OBJECTIVES:A systematic literature review (SLR) of publications from 2000 to 2022 identified terminology for calcium pyrophosphate crystal deposition (CPPD) and revealed substantial heterogeneity and poor adherence to recommendations. This study aimed to standardise CPPD terminology by developing an international consensus on labels and definitions. METHODS:Members of the Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) were invited by email to participate in a 3-round Delphi exercise. A steering committee identified key components of CPPD aetiology, pathophysiology, and clinical presentation among elements appearing in >10% of SLR papers, adding or removing items when scientifically justified. Participants selected preferred labels for each element. Respondents to the first round were invited to subsequent rounds. This paper reports the resulting G-CAN CPPD nomenclature. RESULTS:Consensus was reached for 'calcium pyrophosphate (CPP) crystal' and 'calcium pyrophosphate crystal deposition (CPPD)' to describe the deposition process. The unified term 'calcium pyrophosphate crystal deposition on imaging' was adopted across imaging modalities, whereas 'chondrocalcinosis' was redefined as conventional radiographic cartilage calcification consistent with CPPD. Four clinical manifestations were identified: 'acute CPP crystal arthritis' (with 'flare' for acute episodes), 'chronic CPP crystal arthritis', 'crowned dens syndrome', and 'osteoarthritis with CPPD'; the term 'pseudogout' received no support. The condition is now classified as 'asymptomatic CPPD' or 'CPPD disease' for symptomatic presentations. CONCLUSIONS:This G-CAN nomenclature is the first systematic effort to align CPPD terminology with contemporary biological and imaging evidence. By resolving longstanding ambiguities-particularly regarding 'chondrocalcinosis'-it provides a framework for consistent research definitions, clinical trial homogeneity, and improved patient care.

OBJECTIVE:Body mass index (BMI), glomerular filtration rate (GFR), and pretreatment urate levels have been reported to influence the urate-lowering response to allopurinol. We investigated whether the fractional excretion of uric acid (FEUA) also modulates this response and relates to oxypurinol concentrations. We further evaluated its potential influence on febuxostat, not as a direct comparison, but to determine whether the effect of FEUA was specific to allopurinol. METHODS:The data are from n = 1,547 and n = 296 patients starting allopurinol and febuxostat, respectively. The relationship between FEUA (≤5.5% or >5.5%) and the dose response to allopurinol or febuxostat was assessed by linear mixed-effects regression models on serum urate levels and adjusted for BMI, estimated GFR (eGFR), and treatment doses. Concentrations of oxypurinol were measured in a subgroup of patients (n = 181). A multiple linear regression model was used to assess the association between FEUA and oxypurinol concentrations, adjusted for BMI, eGFR, allopurinol dosage, and serum urate levels. RESULTS:The median FEUA in the whole population was 4.0% (quartile 1-3: 3%-5.1%). The changes in serum urate levels for each 150-mg increase in allopurinol in patients with FEUA ≤5.5% or >5.5% were -72.37 (confidence interval [CI] -74.81 to -69.94) μM and -65.96 (CI -71.29 to -60.62) μM, respectively (P = 0.032). We found higher oxypurinol concentrations in patients with the lowest FEUA (P = 0.032). However, we did not observe any interaction between the febuxostat response and FEUA (P = 0.13). CONCLUSION:Allopurinol is more effective in patients with low FEUA, probably because of the reduced renal excretion of oxypurinol. These data highlight the similarity between the renal handling of oxypurinol and urate.

The objective of this study is to determine the prevalence of hypomagnesemia in patients with calcium pyrophosphate (CPP) arthritis and the role of diuretics on inducing hypomagnesemia. This was an observational, cross-sectional, prospectively recruited, case–control study. Cases were confirmed by both chondrocalcinosis in plain X-ray and CPP crystals in synovial fluid. Serum creatinine, magnesium, calcium, phosphate, 25-OH-vitamin D, parathyroid hormone, ferritin and transferrin saturation were measured. Diuretic use, class, and dosage were also recorded. A total of 568 patients were included, 298 cases and 270 controls. Lower serum magnesium levels were found more frequently among cases, 16

Introducción La artritis reumatoide (AR) es la enfermedad reumática inflamatoria crónica más común, y su manejo y morbilidad suponen una gran carga para los sistemas de salud. El desarrollo y uso de fármacos antirreumáticos modificadores de la enfermedad han contribuido a mejoras para los pacientes, sin embargo, los altos costes han impedido su uso generalizado. La aparición de los biosimilares está cambiando este paradigma al ofrecer el mismo perfil de beneficio-riesgo a un menor coste. El objetivo es analizar el coste-efectividad de tocilizumab biosimilar (bsTCZ) subcutáneo en pacientes con AR moderada-severa en España desde la perspectiva del sistema de salud. Métodos Se desarrolló un modelo de Markov con un horizonte temporal de toda la vida incluyendo cinco estados de salud: remisión de la enfermedad; actividad baja, moderada o alta; y muerte. Mediante una búsqueda PICO-S-T se identificó la eficacia de los tratamientos en metanálisis y metanálisis en red, y se complementó con evidencia de ensayos clínicos publicados. Los costes farmacológicos se obtuvieron de la base de datos BotPlus, y los de recursos de las tarifas regionales. Se realizaron análisis de sensibilidad determinísticos y probabilísticos para validar la robustez de los resultados. Se calculó la ratio coste-efectividad incremental (RCEI) para el coste/porcentaje de remisión y el coste/años de vida ganados ajustados por calidad (AVAC). Resultados El coste durante toda la vida de bsTCZ fue 183.741€ (más bajo) frente a los comparativos que oscilaban entre 184.317€ para infliximab y 201.972€ (más alto) para certolizumab. Los AVAC fueron 13,74 para upadacitinib y 13,73 para sarilumab y tocilizumab, con valores entre 13,53 y 13,72 para los comparadores. El RCEI en €/remisión y €/AVAC mostraron que bsTCZ fue dominante o la alternativa más coste-efectiva en la mayoría de las comparaciones. Los análisis de sensibilidad mostraron que el coste a largo plazo de bsTCZ y la transición de baja a moderada fueron los factores más influyentes. Además, bsTCZ fue dominante o coste-efectivo en todas las comparaciones. Conclusiones bsTCZ demostró ser una alternativa coste-efectiva y que genera ahorros en el tratamiento de pacientes con AR en España en comparación con las alternativas terapéuticas disponibles.

Aim: To evaluate the efficacy and tolerability of febuxostat (FBX) and benzbromarone (BNZ) combination therapy in patients with difficult-to-treat (D2T) gout. Methods: This observational study was performed at two centers and included patients fulfilling the 2015 European Alliance of Associations for Rheumatology/American College of Rheumatology (EULAR/ACR) gout classification criteria, with clinical tophi and suboptimal response to standard urate-lowering therapy. A two-step treatment regimen was implemented: a 6-month dose escalation of the FBX dose followed by add-on BNZ. Demographic, clinical, and laboratory data—including cardiovascular risk factors (CVRFs), history of nephrolithiasis, liver enzymes, and estimated glomerular filtration rate (eGFR)—were recorded. Changes in serum urate (SUA) and eGFR were analyzed using paired t-tests. Results: The study population comprised 15 patients (87% male, median age 59 years) with longstanding gout [median 15 years, range 3–31; interquartile range (IQR) 8–25]. Baseline SUA was 10.3 ± 1.7 mg/dL; mean eGFR was 63.7 ± 23.6 mL/min. CVRFs were common (hypertension, 93%; dyslipidemia, 73%: major adverse cardiovascular events, 13%; diabetes, 7%). At 12 months, SUA had decreased significantly to 2.9 ± 1.1 mg/dL (Δ = 7.4 mg/dL; p < 0.01), with FBX alone contributing to a Δ of 5.4 mg/dL and BNZ an additional Δ of 2.1 mg/dL (both p < 0.01). Tophi resolved in 60% of patients. No serious adverse events or significant changes in liver or renal function were observed. One unrelated death was recorded. Conclusions: FBX + BNZ was effective and well-tolerated in patients with severe D2T gout, achieving a substantial reduction in SUA and clinically significant dissolution of tophi.

INTRODUCTION:Rheumatoid arthritis (RA) is the most common chronic inflammatory rheumatic disease, its management and morbidity impose a great burden to healthcare systems. Development and rollout of biological disease modifying anti-rheumatic drugs has contributed to improvements for patients, however, high costs have prevented them to be widely used. This is being addressed with biosimilars, with equal benefit-risk profile and reduced costs. The objective is to analyze the cost-effectiveness of subcutaneous biosimilar tocilizumab (bsTCZ) for patients with moderate-severe RA in Spain from a healthcare system perspective. METHODS:A Markov model was developed with a lifetime horizon including 5 health states: remission of the disease; low, moderate, or high activity; and death. A PICO-S-T search retrieved efficacy of treatments in meta-analysis and network meta-analysis, and was further complemented with published clinical trials. Pharmacological costs were obtained from the BotPlus database, and medical resources costs from regional tariffs. Deterministic and probabilistic sensitivity analysis were performed to validate the robustness of results. Incremental cost-effectiveness ratio (ICER) for cost/percentage of remission and cost/quality-adjusted life year (QALY) gain were calculated. RESULTS:Lifetime cost of bsTCZ was 183 741€ (lowest) versus comparative costs ranging from 184 317€ for infliximab to 201 972€ (highest) for certolizumab. QALYs were 13.74 for upadacitinib and 13.73 for sarilumab and tocilizumab with values between 13.53 and 13.72 for the comparators. ICERs as €/remission and €/QALY showed that bsTCZ was either dominant in most of the comparisons or the most cost-effective alternative. The sensitivity analysis showed that bsTCZ long term cost, and transition from low to moderate disease activity health status were the most influential factors. Moreover, bsTCZ was either dominant or cost-effective in all the comparisons. CONCLUSIONS:bsTCZ demonstrated to be a cost-effective and cost-saving alternative for the treatment of patients with RA in Spain when compared to all the available therapeutic alternatives.

Aim: To compare the rate of acute kidney injury (AKI) associated with non-steroidal anti-inflammatory drugs (NSAIDs) through two consecutive decades in patients with gout and to study factors associated with AKI events. Methods: Retrospective analysis of data from Jan 1994 to Dec 2024. Data on AKI and upper gastrointestinal bleeding (UGB) were collected during the same period (2005–2024), along with general (age, gender, time from onset), gout-related (tophi, imaging, clinical distribution, number of flares), treatment-related (diuretic and urate-lowering medications, exposure to the triple whammy), and comorbidities-related variables (hypertension, hyperlipidemia, diabetes, chronic kidney disease). Analysis was made for the whole cohort and comparing decades with each other. Survival analysis was performed to evaluate those variables independently associated with a higher risk of AKI. Results: 1,207 cases were available for analysis. The overall cumulated rate of AKI was 13.3%, showing an increase from 9.9% to 16.1% from the first to the second decades, respectively, but no change in the severity of AKI was observed. In contrast, there was no change in the rate of UGB through the two decades (close to 2%). There was an increase in the frequency of gout severity variables, triple whammy exposure, and comorbid conditions through the two decades. Age, tophaceous gout, chronic kidney disease, triple whammy exposure, were variables independently associated with a higher risk of AKI, while urate-lowering prescription was associated with a lower risk. Conclusions: An increase in the rate of AKI was observed through the two decades studied, associated with an increase in gout severity, comorbidity, and exposure to triple whammy. Chronic kidney disease and exposure to triple whammy in older patients with severe (tophaceous) gout seem to define the combination for the highest risk, in whom the avoidance of NSAIDs should be carefully considered.

BACKGROUND:Gout is a chronic disease of monosodium urate crystal deposition caused by elevated serum urate (SU). Gout may progress from acute episodic attacks to a disabling chronic deforming arthropathy. Allopurinol and febuxostat are the most widely prescribed urate-lowering drugs, however, these agents have potential adverse events and are seldom titrated to achieve a target SU level. Tigulixostat is a novel non-purine selective xanthine oxidase inhibitor for gout with hyperuricemia which has demonstrated potent in vitro and in vivo urate lowering activity and is being further investigated in humans for regulatory approvals. METHODS:The Phase 3 program for tigulixostat consists of two clinical trials: EURELIA 1 and EURELIA 2. EURELIA 1 is a randomized, multi-regional, double-blind, parallel-group, placebo-controlled study to assess the safety and efficacy of 6 months of tigulixostat (100, 200, or 300 mg) in gout patients with hyperuricemia (n = 350). EURELIA 2 is a randomized, multi-regional, double-blind, double-dummy, parallel-group, active comparator (allopurinol titrated up to 800 mg) and placebo-controlled study to assess the safety and efficacy of tigulixostat (100, 200, or 300 mg) up to 12 months in gout patients with hyperuricemia (n = 2542). The primary endpoint for both studies is to determine the proportion of patients with SU levels <6.0 mg/dL sustained at for 3 months (Months 4, 5, and 6). CONCLUSIONS:EURELIA 1 and EURELIA 2 studies will be able to adequately determine the efficacy and safety of tigulixostat compared to both placebo and allopurinol. TRIAL REGISTRATION NUMBER:For EURELIA 1, the clinicaltrials.gov identifier is NCT05586958. For EURELIA 2, the clinicaltrials.gov identifier is NCT05586971 and the EU CT number is 2022-501421-20-00. The sponsor for both trials is LG Chem, Ltd. (Seoul, South Korea).

This sub-analysis of the PROPER study aimed to evaluate outcomes following the transition from reference adalimumab (ADL) to SB5 (Imraldi™) in routine clinical practice in Spanish patients with rheumatoid arthritis (RA). Adult Spanish patients (n = 73) with RA who initiated SB5 as part of routine clinical practice following treatment with reference ADL were recruited. Outcome measures included persistence on SB5, clinical characteristics, and disease activity scores at the time of transition to SB5 treatment, clinical management over time, and safety. At Week 48, the Kaplan-Meier [95% confidence interval (CI)] estimate of the probability of persistence on SB5 after switching from reference ADL was 0.84 (0.73–0.90) and 83.6% (46/55) of patients were in remission or had low disease activity. The majority of patients [83.6% (61/73)] experienced no disease flare during the study period and reported that the injection was “simple or very simple” to administer (baseline: 66.7%; Week 48: 69.0%) and were generally “satisfied or very satisfied” with the duration of the injection. In total, 21 patients (21/73, 28.8%) reported at least one drug-related adverse event, which were mild in most cases (17/21, 80.9%). In a Spanish cohort of patients with RA transitioning from reference ADL to SB5, the probability of SB5 persistence was high and treatment effectiveness was maintained for up to 48 weeks. There were no new safety signals and SB5 was well tolerated. These findings suggest that there is no evidence to mitigate against transition from reference ADL to SB5 in patients with RA (Clinicaltrials.gov listing: NCT04089514).

Background: Some patients with gout have multiple comorbidities and subcutaneous tophi refractory to conventional monotherapy with urate-lowering treatments (ULT). Uricases may be helpful drugs, but they are not always available. Combined treatment with two potent ULT, such as FBX and BNZ, could achieve a uricase-like effect and be a therapeutic alternative for these patients. Objectives: To evaluate the efficacy and tolerance of the combined treatment of benzbromarone BNZ with FBX in patients with difficult-to-treat (D2T) tophaceous gout. Methods: Multicenter observational study with patients diagnosed with gout according to EULAR/ACR 2015 criteria, subcutaneous tophi, and poor response to standard of care treated with a combination of BNZ and FBX according to a 12-month two-step regimen: FBX monotherapy for the first 6 months (individualized dose optimization), followed by subsequent addition of BNZ (50 mg/day, progressively escalating to 100 mg, whenever possible). Demographic and clinical variables related to gout, cardiovascular risk factors (CVRF), nephrolithiasis, estimated glomerular filtration rate (eGFR), and liver enzymes were collected. A descriptive analysis of the sample was performed using frequencies and percentages for qualitative variables and measures of central tendency and dispersion for quantitative variables. T-test for paired samples was used to analyze changes in uric acid (UA) levels and eGFR. Results: Fifteen patients were recruited from two hospitals, 87% male, with a median age of 59 years (range 43-93), oligo/polyarticular arthritis and a mean of 5.7±3.7 attacks in the year before starting BNZ. Most of them had advanced gout (mean 16.2±8.8 years), with high basal UA levels (mean 10.3±1.7 mg/dl), a marked presence of CVRF (93% hypertension, 73% dyslipidemia, 13% major cardiovascular event, 7% diabetes), and renal impairment (mean eGFR 63.7±23.6 ml/min; mean creatinine 1.21±0.37 mg/dl). Only one patient had a history of nephrolithiasis. Before starting combination therapy, 80% had received monotherapy with a xanthine oxidase inhibitor: 27% allopurinol (median 200 mg/day, range 100-300), 53% FBX (median 100 mg/day, range 40-120). Adding BNZ to FBX treatment resulted in a significant reduction in UA at 12 months (Δ=2.1 mg/dl [95CI: 1.2-2.9], p<0.001), in addition to the initial decrease achieved by FBX alone (Δ=2.3 mg/dl [95CI: 1.1-3.6], p=0.002; Figure 1), with tophi dissolution in 60% (9/15) of patients. The median duration of follow-up was 18 months (range 9-44); median exposure to BNZ 12 months (range 6-38). Reasons for discontinuation of BNZ were tophi dissolution in nine patients, loss of follow-up in three patients and poor clinical tolerance in one patient. There were no serious adverse events, renal colic or significant changes in liver enzymes or kidney function after 12 months compared to baseline values (eGFR12m 61.6 vs eGFRbaseline 63.7 ml/min; n.s.). One death was recorded (no treatment-related; elderly, history of aortic regurgitation). Conclusion: In our sample, the combination of BNZ and FBX was effective in patients with D2T tophaceous gout, with an intensive reduction in UA and rapid tophi dissolution. Combined therapy was well-tolerated by most patients. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Enrique Calvo-Aranda: None declared, Claudia Maria Gomez-Gonzalez: None declared, Marta Novella-Navarro: None declared, Fernando Perez-Ruiz Menarini Central America, Anlylam, Arthriti and Protalix.

Objective To formulate evidence-based recommendations and overarching principles on the use of imaging in the clinical management of crystal-induced arthropathies (CiAs). Methods An international task force of 25 rheumatologists, radiologists, methodologists, healthcare professionals and patient research partners from 11 countries was formed according to the EULAR standard operating procedures. Fourteen key questions on the role of imaging in the most common forms of CiA were generated. The CiA assessed included gout, calcium pyrophosphate deposition disease and basic calcium phosphate deposition disease. Imaging modalities included conventional radiography, ultrasound, CT and MRI. Experts applied research evidence obtained from four systematic literature reviews using MEDLINE, EMBASE and CENTRAL. Task force members provided level of agreement (LoA) anonymously by using a Numerical Rating Scale from 0 to 10. Results Five overarching principles and 10 recommendations were developed encompassing the role of imaging in various aspects of patient management: making a diagnosis of CiA, monitoring inflammation and damage, predicting outcome, response to treatment, guided interventions and patient education. Overall, the LoA for the recommendations was high (8.46-9.92). Conclusions These are the first recommendations that encompass the major forms of CiA and guide the use of common imaging modalities in this disease group in clinical practice.

Aim: To ascertain the prevalence of calcium pyrophosphate arthritis (CPPA) at diagnosis and during follow-up of patients with gout. Methods: Inception cohort of patients with gout prospectively recruited and followed-up from 1994–2023. Gout-case was defined as crystal-proved tophus or arthritis, or the presence of tophus plus double contour with ultrasonography. CPPA was defined as the presence of intra-leukocyte calcium pyrophosphate (CPP) crystals in synovial fluid (SF) and neat chondrocalcinosis in plain radiographs. Age, gender, time from onset of symptoms, number of flares, joint distribution, previous and prescribed treatments, colchicine prophylaxis, comorbidities, alcohol intake, use of diuretics, renal function, and previous vascular disease were available for analysis. Results: A total of 1,544 patients with gout, with an average of 4-year follow-up, were available for analysis. CPPA was observed in 127/1,544 cases (8.2%). In 37/1,544 patients (2.4%) CPP and monosodium urate (MSU) crystals were observed in the same SF sample at gout diagnosis, and 90/1,544 (5.8%) showed CPP crystals apart from the diagnosis of gout. CPPA-gout cases had more flares per year, but no more frequent polyarticular distribution at baseline compared to non-CPPA-gout. CPPA-gout cases were older at baseline and showed lower renal function. Women, patients using diuretics, patients with hypertension, and those with previous vascular events showed CPPA more frequently. Multivariate analysis showed that only age and use of diuretics were independently associated with CPPA, as other variables apparently associated were dependent on aging. Interestingly, an analysis of the prevalence in the three decades available showed an increased CPPA diagnosis through time, probably associated with increased awareness of the association. Conclusions: (1) CPPA is not infrequent in patients with gout; (2) it is associated with aging and diuretic use; (3) awareness of this association may increase the rate of diagnosis.

Aim: To evaluate the impact of prescription, cost, and switching policy on the rate of switching from reference products to biosimilars. Methods: Analysis of an administrative database for prescription in a rheumatology division. Biosimilars for adalimumab and etanercept were available in 2019. Blinded costs and prescription data were not shared with prescribing physicians until 2021. The rate of prescription, persistence of therapy after switching, and reduction of cost were analyzed from 2019 to 2022. A new etanercept biosimilar was prioritized in 2022, and a new switching wave from biosimilar to biosimilar etanercept was implemented. Results: Overall switching from 2019 to 2022 comprised 132/135 (97.8%) of patients. The rate of switching increased from 13.3% to 34%, 79%, and 95.5% of patients on reference products during 2019, 2020, 2021, and 2022, respectively. In 2022, after sharing information, the switch comprised 55/135 (40.7%) of overall switching. The rate of persistence on therapy after switching was 86.8% for etanercept and 79.7 for adalimumab. During 2023, a rate of 76.6% switching etanercept reference-biosimilar-biosimilar was achieved. The reduction in the overall biologic budget in 2021 was 19.2% and 29.0% for the patient-year cost. Conclusions: Information to prescribers may improve switching policies. Persistence on biosimilar medications after switching is as high as previously reported.

Gout is a chronic disease that is caused by an innate immune response to deposited monosodium urate crystals in the setting of hyperuricemia. Here, we provide insights into the molecular mechanism of the poorly understood inflammatory component of gout from a genome-wide association study (GWAS) of 2.6 million people, including 120,295 people with prevalent gout. We detected 377 loci and 410 genetically independent signals (149 previously unreported loci in urate and gout). An additional 65 loci with signals in urate (from a GWAS of 630,117 individuals) but not gout were identified. A prioritization scheme identified candidate genes in the inflammatory process of gout, including genes involved in epigenetic remodeling, cell osmolarity and regulation of NOD-like receptor protein 3 (NLRP3) inflammasome activity. Mendelian randomization analysis provided evidence for a causal role of clonal hematopoiesis of indeterminate potential in gout. Our study identifies candidate genes and molecular processes in the inflammatory pathogenesis of gout suitable for follow-up studies.

Background: Rheumatoid arthritis (RA) is the most common chronic inflammatory rheumatic disease. It entails a considerable burden to healthcare systems worldwide due to both its management and associated morbidity. Biological and targeted drugs, although achieving undeniable improvements for patients, result in high costs from a lifetime perspective which limit their broader or earlier use. Biosimilars have addressed such an issue, with an equal benefit-risk profile but reduced costs. A recent analysis in Spain demonstrated cost-effectiveness of adalimumab for American College of Rheumatology 20/50 endpoints in RA but results also remarked that tocilizumab hinted to be the most cost-effective in Disease Activity Score (DAS) 28 evaluated efficacy. Therefore, we advanced the depth of work around DAS-28 comparative analysis, given that it is the most used activity index in Spain (Martínez-Sesmero et al., 2023) Objectives: To analyse the cost-effectiveness of tocilizumab biosimilar versus available biological or targeted synthetic DMARDs (disease modifying antirheumatic drugs) therapeutic alternatives for the treatment of patients suffering moderate-severe rheumatoid arthritis in Spain from a lifelong and healthcare system perspective. Methods: Cost-effectiveness analysis using a Markov model including the following health states: remission of the disease, low activity, moderate activity, high activity, and death; with a lifetime horizon and abatacept, adalimumab, baricitinib, certolizumab, etanercept, filgotinib, golimumab, infliximab, rituximab, sarilumab, biological tocilizumab, tofacitinib, and upadacitinib as the comparators. A PICO-S-T search was carried out to retrieve the efficacy in meta-analysis as measured by DAS28, additionally complemented with data from clinical trials. Pharmacological costs were obtained from a hospital pharmacy nationwide database (Consejo general de colegios de farmacéuticos de España, 2021) and medical resources costs from regional published tariffs. Robustness was validated through a deterministic and probabilistic sensitivity analysis. Further calculations were included, such as the incremental cost-effectiveness ratio (ICER) for cost per percentage of remission and cost per quality-adjusted life year (QALY) gain. Results: The lifetime cost of tocilizumab biosimilar was 183,741€ versus costs ranging from 184,317€ for infliximab and up to 201,972€ for certolizumab. QALYs were 13.73 for tocilizumab biosimilar and values between 13.53-13.74 for the comparators. ICERs expressed either as €/remission or €/QALY showed that tocilizumab biosimilar was either dominant in most of the comparisons or the most cost-effective alternative. Conclusion: Tocilizumab biosimilar proved to be a cost-effective and a cost-saving alternative for the treatment of patients with rheumatoid arthritis in Spain when compared to all the available biological or targeted synthetic DMARDs therapeutic alternatives. REFERENCES: [1] Consejo general de colegios de farmacéuticos de España. (2021). Base de datos de medicamentos BotPLUS.[2] Martínez-Sesmero, J. M., Crespo-Diz, C., Cerezales, M., Crespo, C., Guigini, M. A., & Schoenenberger-Arnaiz, J. A. (2023). Cost-effectiveness analysis of adalimumab in patients with immune-mediated inflammatory diseases in Spain. OFIL ILAPHAR, First onli. https://www.ilaphar.org/cost-effectiveness-analysis-of-adalimumab-in-patients-with-immunemediated-inflammatory-diseases-in-spain/ Acknowledgements: NIL. Disclosure of Interests: Fernando Pérez-Ruiz Biogen, Menarini, Arthrosi, LG Pharma, Novartis, Protalix, Selecta, Carlos Crespo-Diz Abbvie, AstraZeneca, Fresenius Kabi, Gilead, GSK, Janssen, Pfizer, Abbvie, Amgen, AstraZeneca, Bayer, BeiGene, Fresenius Kabi, Gilead, Janssen, Pfizer, Abbvie, Amgen, AstraZeneca, Janssen, Kern Pharma, Novartis, Pfizer, Roche, Rovi, Antonio Gómez-de Póo Antonio is an employee of a consultancy company working for several pharmaceutical and medical devices companies, Carlos Crespo Carlosis an employee of a consultancy firm working for several pharmaceutical and medical devices companies, Marcelo Alejandro Guigini Marcelo Alejandro is an employee of Fresenius Kabi, Jose Ignacio Peinado-Fabregat José Ignacio is an employee of Fresenius Kabi, Joan Antoni Schoenenberger-Arnaiz Fresenius Kabi, Gilead, Pfizer, Bayer, Mónica Climente Novartis, Pfizer, AstraZeneca, Kern Pharma, Alexion, Roche Farma, Sanofi, Novartis, Pfizer, Fresenius, MSD.

OBJECTIVE:The selection and reporting of core outcome measures in clinical trials is essential for patients, researchers, and healthcare providers for clinical research to have an impact on healthcare. In this systematic scoping review, we aimed to quantify the extent to which gout clinical trials are collecting and reporting data in accordance with the core outcome domains from Outcome Measures in Rheumatology (OMERACT) published in 2009 applicable for both acute and chronic trials and evaluate the reporting according to the core domains before and after the 2009 OMERACT endorsement. METHODS:We searched multiple databases PubMed, EMBASE, the Cochrane Library including the Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane Database of Systematic Reviews (CDSR) and www. CLINICALTRIALS:gov for randomized controlled trials (RCTs) allocating people with gout versus an active pharmacological gout treatment or a control comparator (no date limitation). We extracted the data in accordance with the core outcome sets, focusing individually on core outcome domains and the core outcome measurements for acute and chronic trials, respectively. In this study 'Acute trials' reflect studies that describe interventions for short term management of gout flares, and 'chronic trials' describe interventions for long-term urate lowering therapy in the management of gout. RESULTS:From 8,522 records identified in the database search, 134 full text papers were reviewed, and 71 trials were included, of which 36 were acute and 35 were chronic. Only 3 of 36 (8%) acute trials reported all five core domains and none of the 35 included chronic trials reported all 7 core domains. In the acute trials, twenty-seven unique measurement instruments across the 5 core domains were identified. For chronic trials there were 31 unique measurement instruments used across the 7 core domains. Serum urate was reported in 100% of the chronic trials and gout flares in 80%. However, other core domains were reported in <30% of chronic trials. In particular the patient-important domains such as HR-QOL, patient global assessment and activity limitations were rarely reported. A broad variety of different measurement instruments were used to assess each endorsed core domain, a minority of trials used the OMERACT endorsed instruments. For acute trials, the number reporting on all core domains was consistently low and no change was detected before and after the endorsement of the core domains in 2009. None of the included chronic trials reported on all 7 endorsed core domains at any time. CONCLUSION:In this study we found a low adherence with the intended endorsed (i.e., core) outcome domains for acute and chronic gout studies which represents a poor uptake of the global OMERACT efforts for the minimum of what should be measured in clinical trials. In addition, there is a significant variation in how the OMERACT endorsed outcome domains have been measured. This systematic review demonstrates the need for continuous encouragement among gout researchers to adhere to OMERACT core domains as well as further guidance on outcome measurements reporting. REGISTRATION:Prospero: CRD42019151316.

The scientific and clinical landscape of musculoskeletal diseases (MDs) has revolutionized in the last decades, becoming a promising field for investigation, either basic or clinical, and therefore for publishing. MDs enclose the most prevalent pathology in the adult population. It is an increasing tide of prevalence as the aging of populations all over the world is associated with an increasing prevalence of both spinal and peripheral joint diseases, mainly osteoarthritis (OA). The most recent data from the Global Burden of Disease show that from 1990 to 2019 MDs ranked first in adults in years lived with disability (YLDs) and rose to rank third in disease-adjusted life-years (DALYs) and within the top twenty years of life lost (YLLs) [1]. It is not only the impact on the diseased population, for example, the health-related cost in the USA of MDs ranks first in the country [2], and yet it is not only health-related costs, but work, social, and personal costs that have also to be considered. In most recent years genetics and mechanisms of inflammation, such as interleukin (IL) or Janus kinase (JAK) pathways have transformed the therapeutic opportunities, as new medications have developed once the diverse mechanisms of inflammation have been elucidated. The blocking of one of the primers and shared pathways of inflammation in MDs, as tumor necrosis factor is, changed the face of clinical practice of the approach to the treatment of rheumatic diseases all over the world. Then IL-1 blockade for crystal-induced and autoinflammatory diseases, IL-6 receptor inhibition for rheumatoid arthritis, giant cell vasculitis, and Still’s disease, and most recently agents that inhibit IL-17A and the IL-12/23 pathway have made the start of the end of the XXth century and the start of the XXIst, the era of the biologics, one of the most evolving periods in MD medicine [3]. In addition, new JAK inhibitors [4], some of them polyvalent, such as upadacitinib for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, have been developed and approved, providing even more options to achieve proper health-related outcomes in MDs. These new developments have been associated with increasing costs in available treatments, and a new field is open to those interested in management: health cost and efficiency analysis. The uprise in the number of biosimilars of biologic agents has also been a challenge for managers, clinicians, and clinicians Open Access Editorial

OBJECTIVE:To determine whether a gout polygenic risk score (PRS) is associated with age at gout onset and tophaceous disease in European, East Polynesian, and West Polynesian men and women with gout.METHODS:A 19-variant gout PRS was produced in 7 European gout cohorts (N = 4,016), 2 East Polynesian gout cohorts (N = 682), and 1 West Polynesian gout cohort (N = 490). Sex-stratified regression models were used to estimate the relationship between the PRS and age at gout onset and tophaceous disease.RESULTS:The PRS was associated with earlier age at gout onset in men (β = -3.61 in years per unit PRS [95% confidence interval (95% CI) -4.32, -2.90] in European men; β = -6.35 [95% CI -8.91, -3.80] in East Polynesian men; β = -3.51 [95% CI -5.46, -1.57] in West Polynesian men) but not in women (β = 0.07 [95% CI -2.32, 2.45] in European women; β = 0.20 [95% CI -7.21, 7.62] in East Polynesian women; β -3.33 [95% CI -9.28, 2.62] in West Polynesian women). The PRS showed a positive association with tophaceous disease in men (odds ratio [OR] for the association 1.15 [95% CI 1.00, 1.31] in European men; OR 2.60 [95% CI 1.66, 4.06] in East Polynesian men; OR 1.53 [95% CI 1.07, 2.19] in West Polynesian men) but not in women (OR for the association 0.68 [95% CI 0.42, 1.10] in European women; OR 1.45 [95% CI 0.39, 5.36] in East Polynesian women). The PRS association with age at gout onset was robust to the removal of ABCG2 variants from the PRS in European and East Polynesian men (β = -2.42 [95% CI -3.37, -1.46] and β = -6.80 [95% CI -10.06, -3.55], respectively) but not in West Polynesian men (β = -1.79 [95% CI -4.74, 1.16]).CONCLUSION:Genetic risk variants for gout also harbor risk for earlier age at gout onset and tophaceous disease in European and Polynesian men. Our findings suggest that earlier gout onset involves the accumulation of gout risk alleles in men but perhaps not in women, and that this genetic risk is shared across multiple ancestral groups.