Exploring complement biomarkers in suspected axial spondyloarthritis.

OBJECTIVES: To investigate lectin pathway proteins (LPPs) as biomarkers for axial spondyloarthritis (axSpA) in a cross-sectional cohort with a suspicion of axSpA, comprising newly diagnosed axSpA and chronic low back pain (cLBP) individuals. METHODS: Serum samples from 515 participants within the OptiRef cohort, including 151 axSpA patients and 364 cLBP patients, were measured using immunoassays for LPPs (mannan-binding lectin (MBL), collectin liver-1 (CL-L1), M-ficolin, H-ficolin and L-ficolin, MBL-associated serine proteases (MASP)-1, -2 and -3, MBL-associated proteins (MAp19 and MAp44) and the complement activation product C3dg). RESULTS: Serum levels of L-ficolin, MASP-2 and C3dg were elevated in axSpA patients, whereas levels of MASP-3 and CL-L1 were decreased, and this remained significant for C3dg and MASP-3 after adjustment for C reactive protein (CRP). A univariate regression analysis showed serum levels of CL-L1, MASP-2, MASP-3 and C3dg to predict the diagnosis of axSpA, and MASP-3 and C3dg remained significant in a multivariate logistic regression analysis. Assessment of the diagnostic potential showed that a combination of human leukocyte antigen B27 (HLA-B27) and measurements of L-ficolin, MASP-3 and C3dg increased the diagnostic specificity for axSpA, however, with a concomitant loss of sensitivity. CONCLUSIONS: Serum levels of complement activation, that is, C3dg, and MASP-3 differed significantly between axSpA and cLBP patients after adjustment for CRP. Although combining HLA-B27 with measurements of L-ficolin, MASP-3 and C3dg increased the diagnostic specificity for axSpA, this seems unjustified due to the concomitant loss of sensitivity. However, both C3dg and MASP-3 were associated with axSpA diagnosis in multivariate logistic regression, suggesting an involvement of complement in the inflammatory processes and possibly pathogenesis in axSpA.

Comparative study of two laboratory techniques for the detection of HLA-B27 in patients with axial spondyloarthritis: a cross-sectional analysis.

BACKGROUND: The diagnostic and prognostic relevance of Human Leukocyte Antigen B-27 (HLA-B27) in Axial Spondyloarthritis (AxSpA) is undeniable, with 70% of Ankylosing Spondylitis (AS) patients carrying the B27 gene, contrasted with a mere 4.35% in the general population. Flow cytometry (FC) and Polymerase Chain Reaction (PCR) have emerged as the predominant techniques for routine HLA-B27 typing. While various studies have compared these methods, none have catered to the unique characteristics of the Brazilian demographic. Therefore, this research aims to compare FC and PCR in a Brazilian cohort diagnosed with AxSpA. METHODS: An analytical cross-sectional study was undertaken involving 62 AxSpA outpatients from a Brazilian University Hospital. Both FC and PCR-SSP assays were utilized to ascertain HLA-B27 typing. The outcomes (either confirming or refuting the allele's presence) underwent rigorous scrutiny. Agreement between the methodologies was assessed using the kappa statistic. A p-value of < 0.05 was deemed statistically significant. RESULTS: Of the participants, 90.3% (n = 56) were HLA-B27 positive according to FC, while 79% (n = 49) were identified as positive using the PCR method. FC exhibited a sensitivity rate of 98% paired with a specificity of 38.5%. The Positive Predictive Value for FC stood at 85.7%, and the Negative Predictive Value was 83.5%. Consequently, the overall accuracy of the FC method was gauged at 85.5%. A kappa coefficient of κ = 0.454 was derived. CONCLUSIONS: FC demonstrated noteworthy sensitivity and satisfactory accuracy in HLA-B27 detection, albeit with a reduced specificity when contrasted with PCR-SSP. Nevertheless, given its cost-effectiveness and streamlined operation relative to PCR, FC remains a pragmatic option for preliminary screening in clinical practice, especially in low-income regions. To optimize resource allocation, we advocate for a refined algorithm that initiates by assessing the relevance of HLA-B27 typing based on Choosing Wisely recommendations. It then leans on FC, and, if results are negative yet clinical suspicion persists, advances to PCR. This approach aims to balance diagnostic accuracy and financial prudence, particularly in regions contending with escalating medical costs.

Navigating the complexity of pain in psoriatic arthritis and axial spondyloarthritis.

PURPOSE OF REVIEW: Pain is the most common and often most troublesome feature of chronic autoimmune diseases such as psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA). A predominant concept is that the main source of pain is from disease-induced tissue inflammation and structural damage, activating peripheral nerve fibers which relay to the central nervous system. This mechanism is nociceptive pain and the presumption has been that controlling inflammation will be sufficient to reduce this form of pain. However, despite control of inflammation, patients may still have significant residual pain. RECENT FINDINGS: We are learning that there are additional pain mechanisms, neuropathic and nociplastic, that are often operative in patients with rheumatologic conditions, that can significantly influence pain experience, quantitation of disease activity, and may benefit from therapeutic approaches distinct from immunotherapy. Neuropathic pain arises from diseased or damaged nerve tissue and nociplastic pain reflects sensitization of the central nervous system due to multiple genetic, neurobiologic, neural network dysregulation, and psychosocial factors. Pain arising from these mechanisms influence assessment of disease activity and thus needs to be factored into decision-making about immunotherapy efficacy. SUMMARY: This review addresses the importance of accurately assessing the complex mechanisms of pain experience in patients with PsA and AxSpA to more appropriately manage immunomodulatory, neuromodulatory, and nonpharmacologic therapies.

Disease modification in axial spondyloarthritis - still a controversy?

PURPOSE OF REVIEW: This review evaluates recent advancements in disease-modifying therapies for axial spondyloarthritis (axSpA). RECENT FINDINGS: A recent study could not demonstrate an additional effect of NSAID therapy on golimumab [Tumor Necrosis Factor-α inhibitor (TNFi)] on structural progression; however, this might be due to the fact that the study was underpowered. While DMARDs have shown promise in suppressing inflammation, their impact on structural progression remains uncertain. A well powered trial showed no difference in spinal progression between secukinumab [Interleukin17A inhibitor (IL17Ai)] and adalimumab-biosimilar (TNFi). Preliminary data on Janus kinase inhibitors (JAKi) focus on MRI findings but lack evidence on radiographic spinal progression. While some studies suggest promising outcomes, others reveal limitations and inconclusive findings. SUMMARY: Recent studies explore the effectiveness of NSAIDs, biological disease-modifying antirheumatic drugs like TNFi and IL-17i, as well as JAK inhibitors in axSpA. Conflicting evidence surrounds these therapies' ability to impede structural progression, with challenges in study design and interpretation. Moreover, changes in demographics and treatment methods underscore the importance of examining trends over time when assessing disease outcomes. Ultimately, ongoing research could benefit from new imaging tools when evaluating therapeutic strategies for modifying disease progression in axSpA.

Evaluation of a hybrid telehealth care pathway for patients with axial spondyloarthritis including self-sampling at home: results of a longitudinal proof-of-concept mixed-methods study (TeleSpactive).

Patients with axial spondyloarthritis (axSpA) require close monitoring to achieve the goal of sustained disease remission. Telehealth can facilitate continuous care while relieving scarce healthcare resources. In a mixed-methods proof-of-concept study, we investigated a hybrid telehealth care axSpA pathway in patients with stable disease over 6 months. Patients used a medical app to document disease activity (BASDAI and PtGA bi-weekly, flare questionnaire weekly). To enable a remote ASDAS-CRP (TELE-ASDAS-CRP), patients used a capillary self-sampling device at home. Monitoring results were discussed and a decision was reached via shared decision-making whether a pre-planned 3-month on-site appointment (T3) was necessary. Ten patients completed the study, and eight patients also completed additional telephone interviews. Questionnaire adherence was high; BASDAI (82.3%), flares (74.8%) and all patients successfully completed the TELE-ASDAS-CRP for the T3 evaluation. At T3, 9/10 patients were in remission or low disease activity and all patients declined the offer of an optional T3 on-site appointment. Patient acceptance of all study components was high with a net promoter score (NPS) of +50% (mean NPS 8.8 ± 1.5) for self-sampling, +70% (mean NPS 9.0 ± 1.6) for the electronic questionnaires and +90% for the T3 teleconsultation (mean NPS 9.7 ± 0.6). In interviews, patients reported benefits such as a better overview of their condition, ease of use of telehealth tools, greater autonomy, and, most importantly, travel time savings. To our knowledge, this is the first study to investigate a hybrid approach to follow-up axSpA patients including self-sampling. The positive results observed in this scalable proof-of-concept study warrant a larger confirmatory study.

Axial spondyloarthritis guidelines - aiming for maximum impact.

PURPOSE OF REVIEW: This review discusses international clinical practice guidelines (CPGs) for axial spondyloarthritis (axSpA) focusing on methodology, guideline quality, and implementation. RECENT FINDINGS: The Assessment of SpondyloArthritis International Society/European Alliance of Associations for Rheumatology (ASAS/EULAR) and Pan-American League of Associations for Rheumatology (PANLAR) recently published axSpA CPGs and updates of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network (ACR/SAA/SPARTAN) and Asia-Pacific League of Associations for Rheumatology (APLAR) CPGs are expected. GRADE has emerged as the dominant framework for CPG development and has been used by three of the four international axSpA guidelines. Notable differences exist among these guidelines in the way that the recommendations are presented. Two of the four acknowledge the need for implementation strategies, but little detail about this is provided. The few studies that have evaluated the implementation of axSpA CPGs have identified poor adherence to recommendations on physical therapy/exercise and disease activity monitoring. Implementation science has identified many barriers and facilitators affecting guideline uptake, including those related to healthcare professionals and to the guidelines themselves. Creation of a tailored implementation plan simultaneously with the CPG is recommended. SUMMARY: While methodological rigor in the creation of evidence-based recommendations is the focus of CPG development, recommendations must be presented in a user-friendly format that makes them easy to apply. 'Living guidelines' could facilitate keeping content up to date. Implementation is critical for the success of a CPG and should be emphasized in future axSpA guideline updates. Further research is needed to better understand the factors impacting the successful implementation of axSpA CPGs.

Sociodemographic and clinical variables associated with negative illness perception in patients newly diagnosed with rheumatoid arthritis, axial spondyloarthritis, or psoriatic arthritis-a survey based cross-sectional study.

When newly diagnosed with inflammatory arthritis (IA), acquiring self-management skills is beneficial, to enhance quality of life. The personal beliefs and mental representations patients hold about their illness, known as illness perception, significantly influence the development of these skills. Recognizing characteristics that affect illness perception is key to identifying patients requiring additional support for the development of self-management skills. This study aimed at identifying the sociodemographic and clinical characteristics associated with a negative illness perception. This cross-sectional study was based on survey data from patients diagnosed for ≤ 2 years. The Brief Illness Perception Questionnaire (B-IPQ) was used to measure illness perception. After psychometric testing, we divided the B-IPQ into two domains: (1) a control domain and (2) a consequence domain. We performed logistic regression analyses with multiple imputations. A total of 1,360 patients (61% females) were included. Among them, 64%, 20%, and 16% were diagnosed with rheumatoid arthritis, psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), respectively. Younger patients with lower socioeconomic status, a diagnosis of PsA or axSpA, high disease activity (OR 3.026, CI 2.208;4.147), severe physical disability (OR 4.147. CI 2.883;6.007), severe pain (OR 3.034, CI 1.991;4.622), and severe fatigue (OR 2.612, CI 1.942;3.513) were significantly more likely to report having a negative illness perception. Younger patients with a higher symptom burden, increased disease activity, lower socioeconomic status, and a diagnosis of PsA or axSpA may require additional attention and support in rheumatology clinical practice to aid in the development of their self-management skills.

Clinical, Laboratory, and Imaging Features Between Men and Women With Axial Spondyloarthritis in a Specialized Center in Argentina.

OBJECTIVES: The aims were to estimate the frequency of axial spondyloarthritis (axSpA) in women and to analyze the clinical, laboratory, and imaging differences with respect to men at the time of diagnosis. METHODS: Consecutive patients older than 18 years with a diagnosis of axSpA admitted to the "Reumacheck" SpA program were included between 2017 and 2022. At baseline, all patients underwent clinical assessment, laboratory tests including C-reactive protein and human leukocyte antigen B27, and imaging (plain radiography and magnetic resonance imaging of sacroiliac joints, and ultrasound of heel entheses). All evaluators were blinded to the results of the other evaluations. RESULTS: One hundred sixteen patients with a diagnosis of axSpA were included. The frequency at diagnosis in women was 61.55%. In the univariate analysis, the significant differences between women and men at diagnosis of axSpA were good response to nonsteroidal anti-inflammatory drugs, elevated C-reactive protein, New York Criteria (+), enthesis ultrasound (+), years of education, number of swollen joints, erythrosedimentation rate, and the very low frequency of bone bridges in the magnetic resonance imaging of the sacroiliac joints. In the logistic regression analysis, the dependent variable was "men," and the only feature that was independently associated was having radiographic compromise according to the New York criteria (odds ratio, 2.6). CONCLUSIONS: The frequency of axSpA in women was 61.55%; clinical, laboratory, and imaging differences were observed. Women experienced less radiographic compromise.

Artificial intelligence and machine learning in axial spondyloarthritis.

PURPOSE OF REVIEW: To evaluate the current applications and prospects of artificial intelligence and machine learning in diagnosing and managing axial spondyloarthritis (axSpA), focusing on their role in medical imaging, predictive modelling, and patient monitoring. RECENT FINDINGS: Artificial intelligence, particularly deep learning, is showing promise in diagnosing axSpA assisting with X-ray, computed tomography (CT) and MRI analyses, with some models matching or outperforming radiologists in detecting sacroiliitis and markers. Moreover, it is increasingly being used in predictive modelling of disease progression and personalized treatment, and could aid risk assessment, treatment response and clinical subtype identification. Variable study designs, sample sizes and the predominance of retrospective, single-centre studies still limit the generalizability of results. SUMMARY: Artificial intelligence technologies have significant potential to advance the diagnosis and treatment of axSpA, providing more accurate, efficient and personalized healthcare solutions. However, their integration into clinical practice requires rigorous validation, ethical and legal considerations, and comprehensive training for healthcare professionals. Future advances in artificial intelligence could complement clinical expertise and improve patient care through improved diagnostic accuracy and tailored therapeutic strategies, but the challenge remains to ensure that these technologies are validated in prospective multicentre trials and ethically integrated into patient care.

How to Monitor Disease Activity of Axial Spondyloarthritis in Clinical Practice.

PURPOSE OF REVIEW: Treatment guided by periodic and quantitative data assessment results in better outcomes compared to using clinical gestalt. While validated generic as well as specific disease activity measures for axial spondyloarthritis (axSpA) are available, there is vast scope to improve their actual utilization in routine clinical practice. In this review, we discuss available disease activity measures for axSpA, describe results from the survey conducted among general rheumatologists as well as Spondyloarthritis Research and Treatment Network (SPARTAN) members about disease activity measurement in daily practice, and discuss ways to improve axSpA disease activity using technological advances. We also discuss the definitions of active disease and target for the treatment of axSpA. RECENT FINDINGS: The 2019 American College of Rheumatology (ACR)/Spondylitis Association of America (SAA)/Spondyloarthritis Research and Treatment Network (SPARTAN) axSpA treatment guidelines conditionally recommend the regular monitoring of disease activity using a validated measure such as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) or Ankylosing Spondylitis Disease Severity Index (ASDAS). Assessment of Spondyloarthritis International Society (ASAS)-European Alliance of Associations for Rheumatology (EULAR) guidelines recommend ASDAS as the most appropriate instrument for the assessment of disease activity, preferably calculated using C-reactive protein (CRP). ASAS has selected a core set of variables which were updated recently and have been endorsed by the Outcome Measures in Rheumatology Clinical Trials (OMERACT) group in order to bring homogeneity in assessment of axSpA. In a recent study, Patient-Reported Outcomes Measurement Information System (PROMIS®) measures were able to discriminate inactive, moderate, and high-very high ASDAS activity groups. A newly developed semi-objective index P4 (pain, physical function, patient global, and physician global) correlates well with BASDAI and ASDAS in axSpA and can also be used for other rheumatic diseases in busy clinical practices. Regular disease activity monitoring is critical for long-term management of axSpA and shared decision-making. The integration of electronic health records and smart devices provides a great opportunity to capture patient-reported data. Automated capture of electronic patient-reported outcome measures (ePROMs) is a highly efficient way and results in consistent regular monitoring and may improve the long-term outcomes. While currently used measures focus only on musculoskeletal symptoms of axSpA, a composite disease activity measure that can also incorporate extra-articular manifestations may provide a better assessment of disease activity.

Serum biomarkers and their relationship to axial spondyloarthritis associated with inflammatory bowel diseases.

Spondyloarthritis (SpA) constitute a group of chronic inflammatory immune-mediated rheumatic diseases characterized by genetic, clinical, and radiological features. Recent efforts have concentrated on identifying biomarkers linked to axial SpA associated with inflammatory bowel disease (IBD), offering predictive insights into disease onset, activity, and progression. Genetically, the significance of the HLA-B27 antigen is notably diminished in ankylosing spondylitis (AS) associated with IBD, but is heightened in concurrent sacroiliitis. Similarly, certain polymorphisms of endoplasmic reticulum aminopeptidase (ERAP-1) appear to be involved. Carriage of variant NOD2/CARD15 polymorphisms has been demonstrated to correlate with the risk of subclinical intestinal inflammation in AS. Biomarkers indicative of pro-inflammatory activity, including C-reactive protein (CRP) along with erythrocyte sedimentation rate (ESR), are among the consistent predictive biomarkers of disease progression. Nevertheless, these markers are not without limitations and exhibit relatively low sensitivity. Other promising markers encompass IL-6, serum calprotectin (s-CLP), serum amyloid (SAA), as well as biomarkers regulating bone formation such as metalloproteinase-3 (MMP-3) and Dickkopf-related protein 1 (DKK-1). Additional candidate indicators of structural changes in SpA patients include matrix metalloproteinase-3 (MMP-3), vascular endothelial growth factor (VEGF), tenascin C (TNC), and CD74 IgG. Fecal caprotein (f-CLP) levels over long-term follow-up of AS patients have demonstrated predictive value in anticipating the development of IBD. Serologic antibodies characteristic of IBD (ASCA, ANCA) have also been compared; however, results exhibit variability. In this review, we will focus on biomarkers associated with both axial SpA and idiopathic intestinal inflammation, notably enteropathic spondyloarthritis.

Ten-year clinical outcome of recent-onset axial spondyloarthritis: Results from the DESIR inception Cohort.

OBJECTIVES: This study aimed to evaluate the 10-year clinical outcome of patients with recent-onset axial spondyloarthritis (axSpA). METHODS STUDY DESIGN: The DESIR cohort is an inception cohort of axSpA patients. METHODS DIAGNOSIS AND MANAGEMENT: The diagnosis and management of patients were based on the decision of the treating rheumatologist. METHODS STATISTICAL ANALYSIS: Both complete cases and imputed data analyses were conducted. RESULTS: Of the 708 enrolled patients, 45 were excluded due to a change in the baseline diagnosis, 3 patients died, and 300 were lost to follow-up over the 10years. In the completer population, one patient required bilateral total hip replacement, and 56 patients received a pension due to invalidity. The prevalence of main extra-musculoskeletal features increased from baseline to year 10: psoriasis from 18% to 30%, acute anterior uveitis from 10% to 18%, and inflammatory bowel disease from 5% to 10%. The most frequent comorbidity was hypertension, with an increase from 5% to 15% from baseline to year 10. In the imputed data analysis the estimated proportions of patients with an acceptable status at year 10 were 70% [95% CI: 63; 77] for acceptable PASS, 43% [95% CI: 37; 49] for BASDAI<3, and 48% [95% CI: 41; 56] for ASDAS<2.1. CONCLUSION: These findings suggest that despite a quite favorable 10-year outcome exists for severe outcomes, a large proportion of patients present with an important disease burden reflected by patient-reported outcomes. This information can be valuable for providing patients with information at the time of diagnosis.

Depression as a possible determinant of fatigue in patients with axial spondyloarthritis.

OBJECTIVES: Fatigue is a common comorbidity in patients with axial spondyloarthritis (axSpA), often reported also by those in clinical remission or with moderate disease activity. The aim of this study is to assess the prevalence of fatigue in patients with axSPA, and to investigate possible non-disease-related determinants, with a special focus on depression. METHODS: Patients with axSpA were assessed using the Chalder's Fatigue Questionnaire (CFQ) for fatigue, and the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D) for depression. Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index (BASFI) and Health Assessment Questionnaire (HAQ) were also used to assess disease activities and disability. Univariate and multivariate linear regressions were performed to identify possible predictors of fatigue. RESULTS: Out of 119 patients, 53 (44.5%) had fatigue. Patients with fatigue had higher HADS-D, ASDAS, BASFI, HAQ scores. HADS-D was predictive of CFQ score in univariate and multivariate regressions for total CFQ, and for mental and physical subscales. The correlation between HADS-D and CFQ total score was statistically significant also when taking into consideration only patients in clinical remission and with moderate disease activity. Depressed patients had higher CFQ score compared to non-depressed ones, and did not show any difference in CFQ scores when stratified for disease activity or systemic inflammation. CONCLUSIONS: The study found correlation between fatigue and disease activity and depression in patients with axSpA. These findings suggest that depression could represent the major determinant of fatigue in patients with axSpA, independently of clinical activity.

Teste de detecção de HLA-B27para indivíduos com suspeita de espondiloartrite axial e para avaliação prognóstica da doença / HLA-B27 detection test for individuals suspected of having axial spondyloarthritis and for prognostic assessment of the disease

INTRODUÇÃO: A Espondiloartrite Axial (EpA) é uma doença inflamatória crônica, de origem autoimune, caracterizada por dor intensa, enrijecimento das articulações (anquilose) com inflamação nas inserções dos tendões, limitação funcional progressiva, provocando danos estruturais irreversíveis das articulações sacroilíacas e espinhais, que cursam com alterações radiográficas e formação óssea excessiva. O antígeno HLA-B27 está fortemente correlacionado com o aparecimento da doença e um teste positivo para esse marcador é encontrado na maioria dos casos. No Brasil, diversos estudos sugerem que os portadores do antígeno HLA-B27 representam em torno de 60-70% dos pacientes. PERGUNTA: Em indivíduos com suspeita de espondiloartrite axial, qual a sensibilidade, especificidade e utilidade diagnóstica do teste HLA-B27 em comparação aos critérios ASAS, de Nova Iorque e diagnóstico por radiologista? EVIDÊNCIAS CLÍNICAS: Nos estudos incluídos, conduzidos em sua maioria em países europeus, foram comparados o teste HLA-B27 e os critérios de diagnóstico ASAS ou Nova Iorque. A sensibilidade do teste HLA-B27 foi de 68% (IC95%: 67-69%) e a especificidade de 88% (IC95%: 87-88%). Além disso, o valor preditivo positivo do teste foi em média de 0,71 (± 0,21), enquanto o valor preditivo negativo foi em média de 0,74 (± 0,20); a razão de verossimilhança positiva e negativa foi de 4,85 (IC95% 3,83-6,14) e 0,36 (IC95% 0,29-0,45). Foram realizadas análises de subgrupo considerando os diferentes comparadores: 1) critérios de diagnóstico ASAS, a sensibilidade estimada de HLAB27 foi de 67% (IC95%: 65-69%), e a especificidade foi de 92% (IC95%: 91-92%), 2) critérios de diagnóstico Nova Iorque modificado, a sensibilidade estimada de HLA-B27 foi de 85% (IC95%: 83- 87%), e a especificidade foi de 83% (IC95%: 81-85%). A partir da análise de dois estudos, observou-se que a associação de HLA-B27 e parâmetros clínicos ainda possibilitou o alcance de uma sensibilidade e especificidade comparável ou maior do que a combinação de exame de imagem (RMN ou radiografia) e parâmetros clínicos, ou apenas os parâmetros clínicos. No geral, estes estudos foram classificados como de alto ou incerto risco de viés, especialmente no domínio "seleção dos pacientes" devido à ausência de informação sobre o processo ou por uso de amostra não randomizada/consecutiva. O alto e incerto risco de viés aliado à elevada heterogeneidade e evidência indireta foram responsáveis pela classificação da qualidade da evidência como muito baixa para sensibilidade e especificidade. AVALIAÇÃO ECONÔMICA (AE): Foi desenvolvida uma análise de custo-efetividade comparando teste HLA-B27 + avaliação clínica versus i) avaliação clínica; e ii) avaliação clínica ± sacroileíte em exame de imagem (radiografia simples ou ressonância magnética). Para ambas as comparações foi elaborada uma árvore de decisão acoplada ao modelo de estados transicionais (Markov). Na comparação com avaliação clínica, o teste HLA-B27 + avaliação clínica este próximo do limiar de custo-efetividade custo-efetivo (R$ 43 mil reais por AVAQ). Além disso, apresentou custo incremental de R$ 298 por diagnóstico correto incremental. Na comparação com avaliação clínica ± exame de imagem, o teste de HLA-B27 + avaliação clínica dominou (menor custo e maior efetividade) o comparador, e foi considerado custo-efetivo na análise de cenário considerando como desfecho e apresentou custo incremental de R$ 2 mil por diagnóstico correto incremental. ANÁLISE DE IMPACTO ORÇAMENTÁRIO (AIO): No cenário atual foram considerados os critérios de classificação ASAS sem o teste HLA-B27 como alternativa disponível no SUS, a saber: avaliação clínica (49%) ou avaliação clínica + sacroileíte identificada por radiografia simples (49%) ou ressonância magnética (2%). O market share do cenário atual foi estabelecido com base em literatura científica, dados do Sistema de Informação Ambulatorial - produção ambulatorial e opinião de especialista. Por demanda aferida, foram estimados em torno de 15 a 18 mil indivíduos por ano com suspeita de espondiloartrite axial e 5,7 a 6,9 mil indivíduos com resultados negativos ou incerto pela avaliação clínica e de imagem. Observou-se que a incorporação de HLA-B27 no SUS para indicação proposta teria como resultado um incremento de custos de R$ 638 mil no primeiro ano, chegando a R$ 770 mil no quinto ano de análise. MONITORAMENTO DE HORIZONTE TECNOLÓGICO: Foram realizadas buscas estruturadas nas bases de dados ClinicalTrials.gov e Cortellis™ nos dias 22/11/2023 e 23/11/2023 para a localização de outros dispositivos utilizados na detecção do antígeno HLA-B27 em indivíduos com suspeita de espondiloartrite axial. As pesquisas nas bases de dados não apresentaram resultados para novos dispositivos. CONSIDERAÇÕES FINAIS: Os resultados dos parâmetros diagnósticos resultantes da utilização do teste HLA-B27 no contexto da espondiloatrite axial foram relacionados a alta grau de incerteza, o que dificulta a elaboração de conclusão mais definitivas. Nas avaliações econômicas foi demonstrado que o exame pode ser custo-efetivo, e exigirá, caso incorporado, um investimento do SUS, conforme observado na análise de impacto orçamentário. RECOMENDAÇÃO PRELIMINAR DA CONITEC: Os membros do Comitê de Produtos e Procedimentos presentes na 17ª Reunião Extraordinária da Conitec, realizada no dia 08 de dezembro de 2023, deliberaram, por unanimidade, que a matéria fosse disponibilizada em consulta pública com recomendação preliminar favorável à incorporação do teste de detecção de HLA-B27 para indivíduos com suspeita de espondiloartrite axial, que apresentem critérios clínicos da doença e que não apresentem alterações nos exames de imagem. CONSULTA PÚBLICA: A consulta pública nº 68 ficou aberta entre 29 de dezembro de 2023 e 17 de janeiro de 2024. Foram recebidas 95 contribuições, sendo 32 de experiência ou opinião e 63 técnico-cientificas. As contribuições técnicas-cientificas concordaram com a recomendação preliminar, reforçando a importância do teste e os achados deste relatório. Não foram identificadas contribuições técnico-científicas que fundamentassem a necessidade de análises adicionais de evidência clínica, avaliação econômica e análise de impacto orçamentário. Em relação às contribuições de experiência e opinião, os participantes, em sua maioria, concordaram com a recomendação preliminar da Conitec e se posicionaram favoravelmente à incorporação, no SUS, do teste de detecção de HLA-B27, argumentando, sobretudo, sobre a acurácia do teste e seus benefícios para o diagnóstico da condição de saúde em questão. Os participantes que usaram a tecnologia em avaliação destacaram, como aspectos positivos, a acurácia do teste, a sua contribuição para fechar o diagnóstico e o fato de ser um exame não invasivo. Como aspectos negativos, foram mencionados a dificuldade de acesso e o custo elevado. Em relação à experiência com outras tecnologias, os participantes pontuaram que estas contribuíram para concluir o diagnóstico e iniciar o tratamento, contudo, apontaram como aspectos negativos a dificuldade de acesso e o tempo de espera para realizar esses exames, impossibilitando o diagnóstico. RECOMENDAÇÃO FINAL DA CONITEC: Os membros do Comitê de Produtos e Procedimentos presentes na 127ª Reunião Ordinária da Conitec, realizada no dia 08 de março de 2024, deliberaram, por unanimidade, recomendar a incorporação do teste de detecção de HLA-B27 para indivíduos com suspeita de espondiloartrite axial, conforme Protocolo Clínico do Ministério da Saúde. O Comitê concluiu que o teste aumenta a acurácia quando associado a outras estratégias diagnósticas, com o potencial de ser custo-efetivo. Foi assinado o Registro de Deliberação nº 888/2024. DECISÃO: incorporar, no âmbito do Sistema Único de Saúde - SUS, o teste de detecção de HLAB27 para indivíduos com suspeita de espondiloartrite axial, conforme Protocolo Clínico do Ministério da Saúde, publicada no Diário Oficial da União nº 77, seção 1, página 177, em 22 de abril de 2024.

Both ASDAS and ADC are associated with spinal mobility in active axial spondyloarthritis: A comparison between early and later disease.

OBJECTIVE: Using diffusion-weighted imaging (DWI)-derived apparent diffusion coefficient (ADC), we aimed to determine the relationship between intensity of spinal inflammation and mobility in patients with axial spondyloarthritis (SpA) in early and later stages of active disease. The Ankylosing Spondylitis Disease Activity Score (ASDAS) was also used for a more comprehensive evaluation. METHODS: Participants with axial SpA and back pain were recruited from 10 rheumatology centers. Clinical, biochemical and radiological parameters were collected. Short tau inversion recovery (STIR) sequence magnetic resonance imaging (MRI) and DWI of the spine and sacroiliac (SI) joints were performed. ADC maps were generated. Participants were examined for Bath Ankylosing Spondylitis Metrology Index (BASMI). Linear regression models were used to determine associations between BASMI and various clinical, radiological, and MRI parameters in participants with active inflammation on spinal ADC maps. RESULTS: One-hundred and twenty-seven participants were included in the analyses. Multivariate linear regression showed that mean ADC spine (ß = .16; P = .03), ASDAS-C-reactive protein (CRP) (ß = .29, P < .001), and ASDAS-erythrocyte sedimentation rate (ESR) (ß = .25, P < .01) were associated with BASMI. In participants with duration of back pain ≤3 years, mean spine ADC (ß = .37; P = .03), ASDAS-CRP (ß = .44; P = .01), and ASDAS-ESR (ß = .42; P = .01) were associated with BASMI after adjustment for confounding factors. In participants with duration of back pain >3 years, only ASDAS-CRP (ß = .25; P < .01) and ASDAS-ESR (ß = .20; P = .20) were associated with BASMI. CONCLUSION: Intensity of inflammation and clinical disease activity were independently associated with impairment of spinal mobility. The associations were stronger in early (≤3 years) than later disease.

Diagnostic delay is common for patients with axial spondyloarthritis: results from the National Early Inflammatory Arthritis Audit.

OBJECTIVES: Updated guidelines for patients with axial SpA (axSpA) have sought to reduce diagnostic delay by raising awareness among clinicians. We used the National Early Inflammatory Arthritis Audit (NEIAA) to describe baseline characteristics and time to diagnosis for newly referred patients with axSpA in England and Wales. METHODS: Analyses were performed on sociodemographic and clinical metrics, including time to referral and assessment, for axSpA patients (n = 784) recruited to the NEIAA between May 2018 and March 2020. Comparators were patients recruited to the NEIAA with RA (n = 9270) or mechanical back pain (MBP; n = 370) in the same period. RESULTS: Symptom duration prior to initial rheumatology assessment was longer in axSpA than RA patients (P < 0.001) and non-significantly longer in axSpA than MBP patients (P = 0.062): 79.7% of axSpA patients had symptom durations of >6 months, compared with 33.7% of RA patients and 76.0% of MBP patients. Following referral, the median time to initial rheumatology assessment was longer for axSpA than RA patients (36 vs 24 days; P < 0.001) and similar to MBP patients (39 days; P = 0.30). Of the subset of patients deemed eligible for early inflammatory arthritis pathway follow-up, fewer axSpA than RA patients had disease education provided (77.5% vs 97.8%) and RA patients reported a better understanding of their condition and treatment. CONCLUSION: Diagnostic delay in axSpA remains a major challenge despite improved disease understanding and updated referral guidelines. Disease education is provided to fewer axSpA than RA patients, highlighting the need for specialist clinics and support programmes for axSpA patients.

Identifying parameters associated with delayed diagnosis in axial spondyloarthritis: data from the European map of axial spondyloarthritis.

OBJECTIVE: To identify the parameters associated with self-reported diagnostic delay (DD) in axial spondyloarthritis (axSpA) patients across Europe. METHODS: Data from 2652 patients from 13 countries who participated in the European Map of Axial Spondyloarthritis (EMAS) were collected through an online survey (2017-2018). DD was calculated as the difference between age at diagnosis and age at symptom onset reported by participants. Associations between DD and sociodemographic characteristics, as well as disease-related factors were explored through univariable and multivariable linear regression analysis. RESULTS: Average DD was 7.4 (8.4) years with a variation between countries. The variables associated with longer DD in the final multivariable regression model were: younger age at symptom onset (b = -0.26; 95% CI: -0.28, -0.23), female gender (b = 1.34; 95% CI: 0.73, 1.96) and higher number of health-care professionals (HCPs) seen before diagnosis (b = 1.19; 95% CI: 0.95, 1.43). There was a significant interaction between the female gender and the number of HCPs seen before diagnosis. A substantial variation of the DD across European countries was observed. CONCLUSION: In this sample of axSpA patients, average DD was greater than 7 years. Younger age at symptom onset, female gender, higher number of HCPs seen before diagnosis, and being diagnosed by rheumatologist were the parameters associated with a longer DD in axSpA. These findings indicate a need for continuing efforts dedicated to recognition of patients with a high probability of axSpA on the level of non-rheumatology specialists and facilitating referral to a rheumatologist for timely diagnosis.