Abstract Objective The aim of this study was to assess the relationship between self-reported non-adherence, non-trough drug levels, immunogenicity and conventional synthetic DMARD (csDMARD) co-therapy in TNF inhibitor (TNF-i) drug response in PsA. Methods Serum samples and adherence questionnaires were collected at baseline, 3, 6 and 12 months for PsA patients prescribed TNF-i. Non-trough adalimumab (ADL) and etanercept (ETN) drug levels were measured at 3 and 6 months using commercially available ELISAs. Clinical response was assessed using PsA response criteria (PsARC) and change in 28-joint DAS (ΔDAS28) between baseline and 3, 6 and 12 months. Results In 244 PsA patients (52.5% ADL and 47.5% ETN), self-reported non-adherence was associated with PsARC non-response over 12 months using generalized estimating equation (GEE) modelling (P = 0.037). However, there was no significant difference between non-trough ADL or ETN drug levels based on self-reported non-adherence. Higher ETN levels at 3 months were associated with PsARC response at 3 (P = 0.015), 6 (P = 0.037) and 12 months (P = 0.015) and over 12 months using GEE modelling (P = 0.026). Increased ADL drug levels at 3 months were associated with greater ΔDAS28 at 3 months (P = 0.019). ADL anti-drug antibody-positive status was significantly associated with lower 3- and 6-month ADL levels (P < 0.001) and ΔDAS28 and PsARC response at 3, 6 and 12 months. Meanwhile, MTX co-therapy was associated with a reduction in immunogenicity at 3 and 6 months (P = 0.008 and P = 0.024). Conclusion Although both were associated with reduced response, the objectively measured non-trough drug levels showed more significant associations with drug response than self-reported non-adherence measures.
Abstract Background/Aims Opioid prescribing has increased considerably over the 15 years for chronic non-cancer pain in the UK, including for musculoskeletal conditions. Whilst there are national and international guidelines to reduce inappropriate opioid prescribing, these are not always adhered to in practice. Audit and feedback is a common intervention for supporting clinical behaviour change. Little is known if such tools have been used to support safer opioid prescribing to date. This systematic review aimed to describe audit and feedback tools that were designed, implemented and led to changes in opioid prescribing practices. Methods A systematic review of the literature was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework (PRISMA). Both Embase and MEDLINE were searched to identify studies that included audit and feedback tools in patients prescribed opioids with chronic non-cancer pain until the 31st of May 2021. Results Of the 539 studies imported, following removal of duplicates, 497 studies were screened. Following title and abstract review 6 full-text studies were assessed for eligibility. A total of three studies were deemed to meet inclusion criteria. Approaches found included: The Controlled Medication Advisory Board (CMAB), Systems Consultation and the Opioid Safety Initiative (OSI). CMAB involved the use of a dashboard to provide feedback to clinicians on referred patients. As a result the opioid prescribing rate per 100 patient visits decreased by 31% and the rate of co-prescription of benzodiazepines and opioids decreased by 56%. Systems Consultation involved the use of audit and feedback, academic detailing and external facilitation to reduce opioid prescribing. Systems consultation resulted in a statistically significant reduction in the morphine equivalent daily doses. The OSI used automatic electronic medical records auditing to enable clinic leaders to identify physician prescribing patterns via a dashboard. OSI enabled a 9.9% reduction in opioid prescriptions from 571,476 to 514,883. Conclusion Computerised audit and feedback tools may be effective interventions to support opioid stewardship initiative and promote safer opioid prescribing. Such approaches being used internationally could pave the way for similar initiatives in the UK and future research evaluating their impact on patient safety. Disclosure J. Feldman: None. M. Jani: Grants/research support; National Institute for Health and Care Research Advanced Fellowship (NIHR301413).
Executive Summary Pain is a common symptom in people with inflammatory arthritis (IA), which has far-reaching impacts on their lives. Recent electronic health record studies demonstrate that UK-based pain care in people with IA commonly involves the prescribing of long-term opioids and gabapentinoids, despite an absence of trial evidence for their efficacy. Patient surveys suggest that non-pharmacological pain management is underused. A UK-specific guideline on pain management for people with IA is required to resolve this. This scoping document outlines the context and prioritized clinical questions for the first British Society for Rheumatology (BSR) guideline on pain management for people with IA. The guideline aims to provide evidence-based recommendations on how pain can be best managed in people with IA (including its assessment, and pharmacological and non-pharmacological treatments), ensuring that people with IA in the UK are offered evidence-based pain management strategies. The guideline is for healthcare professionals involved in the care of people with IA of all ages and genders, people with IA and their families and carers, NHS managers and healthcare commissioners, and other relevant stakeholders such as patient organizations. It will be developed using the methods outlined in the BSR’s ‘Creating Clinical Guidelines’ protocol.
TNF-blocking agents, non-biological disease-modifying anti-rheumatic drugs (nbDMARDs) and non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed treatments in psoriatic arthritis. A large proportion of patients do not respond to these medications, although unfortunately clinically useful biomarkers that predict future response are currently lacking. Several candidate gene polymorphisms have been associated with responses to biologic therapies and nbDMARDs; however, replication and validation of these variants in large prospective psoriatic arthritis cohorts are required before translating these to clinical practice. In this review, we discuss the advances made in pharmacogenetics of treatment response in psoriatic arthritis to date, with focus on biologic therapies approved for use, nbDMARDs and NSAIDs, as well as outline emerging methodologies to obtain data that will help inform a future precision medicine approach in this condition.
Early career researchers (ECRs) across Europe face a number of challenges as highlighted by the European federation of education employers (EFEE) (1). Understanding the unmet needs of ECRs in rheumatology would allow development of targeted educational resources and support where required.
Objectives
To perform a Europe wide survey on the demographics of ECRs, current unmet needs and perceptions of possible solutions.
Methods
Clinical and non-clinical researchers who work in the field of rheumatology and under the age of 40, were invited to participate in an online-based survey. EMEUNET is a Europe-wide network of >2000 young researchers in rheumatology addressing educational needs and promoting research interests. Survey questions were devised and modified in collaboration with members of the EMEUNET education subgroup and steering committee. It was disseminated to EMEUNET members and national young rheumatology organisations. Participants were allowed to choose ≥1 answer options where applicable.
Results
339 participants’ anonymised responses were collected from 53 countries. The majority of participants were between 31-35 years (38.1%) and female (63.4%). Most were clinical researchers (including 33.3% rheumatology trainees) and 24.1% were non-clinical, including allied health professionals. The area of research of the participants was as follows: Epidemiology (40.0%), basic science/translational (39.6%), clinical trials (38.1%), imaging (17.7%), health services research (14.7%), other (7.5%). 48.6% did not feel they had adequate educational resources to develop their research skills locally. Obtaining grant funding as ECRs was deemed to be difficult (43.3%) or very difficult (31.4%) in their respective institutions/countries. Reasons listed are presented in figure 1. 98% were interested in developing new European collaborations in their research area either through: face to face interactions at conferences (82.1%), website forum (50.8%), email interactions (61.1%), teleconferences (43.5%). In addition, 93.7% felt they would apply for small European grants for ECRs, 81.6% would be interested in funding to spend short periods (4-8 weeks) at another European institute and 87.5% in focussed deep dive sessions on a topic of interest. The top 3 research skills that participants felt they would benefit from having more resources for as ECRs were: 1. Writing a study protocol (64.9%), 2. Writing a first grant application (64.0%), 3. Performing a systematic review (51.1%) (Figure 2).
Conclusion
A large proportion of ECRs in rheumatology felt they lack resources to develop their research skills locally. Small grant funding, research opportunities for pan-European collaborations, short periods of exchange to other institutes and targeted support to develop research skills can help address some of the current needs of ECRs.
References
[1] Supporting Early Career Researchers in Higher Education: Summary report Feb 2015 https://www.ucea.ac.uk/en/empres/rs/ecr.cfm
Abstract Objectives Interventions aimed at increasing TNF-α inhibitor serum drug levels (SDLs) may improve treatment response; however, previous studies suggesting SDL cut-offs have not accounted for treatment adherence. The aim of this study was to establish the relationship between adalimumab/certolizumab SDLs and EULAR good vs non-/moderate response and to define SDL cut-offs associated with good response in fully adherent patients. Methods In a prospective observational study, 475 patients with RA were treated with certolizumab (n = 192) or adalimumab (n = 283). At baseline and 3, 6 and 12 months, patients had 28-joint DAS, self-reported treatment adherence and SDLs measured. Fully adherent patients were analysed as a subgroup. Follow-up data at 3, 6 and 12 months were analysed separately. Median SDLs were compared in good vs non-/moderate response patients and receiver operating characteristics (ROC) curves were used to establish cut-off SDLs. Results Fully adherent good responders had significantly higher median adalimumab/certolizumab SDLs compared with non-/moderate responders (P = 0.04 and P = 0.0005, respectively). ROC analysis reported 3 month non-trough adalimumab SDLs discriminated good vs non-/moderate response with an area under the curve (AUC) of 0.63 (95% CI 0.52, 0.75), with a cut-off of 7.5 mg/l being 39.1% specific and 80.9% sensitive. Similarly, 3 month non-trough certolizumab SDLs discriminated good vs non-/moderate response with an AUC of 0.65 (95% CI 0.51, 0.78), with a cut-off of 26.0 mg/l being 43.9% specific and 77.8% sensitive. Conclusion In fully adherent patients, higher SDLs are detected in good responders, suggesting that interventions to improve SDLs, such as encouraging adherence, could improve treatment response. The 3 month non-trough SDL cut-offs of 7.5 mg/l for adalimumab and 26.0 mg/l for certolizumab may be useful in clinical practice.
TNF-α inhibitor (TNFi) therapies have transformed the treatment of several rheumatic musculoskeletal diseases. However, the majority of TNFi's are immunogenic and consequent anti-drug antibodies formation can impact on both treatment efficacy and safety. Several controversies exist in the area of immunogenicity of TNFis and drug safety. While anti-drug antibodies to TNFis have been described in association with infusion reactions; serious adverse events (AEs) such as thromboembolic events, lupus-like syndrome, paradoxical AEs, for example, vasculitis-like events and other autoimmune manifestations have also been reported. The expansion of the biologic armamentarium, new treatment strategies such as introduction/switching to biosimilars and cost-saving approaches such as TNFi tapering, may all have a potential impact on immunogenicity and clinical sequelae. In this review we evaluate how evolution of biologics relates to drug safety and immunogenicity, appraise relevant evidence from trials, spontaneous pharmacovigilance and observational studies and outline the areas of uncertainty that still exist.
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