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1.
Semin Arthritis Rheum ; 51(2): 464-468, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33774593

RESUMO

BACKGROUND/PURPOSE: A universally accepted definition of axial psoriatic arthritis (axPsA) is lacking. We aimed to 1) assess the presence of axial involvement as defined by "at least unilateral grade 2 sacroiliitis (Uni2SI)" and 2) assess the radiographic progression of Uni2SI and identify risk factors for progression. METHODS: PsA patients participating in a prospective observational cohort were classified according to their highest sacroiliitis grade. The baseline features of patients with Uni2SI were compared to patients meeting the radiographic criteria of the modified New York Ankylosing Spondylitis (mNY AS) criteria. Risk factors were examined for progression from Uni2SI in a sub-group of patients with >1 follow-up radiographs. Logistic regression and a survival analysis were carried out and identified risk factors associated with radiographic mNY AS compared to Uni2SI. RESULTS: Axial disease defined as ≥Uni2SI was detected in 612/1354 patients (45%). mNY AS sacroiliitis was observed in 477 patients (35%). Radiographic progression of Uni2SI was assessed in 154 patients, 80 (52%) progressed to mNY AS criteria within 5.5 years. At baseline, progressors were diagnosed at a younger age (35.6 vs. 38.9, p = 0.05), had less degenerative disc disease (OR = 0.47, p = 0.02), worse peripheral radiographic damage (OR=1.02, p = 0.03) and worse psoriasis (OR = 1.09, p = 0.01) compared to non-progressors. Patients with an elevated erythrocyte sedimentation rate were more likely to progress (HR = 1.83, p = 0.02), while patients with longer disease duration were less likely to progress (HR = 0.95, p = 0.02). CONCLUSION: The radiographic mNY AS criteria appear to be suitable for defining axial PsA according to radiographs. MRI definitions are needed as well for the most appropriate definition of axial PsA.

3.
Semin Immunopathol ; 43(2): 245-253, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33532928

RESUMO

The strong association of HLA-B*27 with ankylosing spondylitis (AS) was first reported nearly 50 years ago. However, the mechanistic link between HLA-B*27 and AS has remained an enigma. While 85-90% of AS patients possess HLA-B*27, majority of HLA-B*27 healthy individuals do not develop AS. This suggests that additional genes and genetic regions interplay with HLA-B*27 to cause AS. Previous genome-wide association studies (GWAS) identified key genes that are distinctively expressed in AS, including the Endoplasmic Reticulum Aminopeptidase (ERAP) 1 and ERAP2. As these gene-encoding molecules are primarily implicated in the process of peptide processing and presentation, potential pathological interaction of these molecules with HLA-B*27 may operate to cause AS by activating downstream immune responses. The aberrant peptide processing also gives rise to the accumulation of unstable protein complex in endoplasmic reticulum (ER), which drives endoplasmic reticulum-associated protein degradation (ERAD) and unfolded protein response (UPR) and activates autophagy. In this review, we describe the current hypotheses of AS pathogenesis, focusing on antigen processing and presentation operated by HLA-B*27 and associated molecules that may contribute to the disease initiation and progression of AS.

4.
Curr Rheumatol Rep ; 23(1): 5, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33403528

RESUMO

PURPOSE OF REVIEW: Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) emerged in December 2019, rapidly reaching global pandemic proportions. Coronavirus disease 2019 (COVID-19) has presented unique challenges to the rheumatology community. It is known that many individuals with rheumatic disease are at increased risk of severe disease from other infections, sparking a similar fear for COVID-19. In addition, medications routinely used in rheumatology practice are being trialled as treatments, with the potential for drug shortages for rheumatology patients. RECENT FINDINGS: Underlying comorbidities and active disease are associated with worse COVID-19 outcomes in patients with rheumatic disease. Tocilizumab and hydroxychloroquine have not proven to be effective treatments in the management of COVID-19. Telehealth has become an essential tool for the rheumatology community to monitor patients during the pandemic. In this article, we summarise the available COVID-19 evidence that is of relevance to the rheumatology community. We discuss the risk of contracting COVID-19 in individuals with rheumatic disease, along with presenting features and clinical outcomes. We provide an overview of the treatments for COVID-19 which have significance for rheumatology. We highlight published recommendations which can guide our management of rheumatic disease populations during this pandemic. Finally, we discuss the challenges in delivering effective care virtually and present methods and tools which could be adapted for use.


Assuntos
/complicações , Doenças Reumáticas/complicações , Doenças Reumáticas/terapia , Reumatologia , Antirreumáticos/uso terapêutico , Humanos , Telemedicina
5.
ACR Open Rheumatol ; 2(9): 533-539, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32893508

RESUMO

OBJECTIVE: Response to the coronavirus disease 2019 (COVID-19) pandemic has resulted in shelter-in-place orders and major changes to individuals' daily lives. The impact of such stressors on disease activity in individuals with axial spondyloarthritis (axSpA) is unclear. The aim of this study is to examine whether stress, anxiety, and depression are associated with patient-reported disease activity, after accounting for important factors. METHODS: We administered a survey to an axSpA cohort from a single center with well-defined demographic and disease characteristics. We included questions about job status changes, exercise, medication use, disease activity (by the Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), and psychological factors (stress, depressive symptoms, and anxiety). Separate multivariable linear models examined the associations between perceived stress, anxiety, and depression with the BASDAI. RESULTS: After adjustment for potential confounders, those with higher levels of stress had a statistically significant 0.54-point higher BASDAI, on average, compared with those with lower levels of stress (95% confidence interval [CI]: 0.11, 0.97). Those with higher levels of anxiety also had a statistically significant higher BASDAI, on average, compared with those with lower levels of anxiety (ß: 0.95, 95% CI: 0.18, 0.99). The association between depression and BASDAI was not statistically significant. We did not find differences in these associations among subgroups of age, job status, or county of residence. CONCLUSION: Individuals with axSpA with higher levels of stress and anxiety had significantly higher disease activity levels, although with a difference below clinical importance. Further planned studies will evaluate the trajectory of disease activity.

6.
Ther Adv Musculoskelet Dis ; 12: 1759720X20921710, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32550868

RESUMO

Background: Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are associated with mental illness. Whether acute mental health (MH) service utilization (i.e. emergency visits or hospitalizations) is increased in RA or AS is not known. Methods: Two population-based cohorts were created where individuals with RA (n = 53,240) or AS (n = 13,964) were each matched by age, sex, and year to unaffected comparators (2002-2016). Incidence rates per 1000 person-years (PY) were calculated for a first MH emergency department (ED) presentation or MH hospitalization. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated, adjusting for demographic, clinical, and health service use variables. Results: Individuals with RA had higher rates of ED visits [6.59/1000 person-years (PY) versus 4.39/1000 PY in comparators] and hospitalizations for MH (3.11/1000 PY versus 1.80/1000 PY in comparators). Higher rates of ED visits (7.92/1000 PY versus 5.62/1000 PY in comparators) and hospitalizations (3.03/1000 PY versus 1.94/1000 PY in comparators) were also observed in AS. Overall, RA was associated with a 34% increased risk for MH hospitalization (HR 1.34, 95% CI 1.22-1.47) and AS was associated with a 36% increased risk of hospitalization (HR 1.36, 95% CI 1.12-1.63). The risk of ED presentation was attenuated, but remained significant, after adjustment in both RA (HR 1.08, 95% CI 1.01-1.15) and AS (HR 1.14, 95% CI 1.02-1.28). Conclusions: RA and AS are both independently associated with a higher rate and risk of acute ED presentations and hospitalizations for mental health conditions. These findings underscore the need for routine evaluation of MH as part of the management of chronic inflammatory arthritis. Additional research is needed to identify the underlying individual characteristics, as well as system-level variation, which may explain these differences, and to help plan interventions to make MH service use more responsive to the needs of individuals living with RA and AS.

7.
Int J Rheum Dis ; 23(6): 728-743, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32419337

RESUMO

To review the effect of tumor necrosis factor-alpha inhibitor (TNFi) therapies on radiographic progression in ankylosing spondylitis (AS) patients as evaluated by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Pubmed, MEDLINE, EMBASE, and the Cochrane Library databases were searched from inception to August 2019. All comparative and non-comparative studies that evaluated the clinical effectiveness of TNFi on radiographic progression as assessed by mSASSS change at a minimum follow-up of 1 year were included. The Newcastle-Ottawa Scale and Cochrane Collaboration Risk of Bias Tool were utilized to assess the methodological quality. Pooled analysis was performed for continuous and binomial variables where appropriate. Inter-rater reliability of mSASSS status and change scores were assessed with intra-class coefficients (ICC). Twenty-one studies were identified with a total of 4460 patients (mean age: 40.4 years [range 25.3-50 years]; 76% male; mean baseline mSASSS: 12.7 units [range 5.5-19.8 units]). All studies (3 randomized and 18 observational studies) were considered to have moderate-to-high methodological quality. The inter-rater reliability of mSASSS status and change scores from 14 of the 21 studies were excellent (ICC ranges, 0.91-0.99) and moderate-to-excellent (ICC ranges, 0.58-0.90), respectively. From the 21 studies, 11/21 (50%) demonstrated a delayed effect in mSASSS in AS patient administered TNFi. When stratifying these studies into those with ≤4 years of follow-up and >4 years follow-up, 3/11 (27%) and 8/10 (80%) studies respectively indicated a delayed effect of mSASSS with TNFi in AS patients. Pooling for meta-analysis from 3 studies (1159 patients) with study durations ranging 4-8 years, indicated that TNFi-treated patients had reduced odds of structural progression (odds ratio 0.81; 95% CI 0.68-0.96; P = .01; I2  = 0%). Mean rate of mSASSS change from 16 studies ranged from -0.15 to 7.3 mSASSS units for all AS patients. Meta-analysis indicated a numerical, but statistically non-significant, reduction in the rate of mSASSS change with TNFi treatment (7 studies [1438 patients]; mean difference, -0.24; 95% CI, -0.49-0.01; P = .06; I2  = 0%). This systematic review and meta-analysis indicated that >4 years of TNFi usage was associated with delayed structural progression by mSASSS. The narrative analysis of the data from 21 studies further confirmed that studies with >4 years of follow-up had delayed structural progression with TNFi use in AS patients. The systematic review also confirmed that mSASSS has good-to-excellent inter-rater reliability in AS.

8.
PLoS One ; 15(2): e0229273, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32084192

RESUMO

OBJECTIVE: Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are associated with mental illness. The risk of serious mental illness, including deliberate self-harm (DSH), in these conditions is not well known. We aimed to determine if RA or AS independently increases the risk for DSH. METHODS: We conducted retrospective, population-based cohort studies using administrative health data for the province of Ontario, Canada between April 1, 2002 and March 31, 2014. Individuals with incident RA (N = 53,240) or AS (N = 13,964) were separately matched 1:4 by age, sex, and year with comparators without RA or AS. The outcome was a first DSH attempt identified using emergency department data. We estimated hazard ratios (HR) and 95% confidence intervals (95% CI) for risk of DSH in RA and AS versus comparators, adjusting for demographic, clinical and health service utilization variables. RESULTS: Subjects with AS were significantly more likely to self-harm (crude incidence rate [IR] of 0.68/1,000 person years [PY] versus 0.32/1,000 PY in comparators), with an adjusted HR of 1.59 (95% CI 1.15 to 2.21). DSH was increased for RA subjects (IR 0.35/1,000 PY) versus comparators (IR 0.24/1,000 PY) only before (HR 1.43, 95% CI 1.16 to 1.74), but not after covariate adjustment (HR 1.07, 95% CI 0.86 to 1.33). CONCLUSIONS: AS carries an increased risk for DSH but no such risk was observed in RA. Further evaluation of at-risk AS subjects is needed, including the longitudinal effects of disease and arthritis therapies on self-harm behaviour. This will inform whether specific risk-reduction strategies for DSH in inflammatory arthritis are needed.


Assuntos
Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico , Comportamento Autodestrutivo/complicações , Espondilite Anquilosante/complicações , Espondilite Anquilosante/diagnóstico , Artrite Reumatoide/psicologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Espondilite Anquilosante/psicologia
9.
Rheumatology (Oxford) ; 59(6): 1340-1346, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31593590

RESUMO

OBJECTIVE: The aim of this study was to compare patients with ankylosing spondylitis with psoriasis (ASP) and without psoriasis (AS), to axial PsA (axPsA) patients. METHODS: Two adult cohorts were recruited from the AS clinic: ASP and AS. These two cohorts were compared with two adult cohorts recruited from the PsA clinic: axPsA (radiographic sacroiliitis: ⩾bilateral grade 2 or unilateral grade 3 or 4); and Peripheral PsA. All patients were followed prospectively according to the same protocol. The demographic, clinical and radiographic variables were compared. Adjusted means were used to account for varying intervals between visits. A logistic regression was performed and adjusted for follow-up duration. RESULTS: There were 477 axPsA patients, 826 peripheral PsA, 675 AS and 91 ASP patients included. AS patients were younger (P < 0.001), more male and HLA-B*27 positive (76%, 72% vs 64%, P ⩽ 0.001, 82%, 75%, vs 19%, P = 0.001). They had more back pain at presentation (90%, 92% vs 19%, P = 0.001), worse axial disease activity scores (bath ankylosing spondylitis disease activity index: 4.1, 3.9 vs 3.5 P = 0.017), worse back metrology (bath ankylosing spondylitis metrology index: 2.9, 2.2 vs 1.8, P < 0.001), worse physician global assessments (2.4, 2.2 vs 2.1, P < 0.001), were treated more with biologics (29%, 21% vs 7%, P = 0.001) and had a higher grade of sacroiliitis (90%, 84% vs 51%, P < 0.001). Similar differences were detected in the comparison of ASP to axPsA and in a regression model. CONCLUSION: AS patients, with or without psoriasis, seem to be different demographically, genetically, clinically and radiographically from axPsA patients. axPsA seems to be a distinct entity.


Assuntos
Artrite Psoriásica/diagnóstico por imagem , Psoríase/complicações , Espondilite Anquilosante/diagnóstico por imagem , Adulto , Artrite Psoriásica/complicações , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Espondilite Anquilosante/complicações , Adulto Jovem
10.
J Rheumatol ; 47(4): 524-530, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31043543

RESUMO

OBJECTIVE: To compare clinical impression and confidence of extended role practitioners (ERP) with those of rheumatologists experienced in axial spondyloarthritis (axSpA) according to (1) evaluation of patients with chronic back pain assessed for axSpA; and (2) magnetic resonance imaging (MRI) recommendation for further investigation of these patients. METHODS: Patients with ≥ 3 months of back pain and age of onset < 45 years were referred for axSpA evaluation. An ERP assessed consecutive patients and recorded standardized clinical information in written form. Three rheumatologists subsequently evaluated each patient based on the recorded information. Patients were classified as having axSpA or mechanical back pain based on clinical and investigative findings. Level of confidence was noted for classification and MRI indication. Agreement between assessors was evaluated using percentage agreement and κ coefficient. RESULTS: Fifty-seven patients were assessed. Interobserver agreement of clinical impression for all raters was moderate (κ = 0.52). Agreement of clinical impression between ERP and rheumatologists ranged between 71.2% (κ = 0.41) and 79.7% (κ = 0.57). Agreement of clinical impression among rheumatologists ranged from 74.1% (κ = 0.49) to 79.7% (κ = 0.58). All rater agreement for MRI indication was fair (κ = 0.37). ERP agreement with rheumatologist for MRI recommendation ranged from 64.2% (κ = 0.32) to 75% (κ = 0.48). Agreement for MRI indication among rheumatologists ranged from 62.9% (κ = 0.27) to 74% (κ = 0.47). Confidence in clinical impression was similar among all practitioners. CONCLUSION: ERP with specialty training in inflammatory arthritis demonstrate clinical impressions comparable with those of rheumatologists in the assessment of axSpA. Incorporation of such roles into existing models of care may assist in early detection of axSpA.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31675169

RESUMO

OBJECTIVES: Using a longitudinal observational cohort of ankylosing spondylitis (AS) patients, we sought to identify progression rates, and factors predictive of spinal progression. As a secondary aim we analyzed the effect of tumor necrosis factor inhibitor (TNFi) treatment on radiographic progression. METHODS: AS patients who had baseline and follow-up cervical and lumbar X-rays were included in the study. Radiographic damage was assessed by the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). A change of 2 mSASSS units in 2 years was defined as progression. The characteristics of the study group such as demographic, clinical, laboratory, and treatment history were collected. RESULTS: There were 350 patients in the study. The mean mSASSS increased from 9.3 (15.8) units at baseline to 17.7 (21.7) units by the 6th year. Change in mSASSS scores between the 0 to 2, 2 to 4 and 4 to 6 years were 1.23 (2.68), 1.47 (2.86), and 1.52 (3.7) units respectively. Overall 24.3% of the group progressed in 2 years' time. Male sex (HR 2.46, 95%CI 1.05, 5.76), presence of baseline damage (HR 7.98, 95%CI 3.98, 16), increased inflammatory markers (logCRP; HR 1.35, 95%CI 1.07, 1.70) and TNFi use (HR 0.82, 95%CI 0.70, 0.96) were predictive of radiographic progression. There was a 20% reduction in the rate of progression with TNFi. CONCLUSION: Male sex, presence of baseline damage, active disease state and higher inflammatory markers confer a high-risk group for disease progression. Treatment with TNFi showed a disease modifying effect by slowing the rate of radiographic progression.

12.
Arthritis Care Res (Hoboken) ; 71(10): 1285-1299, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31436026

RESUMO

OBJECTIVE: To update evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). METHODS: We conducted updated systematic literature reviews for 20 clinical questions on pharmacologic treatment addressed in the 2015 guidelines, and for 26 new questions on pharmacologic treatment, treat-to-target strategy, and use of imaging. New questions addressed the use of secukinumab, ixekizumab, tofacitinib, tumor necrosis factor inhibitor (TNFi) biosimilars, and biologic tapering/discontinuation, among others. We used the Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the quality of evidence and formulate recommendations and required at least 70% agreement among the voting panel. RESULTS: Recommendations for AS and nonradiographic axial SpA are similar. TNFi are recommended over secukinumab or ixekizumab as the first biologic to be used. Secukinumab or ixekizumab is recommended over the use of a second TNFi in patients with primary nonresponse to the first TNFi. TNFi, secukinumab, and ixekizumab are favored over tofacitinib. Co-administration of low-dose methotrexate with TNFi is not recommended, nor is a strict treat-to-target strategy or discontinuation or tapering of biologics in patients with stable disease. Sulfasalazine is recommended only for persistent peripheral arthritis when TNFi are contraindicated. For patients with unclear disease activity, spine or pelvis magnetic resonance imaging could aid assessment. Routine monitoring of radiographic changes with serial spine radiographs is not recommended. CONCLUSION: These recommendations provide updated guidance regarding use of new medications and imaging of the axial skeleton in the management of AS and nonradiographic axial SpA.


Assuntos
Pesquisa Biomédica/normas , Reumatologia/normas , Espondilartrite/diagnóstico por imagem , Espondilite Anquilosante/diagnóstico por imagem , Antirreumáticos/uso terapêutico , Pesquisa Biomédica/métodos , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/normas , Humanos , Reumatologia/métodos , Espondilartrite/epidemiologia , Espondilartrite/terapia , Espondilite Anquilosante/epidemiologia , Espondilite Anquilosante/terapia , Resultado do Tratamento , Estados Unidos/epidemiologia
13.
Arthritis Rheumatol ; 71(10): 1599-1613, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31436036

RESUMO

OBJECTIVE: To update evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). METHODS: We conducted updated systematic literature reviews for 20 clinical questions on pharmacologic treatment addressed in the 2015 guidelines, and for 26 new questions on pharmacologic treatment, treat-to-target strategy, and use of imaging. New questions addressed the use of secukinumab, ixekizumab, tofacitinib, tumor necrosis factor inhibitor (TNFi) biosimilars, and biologic tapering/discontinuation, among others. We used the Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the quality of evidence and formulate recommendations and required at least 70% agreement among the voting panel. RESULTS: Recommendations for AS and nonradiographic axial SpA are similar. TNFi are recommended over secukinumab or ixekizumab as the first biologic to be used. Secukinumab or ixekizumab is recommended over the use of a second TNFi in patients with primary nonresponse to the first TNFi. TNFi, secukinumab, and ixekizumab are favored over tofacitinib. Co-administration of low-dose methotrexate with TNFi is not recommended, nor is a strict treat-to-target strategy or discontinuation or tapering of biologics in patients with stable disease. Sulfasalazine is recommended only for persistent peripheral arthritis when TNFi are contraindicated. For patients with unclear disease activity, spine or pelvis magnetic resonance imaging could aid assessment. Routine monitoring of radiographic changes with serial spine radiographs is not recommended. CONCLUSION: These recommendations provide updated guidance regarding use of new medications and imaging of the axial skeleton in the management of AS and nonradiographic axial SpA.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Espondilite Anquilosante/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Produtos Biológicos/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Desprescrições , Humanos , Imagem por Ressonância Magnética , Piperidinas/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Radiografia , Sociedades Médicas , Espondiloartropatias/diagnóstico por imagem , Espondiloartropatias/tratamento farmacológico , Espondilite Anquilosante/diagnóstico por imagem
15.
Arthritis Rheumatol ; 71(7): 1101-1111, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30848558

RESUMO

OBJECTIVE: The natural history of nonradiographic axial spondyloarthritis (SpA) is incompletely characterized, and there are concerns that nonsteroidal antiinflammatory drugs provide inadequate disease control in patients with active disease. This study was undertaken to investigate the effects of certolizumab pegol (CZP), an anti-tumor necrosis factor treatment, in patients with nonradiographic axial SpA with objective signs of inflammation. METHODS: In this ongoing parallel-group double-blind study, adults with active disease were recruited from 80 centers in Australia, Europe, North America, and Taiwan, and were randomized 1:1 to receive placebo or CZP (400 mg at weeks 0, 2, and 4, followed by 200 mg every 2 weeks) in addition to nonbiologic background medication (NBBM). Switching to open-label CZP (or other biologic) or making background medication changes was permitted at any point during the trial, although changes before week 12 were discouraged. The primary end point was the proportion of patients achieving major improvement (MI) (i.e., a ≥2.0-point decrease in the score from baseline or achievement of the lowest possible score [0.6]) in the Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 52. RESULTS: A total of 317 patients were randomized to receive placebo plus NBBM (n = 158) or CZP plus NBBM (n = 159). ASDAS-MI at week 52 was achieved in 47.2% (75 of 159) of CZP plus NBBM patients, which was significantly greater (P < 0.0001) than the 7.0% (11 of 158) of placebo plus NBBM patients in whom ASDAS-MI was achieved. Of the placebo plus NBBM patients, 60.8% (96 of 158) switched to open-label treatment before week 52 compared to 12.6% (20 of 159) of the CZP plus NBBM patients. CONCLUSION: Adding CZP to background medication is superior to adding placebo in patients with active nonradiographic axial SpA. These results indicate that remission in nonradiographic axial SpA treated without biologics occurs infrequently, demonstrating the need for treatment beyond nonbiologic therapy.


Assuntos
Certolizumab Pegol/uso terapêutico , Sacroileíte/diagnóstico por imagem , Espondiloartropatias/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Proteína C-Reativa/imunologia , Método Duplo-Cego , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Espondiloartropatias/diagnóstico por imagem , Espondiloartropatias/imunologia , Resultado do Tratamento
17.
Best Pract Res Clin Rheumatol ; 33(6): 101491, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-32305314

RESUMO

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.


Assuntos
Osteogênese , Espondilartrite , Osso e Ossos , Proteínas Hedgehog , Humanos , Inflamação , Espondilartrite/metabolismo
18.
Ann Rheum Dis ; 78(1): 111-121, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30287418

RESUMO

OBJECTIVES: We recently identified microRNA-181a-5p (miR-181a-5p) as a critical mediator involved in the destruction of lumbar facet joint (FJ) cartilage. In this study, we tested if locked nucleic acid (LNA) miR-181a-5p antisense oligonucleotides (ASO) could be used as a therapeutic to limit articular cartilage degeneration. METHODS: We used a variety of experimental models consisting of both human samples and animal models of FJ and knee osteoarthritis (OA) to test the effects of LNA-miR-181a-5p ASO on articular cartilage degeneration. Histopathological analysis including immunohistochemistry and in situ hybridisation were used to detect key OA catabolic markers and microRNA, respectively. Apoptotic/cell death markers were evaluated by flow cytometry. qPCR and immunoblotting were applied to quantify gene and protein expression. RESULTS: miR-181a-5p expression was increased in human FJ OA and knee OA cartilage as well as injury-induced FJ OA (rat) and trauma-induced knee OA (mouse) cartilage compared with control cartilage, correlating with classical OA catabolic markers in human, rat and mouse cartilage. We demonstrated that LNA-miR-181a-5p ASO in rat and mouse chondrocytes reduced the expression of cartilage catabolic and chondrocyte apoptotic/cell death markers in vitro. Treatment of OA-induced rat FJ or mouse knee joints with intra-articular injections of in vivo grade LNA-miR-181a-5p ASO attenuated cartilage destruction, and the expression of catabolic, hypertrophic, apoptotic/cell death and type II collagen breakdown markers. Finally, treatment of LNA-miR-181a-5p ASO in cultures of human knee OA chondrocytes (in vitro) and cartilage explants (ex vivo) further demonstrated its cartilage protective effects. CONCLUSIONS: Our data demonstrate, for the first time, that LNA-miR-181a-5p ASO exhibit cartilage-protective effects in FJ and knee OA.


Assuntos
Cartilagem Articular/efeitos dos fármacos , MicroRNAs/metabolismo , Oligonucleotídeos Antissenso/farmacologia , Osteoartrite/genética , Substâncias Protetoras/farmacologia , Animais , Apoptose/genética , Condrócitos/metabolismo , Humanos , Articulação do Joelho/efeitos dos fármacos , Vértebras Lombares , Camundongos , Ratos , Articulação Zigapofisária/efeitos dos fármacos
19.
Curr Rheumatol Rep ; 20(12): 82, 2018 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-30406859

RESUMO

PURPOSE OF REVIEW: Pain, functional limitation, and spinal damage are the three main domains that have significant impact on various aspects of axial spondyloarthritis (axSpA). RECENT FINDINGS: Several randomized controlled trials (RCTs) showed a beneficial effect of non-steroid ant-inflammatory drugs (NSAIDs) and biologic treatments on pain and function. The effect of available treatments on spinal damage is still of interest and is being studied. In this article, we review the literature on radiographic progression in axSpA. We discuss the natural course of spinal progression, predictors of spinal damage, and the effect of lifestyle changes and medications on radiographic progression in axSpA.


Assuntos
Coluna Vertebral/diagnóstico por imagem , Espondilite Anquilosante/diagnóstico por imagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Progressão da Doença , Humanos , Prognóstico , Espondilite Anquilosante/tratamento farmacológico , Resultado do Tratamento
20.
Arthritis Rheumatol ; 70(12): 2003-2013, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29869839

RESUMO

OBJECTIVE: Gut-derived innate lymphoid cell 3 (ILC3) has been shown to participate in the pathogenesis of ankylosing spondylitis (AS). CX3 CR1+ mononuclear phagocytes (MNPs) have been demonstrated to modulate ILC3 function in the gut. This study was undertaken to investigate the role of proinflammatory CX3 CR1+CD59+ MNPs in modulating ILC3 function in AS patients. METHODS: MNP subsets in the blood of AS patients and controls were analyzed by flow cytometry. The presence of CX3 CR1+CD59+ cells in tissue was confirmed by confocal microscopy. Expression of the proinflammatory chemokines CX3 CL1 and CCL2 and decoy receptor 6 (DcR-6) was analyzed. Peripheral CX3 CR1+CD59+ cells were cocultured with ILC3, and changes in their frequency were evaluated by flow cytometry. Transcriptome analysis of circulating CX3 CR1+ monocytes was also performed. RESULTS: DcR-6 deficiency and CCL2 overexpression were observed in inflamed tissues from AS patients. In the gut, the proinflammatory CX3 CR1+CD59+ MNP population was expanded, correlated with the presence of bacteria, and produced high levels of tumor necrosis factor-like molecule 1A (TL1A) and interleukin-23 (IL-23). MNPs positive for CD11b, CD11c, and major histocompatibility complex class II, predominantly expressing CX3 CR1, were also expanded in the small intestines of treatment-naive SKG relative to BALB/c mice. The frequency of gut-derived CX3 CR1+CD59+CCR9+TL1A+IL-23+ MNPs was significantly higher in the peripheral blood and synovial fluid of AS patients than controls. CCR9+CX3 CR1+CD59+ monocytes were also expanded in AS synovial and bone marrow samples. Transcriptome analysis of isolated CX3 CR1+CD59+ monocytes demonstrated a specific proinflammatory profile in AS. Isolated proinflammatory CX3 CR1+CD59+ MNPs from AS patients induced the expansion and activation of ILC3. CONCLUSION: Proinflammatory CX3 CR1+CD59+TL1A+IL-23+ MNPs are expanded in AS patients and display a specific proinflammatory transcriptome profile. Given the ability of these cells to support ILC3 expansion, they may promote a sustained proinflammatory status in AS.


Assuntos
Imunidade Inata , Linfócitos/imunologia , Monócitos/imunologia , Sistema Fagocitário Mononuclear/imunologia , Espondilite Anquilosante/imunologia , Adulto , Antígenos CD59/imunologia , Receptor 1 de Quimiocina CX3C/imunologia , Estudos de Casos e Controles , Feminino , Humanos , Interleucina-23/imunologia , Masculino , Pessoa de Meia-Idade , Receptores Tipo I de Fatores de Necrose Tumoral/imunologia
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