RESUMO
Management guidelines assume that results from clinical trials can be generalised, although seldom is data available to test this assumption. We aimed to determine the proportion of patients commencing tumour necrosis factor inhibition (TNFi) who would have been eligible for relevant clinical trials, and whether treatment response differs between these groups and the trials themselves. The British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS) recruited a real-world cohort of TNFi-naïve spondyloarthritis patients with data collection from clinical records and patient questionnaires. Participant characteristics were extracted from trials identified from a recent Health Technology Assessment of TNFi for ankylosing spondylitis/non-radiographic axial spondyloarthritis. Descriptive statistics were used to determine the differences, including treatment response, between BSRBR-AS participants who would/would not have been eligible for the clinical trials and with trial participants. Among 2420 BSRBR-AS participants, those commencing TNFi (34%) had shorter symptom duration (15 vs 22 years) but more active disease (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 6.4 vs 4.0; Bath Ankylosing Spondylitis Disease Functional Index (BASFI) 6.2 vs 3.8). Of those commencing TNFi, 41% met eligibility criteria for ≥1 of fourteen relevant trials; they reported higher disease activity (BASDAI 6.9 vs 6.1) and poorer function (BASFI 6.6 vs 6.0). 61.7% of trial participants reported a positive treatment response, vs 51.3% of BSRBR-AS patients (difference: 10.4%; 95% CI 4.4% to 16.5%). Potential eligibility for trials did not influence treatment response (difference 2.0%; -9.4% to 13.4%). Fewer patients in the real world respond to TNFi than is reported in the trial literature. This has important implications for the generalisability of trial results, and the cost-effectiveness of TNFi agents.
Assuntos
Antirreumáticos/uso terapêutico , Ensaios Clínicos como Assunto/estatística & dados numéricos , Definição da Elegibilidade/estatística & dados numéricos , Espondilartrite/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Produtos Biológicos/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
OBJECTIVE: To determine modifiable factors associated with poor quality of life (QoL) in patients with axial spondyloarthritis (axSpA). METHODS: Analysis of data from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) and validation of a previous model using data from 1810 patients with axSpA recruited during 2012-2017. Data collected included clinical and patient-reported measures. QoL was assessed using the Ankylosing Spondylitis Quality of Life (ASQoL) measure. Linear regression models predicting ASQoL scores were used first to validate a previous model from a national study, to extend this with additional information available in BSRBR-AS and finally to identify a 'de novo' model from BSRBR-AS of which factors impact on poor QoL. RESULTS: Four out of five factors included in a previous model of poor QoL in patients with axSpA were confirmed: Bath Ankylosing Spondylitis Disease Activity Index and Bath Ankylosing Spondylitis Functional Index, fatigue and widespread pain, although the performance of the model was improved by the addition of measures of mood and sleep disturbance. In a de novo model in BSRBR-AS, there were six factors (other than disease activity and function) that predicted ASQoL: depression (ß=0.16), sleep disturbance (ß=0.08), activity impairment (ß=0.04), fibromyalgia (Symptom Severity Scale (ß=0.24) and Widespread Pain Index (ß=0.10)) and tobacco smoking (ß=0.66). CONCLUSION: This study confirms that poor QoL in patients with axSpA, in addition to high disease activity and poor function, is independently influenced by sleep disturbance, mood and widespread pain. These additional factors are not considered targets for treatment in current European League Against Rheumatism (EULAR) guidelines for managing the condition.
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Desempenho Físico Funcional , Qualidade de Vida , Reumatologia/estatística & dados numéricos , Índice de Gravidade de Doença , Espondilartrite/psicologia , Adulto , Afeto , Depressão/etiologia , Depressão/psicologia , Fadiga/etiologia , Fadiga/psicologia , Feminino , Fibromialgia/etiologia , Fibromialgia/psicologia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Dor/psicologia , Estudos Prospectivos , Sistema de Registros , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/psicologia , Espondilartrite/complicações , Fumar Tabaco/psicologiaRESUMO
OBJECTIVES: While many axSpA patients, eligible to receive anti-TNFα therapy, derive benefit when prescribed them, some patients do not. The current study aims to identify modifiable targets to improve outcome as well as non-modifiable targets that identify groups less likely to derive benefit. METHODS: The BSRBR-AS is a prospective cohort study of axSpA patients who, at recruitment, were naïve to biologic therapy. Those in the 'biologic' sub-cohort commenced their first anti-TNFα therapy at recruitment or during follow-up. Prior to commencement, information was collected on socio-economic, clinical and patient-reported factors. Outcome was assessed according to ASAS20, ASAS40, ASDAS reduction and achieving a moderate/inactive ASDAS disease state. RESULTS: 335 participants commenced their first anti-TNFα therapy and were followed up at a median of 14 (inter-quartile range 12-17) weeks. Response varied between 33% and 52% according to criteria used. Adverse socio-economic factors, fewer years in education predicted lower likelihood of response across outcome measures as did not working full-time. Co-morbidities and poor mental health were clinical and patient-reported factors, respectively, associated with lack of response. The models, particularly those using ASDAS, were good at predicting those who did not respond (negative predictive value (NPV) 77%). CONCLUSION: Some factors predicting non-response (such as mental health) are modifiable but many (such as social/economic factors) are not modifiable in clinic. They do, however, identify patients who are unlikely to benefit from biologic therapy alone. Priority should focus on how these patients receive the benefits that many derive from such therapies.
Assuntos
Terapia Biológica , Espondilite Anquilosante , Inibidores do Fator de Necrose Tumoral , Adulto , Terapia Biológica/economia , Terapia Biológica/métodos , Terapia Biológica/psicologia , Terapia Biológica/estatística & dados numéricos , Estudos de Coortes , Comorbidade , Modificador do Efeito Epidemiológico , Feminino , Humanos , Masculino , Saúde Mental/estatística & dados numéricos , Gravidade do Paciente , Medidas de Resultados Relatados pelo Paciente , Seleção de Pacientes , Medição de Risco/métodos , Fatores Socioeconômicos , Espondilite Anquilosante/epidemiologia , Espondilite Anquilosante/psicologia , Espondilite Anquilosante/terapia , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Reino Unido/epidemiologiaRESUMO
OBJECTIVES: To quantify, among patients with axial spondyloarthritis (axSpA), the benefit on work outcomes associated with commencing biologic therapy. METHODS: The British Society for Rheumatology Biologics Register in Axial Spondyloarthritis (BSRBRAS) recruited patients meeting Assessment of SpondyloArthritis International Society criteria for axSpA naïve to biological therapy across 83 centres in Great Britain. Work outcomes (measured using the Work Productivity and Activity Impairment Index) were compared between those starting biological therapy at the time of recruitment and those not. Differences between treatment groups were adjusted using propensity score matching. Results from BSRBR-AS were combined with other studies in a meta-analysis to calculate pooled estimates. RESULTS: Of the 577 participants in this analysis who were in employment, 27.9% were starting biological therapy at the time of recruitment. After propensity score adjustment, patients undergoing biological therapy, at 12-month follow-up, experienced significantly greater improvements (relative to non-biological therapy) in presenteeism (-9.4%, 95% CI -15.3% to -3.5%), overall work impairment (-13.9%, 95% CI -21.1% to -6.7%) and overall activity impairment (-19.2%, 95% CI -26.3% to -12.2%). There was no difference in absenteeism (-1.5%, 95% CI -8.0 to 4.9). Despite these improvements, impact on work was still greater in the biological treated cohort at follow-up. In the meta-analysis including 1109 subjects across observational studies and trials, treatment with biological therapy was associated with significantly greater improvements in presenteeism, work impairment and activity impairment, but there was no difference in absenteeism. CONCLUSIONS: There is consistent evidence that treatment with biological therapy significantly improves work productivity and activity impairment in people with axSpA. However, there remain substantial unmet needs in relation to work.
Assuntos
Antirreumáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Eficiência/efeitos dos fármacos , Espondilartrite/reabilitação , Absenteísmo , Adulto , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Presenteísmo/estatística & dados numéricos , Sistema de Registros , Índice de Gravidade de Doença , Espondilartrite/tratamento farmacológico , Espondilartrite/epidemiologia , Resultado do Tratamento , Reino Unido/epidemiologiaRESUMO
Objective: To quantify the extent to which co-morbid FM is associated with higher disease activity, worse quality of life (QoL) and poorer response to TNF inhibitors (TNFis) in patients with axial SpA. Methods: A prospective study recruiting across 83 centres in the UK. Clinical information and patient-reported measures were available, including 2011 criteria for FM. Multivariable linear regression was used to model the effect of meeting the FM criteria on disease activity, QoL and response to TNFis. Results: A total of 1757 participants were eligible for analyses, of whom 22.1% met criteria for FM. Those with co-morbid FM criteria had higher disease activity [BASDAI average difference FM+ - FM- 1.04 (95% CI 0.75, 1.33)] and worse QoL [Ankylosing Spondylitis Quality of Life score difference 1.42 (95% CI 0.88, 1.96)] after adjusting for demographic, clinical and lifestyle factors. Among 291 participants who commenced biologic therapy, BASDAI scores in those with co-morbid FM were 2.0 higher at baseline but decreased to 1.1 higher at 12 months. There was no significant difference in the likelihood of meeting Assessment of SpondyloArthritis international Society 20 criteria at 12 months. Less improvement in disease activity and QoL over 3 months of TNFi therapy was most strongly related to high scores on the FM criteria symptom severity scale component. Conclusion: Fulfilling criteria for FM has a modest impact on the assessment of axial SpA disease activity and QoL and does not significantly influence response to biologic therapy. Those with a high symptom severity scale on FM assessment may benefit from additional specific management for FM.
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Antirreumáticos/uso terapêutico , Fibromialgia/complicações , Espondilartrite/complicações , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Índice de Gravidade de Doença , Espondilartrite/diagnóstico , Espondilartrite/tratamento farmacológico , Resultado do Tratamento , Nações UnidasRESUMO
BACKGROUND: Axial spondyloarthropathy typically has its onset in early adulthood and can impact significantly on quality of life. In the UK, biologic anti-tumour necrosis factor therapy is recommended for patients who are unresponsive to non-steroidal anti-inflammatory drugs. There remain several unresolved issues about the long-term safety and quality of life outcomes of biologic treatment in axial spondyloarthropathy. Long-term "real-world" surveillance data are required to complement data from randomised controlled trials. METHODS/DESIGN: We are conducting a UK-wide prospective cohort study of patients with axial spondyloarthropathy who are naïve to biologic therapy at the time of recruitment. Those about to commence anti-tumour necrosis factor biologic therapy will enter a "biologic" sub-cohort with other patients assigned to a "non-biologic" sub-cohort. The primary objective is to determine whether the use of biologic therapy is associated with an increased risk of serious infection, while secondary objectives are to assess differences in malignancy, serious comorbidity, all-cause mortality but also assess impact on specific clinical domains (physical health, mental health and quality of life) including work outcomes between biologic and non-biologic patient cohorts. Patients will be followed-up for up to 5 years. Data are obtained at baseline and at standard clinical follow-up visits - at 3, 6 and 12 months and then annually for the biologic cohort and annually for the non-biologic cohort. This study will also collect biological samples for genetic analysis. DISCUSSION: Although biologic therapy is widely used for ankylosing spondylitis patients who are unresponsive to non-steroidal anti-inflammatory drugs, the majority of the available safety information comes from rheumatoid arthritis, where increased infection risk has consistently been shown. However, given the typical demographic differences between rheumatoid arthritis and axial spondyloarthropathy patients, it is important to develop an epidemiologically rigorous cohort of patients receiving biologic therapy to effectively evaluate outcomes with regard not only to safety but also to quantify benefits across clinical, psychosocial and work outcomes. CLINICAL TRIAL REGISTRATION: This is an observational cohort study and clinical trial registration was not required or obtained.
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Antirreumáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Espondilite Anquilosante/tratamento farmacológico , Humanos , Estudos Prospectivos , Projetos de Pesquisa , Reumatologia , Reino UnidoRESUMO
OBJECTIVES: To evaluate the efficacy and safety of an oral phosphodiesterase 4 inhibitor, apremilast, in treatment of ankylosing spondylitis (AS) by monitoring symptoms and signs in a pilot study including exploratory investigation of effects of PDE4 inhibition on blood biomarkers of bone biology. METHODS: In this double-blind, placebo-controlled, single-centre, Phase II study, patients with symptomatic AS with active disease on MRI were randomised to apremilast 30 mg BID or placebo over 12 weeks. Bath Indices were monitored serially. Patients were followed for 4 weeks after stopping medication. Bone biomarkers were assessed at baseline and day 85. RESULTS: 38 subjects were randomised and 36 subjects completed the study. Although the primary end-point (change in BASDAI at week 12) was not met, apremilast was associated with numerically greater improvement from baseline for all clinical assessments compared with placebo with mean change in BASDAI (-1.59±1.48 vs -0.77±1.47), BASFI (-1.74±1.91 vs -0.28±1.61) and BASMI (-0.51±1.02 vs -0.21±0.67); however, differences did not achieve statistical significance. The clinical indices returned to baseline values by 4 weeks after cessation of apremilast. Six apremilast patients (35.3%) vs 3 placebo (15.8%) achieved ASAS20 responses (p=0.25). There were statistically significant decreases in serum RANKL and RANKL:osteoprotegrin ratio and plasma sclerostin but no significant changes in serum DKK-1, bone alkaline phosphatase, TRAP5b, MMP3, osteoprotegrin, or osteocalcin. CONCLUSIONS: Although a small pilot study, these results suggest that apremilast may be effective and well tolerated in AS and modulates biomarkers of bone biology. These data support further research of apremilast in axial inflammation.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Inibidores da Fosfodiesterase 4/uso terapêutico , Espondilite Anquilosante/tratamento farmacológico , Talidomida/análogos & derivados , Proteínas Adaptadoras de Transdução de Sinal , Administração Oral , Adulto , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Biomarcadores/sangue , Proteínas Morfogenéticas Ósseas/sangue , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Avaliação da Deficiência , Método Duplo-Cego , Feminino , Marcadores Genéticos , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Osteoprotegerina/sangue , Inibidores da Fosfodiesterase 4/efeitos adversos , Projetos Piloto , Ligante RANK/sangue , Índice de Gravidade de Doença , Espondilite Anquilosante/sangue , Espondilite Anquilosante/patologia , Espondilite Anquilosante/fisiopatologia , Talidomida/efeitos adversos , Talidomida/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVES: To establish if changes in Th1/Th17 cell populations previously reported in experimental arthritis occur in patients with rheumatoid arthritis (RA) treated with anti-tumour necrosis factor α (TNFα) agents, and whether the therapeutic response to anti-TNFα is compromised in patients and mice because of elevated Th17/IL-17 levels. Finally, to assess the efficacy of combined blockade of anti-TNFα and anti-IL-17 in experimental arthritis. METHODS: A longitudinal study of two independent cohorts (cohort 1, n=24; cohort 2, n=19) of patients with RA treated with anti-TNFα biological agents was carried out to assess their Th17/IL-17 levels before and after the start of anti-TNFα therapy. IL-12/23p40 production was assessed in plasma Peripheral blood lymphocytes (PBLs) and monocytes. Mice with collagen-induced arthritis (CIA) were treated with anti-TNFα alone, anti-IL17 alone or a combination of the two. Efficacy of treatment and response was assessed from changes in Disease Activity Score 28-erythrocyte sedimentation rate scores in patients, and in clinical scores and histological analysis in CIA. RESULTS: Significant increases in circulating Th17 cells were observed in patients after anti-TNFα therapy and this was accompanied by increased production of IL-12/23p40. There was an inverse relationship between baseline Th17 levels and the subsequent response of patients with RA to anti-TNFα therapy. In addition, PBLs from non-responder patients showed evidence of increased IL-17 production. Similarly, in anti-TNFα-treated mice, there was a strong correlation between IL-17 production and clinical score. Finally combined blockade of TNFα and IL-17 in CIA was more effective than monotherapy, particularly with respect to the duration of the therapeutic effect. CONCLUSIONS: These findings, which need to be confirmed in a larger cohort, suggest that a Th17-targeted therapeutic approach may be useful for anti-TNFα non-responder patients or as an adjunct to anti-TNFα therapy, provided that safety concerns can be addressed.
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Artrite Reumatoide/imunologia , Resistência a Medicamentos/imunologia , Interleucina-17/imunologia , Células Th17/imunologia , Animais , Antirreumáticos/uso terapêutico , Artrite Experimental/tratamento farmacológico , Artrite Experimental/imunologia , Artrite Reumatoide/tratamento farmacológico , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Estudos Longitudinais , Masculino , Camundongos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
BACKGROUND: Preference-based health-state utility values (HSUVs), such as the EuroQol five-dimensional questionnaire (EQ-5D-5L), are needed to calculate quality-adjusted life-years (QALYs) for cost-effectiveness analyses. However, these are rarely used in clinical trials of interventions in axial spondyloarthritis (axSpA). In these cases, mapping can be used to predict HSUVs. OBJECTIVE: To develop mapping algorithms to estimate EQ-5D-5L HSUVs from the Bath Ankylosing Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI). METHODS: Data from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) provided 5122 observations with complete BASDAI, BASFI, and EQ-5D-5L responses covering the full range of disease severity. We compared direct mapping using adjusted limited dependent variable mixture models (ALDVMMs) and optional inclusion of the gap between full health and the next feasible value with indirect response mapping using ordered probit (OPROBIT) and generalised ordered probit (GOPROBIT) models. Explanatory variables included BASDAI, BASFI, and age. Metrics to assess model goodness-of-fit and performance/accuracy included Akaike and Bayesian information criteria (AIC/BIC), mean absolute error (MAE) and root mean square error (RMSE), plotting predictive vs. observed estimates across the range of BASDAI/BASFI and comparing simulated data with the original data set for the preferred/best model. RESULTS: Overall, the ALDVMM models that did not formally include the gap between full health and the next feasible value outperformed those that did. The four-component mixture models (with squared terms included) performed better than the three-component models. Response mapping using GOPROBIT (no squared terms included) or OPROBIT (with squared terms included) offered the next best performing models after the three-component ALDVMM (with squared terms). Simulated data of the preferred model (ALDVMM with four-components) did not significantly underestimate uncertainty across most of the range of EQ-5D-5L values, however the proportion of data at full health was underrepresented, likely due in part to model fitting on a small number of observations at this point in the actual data (4%). CONCLUSIONS: The mapping algorithms developed in this study enabled the generation of EQ-5D-5L utilities from BASDAI/BASFI. The indirect mapping equations reported for the EQ-5D-5L facilitate the calculation of the EQ-5D-5L utility scores using other UK and country-specific value sets.
Assuntos
Espondiloartrite Axial , Produtos Biológicos , Espondilite Anquilosante , Teorema de Bayes , Humanos , Qualidade de Vida , Sistema de Registros , Inquéritos e Questionários , Reino UnidoRESUMO
OBJECTIVE: To determine among patients with axial spondyloarthritis (SpA) the factors associated with decreased spinal mobility and to determine whether poor mobility is a predictor of response to anti-tumor necrosis factor (anti-TNF) therapy. METHODS: This was a prospective UK cohort study of persons meeting Assessment of Spondylarthritis international Society (ASAS) criteria for axial SpA. At recruitment, clinical and patient-reported factors independently associated with spinal mobility (measured by the Bath Ankylosing Spondylitis Metrology Index [BASMI]) were determined. Among those commencing anti-TNF therapy, factors that were independent predictors of response were determined using ASAS criteria, quality of life, and Ankylosing Spondylitis Disease Activity Score (ASDAS) response criteria. RESULTS: A total of 1,960 participants were eligible; 70% were male, the median age was 48 years (interquartile range [IQR] 37, 59), and the median BASMI score 3.6 (IQR 2.2, 5.3). Factors independently associated with poor spinal mobility were poorer function, meeting radiographic criteria for AS, longer symptom duration, higher levels of inflammation (measured by C-reactive protein level), older age, male sex, not being currently employed, and lower levels of education. For 51% of participants, the measured BASMI score was within 1 of that estimated. Poorer mobility (higher BASMI score) was an independent predictor of not meeting response criteria for ASAS 20% improvement (odds ratio [OR] per increasing score 0.80 [IQR 0.66, 0.98]), ASAS 40% improvement (OR 0.69 [IQR 0.50, 0.95]), and quality of life (measured by the Ankylosing Spondylitis Quality of Life Questionnaire) (ß = 0.64 [IQR 0.26, 1.02]), but was not related to meeting ASDAS response criteria. CONCLUSION: The BASMI score was estimated moderately well by other routinely measured factors in patients with axial SpA and was an independent predictor of response to biologic therapy for some, but not all, commonly used measures. Consensus around its role in disease monitoring and clinical decisions, particularly in the likely context of face-to-face consultations becoming less frequent, remains to be established.
Assuntos
Espondiloartrite Axial , Produtos Biológicos , Reumatologia , Espondilartrite , Espondilite Anquilosante , Produtos Biológicos/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Índice de Gravidade de Doença , Espondilartrite/diagnóstico , Espondilartrite/tratamento farmacológico , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/epidemiologia , Inibidores do Fator de Necrose TumoralRESUMO
Inflammatory back pain is characteristic of spondyloarthritis (SpA); however, this pain may not respond to treatment with NSAIDs or biologics. Pain is multifactorial and a combination of mechanical and inflammatory factors. A growing body of literature examines the impact of emotions on pain in SpA; many patients with this condition suffer from depression and fibromyalgia. Advanced imaging techniques can investigate the interplay of various brain networks in pain perception. Animal models have helped understand the interplay between the immune and nervous systems in pain generation and have highlighted differences in pain perception between the sexes.
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Fibromialgia , Espondilartrite , Animais , Dor nas Costas , Encéfalo/diagnóstico por imagem , Humanos , Neuroimagem , Espondilartrite/complicações , Espondilartrite/diagnóstico por imagemRESUMO
Axial spondyloarthritis (SpA) is a chronic disease characterised by new bone formation (NBF) in the axial skeleton as well as at peripheral entheseal sites. NBF is thought to arise in areas of previous inflammation or osteitis visualised on MRI, with mechanical stress playing a role in disease pathogenesis. The interface between bone and immune cells is complex with the RANKL-OPG system being key to NBF. The IL-17/23 axis and other cytokines such as TNFα and MIF are thought to play a central role. The transition from inflammation to NBF is mediated via the Wnt, BMP and Hedgehog signalling pathways. An altered microbiome has been reported in SpA, which is a potential trigger of NBF in SpA. There is now data to show that treatment with TNF inhibitors prevents NBF and hence modifies disease progression. More research into identifying newer targets for disease modification is needed to alter the course of the disease.
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Osteogênese , Espondilartrite , Osso e Ossos , Proteínas Hedgehog , Humanos , Inflamação , Espondilartrite/metabolismoRESUMO
OBJECTIVE: First, to test the hypothesis that, among working patients with axial spondyloarthritis (axSpA), those who report issues with reduced productivity at work (presenteeism) are at higher risk of work absence (absenteeism), and patients who report absenteeism are at higher risk of subsequently leaving the workforce. Second, to identify characteristics of workers at high risk of poor work outcome. METHODS: The British Society for Rheumatology Biologics Register in Ankylosing Spondylitis has recruited patients meeting Assessment of Spondyloarthritis international Society criteria for axSpA from 83 centers. Data collection involved clinical and patient-reported measures at recruitment and annually thereafter, including the Work Productivity and Activity Impairment scale. Generalized estimating equations were used to identify factors associated with poor work outcomes. RESULTS: Of the 1188 participants in this analysis who were working at recruitment, 79% reported some presenteeism and 19% some absenteeism in the past week owing to their axSpA. Leaving employment was most strongly associated with previous absenteeism (RR 1.02 per % increase in absenteeism, 95% CI 1.01-1.03), which itself was most strongly associated with previous presenteeism, a labor-intensive job, and peripheral joint involvement. High disease activity, fatigue, a labor-intensive job, and poorer physical function were all independently associated with future presenteeism. CONCLUSION: Clinical and patient-reported factors along with aspects of work are associated with an increased risk of axSpA patients having a poor outcome in relation to work. This study has identified modifiable factors as targets, facilitating patients with axSpA to remain productive at work.
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Absenteísmo , Presenteísmo , Espondilite Anquilosante/epidemiologia , Espondilite Anquilosante/fisiopatologia , Desempenho Profissional , Adulto , Idoso , Emprego , Fadiga/complicações , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Fatores de Risco , Índice de Gravidade de Doença , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Around 1 in 8 patients with axial spondyloarthritis (axSpA) also meet criteria for fibromyalgia and such patients have considerable unmet need. Identifying effective therapy is important but to what extent fibromyalgia-like symptoms relate to axSpA disease severity has not been established. The aim of the current analysis was to determine whether distinct clusters of axSpA patients exist and if so to determine a) whether they differ in terms of prevalence of fibromyalgia and b) the features of patients in clusters with high prevalence. METHODS: The British Society for Rheumatology Biologics Register (BSRBR-AS) recruited axSpA patients from 83 centres 2012-2017. Clinical data, and information from patients was collected (including research criteria for fibromyalgia). Cluster analysis was undertaken using split samples for development and validation both in the whole population and the sub-group which met fibromyalgia criteria. RESULTS: One thousand three hundred thirty-eight participants were included of whom 23% met research criteria for fibromyalgia. Four clusters were identified. Two exhibited very high disease activity, one which was primarily axial (n = 347) and a smaller cluster (n = 32) with axial and peripheral disease, and in both groups more than half of members met criteria for fibromyalgia. The remaining two clusters (n = 437, n = 462) had overall less severe disease however the one which showed greater disease activity and poorer quality of life had a higher proportion meeting fibromyalgia criteria (16% v. 4%). Within those meeting fibromyalgia criteria there were three clusters. The two main groups were defined by level of symptom severity with a smaller third cluster noted to have high average swollen and tender joint counts and high levels of comorbidity. CONCLUSIONS: The major feature defining clusters with a high proportion of persons meeting criteria for fibromyalgia is high axSpA disease activity although clusters with features of fibromyalgia in the absence of high disease activity also show moderately high prevalence. Management may be most successful with pharmacologic therapy to target inflammation but enhanced by the concurrent use of non-pharmacologic therapy in such patients.
RESUMO
Ankylosing Spondylitis (AS) is an inflammatory rheumatic disease that affects the axial skeleton and the sacroiliac joints. Recent studies investigated the link between AS and oral diseases, particularly periodontitis. Others suggested that periodontitis may have a role in the pathogenesis of rheumatic diseases. OBJECTIVE: The aim of this study is to investigate the association between AS and oral conditions. MATERIAL AND METHODS: This research was conducted using the UK Biobank Resource under Application Number 26307. The UK Biobank recruited around 500000 participants throughout Great Britain. Clinical records were available for 2734 participants. Two case-control studies were conducted based on whether AS was self-reported or clinically diagnosed. Oral conditions were identified using self-reported reports of oral ulcers, painful gums, bleeding gums, loose teeth, toothache, and dentures. The association between AS and oral conditions was assessed using logistic regression adjusted for age, gender, educational level, smoking status, alcohol consumption, and body mass index. RESULTS: A total of 1307 cases and 491503 control participants were eligible for the self-reported AS study. The mean age was 58 years for the cases [7.5 standard deviation (SD)] and 57 years for the control groups (8.1 SD). Also, 37.1% of the cases and 54.2% of the control participants were females. Among the oral conditions, only oral ulcers were strongly associated with AS [1.57 adjusted odds ratio (OR); 95% confidence interval (CI) 1.31 to 1.88]. For the study of clinically diagnosed AS, 153 cases and 490351 control participants were identified. The mean age for both cases and control groups was 57 years; 7.6 SD for the cases and 8.1 for the control group. Females corresponded to 26.1% of the cases, and 54.2% of the control participants. Clinically diagnosed AS was associated with self-reported oral ulcers (2.17 adjusted OR; 95% CI 1.33 to 3.53). CONCLUSION: Self-reported and clinically diagnosed AS populations have increased risk of reporting oral ulcers. Further investigations are required to assess the link between a specific type of oral condition and AS.
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Saúde Bucal/estatística & dados numéricos , Úlceras Orais/epidemiologia , Úlceras Orais/etiologia , Espondilite Anquilosante/complicações , Espondilite Anquilosante/epidemiologia , Adulto , Idoso , Bancos de Espécimes Biológicos , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Periodontite/etiologia , Prevalência , Fatores de Risco , Autorrelato , Reino Unido/epidemiologiaRESUMO
The question of whether diet plays a role in the onset of ankylosing spondylitis (AS) or can affect the course of the disease is an important one for many patients and healthcare providers. The aims of this study were to investigate whether: 1) patients with AS report different diets to those without AS; 2) amongst patients with AS, diet is related to severity; 3) persons with particular diets are less likely to develop AS; 4) specific dietary interventions improve the AS symptoms. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Medline, Embase, Cochrane Library, and reference lists of relevant articles were searched. Two authors independently selected eligible studies, assessed the quality of included trials, and extracted the data. Sixteen studies (nine observational and seven interventions) were included in the review. Due to the heterogeneity of the study designs and analyses, the results could not be aggregated. Evidence on a possible relationship between AS and diet is extremely limited and inconclusive due to the majority of included studies being small, single studies with moderate-to-high risk of bias, and insufficient reporting of results.
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Pain in spondyloarthritis is usually attributed to inflammation. However, treatment with potent biologic agents that control inflammation does not always control the pain. Pain is hence likely to be multifactorial. Fatigue is another prominent feature of this condition which again tends to respond poorly to potent biologic agents. There is also a growing interest in coexisting fibromyalgia in this group of patients and how this affects response to biologic therapies. Advances in neuroimaging have helped in better understanding the dynamic nature of brain networks in the perception of pain. Animal models have helped in developing concepts of peripheral and central sensitization in pain transmission. This review discusses the neuroimmune basis of pain in ankylosing spondylitis, with an emphasis on brain networks and the complex interactions between the nervous system and the immune system at various levels. It also provides some insights into the differences in pain perception between men and women.
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Neuroimunomodulação/fisiologia , Percepção da Dor/fisiologia , Dor/etiologia , Espondilartrite/complicações , Animais , Sensibilização do Sistema Nervoso Central/fisiologia , Feminino , Humanos , MasculinoRESUMO
OBJECTIVES: To investigate the link between self-reported oral health and arthritis in the Scottish population using data from the Scottish Health Survey. MATERIAL AND METHODS: Data were available from 2008 to 2013 on self-reported arthritis, oral health conditions and oral hygiene habits from the Scottish Health Survey. Arthritis was defined in this survey by self-reported long standing illness, those who reported having arthritis, rheumatism and/or fibrositis. Oral conditions were defined by self-reported bleeding gums, toothache, biting difficulties and/or edentulousness. Oral hygiene habits were defined by self-reported brushing teeth and/or using dental floss on daily basis. Logistic regression was used for statistical analysis adjusted for age, gender, qualification, smoking and body mass index. RESULTS: Prevalence of self-reported arthritis was 9.3% (95% confidence interval [CI] = 9.03 to 9.57). Those who reported having bleeding gums (adjusted odds ratio [OR] = 1.63; 95% CI = 1.35 to 1.96), toothache (OR = 1.32; 95% CI = 1.16 to 1.5), biting difficulties (OR = 1.95; 95% CI = 1.62 to 2.34), and being edentulous (OR = 1.22; 95% CI = 1.08 to 1.37) had an increased risk of arthritis. Brushing teeth (OR = 1.25; 95% CI = 0.74 to 2.12), and using dental floss (OR = 1.11; 95% CI = 0.89 to 1.39) were not associated with arthritis. CONCLUSIONS: Self-reported oral conditions were associated with increased risk of self-reported arthritis. Oral hygiene habits were not associated with self-reported arthritis. Further investigation is required to assess the causal association between oral hygiene, oral disease and arthritis.
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OBJECTIVE: To estimate the proportion of patients with axial spondyloarthritis (SpA) in a UK national biologics registry who met criteria for fibromyalgia (FM), and to delineate the characteristics of these patients. METHODS: Two cohorts of patients are prospectively recruited from across 83 centers in the UK for the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS). All patients are required to meet Assessment of SpondyloArthritis international Society (ASAS) criteria for axial SpA. Patients are either newly starting biologic therapy (biologics cohort) or are naive to treatment with biologic agents (non-biologics cohort) at the time of recruitment, and all patients are followed up prospectively. At recruitment and follow-up, clinical information and measurements are recorded while patients complete the 2011 research criteria for FM and assessments of the level of disease activity and work impact. RESULTS: Of the patients registered in the BSRBR-AS, 1,504 (68% male) were eligible for the current analysis, of whom 311 (20.7%) met the 2011 research criteria for FM. Prevalence of FM was similar between patients who fulfilled the modified New York criteria for AS (19.7%) and those who fulfilled ASAS imaging criteria but not the modified New York criteria (25.2%); however, among those who fulfilled only the ASAS clinical criteria, the prevalence of FM was lower (9.5%). Patients who met FM criteria reported significantly worse disease activity, function, global severity scores, and quality of life, and were more likely to have moderate or severe levels of mood disorder and clinically important fatigue. Patients who met FM criteria reported experiencing work impairment around half their working time. Meeting FM criteria was not related to elevated C-reactive protein levels or most extraspinal manifestations, but was associated with a higher likelihood of having received biologic therapy. CONCLUSION: Developing management approaches that would address the significant unmet clinical needs of the 1 in 5 patients with axial SpA who meet criteria for FM should be a research priority.
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Fibromialgia/epidemiologia , Sistema de Registros , Espondiloartropatias/epidemiologia , Atividades Cotidianas , Adulto , Antirreumáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Proteína C-Reativa/metabolismo , Comorbidade , Fadiga/epidemiologia , Feminino , Fibromialgia/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/epidemiologia , Prevalência , Qualidade de Vida , Índice de Gravidade de Doença , Espondiloartropatias/tratamento farmacológico , Espondiloartropatias/metabolismo , Espondiloartropatias/fisiopatologia , Reino Unido/epidemiologiaRESUMO
A case of Kikuchi-Fujimoto disease is presented in the context of pyrexia of unknown origin. Although no specific etiology has been identified, several reported cases are associated with a variety of viruses, toxoplasma, or systemic lupus erythematosus. We present a case and discuss the implications for management.