Management Of Inflammatory Arthritis Research Articles

E010 Impact of rheumatologist ultrasound clinic on the management of inflammatory arthritis at a tertiary centre rheumatology department

Abstract Background/Aims Musculoskeletal ultrasound plays an important role in the assessment and management of inflammatory arthritis, enabling early diagnosis and prompt initiation of disease modifying therapy, as well as escalation of therapy as part of a treat-to-target strategy. It can help clinicians distinguish between true joint inflammation and non-inflammatory causes of increased pain scores. We reviewed our weekly rheumatology ultrasound clinic service where patients are referred to aid in clinical decision making. The study aimed to evaluate the cohort of patients attending the rheumatology ultrasound clinic at University Hospitals of Leicester, a busy tertiary centre, serving a multi-ethnic population, and to assess the impact of this clinic on the management of inflammatory arthritis in these patients. Methods Data was collected retrospectively from the ultrasound clinic at University Hospitals of Leicester between June 2022 and June 2023. Outcome measures included: date of scan request, date of scan, underlying disease, C - reactive protein (CRP), anti-CCP level, presence of radiographic erosions, presence of active synovitis or erosions on ultrasound, other rheumatologic disease and how the ultrasound findings changed the patient’s management. Results The total number of patients attending the clinic during the study period was 91. Of these, 70% were female and 30% male. Over the study period, 11.8% of patients did not attend their appointment. At the time of referral, 68% of patients had a CRP<5, 91% had a negative anti-CCP and 83% had no radiographic erosions. Following the scan, 13% of the patients had active synovitis, and 10% received at least one steroid injection. Interestingly, 86% had no active inflammation and no indication to escalate their disease modifying drug. In our patient cohort, 16% had pre-existing fibromyalgia. In all appointments, the clinician performing the scan showed the ultrasound images to the patient and explained the findings. Conclusion This ultrasound clinic is a key part of the treat-to-target strategy for inflammatory arthritis, enabling escalation of disease modifying therapy where indicated. It allows ultrasound guided and marked injections to be given when needed and identifies patients with non-inflammatory causes of increased pain scores, preventing patients from receiving unnecessary immunosuppression. Disclosure A. Mohammed Murad: None. A. Jubber: None. A. Moorthy: None.

Should All Patients Trial Subcutaneous Methotrexate Prior to Commencing Biologic Therapy? A Real World Study.

Methotrexate (MTX) is the bed rock of inflammatory arthritis management. However, intolerance is a limiting factor for drug optimisation and retention. There is data to suggest subcutaneous (SC) MTX is better tolerated. It is less clear whether this strategy is effective in those where the oral preparation is inefficacious and its potential to avoid escalation to biologic therapy. To analyse the reasons for switching to SC MTX in a real-world setting, clinical outcomes achieved and proportion requiring biologic prescription. A retrospective survey of patients prescribed SC MTX in a university teaching hospital identified 352 patients. 298 switched from oral to SC MTX- 164 stopped oral MTX due to side effects, 134 stopped due to inefficacy, and 54 started SC MTX as first line therapy. 103 patients progressed to biologic therapy. Rheumatoid arthritis (RA): DAS-28 improved from a mean of 4.06 (0.63-8.06) to 2.83 (0.14-7.32) following the switch (p<0.0001). Psoriatic arthritis (PsA): total joint count improved from a mean of 7 (0-42) to 2 (0-25) (p<0.0001). Swollen joint count improved from a mean of 2 (0-26) to 1 (0-6) (p=0.09). SC MTX is an effective solution for RA and PsA, irrespective of whether oral MTX is inefficacious or intolerable. Where oral MTX was ineffective, a switch to SC achieved low disease activity despite multi-morbidity, long disease course and protracted oral MTX exposure. This intervention prevented over two-thirds of patients requiring biologics. SC MTX is a durable strategy with excellent disease outcomes and substantial economic benefits.

The identification, goals and principles of difficult-to-treat inflammatory arthritis: a consensus statement

BackgroundDespite the recent advances in the management of inflammatory arthritis, a considerable proportion of arthritis patients remain symptomatic. This cohort has recently been identified as ‘difficult to treat’ (D2T). In view of the limited evidence base, management of these patients has been a challenge particularly in view of its associated significant economic health burden. A better understanding of the D2T may help recognise or develop new therapeutic targets and facilitate earlier intervention in the disease course to prevent the progression of such condition.The aim of this work is to address the unmet needs in the management of D2T arthritis and develop a comprehensive approach towards the identification and proper assessment of those patients.ResultsAt the completion of round 3 Delphi process, a total of 20 items were obtained and divided into 5 domains. From 88.9 to 100% of respondents agreed with the recommendations (ranks 7–9). All 20 of the clinical standards that the scientific committee identified were agreed upon in terms of wording, recommendation grade, and level of evidence (i.e. 75% of respondents strongly agreed or agreed).ConclusionD2T inflammatory arthritis remains a relevant clinical challenge, despite the endorsement of the treat-to-target approach and the availability of a broad range of targeted arthritis medications. This study provided a comprehensive definition of the condition to facilitate the identification of this patients’ group. It also highlighted the goals and principles aiming at providing an effective framework for D2T assessment, closely monitor and set up a strategy to intervene in standard clinical practice.

Prioritization of clinical questions for the Australian Living Guideline for the Pharmacological Management of Inflammatory Arthritis.

Living guidelines aim to reduce delays in translating new knowledge into practice by updating individual recommendations as soon as relevant new evidence emerges. We surveyed members of the Australian Rheumatology Association (ARA) to develop a list of priority questions for the Australian Living Guideline for the Pharmacological Management of Inflammatory Arthritis (ALG) and to explore clinicians' use of clinical practice guidelines. An electronic survey of ARA members was performed in two phases. The first survey contained questions about current guideline use and beliefs and invited participants to submit at least three questions relevant to the management of rheumatoid arthritis (RA). In the second round, participants selected 10 questions they considered to be the highest priority from the collated list and ranked them in priority order. The sum of ranks was used to generate a final priority list. There were 115 (21%) and 78 (14%) responses to the first and second survey rounds respectively. 87% of respondents use existing rheumatology guidelines in their usual practice, primarily EULAR guidelines. Most respondents favored the development of Australian rheumatology guidelines. In total, 34 potential recommendation topics were identified and ranked in order of priority. A list of 34 clinical questions about RA management, ranked in order of importance by clinicians, has informed the development of the ALG. Similar prioritization exercises in other contexts may permit guidelines to be tailored to the needs of guideline users in their specific context, which may facilitate international collaboration and promote efficient translation of evidence to practice.

AKT question relating to management of inflammatory arthritis

AKT question relating to management of inflammatory arthritis

AKT answer relating to management of inflammatory arthritis

AKT answer relating to management of inflammatory arthritis

AB1623 INFLAMMATORY RHEUMATISM AND WORK: WHAT DIFFICULTIES IN RELATION WITH THE CHARACTERISTICS OF THE JOB?

BackgroundDespite improvements in the management of inflammatory arthritis (IA), the disease still has a significant impact on work and the support for patients with professional difficulties remains insufficient. Occupational physicians and occupational health specialists are not all aware of the specific impact of IA on difficulties at work and sometimes think that all patients complaining of physical limitations are identical and require the same support.ObjectivesThe objective of the study is to better understand the difficulties at work, in particular difficulties related to the employment characteristics of patients with IA.Methods32 individual semi-directed interviews and 2 group interviews were conducted with patients with IA recruited in consultations or by patient associations. The participants were recruited according to a.purposive sampling with maximum variation. Inclusion criteria were: age 18 to 65 years, have IA, be professionally active, have difficulties or concerns at work due to the disease. The interviews.were conducted with an interview guide and were recorded and transcribed in full. The thematic analyses were conducted using an inductive approach.ResultsThe analysis of difficulties related to the characteristics of the employment of patients with IA are numerous: physical load of the workstation; speed required by the job; simultaneous tasks; multiple tasks and flexibility; workload; working hours and schedules; routine, scheduling, commuting, job awareness, responsibilities and moral demands; cognitive characteristics; conflict of values; skills and experience; interpersonal characteristics; lack of material resources, inappropriate premises; autonomy, environment and culture of the company; productivity demands and evaluations,job insecurity or security; perceived maladjustment; isolation; lack of recognition.The difficulties are not always specific to patients with IA but are clearly aggravated by the disease for a good number of them. The patients describe the specificities of their difficulties.ConclusionPatients discuss multiple characteristics of employment that can be a hardship or an advantage. They explain how the disease makes these characteristics difficult for them. These data will be useful to occupational health occupational health professionals and clinicians to help patients keep their jobs in good condition and develop appropriate services.These data will help to improve the training of occupational health occupational and to develop a questionnaire for the assessment of the work situation of patients with IA.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsAnne-Christine Rat Speakers bureau: Pfizer, Lilly, Sanofi Genzyme, Abbvie, BMS, Galapagos, novartis, Isabelle Thaon: None declared, Deboreh Loyal: None declared.

Australian recommendations on perioperative use of disease-modifying anti-rheumatic drugs in people with inflammatory arthritis undergoing elective surgery.

Disease-modifying anti-rheumatic drugs (DMARDs) are effective treatments for inflammatory arthritis but carry an increased risk of infection. For patients undergoing surgery, there is a need to consider the trade-off between a theoretical increased risk of infection with continuation of DMARDs perioperatively versus an increased risk of disease flare if they are temporarily withheld. We used the Grading of Recommendations Assessment, Development and Evaluation methodology to develop recommendations for perioperative use of DMARDs for people with inflammatory arthritis undergoing elective surgery. The recommendations form part of the National Health and Medical Research Council-endorsed Australian Living Guideline for the Pharmacological Management of Inflammatory Arthritis. Conditional recommendations were made against routinely discontinuing conventional synthetic and biologic (b) DMARDs in the perioperative period but to consider temporary discontinuation of bDMARDs in individuals with a high risk of infection or where the impact of infection would be severe. A conditional recommendation was made in favour of temporary discontinuation of targeted synthetic DMARDs in the perioperative period.

OA19 Incidence and management of inflammatory arthritis in England before and during the COVID-19 pandemic: a population-level cohort study using OpenSAFELY

Abstract Background/Aims The impact of the pandemic on the incidence and management of inflammatory arthritis (IA) is not understood. Routinely-captured data in secure platforms, such as OpenSAFELY, offer unique opportunities to understand how IA was impacted upon by the pandemic. Our objective was to use OpenSAFELY to assess the effects of the pandemic on diagnostic incidence and care delivery for IA in England, and replicate key metrics from the National Early Inflammatory Arthritis Audit. Methods With the approval of NHS England, we used primary care and hospital data for 17 million adults registered with general practices using TPP health record software, to explore the following outcomes between 1 April 2019 and 31 March 2022: 1) incidence of IA diagnoses (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, undifferentiated IA) recorded in primary care; 2) time to first rheumatology assessment; 3) time to first prescription of a conventional synthetic DMARD (csDMARD) in primary care, and choice of first csDMARD. Results From 17,683,500 adults (representing 40% of the English population), there were 31,280 incident IA diagnoses recorded between April 2019 and March 2022. New IA diagnoses decreased by 39.7% in the early months of the pandemic. Overall, a 20.3% decrease in IA diagnoses was seen in the year commencing April 2020, relative to the preceding year (5.1 vs. 6.4 diagnoses per 10,000 adults, respectively). Further decreases coincided with rising COVID-19 numbers, before returning to pre-pandemic levels by the end of the study period. No rebound increase in IA incidence was observed as of April 2022. The median time from referral to first rheumatology assessment was shorter during the pandemic (18 days; IQR 8-35 days) than before (21 days; 9-41 days). The proportion of patients prescribed csDMARDs in primary care was comparable to before the pandemic; however, fewer people were prescribed methotrexate or leflunomide, and more were prescribed sulfasalazine or hydroxychloroquine. Conclusion IA diagnoses decreased markedly during the early phase of the pandemic; however, the impact on rheumatology assessment times and DMARD prescribing was less marked than might have been anticipated. This study demonstrates the feasibility of using routinely-captured, near real-time data in the secure OpenSAFELY platform to benchmark care quality on a national scale, without the need for manual data collection. Disclosure M.D. Russell: Honoraria; Lilly, Menarini, Biogen. Other; Lilly, Pfizer, Janssen, UCB. J.B. Galloway: Honoraria; Abbvie, Biovitrum, BMS, Celgene, Chugai, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi, UCB. C.D. Andrews: None. B. MacKenna: None. B. Goldacre: Grants/research support; Laura and John Arnold Foundation, NIHR, Mohn-Westlake Foundation, Wellcome Trust, Good Thinking Foundation, Health Data Research UK, Health Foundation, World Health Organisation, UKRI, Asthma UK, British Lung Foundation, and National Core Studies programme. A. Mehrkar: Other; Former employee and interim CMO of NHS Digital, and RCGP representative on GP Data Professional Advisory Group to NHS Digital. H.J. Curtis: None. B. Butler-Cole: None. T. O'Dwyer: None. S. Qureshi: Grants/research support; BMS. J.M. Ledingham: Other; Clinical director for NEIAA, Secretary for The Federation of Joint Royal Colleges of Physicians SCE Board, and trustee of the BSR. A. Mahto: Honoraria; Abbvie, Galapagos. Other; Lilly. A.I. Rutherford: Other; Lilly. M.A. Adas: None. E. Alveyn: None. S. Norton: None. A.P. Cope: Consultancies; BMS, Abbvie, GSK/Galvini. Member of speakers’ bureau; BMS, Abbvie. Grants/research support; BMS. Other; Executive committee of the EULAR research centre. K. Bechman: Grants/research support; Versus Arthritis and Pfizer Global Medical Grants.

Balancing the evidence: An update on analgesic use in rheumatic and musculoskeletal diseases

Pain management has been a challenging issue for people living with rheumatic and musculoskeletal diseases (RMDs) and health professionals for decades. Pharmacological treatments remain a core element of pain management of inflammatory arthritis and osteoarthritis. Yet balancing the benefits/harms in pain management within RMDs can be difficult to navigate due to limited effective options, and emerging adverse events in a population where individual risk is important to consider due to patient multimorbidity, immunosuppression and polypharmacy. Paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) analgesics are widely used among RMD patients, however both classes of drugs have been associated with new safety concerns in the last two decades. Perhaps as a result in combination with multifactorial influences, opioid prescribing has increased from the 2000s–2010s in the majority of RMD focussed studies, accompanied with a rising trend of long-term opioid use, despite limited evidence on efficacy. Gabapentinoids have also shown increasing trends more recently, despite an unclear role in chronic pain management for RMDs within current guidelines. Antidepressants are recommended as the first line of pharmacological treatment of chronic primary pain (e.g., fibromyalgia) by the latest National Institute for Health and Care Excellence (NICE) guideline released in April 2021. This concise narrative review will discuss pharmacological options for pain management, based on the latest evidence that includes the main analgesic drug classes: paracetamol, NSAIDs, opioids, antidepressants, and gabapentinoids. We will discuss the efficacy of these analgesics in RMDs and emerging safety concerns to enable more informed shared decisions with patients commencing such medications.

Incidence and management of inflammatory arthritis in England before and during the COVID-19 pandemic: a population-level cohort study using OpenSAFELY.

The impact of the COVID-19 pandemic on the incidence and management of inflammatory arthritis is not understood. Routinely captured data in secure platforms, such as OpenSAFELY, offer unique opportunities to understand how care for patients with inflammatory arthritis was impacted upon by the pandemic. Our objective was to use OpenSAFELY to assess the effects of the pandemic on diagnostic incidence and care delivery for inflammatory arthritis in England and to replicate key metrics from the National Early Inflammatory Arthritis Audit. In this population-level cohort study, we used primary care and hospital data for 17·7 million adults registered with general practices using TPP health record software, to explore the following outcomes between April 1, 2019, and March 31, 2022: (1) incidence of inflammatory arthritis diagnoses (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and undifferentiated inflammatory arthritis) recorded in primary care; (2) time to first rheumatology assessment; (3) time to first prescription of a disease-modifying antirheumatic drug (DMARD) in primary care; and (4) choice of first DMARD. Among 17 683 500 adults, there were 31 280 incident inflammatory arthritis diagnoses recorded between April 1, 2019, and March 31, 2022. The mean age of diagnosed patients was 55·4 years (SD 16·6), 18 615 (59·5%) were female, 12 665 (40·5%) were male, and 22 925 (88·3%) of 25 960 with available ethnicity data were White. New inflammatory arthritis diagnoses decreased by 20·3% in the year commencing April, 2020, relative to the preceding year (5·1 vs 6·4 diagnoses per 10 000 adults). The median time to first rheumatology assessment was shorter during the pandemic (18 days; IQR 8-35) than before (21 days; 9-41). The proportion of patients prescribed DMARDs in primary care was similar before and during the pandemic; however, during the pandemic, fewer people were prescribed methotrexate or leflunomide, and more were prescribed sulfasalazine or hydroxychloroquine. Inflammatory arthritis diagnoses decreased markedly during the early phase of the pandemic. The impact on rheumatology assessment times and DMARD prescribing in primary care was less marked than might have been anticipated. This study demonstrates the feasibility of using routinely captured, near real-time data in the secure OpenSAFELY platform to benchmark care quality on a national scale, without the need for manual data collection. None.

Anti-Arthritic and Anti-Inflammatory Effects of Andaliman Extract and Nanoandaliman in Inflammatory Arthritic Mice.

Inflammatory arthritis is a severe joint disease that causes long-lasting pain that reduces a patient's quality of life. Several commercial medicines have been used to reduce the inflammation in arthritis. However, they have side effects that affect other organs and increase the infection rate in the patient. Therefore, searching for alternative medicines from natural herbs to use as a substitute for chemical drugs and reduce the side effects of drugs has become the focus of investigation. Zanthoxylum acanthopodium DC., known as andaliman, is an endemic spice that originates from Tapanuli, North Sumatera (Indonesia). Our previous study confirmed that andaliman exerts anti-inflammatory and xanthin oxidase enzymatic inhibitory activities. Unfortunately, there are no in vivo studies on the efficacy of andaliman in reducing inflammation in arthritis. This research aimed to produce an andaliman extract rich in essential oils, to formulate andaliman extract in a nanoemulsion product, and to test their anti-arthritic and anti-inflammatory effects on suppressing the gene expression of inflammatory arthritis in vivo. Several steps were used to conduct this experiment, including andaliman extraction, bioactive compound identification, nanoandaliman formulation, in vivo inflammatory arthritis mice modeling using complete Freund's adjuvant (CFA), and gene expression quantification using quantitative PCR (qPCR). Andaliman extract and nanoandaliman effectively reduced arthritic scores in CFA-induced arthritic mice. Both treatments also demonstrated anti-inflammatory potential via blocking several arthritic inflammatory gene expressions from cartilage tissue and brain in CFA-induced mice. Nanoandaliman at low dose (25 mg/kg bw) exerted a higher suppressive effect against the gene expression of cox-2, il-ib, inos, and mmp-1 compared to that of andaliman extract. At high dose (100 mg/kg bw), andaliman extract effectively inhibited the expression of il-ib, inos, and mmp-1 genes in arthritic mice. These data suggest that nanoandaliman may be an alternative, natural anti-arthritic and anti-inflammatory candidate for the management of inflammatory arthritis.

Australian recommendations on tapering of biologic and targeted synthetic disease‐modifying anti‐rheumatic drugs in inflammatory arthritis

Biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) have been an important advance in the management of inflammatory arthritis, but are expensive medications, carry a risk of infection and other adverse effects, and are often perceived as a burden by patients. We used GRADE methodology to develop recommendations for dose reduction and discontinuation of b/tsDMARD in people with rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA) and psoriatic arthritis (PsA) who have achieved a low disease activity state or remission. The recommendations form part of the Australian Living Guideline for the Pharmacological Management of Inflammatory Arthritis, an NHMRC-endorsed 'living' guideline, in which recommendations are updated in near real-time as new evidence emerges. Conditional recommendations were made in favour of dose reduction in RA and AxSpA but not in PsA. Abrupt discontinuation of b/tsDMARD is not recommended in any of the three diseases.

Use of a bDMARD or tsDMARD for the management of inflammatory arthritis under checkpoint inhibitors: an observational study

ObjectiveThere is limited experience regarding the use of biological disease-modifying antirheumatic drug (bDMARD) and JAK inhibitor (JAKi) for the management of immune checkpoint inhibitors (ICI)-induced inflammatory arthritis. We aimed to...

Role of Lysine-Specific Demethylase 1 in Metabolically Integrating Osteoclast Differentiation and Inflammatory Bone Resorption Through Hypoxia-Inducible Factor 1α and E2F1.

Hypoxia occurs in tumors, infections, and sites of inflammation, such as in the affected joints of patients with rheumatoid arthritis (RA). It alleviates inflammatory responses and increases bone resorption in inflammatory arthritis by enhancing osteoclastogenesis. The mechanism by which the hypoxia response is linked to osteoclastogenesis and inflammatory bone resorption is unclear. This study was undertaken to evaluate whether the protein lysine-specific demethylase 1 (LSD1) metabolically integrates inflammatory osteoclastogenesis and bone resorption in a state of inflammatory arthritis. LSD1-specific inhibitors and gene silencing with small interfering RNAs were used to inhibit the expression of LSD1 in human osteoclast precursor cells derived from CD14-positive monocytes, with subsequent assessment by RNA-sequencing analysis. In experimental mouse models of arthritis, inflammatory osteolysis, or osteoporosis, features of accelerated bone loss and inflammatory osteolysis were analyzed. Furthermore, in blood samples from patients with RA, cis-acting expression quantitative trait loci (cis-eQTL) were analyzed for association with the expression of hypoxia-inducible factor 1α (HIF-1α), and associations between HIF-1α allelic variants and extent of bone erosion were evaluated. In human osteoclast precursor cells, RANKL induced the expression of LSD1 in a mechanistic target of rapamycin-dependent manner. Expression of LSD1 was higher in synovium from RA patients than in synovium from osteoarthritis patients. Inhibition of LSD1 in human osteoclast precursors suppressed osteoclast differentiation. Results of transcriptome analysis identified several LSD1-mediated hypoxia and cell-cycle pathways as key genetic pathways involved in human osteoclastogenesis. Furthermore, HIF-1α protein, which is rapidly degraded by the proteasome in a normoxic environment, was found to be expressed in RANKL-stimulated osteoclast precursor cells. Induction of LSD1 by RANKL stabilized the expression of HIF-1α protein, thereby promoting glycolysis, in conjunction with up-regulation of the transcription factor E2F1. Analyses of cis-eQTL revealed that higher HIF-1α expression was associated with increased bone erosion in patients with RA. Inhibition of LSD1 decreased pathologic bone resorption in mice, both in models of accelerated osteoporosis and models of arthritis and inflammatory osteolysis. LSD1 metabolically regulates osteoclastogenesis in an energy-demanding inflammatory environment. These findings provide potential new therapeutic strategies targeting osteoclasts in the management of inflammatory arthritis, including in patients with RA.

P029 Evaluating the uptake and impact of National Institute for Health and Care Excellence guidance on arthritis

Abstract Background/Aims National Institute for Health and Care Excellence (NICE) impact reports review how NICE recommendations for evidence-based and cost-effective care are being used in priority areas of the health and care system. Musculoskeletal (MSK) conditions, including arthritis, affect over 20 million people in the UK, and represent a significant burden of ill health, both to the individual and the wider healthcare system. This report summarises the progress made by the healthcare system in England towards implementing NICE’s suite of guidance on arthritis. Methods Published data collected from national audits, reports, surveys, journals and indicator frameworks was reviewed to provide insight on the uptake and impact of NICE’s recommendations and quality standards on osteoarthritis, rheumatoid arthritis and spondyloarthritis. Stakeholders were engaged to provide expert advice and an understanding of real-world experiences and working practices. A report was produced, including examples of NICE guidance in practice, patient quotes and outcomes data, alongside uptake data. The report highlights implementation gaps and considers what NICE will do next to support the system to improve uptake in these areas. Results Data were presented, focusing on the following topic areas: diagnosis and management of osteoarthritis, referral and diagnosis of inflammatory arthritis, and management of inflammatory arthritis. The report highlights areas of high uptake: significant progress has been made in reducing the number of unnecessary knee arthroscopies for people with osteoarthritis; Improvements are being made towards achieving rheumatology referral targets for people with suspected inflammatory arthritis, as well as ensuring pharmacological treatment is started promptly. There is an ongoing transition to the use of biosimilar drugs as a cost-saving measure. This has reduced rheumatology drug spend by over £80 million between 2017 and 2019;. There is high provision of education and support for people with arthritis, including access to specialist advice to manage flares. The report also highlights areas where there are gaps in implementation: there is a need for improved data collection on the diagnosis and management of osteoarthritis in primary care. There is a need for the increased provision of pre- and post-surgical physiotherapy and rehabilitation for people having joint surgery. There are severe delays in the referral and diagnosis of axial spondyloarthritis, highlighting the need to raise awareness of the condition in primary care, and in other specialist secondary care areas. There is a need to improve access to psychological services for people living with a long-term physical health condition. Conclusion Arthritis remains one of the most significant causes of disability in the UK. Evaluating the uptake of evidence-based guidance and improving implementation is central to improving outcomes. Throughout this report, we have identified areas of high and low uptake of NICE guidance and will work closely with stakeholders to address gaps in implementation. Disclosure J. Wray: None. J. Beveridge: None. V. Carter: None.

POSB99 The Cost-Effectiveness of Biologic/Targeted Synthetic/Biosimilar Disease Modifying Antirheumatic Drugs: A Systematic Review

The clinical efficacy of biologic/targeted synthetic/biosimilar disease modifying antirheumatic drugs (b/ts/biosimilar DMARDs) in treating inflammatory arthritis is well documented, while the economic performance of these agents remains vague. This systematic review aims to identify the updated evidence of b/ts/biosimilar DMARDs cost-effectiveness in the management of inflammatory arthritis to inform prescribing and formulary listing decisions.

P17 A case of treatment resistant severe destructive arthritis in a young boy

Case report - IntroductionMajor advances in medical and therapy management of inflammatory arthritis has been associated with marked improvement in outcomes. We present a very unusual case of a young boy with destructive and incapacitating arthritis of knees, feet and ankles refractory to such management. He is now wheelchair dependent. We have evidence of reversal of bone loss after treatment. However, synovitis and joint destruction has left few surgical options with above knee amputation considered to have the best long-term functional outcome.Case report - Case descriptionAge five, he had persistent pain and swelling of the right knee after a minor fall. In the emergency department a sclerotic, lucent area was highlighted on X-ray. Neoplasia was ruled out and the changes were felt to be a result of erosive arthropathy.By the time of rheumatology referral, symptoms progressed to significant bilateral knee effusions with left ankle inflammation. All three joints underwent steroid injections which had a good response, but unfortunately this was short-lived and they were repeated. A synovial biopsy was sent to exclude other pathologies and loose bone fragments were removed from both knees. Biopsy confirmed chronic inflammation and methotrexate was commenced. Unfortunately, there was minimal response.Over the next 5 years he trialled etanercept, infliximab, tocilizumab, pamidronate, azathioprine and abatacept. His destructive arthritis of the knees, ankles and feet continued to progress with relentless bone loss and associated osteochondritis dissecans (OCD).Opinions from five other tertiary rheumatology units worldwide, three radiology departments and four orthopaedic units were sought. Unable to control the synovitis and in the presence of complete loss of the lateral femoral condyle we elected to refocus our attention to bone integrity and preparation for definitive surgery. This included the use of denosumab. Serial radiology showed reversal of some bone loss over 2 years but surgical teams could not identify intervention to optimise weight-bearing capacity. Mobility deteriorated to leave our patient wheelchair dependent outside, using crutches or his knees to move around inside. Further surgical consideration has indicated the best long-term will be associated with above knee amputations.Case report - DiscussionOur team are aware of one less severe case in a 13-year-old male in Oxford that stabilised after 5 years, allowing definitive treatment with bilateral knee replacement followed by excellent recovery with full mobility. None of the international centres we contacted reported a case as severe as ours. From discussions with our paediatric and adult orthopaedic colleagues, the only comparable patients they have seen this level of bony knee destruction in has been uncontrolled haemophilia patients. However, the damage is not seen at such a young age which affects the surgical options due to ongoing growth in childhood and adolescence. This caused us to question; why was our patient so severely affected? Would a different treatment course have been feasible? And would this have changed the outcome?Despite trial of many immunomodulatory agents, both those routinely used for arthritis and those used in treatment resistance, the persistent inflammation and destruction progressed. As a result he developed persistent and problematic OCD. OCD is considered a relatively common diagnosis that can occur in adults and children of unclear aetiology. A small subchondral bone fragment becomes loose in the joint space as a result of disrupted blood supply. OCD seems to be more common in males and is often managed conservatively. In children, the knee is the most commonly affected joint and inflammation is hypothesised as a possible cause which we will elaborate on in our presentation. For cases requiring surgical intervention this is normally localised drilling, fixation or bone grafts; however, most cases only affect one site, with one loose fragment which was very different from our patient.Case report - Key learning pointsFrom this case we have been reminded that each patient follows a different clinical course and response to medications is difficult to predict. We have gained experience managing difficult inflammatory arthritis-related OCD working closely with our orthopaedic colleagues. Although we managed to control the destructive inflammatory process this did not reverse the damage to the patient’s joints and we have been left with no choice but to progress to surgical treatment options.By sharing this case we hope to learn from any similar experiences or challenges faced by other clinical teams to help inform our practice for any other cases in the future.

Development and Validation of Adherence Score for Subcutaneous Biologic Disease-Modifying Antirheumatic Drugs.

Background: The biologic disease-modifying antirheumatic drugs (bDMARDs) are currently incorporated as part of the pharmacotherapy management of inflammatory arthritis (IA). Adherence to bDMARDs is crucial to ensure treatment success in IA. However, most of the recent studies evaluated adherence level in patients using subcutaneous injections of bDMARDs utilized the indirect methods adapted from adherence assessment for oral medication. Aim: This study aimed to develop a questionnaire to assess adherence to the self-injectable subcutaneous bDMARDs. Methods: The development of the Subcutaneous bDMARDs Adherence Score (SCADS) involved evaluation of content validity. Literature reviews provide the basis for domain identification and item formation. Four experts evaluated the instrument by using a four-point ordinal scale with a rubric scoring on relevance, importance, and clarity of each item in measuring the overarching construct. The item-level content validity index (I-CVI) and the scale-level content validity index (S-CVI) were calculated. The factor structure and internal consistency reliability of SCADS were estimated using principal component analysis (PCA) and Cronbach’s alpha, respectively. Results: Both S-CVI/UA (universal agreement) and the average item-level content validity index (S-CVI/Ave) (average) for the entire instrument showed excellent criteria with a value of >0.90. Cronbach’s alpha coefficient value for SCADS was 0.707 indicating good internal consistency. All items showed corrected item-total correlation coefficients above 0.244. Questionnaire items with a factor loading of 0.30 or above were considered in the final factor solution. The factor analysis resulted in 3-factor solutions, which corresponded to 66.62% of the total variance. Conclusion: The SCADS is a consistent and reliable instrument for evaluating adherence among IA patients using the subcutaneous bDMARDs. It is simple to use, yet comprehensive but still requiring further clinical and international validation.

Structural optimization of HPMA copolymer-based dexamethasone prodrug for improved treatment of inflammatory arthritis

Despite their notorious adverse effects, glucocorticoids (GC, potent anti-inflammatory drugs) are used extensively in clinical management of rheumatoid arthritis (RA) and other chronic inflammatory diseases. To achieve a sustained therapeutic efficacy and reduced toxicities, macromolecular GC prodrugs have been developed with promising outcomes for the treatment of RA. Fine-tuning the activation kinetics of these prodrugs may further improve their therapeutic efficacy and minimize the off-target adverse effects. To assess the feasibility of this strategy, five different dexamethasone (Dex, a potent GC)-containing monomers with distinctively different linker chemistries were designed, synthesized, and copolymerized with N-(2-hydroxypropyl) methacrylamide (HPMA) to obtain 5 macromolecular Dex prodrugs. Their Dex releasing rates were analyzed in vitro and shown to display a wide spectrum of activation kinetics. Their therapeutic efficacy and preliminary toxicology profiles were assessed and compared in vivo in an adjuvant-induced arthritis (AA) rat model in order to identify the ideal prodrug design for the most effective and safe treatment of inflammatory arthritis. The in vivo data demonstrated that the C3 hydrazone linker-containing prodrug design was the most effective in preserving joint structural integrity. The results from this study suggest that the design and screening of different activation mechanisms may help to identify macromolecular prodrugs with the most potent therapeutic efficacy and safety for the management of inflammatory arthritis.