Adalimumab or Etanercept as first line biologic therapy in Enthesitis related arthritis (ERA) - a drug-survival single centre study spanning 10 years

Objectives: To analyse and compare drug-survival of adalimumab and etanercept (and their biosimilars) in biologic-naïve patients with ERA (Enthesitis-Related Arthritis). // Methods: In this retrospective observational study, conventional statistics and machine-learning were applied to compare drug-survival (adalimumab, etanercept and their biosimilars initiated: 2009–2019) in ERA and identify determinants. The primary outcome was discontinuation of treatment due to primary- or secondary-failure and adverse drug-reactions. // Results: During the observation period, 99 of 188 patients with ERA on first-line TNF inhibitors (etanercept-n=108, adalimumab-n=80) discontinued their treatment (median survival-time 3.9years, 95%CI 2.6-4.9years). Adalimumab was associated with longer drug-survival compared to etanercept especially after an initial positive response, with the median time to treatment discontinuation 4.9years (95% CI 3.9–5.7) for adalimumab, compared to 2years (95%CI 1.4–4.0) for etanercept (HR of treatment-discontinuation-0.49, 95%CI 0.32–-0.75, p=0.001). Adjusted by propensity-score, adalimumab-methotrexate combination was associated with longer drug survival, compared to adalimumab-monotherapy (HR-0.41, 95%CI 0.20–0.85), etanercept-monotherapy (HR-0.28, 95%CI 0.15–0.53), and etanercept-methotrexate combination (HR-0.39, 95%CI 0.21–0.73). The presence of HLA-B27 was associated with longer drug-survival (HR-0.50, 95%CI 0.29–0.87) following an initial positive response. Higher-CRP at baseline was associated with higher rate of primary-failure (HR-1.68, 95%CI 1.08–2.62). Axial-ERA (sacroiliitis±spinal-involvement) was associated with poorer drug-survival for both primary- and secondary-failure (overall HR-2.03, 95%CI 1.22–3.40). Adjusted by propensity-score, shorter drug-survival was observed in patients with baseline-CRP≥12.15 mg/L, but only in the context of axial-ERA, not in peripheral-ERA (no sacroiliitis/spinal-involvement) (HR-2.28, 95%CI 1.13–-3.64). // Conclusion: Following an initial positive primary response, continuing methotrexate with adalimumab was associated with the longest drug-survival compared to adalimumab-monotherapy or etanercept-based regimens. Axial-ERA was associated with a poorer drug-survival. A CRP >12.15 in patients with axial-ERA was associated with a higher rate of primary-failure. Further prospective studies are required to confirm these findings

A simple, clinically usable whole-body MRI system of joint assessment in adolescents and young people with juvenile idiopathic arthritis

OBJECTIVE: To introduce and evaluate a simple method for assessing joint inflammation and structural damage on whole-body MRI (WBMRI) in juvenile idiopathic arthritis (JIA), which is usable in clinical practice. METHODS: The proposed system utilises post-contrast Dixon WBMRI scans. Joints are assessed for synovitis (grade 0–2) and structural damage (present/absent) at 81 sites. The synovitis grading is based on features including above-normal intensity synovial enhancement, synovial hypertrophy, joint effusion, subarticular bone marrow oedema and peri-articular soft tissue oedema. This system was evaluated in a prospective study of 60 young people (47 patients with JIA and 13 controls with non-inflammatory musculoskeletal pain) who underwent a WBMRI. Three readers (blinded to diagnosis) independently reviewed all images and re-reviewed 20 individual scans. The intra- and inter-reader overall agreement (OA) and the intra- and inter-reader Gwet’s agreement coefficients 2 (GAC2) were measured for the detection of a) participants with ≥1 joint with inflammation or structural damage and b) joint inflammation or structural damage for each joint. RESULTS: The inter-reader OA for detecting patients with ≥1 joint with inflammation, defined as grade 2 synovitis (G2), and ≥1 joint with structural damage were 80% and 73%, respectively. The intra-reader OA for readers 1–3 were 80–90% and 75–90% respectively. The inter-reader OA and GAC2 for joint inflammation (G2) at each joint were both ≥85% for all joints but were lower if grade 1 synovitis was included as positive. CONCLUSION: The intra- and inter-reader agreements of this WBMRI assessment system are adequate for assessing objective joint inflammation and damage in JIA

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Adverse childhood experiences and chronic pain in adults aged 86:findings from the Lothian Birth Cohort 1936

Background: Chronic pain, a major cause of disability, is prevalent in older people. Exposure to multiple adverse childhood experiences (ACEs) is associated with increased levels of chronic pain in later life. However, this association has not been investigated in people aged older than 80 years. Therefore, the primary objective of this study was to explore the relationship between ACEs and chronic pain in people with a mean age of 86 years, participants of the Lothian Birth Cohort 1936. Methods: A survey co-developed by researchers, clinicians and people with lived experience (PWLE) that assessed chronic pain and ACEs was completed by 229 participants (response rate 67%). Associations between ACE exposure and chronic pain were investigated using multinomial logistic regression. Results: Results showed that 58% reported chronic pain, with a higher prevalence in females. Furthermore, 69% of participants with chronic pain reported moderate or severe pain interference and 82% reported at least 1 ACE, with 25% indicating exposure to ≥4 ACEs. The most frequently reported exposure was community violence (48%). Males were more likely to report any ACE, physical neglect, bullying, and community violence. No significant association was found between ACEs and chronic pain status, severity, or interference in this cohort. Discussion: This study, the first to adapt ACE and chronic pain questionnaires with input from PWLE, suggests that the relationship between ACEs and chronic pain may be less relevant in people in their eighties compared to younger populations. These findings have implications for trauma-informed care and pharmacological treatment in older adults

Developing and Evaluating JIApp: Acceptability and Usability of a Smartphone App System to Improve Self-Management in Young People With Juvenile Idiopathic Arthritis

Background: Flare-ups in juvenile idiopathic arthritis (JIA) are characterized by joint pain and swelling and often accompaniedwith fatigue, negative emotions, and reduced participation in activities. To minimize the impact of JIA on the physical andpsychosocial development and well-being of young people (YP), it is essential to regularly monitor disease activity and sideeffects, as well as to support self-management such as adherence to treatment plans and engagement in general health-promotingbehaviors. Smartphone technology has the potential to engage YP with their health care through convenient self-monitoring andeasy access to information. In addition, having a more accurate summary of self-reported fluctuations in symptoms, behaviors,and psychosocial problems can help both YP and health care professionals (HCPs) better understand the patient’s condition,identify barriers to self-management, and assess treatment effectiveness and additional health care needs. No comprehensivesmartphone app has yet been developed in collaboration with YP with JIA, their parents, and HCPs involved in their care.Objectives: The objective of this study was to design, develop, and evaluate the acceptability and usability of JIApp, aself-management smartphone app system for YP with JIA and HCPs.Methods: We used a qualitative, user-centered design approach involving YP, parents, and HCPs from the rheumatology team.The study was conducted in three phases: (1) phase I focused on developing consensus on the features, content, and design ofthe app; (2) phase II was used for further refining and evaluating the app prototype; and (3) phase III focused on usability testingof the app. The interview transcripts were analyzed using qualitative content analysis.Results: A total of 29 YP (aged 10-23, median age 17) with JIA, 7 parents, and 21 HCPs were interviewed. Major themesidentified as the ones that helped inform app development in phase I were: (1) remote monitoring of symptoms, well-being, andactivities; (2) treatment adherence; and (3) education and support. During phase II, three more themes emerged that informedfurther refinement of the app prototype. These included (4) adapting a reward system to motivate end users for using the app; (5)design of the app interface; and (6) clinical practice integration. The usability testing during phase III demonstrated high rates ofoverall satisfaction and further affirmed the content validity of the app.Conclusions: We present the development and evaluation of a smartphone app to encourage self-management and engagementwith health care for YP with JIA. The app was found to have high levels of acceptability and usability among YP and HCPs and has the potential to improve health care and outcomes for this age group. Future feasibility testing in a prospective study willfirmly establish the reliability, efficacy, and cost-effectiveness of such an app intervention for patients with arthritis

Characteristics of refractory disease and persistent symptoms in inflammatory arthritis: Qualitative framework analysis of interviews with patients and health care professionals

ObjectivesThis study aims to explore patients' and clinicians' understanding and experiences of refractory disease (RD) and persistent physical and emotional symptoms (PPES) in patients with inflammatory arthritis (IA), namely rheumatoid arthritis or polyarticular juvenile idiopathic arthritis from their perspectives through interviews and/or focus groups.DesignA qualitative study was conducted, following a pragmatic epistemology approach with framework analysis employed.MethodsSemi-structured interviews or focus groups with IA patients (n = 25) and multi-disciplinary rheumatology HCPs (n = 32) were conducted at one time point to obtain participants respective understanding and experiences of managing RD/PPES, and its impact on the patient-professional relationship.ResultsThree key themes were identified from both patients and professionals' experiences of RD/PPES: (1) relevant treatment experiences, (2) symptoms (with or without inflammation) and (3) impact: physical, psychological and social. These themes included 28 specific categories that would be considered as components characterizing RD/PPES, most common to both patients and HCPs with six being patient-specific and only one HCP-specific. The specific biopsychosocial symptoms and impacts of RD/PPES pertain to pain, fatigue, stiffness, joint involvement and physical, psychological and social functioning and quality of life, covering disease-related distress, mobility and independence. Wider influential factors such as comorbidities, non-adherence, health/medication beliefs and behaviours and social support were also identified.ConclusionCommon persistent symptoms that have both mental and physical impact characterize RD/PPES in IA and therefore a more integrated holistic approach to treatment is needed from multi-disciplinary HCPs, including health psychologists