Dennis McGonagle PhD FRCPI

Objective: New modes of action and more data on the efficacy and safety of existing drugs in psoriatic arthritis (PsA) required an update of the EULAR 2019 recommendations for the pharmacological treatment of PsA.Methods: Following EULAR standardised operating procedures, the process included a systematic literature review and a consensus meeting of 36 international experts, in April 2023. Levels of evidence and grades of recommendations were determined.Results: The updated recommendations comprise 7 overarching principles and 11 recommendations, and provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs should be used in monotherapy only for mild PsA and short-term; oral glucocorticoids are not recommended. In patients with peripheral arthritis, rapid initiation of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) is recommended, and methotrexate preferred. If the treatment target is not achieved with this strategy, a biological (bDMARD) should be initiated, without preference among modes of action. Relevant skin psoriasis should orient towards bDMARDs targeting IL-23p40, IL-23-p19, IL-17A and IL-17A/F inhibitors. In case of predominant axial or entheseal disease, an algorithm is also proposed. Use of Janus kinase-inhibitors is proposed primarily after bDMARD failure taking relevant risk factors into account, or in case bDMARDs are not an appropriate choice. Inflammatory bowel disease and uveitis, if present, should influence drug choices with monoclonal TNF inhibitors proposed. Drug switches and tapering in sustained remission are also …

Background/Aims Psoriatic arthritis (PsA) is a chronic disease affecting multiple domains; however, patients can experience loss of response with long-term therapy. Therefore, maintaining long-term treatment responses is important. Bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A, demonstrated rapid and clinically meaningful improvements in joint and skin efficacy outcomes to Week 16, vs placebo (PBO), that were sustained to Week 52. The objective of this analysis was to report maintenance of response in joint, skin and composite efficacy outcomes to 52 weeks in BKZ-treated patients with PsA who were Week 16 responders. Methods BE COMPLETE (NCT03896581), a 16-week double-blind phase 3 study, included patients with active PsA who had inadequate response or intolerance to 1-2 TNF inhibitors (TNFi-IR …

Background/Aims Psoriatic arthritis (PsA) is a chronic inflammatory arthritis characterised by heterogenous clinical features including peripheral arthritis, spondylitis, enthesitis, dactylitis, skin and nail disease. Historically, outcome measures in PsA trials focused on the articular manifestations of disease, with a recent emphasis in composite tools. The Psoriatic Arthritis Disease Activity Score (PASDAS) is a validated, composite measure with defined cut-off and excellent responsiveness when compared with other PsA-specific and non-specific composite measures. Although PASDAS is one of the recommended GRAPPA measures for research trials, data on its test-retest reliability are limited particularly in PsA of short disease duration. Aims and Objectives - To assess the test-retest reliability of the PASDAS composite index in a cohort of early, untreated PsA patients. Methods …

Psoriatic arthritis (PsA) is a multifaceted condition that can manifest with axial and peripheral joint involvement, enthesitis, dactylitis, and skin and nail disease. In particular, the accurate diagnosis of axial PsA (axPsA) remains problematic, even though a better understanding of its distinct immunopathogenesis from ankylosing spondylitis (AS) is now starting to emerge [1].Diagnosing PsA, especially the axial form, is hindered by significant diagnostic delays, leading to potentially irreversible segmental spinal fusion which is further complicated by the fact that axial PsA may be completely asymptomatic. Notably, skin psoriasis typically predates axial involvement, reinforcing the significance of recognising cutaneous signs as a potential early pointer to axial PsA in subjects with unexplained back pain. Nail psoriasis has consistently been identified as a key precursor of peripheral PsA, and more recently has also been …

ObjectivesTo investigate the prevalence of poly‐refractory RA defined as failure of all biologic (b)/targeted synthetic (ts)‐DMARDs. To further investigate whether Persistent inflammatory refractory RA (PIRRA) and non‐inflammatory refractory RA (NIRRA) patients, determined by objective ultrasound (US) synovitis, have distinct clinical phenotypes in both EULAR difficult‐to‐treat Rheumatoid Arthritis (D2T‐RA) and poly‐refractory RA groups.MethodsA cross‐sectional study of 1591 RA patients on biologic b/tsDMARDs that evaluated D2T‐RA criteria and subclassified as poly‐refractory if inefficacy/toxicity to at least one drug of all classes. PIRRA was defined if US synovitis in≥ 1 swollen joint (SJ) and NIRRA if absent. Univariate tests and multivariate logistic regression were conducted to investigate factors associated with poly‐refractory, PIRRA, and NIRRA phenotypes.Results122/1591 were excluded due to missing data. 247/1469 (16.8%) had D2T‐RA and only 40/1469 (2.7%) poly‐refractory RA. This latter group had higher DAS‐28‐CRP (median 5.4 vs 5.02, p< 0.05), CRP levels (median 13 vs 5mg/l, p< 0.01), and smoking (ever) rates (20% vs 4%, p< 0.01) compared to other D2T patients. Smoking was associated with poly‐refractory RA (OR= 5.067, 95% CI [1.774‐14.472], p= 0.002). Of 107 D2T‐RA patients with recent US, 61 (57%) were PIRRA and 46 (43%), NIRRA. NIRRA patients had elevated BMI (median 30 vs 26, p< 0.001) and higher fibromyalgia prevalence (15% vs 3%, p< 0.05), lower SJ count (median: 2 vs 5, p< 0.001) and lower CRP levels (5 vs 10, p< 0.01).ConclusionOnly 2.7% of D2T‐RA failed all classes of b/tsDMARDs …

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 …

Purpose (the aim of the study): Background and Objective: Synovial fluid mesenchymal stem cells (SF-MSCs) are elevated in osteoarthritis (OA) but synovial fluid hyaluronin prevents their adhesion to cartilage. Utilizing the stem cell-mobilizing device (STEM), our prior investigations demonstrated a substantial elevation in SF-MSCs via intraoperative synovial brushing, showcasing robust chondrogenesis potential without necessitating culture expansion. Noteworthy is the inadvertent removal of growth factors and SF-MSCs during standard arthroscopic procedures, including joint irrigation. This study aims to validate the potential of intraoperatively augmenting MSCs in joint cavity during microfracture arthroscopy, employing an innovative STEM device, and correlating this approach with enhanced joint repair, as evidenced by improved MRI cartilage outcomes at 6 and 12 months, along with patient-reported outcomes …

Background/Aims Nail psoriasis (PsO) is a strong predictor for the development of psoriatic arthritis (PsA) and has been reported in 63-83% of patients with PsA. Psoriatic nails are linked to arthritis in the adjacent distal interphalangeal joint (DIP) of fingers or interphalangeal joint of thumbs, and both can lead to severe functional impairment. In the SPIRIT-H2H study of adults with PsA, 354 of 566 participants had nail PsO and adjacent joint disease in at least one digit at baseline. At the group level, SPIRIT-H2H patients treated with ixekizumab (IXE) achieved significantly greater improvements in nail PsO compared to those treated with adalimumab (ADA). This analysis aimed to assess the treatment effects of IXE and ADA at the individual digit level among patients with PsA, nail PsO, and adjacent joint disease. Methods This post hoc analysis included 354 patients from SPIRIT …

Background/Aims Rapid access to magnetic resonance imaging (MRI) of the spine and sacroiliac joints is essential for the timely diagnosis of axial spondyloarthritis (axSpA). A recent NASS/BRITSpA national FOI survey highlighted deteriorating waiting times to access MRI for the assessment of inflammatory back pain in the UK, with only 73% of Trusts reporting access within 8 weeks, compared to 90% in 2017. In addition, NHS England and the Royal College of Radiologists have recently published a target of 28 days for turn-around time (TAT) for a verified report to be provided after image acquisition in any circumstance. Aims: To evaluate the usage of MRI performed under the “inflammatory back pain protocol” at a large tertiary centre, including the time from MRI request to scan being performed, TAT for reporting and whether this has changed over time. Methods A service …

Still’s disease is a rare inflammatory syndrome that encompasses systemic juvenile idiopathic arthritis and adult-onset Still’s disease, both of which can exhibit life-threatening complications, including macrophage activation syndrome (MAS), a secondary form of haemophagocytic lymphohistiocytosis. Genetic insights into Still’s disease involve both HLA and non-HLA susceptibility genes, suggesting the involvement of adaptive immune cell-mediated immunity. At the same time, phenotypic evidence indicates the involvement of autoinflammatory processes. Evidence also implicates the type I interferon signature, mechanistic target of rapamycin complex 1 signalling and ferritin in the pathogenesis of Still’s disease and MAS. Pathological entities associated with Still’s disease include lung disease that could be associated with biologic DMARDs and with the occurrence of MAS. Historically, monophasic, recurrent and …

Many children with pervasive developmental disorders (PDD) exhibit behaviors and symptoms of attention-deficit/hyperactivity disorder (ADHD). We sought to determine the relative efficacy of medications for treating ADHD symptoms in children with PDD by identifying all double-blind, randomized, placebo-controlled trials examining the efficacy of medications for treating ADHD symptoms in children with PDD. We located seven trials involving 225 children. A random effects meta-analysis of four methylphenidate trials showed methylphenidate to be effective for treating ADHD symptoms in children with PDD (ES = .67). Several adverse events were greater for children were taking methylphenidate compared to placebo. An individual trial of clonidine and two trials of atomoxetine suggest these agents may also be effective in treating ADHD symptoms in children with PDD.

Psoriatic arthritis (PsA) is a highly heterogeneous disease with involvement of multiple tissues, underpinned by complex pathogenesis. Despite major improvements in the range and availability of efficacious treatment options, including biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), 1 significant clinical unmet needs remain, with overall low rates of achievement of disease remission. 2 Furthermore, a divergence of response is often seen between tissues, particularly skin and joints, or poor response in the presence of comorbidities, including mental health and other factors, leading to a growing number of patients having ongoing symptoms and apparent difficult to treat or manage PsA. Similar to rheumatoid arthritis (RA), a proportion of PsA patients exhibit disease which is refractory or resistant to more than one class of b/tsDMARD. 3 4 The European Alliance of Associations …

ObjectiveSubjects with subclinical psoriatic arthritis (PsA), defined as the presence of arthralgia in psoriasis (PsO), are at higher risk of PsA but scant real-world data exist. Our aims were to (1) estimate the probability of PsA development in subclinical PsA, (2) characterise subclinical PsA symptoms and (3) determine the clinical patterns at PsA diagnosis.MethodsPatients with PsO, mainly subclinical PsA, were evaluated longitudinally in two European cohorts. The key outcome was new-onset PsA. Musculoskeletal symptoms including inflammatory and non-inflammatory symptoms before PsA diagnosis were collected. Occurrence of PsA was analysed with survival analysis and cumulative incidence functions (CIFs).Results384 patients with PsO were included with a mean follow-up of 33.0 (±20.9) months. 311 of 384 (80.9%) had subclinical PsA with a PsA incidence rate of 7.7 per 100 patient-years. Subclinical PsA …

Background/Aims Given the chronic nature of psoriatic arthritis (PsA), sustaining high levels of disease control with treatment is important. Assessing maintenance of response in patients that achieve treatment targets is of interest as loss of response can occur with long-term therapy. Bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated rapid, clinically meaningful joint and skin efficacy responses at Week (Wk) 16 versus placebo (PBO) in patients with PsA; responses were sustained to Wk52. We report the maintenance of response in joint and skin efficacy outcomes to 52 wks in BKZ-treated patients with PsA who responded at Wk16. Methods BE OPTIMAL (NCT03895203), which included a 16-wk double-blind, PBO-controlled period and a 36-wk active treatment-blind period, assessed BKZ in …

Background/Aims Among adults with psoriatic arthritis (PsA) in the SPIRIT H2H study, 65% had nail psoriasis (PsO) at baseline and of these, 96.2% had simultaneous distal interphalangeal joint (DIP) disease in ≥ 1 digits at baseline. This analysis describes the impact of ixekizumab (IXE) and adalimumab (ADA) on quality of life (QoL), function and joint pain. Methods This post-hoc analysis included patients from SPIRIT-H2H (NCT03151551) treated with either IXE or ADA who had simultaneous nail and DIP involvement (swelling or tenderness) in ≥ 1 digits at baseline. Nail PsO was measured using Nail Psoriasis Severity Index (NAPSI). Joint involvement was measured by tender/swollen joint count scores. Joint pain was measured by patient’s assessment of pain using Visual Analogue Scale (100 mm). QoL measures included Dermatology Life Quality Index (DLQI …

Objectives To evaluate enthesitis treatment response, including time to resolution and data from multiple enthesitis instruments, in patients with PsA treated with secukinumab or adalimumab for 52 weeks. Methods In this post hoc analysis of the EXCEED study, patients receiving secukinumab 300 mg or adalimumab 40 mg per the label were grouped by presence or absence of baseline enthesitis based on the Leeds Enthesitis Index (LEI) and the Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC). Efficacy was assessed according to several enthesitis-related instruments using non-responder imputation for the achievement of enthesitis resolution (LEI/SPARCC = 0), Kaplan–Meier analysis for time to resolution, and as-observed data for other outcomes. Results Enthesitis was present at baseline in 498 of 851 patients (58.5 …

Objective To conduct a systematic review of the effectiveness and safety of pharmacological treatments for adult-onset Still9s disease (AOSD). Methods Six databases, two trial registries and conference abstracts were searched from 2012 to February 2023 for studies of pharmacological interventions in people with AOSD. Outcomes were rates of remission and response, discontinuation of concurrent treatments, complications of AOSD and treatment-related adverse events. Risk of bias was assessed with the Cochrane RoB tool and the Joanna Briggs Institute tool for case series. Results 44 studies evaluated treatments, including non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and biologic DMARDs (bDMARDs). For bDMARDS, tocilizumab, anakinra and canakinumab had the most available data. Although three …

Objective The aim was to assess the use and drug survival of IL-17Ai in a real-world cohort of axial SpA (axSpA) and PsA patients. Methods Patients ever commenced on an IL-17Ai (secukinumab or ixekizumab) for axSpA or PsA at the Leeds Specialist Spondyloarthritis Service were identified. Demographics, IL-17Ai treatment length and reason for cessation were collected. Drug survival data were plotted as a Kaplan–Meier curve, with log rank test of median survival compared between axSpA and PsA. Cox regression analysis was performed to investigate the relationship between diagnosis and length of drug survival. Results In total, 228 patients (91 axSpA and 137 PsA) were exposed to IL-17Ai. Drug survival for all patients at 12 months was 69% (95% Confidence Interval (CI) 63, 75%) and at 24 months 60% (95% CI 54, 67%). In axSpA and PsA, drug …

AimsTo investigate the prevalence and distribution of bone erosions in an early psoriatic arthritis (PsA) population using conventional radiography (CR) and to explore the agreement between CR and ultrasound (US) detected bone erosions.MethodsNewly diagnosed, treatment naïve PsA patients fulfilling the ClASsification for Psoriatic Arthritis (CASPAR) classification criteria of ≤5 years symptom duration were recruited as part of the Leeds Spondyloarthropathy Register for Research and Observation and underwent CR and US examination of hands and feet.ResultsOverall, 4655 hand and feet joints were assessed in 122 patients. CR erosions were detected in 24.6% (n=30) with lowest prevalence seen below 8 months of symptoms (17.5% vs 24.3%>24 months). The number of erosions was higher on CR (1.55% (63/4,655); US 1.04% (34/3,270)), with 5th metatarsophalangeal (MTP) joint being the most affected …

Background/Aims Bimekizumab (BKZ), a humanised monoclonal IgG1 antibody that inhibits IL-17A and IL-17F, has demonstrated rapid efficacy in joint and skin outcomes for patients with active psoriatic arthritis (PsA) who are bDMARD-naïve (BE OPTIMAL; NCT03895203) and TNFi-inadequate responders (TNFi-IR) (BE COMPLETE; NCT03896581). Here we report longer-term PsA response criteria (PsARC) response, along with health-related quality of life (HRQoL) outcomes in BE OPTIMAL and BE COMPLETE. Methods BE OPTIMAL and BE COMPLETE were randomised multicentre, double-blind, placebo (PBO)-controlled, parallel-group, phase 3 trials. BE OPTIMAL included a 16-week (Wk) double-blind, PBO-controlled period and a 36-Wk active-treatment period. Patients were randomised (3:2) to receive BKZ 160mg Q4W, or PBO. At Wk16, PBO patients switched to BKZ …