RESUMO
OBJECTIVES: Identifying that dysfunction of the IL-23/17 axis underlies PsA has led to the development of effective targeted therapies such as the IL-17A inhibitor secukinumab. As IL-17A stimulates the secretion of neutrophil chemoattractants, such as CXCL8 (IL-8), we examined the effect of secukinumab on neutrophil function in PsA. METHODS: Nineteen patients with active PsA were treated with secukinumab. Clinical response [PsA Response Criteria (PsARC) and Psoriasis Area and Severity Index (PASI)] and peripheral blood neutrophil function (apoptosis, receptor expression, phagocytosis/killing, chemotaxis and RNA expression) were measured at 12 week intervals for 48 weeks and compared with age- and sex-matched healthy controls. RESULTS: At 12 weeks, 12/16 (75%) patients had a PsARC response (100% at 36 weeks) and 10/14 (71%) achieved a 90% PASI response. At baseline, there were no differences in PsA neutrophil reactive oxygen species generation, constitutive or cytokine-delayed apoptosis, chemotaxis or phagocytosis of opsonized Staphylococcus aureus compared with healthy controls. Similarly, there were no differences in these functions from baseline to 12 weeks of therapy. However, surface levels of CD11b/CD18 and CD63 increased and expression of CD16 decreased during therapy. In addition, in a subgroup of early (12 week) responders to secukinumab, RNA sequencing revealed transcriptome changes predicting down-regulation of cytokine signalling and chemotaxis pathways and up-regulation of de novo gene expression pathways, including translation initiation, mRNA catabolism and translation. CONCLUSION: Complex changes in the properties of circulating neutrophils occur with secukinumab treatment in PsA that may indicate altered responsiveness to changes in both local and systemic levels of pro-inflammatory cytokines. However, host defence processes of neutrophils were unaltered.
Assuntos
Artrite Psoriásica , Psoríase , Humanos , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/induzido quimicamente , Neutrófilos , Interleucina-17 , Anticorpos Monoclonais/uso terapêutico , Psoríase/tratamento farmacológico , Resultado do TratamentoRESUMO
OBJECTIVE: To determine, among patients with axial spondyloarthritis (axSpA), whether the risk of inflammatory bowel disease (IBD) varies between patients treated with biologic therapies and those treated with other therapies and, specifically, whether the risk is higher in patients treated with etanercept (ETN). METHODS: The British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) was used to determine the incidence of IBD during follow-up and to calculate the incidence rate difference (IRD) per 1000 person-years (PY), between biologic treatment and other treatment groups. We then conducted a systematic review, involving observational studies and randomized controlled trials (RCTs), to perform a metaanalysis to quantify the difference in incidence of IBD between treatment groups. RESULTS: According to the BSRBR-AS, among people with axSpA, exposure to biologic therapy was associated with an increased incidence of IBD compared to those who were not exposed to biologic therapy (IRD 11.9, 95% CI 4.3-19.6). This finding was replicated across observational studies but was not seen in placebo-controlled RCTs (IRD 2.2, 95% CI -4.1 to 8.5). Data from the BSRBR-AS do not suggest that excess incidence of IBD is associated with exposure to ETN compared to other anti-tumor necrosis factor (TNF) therapies (IRD -6.5, 95% CI -21.3 to 8.5). RCTs and their extensions suggest a small-yet not statistically significant-absolute increased incidence associated with ETN of between 2.1 and 5.8 per 1000 PY compared to other anti-TNF therapies. CONCLUSION: There was an excess risk of IBD among persons treated with biologics in observational studies. Only evidence from RCTs suggested that ETN was associated with an increased risk compared to other anti-TNF therapies, albeit with considerable uncertainty.
Assuntos
Antirreumáticos , Produtos Biológicos , Doenças Inflamatórias Intestinais , Espondilite Anquilosante , Humanos , Antirreumáticos/efeitos adversos , Produtos Biológicos/efeitos adversos , Etanercepte/efeitos adversos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/induzido quimicamente , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/epidemiologia , Fator de Necrose Tumoral alfa , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Few data exist on the association between increased BMI and response to conventional synthetic DMARDs (csDMARDs) in RA. We aimed to explore the association between increased (overweight or obese) BMI on csDMARD prescribing, MTX dose and disease activity over 12 months. METHODS: Participants in an international RA database were stratified into early (<1 year post-diagnosis) and established RA. EULAR response, 28-joint DAS (DAS28) remission and treatments were recorded at baseline, 6 months and 12 months. Increased BMI was explored in early and established RA as predictors of good EULAR response, DAS28 remission, number of csDMARDs and MTX dose, using logistic and linear regression. RESULTS: Data from 1313 patients, 44.3% with early RA, were examined. In early RA, increased BMI was not significantly associated with remission. In established RA, obese patients on monotherapy were significantly less likely to achieve good EULAR response or DAS28 remission at 6 months and more likely to be treated with combination csDMARDs compared with normal BMI. In patients taking MTX, overweight and obese patients with early and established RA were exposed to higher MTX doses (mono- and combination therapy), with a mean dose of 20 mg/week, compared with 15 mg/week in those of normal BMI. CONCLUSION: We observed that compared with patients with normal BMI, overweight and obese individuals experienced more intensive csDMARD exposures. Similar response rates were observed in early RA but increased BMI was associated with reduced response in established RA. Optimization of targeted RA treatment remains important, particularly in those with increased BMI where response in established disease may be attenuated.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Índice de Massa Corporal , Metotrexato/uso terapêutico , Antirreumáticos/administração & dosagem , Artrite Reumatoide/complicações , Bases de Dados como Assunto , Feminino , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Obesidade/complicações , Gravidade do Paciente , Resultado do TratamentoRESUMO
OBJECTIVES: Depression and anxiety are associated with more severe disease in cross-sectional studies of axial spondyloarthritis (axSpA). We examined the association between baseline symptoms of depression or anxiety and response to TNF inhibitors (TNFi) in axSpA. METHODS: Biologic naïve participants from a national axSpA register completed the Hospital Anxiety and Depression Scale (HADS) before initiating TNFi. Symptoms of anxiety and depression were each categorized as moderate-severe (≥11), mild (8-10) and 'none' (≤7), and compared against change in disease indices [BASDAI and AS Disease Activity Score (ASDAS)] over time and time to treatment discontinuation using marginal structural models. Inverse-probability weights balanced baseline age, gender, BMI, deprivation, education and baseline values of respective disease indices. RESULTS: Of the 742 participants (67% male, mean age 45 years), 176 (24%) had moderate-severe and 26% mild depression; 295 (40%) had moderate-severe and 23% mild anxiety. Baseline disease activity was higher in higher HADS symptom categories for both depression and anxiety. Participants with moderate-severe depression had significantly poorer response compared with those with 'none' throughout follow-up. At 6 months, the difference was approximately 2.2 BASDAI and 0.8 ASDAS units after balancing their baseline values. Equivalent comparisons for anxiety were 1.7 BASDAI and 0.7 ASDAS units. Treatment discontinuation was 1.59-fold higher (hazard ratio 95% CI: 1.12, 2.26) in participants with moderate-severe anxiety compared with 'none'. CONCLUSIONS: Symptoms of depression and anxiety at TNFi initiation are associated with poorer treatment outcomes. Targeted interventions to optimize mental health have potential to substantially improve treatment response and persistence.
Assuntos
Ansiedade/complicações , Espondiloartrite Axial/tratamento farmacológico , Cognição/efeitos dos fármacos , Depressão/complicações , Saúde Mental , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Ansiedade/fisiopatologia , Ansiedade/prevenção & controle , Espondiloartrite Axial/complicações , Cognição/fisiologia , Estudos Transversais , Depressão/fisiopatologia , Depressão/prevenção & controle , Escolaridade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Delay to diagnosis in axial SpA (axSpA) is longer than in many other rheumatic diseases. Prolonged delay is associate with poorer outcomes, including functional impairment and quality of life. Our aims were to describe global variation in delay to diagnosis, factors associated with delay, and delay compared with PsA. METHODS: We searched MEDLINE, PubMed, Embase and Web of Science using a predefined protocol. Diagnostic delay was defined as years between the age at symptom onset and at diagnosis. We pooled the mean delay using random effects inverse variance meta-analysis. We examined variations in pooled estimates using prespecified subgroup analyses and sources of heterogeneity using meta-regression. RESULTS: A total of 64 studies reported the mean diagnostic delay in axSpA patients. The pooled mean delay was 6.7 years (95% CI 6.2, 7.2) with high levels of heterogeneity. Delay to diagnosis did not improve over time when stratifying results by year of publication. Studies from high-income countries (defined by the World Bank) reported longer delays than those from middle-income countries. Factors consistently reported to be associated with longer delays were lower education levels, younger age at symptom onset and absence of extra-articular manifestations (EAMs). The pooled estimate for diagnostic delay from 8 PsA studies was significantly shorter, at 2.6 years (95% CI 1.6, 3.6). CONCLUSION: For axSpA patients, delay to diagnosis remains unacceptably prolonged in many parts of the world. Patient factors (e.g. education) and disease presentation (onset age and EAMs) should inform campaigns to improve delay.
Assuntos
Artrite Psoriásica/diagnóstico , Espondilartrite/diagnóstico , Espondilite Anquilosante/diagnóstico , Diagnóstico Tardio , Feminino , Humanos , MasculinoRESUMO
OBJECTIVE: Whether comorbidities influence disease activity assessment in axial SpA (axSpA) is unclear. Comorbidities inflate DAS28 in rheumatoid arthritis through the patient global score. We examined whether axSpA disease activity measures are differentially affected, and whether comorbidities inflate the AS disease activity score (ASDAS) through the patient global component. METHODS: We used baseline data from the British Society for Rheumatology Biologics Register for AS, including 14 physician diagnosed comorbidities. Linear models were used to compare disease activity (BASDAI, spinal pain, ASDAS) and ESR/CRP according to comorbidity count, adjusted for age, gender, BMI, smoking, socioeconomic status, and education. The same models were used to examine whether the patient global score was associated with comorbidities, additionally adjusting for other ASDAS components. RESULTS: The number of participants eligible for analysis was 2043 (67% male, mean age 49 years); 44% had at least one comorbidity. Each additional comorbidity was associated with higher BASDAI by 0.40 units (95% CI: 0.27, 0.52) and spinal pain by 0.53 (95% CI: 0.37, 0.68). Effect size for ASDAS (0.09 units; 95% CI: 0.03, 0.15) was not clinically significant. ESR and CRP were not associated with comorbidity count. Depression, heart failure and peptic ulcer were consistently associated with higher disease activity measures, but not CRP/ESR. Patient global was associated with comorbidity count, but not independently of other ASDAS components (P = 0.75). CONCLUSION: Comorbidities were associated with higher patient reported disease activity in axSpA. Clinicians should be mindful of the potential impact of comorbidities on patient reported outcome measures and consider additionally collecting ASDAS when comorbidities are present.
Assuntos
Transtorno Depressivo/epidemiologia , Insuficiência Cardíaca/epidemiologia , Úlcera Péptica/epidemiologia , Espondiloartropatias/fisiopatologia , Adulto , Idoso , Sedimentação Sanguínea , Proteína C-Reativa/imunologia , Comorbidade , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Espondiloartropatias/epidemiologia , Espondiloartropatias/imunologiaRESUMO
OBJECTIVE: Comorbidities influence disease assessment in axial spondyloarthritis (axSpA), but their association with response to TNF inhibitors (TNFi) is unclear. We examined associations between comorbidity history at TNFi initiation and: (i) change in disease indices over time; (ii) binary response definitions; and (iii) time to treatment discontinuation. METHODS: We studied participants starting their first TNFi from a national axSpA register. Comorbidity categories were created from 14 physician-diagnosed conditions and compared against: change in disease indices over time using linear mixed effects models; BASDAI50/2 (50% or 2-unit reduction) and BASDAI < 4 at 6 months using logistic models; and time to treatment discontinuation using Cox models. Models were adjusted for age, gender, BMI, deprivation and education. RESULTS: In total, 994 were eligible for analysis (68% male, mean age 45 years); 21% had one comorbidity and 11% had ≥2. Baseline disease severity was higher in those with comorbidities across all indices, but absolute improvement over time was comparable for BASDAI and spinal pain. Participants with ≥2 comorbidities had smaller absolute improvement in BASFI and quality of life. This group also had numerically reduced odds of achieving BASDAI50/2 [odds ratio (OR) 0.81; 95% CI: 0.45, 1.45] and BASDAI < 4 (OR 0.57; 95% CI: 0.32, 1.04). Treatment discontinuation was increased in those with two comorbidities [hazard ratio (HR) 1.32; 95% CI: 0.88, 2.00] and ≥3 comorbidities (HR 2.18; 95% CI: 1.20, 3.93) compared with none. CONCLUSIONS: Participants with multiple comorbidities had poorer treatment outcomes, particularly increased treatment discontinuation and poorer improvements in function and quality of life. These results inform clinicians and educate patients about response to the first TNFi given comorbidity burden.
Assuntos
Antirreumáticos/uso terapêutico , Espondilartrite/epidemiologia , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Sistema de Registros , Índice de Gravidade de Doença , Espondilartrite/diagnóstico , Espondilartrite/tratamento farmacológico , Resultado do TratamentoRESUMO
OBJECTIVES: Comorbidities are common in people with axial spondyloarthritis (axSpA). In this systematic review and meta-analysis, we aimed to: (i) describe the prevalence of commonly reported comorbidities, (ii) compare comorbidities between axSpA and control populations, and (iii) examine the impact of comorbidity burden on axSpA outcomes. METHODS: We systematically searched Medline, PubMed, Scopus and Web of Science using a predefined protocol in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. We excluded studies of only one comorbid condition or a few closely related diseases within one organ system. Where possible, meta-analysis was performed using random-effects models. RESULTS: A total of 40 studies were included for analysis. 36 studies reported prevalence of comorbidities, amounting to a combined sample size of 119 427 patients. The number of comorbidities studied ranged from 3 to 43. The most prevalent individual comorbidities were hypertension (pooled prevalence 23%), hyperlipidaemia (17%) and obesity (14%). Eleven studies consistently showed higher prevalence of comorbidities in axSpA than controls, particularly large differences were seen for depression [pooled odds ratio (OR) 1.80] and heart failure (OR 1.84). Comorbidities (total number of and individual conditions) were also associated with axSpA disease activity, functional impairment, quality of life, work productivity and mortality. CONCLUSIONS: Comorbidities are common in axSpA, particularly cardiovascular diseases and risk factors. Most comorbidities were more prevalent in axSpA patients than in control populations. Overall comorbidity burden, and many individual conditions, were associated with axSpA outcomes including worse disease severity, work productivity and mortality.
Assuntos
Espondilartrite/epidemiologia , Comorbidade , Humanos , Hiperlipidemias/epidemiologia , Hipertensão/epidemiologia , Obesidade/epidemiologia , PrevalênciaRESUMO
Tobacco smoking is a major threat to health. There is no doubt about the need to promote and support cessation at every opportunity. Smoking has a clear role in RA, but what evidence is there that the same relationship exists in SpA? In this review, we examine (the less cited) paradoxes and contradictions in the existing axial SpA (axSpA) and PsA literature; for example, smoking appears to be 'protective' for some axSpA manifestations. We also highlight findings from higher quality evidence: smoking is associated with increased risk of PsA and the risk of psoriasis in axSpA. The relationship between smoking and SpA is far from simple. Our aim is to highlight the harms of smoking in SpA and bring attention to inconsistencies in the literature to inform further research.
Assuntos
Artrite Psoriásica/epidemiologia , Fumar/epidemiologia , Idade de Início , Humanos , Fatores de Proteção , Psoríase/epidemiologia , Fatores de Risco , Índice de Gravidade de Doença , Abandono do Hábito de Fumar , Espondiloartropatias/epidemiologiaRESUMO
OBJECTIVES: To develop classification algorithms that accurately identify axial SpA (axSpA) patients in electronic health records, and compare the performance of algorithms incorporating free-text data against approaches using only International Classification of Diseases (ICD) codes. METHODS: An enriched cohort of 7853 eligible patients was created from electronic health records of two large hospitals using automated searches (⩾1 ICD codes combined with simple text searches). Key disease concepts from free-text data were extracted using NLP and combined with ICD codes to develop algorithms. We created both supervised regression-based algorithms-on a training set of 127 axSpA cases and 423 non-cases-and unsupervised algorithms to identify patients with high probability of having axSpA from the enriched cohort. Their performance was compared against classifications using ICD codes only. RESULTS: NLP extracted four disease concepts of high predictive value: ankylosing spondylitis, sacroiliitis, HLA-B27 and spondylitis. The unsupervised algorithm, incorporating both the NLP concept and ICD code for AS, identified the greatest number of patients. By setting the probability threshold to attain 80% positive predictive value, it identified 1509 axSpA patients (mean age 53 years, 71% male). Sensitivity was 0.78, specificity 0.94 and area under the curve 0.93. The two supervised algorithms performed similarly but identified fewer patients. All three outperformed traditional approaches using ICD codes alone (area under the curve 0.80-0.87). CONCLUSION: Algorithms incorporating free-text data can accurately identify axSpA patients in electronic health records. Large cohorts identified using these novel methods offer exciting opportunities for future clinical research.
Assuntos
Registros Eletrônicos de Saúde/estatística & dados numéricos , Processamento de Linguagem Natural , Melhoria de Qualidade , Espondilartrite/classificação , Espondilite Anquilosante/classificação , Idoso , Algoritmos , Área Sob a Curva , Estudos de Coortes , Feminino , Humanos , Classificação Internacional de Doenças , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Espondilartrite/epidemiologia , Espondilite Anquilosante/epidemiologiaRESUMO
OBJECTIVE: In this systematic review and meta-analysis of psoriatic arthritis (PsA) studies, we pooled data from existing literature to (1) estimate the prevalence of mental health disorders in PsA patients and (2) compare disease activity in PsA patients with and without these comorbidities. METHOD: We searched PubMED, Web of Science, Scopus, PsycINFO and the Cochrane Library using a predefined protocol in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Where possible, meta-analysis was performed using random effects model. Prevalence estimates were pooled according to the severity of mental health disorders. RESULTS: A total of 24 studies, amounting to 31,227 PsA patients, were included for review. Anxiety and depression were the only consistently reported mental health disorders, defined using a range of screening criteria/thresholds. Anxiety prevalence ranged from 4 to 61% with a pooled estimate of 33% (95%CI 17 to 53%) having at least mild anxiety and 21% (95%CI 14 to 29%) at least moderate. Depression prevalence ranged from 5 to 51%, with 20% (95%CI 8 to 35%) having at least mild and 14% (95%CI 8 to 21%) at least moderate. Only two studies compared disease activity according to the presence of mental health comorbidities; both reported higher disease activity and pain among those with comorbid anxiety and depression. CONCLUSIONS: Anxiety and depression are highly prevalent among PsA patients. Studies of other mental health disorders were scarce. More studies are needed on the impact of these comorbidities on disease activity and long-term outcomes.Key Points⢠One in three patients with psoriatic arthritis has at least mild anxiety, while 1 in 5 reported at least mild depression.⢠PsA patients with anxiety and/or depression reported greater disease activity.⢠More research is needed on other mental health comorbidities, particularly sleep, suicide/self-harm and substance misuse.
Assuntos
Ansiedade/epidemiologia , Artrite Psoriásica/epidemiologia , Depressão/epidemiologia , Artrite Psoriásica/psicologia , Comorbidade , Humanos , Saúde Mental , PrevalênciaRESUMO
OBJECTIVE: Observational data facilitate examination of treatment-effect heterogeneity, but the risk of bias is substantial. The present study was undertaken to highlight methodologic considerations through an analysis of whether smoking affects response to tumor necrosis factor inhibitors (TNFi) in axial spondyloarthritis (SpA). METHODS: We used longitudinal data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis. Participants fulfilling the Assessment of SpondyloArthritis international Society criteria for axial SpA who started their first TNFi were eligible for analysis. In comparing the impact of smoking status, weighted generalized estimating equations were used to examine changes in several continuous outcome measures, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS). Inverse probability weights were used to account for differences in baseline covariates and excluded participants. We separately assessed response in the first 3 months to account for nonrandom dropout. RESULTS: For 840 participants who started on TNFi, 1,641 assessments from 627 individuals were analyzed (69% male, mean age 46 years). A total of 33% were current smokers and 30% ex-smokers. Ex-smokers and current smokers had worse disease than never smokers at baseline. Accounting for these differences, response did not differ according to smoking status. Compared to never smokers, ex-smokers (ß = -0.6, 95% confidence interval [95% CI] -1.4, 0.3) and current smokers (ß = -0.4, 95% CI -1.1, 0.4) had a similar response according to the BASDAI and ASDAS (ex-smokers ß = -0.1, 95% CI -0.5, 0.3; current smokers ß = -0.01, 95% CI -0.4, 0.4) at 3 months. CONCLUSION: TNFi response did not differ according to baseline smoking status in this UK cohort. Conflicting results from previous studies were likely due to methodologic differences. This analysis highlights potential sources of bias that should be addressed in future studies.
Assuntos
Antirreumáticos/uso terapêutico , Fumar , Espondilartrite/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Índice de Gravidade de Doença , Espondilartrite/diagnóstico , Resultado do Tratamento , Reino UnidoRESUMO
Fibromyalgia (FM) is one of the most common conditions that rheumatologists encounter. It is characterised by chronic widespread pain, fatigue, sleep disturbances and impaired cognition. The prevalence of comorbid FM among populations with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) are considerably higher than among the general population, with pooled prevalence estimates of 18-24% in RA, 14-16% in axSpA and 18% in PsA. Prevalence estimates should be interpreted with care as the criteria for FM have not been validated for use in patients with inflammatory arthritis. Comorbid FM appears to affect assessment of disease severity in these conditions, particularly patient-reported outcome measures, and may influence response to treatment. There is a need for better identification, classification and management of FM in the context of inflammatory rheumatic diseases.
Assuntos
Artrite Psoriásica/complicações , Artrite Reumatoide/complicações , Fibromialgia/epidemiologia , Espondilartrite/complicações , Adulto , Artrite Psoriásica/epidemiologia , Artrite Reumatoide/epidemiologia , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Espondilartrite/epidemiologiaRESUMO
BACKGROUND: The impact of smoking on TNF inhibition (TNFi) therapy is unclear. We examined the effect of smoking on all-cause and cause-specific TNFi discontinuation in axial spondyloarthritis (axSpA). METHODS: We used longitudinal data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS). Patients fulfilling the ASAS criteria for axSpA, who started their first TNFi, were eligible for analysis. Inverse-probability weights were used to balance differences in baseline disease severity and other confounders. We used marginal structural Cox proportional hazard models to estimate hazard ratios (HR) for TNFi discontinuation according to smoking status. In analyses of cause-specific discontinuation, competing risk events were considered as censoring, using inverse-probability weights. RESULTS: A total of 758 participants were included in the analysis (66% male, mean age 45 years), providing 954 patient-years of follow-up. TNFi was discontinued in 174 (23%) patients, among whom 26% stopped due to infections, 20% due to other adverse events and 44% due to inefficacy or other reasons. Thirty-four percent were current smokers and 30% ex-smokers. Compared to never smokers, current smokers' risk of TNFi discontinuation was HR 0.79 (95%CI 0.53 to 1.20) and ex-smokers HR 0.68 (95%CI 0.45 to 1.04). Our data did not show evidence that current smoking influenced discontinuation due to infections (HR 0.79, 95%CI 0.40 to 1.54), other adverse events (HR 0.86, 95%CI 0.41 to 1.78) or inefficacy/other causes (HR 1.44, 95%CI 0.86 to 2.41). CONCLUSION: Baseline smoking status did not impact TNFi discontinuation in this UK cohort of axSpA participants.
Assuntos
Fumar/efeitos adversos , Espondilartrite/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Suspensão de Tratamento , Adulto , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos ProspectivosRESUMO
OBJECTIVES: To examine how comorbidities cluster in axial spondyloarthritis (axSpA) and whether these clusters are associated with quality of life, global health and other outcome measures. METHODS: We conducted a cross-sectional study of consecutive patients meeting ASAS criteria for axSpA in Liverpool, UK. Outcome measures included quality of life (EQ5D), global health and disease activity (BASDAI). We used hierarchical cluster analysis to group patients according to 38 pre-specified comorbidities. In multivariable linear models, the associations between distinct comorbidity clusters and each outcome measure were compared, using axSpA patients with no comorbidities as the reference group. Analyses were adjusted for age, gender, symptom duration, BMI, deprivation, NSAID-use and smoking. RESULTS: We studied 419 patients (69% male, mean age 46 years). 255 patients (61%) had at least one comorbidity, among whom the median number was 1 (range 1-6). Common comorbidities were hypertension (19%) and depression (16%). Of 15 clusters identified, the most prevalent clusters were hypertension-coronary heart disease and depression-anxiety. Compared with patients with no comorbidities, the fibromyalgia-irritable bowel syndrome cluster was associated with adverse patient-reported outcome measures; these patients reported 1.5-unit poorer global health (95%CI 0.01, 2.9), reduced quality of life (0.25-unit lower EQ5D; 95%CI -0.37, -0.12) and 1.8-unit higher BASDAI (95% CI 0.4, 3.3). Similar effect estimates were found for patients in the depression-anxiety cluster. CONCLUSION: Comorbidity is common among axSpA patients. The two most common comorbidities were hypertension and depression. Patients in the depression-anxiety and fibromyalgia-IBS clusters reported poorer health and increased axSpA severity.
Assuntos
Efeitos Psicossociais da Doença , Depressão/epidemiologia , Hipertensão/epidemiologia , Índice de Gravidade de Doença , Espondilartrite/epidemiologia , Adulto , Ansiedade/epidemiologia , Análise por Conglomerados , Comorbidade , Doença das Coronárias/epidemiologia , Estudos Transversais , Feminino , Fibromialgia/epidemiologia , Humanos , Síndrome do Intestino Irritável/epidemiologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Espondilartrite/psicologia , Reino Unido/epidemiologiaRESUMO
OBJECTIVES: This study aimed to compare comorbidities and biologic DMARD (bDMARD) use between AS and non-radiographic axial SpA (nr-axSpA) patients, using a large cohort of patients from routine clinical practice in the United States. METHODS: We performed a cross-sectional study using electronic medical records from two academic hospitals in the United States. Data were extracted using automated searches (⩾3 ICD codes combined with text searches) and supplemented with manual chart review. Patients were categorized into AS or nr-axSpA according to classification criteria. Disease features, comorbidities (from a list of 39 chronic conditions) and history of bDMARD prescription were compared using descriptive statistics. RESULTS: Among 965 patients identified, 775 (80%) were classified as having axSpA. The cohort was predominantly male (74%) with a mean age of 52.5 years (s.d. 16.8). AS patients were significantly older (54 vs 46 years), more frequently male (77% vs 64%) and had higher serum inflammatory markers than those with nr-axSpA (median CRP 3.4 vs 2.2 mg/dl). Half of all patients had at least one comorbidity. The mean number of comorbidities was 1.5 (s.d. 2.2) and similar between AS and nr-axSpA groups. A history of bDMARD-use was seen in 55% of patients with no difference between groups. The most commonly prescribed bDMARDs were adalimumab (31%) and etanercept (29%). Ever-prescriptions of individual bDMARDs were similar between AS and nr-axSpA. CONCLUSION: Despite age differences, nr-axSpA patients had similar comorbidity burdens as those with AS. Both groups received comparable bDMARD treatment in this United States clinic-based cohort.
Assuntos
Antirreumáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Doença Crônica/epidemiologia , Espondilartrite/epidemiologia , Espondilite Anquilosante/epidemiologia , Adulto , Idoso , Doença Crônica/tratamento farmacológico , Comorbidade , Estudos Transversais , Feminino , Humanos , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Espondilartrite/sangue , Espondilartrite/tratamento farmacológico , Espondilite Anquilosante/sangue , Espondilite Anquilosante/tratamento farmacológico , Estados UnidosRESUMO
This study examined the relationship between spondyloarthritis (SpA) duration and gastrointestinal comorbidities other than inflammatory bowel disease (IBD). We evaluated the association between SpA duration and upper gastrointestinal ulcers, hepatitis B (HBV), hepatitis C (HCV) and diverticulitis using data from a large international cross-sectional study. Binary regression models were created, adjusted for age, sex, body mass index (BMI), smoking, alcohol, non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), biologics, steroids, IBD history and country. Subgroup analysis was performed by disease phenotype. The data of 3923 participants were analysed. The prevalence of gastrointestinal conditions were 10.7% upper gastrointestinal ulcers; 4.7% viral hepatitis and 1.5% diverticulitis. While SpA duration was not associated with upper gastrointestinal ulcers, HBV or HCV, longer SpA duration was significantly associated with diverticulitis (odds ratios (OR) = 1.18, 95% confidence interval (CI): 1.03â»1.34), reflecting an 18% increase for every five years of SpA duration. Other significant associations with diverticulitis were age and high alcohol intake but not medication history. In subgroup analyses, the association was strongest with those with axial SpA. The reasons for this association of increased diverticulitis with disease duration in SpA, especially those with axial disease, are unclear but may reflect shared underlying gut inflammation. Diverticulitis should be considered, in addition to IBD, when SpA patients present with lower gastrointestinal symptoms.
RESUMO
OBJECTIVE: Spondyloarthritis (SpA) is associated with a number of cardiovascular (CV) comorbidities. We examined the association of SpA disease duration and delay in diagnosis with CV-related conditions. METHODS: Using data from the COMOSPA study, the associations between SpA disease duration and CV-related conditions were evaluated in univariable and multivariable logistic regression models. Each model examined 1 CV-related factor as dependent and "SpA disease duration" as a predictor, adjusted for relevant confounders. RESULTS: Data from 3923 subjects (median SpA disease duration 5.1 yrs, interquartile range 1.3-11.8 yrs) were available for analysis. The main CV-related conditions were hypertension (HTN; 22.4%), ischemic heart disease (2.6%), stroke (1.3%), and diabetes mellitus (5.5%). HTN was associated with SpA disease duration in both univariable and multivariable analysis, with an OR of 1.129 (95% CI 1.072-1.189; p < 0.001) for each 5-year increase in SpA disease duration. Other factors associated with HTN were age, male sex, current body mass index, ever steroid therapy, and ever synthetic disease-modifying antirheumatic drug therapy, but not nonsteroidal antiinflammatory drugs (NSAID). In subgroup analysis, the strongest association of HTN and disease duration was seen in subjects with the axial-only SpA phenotype (OR 1.202, 95% CI 1.053-1.372) but not in those with peripheral-only SpA (OR 0.902, 95% CI 0.760-1.070). The other CV conditions were not associated with SpA disease duration. CONCLUSION: Duration of SpA disease in the ASAS-COMOSPA cohort is associated with higher odds of HTN, particularly in those with axial disease, but not with other CV-related conditions. The association with HTN does not appear to be related to NSAID exposure.