PsA and the increased impact of disease, especially musculoskeletal disease, among patients who screen positive for PsA. The high percentage of patients not at an acceptable symptom state in the PsA and screen-positive groups highlights the need to optimize care in PsA. [ABSTRACT FROM AUTHOR]

Objectives: An acidogenic diet, by disrupting the blood pH equilibrium, can contribute to metabolic acidosis and lead to inflammation. Therefore, we hypothesized that dietary acid load (DAL) increases disease activity and inflammation in psoriatic arthritis (PsA) patients. Methods: This study was conducted with 58 obese/overweight patients, aged 20–65 years. Dietary intake was assessed using a 3-consecutive-day 24-hour recall. The DAL was evaluated through the PRAL (potential renal acid load) and NEAP (net endogenous acid production) and divided into the low and high groups by their median values. The disease activity assessments, anthropometric measurements, dietary data, and blood parameters of patients were recorded and compared at the low and high DAL groups. Results: We observed that patients in the high NEAP and PRAL groups had worse PsA pattern scores (P < 0.05). Also, PRAL and NEAP scores were positively associated with Disease Activity Index for Psoriatic Arthritis, Health Assessment Questionnaire, and Psoriatic Arthritis Impact of Disease-12 (PSAID-12) scores. After adjusting age, sex, smoking, and body mass index, 1 mEq increase in PRAL and NEAP was associated with an elevation of Disease Activity Index for Psoriatic Arthritis (0.506 and 0.486 points, respectively). Conclusions: These results showed a close relationship between DAL and PsA symptoms. An acidogenic diet may negatively affect PsA prognosis. Healthy eating recommendations should be part of the management of the disease. [ABSTRACT FROM AUTHOR]

Objective: While biologics have been used for the patients with psoriatic arthritis, there remains to be unknown concerning long-term retention rates. This study aims to present real-world data about long-term retention rates of biologics for the patients with psoriatic arthritis, and to undertake an analysis of the contributing factors. Methods: We examined retention rates and the reasons for discontinuation for biologics (adalimumab, certolizumab pegol, secukinumab, and ixekizumab) in 146 prescriptions (of which, 109 prescriptions were as naive) at our hospital since March 2010. Results: Throughout the entire course of the study, the 10-year retention rates were approximately 70% for adalimumab, 50% for ixekizumab, and 40% for secukinumab. When evaluating retention rates in the biologic-naïve subgroups, the 10-year retention rates were all approximately 70%. Regarding certolizumab pegol, the 3-year retention rate was approximately 75%. For adalimumab, a higher degree of arthritis at the initiation of treatment was found to correlate with an increased likelihood of secondary inefficacy. The main reason for discontinuation was secondary inefficacy, except for ixekizumab. Conclusions: Each biologic exhibited a favourable long-term retention rate. The main reason for discontinuation was secondary inefficacy. Regarding adalimumab, secondary inefficacy was linked to the extent of arthritis upon treatment initiation. [ABSTRACT FROM AUTHOR]

Objectives Although physical therapy is recommended as part of the non-pharmacological management of patients with psoriatic arthritis (PsA), the evidence is still unclear. Therefore, this study aimed to systematically review and appraise the quality of research on physical therapy in the management of patients with PsA. Methods In June 2024, a systematic literature search using four different databases (Medline, Embase, Web of Science and the Cochrane Library) was performed to include interventional and observational studies examining physical therapy in patients with PsA (PROSPERO ID 255501). A risk of bias assessment was conducted. Due to the wide variety of interventions and outcomes, a narrative synthesis was used. Results Of 9442 abstracts, 15 papers examining physical therapy uptake in clinical practice (N  = 2) and different physical therapy interventions (N  = 13) were included: cardiorespiratory exercises (N  = 5), resistance exercises (N  = 2), therapeutic modalities (N  = 4) and mixed rehabilitation programs (N  = 2). A low risk of bias was scored in only one RCT assessing cardiorespiratory exercises. The well-tolerated 11-week high-intensity interval training resulted in a long-term increase in peak oxygen uptake and a short-term decrease in truncal fat percentage in patients with low disease activity. Resistance training in patients with active disease did not increase muscle strength, but improved functional capacity, disease activity, pain and general health after the intervention. Evidence for other modalities was inconclusive. Conclusion High-quality evidence on physical therapy in PsA was scarce. Cardiorespiratory and resistance exercises demonstrated promising results to positively influence cardiometabolic risk as well as disease-related outcomes. Future research on physical therapy in PsA with adequate methodological quality is needed. [ABSTRACT FROM AUTHOR]

Background Postinfectious Lyme arthritis (LA) is associated with dysregulated immunity and autoreactive T- and B-cell responses in joints. Here we explored the role of host genetic variation in this outcome. Methods The frequency of 253 702 single-nucleotide polymorphisms (SNPs) was determined in 147 patients with LA (87 with postinfectious LA and 60 with antibiotic-responsive LA), and for comparison in 90 patients with erythema migrans or the general population (n = 2504). Functional outcome of candidate SNPs was assessed by evaluating their impact on clinical outcome and on immune responses in blood and synovial fluid in patients with LA. Results Six SNPs associated with late cornified envelope (LCE3) genes were present at greater frequency in patients with postinfectious LA compared to those with antibiotic-responsive LA (70% vs 30%; odds ratio, 2; P <.01). These SNPs were associated with heightened levels of inflammatory Th17 cytokines in serum but lower levels of interleukin 27, a regulatory cytokine, implying that they may contribute to dysregulated Th17 immunity in blood. Moreover, in patients with postinfectious LA, the levels of these Th17 mediators correlated directly with autoantibody responses in synovial fluid, providing a possible link between LCE3 SNPs, maladaptive systemic Th17 immunity, and autoreactive responses in joints. Conclusions Variation in the LCE3 locus, a known genetic risk factor in psoriasis and psoriatic arthritis, is associated with dysregulated systemic Th17 immunity and heightened autoantibody responses in joints. These findings underscore the importance of host genetic predisposition and systemic Th17 immunity in the pathogenesis of postinfectious (antibiotic-refractory) Lyme arthritis. [ABSTRACT FROM AUTHOR]

Objective There is growing interest in the early identification of patients with axial PsA (axPsA). We aimed to evaluate whether a dermatology-based screening strategy could help to identify axPsA patients. Methods The dermatologist-centred screening (DCS) questionnaire was administrated by dermatologists to consecutive patients fulfilling the inclusion criteria [(i) age ≥18 years and (ii) clinical diagnosis of psoriasis made by a dermatologist] to identify patients eligible (affirmative answers 1–3c of the DCS) for rheumatological evaluation. Clinical, laboratory, genetic and imaging data were collected from all referred patients. Results Among the 365 patients screened, 265 fulfilled the inclusion criteria and 124/265 (46.8%) were eligible for rheumatological referral. Diagnosis of axPsA, with or without peripheral PsA (pPsA), was made in 36/124 (29.0%) patients; pPsA without axial involvement was found in 21/124 (16.9%) patients. Back pain at screening was recorded in 174 (66%) patients, with 158 (60%) reporting a back pain duration longer than 3 months and 140 (53%) reporting back pain onset before the age of 45 years. Active inflammatory and/or structural post-inflammatory changes in the sacroiliac joints and/or spine were observed in all axPsA patients. Patients with PsA showed a numerically longer duration of back pain and higher CRP levels in comparison with patients with psoriasis without PsA. Conclusion The DCS tool proved to be a valuable screening strategy for detecting and characterizing patients with axPsA in a real-life cohort of psoriasis patients in a dermatological setting and helped to identify a substantial number of patients affected by undiagnosed pPsA. [ABSTRACT FROM AUTHOR]

Background Smoking is a known risk factor for psoriasis; however, the impact of smoking cessation on psoriasis has seldom been evaluated. Objectives We aimed to examine the effects of smoking cessation on the development of psoriasis vulgaris (PsV), palmoplantar pustulosis (PPP) and generalized pustular psoriasis (GPP). Methods Using the Korean National Health Insurance Service database, we retrospectively compiled a cohort of 5 784 973 participants without psoriasis, analysed their changes in smoking status from 2004 to 2007 and followed up new cases of psoriasis until 2021. The psoriasis risks were compared with those of sustained smokers, smoking quitters, sustained ex-smokers and never smokers using multivariate Cox proportional hazard models. Results The mean age of the participants was 47.1 years (SD 13.5) and 3 092 426 (53.5%) were male. During 77 990 688 person-years, 67 364 psoriasis cases were identified. Compared with sustained smokers, smoking quitters showed a reduced risk of developing psoriasis [adjusted hazard ratio (aHR) 0.91; 95% confidence interval (CI) 0.87–0.95], specifically PsV (aHR 0.92; 95% CI 0.88–0.97) and PPP (aHR 0.71; 95% CI 0.63–0.79). The reduction in risk due to smoking cessation was more prominent in sustained ex-smokers (psoriasis: aHR 0.77, 95% CI 0.74–0.79; PsV: aHR 0.76, 95% CI 0.73–0.79; PPP: aHR 0.56, 95% CI 0.51–0.61; GPP: aHR 0.64; 95% CI 0.52–0.78). When conducting sensitivity analyses to address the potential for changes in smoking habits after 2007, the results and trends were consistent with the main findings, and a more pronounced significance was observed. Conclusions Compared with continuous smoking, smoking cessation was associated with a decreased risk of developing psoriasis. The risk-reducing effect of smoking cessation was more pronounced in those maintaining a smoke-free status. Smoking cessation and the maintenance of a smoke-free status should be encouraged to prevent the development of psoriasis and all other smoking-related diseases. [ABSTRACT FROM AUTHOR]

Objectives The objectives of this study were to investigate the incidence of demyelinating disease (DD) among SpA patients and to identify risk factors that predict DD in this patient population. Methods Axial SpA (axSpA) and PsA patients were identified from a longitudinal cohort database. Each group was analysed according to the presence or absence of DD. Incidence rates (IRs) of DD were obtained, with competing risk analysis. Cox regression analysis (with Fine and Gray's method) was used to evaluate predictors of DD development. Results Among 2260 patients with follow-up data, we identified 18 DD events, corresponding to an average IR of 31 per 100 000 persons per year for SpA. The IR of DD at 20 years was higher in axSpA than in PsA (1.30% vs 0.13%, P  = 0.01). The risk factors retained in the best predictive model for DD development included ever- (vs never-) smoking [hazard ratio (HR) 2.918, 95% CI 1.037–8.214, P  = 0.0426], axSpA (vs PsA) (HR 8.790, 95% CI 1.242–62.182, P  = 0.0294) and presence (vs absence) of IBD (HR 5.698, 95% CI 2.083–15.589, P  = 0.0007). History of TNF-α inhibitor therapy was not a predictor of DD. Conclusion The overall incidence of DD in this SpA cohort was low. Incident DD was higher in axSpA than in PsA. A diagnosis of axSpA, the presence of IBD, and ever-smoking predicted the development of DD. History of TNF-α inhibitor use was not found to be a predictor of DD in this cohort. [ABSTRACT FROM AUTHOR]

Objective To assess current evidence for effectiveness of sequential lines of biologic and targeted small-molecule disease-modifying anti-rheumatic drugs (b/tsDMARDs) when used beyond first-line for psoriatic arthritis (PsA). Methods A systematic search of the literature (Medline, Embase, bibliographic searches) was undertaken (October and December 2022) to find studies meeting the criteria of assessing effectiveness of b/tsDMARDs beyond first-line in adults with PsA (PROSPERO CRD42022365298). Risk of bias assessment was undertaken (ROBINS-I/Cochrane RoB2). Results Of 2666 abstracts identified and following a full text review of 177 psoriatic disease studies, 12 manuscripts and two abstracts were eligible. Of the 12 manuscripts, 11 were observational and one was a sub-analysis of a RCT (n  = 16 081: average age 49.5 years, female 53.3%). Two abstracts (n  = 7186) were included. All studies comparing first- and second-line (three studies) found a reduced response in second-line. On average, DAPSA remission (most reported outcome, eight studies) was achieved in 26%, 19% and 10% first-, second- and third-line TNFi, and 22%, 13% and 11% first-, second- and third-line other bDMARDs, respectively. Responses varied to third-line bDMARDs; four studies found comparable second- and third-line responses, five studies found diminishing responses in sequential lines. Conclusion Predominantly observational studies, inherently at high risk of bias, indicate bDMARDs can be effective to third-line in PsA, but that response is reduced after first line. There is very limited data for more advanced lines of b/tsDMARD. Prospective studies are required to better understand clinical response to advanced lines of treatment in PsA. [ABSTRACT FROM AUTHOR]

Objectives To understand the relative efficacy and safety of bimekizumab, a selective inhibitor of IL-17F in addition to IL-17A, vs other biologic and targeted synthetic DMARDs (b/tsDMARDs) for PsA using network meta-analysis (NMA). Methods A systematic literature review (most recent update conducted on 1 January 2023) identified randomized controlled trials (RCTs) of b/tsDMARDs in PsA. Bayesian NMAs were conducted for efficacy outcomes at Weeks 12–24 for b/tsDMARD-naïve and TNF inhibitor (TNFi)-experienced patients. Safety at Weeks 12–24 was analysed in a mixed population. Odds ratios (ORs) and differences of mean change with the associated 95% credible interval (CrI) were calculated for the best-fitting models, and the surface under the cumulative ranking curve (SUCRA) values were calculated to determine relative rank. Results The NMA included 41 RCTs for 22 b/tsDMARDs. For minimal disease activity (MDA), bimekizumab ranked 1st in b/tsDMARD-naïve patients and 2nd in TNFi-experienced patients. In b/tsDMARD-naïve patients, bimekizumab ranked 6th, 5th and 3rd for ACR response ACR20/50/70, respectively. In TNFi-experienced patients, bimekizumab ranked 1st, 2nd and 1st for ACR20/50/70, respectively. For Psoriasis Area and Severity Index 90/100, bimekizumab ranked 2nd and 1st in b/tsDMARD-naïve patients, respectively, and 1st and 2nd in TNFi-experienced patients, respectively. Bimekizumab was comparable to b/tsDMARDs for serious adverse events. Conclusion Bimekizumab ranked favourably among b/tsDMARDs for efficacy on joint, skin and MDA outcomes, and showed comparable safety, suggesting it may be a beneficial treatment option for patients with PsA. [ABSTRACT FROM AUTHOR]

Objectives We aimed to identify determinants of health-related quality of life (HRQoL) and global functioning and health (GH) in axial SpA (axSpA), peripheral SpA (pSpA) and (PsA). Methods The ASAS-perSpA study data were analysed. Models for the three patient groups were run separately to explore factors associated with HRQoL and GH, assessed by EQ-5D and ASAS-HI, respectively. Results The analyses included 4185 patients: 2719 with axSpA, 433 with pSpA, and 1033 with PsA. In axSpA, disease activity (β = –0.061), physical function (β = –0.041), female sex (β = –0.019) and fibromyalgia (FM) (β = –0.068) were associated with worse HRQoL; age (β = 0.001) and university education (β = 0.014) were associated with better HRQoL. In pSpA, disease activity (β = –0.04) and physical function (β = –0.054) were associated with worse HRQoL. In PsA, disease activity (β = –0.045), physical function (β = –0.053), axial disease (β = –0.041) and female sex (β = –0.028) were associated with worse HRQoL. In axSpA, disease activity (β = 0.889), physical function (β = 0.887), peripheral disease (β = 0.564), female sex (β = 0.812) and FM (β = 1.639) were associated with worse GH; age (β = –0.013) and university education (β = –0.274) were associated with better GH. In pSpA, physical function (β = 1.142) and female sex (β = 1.060) were associated with worse GH; university education (β = –0.611) was associated with better GH. In PsA, disease activity (β = 0.703), physical function (β = 1.025), axial involvement (β = 0.659), female sex (β = 0.924) and FM (β = 1.387) were associated with worse GH; age (β = –0.024) and university education (β = –0.856) were associated with better GH. Conclusion Disease activity and physical function are major HRQoL and GH determinants across SpA types, and clinical characteristics and sociodemographic factors play an important role, highlighting the importance of a holistic approach for individual patients. [ABSTRACT FROM AUTHOR]

Objective The possibility of combining real and virtual environments is driving the increased use of augmented reality (AR) in education, including medical training. The aim of this multicentre study was to evaluate the students' perspective on the AR-based Rheumality GO!® app as a new teaching concept, presenting six real anonymized patient cases with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). Methods The study encompassed 347 undergraduate medical students (232 women and 115 men) from four medical universities in Germany (Jena, Bad Nauheim/Gießen, Nuremberg, Erlangen). The course was divided into a theoretical refresher lecture followed by six AR-based cases in each of the three indications presented in the Rheumality GO! app. All participants evaluated the course after completion, assessing the benefit of the app from a student's perspective using a questionnaire with 16 questions covering six subject areas. Results The use of the AR-based app Rheumality GO! improved the understanding of pathologies in RA, PsA and axSpA for 99% of the participants. For 98% of respondents, the concept of AR with real patient data has made a positive impact on the teaching environment. On the other hand, 82% were in favour of the use of virtual tools (e.g. AR) in addition to this conventional approach. Conclusion The results of our survey showed that from the medical students' perspective, an AR-based concept like the Rheumality GO! app can complement rheumatology teaching in medical school as an effective and attractive tool though not replace bedside teaching. [ABSTRACT FROM AUTHOR]

Background Psoriasis is a genetically determined systemic skin disease, although environmental trigger factors are required for disease manifestation. Some of these triggers, such as stress, infections and drug exposure, have been identified. Objectives To explore the role of early nutrition as a risk factor for the development of psoriasis. Methods Parents in the All Babies in Southeast Sweden (ABIS) prospective birth cohort (n = 16 415) answered questionnaires at birth and when their children were aged 1 and 3 years. A diagnosis of psoriasis was determined from the Swedish National Patient Register and National Drug Prescription Register. Statistical analyses were conducted using custom-written R scripts. Results Individuals breastfed for < 4 months and who received infant formula before 4 months of age had a higher risk of psoriasis [odds ratio (OR) 1.84 (P = 0.02) and OR 1.88 (P = 0.02), respectively]. At the 3-year follow-up, the increased consumption of fish, especially from the Baltic Sea, increased the risk of psoriasis (OR 9.61; P = 0.003). In addition, the risk of psoriasis increased following the consumption of a large volume of milk (OR 2.53; P = 0.04). Conclusions Our study underscores, for the first time, the impact of very early nutrition on the manifestation of psoriasis through early adulthood. Exclusive breastfeeding for 4 months appears to be protective. [ABSTRACT FROM AUTHOR]

Objectives To compare the tolerability and effectiveness of two different classes of biological DMARDs [IL-17 and IL-23(p19) inhibitors, IL-17i and IL-23(p19)i] relative to TNF inhibitors (TNFi) regarding the drug survival rates and treatment outcomes in patients with PsA. Methods We emulated a target trial on comparative effectiveness using observational data from a prospective cohort study based on the Parker Institute's PsA cohort (the PIPA cohort). All patients underwent interview and a clinical examination programme at baseline and at follow-up visits at 4 and 12 months. The primary endpoint, drug survival, was assessed up to 12 months from baseline. We estimated hazard ratios from proportional hazards model and used propensity score adjustment in an attempt to deconfound and emulate a random treatment assignment. Results We included a total of 109 patients in the intention-to-monitor population at baseline initiating either TNFi (75 patients), IL-17i (26 patients) or IL-23(19)i (8 patients). Hazard ratios in the propensity adjusted model comparing IL-17i and IL-23(p19)i with TNFi were 1.36 (95% CI 0.59–3.14) and 0.56 (95% CI 0.10–3.24), respectively. TNFi and IL-17i had comparable effects regarding response rates and changes in clinical outcomes after 12 months, whereas IL-23(p19)i tended to perform better overall. Conclusion No decisive differences between drugs were observed at group level regarding drug survival and clinical outcomes after 12 months. TNFi, IL-17i and IL-23(p19)i may all be considered equally effective in the treatment of patients with PsA, advocating for investigating more in personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Objectives Despite little evidence that analgesics are effective in inflammatory arthritis (IA), studies report substantial opioid prescribing. The extent this applies to other analgesics is uncertain. We undertook a comprehensive evaluation of analgesic prescribing in patients with IA in the Clinical Practice Research Datalink Aurum to evaluate this. Methods From 2004 to 2020, cross-sectional analyses evaluated analgesic prescription annual prevalence in RA, PsA and axial spondyloarthritis (axSpA), stratified by age, sex, ethnicity, deprivation and geography. Joinpoint regression evaluated temporal prescribing trends. Cohort studies determined prognostic factors at diagnosis for chronic analgesic prescriptions using Cox proportional hazards models. Results Analgesic prescribing declined over time but remained common: 2004 and 2020 IA prescription prevalence was 84.2/100 person-years (PY) (95% CI 83.9, 84.5) and 64.5/100 PY (64.2, 64.8), respectively. In 2004, NSAIDs were most prescribed (56.1/100 PY; 55.8, 56.5), falling over time. Opioids were most prescribed in 2020 (39.0/100 PY; 38.7, 39.2). Gabapentinoid prescribing increased: 2004 prevalence 1.1/100 PY (1.0, 1.2); 2020 prevalence 9.9/100 PY (9.7, 10.0). Most opioid prescriptions were chronic (2020 prevalence 23.4/100 PY [23.2, 23.6]). Non-NSAID analgesic prescribing was commoner in RA, older people, females and deprived areas/northern England. Conversely, NSAID prescribing was commoner in axSpA/males, varying little by deprivation/geography. Peri-diagnosis was high-risk for starting chronic opioid/NSAID prescriptions. Prognostic factors for chronic opioid/gabapentinoid and NSAID prescriptions differed, with NSAIDs having no consistently significant association with deprivation (unlike opioids/gabapentinoids). Conclusion IA analgesic prescribing of all classes is widespread. This is neither evidence-based nor in line with guidelines. Peri-diagnosis is an opportune moment to reduce chronic analgesic prescribing. [ABSTRACT FROM AUTHOR]

Objective A lack of representation in pivotal trials currently limits guidance for the use of biologic DMARDs (bDMARDs) in PsA patients with a low number of actively inflamed joints. The aim of this study was to compare the effectiveness of a first bDMARD in PsA patients with a low vs high number of affected joints. Methods PsA patients with available 66/68 joint count assessments were divided into low joint count (LJC) patients when presenting with <3 tender or <3 swollen joints or high joint count (HJC) patients with ≥3 joints in both categories. We studied drug retention as a joint count independent effectiveness variable in LJC and HJC patients in univariate and multivariable adjusted Cox regression models. Results A total of 197 LJC patients differed not only in joint counts, but also had lower enthesitis scores, less often dactylitis, less disability and a better health-related quality of life at first bDMARD initiation than 190 HJC patients. However, LJC patients were less often on conventional synthetic DMARDs (csDMARDs). Despite these differences at baseline, bDMARD retention was not significantly different between LJC and HJC patients in both crude and adjusted analyses [hazard ratio (HR) 1.09 (95% CI 0.76, 1.58), P  = 0.52]. Furthermore, bDMARD retention was significantly better [HR 0.63 (95% CI 0.47, 0.85), P  < 0.002] when administered with csDMARD co-therapy. Conclusions bDMARDs were similarly effective in terms of drug retention in patients with low and high joint counts. In the setting of absent remission and a significant disease burden, bDMARDs should not be withheld from patients because they exhibit only a low joint count. [ABSTRACT FROM AUTHOR]

Objectives To compare the risk of PsA in psoriasis (PsO) patients treated with acitretin vs DMARDs. Methods This retrospective study used Taiwan's National Health Insurance Research Database from 1997 to 2013. Adult PsO patients without PsA prescribed acitretin or DMARDs for ≥30 days within a year were assigned to the acitretin cohort or DMARDs cohort, respectively. Patients in the acitretin cohort prescribed DMARDs for >7 days, or in the DMARDs cohort prescribed acitretin for >7 days, were excluded. Cumulative incidence of PsA were determined within both cohorts using the Kaplan–Meier method. The hazard ratio (HR) comparing acitretin to DMARDs was calculated with Cox regression models, adjusting for demographic and clinical covariates including the use of NSAIDs and comorbidities. Results The study included 1948 patients in each cohort. The 5-year cumulative incidence of PsA in the acitretin cohort was lower than that in the reference cohort (7.52% vs 9.93%; P  = 0.005), with a more pronounced difference in the subpopulation receiving NSAIDs treatment. However, in subpopulations without NSAIDs treatment, the 5-year cumulative incidence of PsA in the acitretin cohort was comparable to the DMARDs cohort (5.26% vs 6.98%; P  = 0.106). Acitretin was not associated with PsA development in PsO (HR 0.83, 95% confidence interval 0.65–1.05). This risk remained consistent regardless of adjustments for NSAID treatment and comorbidities. Other independent risk factors for PsA included female and NSAIDs treatment. Conclusion Compared with DMARDs, acitretin was not associated with increased PsA risk in PsO patients. [ABSTRACT FROM AUTHOR]

Objectives To assess the effectiveness and tolerability of first- and second-line interleukin (IL)-17A inhibitor treatment in PsA patients from 2014 to 2021 using data from the Danish Rheumatology Registry (DANBIO) by investigating adherence to therapy. Method PsA patients recorded in the DANBIO who received a first- or second-line IL-17A inhibitor treatment were included in this study. All patients included had previously received one or more TNF inhibitor treatment. Baseline characteristics were analysed in subgroups as first-line IL-17A inhibitor treatment and second-line IL-17A inhibitor treatment. Adherence to therapy of first- or second-line IL-17A inhibitor treatments was reported as Kaplan–Meier plots. Results A total of 534 patients were included in the study, with 534 first-line switchers (secukinumab: 510, ixekizumab: 24) and 102 second-line switchers (secukinumab: 35, ixekizumab: 67). Baseline characteristics showed a similar HAQ and visual analogue scale (VAS) for pain. VAS global, 28-joint DAS with CRP and the previous number of biologic DMARD treatments were similar, with a greater value for second-line switchers. First-line ixekizumab-treated patients present a younger age, greater percentage of females, a lower disease duration and a lower CRP value. Concomitant MTX use was greater for the first-line secukinumab-treated patients. First- and second-line switchers had a similar adherence to therapy. Second-line secukinumab and second-line ixekizumab switchers showed a similar adherence to treatment. Conclusion PsA patients receiving first- or second-line IL-17A inhibitors showed homogeneous baseline characteristics and similar adherence to therapy. Treatment failure of the first IL-17A inhibitor treatment should not preclude a second-line IL-17A inhibitor treatment. [ABSTRACT FROM AUTHOR]

The authors discuss research published within the issue which investigated the use of ultrasound for early and accurate diagnosis of psoriatic arthritis (PsA), conducted by Y. Wang and colleagues. Topics explored include the necessity of early PsA diagnosis to prevent the development of chronic arthritis, the concerns raised regarding the diagnostic use of musculoskeletal ultrasound (MSUS), and the identification of lesions that would distinguish PsA from other rheumatic ailments.

Objectives Autoantibody-negative RA differs from autoantibody-positive RA in several clinical aspects, possibly underpinned by pathogenetic differences. At present, the role of adaptive immune responses in autoantibody-negative RA remains unclear. Here, we investigated the synovial and serum immunophenotype indicative of B lymphocyte involvement across the spectrum of autoantibody-positive and -negative chronic arthritides. Methods Ultrasound-guided synovial biopsies were retrieved from 131 patients: 43 autoantibody-positive RA, 35 autoantibody-negative RA, 25 polyarticular PsA and 28 oligoarticular PsA. Samples were analysed for the degree of histological inflammation, B lymphocyte infiltration and the distribution of different pathotypes (lympho-myeloid, myeloid, pauci-immune). Serum levels of the B cell chemoattractant CXCL13 were compared among groups. Results Synovitis scores and CD68+ sublining macrophage infiltration were comparable irrespective of clinical diagnosis and disease subtype. In contrast, the degree of B lymphocyte infiltration and the frequency of lympho-myeloid synovitis in autoantibody-negative RA were lower than those of autoantibody-positive RA (mean [ s. d.] 1.8 [1] vs 2.4 [0.6], P  = 0.03, and 38.2% vs 62.9%, P  = 0.07, respectively), and similar to polyarticular PsA. Oligoarticular PsA had the lowest B cell scores. Serum CXCL13 was associated with lympho-myeloid synovitis and followed a similar gradient, with the highest levels in autoantibody-positive RA, intermediate and comparable levels in autoantibody-negative RA and polyarticular PsA, and low levels in oligoarticular PsA. Conclusions The synovial and serum immunophenotype indicative of B lymphocyte involvement in autoantibody-negative RA differs from that of autoantibody-positive RA and more closely resembles that observed in polyarticular PsA. The pathobiological stratification of chronic inflammatory arthritides beyond clinical diagnosis may fuel personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Objectives Juvenile PsA (JPsA) has varied clinical features that are distinctive from other JIA categories. This study investigates whether such features impact patient-reported and clinical outcomes. Methods Children and young people (CYP) were selected if recruited to the Childhood Arthritis Prospective Study, a UK multicentre JIA inception cohort, between January 2001 and March 2018. At diagnosis, patient/parent-reported outcomes (as age-appropriate) included the parental global assessment (10 cm visual analogue scale), functional ability (Childhood Health Assessment Questionnaire (CHAQ)), pain (10 cm visual analogue scale), health-related quality of life (Child Health Questionnaire PF50 psychosocial score), mood/depressive symptoms (Moods and Feelings Questionnaire) and parent psychosocial health (General Health Questionnaire 30). Three-year outcome trajectories have previously been defined using active joint counts, physician and parent global assessments (PGA and PaGA, respectively). Patient-reported outcomes and outcome trajectories were compared in (i) CYP with JPsA vs other JIA categories and (ii) CYP within JPsA, with and without psoriasis via multivariable linear regression. Results There were no significant differences in patient-reported outcomes at diagnosis between CYP with JPsA and non-JPsA. Within JPsA, those with psoriasis had more depressive symptoms (coefficient = 9.8; 95% CI: 0.5, 19.0) than those without psoriasis at diagnosis. CYP with JPsA had 2.3 times the odds of persistent high PaGA than other ILAR categories, despite improving joint counts and PGA (95% CI: 1.2, 4.6). Conclusion CYP with psoriasis at JPsA diagnosis report worse mood, supporting a greater disease impact in those with both skin and joint involvement. Multidisciplinary care with added focus to support wellbeing in children with JPsA plus psoriasis may help improve these outcomes. [ABSTRACT FROM AUTHOR]

Objective In the absence of axial psoriatic arthritis (axPsA)-specific tools, the BASDAI and Ankylosing Spondylitis Disease Activity Score (ASDAS) are used to assess axial symptoms in patients with PsA. Here, we assessed the performance of BASDAI and ASDAS in patients with PsA. Methods Patients with active PsA in DISCOVER-1 and DISCOVER-2 (ClinicalTrials.gov: NCT03162796 and NCT03158285, respectively) with or without axPsA but with available baseline BASDAI information were analysed; those with investigator-identified axial symptoms and imaging-confirmed sacroiliitis comprised the axPsA cohort. Correlations between BASDAI/ASDAS and clinical variables were assessed with Pearson's coefficient (r). Longitudinal effects of enthesitis (Leeds Enthesitis Index [LEI]), swollen joint count and presence versus absence of axPsA on BASDAI/ASDAS (normalized 0–10 scale) were analysed with mixed models for repeated measures. Results At baseline in the axPsA (n  = 312) and non-axPsA (n  = 124) cohorts, BASDAI scores showed no or weak correlation with swollen joint count (0.18–0.20), tender joint count (0.12–0.29), LEI (–0.04 to 0.24) and physician global assessment (0.35–0.43); moderate correlation with fatigue (both −0.56); and strong correlation with patient global assessment of disease activity (0.62–0.69) and patient-reported pain (0.66–0.70). Similar correlations were observed for ASDAS. Axial involvement versus non-involvement was associated with higher BASDAI scores and ASDAS (all β ≥ 0.5), without differences between instruments; longitudinal associations between swollen joint count (β ≤ 0.06)/LEI (β ≤ 0.19) and BASDAI/ASDAS were clinically unimportant. Conclusion BASDAI and ASDAS performed similarly in patients with active PsA and axial involvement, independent of peripheral disease involvement, supporting their performance in assessing axial disease activity. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov , NCT03162796 and NCT03158285. [ABSTRACT FROM AUTHOR]

Objectives The objective of this study was to compare the performance of three PsA screening questionnaires in a primary care psoriasis surveillance study. Methods Participants with psoriasis, and not known to have PsA, were identified from general practice databases and invited to attend a secondary care centre for a clinical assessment. The three patient-completed screening questionnaires (PEST, CONTEST and CONTESTjt) were administered, along with other patient-reported measures, and a clinical examination of skin and joints was performed. Participants who demonstrated signs of inflammatory arthritis suggestive of PsA were referred, via their GP, for a further assessment in a secondary care rheumatology clinic. Results A total of 791 participants attended the screening visit, and 165 participants were judged to have signs and symptoms of inflammatory arthritis, of which 150 were referred for assessment. Of these, 126 were seen and 48 were diagnosed with PsA. The results for each questionnaire were as follows: PEST: sensitivity 0.625 (95% CI 0.482, 0.749), specificity 0.757 (0.724, 0.787); CONTEST: sensitivity 0.604 (0.461, 0.731), specificity 0.768 (0.736, 0.798); and CONTESTjt: sensitivity 0.542 (0.401, 0.676), specificity 0.834 (0.805, 0.859). CONTESTjt demonstrated marginally superior specificity to PEST, though the area under the ROC curve was similar for all three instruments. Conclusion Minimal differences between the three screening questionnaires were found in this study, and no preferred questionnaire is indicated by these results. The choice of which instrument to choose will depend on other factors, such as simplicity and low patient burden. [ABSTRACT FROM AUTHOR]

Objectives In bio-naïve patients with PsA initiating a TNF inhibitor (TNFi), we aimed to identify baseline predictors of Disease Activity index for PsA in 28 joints (DAPSA28) remission (primary objective) and DAPSA28 moderate response at 6 months, as well as drug retention at 12 months across 13 European registries. Methods Baseline demographic and clinical characteristics were retrieved and the three outcomes investigated per registry and in pooled data, using logistic regression analyses on multiply imputed data. In the pooled cohort, selected predictors that were either consistently positive or negative across all three outcomes were defined as common predictors. Results In the pooled cohort (n  = 13 369), 6-month proportions of remission, moderate response and 12-month drug retention were 25%, 34% and 63% in patients with available data (n  = 6954, n  = 5275 and n  = 13 369, respectively). Five common baseline predictors of remission, moderate response and 12-month drug retention were identified across all three outcomes. The odds ratios (95% CIs) for DAPSA28 remission were: age, per year: 0.97 (0.96–0.98); disease duration, years (<2 years as reference): 2–3 years: 1.20 (0.89–1.60), 4–9 years: 1.42 (1.09–1.84), ≥10 years: 1.66 (1.26–2.20); men vs women: 1.85 (1.54–2.23); CRP of >10 vs ≤10 mg/l: 1.52 (1.22–1.89) and 1 mm increase in patient fatigue score: 0.99 (0.98–0.99). Conclusion Baseline predictors of remission, response and adherence to TNFi therapy were identified, of which five were common for all three outcomes, indicating that the predictors emerging from our pooled cohort may be considered generalizable from country level to disease level. [ABSTRACT FROM AUTHOR]

A study published in the Clinical & Experimental Dermatology journal examined the relationship between psoriasis and migraine disorders in a diverse population. The study used the All of Us database to identify 7,472 adult psoriasis cases and found that 21.2% of the psoriasis cohort had been diagnosed with migraines, compared to 12.2% of the control cohort. The study also found a higher prevalence of alcohol use disorder and hypertension in the psoriasis population. The analysis controlled for relevant factors and found that the risk of migraines was higher in non-White individuals with psoriasis. Further research is needed to understand the underlying causes of this relationship. [Extracted from the article]

The authors comment on the article "Evidence on treat to target strategies in polymyalgia rheumatica and giant cell arteritis: a systemic literature review" by Hysa and colleagues. Topics discussed include treat-to-target (T2T) for polymalgia rhuematica (PMR) and giant cell arteritis (GCA), important lessons for PMR and GCA, and work required to T2T to succeed in PMR and GCA.

The author reflects on his experiences during his tenure as the journal's editor-in-chief for five years. He discusses the challenges he faced at work during the COVID-19 pandemic, the developments within rheumatology during his tenure, and his wishes for the incoming editor-in-chief and professor Ernest Choy.

Objectives Clinical inertia, or therapeutic inertia (TI), is the medical behaviour of not initiating or intensifying treatment when recommended by clinical recommendations. To our knowledge, our survey is the first to assess TI around psoriatic arthritis (PsA). Methods Eight hundred and twenty-five French rheumatologists were contacted via email between January and March 2021 and invited to complete an online questionnaire consisting of seven clinical vignettes: five cases ('oligoarthritis', 'enthesitis', 'polyarthritis', 'neoplastic history', 'cardiovascular risk') requiring treatment OPTImization, and two 'control' cases (distal interphalangeal arthritis, atypical axial involvement) not requiring any change of treatment—according to the most recent PsA recommendations. Rheumatologists were also questioned about their routine practice, continuing medical education and perception of PsA. Results One hundred and one rheumatologists completed this OPTI'PsA survey. Almost half the respondents (47%) demonstrated TI on at least one of the five vignettes that warranted treatment optimization. The complex profiles inducing the most TI were 'oligoarthritis' and 'enthesitis' with 20% and 19% of respondents not modifying treatment, respectively. Conversely, clinical profiles for which there was the least uncertainty ('polyarthritis in relapse', 'neoplastic history' and 'cardiovascular risk') generated less TI with 11%, 8% and 6% of respondents, respectively, choosing not to change the current treatment. Conclusion The rate of TI we observed for PsA is similar to published data for other chronic diseases such as diabetes, hypertension, gout or multiple sclerosis. Our study is the first to show marked clinical inertia in PsA, and further research is warranted to ascertain the reasons behind this inertia. [ABSTRACT FROM AUTHOR]

Objectives To examine the prevalence of extra-musculoskeletal manifestations (EMM) and the association between diagnostic delay and their incidence in AS and PsA. Methods This was a retrospective, cohort study comprising two single centre cohorts in Europe and one multicentre cohort in Latin America (RESPONDIA). Crude prevalence of EMMs (uveitis, IBD and psoriasis) was calculated across geographic area and adjusted by direct standardization. Cox proportional hazard analysis was performed to assess the association between diagnostic delay and EMM incidence. Results Of 3553 patients, 2097 had AS and 1456 had PsA. The overall prevalence of uveitis was 22.9% (95% CI: 21.1, 24.8) in AS and 3.8% (95% CI: 2.9, 5.0) in PsA; 8.1% (95% CI: 7.0, 9.4) and 2.1% (1.3, 2.9), respectively, for IBD; and 11.0% (95% CI: 9.7, 12.4) and 94.6% (93.0, 95.9), respectively, for psoriasis. The EMM often presented before the arthritis (uveitis 45.1% and 33.3%, and IBD 37.4% and 70%, in AS and PsA, respectively). In the multivariable model, longer diagnostic delay (≥5 years) associated with more uveitis (hazard ratio [HR] 4.01; 95% CI: 3.23, 4.07) and IBD events (HR 1.85; 95% CI: 1.28, 2.67) in AS. Diagnostic delay was not significantly associated with uveitis (HR 1.57; 95% CI: 0.69, 3.59) or IBD events (HR 1.59; 95% CI: 0.39, 6.37) in PsA. Conclusion EMMs are more prevalent in AS than PsA and often present before the onset of the articular disease. A longer diagnostic delay is associated with the ' de novo ' appearance of uveitis and IBD in AS, highlighting the need to enhance diagnostic strategies to shorten the time from first symptom to diagnosis in SpA. [ABSTRACT FROM AUTHOR]

The emergence of biologics with different modes of action (MoAs) and therapeutic targets has changed treatment patterns in patients with inflammatory rheumatic diseases. While tumour necrosis factor inhibitors (TNFis) are often utilized as the first biologic disease-modifying antirheumatic drug, some patients may not respond adequately (primary failure), fail to sustain response over time (secondary failure), or experience intolerable adverse events. Whether these patients would benefit more from cycling to a different TNFi or switching to a biologic with a different MoA is still unclear. We discuss here treatment outcomes of TNFi cycling versus MoA switching after treatment failure with a first TNFi in patients with inflammatory rheumatic diseases, focusing specifically on rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and juvenile idiopathic arthritis. Treatment guidelines for these patients are ambiguous and, at times, contradictory in their recommendations. However, this is due to a lack of high-quality head-to-head data to definitively support cycling between TNFis after failure to a first-line TNFi over switching to a different MoA. [ABSTRACT FROM AUTHOR]

Objectives To examine the association between sonographic enthesitis with sonographic synovitis and tenosynovitis in PsA patients, and the association between sonographic enthesitis and clinical characteristics. Methods Consecutive PsA patients that fulfilled the ClASsification criteria for Psoriatic ARthritis (CASPAR) were prospectively recruited. Each patient was evaluated by comprehensive clinical and sonographic assessment (greyscale and Doppler), the latter including 52 joints, 40 tendons and 14 entheses [according to MAdrid Sonography Enthesitis Index (MASEI) plus lateral epicondyles] performed by an experienced sonographer blinded to the clinical data. The US enthesitis score was further categorized to inflammatory (hypoechogenicity, thickening, bursitis and Doppler) and structural (enthesophytes/calcifications and erosions) subcategories. Multivariate linear regression models assessed the association between enthesitis and the selected variables. Results A total of 158 PsA patients [mean (s. d.) age 52.3 (13) years, 88 (55.7%) females] were analysed. Multivariate linear regression analyses showed a significant association between sonographic enthesitis and sonographic synovitis (β = 0.18, P  = 0.008) and between sonographic enthesitis and sonographic tenosynovitis (β = 0.06, P  = 0.02). These associations were derived from the enthesitis inflammatory subcategory of the MASEI (P   <  0.05). Associations between enthesitis and synovitis were also demonstrated on the level of the elbow, knee and ankle joints (P   <  0.05). In addition, sonographic enthesitis was significantly associated with older age, male sex, swollen joint count, CRP level and physical occupation. Conclusions Sonographic enthesitis is associated with sonographic synovitis and tenosynovitis. The severity of sonographic enthesitis may represent a marker for inflammatory activity in other musculoskeletal domains. [ABSTRACT FROM AUTHOR]

Objectives Approximately 20% of people with psoriasis develop PsA. Although genetic, clinical and environmental risk factors have been identified, it is not known why some people with psoriasis develop PsA. The skin disease is traditionally considered the same in both. This study compares transcriptional changes in psoriasis and PsA skin for the first time. Methods Skin biopsies were collected from healthy controls (HC), and uninvolved and lesional skin from patients with PsA. Bulk tissue sequencing was performed and analysed using the pipeline Searchlight 2.0. Transcriptional changes in PsA skin were compared with existing sequencing data from participants with psoriasis without PsA (GSE121212). Psoriasis and PsA datasets could not be directly compared as different analysis methods were used. Data from participants with PsA in the GSE121212 dataset were used for validation. Results Skin samples from 9 participants with PsA and 9 HC were sequenced, analysed and compared with available transcriptomic data for 16 participants with psoriasis compared with 16 HC. Uninvolved skin in psoriasis shared transcriptional changes with lesional skin in psoriasis, but uninvolved skin in PsA did not. Most transcriptional changes in psoriasis and PsA lesional skin were shared, but immunoglobulin genes were upregulated in PsA lesional skin specifically. The transcription factor POU2F1, which regulates immunoglobulin gene expression, was enriched in PsA lesional skin. This was confirmed in the validation cohort. Conclusions Immunoglobulin genes are upregulated in PsA but not in psoriasis skin lesions. This may have implications for the spread from the cutaneous compartment to other tissues. [ABSTRACT FROM AUTHOR]

Objectives To evaluate enthesitis treatment response, including time to resolution and data from multiple enthesitis instruments, in patients with PsA treated with secukinumab or adalimumab for 52 weeks. Methods In this post hoc analysis of the EXCEED study, patients receiving secukinumab 300 mg or adalimumab 40 mg per the label were grouped by presence or absence of baseline enthesitis based on the Leeds Enthesitis Index (LEI) and the Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC). Efficacy was assessed according to several enthesitis-related instruments using non-responder imputation for the achievement of enthesitis resolution (LEI/SPARCC = 0), Kaplan–Meier analysis for time to resolution, and as-observed data for other outcomes. Results Enthesitis was present at baseline in 498 of 851 patients (58.5%) as assessed by LEI and in 632 of 853 patients (74.1%) as assessed by SPARCC. Patients with baseline enthesitis generally presented with greater disease activity. Similar proportions of patients receiving secukinumab or adalimumab achieved resolution of LEI and SPARCC at weeks 24 (secukinumab: LEI/SPARCC, 49.6%/45.8%; adalimumab: LEI/SPARCC, 43.6%/43.5%) and 52 (secukinumab: LEI/SPARCC, 60.7%/53.2%; adalimumab: LEI/SPARCC, 55.3%/51.4%), with comparable mean time to enthesitis resolution. Improvements were similar for both drugs at individual enthesitis sites. Resolution of enthesitis with secukinumab or adalimumab was associated with improvements in quality of life at week 52. Conclusion Secukinumab and adalimumab showed similar efficacy, including time to resolution, with respect to resolution of enthesitis. Inhibition of IL-17 with secukinumab reduced clinical enthesitis similarly to TNF-α inhibition. Trial registration ClinicalTrials.gov , NCT02745080 [ABSTRACT FROM AUTHOR]

Objective The current analysis of the MAXIMISE trial was conducted to investigate the presence of post-inflammatory and degenerative spinal changes and inflammatory changes in spinal processes identified in baseline MRIs and their potential for predicting differential treatment effects in a cohort of PsA patients with axial manifestations. Methods Baseline spinal MRIs from the MAXIMISE trial were re-read to identify additional inflammatory (spinal process), post-inflammatory, and degenerative changes, and investigate the differential treatment effect of these imaging features using logistic regression modelling. Results In addition to bone marrow oedema assessed at primary analysis, spinal process inflammation and post-inflammatory changes evaluated by FAt Spondyloarthritis Spine Score were documented in 11.1% and 20.2% patients, respectively. At least one type of degenerative change was noted in 64% patients, with Pfirrmann grade ≥3 (51.1%) being the most common. Combining primary and re-read MRI findings, 67.1% of patients presented with inflammatory or post-inflammatory changes while 21.2% had degenerative changes alone. Although not statistically significant, post-inflammatory changes were associated with a trend for better efficacy outcomes in terms of ASAS20, ASAS40 and BASDAI50 responses; a trend for worse outcomes was observed in the presence of degenerative changes. Conclusion The current analysis revealed the occurrence of additional inflammatory and post-inflammatory changes suggestive of axial PsA (axPsA) and a trend for better clinical outcomes for patients treated with secukinumab. These results elucidate the imaging characteristics and improve our current understanding of axPsA thereby supporting the interpretation of future trials. Trial registration ClinicalTrials.gov, NCT02721966. [ABSTRACT FROM AUTHOR]

Objective The aim was to assess the use and drug survival of IL-17Ai in a real-world cohort of axial SpA (axSpA) and PsA patients. Methods Patients ever commenced on an IL-17Ai (secukinumab or ixekizumab) for axSpA or PsA at the Leeds Specialist Spondyloarthritis Service were identified. Demographics, IL-17Ai treatment length and reason for cessation were collected. Drug survival data were plotted as a Kaplan–Meier curve, with log rank test of median survival compared between axSpA and PsA. Cox regression analysis was performed to investigate the relationship between diagnosis and length of drug survival. Results In total, 228 patients (91 axSpA and 137 PsA) were exposed to IL-17Ai. Drug survival for all patients at 12 months was 69% (95% Confidence Interval (CI) 63, 75%) and at 24 months 60% (95% CI 54, 67%). In axSpA and PsA, drug survival at 12 months was 63% (CI 54, 74%) and 73% (CI 66, 81%), respectively, and at 24 months it was 53% (CI 44, 65%) and 65% (CI 57, 75%), respectively. Median survival did not differ significantly between both diseases (log rank test 0.65). There was no association between diagnosis and survival (hazard ratio 0.92, 95% CI 0.63, 1.33), including when adjusting for age, previous biologic DMARD usage and sex (hazard ratio 0.89, 95% CI 0.61, 1.13). Conclusion This is the first study, to our knowledge, to analyse and compare real-world IL-17Ai drug survival in patients with axSpA and PsA from a single centre. We demonstrate that there is no difference in IL-17Ai survival rates and no relationship between diagnosis and drug survival. These results contribute to the body of real-world evidence confirming the role of IL-17Ai in the management of axSpA and PsA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective We investigated the impact of concomitant MTX on ustekinumab (UST) levels and antidrug antibody (ADA) formation in PsA and evaluated consequences in pharmacodynamics and pharmacokinetics. Methods We conducted a post-hoc analysis on 112 PsA serum samples of subjects treated with open-label UST and either concomitant MTX (UST/MTX, n  = 58) or placebo (UST/pbo, n  = 54) obtained in a randomized (1:1), double-blind, multicentre trial. A validated antibody-binding-based multitiered testing was used to detect ADA and ADA with neutralizing capacity (nADA). The impact of MTX on UST immunogenicity was analysed by comparison of UST/pbo with UST/MTX cohorts at different time points. Patient- and disease-related predispositions for ADA formation were investigated with multiple linear regression analysis. Immunogenicity impact on pharmacokinetics, safety and efficacy was determined by cohort comparison between patients with and without ADA formation. Results Over 52 weeks, 11 UST/pbo- and 19 UST/MTX-treated patients developed ADA (P  > 0.05). In the UST/pbo cohort, the visit-dependent UST levels were in the range of 0.047 (0.05) –0.110 (0.07) µg/ml overall, and 0.037 (0.04)–0.091 (0.08) µg/ml in ADA-confirmed subjects. In UST/MTX-treated patients, the UST levels exhibited an intervisit variation in the range of 0.0502 (0.04)–0.106 (0.07) µg/ml overall and 0.029 (0.03)–0.097 (0.07) µg/ml in ADA positive subjects (P  > 0.05). At week 52, ADA-confirmed patients did not differ significantly (P  > 0.05) in safety or clinical outcomes from ADA-negative patients. Conclusion Concomitant MTX had no significant impact on UST immunogenicity. Furthermore, ADA formation was not associated with impairments in UST safety, efficacy or trough levels. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov , NCT03148860. [ABSTRACT FROM AUTHOR]

A study published in the British Journal of Dermatology examined the use of deucravacitinib as an additional therapy for patients with psoriasis and psoriatic arthritis (PsA) who did not respond well to monotherapy. The study included 20 patients who were already on biologic therapy for more than 6 months. The results showed that combining deucravacitinib with biologic therapy had an additive effect in reducing symptoms of refractory psoriasis. However, the results for PsA were mixed, with some patients experiencing improvement and others seeing little change. The study suggests that dual therapy may be a potential treatment option, but acknowledges the need for further research with larger cohorts and longer follow-up periods. [Extracted from the article]

Advances in single-cell sequencing and data analysis have made it possible to infer biological trajectories spanning heterogeneous cell populations based on transcriptome variation. These trajectories yield a wealth of novel insights into dynamic processes such as development and differentiation. However, trajectory analysis relies on an assumption of trajectory continuity, and experimental limitations preclude some real-world scenarios from meeting this condition. The current lack of assessment metrics makes it difficult to ascertain if/when a given trajectory deviates from continuity, and what impact such a divergence would have on inference accuracy is unclear. By analyzing simulated breaks introduced into in silico and real single-cell data, we found that discontinuity caused precipitous drops in the accuracy of trajectory inference. We then generate a simple scoring algorithm for assessing trajectory continuity, and found that continuity assessments in real-world cases of intestinal stem cell development and CD8 + T cells differentiation efficiently identifies trajectories consistent with empirical knowledge. This assessment approach can also be used in cases where a priori knowledge is lacking to screen a pool of inferred lineages for their adherence to presumed continuity, and serve as a means for weighing higher likelihood trajectories for validation via empirical studies, as exemplified by our case studies in psoriatic arthritis and acute kidney injury. This tool is freely available through github at qingshanni/scEGRET. [ABSTRACT FROM AUTHOR]

Objective To investigate the association of the triglyceride-glucose (TyG) index with atherosclerotic risk among patients with PsA. Methods This cross-sectional study included 165 consecutive PsA patients receiving carotid ultrasonography with integrated TyG index, calculated as ln [fasting triglycerides (mg/dl)  × fasting glucose (mg/dl)/2]. Logistic regression models were applied to analyse the association of TyG index as continuous variables and tertiles with carotid atherosclerosis and carotid artery plaque. Fully adjusted model included sex, age, smoking, BMI, comorbidities and psoriatic-related variables. Results Overall, PsA patients with carotid atherosclerosis had substantially higher TyG index than those without [8.82 (0.50) vs 8.54 (0.55), P  = 0.002]. The frequency of carotid atherosclerosis was increased with increases in TyG index tertiles, showing 14.8%, 34.5%, 44.6% for tertile 1, 2 and 3, respectively (P  = 0.003). Multivariate logistic analyses showed that each 1-unit increase in TyG index was significantly associated with prevalent carotid atherosclerosis [unadjusted odds ratio (OR) 2.65 (1.39–5.05); fully adjusted OR 2.69 (1.02–7.11)]. Compared with patients in tertile 1 of TyG index, the unadjusted and fully adjusted OR for occurrence of carotid atherosclerosis were 4.64 (1.85–11.60) and 5.10 (1.54–16.93) in patients in tertile 3. Similarly, higher prevalent carotid artery plaque was observed with increasing TyG index [unadjusted OR 3.11 (1.54–6.26); fully adjusted OR 3.61 (1.15–11.38)] or in tertile 3 vs tertile 1 [unadjusted OR 10.20 (2.83–36.82); fully adjusted OR 17.89 (2.88–111.11)]. Additionally, TyG index provided incremental predictive capacity beyond established risk factors, shown by an increase in discrimination ability (all P  < 0.001). Conclusions TyG index was positively correlated with the burden of atherosclerosis in PsA patients, independent of traditional cardiovascular risk factors and psoriatic-related factors. These findings suggest that TyG index may be a promising atherosclerotic marker for the PsA population. [ABSTRACT FROM AUTHOR]

IL-17A+ CD8+ T-cells, termed Tc17 cells, have been identified at sites of inflammation in several immune-mediated inflammatory diseases. However, the biological function of human IL-17A+ CD8+ T-cells is not well characterized, likely due in part to the relative scarcity of these cells. Here, we expanded IL-17A+ CD8+ T-cells from healthy donor PBMC or bulk CD8+ T-cell populations using an in vitro polarization protocol. We show that T-cell activation in the presence of IL-1β and IL-23 significantly increased the frequencies of IL-17A+ CD8+ T-cells, which was not further enhanced by IL-6, IL-2, or anti-IFNγ mAb addition. In vitro-generated IL-17A+ CD8+ T-cells displayed a distinct type-17 profile compared with IL-17A− CD8+ T-cells, as defined by transcriptional signature (IL17A, IL17F, RORC, RORA, MAF, IL23R, CCR6), high surface expression of CCR6 and CD161, and polyfunctional production of IL-17A, IL-17F, IL-22, IFNγ, TNFα, and GM-CSF. A significant proportion of in vitro-induced IL-17A+ CD8+ T-cells expressed TCRVα7.2 and bound MR1 tetramers indicative of MAIT cells, indicating that our protocol expanded both conventional and unconventional IL-17A+ CD8+ T-cells. Using an IL-17A secretion assay, we sorted the in vitro-generated IL-17A+ CD8+ T-cells for functional analysis. Both conventional and unconventional IL-17A+ CD8+ T-cells were able to induce pro-inflammatory IL-6 and IL-8 production by synovial fibroblasts from patients with psoriatic arthritis, which was reduced upon addition of anti-TNFα and anti-IL-17A neutralizing antibodies. Collectively, these data demonstrate that human in vitro-generated IL-17A+ CD8+ T-cells are biologically functional and that their pro-inflammatory function can be targeted, at least in vitro, using existing immunotherapy. Here, we describe a protocol for the in vitro induction of IL-17A+ and IL-17F+ CD8+ T-cells from human PBMC or CD8+ T-cell cultures. In vitro -induced IL-17A+ CD8+ T-cells display a type-17 transcriptional and phenotypic signature and comprise both MAIT and conventional T-cell subsets. In vitro -induced IL-17A+ CD8+ T-cells increase the production of proinflammatory cytokines from psoriatic arthritis synovial fibroblasts; this was reduced by IL-17A and TNFα blockade. [ABSTRACT FROM AUTHOR]

Objective Investigate effects of gender on disease characteristics and treatment impact in patients with PsA. Methods PsABio is a non-interventional European study in patients with PsA starting a biological DMARD [bDMARD; ustekinumab or TNF inhibitor (TNFi)]. This post-hoc analysis compared persistence, disease activity, patient-reported outcomes and safety between male and female patients at baseline and 6 and 12 months of treatment. Results At baseline, disease duration was 6.7 and 6.9 years for 512 females and 417 males respectively. Mean (95% CI) scores for females vs males were: clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA), 32.3 (30.3, 34.2) vs 26.8 (24.8, 28.9); HAQ-Disability Index (HAQ-DI), 1.3 (1.2, 1.4) vs 0.93 (0.86, 0.99); total PsA Impact of Disease-12 (PsAID-12) score, 6.0 (5.8, 6.2) vs 5.1 (4.9, 5.3), respectively. Improvements in scores were smaller in female than male patients. At 12 months, 175/303 (57.8%) female and 212/264 (80.3%) male patients achieved cDAPSA low disease activity, 96/285 (33.7%) and 137/247 (55.5%), achieved minimal disease activity (MDA), respectively. HAQ-DI scores were 0.85 (0.77, 0.92) vs 0.50 (0.43, 0.56), PsAID-12 scores 3.5 (3.3, 3.8) vs 2.4 (2.2, 2.6), respectively. Treatment persistence was lower in females than males (P   ≤  0.001). Lack of effectiveness was the predominant reason to stop, irrespective of gender and bDMARD. Conclusions Before starting bDMARDs, females had more severe disease than males and a lower percentage reached favourable disease states, with lower persistence of treatment after 12 months. A better understanding of the mechanisms underlying these differences may improve therapeutic management in females with PsA. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov , NCT02627768 [ABSTRACT FROM AUTHOR]