Treatment Of Inflammatory Arthritis Research Articles

Cost of lost productivity in inflammatory arthritis and osteoarthritis in the year before and after diagnosis: Aninception cohort study.

Existing studies on the cost of inflammatory arthritis (IA) and osteoarthritis (OA) are often cross-sectional and/or involve patients with various disease durations, thus not providing a comprehensive perspective on the cost of illness from the time of diagnosis. In this study, we therefore assessed the cost of lost productivity in an inception cohort of patients with IA and OA in the year before and after diagnosis. Employment status, monthly income, days absent from work, and presenteeism were collected at diagnosis and 1 year later to estimate the annual costs of unemployment, absenteeism, and presenteeism using human capital approach. Non-parametric bootstrapping was performed to account for the uncertainty of the estimated costs. Compared to patients with OA (n = 64), patients with IA (n = 102, including 48 rheumatoid arthritis, 19 spondyloarthritis, 23 psoriatic arthritis, and 12 seronegative IA patients) were younger (mean age: 52.3 vs. 59.5 years) with a greater proportion receiving treatment (99.0% vs. 67.2%) and a greater decrease in presenteeism score (median: 15% vs 10%) 1 year after diagnosis. Annual costs of absenteeism and presenteeism were lower in patients with IA than those with OA both in the year before (USD566 vs. USD733 and USD8,472 vs. USD10,684, respectively) and after diagnosis (USD636 vs. USD1,035 and USD6,866 vs. USD9,362, respectively). Both IA and OA impose substantial cost of lost productivity in the year before and after diagnosis. The greater improvement in productivity seen in patients with IA suggests that treatment for IA improves work productivity.

Clinician and patient views on janus kinase inhibitors in the treatment of inflammatory arthritis: a mixed methods study

BackgroundJanus kinase inhibitors (JAKi) are new targeted synthetic disease-modifying antirheumatic drugs (DMARDs) licenced in the UK to treat rheumatoid and psoriatic arthritides. Unlike currently often prescribed biological DMARDs, they target a different part of the inflammatory pathway and are taken orally. The aim of this study was to explore what UK-based rheumatology clinicians and inflammatory arthritis (IA) patients think about the awareness, prescription and use of JAKi; how they compare with biologics; and how the COVID-19 pandemic has affected how JAKi are viewed and prescribed.MethodsRheumatology clinicians and IA patients completed online surveys and participated in interviews/focus groups between September 2021 and January 2022. Survey data were analysed descriptively, and interview/focus group data underwent an inductive thematic analysis.Results66.6% of patients had at least some awareness of JAKi, 73.0% from their rheumatology team. Problems getting earlier access to these drugs were raised by some patients, with many being prescribed JAKi after multiple other therapies had failed. 91.5% of clinicians prescribed JAKi in keeping with their local guidelines, with 72.3% prescribing them frequently as a monotherapy. Some clinicians had lingering safety concerns over JAKi use. Despite experiencing side effects and knowing of possible long-term risks, patients felt overall the benefits of JAKi outweighed the risks. 39.3% of patients were ‘very satisfied’ on JAKi, compared with 25.0% on biologics. Patients on JAKi appreciated their short half-life when it comes to infections, and their convenience as an oral therapy. When JAKi were discontinued in patients, it was predominantly due to inefficacy and non-cardiovascular adverse events. The COVID-19 pandemic resulted in increased prescription of JAKi as an alternative to injections and infusions, primarily to avoid potentially exposing patients to the coronavirus. Some patients believed their JAKi may confer some protection against developing severe COVID-19.ConclusionJAKi are an effective treatment option for IA and are liked by patients. The COVID-19 pandemic appears to have impacted their prescription favourably. However, clinicians have safety concerns over JAKi use. Any decision to go on a JAKi should be informed and take into account individual patient risk factors, circumstances and preferences.

A systematic review and meta-analysis of the efficacy and safety of iguratimod in the treatment of inflammatory arthritis and degenerative arthritis.

To assess the efficacy and safety of iguratimod (IGU) in the treatment of inflammatory arthritis and degenerative arthritis. Initially, randomized controlled trials (RCTs) on using IGU in treating inflammatory arthritis and degenerative arthritis were systematically gathered from various databases up to February 2024. Subsequently, two researchers independently screened the literature, extracted data, assessed the risk of bias in included studies, and conducted a meta-analysis using RevMan 5.4 software. Fifty-four RCTs involving three inflammatory arthritis were included, including ankylosing spondylitis (AS), osteoarthritis (OA), and rheumatoid arthritis (RA). For AS, the meta-analysis results showed that IGU may decrease BASDAI (SMD -1.68 [-2.32, -1.03], P < 0.00001) and BASFI (WMD -1.29 [-1.47, -1.11], P < 0.00001); IGU may also decrease inflammatory factor [ESR: (WMD -10.33 [-14.96, -5.70], P < 0.0001); CRP: (WMD -10.11 [-14.55, -5.66], P < 0.00001); TNF-α: (WMD -6.22 [-7.97, -4.47], P < 0.00001)]. For OA, the meta-analysis results showed that IGU may decrease VAS (WMD -2.20 [-2.38, -2.01], P < 0.00001) and WOMAC (WMD -7.27 [-12.31, -2.24], P = 0.005); IGU may also decrease IL-6 (WMD -8.72 [-10.00, -7.45], P < 0.00001). For RA, the meta-analysis results showed that IGU may improve RA remission rate [ACR20: (RR 1.18 [1.02, 1.35], P = 0.02); ACR50: (RR 1.32 [1.05, 1.64], P = 0.02); ACR70: (RR 1.44 [1.02, 2.04], P = 0.04)] and decrease DAS28 (WMD -0.92 [-1.20, -0.63], P < 0.00001); IGU may also decrease inflammatory factors [CRP: (SMD -1.36 [-1.75, -0.96], P < 0.00001); ESR: (WMD -9.09 [-11.80, -6.38], P < 0.00001); RF: (SMD -1.21 [-1.69, -0.73], P < 0.00001)]. Regarding safety, adding IGU will not increase the incidence of adverse events. IGU might emerge as a promising and secure therapeutic modality for addressing AS, OA, and RA. Identifier PROSPERO: CRD42021289249.

The impact of anti-tumor necrosis factor alpha drugs on lipid profile of patients with rheumatoid arthritis or seronegative spondyloarthropathy

Background: Inflammatory arthritis is associated with abnormal levels of lipoprotein. The cause is considered to be inflammation. Recently, the use of biologic drugs in the treatment of inflammatory arthritis, especially rheumatoid arthritis (RA) and seronegative spondyloarthropathy, has increased. There are different results of the effect of these drugs on fat profile. Evaluate the impact of anti-tumor necrosis factor (TNF) alpha drugs on lipid profile of patients with RA or seronegative spondyloarthritis. Methods: In this cross-sectional descriptive study, 50 patients with rheumatoid arthritis or seronegative spondyloarthritis, who were candidates for TNF alpha treatment, were included in the study. After obtaining written consent, a checklist was completed for all patients including demographic information such as age, sex, height, weight, place of residence, level of education, type of disease, and lipid profile test results including total cholesterol, triglycerides (TG), low density lipoprotein (LDL) and high density lipoprotein (HDL) were recorded. Then the patients were treated and evaluated for fat profile after 3, 6, 9 months after receiving the relevant treatment regimen. The test results were recorded in checklists. After completing the study, the data were entered into the statistical package for the social sciences (SPSS) 24 software and analyzed. Results: The mean age of patients was 46.38±14.33 years. 54% of patients were female. 54% of patients had rheumatoid arthritis. 62% of patients were treated with Sinora. The results of this study showed that serum triglyceride levels increased during the study period and this increase was statistically significant but the trend of changes in serum cholesterol, HDL and LDL levels was not statistically significant. However, serum LDL levels measured in the ninth month increased significantly compared to the initial measurement. Conclusions: Results showed that there was a significant relationship between lipid profile changes and anti-TNF alpha consumption. Although decreased inflammation appears but other mechanisms may be involved in dyslipidemia.

Exploring the causal relationship between inflammatory cytokines and inflammatory arthritis: A Mendelian randomization study

ObjectivesPrevious studies have reported an association between inflammatory cytokines and inflammatory arthritis, including Ankylosing spondylitis (AS), rheumatoid arthritis (RA), and psoriatic arthritis (PsA). This study aims to explore the causal relationship between inflammatory cytokines and AS, RA, and PsA using Mendelian randomization (MR). MethodsWe conducted a bidirectional two-sample MR analysis using genetic summary data from a publicly available genome-wide association study (GWAS) that included 41 genetic variations of inflammatory cytokines, as well as genetic variant data for AS, RA, and PsA from the FinnGen consortium. The main analysis method used was Inverse variance weighted (IVW) to investigate the causal relationship between exposure and outcome. Additionally, other methods such as MR Egger, weighted median (WM), simple mode, and weighted mode were employed to strengthen the final results. Sensitivity analysis was also performed to ensure the reliability of the findings. ResultsThe results showed that macrophage colony-stimulating factor (MCSF) was associated with an increased risk of AS (OR = 1.163, 95 % CI = 1.016–1.33, p = 0.028). Conversely, high levels of TRAIL and beta nerve growth factor (β-NGF) were associated with a decreased risk of AS (OR = 0.892, 95 % CI = 0.81–0.982, p = 0.002; OR = 0.829, 95 % CI = 0.696–0.988, p = 0.036). Four inflammatory cytokines were found to be associated with an increased risk of PsA: vascular endothelial growth factor (VEGF) (OR = 1.161, 95 % CI = 1.057–1.275, p = 0.002); Interleukin 12p70 (IL12p70) (OR = 1.189, 95 % CI = 1.049–1.346, p = 0.007); IL10 (OR = 1.216, 95 % CI = 1.024–1.444, p = 0.026); IL13 (OR = 1.159, 95 % CI = 1.05–1.28, p = 0.004). Interleukin 1 receptor antagonist (IL-1rα) was associated with an increased risk of seropositive RA (OR = 1.181, 95 % CI = 1.044–1.336, p = 0.008). Similarly, genetic susceptibility to inflammatory arthritis was found to be causally associated with multiple inflammatory cytokines. Lastly, the sensitivity analysis supported the robustness of these findings. ConclusionsThis study provides additional insights into the relationship between inflammatory cytokines and inflammatory arthritis, and may offer new clues for the etiology, diagnosis, and treatment of inflammatory arthritis.

Predictors of inflammatory arthritis among new rheumatology referrals: a cross-sectional study.

Early diagnosis and treatment of inflammatory arthritis (IA) is essential to optimize disease control. We aimed to identify variables that distinguish IA from non-inflammatory arthropathy by performing a cross-sectional study of rheumatology referral letters and visit records. Further work describes time to assessment and documentation of variables within referral letters. We reviewed rheumatology referral letters and new patient visits over a 6-month period. The diagnosis of IA was based on the clinical judgement of the assessing rheumatologist. IA diagnoses included RA, SpAs, unspecified IA, PMR, crystalline arthropathies and remitting seronegative symmetrical synovitis with pitting oedema. Univariate analysis was performed for each variable. Multivariable logistic regression was performed on statistically significant variables. Of 697 patients referred for arthralgia, 25.7% were diagnosed with IA. Variables predictive of IA included tenderness and swelling on examination and ≥1 h of morning stiffness. Increasing arthralgia duration, fatigue and brain fog were negative predictors. The median time from referral to IA diagnosis was 55 days and 20.7% of these patients were seen within 6 weeks. Among referral letters, documentation of arthralgia duration, morning stiffness or joint examination findings was uncommon (31%, 20.5% and 56.7%, respectively). We identified positive and negative predictors of IA. Referral letters often missed key information required for the triaging process. Future efforts will be directed towards build a triaging tool to improve the referral quality and capture of those patients with IA who need earlier access to rheumatology care.

Prevention and treatment of inflammatory arthritis with traditional Chinese medicine: Underlying mechanisms based on cell and molecular targets.

Inflammatory arthritis, primarily including rheumatoid arthritis, osteoarthritis and ankylosing spondylitis, is a group of chronic inflammatory diseases, whose general feature is joint dysfunction with chronic pain and eventually causes disability in older people. To date, both Western medicine and traditional Chinese medicine (TCM) have developed a variety of therapeutic methods for inflammatory arthritis and achieved excellent results. But there is still a long way to totally cure these diseases. TCM has been used to treat various joint diseases for thousands of years in Asia. In this review, we summarize clinical efficacies of TCM in inflammatory arthritis treatment after reviewing the results demonstrated in meta-analyses, systematic reviews, and clinical trials. We pioneered taking inflammatory arthritis-related cell targets of TCM as the entry point and further elaborated the molecular targets inside the cells of TCM, especially the signaling pathways. In addition, we also briefly discussed the relationship between gut microbiota and TCM and described the role of drug delivery systems for using TCM more accurately and safely. We provide updated and comprehensive insights into the clinical application of TCM for inflammatory arthritis treatment. We hope this review can guide and inspire researchers to further explore mechanisms of the anti-arthritis activity of TCM and make a great leap forward in comprehending the science of TCM.

The impact of the COVID-19 pandemic on referrals to musculoskeletal services from primary care and subsequent incidence of inflammatory rheumatic musculoskeletal disease: an observational study.

The aim was to describe the impact of the COVID-19 pandemic upon referral patterns and incident diagnosis of inflammatory rheumatic and musculoskeletal diseases (iRMDs). UK primary care data were used to describe referral patterns for patients with musculoskeletal conditions. Trends in referrals to musculoskeletal services and incident diagnoses of iRMDs (specifically, RA and JIA) were described using Joinpoint Regression and comparisons made between key pandemic time periods. The incidence of RA and JIA reduced by -13.3 and -17.4% per month, respectively, between January 2020 and April 2020, then increased by 1.9 and 3.7% per month, respectively, between April 2020 and October 2021. The incidence of all diagnosed iRMDs was stable until October 2021. Referrals decreased between February 2020 and May 2020 by -16.8% per month from 4.8 to 2.4% in patients presenting with a musculoskeletal condition. After May 2020, referrals increased significantly (16.8% per month) to 4.5% in July 2020. The time from first musculoskeletal consultation to RA diagnosis and from referral to RA diagnosis increased in the early pandemic period [rate ratio (RR) 1.11, 95% CI 1.07, 1.15 and RR 1.23, 95% CI 1.17, 1.30, respectively] and remained consistently higher in the late pandemic period (RR 1.13, 95% CI 1.11, 1.16 and RR 1.27, 95% CI 1.23, 1.32, respectively), compared with the pre-COVID-19 pandemic period. Patients with underlying RA and JIA that developed during the pandemic might be yet to present or might be in the referral and/or diagnostic process. Clinicians should remain alert to this possibility, and commissioners should be aware of these findings, enabling the appropriate planning and commissioning of services.

Cannabinoids: new friends in bone fracture and in joint disease prevention?

n recent years the endocannabinoid system (ES) has been recognized to play an important role in the regulation of several physiological processes, including pain perception, appetite control, and motor function development. This system has recently been recognized to be present in bone and joint tissues, playing a role in the regulation of bone and joint physiology. The ES seems to play its role mainly by acting on its receptors and thanks to the demonstrated ability of bone cells to synthesize the principal endocannabinoids (i.e., anandamide and 2-arachidonoylglycerol), which can act on bone remodeling and metabolism. Cannabinoids have also been shown to be produced within synovial tissues, and recent studies have shown that cannabinoid receptor ligands are effective in the treatment of inflammatory arthritis. In recent years synthetic endocannabinoid-like compounds and phytocannabinoids, which are the principal components of Cannabis sativa, have also started to be studied as molecules that could play a role not only in bone physiology, but also in the pathogenesis of osteoporosis, the most common bone disease, and in the inflammatory processes underlying osteoarthritis. Accumulating evidence that cannabinoids and their receptors play an important role in bone metabolism and in the regulation of the immune response is now starting to show us the true future therapeutic potential of cannabinoids, and of the phytocannabinoids contained in Cannabis sativa, in the treatment of bone loss and joint diseases. Here we summarize the role of the cannabinoids and their receptors in bone metabolism, osteoporosis, and joint disease.

Safety and efficacy of probiotic supplementation in 8 types of inflammatory arthritis: A systematic review and meta-analysis of 34 randomized controlled trials.

ObjectiveTo evaluate Safety and efficacy of probiotic supplementation in inflammatory arthritis.MethodsThe literature on the treatment of inflammatory arthritis with probiotics has been collected in databases such as CNKI, Pubmed, Cochrane library, Embase, etc. The search time is for them to build the database until May 2022. The included literatures are randomized controlled trials (RCTs) of probiotics in the treatment of hyperuricemia and gout. The Cochrane risk assessment tool was used for quality evaluation, and the Rev Man5.3 software was used for meta-analysis.ResultsA total of 37 records were finally included, involving 34 RCTs and 8 types of autoimmune disease (Hyperuricemia and gout, Inflammatory bowel disease arthritis, juvenile idiopathic arthritis [JIA], Osteoarthritis [OA], Osteoporosis and Osteopenia, Psoriasis, rheumatoid arthritis (RA), Spondyloarthritis). RA involved 10 RCTs (632 participants) whose results showed that probiotic intervention reduced CRP. Psoriasis involved 4 RCTs (214 participants) whose results showed that probiotic intervention could reduce PASI scores. Spondyloarthritis involved 2 RCTs (197 participants) whose results showed that probiotic intervention improved symptoms in patients. Osteoporosis and Ostepenia involving 10 RCTs (1156 participants) showed that probiotic intervention improved bone mineral density in patients. Hyperuricemia and gout involving 4 RCTs (294 participants) showed that probiotic intervention improved serum uric acid in patients. OA involving 1 RCTs (433 participants) showed that probiotic intervention improved symptoms in patients. JIA involving 2 RCTs (72 participants) showed that probiotic intervention improved symptoms in patients. Inflammatory bowel disease arthritis involving 1 RCTs (120 participants) showed that probiotic intervention improved symptoms in patients. All of the above RCTs showed that probiotics did not increase the incidence of adverse events.ConclusionProbiotic supplements may improve Hyperuricemia and gout, Inflammatory bowel disease arthritis, JIA, OA, Osteoporosis and Osteopenia, Psoriasis, RA, Spondyloarthritis. However, more randomized controlled trials are needed in the future to determine the efficacy and optimal dosing design of probiotics.Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021286425, identifier CRD42021286425.

Troxerutin-Mediated Complement Pathway Inhibition is a Disease-Modifying Treatment for Inflammatory Arthritis.

Troxerutin (TXR) is a phytochemical reported to possess anti-inflammatory and hepatoprotective effects. In this study, we aimed to exploit the antiarthritic properties of TXR using an adjuvant-induced arthritic (AIA) rat model. AIA-induced rats showed the highest arthritis score at the disease onset and by oral administration of TXR (50, 100, and 200 mg/kg body weight), reduced to basal level in a dose-dependent manner. Isobaric tags for relative and absolute quantitative (iTRAQ) proteomics tool were employed to identify deregulated joint homogenate proteins in AIA and TXR-treated rats to decipher the probable mechanism of TXR action in arthritis. iTRAQ analysis identified a set of 434 proteins with 65 deregulated proteins (log2 case/control≥1.5) in AIA. Expressions of a set of important proteins (AAT, T-kininogen, vimentin, desmin, and nucleophosmin) that could classify AIA from the healthy ones were validated using Western blot analysis. The Western blot data corroborated proteomics findings. In silico protein–protein interaction study of tissue-proteome revealed that complement component 9 (C9), the major building blocks of the membrane attack complex (MAC) responsible for sterile inflammation, get perturbed in AIA. Our dosimetry study suggests that a TXR dose of 200 mg/kg body weight for 15 days is sufficient to bring the arthritis score to basal levels in AIA rats. We have shown the importance of TXR as an antiarthritic agent in the AIA model and after additional investigation, its arthritic ameliorating properties could be exploited for clinical usability.

Intra-articular injection of biologic anti-rheumatic drugs enhances local exposure to the joint-draining lymphatics

Recent reports have highlighted the role of the lymphatic system and its resident immune cells in the development of inflammatory arthritis. Directing therapeutics to the joint-draining lymphatics could improve access to lymphatic-resident pro-inflammatory immune cells, improve local treatment efficacy and enable the administration of lower drug doses to achieve the same or a better effect. Here, we assessed the delivery of disease modifying anti-rheumatic drugs (DMARDs) to the joint-draining lymphatics as a function of therapeutic size and route of administration (intravenous (IV), subcutaneous (SC) and intra-articular (IA) injection). The model drugs included the low molecular weight conventional DMARD methotrexate and the larger biologic DMARDs etanercept and rituximab. Plasma pharmacokinetics, thoracic lymph fluid concentrations and lymph node deposition of the DMARDS were assessed in male Sprague-Dawley rats after IV, IA or SC injection at or near the knee joint. Administration by IA injection resulted in rapid and higher absorption of all drugs into the systemic circulation, compared to SC administration. The large DMARDs etanercept and rituximab were preferentially transported from the IA and SC injection sites via the lymphatics, but a greater percentage of the absorbed dose was recovered in lymph after IA (49–58%) compared to SC administration (17–20%). Methotrexate was almost exclusively transported from the injection site via the blood after IA injection, consistent with its small size which presents minimal barriers to diffusion across the synovium into blood vessels. Importantly, IA but not SC administration resulted in biologic DMARD access to the knee joint-draining iliac lymph fluid and iliac lymph node that is dysfunctional in inflammatory knee arthritis. Overall, IA injection of biologic DMARDs may provide a simple strategy to improve lymph and lymph node access and thus the treatment of inflammatory arthritis.

METHODS - A randomised controlled trial of METhotrexate to treat Hand Osteoarthritis with Synovitis: study protocol for a randomised controlled trial

BackgroundHand osteoarthritis is a common and disabling problem without effective therapies. Accumulating evidence suggests the role of local inflammation in causing pain and structural progression in hand osteoarthritis, and hand osteoarthritis with synovitis is a commonly encountered clinical phenotype. Methotrexate is a well-established, low-cost, and effective treatment for inflammatory arthritis with a well-described safety profile. The aim of this multicentre, randomised, double-blind, placebo-controlled trial is to determine whether methotrexate reduces pain over 6 months in patients with hand osteoarthritis and synovitis.MethodsNinety-six participants with hand osteoarthritis and synovitis will be recruited through the Osteoarthritis Clinical Trial Network (Melbourne, Hobart, Adelaide, and Perth), and randomly allocated in a 1:1 ratio to receive either methotrexate 20 mg or identical placebo once weekly for 6 months. The primary outcome is pain reduction (assessed by 100 mm visual analogue scale) at 6 months. The secondary outcomes include changes in physical function and quality of life assessed using Functional Index for Hand Osteoarthritis, Australian Canadian Osteoarthritis Hand Index, Health Assessment Questionnaire, Michigan Hand Outcomes Questionnaire, Short-Form-36, tender and swollen joint count, and grip strength, and structural progression assessed using progression of synovitis and bone marrow lesions from magnetic resonance imaging and radiographic progression at 6 months. Adverse events will be recorded. The primary analysis will be by intention to treat, including all participants in their randomised groups.DiscussionThis study will provide high-quality evidence to address whether methotrexate has an effect on reducing pain over 6 months in patients with hand osteoarthritis and synovitis, with major clinical and public health importance. While a positive trial will inform international clinical practice guidelines for the management of hand osteoarthritis, a negative trial would be highly topical and change current trends in clinical practice.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000877381. Registered 15 June 2017, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373124

Health-Care and Societal Costs Associated with Non-Persistence with Subcutaneous TNF-α Inhibitors in the Treatment of Inflammatory Arthritis (IA): A Retrospective Observational Study.

ObjectiveA few studies have suggested that patients with inflammatory arthritis (IA) who remain persistent with subcutaneous TNF-α inhibitors (SC-TNFi) incur lower health care costs than patients who discontinue treatment, whereas data on the impact of non-persistence on indirect costs are largely lacking. Furthermore, existing estimates are based on fixed follow-ups, in relation to treatment initiation, and therefore do not measure costs in direct relation to treatment discontinuation. Therefore, by capturing costs in direct relation to treatment discontinuation, this study aimed to estimate direct and indirect costs associated with non-persistence with SC-TNFis in IA.MethodsAdult Swedish biologic-naïve IA patients initiating biologic treatment with a SC-TNFi (adalimumab, etanercept, certolizumab or golimumab) between May 6, 2010, and December 31, 2017, were identified in population-based registers with almost complete coverage. IA was defined as a diagnosis of rheumatic arthritis, ankylosing spondylitis/unspecified spondyloarthritis or psoriatic arthritis. Non-persistent patients were matched on propensity score to patients persistent with treatment by at least an additional 12 months. This enabled comparisons of direct healthcare costs and indirect costs for sick leave and disability pension, respectively, 12 months before and 12 months after treatment discontinuation.ResultsA balanced cohort of 486 matched pairs was generated. The total direct and indirect costs were significantly higher among non-persistent patients already during the 12 months before index ($20,802 [18,335–23,429] vs. $16,600 [14,331–18,696]). However, while non-persistent patients increased their total direct and indirect costs, persistent patients significantly decreased the same, further widening the difference in costs during the 12-month period after index date ($22,161 [19,754–24,556] vs. $13,465 [11,415–15,729]).ConclusionsAmong biologic-naïve Swedish IA patients treated with SC-TNFis, persistent patients incurred about 40% lower aggregated direct and indirect costs compared to non-persistent patients the year following SC-TNFi discontinuation. This highlights the impact of treatment persistence from an economic viewpoint, adding further aspects to the clinical perspective.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01970-w.

O03 Continuation of golimumab (anti-TNF) in a patient with SpA and low-risk prostate cancer, what is the right decision?

Case report - IntroductionGolimumab is an anti-TNF alpha drug used in the treatment of inflammatory arthritis including spondyloarthritis (SpA). The introduction of this drug class has revolutionised the treatment of SpA over the last 20 years with significantly improved patient outcomes.Despite their treatment benefits multiple adverse effects of TNF-alpha inhibition have been reported through clinical trials including a possible increased risk of malignancy.We describe a case of a patient with known ankylosing spondylitis (AS) on golimumab who was diagnosed with low-grade prostate carcinoma and discuss the factors taken into consideration in guiding our decision-making process regarding ongoing treatment. Case report - Case descriptionA 57-year-old gentleman with known AS presented to the rheumatology clinic for routine review. His AS was well controlled, and he had been taking golimumab for the past 3 years. Upon review he was in clinical remission with a CRP <1 and ESR 5. Prior to the initiation of anti-TNF therapy his disease had been poorly controlled. However, following commencement his symptoms had significantly improved and he was able to work as a professional sports coach whilst bringing up a young family.On review he had recently been diagnosed with low-risk cancer of the prostate by his urologist. A prostate biopsy found Gleason 3 + 3 adenocarcinoma involving 2 out of 22 cores on each side, with a prostate specific antigen (PSA) of 3.95ng/ml. An MRI had shown chronic prostatitis. He was in the lowest risk category of grade group 1 prostate cancer and no treatment for his prostate cancer was indicated. The plan from his urology team was active surveillance with PSA monitoring.Whilst being investigated for possible malignancy his golimumab had been held for six months and during this period he had a significant flare in symptoms. He experienced severe back pain that forced him to stop working. Following his prostate cancer diagnosis, golimumab was restarted by his urologist with a subsequent improvement in his AS symptoms.To guide ongoing treatment his case was reviewed in the local biologics multi-disciplinary team meeting, alongside close communication with his urologist. The patient was informed of the risks of continuing golimumab in relation to his malignancy. Despite this he was reluctant to stop anti-TNF therapy or switch to another treatment, citing concerns about the impact it might have on his symptoms and ability to work.Case report - Discussion This case highlights the complexities involved in the management of a patient on anti-TNF therapy, who receives a diagnosis of malignancy, particularly when the diagnosis is classed as low risk. Traditionally anti-TNF therapy was contraindicated for patients with a history of a solid organ tumour within the previous five years. The British Society of Rheumatology (BSR) guidelines recommends that patients should be advised that there is no conclusive evidence for an increased risk of solid organ tumours but that on-going vigilance is required.A holistic patient-centred approach needs to be taken in these contexts, and consideration of cases on an individual basis is needed. Inter-disciplinary and multi-speciality team input, with the effective use of a biologics MDT, is crucial. The patient was understandably reluctant to stop his treatment due to the significant impact this may have on his quality of life.On liaison with his urologist his prostate cancer was in the lowest risk category with 99% 5-year survival rates with low risk of disease progression or spread.Evidence in this field to date has been conflicting and studies have predominantly focused on the safety of anti-TNFs in rheumatoid arthritis patients. Recent large national registry data has been reassuring. Few studies have looked at the AS and psoriatic arthritis anti-TNF treated population; however, a meta-analysis of RCTs found no evidence of increased incidence of malignancy.Taking into account his low-risk cancer, the patient’s wishes and clinical evidence in this field we have made to decision to continue anti-TNF treatment for now but with ongoing surveillance for any tumour progression. The patient will undergo urology follow up alongside regular PSA monitoring, and there will be a low threshold to stop or switch treatment in the futureCase report - Key learning pointsTreatment with anti-TNF therapy in patients with concomitant inflammatory arthritis and malignancy pose a specific challenge that require close co-ordination of care between rheumatologists, oncologists, other relevant teams and may benefit from the use of local biologics MDT to guide ongoing drug therapy.It is important to take a patient centred approach and consider cases on an individual basis taking into account their cancer diagnosis, extent of disease, histology findings and their response to TNF treatment.Patients must always be counselled on the risk of continuing anti-TNF and be involved in the decision-making process.Further research is required to look at the safety of anti-TNF particularly in SpA and if there is an increased risk of malignancy.

Possibilities of personalized approach to genetically engineered biological therapy of rheumatoid arthritis

Rheumatoid arthritis is the most common rheumatic disease characterized by damage to the synovium, progressive destruction of cartilage and bone tissue. As a result of the establishment of the biological role of cytokines, it became possible to intervene in the main links of the pathogenesis of the disease, which led to inhibition of the main pathological process in RA – autoimmune inflammation.The aim. To consider the possibilities of optimizing the biological therapy of rheumatoid arthritis by identifying predictors of anti-inflammatory efficacy among clinical and laboratory markers.Basic provisions. Despite the success of genetically engineered biological drugs in the treatment of inflammatory arthritis, due to the lack of predictive biomarkers, the use of a trial and error approach, empirical therapy, is inevitable, which does not always lead to satisfactory results. The study of the main biomarkers of RA provides new insights into their potential association with various clinical phenotypes.Conclusion. This patient-centered approach offers the prospect of improving treatment outcomes through the use of specific drugs in certain patient groups.

POS1258 MISSING THE WINDOW OF OPPORTUNITY: EARLY ARTHRITIS CLINICS IN TIMES OF COVID-19

Background:The outcomes of patients with chronic inflammatory arthritis (IA), such as rheumatoid arthritis (RA), have dramatically improved over the past 20 years. Earlier identification of IA and prompter treatment institution have been key advancements, promoted by the constitution of Early Arthritis Clinics (EAC) and the development of more sensitive classification criteria for RA. The outbreak of new COronaVIrus Disease 2019 (COVID-19) has quickly become a global health emergency and has forced a rearrangement in the management of other non-COVID-19 diseases. The impact of the lock-down of the healthcare systems on chronic inflammatory diseases such as RA is expected to be significant but is at present unknown.Objectives:To assess the effects of the lock-down imposed by the COVID-19 pandemic on the referral and clinical presentation of patients with new-onset RA.Methods:Data were retrieved from the Pavia EAC inception cohort, established in 2005 for the early identification of patients with new-onset IA. Referral criteria to the EAC include: ≥3 swollen joints (SJ) and/or &lt;3 SJ and positive squeeze test and/or &lt;3 SJ and morning stiffness &gt;30 min. Demographic and clinical characteristics of the patients are assessed at baseline and regularly over follow-up.At 31 Dec 2020, the Pavia EAC collects information on 2.508 patients. For this study, baseline characteristics of the patients referred in the semester following the COVID-19 lock-down (Jul-Dec 2020) were compared with: (i) patients referred in the semester immediately preceding the lock-down (Jul-Dec 2019); (ii) patients referred in the semester following the publication of the 2010 RA classification criteria (Jan-Jun 2011); (iii) patients referred in the semester preceding the publication of the 2010 criteria (Jul-Dec 2009).Results:In the semester following the lock-down imposed by the COVID-19 pandemic, there was a decrease in the referral of patients with new-onset suspected IA compared with previous periods (n=71 vs n=91 in the semester before the lock-down, n=96 in the first semester of 2011, n=101 in the second semester of 2009). Furthermore, fewer of the referred patients fulfilled RA criteria at presentation (36.6% vs 44.3%, 46.5% and 42.9% in the other semesters). Among patients with RA, more were autoantibody-positive (72% vs 50%, 49.1% and 52.2%). There was a trend for increased diagnostic delay in the overall cohort of RA after the COVID-19 lock-down (Figure 1A). The delay was particularly longer in autoantibody-positive patients, returning to the values seen before the introduction of the 2010 RA criteria (Figure 1B). In contrast, the few autoantibody-negative patients were referred earlier (Figure 1C). Disease activity at presentation was significantly higher in RA patients presenting after the lock-down compared with the progressive trend for reduction observed over the previous years, irrespective of the autoantibody status (Figure 1D-F). Such increase was determined by an inversion of the trend towards lower levels of objective parameters of inflammation, such as the swollen joint count (Figure 1G-I) and acute phase reactants, and a further increase in the secular trend towards worsening of patient-derived measures, such as the tender joint count and patient global assessment (Figure 1J-L).Figure 1.Effects of COVID-19 lock-down on new-onset RA at presentation.Conclusion:The COVID-19 pandemic is posing unprecedented challenges in the management of patients suffering from chronic diseases. RA has returned to be diagnosed outside the window of opportunity, with a significantly higher inflammatory burden at presentation. The many benefits of early diagnosis, which have dramatically changed the outcomes of autoantibody-positive RA, are at risk of vanishing in short times. Equally important, autoantibody-negative RA is at risk of further under-diagnosis and under-treatment.Disclosure of Interests:Bernardo D’Onofrio: None declared, Ludovico De Stefano: None declared, Bianca Lucia Palermo: None declared, Blerina Xoxi: None declared, Antonio Manzo: None declared, Carlomaurizio Montecucco Speakers bureau: BMS, Lilly, Sanofi, Pfizer, Galapagos, Roche, Novartis, Serena Bugatti Speakers bureau: BMS, Lilly, Sanofi, Pfizer, Galapagos

Nanomaterials for the Diagnosis and Treatment of Inflammatory Arthritis.

Nanomaterials have received increasing attention due to their unique chemical and physical properties for the treatment of rheumatoid arthritis (RA), the most common complex multifactorial joint-associated autoimmune inflammatory disorder. RA is characterized by an inflammation of the synovium with increased production of proinflammatory cytokines (IL-1, IL-6, IL-8, and IL-10) and by the destruction of the articular cartilage and bone, and it is associated with the development of cardiovascular disorders such as heart attack and stroke. While a number of imaging tools allow for the monitoring and diagnosis of inflammatory arthritis, and despite ongoing work to enhance their sensitivity and precision, the proper assessment of RA remains difficult particularly in the early stages of the disease. Our goal here is to describe the benefits of applying various nanomaterials as next-generation RA imaging and detection tools using contrast agents and nanosensors and as improved drug delivery systems for the effective treatment of the disease.

Synthesis and characterization of an injectable microparticles integrated hydrogel composite biomaterial: In-vivo biocompatibility and inflammatory arthritis treatment

Polymeric hydrogels and microparticles have been widely used for localized drug delivery applications for the treatment of arthritis. Nonetheless, owing to initial burst drug release, non-specific biodistribution and low retention time at the target site in body, these polymeric drug delivery systems have been found with low in-vivo performance. Hence, the above limitations need to be resolved by designing a smart novel drug delivery system which is the current need in biomedicine. Herein, a novel localized injectable thermoresponsive microparticles embedded hydrogel composite drug delivery system has been developed for the treatment of inflammatory arthritis. In the current study, methotrexate (MTX) loaded alginate microparticles (MTX-Microparticles) are embedded into thermoreversible hydrogel matrix (MTX-MPs-H) prepared by physical blending of sodium hyaluronate and methylcellulose (SHMC). Microparticles-hydrogel composite system exhibited appropriate in-vitro thermoreversibility (sol at 4 °C and gel at 37 °C), biocompatibility (>80 %), hemocompatibility, and controlled drug release profile. The in-vivo biocompatibility studies for 10 days revealed that composite system is non-toxic in nature. The developed MTX-MPs-H composite drug delivery system effectively decreased the swelling/ inflammation of the arthritis affected paw in wistar rats in comparison to only alginate microparticles and pure MTX up to 30 days.

Efficacy and safety of a single switch from etanercept originator to etanercept biosimilar in a cohort of inflammatory arthritis

AntiTNF-α biosimilars are broadly available for the treatment of inflammatory arthritis. There are a lot of data concerning the maintenance of clinical efficacy after switching from originators to biosimilars; therefore, such a transition is increasingly encouraged both in the US and Europe. However, there are reports about flares and adverse events (AE) as a non-medical switch remains controversial due to ethical and clinical implications (efficacy, safety, tolerability). The aim of our work was to evaluate the disease activity trend after switching from etanercept originator (oETA-Enbrel) to its biosimilar (bETA-SP4/Benepali) in a cohort of patients in Turin, Piedmont, Italy. In this area, the switch to biosimilars is stalwartly encouraged. We switched 87 patients who were in a clinical state of stability from oETA to bETA: 48 patients were affected by Rheumatoid Arthritis (RA),26 by Psoriatic Arthritis (PsA) and 13 by Ankylosing Spondylitis (AS).We evaluated VAS-pain, Global-Health, CRP, number of swollen and tender joints, Disease Activity Score on 28 joints (DAS28) for RA, Disease Activity in Psoriatic Arthritis (DAPSA) for PsA, Health Assessment Questionnaire (HAQ) and Health Assessment Questionnaire for the spondyloarthropathies (HAQ-S),Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for AS patients. 11/85 patients (12.6%) stopped treatment after switching to biosimilar etanercept. No difference was found between oETA and bETA in terms of efficacy. However, some arthritis flare and AE were reported. Our data regarding maintenance of efficacy and percentage of discontinuation were in line with the existing literature.