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Ferroptosis is a form of iron-dependent regulated cell death caused by the accumulation of lipid peroxides. In this review, we summarize research on the impact of ferroptosis on disease models and isolated cells in various types of arthritis. While most studies have focused on rheumatoid arthritis (RA) and osteoarthritis (OA), there is limited research on spondylarthritis and crystal arthropathies. The effects of inducing or inhibiting ferroptosis on the disease strongly depend on the studied cell type. In the search for new therapeutic targets, inhibiting ferroptosis in chondrocytes might have promising effects for any type of arthritis. On the other hand, ferroptosis induction may also lead to a desired decrease of synovial fibroblasts in RA. Thus, ferroptosis research must consider the cell-type-specific effects on arthritis. Further investigation is needed to clarify these complexities.
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Ferroptosis , Osteoartritis , Humanos , Animales , Osteoartritis/metabolismo , Osteoartritis/patología , Condrocitos/metabolismo , Condrocitos/patología , Artritis Reumatoide/metabolismo , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/patología , Artritis/metabolismo , Artritis/patología , Fibroblastos/metabolismo , Fibroblastos/patología , Hierro/metabolismoRESUMEN
Biomechanical stress may exacerbate inflammation in psoriatic arthritis (PsA). This study aimed to investigate disease activity, work disability, and drug response/retention rates in PsA patients among two different occupation's types: blue-collar workers (BCol) with manual labor versus white-collar workers (WCol) with sedentary occupations. PsA patients registered in the Swiss cohort (SCQM) were classified as BCol or WCol workers and assessed at the initiation of a biologic or targeted synthetic disease-modifying anti-rheumatic drug (b-/tsDMARD). We compared the baseline characteristics at treatment start and the DAS28-CRP for the 1-year remission. Treatment retention was investigated using Kaplan-Meier curves and Cox regression analysis. Multivariable models were adjusted for potential confounders. Of 564 patients, 29% were BCol, and 71% were WCol workers. Baseline disease activity was comparable between both groups. BCol workers were predominantly male (79.8%) and more work disabled at baseline (84.0% vs. 27.9%; p < 0.01). One hundred seventy-four treatment courses (TCs) of 165 PsA patients were included for longitudinal analysis. Occupation did not significantly influence the achievement of DAS28-CRP remission at 1 year. Kaplan-Meier analysis (n = 671) indicated longer retention for BCol workers (mean retention duration: 3.15 years vs. 2.15 years, (p = 0.006). However, adjusted Cox regression analysis did not corroborate these findings. This study indicates that physically demanding occupations correlate with increased rates of work disability among PsA patients, while treatment response seems to be unaffected by the patients' occupation type. Additional research is required to thoroughly comprehend the relationship between physical workload, disease activity, and treatment outcomes. Key Points ⢠This study indicates that physically demanding occupations correlate with increased rates of work disability among PsA patients. ⢠The treatment response among of PsA patients seems unaffected by the patients' occupation type.
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Objective: To validate the prognostic accuracy of anti-apolipoprotein A-1 (AAA1) IgG for incident major adverse cardiovascular (CV) events (MACE) in rheumatoid arthritis (RA) and study their associations with the lipid paradox at a multicentric scale. Method: Baseline AAA1 IgG, lipid profile, atherogenic indexes, and cardiac biomarkers were measured on the serum of 1,472 patients with RA included in the prospective Swiss Clinical Quality Management registry with a median follow-up duration of 4.4 years. MACE was the primary endpoint defined as CV death, incident fatal or non-fatal stroke, or myocardial infarction (MI), while elective coronary revascularization (ECR) was the secondary endpoint. Discriminant accuracy and incidence rate ratios (IRR) were respectively assessed using C-statistics and Poisson regression models. Results: During follow-up, 2.4% (35/1,472) of patients had a MACE, consisting of 6 CV deaths, 11 MIs, and 18 strokes; ECR occurred in 2.1% (31/1,472) of patients. C-statistics indicated that AAA1 had a significant discriminant accuracy for incident MACE [C-statistics: 0.60, 95% confidence interval (95% CI): 0.57-0.98, p = 0.03], mostly driven by CV deaths (C-statistics: 0.77; 95% CI: 0.57-0.98, p = 0.01). IRR indicated that each unit of AAA1 IgG increase was associated with a fivefold incident CV death rate, independent of models' adjustments. At the predefined and validated cut-off, AAA1 displayed negative predictive values above 97% for MACE. AAA1 inversely correlated with total and HDL cholesterol. Conclusions: AAA1 independently predicts CV deaths, and marginally MACE in RA. Further investigations are requested to ascertain whether AAA1 could enhance CV risk stratification by identifying patients with RA at low CV risk.
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OBJECTIVE: To investigate real-world retention and remission rates in PsA patients initiating a 2nd or 3rd TNFi and the association with reason for discontinuation from the previous TNFi-treatment. METHODS: Prospectively collected routine care data from 12 European registries were pooled. Retention rates (Kaplan-Meier estimation) and crude/LUNDEX-adjusted rates of Disease Activity Score 28 and Disease Activity index for PSoriatic Arthritis (DAS28 and DAPSA28) remission were calculated and compared with adjusted Cox regression analyses and Chi-squared test, respectively). RESULTS: We included 5233 (2nd TNFi) and 1906 (3rd TNFi) patients. Twelve-month retention rates for the 2nd and 3rd TNFi were 68% (95%CI: 67-70%) and 66% (64-68%), respectively. Patients who stopped the previous TNFi due to AE/LOE had 12-month retention rates of 66%/65% (2nd TNFi), and 65%/63% (3rd TNFi), respectively. Patients who stopped the previous TNFi due to LOE after less vs more than 24 weeks had 12-month retention rates of 54%/69% (2nd TNFi), and 58%/65% (3rd TNFi). Six-month crude/LUNDEX-adjusted DAS28 remission rates were 48%/35% and 38%/27%, and DAPSA28 remission rates were 19%/14% and 14%/10%, for the 2nd and 3rd TNFi. CONCLUSION: Two-thirds of patients remained on TNFi at 12months for both the 2nd and 3rd TNFi, while one-third and one-quarter of patients were in DAS28 remission after 6months on the 2nd and 3rd TNFi. While drug effectiveness was similar in patients who stopped the previous TNFi due to AE compared to overall LOE, drug effectiveness was better in patients who had stopped the previous TNF due to secondary LOE compared to primary LOE.
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Artritis Psoriásica , Sistema de Registros , Inducción de Remisión , Índice de Severidad de la Enfermedad , Humanos , Artritis Psoriásica/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Resultado del Tratamiento , Estudios Prospectivos , Inducción de Remisión/métodos , Adulto , Antirreumáticos/uso terapéutico , Europa (Continente) , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Anciano , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
OBJECTIVE: To investigate the clinical phenotype and treatment response in patients with rheumatoid arthritis (RA) with and without concomitant Sjögren's disease (SjD). METHODS: In this observational cohort study, patients with RA from the Swiss Clinical Quality Management in Rheumatic Diseases registry were categorised according to the presence or absence of SjD. To assess treatment effectiveness, drug retention of tumor necrosis factor-α-inhibitors (TNFi) was compared to other mode of action (OMA) biologics and Janus kinase-inhibitors (JAKi) in RA patients with and without SjD. Adjusted hazard ratios (HR) for time to drug discontinuation were compared in crude and adjusted Cox proportional regression models for potential confounders. RESULTS: We identified 5974 patients without and 337 patients with concomitant SjD. Patients with SjD were more likely to be female, to have a positive rheumatoid factor, higher disease activity scores, and erosive bone damage. For treatment response, a total of 6781 treatment courses were analysed. After one year, patients with concomitant SjD were less likely to reach DAS28 remission with all three treatment modalities. Patients with concomitant SjD had a higher hazard for stopping TNFi treatment (adjusted HR 1.3 [95% CI 1.07-1.6]; OMA HR 1.12 [0.91-1.37]; JAKi HR 0.97 [0.62-1.53]). When compared to TNFi, patients with concomitant SjD had a significantly lower hazard for stopping treatment with OMA (adjusted HR 0.62 [95% CI 0.46-0.84]) and JAKi (HR 0.52 [0.28-0.96]). CONCLUSION: RA patients with concomitant SjD reveal a severe RA phenotype, are less responsive to treatment, and more likely to fail TNFi.
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Antirreumáticos , Artritis Reumatoide , Humanos , Femenino , Masculino , Antirreumáticos/uso terapéutico , Suiza/epidemiología , Factor de Necrosis Tumoral alfa , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/complicaciones , Resultado del Tratamiento , BiomarcadoresRESUMEN
BACKGROUND: The Spondyloarthritis Research Consortium of Canada (SPARCC) developers have created web-based calibration modules for the SPARCC MRI sacroiliac joint (SIJ) scoring methods. We aimed to test the impact of applying these e-modules on the feasibility and reliability of these methods. METHODS: The SPARCC-SIJ RETIC e-modules contain cases with baseline and follow-up scans and an online scoring interface. Visual real-time feedback regarding concordance/discordance of scoring with expert readers is provided by a colour-coding scheme. Reliability is assessed in real time by intraclass correlation coefficient (ICC), cases being scored until ICC targets are attained. Participating readers (n=17) from the EuroSpA Imaging project were randomised to one of two reader calibration strategies that each comprised three stages. Baseline and follow-up scans from 25 cases were scored after each stage was completed. Reliability was compared with a SPARCC developer, and the System Usability Scale (SUS) assessed feasibility. RESULTS: The reliability of readers for scoring bone marrow oedema was high after the first stage of calibration, and only minor improvement was noted following the use of the inflammation module. Greater enhancement of reader reliability was evident after the use of the structural module and was most consistently evident for the scoring of erosion (ICC status/change: stage 1 (0.42/0.20) to stage 3 (0.50/0.38)) and backfill (ICC status/change: stage 1 (0.51/0.19) to stage 3 (0.69/0.41)). The feasibility of both e-modules was evident by high SUS scores. CONCLUSION: The SPARCC-SIJ RETIC e-modules are feasible, effective knowledge transfer tools, and their use is recommended before using the SPARCC methods for clinical research and tria.
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Articulación Sacroiliaca , Espondiloartritis , Humanos , Canadá , Imagen por Resonancia Magnética/métodos , Reproducibilidad de los Resultados , Articulación Sacroiliaca/diagnóstico por imagen , Articulación Sacroiliaca/patología , Espondiloartritis/diagnóstico , Espondiloartritis/patologíaRESUMEN
OBJECTIVES: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease affecting mainly the axial skeleton. Peripheral involvement (arthritis, enthesitis and dactylitis) and extra-musculoskeletal manifestations, including uveitis, psoriasis and bowel inflammation, occur in a relevant proportion of patients. AS is responsible for chronic and severe back pain caused by local inflammation that can lead to osteoproliferation and ultimately spinal fusion. The association of AS with the human leucocyte antigen-B27 gene, together with elevated levels of chemokines, CCL17 and CCL22, in the sera of patients with AS, led us to study the role of CCR4+ T cells in the disease pathogenesis. METHODS: CD8+CCR4+ T cells isolated from the blood of patients with AS (n=76) or healthy donors were analysed by multiparameter flow cytometry, and gene expression was evaluated by RNA sequencing. Patients with AS were stratified according to the therapeutic regimen and current disease score. RESULTS: CD8+CCR4+ T cells display a distinct effector phenotype and upregulate the inflammatory chemokine receptors CCR1, CCR5, CX3CR1 and L-selectin CD62L, indicating an altered migration ability. CD8+CCR4+ T cells expressing CX3CR1 present an enhanced cytotoxic profile, expressing both perforin and granzyme B. RNA-sequencing pathway analysis revealed that CD8+CCR4+ T cells from patients with active disease significantly upregulate genes promoting osteogenesis, a core process in AS pathogenesis. CONCLUSIONS: Our results shed light on a new molecular mechanism by which T cells may selectively migrate to inflammatory loci, promote new bone formation and contribute to the pathological ossification process observed in AS.
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Espondilitis Anquilosante , Humanos , Espondilitis Anquilosante/genética , Espondilitis Anquilosante/metabolismo , Osteogénesis/genética , Subgrupos de Linfocitos T/metabolismo , Linfocitos T CD8-positivos/metabolismo , InflamaciónRESUMEN
OBJECTIVE: To evaluate patient-reported outcomes (PROs) after initiation of tumor necrosis factor inhibitor (TNFi) treatment in European real-world patients with psoriatic arthritis (PsA). Further, to investigate PRO remission rates across treatment courses, registries, disease duration, sex, and age at disease onset. METHODS: Visual analog scale or numerical rating scale scores for pain, fatigue, patient global assessment (PtGA), and the Health Assessment Questionnaire-Disability Index (HAQ-DI) from 12,262 patients with PsA initiating a TNFi in 13 registries were pooled. PRO remission rates (pain ≤ 1, fatigue ≤ 2, PtGA ≤ 2, and HAQ-DI ≤ 0.5) were calculated for patients still on the treatment. RESULTS: For the first TNFi, median pain score was reduced by approximately 50%, from 6 to 3, 3, and 2; as were fatigue scores, from 6 to 4, 4, and 3; PtGA scores, from 6 to 3, 3, and 2; and HAQ-DI scores, from 0.9 to 0.5, 0.5, and 0.4 at baseline, 6, 12, and 24 months, respectively. Six-month Lund Efficacy Index (LUNDEX)-adjusted remission rates for pain, fatigue, PtGA, and HAQ-DI scores were 24%, 31%, 36%, and 43% (first TNFi); 14%, 19%, 23%, and 29% (second TNFi); and 9%, 14%, 17%, and 20% (third TNFi), respectively. For biologic-naïve patients with disease duration < 5 years, 6-month LUNDEX-adjusted remission rates for pain, fatigue, PtGA, and HAQ-DI scores were 22%, 28%, 33%, and 42%, respectively. Corresponding rates for patients with disease duration > 10 years were 27%, 32%, 41%, and 43%, respectively. Remission rates were 33%, 40%, 45%, and 56% for men and 17%, 23%, 24%, and 32% for women, respectively. For patients aged < 45 years at diagnosis, 6-month LUNDEX-adjusted remission rate for pain was 29% vs 18% for patients ≥ 45 years. CONCLUSION: In 12,262 biologic-naïve patients with PsA, 6 months of treatment with a TNFi reduced pain by approximately 50%. Marked differences in PRO remission rates across treatment courses, registries, disease duration, sex, and age at onset of disease were observed, emphasizing the potential influence of factors other than disease activity on PROs.
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Antirreumáticos , Artritis Psoriásica , Productos Biológicos , Masculino , Humanos , Femenino , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/diagnóstico , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Antirreumáticos/uso terapéutico , Resultado del Tratamiento , Medición de Resultados Informados por el Paciente , Dolor/tratamiento farmacológico , Productos Biológicos/uso terapéuticoRESUMEN
OBJECTIVE: Women with psoriatic arthritis (PsA) may have reduced tumor necrosis factor inhibitor (TNFi) effectiveness compared to men. We examined sex differences in treatment response and retention rates during 24 months of follow-up among patients with PsA initiating their first TNFi. METHODS: Data from patients with PsA across 13 European Spondyloarthritis Research Collaboration Network registries starting their first TNFi were pooled. Logistic regression was used to analyze the association between sex and treatment response using low disease activity (LDA) according to the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) (<3.2) at six months as the primary outcome. Analyses were adjusted for age, country, conventional synthetic disease-modifying antirheumatic drug treatment, and TNFi start year. Retention rates were explored using the Kaplan-Meier estimator. RESULTS: We analyzed the treatment response of 7,679 patients with PsA (50% women) with available data on LDA at six months. At baseline, women and men had similar characteristics, including mean DAS28-CRP (women vs men, 4.4 [SD 1.2] vs 4.2 [SD 1.2]), though patient-reported outcome measures were worse in women. At six months, 64% of women and 78% of men had LDA (relative risk [RR] 0.82; 95% confidence interval [CI] 0.80-0.84). This difference was similar after adjustment (RR 0.83; 95% CI 0.81-0.85). TNFi retention rates were evaluated in 17,842 patients with PsA. Women had significantly lower retention rates than men at all time points (women 79%, 64%, and 50% vs men 88%, 77%, and 64% at 6, 12, and 24 months, respectively). CONCLUSION: Despite comparable disease characteristics at baseline, women with PsA have reduced treatment response and retention rates to their first TNFi, highlighting the need to consider sex differences in PsA research and management.
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Antirreumáticos , Artritis Psoriásica , Espondiloartritis , Humanos , Femenino , Masculino , Artritis Psoriásica/tratamiento farmacológico , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Caracteres Sexuales , Factor de Necrosis Tumoral alfa , Resultado del Tratamiento , Antirreumáticos/uso terapéutico , Espondiloartritis/tratamiento farmacológicoRESUMEN
OBJECTIVES: In bio-naïve patients with PsA initiating a TNF inhibitor (TNFi), we aimed to identify baseline predictors of Disease Activity index for PsA in 28 joints (DAPSA28) remission (primary objective) and DAPSA28 moderate response at 6 months, as well as drug retention at 12 months across 13 European registries. METHODS: Baseline demographic and clinical characteristics were retrieved and the three outcomes investigated per registry and in pooled data, using logistic regression analyses on multiply imputed data. In the pooled cohort, selected predictors that were either consistently positive or negative across all three outcomes were defined as common predictors. RESULTS: In the pooled cohort (n = 13 369), 6-month proportions of remission, moderate response and 12-month drug retention were 25%, 34% and 63% in patients with available data (n = 6954, n = 5275 and n = 13 369, respectively). Five common baseline predictors of remission, moderate response and 12-month drug retention were identified across all three outcomes. The odds ratios (95% CIs) for DAPSA28 remission were: age, per year: 0.97 (0.96-0.98); disease duration, years (<2 years as reference): 2-3 years: 1.20 (0.89-1.60), 4-9 years: 1.42 (1.09-1.84), ≥10 years: 1.66 (1.26-2.20); men vs women: 1.85 (1.54-2.23); CRP of >10 vs ≤10 mg/l: 1.52 (1.22-1.89) and 1 mm increase in patient fatigue score: 0.99 (0.98-0.99). CONCLUSION: Baseline predictors of remission, response and adherence to TNFi therapy were identified, of which five were common for all three outcomes, indicating that the predictors emerging from our pooled cohort may be considered generalizable from country level to disease level.
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Artritis Psoriásica , Masculino , Humanos , Femenino , Artritis Psoriásica/tratamiento farmacológico , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Fatiga , Inmunoterapia , Sistema de RegistrosRESUMEN
OBJECTIVE: To characterise the population fulfilling the Assessment of SpondyloArthritis international Society (ASAS) consensus definition of early axial spondyloarthritis (axSpA) and to determine the effectiveness of a first tumour necrosis factor inhibitor (TNFi) in early versus established axSpA in a large observational registry. METHODS: A total of 3064 patients with axSpA in the Swiss Clinical Quality Management registry with data on duration of axial symptoms were included (≤2 years=early axSpA, N=658; >2 years=established axSpA, N=2406). Drug retention was analysed in patients starting a first TNFi in early axSpA (N=250) versus established axSpA (N=874) with multiple-adjusted Cox proportional hazards models. Adjusted logistic regression analyses were used to determine the achievement of the ASAS criteria for 40% improvement (ASAS40) at 1 year. RESULTS: Sex distribution, disease activity, impairments of function and health-related quality of life were comparable between patients with early and established axSpA. Patients with established disease were older, had more prevalent axial radiographical damage and had a higher impairment of mobility. A comparable TNFi retention was found in early versus established disease after adjustment for age, sex, human leucocyte antigen-B27 status, education, body mass index, smoking, elevated C reactive protein and sacroiliac inflammation on MRI (HR 1.05, 95% CI 0.78 to 1.42). The adjusted ASAS40 response was similar in the two groups (OR 1.09, 95% CI 0.67 to 1.78). Results were confirmed in the population fulfilling the ASAS classification criteria. CONCLUSION: Considering the recent ASAS definition of early axSpA, TNFi effectiveness seems comparable in early versus established disease.
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Espondiloartritis Axial , Inhibidores del Factor de Necrosis Tumoral , Humanos , Estudios de Cohortes , Consenso , Calidad de Vida , Sistema de Registros , Resultado del Tratamiento , Inhibidores del Factor de Necrosis Tumoral/uso terapéuticoRESUMEN
BACKGROUND AND AIMS: People with familial hypercholesterolaemia are 13 times more likely to develop cardiovascular disease than the general population. However, familial hypercholesterolaemia remains largely underdiagnosed. Tendon xanthoma is a specific clinical feature of familial hypercholesterolaemia and its presence alone implies a probable diagnosis of familial hypercholesterolaemia according to the Dutch Lipid Clinic Network Score (DLCNS). The aim of the study was to determine whether ultrasound detects more Achilles tendon xanthomas (ATX) than clinical examination. METHODS: We recruited 100 consecutive patients with LDL-C ≥4 mmol/l. Achilles tendons were evaluated through clinical examination by trained physicians and sonographic examination by another physician blind to the results of clinical examination. Blind second readings of ultrasound images were performed by an expert in musculoskeletal ultrasound. We compared the proportion of patients with ATX detected by either clinical examination or ultrasound and the proportion of patients with a probable/definite familial hypercholesterolaemia diagnosis on the DLCNS before and after ultrasound. RESULTS: Mean (SD) age was 47 (12) years; mean highest LDL-C was 6.57 mmol/l (2.2). ATX were detected in 23% of patients by clinical examination and in 60% by ultrasound. In consequence, 43% had a probable/definite diagnosis of familial hypercholesterolaemia on the DLCNS using clinical examination compared with 72% when ultrasound was used. CONCLUSION: Compared to clinical examination, ultrasound examination of the Achilles tendon substantially improves the detection of ATX and may help to better identify patients with familial hypercholesterolaemia who are at high risk for premature cardiovascular disease.
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Tendón Calcáneo , Enfermedades Cardiovasculares , Hiperlipoproteinemia Tipo II , Humanos , Persona de Mediana Edad , Tendón Calcáneo/diagnóstico por imagen , LDL-Colesterol , Estudios Transversales , Hiperlipoproteinemia Tipo II/diagnóstico por imagen , UltrasonografíaRESUMEN
Recently, serious infections related to the use of tofacitinib (TOF) for treatment of rheumatoid arthritis (RA) have raised considerable interest. This study aimed to compare the risk for serious infections in patients with RA upon receiving TOF versus biologic disease-modifying antirheumatic drugs (bDMARDs) by age at treatment initiation. We identified adult RA patients exposed to TOF or bDMARDs using data collected by the Swiss registry for inflammatory rheumatic diseases (SCQM) from 2015 to 2018. The event of interest was the first non-fatal serious infection (SI) during drug exposure. Missing or incomplete SI dates were imputed as either the lower (left) or upper (right) limit of the known occurrence interval. The ratio of SI hazards (HR) of TOF versus bDMARDs was estimated as a function of age using covariate-adjusted Cox regression applied to each type of imputed time-to-SI. A total of 1687 patients provided time at risk for a first SI during study participation and drug exposure for 2238 different treatment courses, 345 for TOF and 1893 for bDMARDs. We identified 44 (left imputation) or 43 (right imputation), respectively, first SIs (12/12 on TOF versus 32/31 on bDMARDs). Left and right imputation produced similar results. For patients aged ≥ 69 years, the treatment HR started to be increased (lower limit of 95% confidence intervals (LLCIs) > 1). By the age of 76, the difference between TOF and bDMARDs started to be clinically relevant (LLCIs > 1.25). For patients aged < 65 years, the data were insufficient to draw conclusions. Our results suggest that we should expect an increased risk for SIs in older patients treated with TOF compared to bDMARDs supporting a cautious use of TOF in these patients.
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Antirreumáticos , Artritis Reumatoide , Productos Biológicos , Infecciones , Adulto , Humanos , Anciano , Productos Biológicos/efectos adversos , Artritis Reumatoide/epidemiología , Antirreumáticos/efectos adversos , Factores Biológicos/uso terapéutico , Infecciones/epidemiologíaRESUMEN
OBJECTIVE: A lack of representation in pivotal trials currently limits guidance for the use of biological disease-modifying anti-rheumatic drugs (bDMARDs) in psoriatic arthritis (PsA) patients with a low number of actively inflamed joints. The aim of this study was to compare the effectiveness of a first bDMARD in PsA patients with low vs high number of affected joints. METHODS: PsA patients with available 66/68 joint count assessments were divided into low joint count (LJC) patients when presenting with <3 tender or < 3 swollen joints or high joint count patients (HJC) with > =3 joints in both categories. We studied drug retention as a joint count independent effectiveness variable in LJC and HJC patients in univariate and multivariable adjusted Cox regression models. RESULTS: 197 LJC patients differed not only in joint counts, but also had lower enthesitis scores, less often dactylitis, less disability and a better health related quality of life at first bDMARD initiation than 190 HJC patients. However, LJC were less often on conventional synthetic (cs) DMARDs. Despite these differences at baseline, bDMARD retention was not significantly different between LJC and HJC in both crude and adjusted analyses (Hazard Ratio (HR) 1.09 [0.76-1.58], p= 0.52). Furthermore, bDMARD retention was significantly better (HR 0.63 [0.47-0.85], p< 0.002) when administered with csDMARD co-therapy. CONCLUSIONS: Biological DMARDs were similarly effective in terms of drug retention in patients with low and high joint counts. In the setting of absent remission and a significant disease burden, bDMARDs should not be withheld from patients because they exhibit only a low joint count.
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This is the first report comparing EULAR and national treatment recommendations for PsA patients across Europe, and the first this decade to compare ASAS-EULAR and national treatment recommendations in axSpA patients. An electronic survey was completed from October 2021-April 2022 by rheumatologists in 15 European countries. One and four countries followed all EULAR and ASAS-EULAR recommendations, respectively. Five countries had no national treatment recommendations for PsA and/or axSpA, but followed other regulations. In several countries, national treatment recommendations predated the most recent EULAR/ASAS-EULAR recommendations. Entry criteria for starting biologic/targeted synthetic disease-modifying anti-rheumatic drugs varied considerably. In several countries, for PsA patients with significant skin involvement, interleukin-17 inhibitors were not given preference. The positioning of Janus Kinase inhibitors differed and Phosphodiesterase-4 inhibitors were not in use/reimbursed in most countries. This study may motivate European countries to update their national treatment recommendations, to align them better with the latest international recommendations.
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OBJECTIVE: Obesity is an important comorbidity in axial spondyloarthritis (axSpA); however, the prevalence of obesity in axSpA compared with the general population and associated socioeconomic factors remain unknown. METHODS: This repeated cross-sectional study compared BMI (kg/m2) groups of patients with axSpA to the Swiss population at 3 timepoints (2007, 2012, and 2017). BMI categories were compared by different age, sex, and education categories using the chi-square goodness of fit test. Unpaired, 1-sided t tests were used to compare the BMI in patients with axSpA between the different timepoints. RESULTS: Compared to the general population, patients with axSpA had a higher proportion of overweight and obesity: 18.9% of all patients with axSpA were obese, compared to 11.3% of the Swiss population in 2017. Comparison of BMI groups within sex, age, and education groups consistently showed a trend toward higher rates of overweight and obesity in axSpA. Further, patients with axSpA, especially females, showed a trend of increasing BMI over the studied 10 years. At every time point, overweight and obese patients were significantly more likely to be male, were older, and had higher disease activity than patients with normal weight. Obesity was associated with a deprived socioeconomic status as indicated by a higher proportion of patients with manual labor jobs and lower levels of education. CONCLUSION: The prevalence of obesity was significantly higher among patients with axSpA compared to the Swiss population, with socially disadvantaged individuals being the most affected. There is an urgent need to initiate prevention strategies for obesity in patients with axSpA.
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OBJECTIVE: To investigate sex differences in spinal radiographic progression in axial spondyloarthritis (axSpA). METHODS: AxSpA patients in the Swiss Clinical Quality Management cohort with available spinal radiographs every 2 years were included. Paired radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Progression was defined as an increase of ≥2 mSASSS units in 2 years. The relationship between sex and progression was investigated with binomial generalised estimating equation models, considering baseline spinal damage as an intermediate covariate. Additional analyses included adjustments for explanatory variables and multiple imputations for missingness. RESULTS: In a total of 505 axSpA patients (317 men and 188 women), mean±SD radiographic progression over 2 years was 1.0±2.8 years in men and 0.3±1.1 years in women (p<0.001). Male sex was associated with enhanced progression in a small model not including baseline damage (OR 3.41, 95% CI 1.87 to 6.21). Both a direct effect of male sex on spinal progression, and an indirect effect, via enhancement of baseline spinal damage were significant (OR 2.06, 95% CI 1.15 to 3.67 and OR 1.04, 95% CI 1.01 to 1.07, respectively). A significant impact of male sex on spinal radiographic progression was still demonstrated after multiple adjustments for covariates known to potentially affect spinal radiographic progression (OR 1.97, 95% CI 1.04 to 3.71). CONCLUSIONS: Spinal radiographic progression in axSpA is more severe in men than in women, with three times higher odds of progression in male patients and an effect that is mediated in part through an increase in baseline radiographic damage.
Asunto(s)
Espondilitis Anquilosante , Humanos , Masculino , Femenino , Suiza/epidemiología , Progresión de la Enfermedad , Espondilitis Anquilosante/diagnóstico por imagen , Espondilitis Anquilosante/epidemiología , Columna Vertebral/diagnóstico por imagen , Estudios de CohortesRESUMEN
OBJECTIVE: As anaemia represents a biomarker for increased radiographic damage in rheumatoid arthritis, we aimed to investigate whether it independently predicts spinal radiographic progression in axial spondyloarthritis (axSpA). METHODS: AxSpA patients with available haemoglobin levels from the prospective Swiss Clinical Quality Management Registry were included for comparison of patients with and without anaemia. Spinal radiographic progression was assessed according to the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) in patients with ankylosing spondylitis (AS) if ≥ 2 sets of spinal radiographs were available every 2 years. The relationship between anaemia and progression (defined as an increase ≥ 2 mSASSS units in 2 years) was analysed with generalized estimating equation models after adjustment for the Ankylosing Spondylitis Disease Activity Score (ASDAS) and potential confounding, as well as after multiple imputations of missing values. RESULTS: A total of 212/2522 axSpA patients presented with anaemia (9%). Anaemic patients had higher clinical disease activity, higher acute phase reactants and more severe impairments in physical function, mobility and quality of life. In the subgroup of patients with AS (N = 433), a comparable mSASSS progression was found in anaemic and non-anaemic patients (OR 0.69, 95% CI 0.25 to 1.96, p = 0.49). Age, male sex, baseline radiographic damage and ASDAS were associated with enhanced progression. The results were confirmed in complete case analyses and with progression defined as the formation of ≥ 1 syndesmophyte in 2 years. CONCLUSION: Although anaemia was associated with higher disease activity in axSpA, it did not additionally contribute to the prediction of spinal radiographic progression. Key Points ⢠Anaemia is associated with higher disease activity and more severely impaired physical function, mobility and quality of life in axSpA. ⢠Anaemia does not provide an additional value to ASDAS for prediction of spinal radiographic progression.