Active Psoriatic Arthritis Research Articles

42267 Improvements in Patient-Reported Outcomes Among Patients With Resolution of Enthesitis and/or Dactylitis: Post hoc Analyses From the KEEPsAKE 1 and 2 Trials of Risankizumab in Patients With Active Psoriatic Arthritis

42267 Improvements in Patient-Reported Outcomes Among Patients With Resolution of Enthesitis and/or Dactylitis: Post hoc Analyses From the KEEPsAKE 1 and 2 Trials of Risankizumab in Patients With Active Psoriatic Arthritis

43944 Improvements in Manifestations of Active Psoriatic Arthritis With Risankizumab Treatment After Intolerance or Inadequate Response to Prior Biologic Therapy: Subgroup Analyses From the KEEPsAKE 2 Trial

43944 Improvements in Manifestations of Active Psoriatic Arthritis With Risankizumab Treatment After Intolerance or Inadequate Response to Prior Biologic Therapy: Subgroup Analyses From the KEEPsAKE 2 Trial

Effectiveness of Brodalumab in Patients with Moderate-to-Severe Plaque Psoriasis Located in Difficult-to-Treat Areas.

Recent knowledge of psoriasis pathogenesis has led to the development of selective drugs. Among these, brodalumab is a monoclonal antibody targeting the interleukin (IL)-17A receptor approved for the treatment of moderate-to-severe plaque psoriasis. Biologics may be considered in patients with milder diseases in case of active psoriatic arthritis, severe impact on patient's quality of life, and involvement of sensitive and difficult-to-treat areas. These skin locations commonly require systemic drugs. Recently, psoriasis severity monitoring has also changed. Indeed, the clinical evaluation by means of specific efficacy scores was combined with serological evaluation by means of the assay of specific inflammatory biomarkers. An observational study enrolled patients affected by moderate-to-severe plaque psoriasis involving difficult-to-treat areas, undergoing treatment with brodalumab to evaluate the effectiveness and safety of brodalumab in patients with psoriasis affecting difficult-to-treat areas (scalp and palmoplantar regions). Secondary outcomes were the assessment of the development of serum markers of inflammation during the treatment period as well as the evaluation of the dermoscopic features of the affected sites to quantify disease activity and response to treatment. Twenty-five patients were included in the study. A statistically significant reduction from baseline in PASI, PSSI, ppPASI and DLQI values as early as week 24 was observed, with further improvement up to week 52. Plasma levels of MMP-3, VEGF-A, and hs-PCR decreased during treatment from week 0 to week 52. Our real-life experience suggests brodalumab as a valuable option for the management of psoriasis located in difficult-to-treat areas. Moreover, our study highlights that the use of brodalumab reduces the plasmatic levels of inflammatory biomarkers (MMP-3, VEGF-A and hs-PCR), showing how the drug modulates the skin inflammatory response by reducing systemic inflammation.

Possible diagnostic accuracy of interleukin − 17A for early diastolic dysfunction in patients with psoriatic arthritis

Psoriatic arthritis (PsA) is influenced by a complex genetic predisposition. In patients with PsA, interleukin (IL)-17A plays a key role in triggering a complex autoimmune/autoinflammatory immune response in conjunction with other pro-inflammatory cytokines (such as tumor necrosis factor-alpha, IL-23, monocyte chemotactic protein-1, and IL-6). PsA manifests with various clinical symptoms, including musculoskeletal diseases and extra-articular manifestations. In particular, mediated by the soluble IL-17A presents a higher cardiovascular risk, suggesting connection between inflammation and cardiovascular diseases beyond the traditional risk factors. Moreover, studies have shown that patients with psoriasis are ten times at higher risk of developing dilated cardiomyopathy than those without psoriasis. Therefore, owing to the prominent role of IL-17A and psoriasis in the pathogenesis of PsA and endothelial dysfunction, we hypothesized that IL-17A is crucial in the early development of diastolic dysfunction (DD) and could serve as a tool to identify patients with asymptomatic DD and PsA. Although transthoracic echocardiography is the primary evaluation method for DD, it requires skilled personnel, routine parameters assessment, such as mitral inflow, and tissue Doppler imaging. As a result, assessing parameters such as left atrial deformity using novel techniques could be valuable for a more specific evaluation and diagnosis of DD. Clinical characteristics and laboratory parameters of PsA activity, cardiac ultrasound parameters, or cardiac functional markers like N-terminal pro-brain natriuretic peptide (NT-pro-BNP) can be correlated with the concentration of serum IL-17A. Moreover, determining the diagnostic accuracy of circulating IL-17A for early DD can also serve as a laboratory biomarker for diagnosing DD in asymptomatic patients. Thus, if the diagnostic accuracy of IL-17A for DD can be proven, the identification of biological drugs that inhibit IL-17A could be advantageous in treating patients with PsA and echocardiography-verified asymptomatic DD.

Clinical Significance of Immature Neutrophils in Relation to Disease Activity in Psoriatic Arthritis Patients

Abstract Background Psoriatic arthritis (PsA) is a complex type of progressive inflammatory arthritis associated with psoriasis. Prevalence of PsA has been reported 5.8–40.9% among patients suffering from psoriasis. A recent meta-analysis indicated that there is no gender predilection in patients with PsA. It shares genetic and clinical features with other forms of spondyloarthritis and affects different structures of the musculoskeletal system in addition to the skin and the nail. Neutrophils are crucial responders of the innate immune response, but the role played by neutrophils in psoriasis has not been well characterized. This thesis discussed the current understanding of the role and potential mechanisms of immature neutrophils in psoriatic arthritis. Objective To study the relation between immature neutrophils in blood and disease activity in psoriatic arthritis patients. Methods This randomized control trial, done on 50 PsA patients from Physical medicine, Rheumatology and Rehabilitation and Dermatology outpatient clinics of Ain Shams University hospital, included by CASPAR criteria, subjected to full medical history taking and thorough clinical examination with calculation of SPARCC, ASDAS and PASI scores.laboratory evaluation include CBC with differential white blood cell count for Immature Neutrophils percentage, ESR, CRP and Rheumatoid factor.CBC was compared with 20 age and sex matched healthy controls. Results The Immature Neutrophils mean ± SD(%) was found to be 5.99±1.57 in patients and was statistically significantly higher in them than in controls 2.25±1.16(P < 0.037) and it was statistically significantly correlated with disease activity according to ASDAS score, SPARCC, PASI score, ESR, CRP, RBCS, WBCS, Platelets, Enthesitis, Dactylitis, skin and nail affection. Conclusion This study highlighted the role of immature neutrophils as a novel biomarker for disease activity in psoriatic arthritis.

Examining the functions of the vascular endothelial growth factor/hypoxia-inducible factor signaling pathway in psoriatic arthritis.

The present study aimed to examine the roles of the vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF), and heme oxygenase-1 (HO-1) in psoriatic arthritis (PsA). In this cross-sectional study conducted between November 2020 and May 2021, 64 patients (43 female, 21 male; mean age: 43.2±10.4 years; range, 22 to 60 years) with active PsA were included in the patient group, and 64 healthy volunteers (43 female, 21 male; mean age: 42.8±10.5 years; range, 23 to 61 years) were included in the control group. The demographic features of all cases were recorded. The following indices were used to assess the activity of PsA: Bath Ankylosing Spondylitis Disease Activity Index, Disease Activity Score in 28 joints (DAS28), and Visual Analog Scale. Additionally, Disease Activity in Psoriatic Arthritis (DAPSA) and Psoriasis Area and Severity Index (PASI) were used to evaluate the patients. The biochemical parameters of the patients were calculated. The serum levels of VEGF, HIF, and HO-1 were determined using an enzyme-linked immunosorbent assay. When the molecule levels and clinical features of the groups were evaluated, it was found that the VEGF and HIF-1 levels were higher in the patient group compared to the control group (p<0.05). No difference was observed in the comparison of the HO-1 levels of the patient group and the control group (p<0.05). A positive correlation was found between VEGF, HIF-1, and HO-1 (p<0.05). A positive relationship was found between VEGF and HIF-1 and erythrocyte sedimentation rate, C-reactive protein, DAPSA score, and PASI score (p<0.05). It was also determined that there was a positive relationship between the HIF molecule and DAS28 (p<0.05). According to the results obtained in the present study, VEGF and HIF play a role in the etiology of PsA, and the observation of intermolecular correlation suggests that these molecules move together in pathogenesis.

The Role of Chitinase-3-Like Protein 1(YKL-40) as a Biomarker of Psoriatic Arthritis

Background Psoriatic arthritis (PsA) is a chronic multifaceted inflammatory seronegative arthritis. Plasma YKL-40 is an inflammatory biomarker. Objective To evaluate the role of Chitinase-3-like protein 1 (YKL-40) as a diagnostic biomarker in psoriatic arthritis (PsA) patients and determine its value in assessment of disease activity and severity in PsA patients. Patients and Methods This study included twenty five adult patients with clinical evidence of PsA and twenty five healthy matched age and sex as control group. All underwent history, laboratory investigation, clinical examination, assessment of disease activity using Disease Activity in PSoriatic Arthritis (DAPSA) Score and assessment of severity of PsA using Psoriasis Area and Severity Index (PASI), Nail Psoriasis Severity Index (NAPSI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Leeds Enthesitis Index (LEI) and examination of dactylitis. Results The mean age of patients was 39.72 ± 11.94. Also, The mean age of healthy controls was 42.88 ± 12.11. There was highly statistically significant difference regarding the serum levels of YKL- 40 (P &amp;lt; 0.01) between the patients and the control groups (P &amp;lt; 0.01). The receiver operating characteristic curve (ROC) curve of YKL -40 showed that the sensitivity and the specificity of YKL- 40 in diagnosis of PsA were 96% and 92% respectively. There were statistically significant positive correlations between YKL- 40 levels (μl/mL) and each of PASI score (p = 0.005) (r = 0.539) and DAPSA score (p = 0.007) (r = 0.526). Conclusion YKL- 40 measurement may serve as a diagnostic biomarker for PsA, as it has the potential to contribute to the fundamental processes underlying the pathogenesis of PsA. So, the results of this study suggested that the addition of YKL- 40 as a serological marker has a valuable role in diagnosis of PsA and reflection of disease activity.

Efficacy of tofacitinib on enthesitis in patients with active psoriatic arthritis: analysis of pooled data from two phase 3 studies

BackgroundTofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). This post hoc analysis assessed tofacitinib efficacy on enthesitis by baseline location and severity, and impact on disease activity and patient-reported outcomes (PROs), in patients with PsA.MethodsData were pooled from two phase 3 studies (NCT01877668/NCT01882439) in patients with PsA receiving tofacitinib 5 or 10 mg twice daily to month (M)6 or placebo to M3. Endpoints were: change from baseline in Leeds Enthesitis Index (LEI) or Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC); proportions of patients with enthesitis, relapsed enthesitis after resolution, de novo enthesitis, low disease activity (LDA) or remission (minimal disease activity/very low disease activity; Psoriatic Arthritis Disease Activity Score; Disease Activity Index for Psoriatic Arthritis, and Composite Psoriatic Disease Activity in Psoriatic Arthritis); and PROs (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F] total and arthritis pain Visual Analog Scale scores). Descriptive statistics were generated by visit and treatment. Change from baseline in PROs was evaluated by multivariate linear regression.ResultsSeven hundred ten patients from two studies were included: 479 had LEI > 0; 545 had SPARCC > 0; and 136 had LEI = 0 and SPARCC = 0 at baseline. At baseline, among patients with LEI > 0 or SPARCC > 0, mean LEI and SPARCC across treatments and enthesitis locations/severities ranged from 1.0–4.4 and 1.3–9.4, respectively. Across several baseline enthesitis locations/severities, changes from baseline in LEI and SPARCC up to M3 were greater with tofacitinib (-2.0–0.4 and -3.5–0.2) vs placebo (-‍0.9–‍0.4 and -1.5–1.1). Enthesitis at M6 was more common in patients with greater baseline enthesitis severity. At M6, ≤ 40% of patients with baseline LEI > 0 or SPARCC > 0 whose enthesitis had resolved by M1/M3 experienced a relapse, and < 14% of patients with baseline LEI = 0 and SPARCC = 0 had de novo enthesitis. LDA/remission rates generally increased with tofacitinib over time. Baseline LEI location was significantly associated with change from baseline in arthritis pain score, while baseline SPARCC severity was significantly associated with change from baseline in FACIT-F total and arthritis pain scores.ConclusionTofacitinib treatment resulted in improvements in enthesitis in patients with PsA, regardless of baseline location or severity.Trial registrationNCT01877668;NCT01882439.

Six-Month Persistence and Multi-domain Effectiveness of Guselkumab in Adults with Psoriatic Arthritis: Real-World Data from the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.

The aim of this work is to evaluate treatment persistence and clinical outcomes after 6months of on-label guselkumab use in patients with rheumatologist-diagnosed active psoriatic arthritis (PsA) enrolled in the CorEvitas PsA/Spondyloarthritis Registry. Participants with PsA who initiated and persisted with on-label guselkumab use post-Food and Drug Administration (FDA) approval for active PsA (7/13/2020; subcutaneous 100mg at weeks 0, 4, and every 8weeks) at their 6-month follow-up visit (occurring through 3/31/2023) comprised the primary analysis population (On-Label Persisters). Hierarchical, multiplicity-controlled primary and secondary outcomes were mean (95% confidence interval) changes from baseline at 6months in clinical Disease Activity Index for PsA (cDAPSA; primary), Physician Global Assessment (PGA) of arthritis and psoriasis (visual analog scale [VAS] 0-100), patient-reported pain (VAS 0-100), and percent body surface area with psoriasis (%BSA). Paired ttests determined changes that were statistically significantly different from 0 (α = 0.05). Among 114 patients who initiated on-label guselkumab and had eligible baseline and 6-month visits, 90 (78.9%) had persistent use. Among these On-Label Persisters at baseline, mean duration of PsA symptoms = 13.6years; mean cDAPSA, PGA, and patient-reported pain = 22.0, 42.3, and 57.0, respectively; 94.4% had a history of psoriasis (mean BSA 7.6%); and 18.9% and 73.3%, respectively, previously received 1 or ≥ 2 biologic/targeted synthetic disease-modifying antirheumatic drugs. The mean change (improvement) in cDAPSA was -5.4 (-8.5, -2.3; p < 0.001) at 6months. Significant mean improvements in PGA (-19.0 [-24.2, -13.8]), patient-reported pain (-9.1 [-14.4, -3.8]), and %BSA (-5.1 [-7.6, -2.7]) were also observed (all p < 0.001). In this real-world PsA population, generally characterized by longstanding, treatment-resistant, active disease at baseline, persistent guselkumab use in nearly 80% of patients with on-label use was accompanied by significant improvements in joint and skin symptoms and patient-reported pain at 6months. These registry data support results from randomized clinical trials demonstrating the efficacy of guselkumab in improving PsA signs and symptoms. clinicaltrials.gov: NCT02530268.

Effect of guselkumab on serum biomarkers in patients with active psoriatic arthritis and inadequate response to tumor necrosis factor inhibitors: results from the COSMOS phase 3b study

BackgroundGuselkumab is a selective interleukin (IL)-23 inhibitor targeting the IL-23p19 subunit. In the phase 3b COSMOS trial, guselkumab demonstrated efficacy in treating participants with active psoriatic arthritis (PsA) and inadequate response (IR; lack of efficacy or intolerance) to tumor necrosis factor inhibitors (TNFi).MethodsAdults with active PsA (≥ 3 swollen joints, ≥ 3 tender joints) and IR to one or two TNFi (TNFi-IR) were randomized 2:1 to guselkumab at Weeks 0, 4, then every 8 weeks (Q8W) or placebo➔guselkumab Q8W at Week 24 with possible early escape at Week 16. Levels of serum cytokines, including interferon γ (IFNγ), IL-10, and tumor necrosis factor α (TNFα); T helper 17 (Th17) effector cytokines IL-17A, IL-17F, and IL-22; and acute phase proteins C-reactive protein (CRP), IL-6, and serum amyloid A (SAA), were assessed and compared with demographically matched healthy controls; guselkumab pharmacodynamics through Week 24 were also assessed. Associations between baseline biomarker levels and 1) baseline disease activity (28-joint disease activity score using CRP [DAS28-CRP], psoriasis area and severity index [PASI], and % body surface area [BSA] affected by psoriasis) and 2) clinical response (including ≥ 20% improvement in American College of Rheumatology criteria [ACR20] response) at Week 24 were assessed.ResultsBaseline serum levels of IL-6, IL-10, IL-17A, IL-17F, IL-22, TNFα, and IFNγ were significantly higher in COSMOS TNFi-IR participants than in healthy controls. Baseline IL-6, CRP, and SAA levels were associated with baseline DAS28-CRP. IL-17A and IL-17F levels were associated with baseline PASI score and psoriasis BSA. Baseline swollen or tender joint counts did not associate with baseline biomarker levels. At Week 24, significant decreases from baseline in CRP, SAA, IL-17A, IL-17F, and IL-22 levels were seen in guselkumab-, but not placebo-, treated participants. IL-17F and IL-22 levels at Week 24 in guselkumab-treated participants did not significantly differ from those of healthy controls. Guselkumab-treated participants achieving ACR20 response at Week 24 exhibited higher baseline IL-22 and IFNγ levels versus nonresponders.ConclusionsResults from COSMOS participants with active, TNFi-IR PsA suggest guselkumab reduces levels of effector cytokines associated with the IL-23/IL-17 pathway, including those associated with baseline arthritis and skin disease activity.Trial registrationClinicalTrials.gov: NCT03796858.

Psoriatic arthritis and Hashimoto's thyroiditis in a patient presenting with major depression and subclinical hyperthyroidism: A case report

Psoriatic arthritis (PsA) is a chronic, deforming arthritis associated with psoriatic skin lesions. Numerous patients with PsA carry other co-existing chronic diseases, adding to their overall disease burden and affecting the patient’s quality of life. Depression is a common illness known to coexist in about 20% of patients with PsA. Long-term inflammation conditions can make patients more depressed and make the treatment more difficult. Cushing Syndrome (CS) is a complication of long-term treatment due to the exposure of glucocorticoids given to turn the hypothyroid condition into hyperthyroid because hypercortisolism in humans lowers TSH secretion and TSH pulse amplitude. When PsA combines with depression and CS, it will create complex conditions and treatments. The complexity is all about how we control the disease activity of PsA and the vicious circle of an inflammatory process that is difficult to control. Conventional treatment will fail, and targeted therapy with monoclonal antibodies such as anti-IL-17 Secukinumab, is needed. Secukinumab as an anti-IL-17 will block the inflammation pathway from interleukin-17, decrease the inflammation process, and improve the symptoms of PsA. We report a patient with psoriatic arthritis and Hashimoto's thyroiditis (HT) with a major depressive episode with CS and subclinical hyperthyroidism successfully treated with Secukinumab.

Persistence and Use of Ixekizumab in Patients with Psoriatic Arthritis in Real-World Practice in Spain. The PRO-STIP Study.

Ixekizumab (IXE) is an IgG4-type monoclonal antibody targeting IL-17A indicated alone or in combination with methotrexate, for the treatment of active psoriatic arthritis (PsA) in adult patients with insufficient response or with intolerance to one or more disease-modifying anti-rheumatic drug (DMARD) therapy. The PRO-STIP study aimed to describe persistence, patient characteristics, treatment patterns, and effectiveness in patients with PsA receiving IXE in a real-world clinical setting in Spain. This was an observational, multicentric, retrospective, longitudinal study in adult PsA patients who started IXE between January 2019 and December 2020, with at least 24weeks of follow-up. A descriptive analysis of patient characteristics and treatment patterns was performed. The primary objective, treatment persistence, was estimated by Kaplan-Meier survival curve. Effectiveness was evaluated by Disease Activity in Psoriatic Arthritis (DAPSA) scores at baseline and at 12 and 24weeks. Eighty-nine patients met the selection criteria (55.1% women and mean age 51.5years). The median time from PsA diagnosis to starting IXE was 7.7years (IQR 3.4-14.6). Prior to IXE, 95.5% patients had been treated with at least one biologic or targeted synthetic DMARD (b/tsDMARD). The observed persistence rates were 95.5%, 84.3% and 68.5% at 24, 48, and 104weeks, respectively. The median persistence was not reached in the study period (mean persistence, 86.9 [95% CI 80.6-93.2] weeks). Twenty-eight (31.5%) patients discontinued IXE, 19 patients (21.3%) due to loss of effectiveness and two patients (2.2%) due to adverse events. In patients receiving treatment and with available effectiveness assessment (n = 24), DAPSA decreased significantly from baseline 23.7 (95% CI 19.5-27.9) to 14.8 (95% CI 10.5-19.2) at 12weeks (p = 0.005) and 14.3 (95% CI 11.1-17.4) at 24weeks (p = 0.004). PsA patients treated with IXE in a real-world setting show high treatment persistence through 104weeks and improvements in disease activity after treatment initiation. This suggests that IXE could be an effective treatment for patients with PsA. Date of registration: 25th May 2021.

Golimumab for Polyarticular Juvenile Idiopathic Arthritis and Psoriatic Arthritis: Pharmacologic and Clinical Considerations.

Psoriatic arthritis is a chronic debilitating autoimmune condition, and when diagnosed in patients before the age of eighteen, it is considered pediatric polyarticular juvenile idiopathic arthritis. Monoarticular or polyarticular psoriatic arthritis can be distinguished from other arthropathies by its unique cutaneous manifestations. With numerous treatments already in clinical practice, there are numerous options for treatment. The current literature indicates an elevated level of tumor necrosis factor is present in the epidermis of patients with psoriatic arthritis when compared with the general population. For this reason, anti-tumor necrosis factor therapies have become a hallmark option for psoriatic arthritis patients. Golimumab, a human monoclonal antibody tumor necrosis factor-alpha (TNF-a) receptor antagonist, was chosen as the focus therapy for this investigation. The mechanism of action behind anti-tumor necrosis factor-alpha blockers involves the binding of human TNF-a soluble and transmembrane proteins to competitively inhibit TNF-a from binding to its cellular receptors. The present investigation evaluated current treatment options available for both juvenile- and adult-onset psoriatic arthritis and compared them with the efficacy seen with golimumab use. Pediatric patients included children ages 2-17, while adult populations included adults 18-83 years old. The Food and Drug Administration has approved golimumab for the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, and polyarticular juvenile idiopathic arthritis. The results of four different studies reporting on the therapeutic effects and adverse events of golimumab use in psoriatic arthritis, juvenile psoriatic arthritis, juvenile idiopathic arthritis, and juvenile polyarticular arthritis were used for comparison. The meta-analysis referenced studies including children ages 2-17 with no reference mentioning children less than age 2. Based on the results of each study, it can be concluded that golimumab, a human monoclonal antibody that prevents the activation of cellular inflammatory reactions when it binds to the TNF-a receptor, is an effective option for patients with active psoriatic arthritis and psoriatic juvenile idiopathic arthritis and for patients who are no longer responding to their current treatment with adalimumab. Each study also reported minimal adverse events associated with golimumab use, and the drug can be safely used in the pediatric population.

A new integral enthesial-comorbididity index of psoriatic arthritis activity

To develop an integral index of psoriatic arthritis (PsA) activity. 117 patients with PsA (M/F - 63/54) were included. Patients' age 44±11 years, psoriasis (Ps) duration - 213±153 months, PsA duration - 73.4±78.5 months. Patients underwent standard clinical examination of PsA activity: tender (out of 68) and swollen (out of 66) joint counts (TJC, SJC), LEI, tenderness of the plantar fascia (PF), skin lesion severity (BSA), presence of nail Ps, body mass index (BMI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), DAPSA, FACIT-F. Parametric and nonparametric statistic methods, correlation and ROC analysis were used. Mean DAPSA was 38±21, TJC - 14.2±10.6, SJC - 10.6±8.3, ESR - 30.5±29.5 mm/h, CRP - 23.3±29 mg/l, LEI - 1.2±1.5, FACIT-F - 32±11, BMI - 27.4±6.2 kg/m2. The following significant positive correlations were revealed: between DAPSA and BMI, patients' age, ESR, PsA and Ps duration, TJC, SJC, LEI, presence of PF enthesitis, skin lesion severity, presence of nail Ps. A negative correlation between FACIT-F and male sex was found. Based on the predictive model of parameters, the Entesial-Comorbid Index of PsA (ECIPsA) was created: 3.81×LEI+13.72×PF+0.54×Age-0.25×FACIT-F+7.36×BSA+7.94×PsA duration+5.5×Nail Ps+0.32×BMI-3.52, namely LEI - Leeds Enthesial Index; PF - pain in the PF; patient's age; FACIT-F - fatigue scale; BSA<3%=0, ≥3%=1; PsA duration≤2 years=0, >2 years=1; presence of nail Ps=1, absence=0; ECIPsA≥28 corresponds with high PsA activity according to DAPSA≥28. ROC analysis of sensitivity and specificity of the prognostic model demonstrated high correctness of the index: the area under the ROC curve was 0.768, 95% confidence interval (0.624-0.913). The new PsA activity index corresponds to the existing ones and takes into consideration the clinical heterogeneity and comorbidity of the disease.

Initiating Evaluation of Composite Outcome Measures for Psoriatic Arthritis: 2022 Updates From the GRAPPA-OMERACT Working Group.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis (PsA) working group-comprising rheumatologists, dermatologists, methodologists, and patient research partners-provided updates at the GRAPPA 2022 annual meeting on its work to evaluate composite outcome measures for PsA. Ten composite outcome measures were considered. Initial steps were to define the population, the purpose of use, and the proposed pros and cons of the 10 candidate composite instruments for PsA. Preliminary Delphi exercises within the working group and GRAPPA stakeholders confirmed high priority for evaluating minimal disease activity (MDA); moderate priority for Disease Activity in PsA (DAPSA), American College of Rheumatology (ACR) response criteria, Psoriatic Arthritis Disease Activity Score (PASDAS), Composite Psoriatic Disease Activity Index (CPDAI), 3 visual analog scale (VAS), and 4VAS; and low priority for Disease Activity Score in 28 joints (DAS28), Psoriatic Arthritis Responder Criteria (PsARC), and Routine Assessment of Patient Index Data 3 (RAPID3). Further appraisal of candidate composite instruments is ongoing.

Association of inflammatory biomarkers and disease activity with subclinical myocardial dysfunction in psoriatic arthritis

We examined the role of adipokines and pro-inflammatory cytokines in psoriatic arthritis-associated subclinical myocardial dysfunction, and the relationship between these variables and psoriatic arthritis (PsA) disease activity. Fifty-five PsA patients without cardiovascular risk factors and 25 controls underwent standard and speckle tracking echocardiography with global longitudinal strain (GLS) calculated. Standard anthropometric data and Disease Activity in Psoriatic arthritis (DAPSA) scores were recorded, with low disease activity defined as DAPSA ≤ 14 and moderate and high disease activity DAPSA > 14. Standard biochemical tests, adiponectin, resistin, leptin, tumor necrosis factor (TNF) alfa, interleukin 17 A (IL-17A), B lymphocyte chemoattractant (BLC), and monokine induced by intereferon gamma (MIG) were analyzed. Median age was 53.0 (46.0–61.0), median PsA duration 6.0 (4.0–13.0) years and median DAPSA score 25.5 (13.0–41.5). Lower GLS, tricuspid annular plane systolic excursion (TAPSE) and left ventricular ejection fraction (LVEF) were found in moderate and high PsA disease activity compared to low PsA disease activity and controls. PsA patients with GLS < 20 had higher body mass index (BMI), DAPSA score and uric acid levels, and lower adiponectin levels. Although patients with GLS < 20 had higher IL-17A levels, it was not statistically significant (P = 0.056). However, when we included healthy controls and analyzed differences based on a GLS cut-off of 20% in the entire population, the difference in IL-17A became statistically significant, 0.17 pg/mL (0.06–0.32) vs. 0.43 pg/mL (0.23–0.65), P = 0.017. The association between DAPSA score and GLS and IL-17 remained significant in multivariate analysis. Moreover, the association between GLS and IL-17 and adiponectin was significant after adjustment for age and BMI. Patients with moderate and high PsA disease activity have reduced myocardial function, lower adiponectin, and higher IL-17A levels.

P89 Real-world effectiveness of guselkumab in patients with psoriasis with and without concomitant psoriatic arthritis: retrospective data from the British Association of Dermatologists Biologics and Immunomodulators Register

Abstract Guselkumab is a monoclonal antibody that inhibits interleukin (IL)-23 signalling by binding to its p19 subunit and is approved to treat adults with moderate-to-severe plaque psoriasis and active psoriatic arthritis (PsA). BADBIR collects UK and Eire real-world observational data and includes patients receiving biologic treatments for psoriasis, with PsA being one of the recorded comorbidities at the time of enrolment. Absolute PASI (aPASI) scores can be used to quantify treatment effectiveness in routine clinical practice, and it has been suggested that an aPASI ≤ 2 represents a relevant disease endpoint to inform treat-to-target psoriasis-management strategies. This retrospective analysis evaluated the 1-year, real-world effectiveness of guselkumab on aPASI response in patients with moderate-to-severe plaque psoriasis and the subset of patients with and without concomitant PsA within BADBIR. Analyses were carried out on data collected up to the September 2021 data cutoff. Data were obtained from patients who had initiated guselkumab treatment and had recorded measurements for aPASI at baseline and 12-month follow-up was analysed. Measures of treatment effect for psoriasis included mean aPASI response, as well as the proportion of patients achieving an aPASI score of ≤ 1, ≤ 2, ≤ 3 and ≤ 5. Incomplete data collection limited the sample size of patients available for analysis. Five patients receiving guselkumab were excluded due to stopping treatment prior to the 12-month cutoff. Stratified by diagnosis, 36 (30.8%) patients had a concomitant diagnosis of PsA vs. 81 (69.2%) who did not. In the overall guselkumab-treated cohort (n = 117), mean (SD) aPASI at baseline and the following 12 months of treatment were 11.85 (8.95) and 2.45 (4.24), respectively. Following 12 months of guselkumab treatment in the cohort of patients with psoriasis (without concomitant PsA), 48 (59.3%) achieved an aPASI ≤ 1, 56 (69.1%) an aPASI ≤ 2, 64 (79.0%) an aPASI ≤ 3 and 69 (85.2%) an aPASI ≤ 5. In the concomitant PsA group, 19 (52.8%) achieved an aPASI score of ≤ 1, 22 (61.1%) achieved an aPASI score of ≤ 2, 28 (77.8%) achieved an aPASI ≤ 3 and 30 (83.3%) achieved an aPASI ≤ 5. Over 50% of guselkumab patients achieved an aPASI ≤ 1 at 12 months, supporting the effectiveness of targeting IL-23 with guselkumab for the treatment of psoriasis over 1 year. These results demonstrate that comparable responses were achieved for the treatment of psoriasis with guselkumab in patients with and without a concomitant PsA diagnosis within a real-world cohort.

Formulation Development and Evaluation of Apremilast Nanoemulsion

Apremilast is a selective phosphodiesterase 4 inhibitor administered orally in the treatment of moderate-to-severe plaque psoriasis and active psoriatic arthritis. It is classified as class IV drug as per BCS classification so it indicates low solubility and lower permeability through the skin. Therefore the objective of the research is to improve permeability of Apremilast through the skin and improve solubility by using oil and surfactant by formulating Nanoemulsion. Nanoemulsion was prepared by selecting Captex 355, Cremophore RH 40, Labrafil and Propylene glycol as the oil, surfactant,co-surfactant and co-solvent respectively after solubility study. Pseudo-ternary phase diagrams were constructed to find out the optimum ratio of oil: Smix (surfactant: co-Surfactant). Simple lattice design was applied to the optimization of the prepared nanoemulsion. The nanoemulsion was evaluated for Physical parameter, pH, Droplet size, zeta potential, in-vitro diffusion study etc. Results of Droplet size measurements, zeta potential and % drug diffusion indicated A5 batch optimized batch than other formulation of the nanoemulsion. So, optimized formulation further tested for Skin irritation study and stability study.The Apremilast loaded stable Nanoemulsion system was prepared and various process variables were evaluated. Batch A5 was selected as an optimized batch containing 10 % Captex 355, 40 % Smix (Cremophore RH 40 and Labrafil) and 50% water. Optimized batch was found to be stable after three month at ambient condition of temperature and humidity, giving reproducible results when evaluated.

More than skin-deep: visceral fat is strongly associated with disease activity, function and metabolic indices in psoriatic disease

ObjectiveTo compare body composition between patients with psoriatic disease (PsD), including cutaneous psoriasis (PsO) and psoriatic arthritis (PsA), and controls, and to explore associations between disease activity and measures of function and metabolic derangement.MethodsBody composition was assessed by air displacement plethysmography (ADP) and MRI-derived fat segmentation using an automated pipeline (FatSegNet). Function was assessed by Health Assessment Questionnaire (HAQ) and metabolic status by fasting lipid profile, insulin and adiponectin. Active and inactive PsO and PsA were defined by body surface area (BSA) and Psoriasis Area Severity Index (PASI) and minimal disease activity (MDA), respectively.ResultsThirty patients (median disease duration 15 years; median age 52 years) and 30 BMI-matched controls were enrolled. Compared with controls, all MRI-derived body composition parameters—whole-body volume, subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), abdominal adipose tissue (AAT), VAT/AAT and VAT/SAT—were higher in the PsD group, specifically, those with active disease. Body mass, body fat, whole-body volume and whole-body VAT were correlated with higher triglycerides, cholesterol:HDL (high-density lipoprotein), insulin resistance and lower adiponectin as well as higher HAQ and lower MDA.ConclusionsIn this pilot study, patients with PsD revealed excessive total adipose tissue and a greater volume of metabolically unfavourable ectopic fat, including VAT, compared with BMI-matched controls, which also correlated with HAQ, disease activity and overall dysmetabolism. We also provide the first evidence in patients with PsD for the clinical application of FatSegNet: a novel, automated and rapid deep learning pipeline for providing accurate MRI-based measurement of fat segmentation. Our findings suggest the need for a more integrated approach to the management of PsD, which considers both the metabolic and inflammatory burden of disease. More specifically, visceral fat is a surrogate marker of uncontrolled PsD and may be an important future target for both pharmacological and lifestyle interventions.

Resistin serum levels and its association with clinical profile and carotid intima-media thickness in psoriasis: a cross-sectional study

BackgroundPsoriasis is a protean disease associated with several comorbidities that may have increased levels of adiponectin such as resistin. This may affect the patients atherosclerotic risk. ObjectiveTo study resistin levels in a sample of Brazilian patients with psoriasis and its association with clinical profile, comorbidities, and carotid Intima-Media Thickness (cIMT). MethodsThis is a cross-sectional study of 119 individuals: 34 healthy controls and 85 patients with psoriasis, 42 of which with skin involvement only and 43 with psoriatic arthritis. Clinical and epidemiological data, measurement of PASI (Psoriasis Area Severity Index) and DAPSA (Disease Activity in Psoriatic Arthritis), lipid profile, cIMT by ultrasound were collected from medical records. Resistin serum levels were measured by ELISA. ResultsPatients with psoriasis had higher resistin levels (p=0.009) and worse cIMT (p=0.0002) than controls. In the psoriasis sample, no associations of resistin levels with epidemiological, clinical findings, and activity indexes were found. Resistin serum levels were associated with the presence of diabetes (p=0.008) and metabolic syndrome (p=0.01) and correlated with total cholesterol (r=0.26) and triglycerides (r=0.33) but not with cIMT. Study limitationsThis work is limited by its transversal design and by the limited number of patients included. ConclusionResistin serum levels are elevated in psoriasis patients. In this sample, clinical, epidemiological, and activity indexes were not linked to resistin serum levels, but atherosclerotic risk factors were.