Active PsA Research Articles

P101 Investigating the association between clinical enthesitis and central sensitisation in psoriatic arthritis

Abstract Background/Aims Psoriatic Arthritis (PsA) is an inflammatory arthritis with enthesitis as its characteristic clinical feature. Enthesitis can be clinically challenging to differentiate from the widespread pain associated with Fibromyalgia (FM), the prototype of central sensitisation (CS) present in up to 30% of PsA patients. Algometry is used in CS research to quantify pressure pain threshold (PPT), reflecting increased pain sensitivity when reduced. Ultrasound is a valuable tool to evidence entheseal inflammatory changes in PsA. This study investigates associations between CS, i.e., FM, and entheseal ultrasound outcomes to better characterise pain mechanisms in PsA enthesitis. Methods A total of 20 patients with active PsA about to start a new immunosuppressant were recruited. Ultrasound evaluation of non-dominant knee (left for all patients) using dynamic B-mode and power Doppler was performed alongside the Leeds Enthesitis Index (LEI) collection to assess enthesitis. PPT was measured with algometry at the non-dominant knee (enthesitis), trapezius and calf muscle (CS areas), and collection of the ACR 2011 FM criteria was used to determine the presence of CS. Non-dominant areas were selected because they are less likely to exhibit biomechanical ultrasound alterations; moreover, the non-dominant side is generally more sensitive than the dominant side, thus enabling more precise PPT measurements. Correlations and t-tests were used to test associations between variables collected. SPSS was used to analyse the data. Results The 30% of patients met the FM criteria and presented higher LEI scores and lower PPT evoked threshold than FM-negative patients. Total FM scores significantly correlated with LEI scores (r = 0.69, p < 0.001) and calf PPTs (r=-0.53, p=-0.014), but not with knee and trapezius PPTs (r=-0.49, p = 0.09; r=-0.30, p = 0.19), or US enthesitis (r=-0.04, p = 0.86). PPTs in the areas investigated did not show significant correlations with US enthesitis, while an indirect association was observed between LEI with calf PPT (r=-0.51, p = 0.02) and trapezius PPT (r=-0.41, p = 0.06). No significant correlation was demonstrated between LEI and left knee enthesitis (r=-0.32, p = 0.17). Conclusion FM is frequent in PsA and can mimic entheseal pain, as suggested by the strong correlation with the LEI scores. In our cohort, LEI scores did not efficiently capture inflammatory enthesitis, demonstrated by the lack of association with ultrasound data. Moreover, the association between objective measurement of CS, including calf and trapezius PPTs, supports that LEI score may primarily reflect the presence of central sensitisation rather than inflammation. Therefore, relying solely on clinical detection of enthesitis may result in inappropriate treatment escalation. Ultrasound, conversely, serves as a dependable tool for confirming enthesitis and providing valuable information for making informed treatment decisions. Disclosure N.M. Aldehmi: None. N. Basu: None. J. Dale: None. A. Najm: None. F. Sunzini: None.

E069 Bimekizumab maintained efficacy responses through 52 weeks in patients with psoriatic arthritis and inadequate response or intolerance to tumour necrosis factor inhibitors who were responders at week 16: results from a phase 3, randomised study

E069 Bimekizumab maintained efficacy responses through 52 weeks in patients with psoriatic arthritis and inadequate response or intolerance to tumour necrosis factor inhibitors who were responders at week 16: results from a phase 3, randomised study

BASDAI versus ASDAS in evaluating axial involvement in patients with psoriatic arthritis: a pooled analysis of two phase 3 studies.

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. 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. 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. 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. ClinicalTrials.gov, http://clinicaltrials.gov, NCT03162796 and NCT03158285.

Association between enthesitis/dactylitis resolution and patient-reported outcomes in guselkumab-treated patients with psoriatic arthritis

ObjectivesTo evaluate the association between enthesitis resolution (ER) and dactylitis resolution (DR) and meaningful improvements in patient-reported outcomes (PROs) among biologic-naïve patients with PsA receiving guselkumab in the DISCOVER-2 study.MethodsEnthesitis and dactylitis, characteristic lesions of PsA, were evaluated by independent assessors using the Leeds Enthesitis Index (range, 0–6) and Dactylitis Severity Score (range, 0–60). Proportions of patients with ER or DR (score = 0) among those with score > 0 at baseline were determined at weeks 24, 52, and 100. PROs included: fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue]), pain (0–100 visual analog scale), physical function (Health Assessment Questionnaire-Disability Index [HAQ-DI]), and health-related quality of life (36-item Short-Form Health Survey physical/mental component summary [SF-36 PCS/MCS]). Meaningful responses were defined as: improvements of ≥ 4 for FACIT-Fatigue, ≥ 0.35 for HAQ-DI, and ≥ 5 for SF-36 PCS/MCS and absolute scores of ≤ 15 for minimal pain and ≤ 0.5 for normalized HAQ-DI. Associations between ER/DR status and PRO response status were tested using a Chi-square test.ResultsGuselkumab-treated patients with ER were more likely than those without ER to achieve minimal pain (p < 0.001), normalized HAQ-DI (p < 0.001), and PCS response (p < 0.05) at weeks 24, 52, and 100. Patients with DR were more likely than those without DR to achieve FACIT-Fatigue response at week 24 and week 52 (both p ≤ 0.01) and minimal pain at week 24 and normalized HAQ-DI at week 52 (both p ≤ 0.03).ConclusionIn biologic-naïve patients with active PsA treated with guselkumab, achieving ER or DR was associated with durable improvements in selected PROs, including those of high importance to patients.Trial registrationClinicalTrials.gov (https://clinicaltrials.gov) NCT03158285; Registered: May 16, 2017.Key Points• At week 100, 65% and 76% of guselkumab-treated patients achieved enthesitis and dactylitis resolution (ER/DR).• Achieving ER was associated with achieving DR and vice versa through the end of study.• Achieving ER or DR was associated with durable and meaningful improvements in selected patient-reported outcomes.

Real-world evidence for secukinumab in UK patients with psoriatic arthritis or radiographic axial spondyloarthritis: interim 2-year analysis from SERENA.

The aim was to evaluate retention rates for secukinumab in patients with active PsA or radiographic axial spondyloarthritis (r-axSpA) treated in routine UK clinical practice. SERENA (CAIN457A3403) is an ongoing, non-interventional, international study of patients with moderate-to-severe chronic plaque psoriasis, active PsA or active r-axSpA, who had received secukinumab for ≥16 weeks before enrolment. The primary objective of this interim analysis was to assess treatment retention rates in patients with PsA or r-axSpA who were enrolled and followed for ≥2 years at centres in the UK. The safety analysis set includes all patients who received at least one dose of secukinumab. The target population set includes all patients who fulfilled the patient selection criteria. The safety set comprised 189 patients (PsA, n = 81; r-axSpA, n = 108), and the target population set comprised 183 patients (PsA, n = 78; r-axSpA, n = 105). In the safety set, 107 patients (45 of 81 with PsA and 62 of 108 with r-axSpA) had previously received a biologic agent. Retention rates were similar between patients with PsA and r-axSpA after 1 year (PsA 91.0%, 95% CI: 84.0, 98.0; r-axSpA 89.2%, 95% CI: 82.7, 95.7) and 2 years (PsA 77.6%, 95% CI: 67.6, 87.7; r-axSpA 76.2%, 95% CI: 67.4, 85.0) of observation. Overall, 17.5% of patients (33 of 189) experienced at least one treatment-related adverse event, and 12.7% of patients (24 of 189) discontinued secukinumab because of adverse events. This analysis of real-world data from the UK demonstrates high retention rates for secukinumab over 2 years in patients with PsA or r-axSpA, with a favourable safety profile.

Is the C-reactive protein-to-albumin ratio the most remarkable simple inflammatory marker showing active disease in patients with axial spondyloarthritis, psoriatic arthritis, and rheumatoid arthritis?

To learn which of the simple inflammation markers obtained from routine laboratory tests showed active disease best. The study included 256 patients (102 patients with axial spondyloarthritis [axSpA], 54 with psoriatic arthritis [PsA], and 100 with rheumatoid arthritis [RA]). The results of the routine laboratory tests requested during the outpatient clinic visits of the patients were noted. Inflammation-related ratio/indices were then calculated from these laboratory tests. Active and inactive diseases were defined according to the disease activity scores for each disease. Logistic regression and receiver operating characteristic (ROC) analyses were performed to determine the best laboratory marker(s) showing active disease and its cutoff value for all three diseases. C-reactive protein to albumin ratio (CAR) was significantly higher in patients with active axSpA, PsA, and RA diseases than those with inactive diseases (p < 0.001, p = 0.006, and p < 0.001, respectively). In the logistic regression analysis, the CAR was the most important predictor of active disease in patients with axSpA, PsA, and RA. CAR had also showed the active disease at an acceptable level in axSpA and PsA and very well in RA. The cutoff values for active disease in axSpA, PsA, and RA were 0.75, 0.92, and 0.89, respectively. CAR may be a promising simple laboratory marker to distinguish active disease in patients with axSpA, PsA, and RA. Key Points • Acute phase reactants and circulating blood cells have become an important target because of the search for a disease activity marker that can be used cheaply and quickly in the daily outpatient routine. • One or more of these simple markers have been previously discussed in various studies with different hypotheses. • We aimed to determine which of the inflammation markers obtained from routine laboratory tests showed active disease and to determine a cutoff value for this/these marker(s). • CAR was the most important simple laboratory marker to distinguish active disease in patients with axSpA, PsA, and RA. In addition, CAR showed the active disease at an acceptable level in axSpA and PsA, and very well in RA.

Investigating the role of "Immature Myeloid Cells" as Drivers of Inflammation and Disease Persistence in Psoriatic Arthritis.

Despite the development of treatments targeting T cell co-stimulation and cytokines TNF, IL-12/23, and IL-17, less than half of patients within clinical trials achieve high levels of clinical response. This fact, as well as the absence of prognostic biomarkers represents major unmet clinical needs that necessitate further investigation of the disease pathophysiology. Myeloid cells are critical components of PsA inflammatory mechanisms, being a highly prevalent immune population in biopsies of PsA target tissues, such as the skin and the synovium. Through their antigen-presenting capacity and their pro-angiogenic and pro-inflammatory properties myeloid cells could contribute to persistent inflammation in PsA leading to treatment-resistant disease. To this end, we have recently shown the expansion of monocytes in the blood of PsA patients compared to healthy subjects. Importantly, we have also identified an immature myeloid cell population in patients with highly active, refractory disease, indicating the presence of an "emergency myelopoiesis" process in PsA. In this research protocol, we aim to decipher the pro-inflammatory "myeloid signature" in patients with active PsA and explore the role of immature myeloid cells in disease pathophysiology and their potential as prognostic biomarkers. To address this, we will isolate and analyse monocytes and immature myeloid cells from PsA patients -before and after a 6-month treatment course- focusing on differences between responders and non-responders. In this context, we will perform a thorough phenotypic and functional analysis of these cells, identify their expression signature in an already established whole blood RNA-seq dataset and investigate their presence in target tissues, such as the skin and synovial fluid. This study will elucidate the role of myeloid cells in disease propagation by further defining the involvement of immature myeloid cells in PsA.

P134 Efficacy of Upadacitinib on Psoriatic Arthritis with Axial Involvement Defined by Investigator Assessment and PRO-Based Criteria: Results from two Phase 3 Studies

P134 Efficacy of Upadacitinib on Psoriatic Arthritis with Axial Involvement Defined by Investigator Assessment and PRO-Based Criteria: Results from two Phase 3 Studies

P180 Minimal disease activity response patterns in bio-naïve patients with psoriatic arthritis treated with guselkumab: a machine learning analysis

Abstract Background/Aims Guselkumab, a human monoclonal antibody targeting the interleukin-23 p19 subunit, demonstrated joint and skin efficacy in patients with PsA in the Phase III DISCOVER-1/-2 trials. MDA, a multi-domain composite outcome, is a clinically relevant measure of therapeutic response in PsA. However, response dynamics and the effect of individual domains on achieving MDA are not well understood. This analysis aimed to characterise MDA response clusters according to domain changes over time and identify potential baseline predictors in patients with PsA receiving guselkumab. Methods Data from bio-naïve patients with active PsA receiving guselkumab 100 mg every 4 or 8 weeks were pooled across DISCOVER-1/-2. Unsupervised machine learning using the time-series K-means clustering algorithm was performed to identify clusters according to MDA domain responses over 52 weeks. Missing data were not imputed. Results This analysis included 571 of 669 patients receiving guselkumab and distinguished four response clusters (C1-4; Table 1). Mean age and body mass index were similar across clusters; C3 had a lower proportion of female patients vs. other clusters. Relative to C3, a high burden of baseline disease was observed in C4 across clinical measures and PROs, and across PROs only in C2. Through Week 52, mean values for all MDA domains showed continuous improvement across clusters (Table 1). MDA response rates were highest in C3, in which all individual domain thresholds were rapidly approached, and lowest in C4. In C1 and C2, improvement in clinical measures paralleled that of C3; both met the PASI threshold and showed substantial reduction in SJC. PROs appeared to take longer to improve but did so earlier in C1 than C2. Improvements were slowest in C4, though still substantial given the high baseline disease burden. Conclusion Machine learning differentiated four clusters of patients with PsA receiving guselkumab based on response patterns in individual MDA domains. Response may differ due to baseline disease burden, especially in patients with high pain, PtGA and functional disability scores. These results offer an innovative, complementary approach to identifying treatment response patterns across diverse clusters of bio-naïve patients with PsA, which may facilitate clinical decision-making. Disclosure A. Zabotti: Member of speakers’ bureau; AbbVie, Amgen, Janssen, Lilly, Novartis and UCB. Grants/research support; Novartis. S. Ohrndorf: Other; Speaker fees or travel expense reimbursements from AbbVie, BMS, Janssen, Novartis and Pfizer. W. Tillett: Other; Research funding, consulting, speaker fees and/or honoraria from AbbVie, Amgen, Celgene, GlaxoSmithKline, Janssen, Lilly, MSD, Novartis, Pfizer and UCB. M. Neuhold: Other; Former employee of Janssen and is now an employee of Takeda Pharmaceuticals International AG. M. van Speybroeck: Shareholder/stock ownership; Employee of Janssen and owns stocks in Johnson &amp; Johnson. E. Theander: Other; Former employee of Janssen. C. Contré: Other; Former employee of Janssen and is now an employee of Chiesi. M. Sharaf: Shareholder/stock ownership; Employee of Janssen and owns stocks in Johnson &amp; Johnson. M. Shawi: Shareholder/stock ownership; Employee of Janssen and owns stocks in Johnson &amp; Johnson. M. Perate: Shareholder/stock ownership; Employee of Janssen and owns stocks in Johnson &amp; Johnson. A. Kollmeier: Shareholder/stock ownership; Employee of Janssen and owns stocks in Johnson &amp; Johnson. P. Richette: Other; Received fees from AbbVie, Amgen, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer and UCB.

Apremilast for biologic-naïve, peripheral psoriatic arthritis, including patients with early disease: results from the APROACH observational prospective study

To evaluate the effect of the phosphodiesterase 4 inhibitor apremilast in biologic-naïve patients with early peripheral PsA in terms of disease activity, clinical manifestations, patient-perceived outcomes, as well as apremilast’s safety profile in routine care settings of Greece. Non-interventional, multicenter, 52-week prospective cohort study, enrolling biologic-naïve patients with early active peripheral PsA who started apremilast after intolerance or inadequate response (within the first 12 months of treatment) to an initial conventional synthetic (cs)DMARD treatment. Non-responder imputation was applied for missing data.In total, 167 consecutive patients (mean age: 52.5 years; median PsA duration: 0.9 years) were analyzed. At baseline, the median (interquartile range) clinical Disease Activity in Psoriatic Arthritis (cDAPSA) score was 22.0 (16.0–29.0), with 86.8% of patients having at least moderate (29.3% high) disease activity; 87.4% had skin psoriasis, 37.7% nail psoriasis, 30.7% enthesitis, and 12.4% dactylitis. At 16, 24, and 52 weeks, 28.7, 42.5, and 48.5% of patients, achieved ≥ 50% improvement in their baseline cDAPSA score, respectively. At week 52, 55.6, 50, and 26.8% of evaluable patients achieved complete resolution of enthesitis, dactylitis and nail psoriasis, respectively. Improvements were also observed in patient’s health state assessed by the Psoriatic Arthritis Impact of Disease 12-item questionnaire, and health-related quality of life. The 52-week drug survival rate was 75%, while 13.8% of patients experienced at least one adverse drug reaction.Biologic-naïve patients with early PsA, treated with apremilast experienced significant improvements in disease activity, extra-articular manifestations and patient-centered outcomes, accompanied by a favorable tolerability profile.

Identification of PsA phenotypes with machine learning analytics using data from two phase III clinical trials of guselkumab in a bio-naïve population of patients with PsA

ObjectivesPsoriatic arthritis (PsA) phenotypes are typically defined by their clinical components, which may not reflect patients’ overlapping symptoms. This post hoc analysis aimed to identify hypothesis-free PsA phenotype clusters using...

Neutrophil function following treatment of psoriatic arthritis patients with secukinumab: altered cytokine signalling but no impairment of host defence.

Identifying that dysfunction of the IL-23/17 axis underlies PsA has led to the development of effective targeted therapies such as the IL-17A inhibitor secukinumab. As IL-17A stimulates the secretion of neutrophil chemoattractants, such as CXCL8 (IL-8), we examined the effect of secukinumab on neutrophil function in PsA. Nineteen patients with active PsA were treated with secukinumab. Clinical response [PsA Response Criteria (PsARC) and Psoriasis Area and Severity Index (PASI)] and peripheral blood neutrophil function (apoptosis, receptor expression, phagocytosis/killing, chemotaxis and RNA expression) were measured at 12 week intervals for 48 weeks and compared with age- and sex-matched healthy controls. At 12 weeks, 12/16 (75%) patients had a PsARC response (100% at 36 weeks) and 10/14 (71%) achieved a 90% PASI response. At baseline, there were no differences in PsA neutrophil reactive oxygen species generation, constitutive or cytokine-delayed apoptosis, chemotaxis or phagocytosis of opsonized Staphylococcus aureus compared with healthy controls. Similarly, there were no differences in these functions from baseline to 12 weeks of therapy. However, surface levels of CD11b/CD18 and CD63 increased and expression of CD16 decreased during therapy. In addition, in a subgroup of early (12 week) responders to secukinumab, RNA sequencing revealed transcriptome changes predicting down-regulation of cytokine signalling and chemotaxis pathways and up-regulation of de novo gene expression pathways, including translation initiation, mRNA catabolism and translation. Complex changes in the properties of circulating neutrophils occur with secukinumab treatment in PsA that may indicate altered responsiveness to changes in both local and systemic levels of pro-inflammatory cytokines. However, host defence processes of neutrophils were unaltered.

Intravenous Golimumab in Patients with Polyarticular Juvenile Idiopathic Arthritis and Juvenile Psoriatic Arthritis and Subcutaneous Ustekinumab in Patients with Juvenile Psoriatic Arthritis: Extrapolation of Data from Studies in Adults and Adjacent Pediatric Populations.

ObjectivesTo describe the extrapolation approaches used to support intravenous (IV) golimumab for polyarticular juvenile idiopathic arthritis (pJIA) and juvenile psoriatic arthritis (jPsA) and subcutaneous (SC) ustekinumab for jPsA.MethodsPharmacokinetic, clinical response, and safety data from trials of IV golimumab and SC ustekinumab in polyarticular-course JIA (pc-JIA) (GO-VIVA) or pediatric psoriasis (PsO) (CADMUS and CADMUS Jr) and data from pivotal, phase 3 trials of these agents in adults with similar diseases were used to support extrapolation in pJIA and jPsA. In the phase 3 GO-VIVA trial, patients with pc-JIA aged 2 to < 18 years received IV golimumab 80 mg/m2 at weeks 0, 4, then every 8 weeks (Q8W). In the phase 3, randomized, placebo-controlled CADMUS trial, patients with PsO aged ≥ 12 to < 18 years received ustekinumab at weeks 0, 4, then Q12W. In the phase 3 CADMUS Jr trial, patients with PsO aged ≥ 6 to < 12 years received ustekinumab at weeks 0, 4, then Q12W. The ustekinumab analyses used data only from patients who received the standard ustekinumab dosing regimen (≤ 60 kg: 0.75 mg/kg; > 60 to ≤ 100 kg: 45 mg; > 100 kg: 90 mg).ResultsIn the 127 patients with pc-JIA treated with IV golimumab (GO-VIVA), pharmacokinetic and exposure-response results were similar to those in adults with rheumatoid arthritis treated with IV golimumab. Additionally, pharmacokinetic and clinical response data from five patients with jPsA in GO-VIVA were comparable to those in adults with PsA treated with IV golimumab. No new safety signals were observed in GO-VIVA. Pharmacokinetic and clinical response data observed in the four pediatric patients with PsO and jPsA treated with ustekinumab in CADMUS and CADMUS Jr were similar to those in the 91 pediatric patients with PsO without jPsA in these trials and to those in adults with PsA treated with ustekinumab. Safety was extrapolated from CADMUS or CADMUS Jr; no new signals were observed.ConclusionsThese three sets of analyses corroborate similar exposure and efficacy of IV golimumab in pediatric patients with pc-JIA or jPsA and SC ustekinumab in patients with jPsA to support extrapolation of established adult efficacy. The overall safety profiles of IV golimumab in pediatric patients with pc-JIA or jPsA and SC ustekinumab in pediatric patients with PsO with or without jPsA were consistent with the safety profiles of these agents in the context of their clinical programs and cumulative use. Based on these analyses, the US Food and Drug Administration approved IV golimumab for polyarticular JIA and active PsA in patients 2 years and older and SC ustekinumab for pediatric PsA in patients 6 years and older, highlighting how use of an extrapolation approach can help streamline drug development for pediatric patient populations in whom larger clinical trials are not feasible.Clinical Trial RegistrationGO-VIVA (NCT02277444) was registered at clinicaltrials.gov on 29 October 2014; CADMUS (NCT01090427) was registered on 22 March 2010; and CADMUS Jr (NCT02698475) was registered on 3 March 2016.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40272-022-00533-y.

POS0934 EFFICACY OF UPADACITINIB ON PSORIATIC ARTHRITIS WITH AXIAL INVOLVEMENT DEFINED BY INVESTIGATOR ASSESSMENT AND PRO-BASED CRITERIA: RESULTS FROM TWO PHASE 3 STUDIES

BackgroundPatients with PsA and axial involvement have higher disease activity and greater reductions in quality of life;1 however, there are no accepted criteria for identifying axial involvement in PsA.ObjectivesThe objective of this post-hoc analysis is to assess the efficacy of upadacitinib (UPA), a Janus kinase inhibitor, on axial symptoms in patients with active PsA and axial involvement defined by investigator assessment and PRO-based criteria from two phase 3 SELECT trials.2,3MethodsPatients with active PsA (≥3 swollen joints and ≥3 tender joints) and prior inadequate response or intolerance to ≥1 non-biologic (SELECT-PsA 1) or ≥1 biologic (SELECT-PsA 2) DMARD were randomly assigned to once daily oral UPA 15 mg or 30 mg, placebo (PBO), or every other week subcutaneous adalimumab (ADA) 40 mg (SELECT-PsA 1 only).2,3 At baseline, axial involvement in PsA was determined by investigator assessment based on the totality of clinical information, such as duration and character of back pain, age of onset, and previous imaging. In addition to investigator assessment, PRO-based criteria for axial involvement (BASDAI ≥4 and BASDAI Question 2 ≥4 at baseline) were applied for this analysis to identify patients with active disease. Efficacy in the sub-group of patients defined using both investigator assessment and PRO-based criteria was evaluated at week 24 for UPA 15 mg vs PBO and ADA (SELECT-PsA 1 only). Data were analyzed using mixed-effect model repeated measures (MMRM) or non-responder imputation (NRI), with nominal P-values shown.ResultsBased on investigator assessment alone, 31.3% (n=534/1704) of patients in SELECT-PsA 1 and 34.2% (n=219/641) in SELECT-PsA 2 were defined as having axial involvement. When both investigator assessment and PRO-based criteria were applied, 23.1% (n=393/1704) of patients in SELECT-PsA 1, or 73.6% (n=393/534) of those defined using investigator assessment alone, and 27.5% (n=176/641) in SELECT-PsA 2, or 80.4% (n=176/219) using investigator assessment alone, met the combined criteria for axial involvement. In both studies, UPA 15 mg showed significantly greater clinical responses vs PBO at week 24 across all endpoints assessed (Figure 1). In SELECT-PsA 1, UPA showed numerically greater responses than ADA at week 24 across all BASDAI and Ankylosing Spondylitis Disease Activity Score (ASDAS) endpoints. The proportion of patients achieving ASDAS clinically important improvement (CII) at week 24 was significantly greater with UPA vs ADA based on nominal P-value.ConclusionPatients with active PsA and axial involvement defined by both investigator assessment and PRO-based criteria demonstrated statistically greater clinical responses related to their axial involvement with UPA 15 mg compared to PBO, and consistently numerically higher responses compared to ADA, at week 24 in the SELECT-PsA trials. Findings from this post-hoc analysis are consistent with previous data based on investigator assessment alone.4References[1]Mease PJ et al. J Rheumatol. 2018; 45(10):1389-96[2]McInnes IB et al. N Engl J Med. 2021; 384(13):1227-39[3]Mease PJ et al. Ann Rheum Dis. 2020; 80(3):312-20[4]Deodhar A et al. Arthritis Rheumatol. 2020; 72(Suppl 10)AcknowledgementsAbbVie funded these studies and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. No honoraria or payments were made for authorship. Medical writing support was provided by Monica R.P. Elmore, PhD of AbbVie.Disclosure of InterestsXenofon Baraliakos Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, and UCB, R Ranza Speakers bureau: AbbVie, Janssen, Novartis, and Pfizer, Consultant of: AbbVie, Janssen, Novartis, and Pfizer, Andrew Ostor Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, Gilead, MSD, Novartis, Pfizer, and Roche, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Gilead, MSD, Novartis, Pfizer, and Roche, francesco ciccia Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, MSD, Novartis, Pfizer, Janssen, Sanofi, Sandoz, Galapagos, Sobi, and UCB, Grant/research support from: AbbVie, Celgene, Pfizer, Roche, and UCB, Laura Coates Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, MSD, Novartis, Pfizer, Janssen, Sanofi, Sandoz, Galapagos, Sobi, and UCB, Grant/research support from: AbbVie, Celgene, Pfizer, Roche, and UCB, Simona Rednic Consultant of: AbbVie, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, and Pfizer, Grant/research support from: AbbVie, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Pfizer, and UCB, Jessica A. Walsh Consultant of: AbbVie, Amgen, Eli Lilly, Merck, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Eli Lilly, Merck, Novartis, Pfizer, and UCB, Tianming Gao Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Apinya Lertratanakul Shareholder of: Formerly of AbbVie, Employee of: Former employee of AbbVie, In-Ho Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Fabiana Ganz Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Kevin Douglas Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Atul Deodhar Consultant of: AbbVie, Amgen, Aurinia, BMS, Boehringer Ingelheim, GSK, Janssen, Lilly, MoonLake, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, GSK, Lilly, Novartis, Pfizer and UCB

POS1037 EFFECT OF GUSELKUMAB, A SELECTIVE IL-23p19 INHIBITOR, ON AXIAL-RELATED ENDPOINTS IN PATIENTS WITH ACTIVE PsA: RESULTS FROM A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY THROUGH 2 YEARS

BackgroundGuselkumab (GUS), a selective IL-23p19 inhibitor, showed greater mean improvements in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores vs placebo (PBO) at Week (W) 24 in patients (pts) with active PsA and investigator-confirmed sacroiliitis in pooled post hoc analyses of data from phase 3 DISCOVER (D)-1&amp;2 trials. Improvements in symptoms of axial involvement were maintained through 1 year.1ObjectivesTo assess maintenance of GUS effect on symptoms of axial involvement in biologic-naïve PsA pts with investigator-confirmed sacroiliitis through 2 years of D-2.MethodsIn D-2, 739 bio-naïve pts with active PsA (≥5 swollen + ≥5 tender joints, CRP ≥0.6 mg/dL despite standard therapies) were randomized 1:1:1 to GUS 100 mg every 4W (Q4W; n=245), GUS 100 mg at W0, W4, then Q8W (n=248), or PBO (n=246) with PBO→GUS 100 mg Q4W at W24. Pts with investigator-identified axial symptoms and sacroiliitis (prior X-ray or MRI, or pelvic X-ray at screening) were evaluated. Efficacy was assessed by changes in BASDAI, modified BASDAI (mBASDAI, excluding Q3 [peripheral joint pain]), and BASDAI Q2 (Spinal Pain) scores, and proportions of pts achieving BASDAI 50, Spinal Pain score ≤2, and AS Disease Activity Score (ASDAS) responses through W100. Through W24, pts who met treatment failure criteria or had missing data were considered nonresponders. After W24, missing data were imputed as nonresponse for binary endpoints or no change from baseline for continuous endpoints (nonresponder imputation [NRI]). Axial-related outcomes were also summarized by HLA-B27 status (+/-).Results246 pts had investigator-confirmed sacroiliitis. Baseline characteristics were similar across treatment groups (62% male; mean age 44.4 years; mean BASDAI scores 6.5-6.6). At W24, LS mean/mean changes in BASDAI (-2.4/-2.6) and ASDAS (-1.3/-1.5) scores were greater in GUS- vs PBO-treated pts. Improvements were maintained through W100 in GUS-treated pts: BASDAI, -3.1; Spinal Pain, -3.1; mBASDAI, -3.1; ASDAS, -1.7. Response patterns were similar for BASDAI 50 response rates in GUS-treated pts (W24 38-40%; W100 49-54%). At W24, GUS-treated pts had higher response rates for achievement of ASDAS inactive disease, major improvement, and clinically important improvement vs PBO; response rates (NRI) were maintained, or in some cases further increased, at 2 years. Results were consistent for achievement of ASDAS LDA and Spinal Pain score ≤2 (data not shown). GUS-related improvements in axial symptoms through W100 were generally consistent in HLA-B27+/- pts (data not shown).ConclusionIn bio-naïve pts with active PsA and investigator-confirmed sacroiliitis, GUS provided durable improvements in axial symptoms through W100, with substantial proportions of pts achieving and maintaining clinically meaningful improvements.

AB0891 Deucravacitinib Efficacy in Psoriatic Arthritis by Baseline DMARD Use: Exploratory Analysis From a Phase 2 Study

BackgroundPsoriatic arthritis (PsA) treatment guidelines recommend that patients (pts) inadequately responding to conventional synthetic DMARDs (csDMARDs) can be treated with targeted synthetic DMARDs with or without background use of csDMARDs. Deucravacitinib (DEUC) is a novel, oral, selective, allosteric inhibitor of tyrosine kinase 2 (TYK2) that binds to the unique TYK2 regulatory domain, thereby suppressing signaling of key cytokines (eg, IL-23) involved in PsA pathogenesis. In a Phase 2 trial in pts with active PsA, DEUC was well tolerated and significantly more efficacious than placebo (PBO) after 16 weeks of treatment.1ObjectivesThis analysis further evaluated the effect of DEUC in this Phase 2 trial in pts treated with and without background csDMARDs for 16 weeks.MethodsThis double-blind trial (NCT03881059) enrolled pts with active PsA who had either failed or were intolerant to ≥1 nonsteroidal anti-inflammatory drug, corticosteroid, csDMARD, and/or 1 TNF inhibitor (TNFi; up to 30%). Pts were randomised 1:1:1 to DEUC 6 mg once daily (QD) or 12 mg QD, or PBO. A post hoc subgroup analysis in pts with and without background csDMARD use assessed improvements in select clinical outcomes (ACR 20 response, and change from baseline in ACR components, Psoriasis Area and Severity Index total score, and Psoriatic Arthritis Disease Activity Score) at Week 16.ResultsBaseline (BL) demographics, clinical characteristics, and disease activity were generally similar among pts with and without background csDMARD use. At BL, background csDMARD use was 64.3%, 64.2%, and 66.7% and methotrexate use was 50.0%, 55.2%, and 59.1% in the DEUC 6 mg QD, 12 mg QD, and PBO groups, respectively. Pts with and without background csDMARD use showed similar improvements at Week 16 with DEUC treatment versus PBO on most clinical measures, pt-reported outcomes, and composite measures (Table 1 and Figure 1). No clinically meaningful differences in adverse events (AEs) were observed in pts with or without background csDMARD use.Table 1.Adjusted mean (SE) change from baseline at Week 16 in clinical outcomes by csDMARD usePBO w/o csDMARD (n=22)PBO w csDMARD (n=44)DEUC 6 mg QD w/o csDMARD (n=25)DEUC 6 mg QD w csDMARD (n=45)DEUC 12 mg QD w/o csDMARD (n=24)DEUC 12 mg QD w csDMARD (n=43)Swollen joint count-4.7 (1.4)-5.0 (0.9)-7.4 (1.4)-6.8 (0.9)-8.4 (1.3)-7.7 (1.0)Tender joint count-5.3 (2.2)-6.6 (1.3)-6.4 (2.2)-11.3 (1.3)-11.5 (2.0)-11.6 (1.4)Physician’s Global Assessment of Disease Activity-20.6 (5.6)-20.6 (3.7)-29.1 (5.8)-32.6 (3.5)-30.1 (5.3)-32.1 (3.9)Patients’ Global Assessment of Disease Activity-14.9 (5.8)-13.4 (3.9)-23.0 (5.9)-28.4 (3.8)-28.2 (5.4)-24.9 (4.2)Pain-14.7 (5.6)-14.6 (3.9)-22.7 (5.7)-26.2 (3.7)-25.5 (5.3)-25.5 (4.2)HAQ-DI-0.23 (0.11)-0.04 (0.09)-0.31 (0.11)-0.38 (0.08)-0.48 (0.10)-0.34 (0.09)hsCRP12.0 (5.3)-4.4 (2.1)-10.1 (5.3)-13.3 (2.0)-4.9 (4.9)-10.0 (2.2)PASI total score2.5 (1.4)-2.3 (0.7)-3.7 (1.4)-4.0 (0.6)-4.0 (1.3)-4.9 (0.7)PASDAS-0.9 (0.4)-1.2 (0.3)-1.8 (0.4)-2.1 (0.2)-2.2 (0.3)-2.1 (0.3)The number of patients with data available for individual endpoints may vary.csDMARD, conventional synthetic disease-modifying antirheumatic drug; DEUC, deucravacitinib; HAQ-DI, Health Assessment Questionnaire-Disability Index; hsCRP, high-sensitivity C-reactive protein; PASDAS, Psoriatic Arthritis Disease Activity Score; PASI, Psoriasis Area and Severity Index; PBO, placebo; QD, once daily; SE, standard error; w, with; w/o, without.ConclusionThese analyses demonstrate that the efficacy of DEUC for the treatment of PsA was similar in pts with and without background csDMARD use. The AE profile of DEUC treatment with and without csDMARD use was consistent with findings from the overall Phase 2 PsA trial population.

P275 Association of the improvement of synovitis and enthesitis with quality of life/patient reported outcomes in patients with psoriatic arthritis treated with ixekizumab

Abstract Background/Aims Psoriatic arthritis (PsA) is an inflammatory rheumatic disease with manifestations including synovitis and enthesitis. During extensive study programs, IXE has shown a treatment effect across domains affected by PsA. Ixekizumab (IXE) is an IL17A inhibitor approved for the treatment of active PsA and axial SpA. We sought to determine whether there is any association between the improvement of synovitis with that of enthesitis from baseline (BL) through week (wk) 52 in patients (pts) with PsA treated with IXE. Additionally, the association between the improvement of synovitis and enthesitis on health-related quality of life and patient-reported outcomes was investigated. Methods Data from SPIRIT-P1 (NCT01695239), SPIRIT-P2 (NCT02349295) and SPIRIT-H2H (NCT03151551) were analysed. These were randomized, phase 3 trials involving pts with active PsA either biologic DMARD-naïve (P1, H2H) or TNF-inhibitor-experienced (P2). We examined the patient population randomised to IXE-treatment (80 mg of ixekizumab every 4 weeks [IXEQ4W]), that had both synovitis and enthesitis at BL. For each study, a standardisation procedure was applied to each study data in order to overcome the differences in score range between LEI and SJC. The Pearson correlation coefficient between improvement from BL in enthesitis and synovitis was calculated at each time point. The mean improvement in the SF-36 Physical Component Summary score [PCS], the Patient’s Global Assessment of Disease Activity [Pt GA], and the EuroQOL five dimensions [EQ5D]-visual analogue [VAS] score) was calculated over time for pts who reached or did not reach resolution of both enthesitis and synovitis at wk 52. Missing data were imputed with modified Baseline Carried Out Forward (mBOCF) for continuous outcomes. Non-responder imputation was used for pts with missing resolution of enthesitis or synovitis. Results At BL, 68 (63% of patients treated with IXEQ4W in the ITT population), 68 (56%) and 159 (56%) pts from P1, P2 and H2H respectively, had both synovitis and enthesitis. In all 3 trials, the standardized mean change from baseline in synovitis and enthesitis showed a similar pattern over time. When statistically significant, Pearson correlation coefficient values ranged from 0.16 to 0.40, indicating a positive association between mean improvement in synovitis and enthesitis. We observed an improvement of SF-36 over the 52 wks regardless of the resolution of synovitis or enthesitis. The most pronounced improvement was shown by pts achieving resolution of both synovitis and enthesitis, followed by the pts achieving one or the other. Conclusion Across the SPIRIT trials, treatment with IXE led to the significant improvement in synovitis and enthesitis with a positive association between the improvement of both. Furthermore, pts that resolved both measures at wk 52 experienced an earlier and greater improvement in the SF-36 Physical Component Scale. Disclosure D. McGonagle: Corporate appointments; D. McGonagle has undertaken research and/or educational program activity with: AbbVie, Celgene, Johnson &amp; Johnson, Merck Sharp &amp; Dohme, Pfizer, and UCB Pharma. L. Kristensen: Consultancies; AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Merck Sharp &amp; Dohme, Novartis, Pfizer, and UCB Pharma. Member of speakers’ bureau; AbbVie, Amgen, Biogen, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Merck Sharp &amp; Dohme, Novartis, Pfizer, and UCB Pharma. Grants/research support; Biogen, Janssen Cilag, and UCB Pharma. M. Rudwaleit: Consultancies; AbbVie, Bristol Myers Squibb, Celgene, Chugai Pharmaceutical/Roche, Eli Lilly and Company, Janssen, Merck Sharp &amp; Dohme, Novartis, Pfizer, and UCB Pharma. H. Kameda: Consultancies; AbbVie, Asahi Kasei Pharma, Astellas, Bristol Myers Squibb, Chugai Pharmaceutical, Eisai, Eli Lilly and Company, Janssen, Mitsubishi Tanabe Pharma, Novartis, Sanofi, and Takeda. Member of speakers’ bureau; AbbVie, Asahi Kasei Pharma, Astellas, Bristol Myers Squibb, Chugai Pharmaceutical, Eisai, Eli Lilly and Company, Janssen, Mitsubishi Tanabe Pharma, Novartis, Sanofi, and Takeda. T. Holzkaemper: Shareholder/stock ownership; Eli Lilly and Company. C. El Baou: Other; C. El Baou is an independent contractor working for: Eli Lilly and Company. J. Smolen: Consultancies; AbbVie, Amgen, AstraZeneca, Astro Pharma, Bristol Myers Squibb, Celgene, Celltrion, Chugai Pharmaceutical, Eli Lilly and Company. Grants/research support; Gilead Sciences, GlaxoSmithKline, ILTOO Pharma, Janssen, MedImmune, Merck Sharp &amp; Dohme, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, and UCB Pharma.

P260 Secukinumab in Patients With Psoriatic Arthritis and Axial Manifestations: Predictors of Response From the Double-blind, Randomised, Phase 3b MAXIMISE Trial

Abstract Background/Aims Psoriatic arthritis (PsA) is a heterogeneous disease with variability of response to different therapeutic modalities. Identifying potential demographic and disease characteristics as predictors of treatment response may define personalised treatment optimisation strategies. This post-hoc exploratory analysis of the MAXIMISE trial investigated the differential treatment effect of demographics and baseline characteristics as predictive factors in biologic-naïve patients with active PsA and symptoms of active spinal disease. Methods Full analysis set (FAS) comprised all patients from the randomised set assigned to study treatment, fulfilling the predefined clinical criteria for active axial disease, and for whom Assessment in Ankylosing Spondylitis 20% improvement criteria (ASAS20) data were available at week 12. The research hypothesis was that the odds ratio associated with the effect of treatment on ASAS20 responder status at week 12 would be different depending on 12 pre-specified predictor variables. A logistic regression model was initially fitted to the FAS that included 12 pre-specified covariates. A second logistic regression model was then fitted to the FAS that allowed for all 12 pre-specified variables to interact with treatment. The log-likelihood of the two fitted models were compared using a likelihood ratio test at a pre-specified significance level of 20% (i.e. P-value ≤0.20) to test whether any of the predefined variables interacted with treatment. If the above test was statistically significant at the 20% level, the variables of the second model were formally examined to determine whether overall effect of treatment was not applicable. Hypothesis tests were employed to determine the strength of evidence for each individual variable. Results The likelihood ratio test provided evidence against the assumption that overall effect of treatment is applicable to all patients (P-value, 0.08). Notably, the odds of being an ASAS20 responder if nail dystrophy is present at baseline were 3 times greater in the secukinumab 150-mg group and 5 times greater in the 300-mg group versus placebo (interaction P-value, 0.029). Although males fared worse than females in the placebo group, in the secukinumab 150-mg and 300-mg groups the odds of being a responder were similar to females (interaction P-value, 0.039). Current smokers were less likely to be ASAS20 responders versus never-smokers regardless of treatment group (interaction P-value, 0.589). Age, C-reactive protein level, Berlin MRI spine/SIJ score, time since first axial signs, number of swollen joints, new bone formation, and body mass index did not show a differential treatment effect on ASAS20 responses. Conclusion Of the 12 baseline variables of a unique population of 473 PsA patients with active axial disease diagnosed by clinical criteria, our analyses showed evidence of differential treatment effect, most notably for nail dystrophy, suggesting that the presence of nail dystrophy may predict a better response to secukinumab in PsA patients with axial manifestations. Disclosure L.C. Coates: Consultancies; AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, UCB. Member of speakers’ bureau; AbbVie, Amgen, Biogen, Medac, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, UCB. Grants/research support; AbbVie, Amgen, Celgene, Eli Lilly, Pfizer, Novartis. X. Baraliakos: Consultancies; AbbVie, BMS, Celgene, Chugai, Galapagos, Gilead, MSD, Novartis, Pfizer, UCB. Member of speakers’ bureau; AbbVie, BMS, Celgene, Chugai, MSD, Novartis, Pfizer, UCB. Grants/research support; AbbVie, Novartis. E. Pournara: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. L. Gossec: Consultancies; AbbVie, Amgen, BMS, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB. Grants/research support; Amgen, Galapagos, Lilly, Pfizer, Sandoz, Sanofi. H. Marzo-Ortega: Consultancies; Janssen, Novartis, AbbVie, Celgene, Lilly, Pfizer, Takeda, UCB. Member of speakers’ bureau; AbbVie, Celgene, Janssen, Eli Lilly, Novartis, Pfizer, Takeda, UCB. Grants/research support; Janssen, Novartis, AbbVie, Celgene, Lilly, Pfizer, UCB. P.J. Mease: Consultancies; AbbVie, Amgen, BMS, Boehringer Ingelheim, Galapagos, Celgene, Gilead, Janssen, Lilly, Novartis, Pfizer, SUN Pharma, UCB. Member of speakers’ bureau; AbbVie, Amgen, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB. Grants/research support; AbbVie, Amgen, BMS, Celgene, Galapagos, Genentech, Gilead, Janssen, Lilly, Novartis, Pfizer, SUN, UCB. R. White: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. E. O'brien: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. B. Schulz: Other; Employee of Novartis.

Defining imaging sub-phenotypes of psoriatic arthritis: integrative analysis of imaging data and gene expression in a PsA patient cohort.

To define imaging sub-phenotypes in patients with PsA; determine their association with whole blood gene expression and identify biological pathways characterizing the sub-phenotypes. Fifty-five patients with PsA ready to initiate treatment for active disease were prospectively recruited. We performed musculoskeletal ultrasound assessment of the extent of inflammation in the following domains: synovitis, peritenonitis, tenosynovitis and enthesitis. Peripheral whole blood was profiled with RNAseq, and gene expression data were obtained. First, unsupervised cluster analysis was performed to define imaging sub-phenotypes that reflected the predominant tissue involved. Subsequently, principal component analysis was used to determine the association between imaging-defined sub-phenotypes and peripheral blood gene expression profile. Pathway enrichment analysis was performed to identify underlying mechanisms that characterize individual sub-phenotypes. Cluster analysis revealed three imaging sub-phenotypes: (i) synovitis predominant [n = 31 (56%)]; (ii) enthesitis predominant [n = 13 (24%)]; (iii) peritenonitis predominant [n = 11 (20%)]. The peritenonitis-predominant sub-phenotype had the most severe clinical joint involvement, whereas the enthesitis-predominant sub-phenotype had the highest tender entheseal count. Unsupervised clustering of gene expression data identified three sub-phenotypes that partially overlapped with the imaging sub-phenotypes suggesting biological and clinical relevance of these sub-phenotypes. We therefore characterized enriched differential pathways, which included: immune system (innate system, B cells and neutrophil degranulation), complement system, platelet activation and coagulation function. We identified three sub-phenotypes based on the predominant tissue involved in patients with active PsA. Distinct biological pathways may underlie these imaging sub-phenotypes seen in PsA, suggesting their biological and clinical importance.

Сучасні рекомендації щодо лікування псоріатичного артриту згідно з рекомендаціями Американського коледжу ревматологів і Національної організації з псоріазу 2018 року

Псоріатичний артрит (ПсА) — це хронічне запальне скелетно-м’язове захворювання, асоційоване з псоріазом, яке маніфестує зазвичай з периферичного артриту, дактиліту, ентезиту та/чи спондиліту. Рання ідентифікація та діагностика ПсА, ранній початок терапії важливі для покращення довгострокових наслідків хвороби. Клінічна картина ПсА є гетерогенною, і лікарі досить часто стикаються з проблемами при визначенні стратегій лікування. Метою нашого огляду були надання й інтерпретація рекомендацій Американського коледжу ревматологів (ACR) і Національної організації з псоріазу (NFP) 2018 року з лікування активного ПсА у дорослих з використанням фармакологічних і нефармакологічних методів. Ці рекомендації щодо лікування ПсА можуть допомогти як клініцистам, так і пацієнтам досягти оптимальних рішень щодо менеджменту хвороби. У рекомендаціях наведені стратегії вибору препаратів для лікування активного ПсА при різних клінічних ситуаціях та залежно від проведеної попередньої терапії. Наявність або відсутність коморбідних станів, таких як запальне захворювання кишечника, увеїт, діабет або серйозні інфекції, а також знання попередніх методів лікування є факторами, що дозволяють зробити вибір оптимальної терапії для окремого пацієнта в даний момент часу, застосовуючи індивідуальний підхід. Рекомендації ACR/NFP щодо лікування активного ПсА рекомендують інгібітори фактора некрозу пухлини, а не пероральні низькомолекулярні препарати як препарати першої лінії, саме ці біологічні агенти запобігають прогресуванню захворювання та пошкодженню суглобів. Наголошується на необхідності ранньої та агресивної терапії у пацієнтів з вперше виявленим ПсА.