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PURPOSE OF REVIEW: It is now 50âyears since the concept of spondyloarthritis was introduced by Moll, Wright and co-authors from Leeds, UK. This review will review the original concept and mark significant milestones over the last 50âyears while looking ahead to developments in the future. RECENT FINDINGS: While the diseases included under this rubric in the original description may have changed the core conditions remain and are still characterized by axial inflammation as a common feature. Imaging, animal models, genetics and immunology have contributed to our knowledge of the pathogenesis and classification of these diseases and have led to the development of more effective treatments. SUMMARY: Future developments, facilitated by large research consortia, will help build on our current knowledge and will help clarify disease heterogeneity and provide insights into new therapeutic pathways.
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Espondilartrite , Humanos , Espondilartrite/diagnóstico , Espondilartrite/imunologia , História do Século XX , História do Século XXI , AnimaisRESUMO
OBJECTIVES: The objective of this study was to compare the performance of three PsA screening questionnaires in a primary care psoriasis surveillance study. METHODS: Participants with psoriasis, and not known to have PsA, were identified from general practice databases and invited to attend a secondary care centre for a clinical assessment. The three patient-completed screening questionnaires (PEST, CONTEST and CONTESTjt) were administered, along with other patient-reported measures, and a clinical examination of skin and joints was performed. Participants who demonstrated signs of inflammatory arthritis suggestive of PsA were referred, via their GP, for a further assessment in a secondary care rheumatology clinic. RESULTS: A total of 791 participants attended the screening visit, and 165 participants were judged to have signs and symptoms of inflammatory arthritis, of which 150 were referred for assessment. Of these, 126 were seen and 48 were diagnosed with PsA. The results for each questionnaire were as follows: PEST: sensitivity 0.625 (95% CI 0.482, 0.749), specificity 0.757 (0.724, 0.787); CONTEST: sensitivity 0.604 (0.461, 0.731), specificity 0.768 (0.736, 0.798); and CONTESTjt: sensitivity 0.542 (0.401, 0.676), specificity 0.834 (0.805, 0.859). CONTESTjt demonstrated marginally superior specificity to PEST, though the area under the ROC curve was similar for all three instruments. CONCLUSION: Minimal differences between the three screening questionnaires were found in this study, and no preferred questionnaire is indicated by these results. The choice of which instrument to choose will depend on other factors, such as simplicity and low patient burden.
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Artrite Psoriásica , Psoríase , Humanos , Artrite Psoriásica/complicações , Sensibilidade e Especificidade , Psoríase/epidemiologia , Inquéritos e Questionários , Atenção Primária à Saúde , Programas de Rastreamento/métodosRESUMO
BACKGROUND: Our objective was to determine whether early detection of undiagnosed psoriatic arthritis (PsA) in a primary care psoriasis population improves outcome in physical function at 24 months post-registration. METHODS: A multicentre, prospective, parallel group cluster randomised controlled trial in patients with psoriasis was conducted. Participants with suspected inflammatory arthritis on screening were referred for an assessment of PsA (enhanced surveillance (ES) arm: at baseline, 12 and 24 months; standard care (SC) arm: at 24 months). The primary outcome measure was the Health Assessment Questionnaire Disability Index (HAQ-DI) at 24 months post registration in participants diagnosed with PsA. RESULTS: A total of 2225 participants across 135 GP practices registered: 1123 allocated to ES and 1102 to SC. The primary analysis population consisted of 87 participants with a positive diagnosis of PsA: 64 in ES, 23 in SC. The adjusted odds ratio (OR) for achieving a HAQ-DI score of 0 at 24 months post registration in ES compared with SC was 0.64 (95% CI (0.17, 2.38)), and the adjusted OR of achieving a higher (non-zero) HAQ-DI score at 24 months post registration in ES relative to SC arm was 1.12 (95% CI: 0.67, 1.86), indicating no evidence of a difference between the two treatment groups (p= 0.66). CONCLUSION: The trial was underpowered for demonstrating the prespecified treatment effect; in patients with psoriasis there was no evidence that early diagnosis of PsA by ES in primary care changes physical function at 24 months compared with SC. CLINICAL TRIAL REGISTRATION: The TUDOR trial is registered as ISRCTN38877516.
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OBJECTIVES: The ASSIST study investigated prescribing in routine psoriatic arthritis (PsA) care and whether the patient reported outcome: PsA Impact of Disease questionnaire (PsAID-12), impacted treatment. This study also assessed a range of patient and clinician factors and their relationship to PsAID-12 scoring and treatment modification. METHODS: Patients with PsA were selected across the UK and Europe between July 2021-March 2022. Patients completed the PsAID questionnaire, with the results shared with their physician. Patient characteristics, disease activity, current treatment methods, treatment strategies, medication changes and patient satisfaction scores were recorded. RESULTS: 503 patients recruited. 36.2% had changes made to treatment, 88.8% of this had treatment escalation. Overall, the mean PsAID-12 score was higher for patients with treatment escalation; the PsAID-12 score was associated with odds of treatment escalation (OR: 1.58; p< 0.0001). However, most clinicians reported PsAID-12 did not impact their decision to escalate treatment, instead supporting treatment reduction decisions. Physician's assessment of disease activity had the most statistically significant effect on likelihood of treatment escalation, (OR = 2.68, per 1-point score increase). Escalation was more likely in patients not treated with biologic therapies. Additional factors associated with treatment escalation included: patient characteristics, physician characteristics, disease activity and disease impact. CONCLUSION: This study highlights multiple factors impacting treatment decision making for individuals with PsA. PsAID-12 scoring correlates with multiple measures of disease severity and odds of treatment escalation. However, most clinicians reported the PsAID-12 did not influence treatment escalation decisions. PsAID scoring could be used to increase confidence in treatment de-escalation.
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The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) started in August 2003 with 40 initial participants and celebrated its 20th anniversary with 1036 members, many of whom attended the annual meeting in Dublin, Ireland, on July 15 to 17, 2023. GRAPPA arose from a need experienced by psoriatic arthritis (PsA) and psoriasis (PsO) investigators to meet to address questions related to psoriatic disease (PsD). Though other groups were meeting at the time to classify and discuss PsA, GRAPPA arose from a desire to include international clinical and investigational researchers of both dermatology and rheumatology. The organization has built awareness of PsO and PsA, developed and validated research assessment tools to measure clinical status and disease outcomes, published multiple treatment recommendations, supported basic and clinical research on PsD pathophysiology, fostered interactions across research fields, and educated the future generation of PsO and PsA researchers. The group continues to focus on major priorities affecting patients with PsD and will continue evolving in the next decades.
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Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome and chronic nonbacterial osteomyelitis (CNO) are rare autoinflammatory/autoimmune conditions seen in adults and children. Although osteoarticular manifestations are the primary distinguishing features of SAPHO, over half of patients also have palmoplantar pustulosis (PPP). These and other associated disorders such as acne, inflammatory bowel disease, and hidradenitis suppurativa are characterized, at least in the early stages, by neutrophilic infiltration. The bone and skin manifestations exhibit both innate and adaptive immune responses and therefore share similar pathogenic molecules and overlapping treatment targets. At the Group for Research and Assessment for Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting, a 3-part presentation provided an overview of current efforts at establishing consensus on diagnosis/classification, treatment, and core outcome sets for SAPHO/CNO; an overview of PPP in SAPHO and as a standalone condition; and finally, an overview of the role of the neutrophil in these disorders.
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At the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting, members were updated on a number of ongoing activities during the key project update session. These activities included the Axial Involvement in Psoriatic Arthritis (AXIS) cohort, the Axial Psoriatic Arthritis Molecular and Clinical Characterization study, the Diagnostic Ultrasound Enthesitis Tool (DUET) study, the Sex- and Gender-Based Analysis of the Effectiveness of Advanced Therapies in Psoriatic Arthritis (SAGE-PsA) study, the Health Initiatives in Psoriasis and Psoriatic Arthritis Consortium European States (HIPPOCRATES), the GRAPPA slide library, and the GRAPPA treatment recommendations.
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OBJECTIVE: Psoriatic arthritis (PsA) is a heterogenous condition with musculoskeletal and skin manifestations. The physician global visual analog scale (VAS) is an important component of many composite scores used in clinical trials and observational studies. Currently, no training material exists to standardize this assessment. METHODS: The Psoriatic Arthritis Validation of Physician Global VAS (PAVLOVAS) project describes the development of a novel training infographic with stakeholder involvement, which was then evaluated in a Latin square design in which 20 patients with PsA were assessed by 10 clinicians. For each group of 10 patients, 5 assessors conducted traditional assessment (consisting of 66/68-joint count, body surface area, Leeds Enthesitis Index, and dactylitis and nail counts) and 5 assessors conducted a standardized, thorough general examination informed by the infographic. Assessors switched assessment type between groups. The 3-item (3VAS) and 4VAS informed by traditional and infographic methods were compared, alongside other composite scores. RESULTS: There was strong agreement between traditional and infographic physician global VAS (intraclass correlation coefficient [ICC] 0.69, P = 0.01). This improved to very strong agreement when incorporated into the 3VAS (ICC 0.99, P < 0.001) and 4VAS (ICC 0.99, P < 0.001). The duration of assessment was significantly less for the infographic vs traditional groups (6.5 vs 7.8 mins, P < 0.001). There was moderately high agreement between the 3VAS and 4VAS categories of disease activity, with the same categories defined by Psoriatic Arthritis Disease Activity Score (PASDAS) and Disease Activity Index for Psoriatic Arthritis (DAPSA; Ⲭ2 17.0, P = 0.049). CONCLUSION: Our group developed and validated a novel training infographic that informs a briefer assessment of the physician global VAS than traditional assessments. This tool has potential applications in training and routine clinical practice.
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OBJECTIVES: To identify and prioritize the top 10 research questions for PsA. METHODS: The British Psoriatic Arthritis Consortium (BritPACT) formed a Priority Setting Partnership (PSP) comprising of people living with PsA, carers and clinicians, supported by the James Lind Alliance (JLA). This PSP followed the established three-stage JLA process: first, an online survey of people living with PsA, carers and clinicians to identify PsA questions, asking, 'What do you think are the most important unanswered questions in psoriatic arthritis research?' The questions were checked against existing evidence to establish 'true uncertainties' and grouped as 'indicative questions' reflecting the overarching themes. Then a second online survey ranked the 'true uncertainties' by importance. Finally, a workshop including people living with PsA and clinician stakeholders finalized the top 10 research priorities. RESULTS: The initial survey attracted 317 respondents (69% people living with PsA, 15% carers), with 988 questions. This generated 46 indicative questions. In the second survey, 422 respondents (78% people living with PsA, 4% carers) prioritized these. Eighteen questions were taken forward to the final online workshop. The top unanswered PsA research question was 'What is the best strategy for managing patients with psoriatic arthritis including non-drug and drug treatments?' Other top 10 priorities covered diagnosis, prognosis, outcome assessment, flares, comorbidities and other aspects of treatment (https://www.jla.nihr.ac.uk). CONCLUSION: The top 10 priorities will guide PsA research and enable PsA researchers and those who fund research to know the most important questions for people living with PsA.
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Artrite Psoriásica , Pesquisa Biomédica , Humanos , Artrite Psoriásica/terapia , Prioridades em Saúde , Avaliação de Resultados em Cuidados de Saúde , Inquéritos e Questionários , CuidadoresRESUMO
OBJECTIVES: To evaluate the efficacy of guselkumab for the treatment of active PsA utilizing composite indices. METHODS: Data were pooled from the phase 3 DISCOVER-1 (n = 381) and DISCOVER-2 (n = 739) studies. In both studies, patients were randomized 1:1:1 to subcutaneous guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at week 0, week 4, then Q8W; or placebo Q4W with crossover to guselkumab 100 mg Q4W at week 24. Composite indices used to assess efficacy through week 52 included Disease Activity Index for Psoriatic Arthritis (DAPSA), Psoriatic Arthritis Disease Activity Score (PASDAS), minimal disease activity (MDA), and very low disease activity (VLDA). Through week 24, treatment failure rules were applied. Through week 52, non-responder imputation was used for missing data. RESULTS: Greater proportions of guselkumab- than placebo-treated patients achieved DAPSA low disease activity (LDA) and remission, PASDAS LDA and VLDA, MDA, and VLDA at week 24 vs placebo (all unadjusted P < 0.05). At week 52, in the guselkumab Q4W and Q8W groups, respectively, response rates were as follows: DAPSA LDA, 54.2% and 52.5%; DAPSA remission, 18.2% and 17.6%; PASDAS LDA, 45.3% and 41.9%; PASDAS VLDA, 16.9% and 19.5%; MDA, 35.9% and 30.7%; and VLDA, 13.1% and 14.4%. In the placebo-crossover-to-guselkumab group, response rates for all composite indices increased after patients switched to guselkumab, from week 24 through week 52. CONCLUSION: Treatment with guselkumab provided robust and sustained benefits across multiple PsA domains through 1 year, indicating that guselkumab is an effective therapy for the diverse manifestations of PsA. TRIAL REGISTRATION: NCT03162796; NCT03158285.
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Antirreumáticos , Artrite Psoriásica , Humanos , Artrite Psoriásica/tratamento farmacológico , Antirreumáticos/uso terapêutico , Resultado do Tratamento , Anticorpos Monoclonais Humanizados/uso terapêutico , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: Shared decision-making (SDM) is advocated to improve patient outcomes in Psoriatic arthritis (PsA). We analysed current prescribing practices and the extent of SDM in PsA across Europe. METHODS: The ASSIST study was a cross-sectional observational study of PsA patients aged ≥18 years attending face-to-face appointments between July 2021-March 2022. Patient demographics, current treatment and treatment decisions were recorded. SDM was measured by the clinician's effort to collaborate (CollaboRATE questionnaire) and patient communication confidence (PEPPI-5 tool). RESULTS: 503 patients were included from 24 centres across the UK, France, Germany, Italy and Spain. Physician- and patient-reported measures of disease activity were highest in the UK. Conventional synthetic DMARDs constituted a higher percentage of current PsA treatment in UK than continental Europe (66.4% vs 44.9%), which differed from biologic DMARDs (36.4% vs 64.4%). Implementing treatment escalation was most common in the UK. CollaboRATE and PEPPI-5 scores were high across centres. Of 31 patients with low CollaboRATE scores (<4.5), no patients with low PsAID-12 scores (<5) had treatment escalation. However, of 465 patients with CollaboRATE scores ≥4.5, 59 patients with low PsAID-12 scores received treatment escalation. CONCLUSIONS: Higher rates of treatment escalation seen in the UK may be explained by higher disease activity and a younger cohort. High levels of collaboration in face-to-face PsA consultations suggests effective implementation of the SDM approach. Our data indicate that, in patients with mild disease activity, only those with higher perceived collaboration underwent treatment escalation. Prospective studies should examine the impact of SDM on PsA patient outcomes. TRIAL REGISTRATION: clinicaltrials.gov, NCT05171270.
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PURPOSE OF REVIEW: The purpose of this review is to present the up-to-date evidence on the epidemiology, pathogenesis, musculoskeletal manifestations, and imaging of the synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome and to discuss its relationship with spondyloarthritis (SpA). RECENT FINDINGS: SAPHO is a rare inflammatory disorder of bone, joints, and skin, with a worldwide distribution that predominantly affects the middle-age adults. The hallmark of the syndrome is a constellation of sterile inflammatory osteitis, hyperostosis, and synovitis involving the anterior chest wall, associated with acneiform and neutrophilic dermatoses, such as palmoplantar pustulosis and severe acne. The axial skeleton, sacroiliac, and peripheral joints can be involved in a similar fashion to SpA. The pathogenesis of the syndrome is multifactorial. The diagnosis is mainly based on the clinical and typical radiological features. The treatment approach is based on the off-label use of antibiotics, bisphosphonates, disease-modifying antirheumatic drugs, and anticytokine biologics. SUMMARY: The SAPHO syndrome shares common features with SpA-related diseases, yet also shows some unique pathogenetic and clinical features. The nosology of SAPHO remains a subject of controversy, awaiting further research into the pathogenetic and clinical aspects of this syndrome. A better understanding of these aspects will improve the diagnostics and clinical care of patients with SAPHO.
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Acne Vulgar , Síndrome de Hiperostose Adquirida , Hiperostose , Osteíte , Espondilartrite , Sinovite , Acne Vulgar/tratamento farmacológico , Acne Vulgar/etiologia , Síndrome de Hiperostose Adquirida/diagnóstico , Síndrome de Hiperostose Adquirida/tratamento farmacológico , Síndrome de Hiperostose Adquirida/patologia , Adulto , Humanos , Hiperostose/patologia , Pessoa de Meia-Idade , Osteíte/diagnóstico , Osteíte/tratamento farmacológico , Osteíte/etiologia , Espondilartrite/complicações , Espondilartrite/diagnóstico , Espondilartrite/tratamento farmacológico , Sinovite/patologiaRESUMO
OBJECTIVE: To characterise the impact of dactylitis in disease-modifying antirheumatic drug (DMARD)-naive early psoriatic arthritis (PsA). METHODS: Patients with early PsA meeting the classification criteria for PsA (CASPAR) were recruited. Clinical outcomes were recorded, and ultrasonography was conducted to assess grey scale (GS) and power Doppler (PD) synovitis, periarticular cortical bone erosions and enthesitis. The cohort was dichotomised by the presence or absence of dactylitis. RESULTS: Of 177 patients with PsA, those with dactylitis (dactylitic PsA (81/177, 46%)) had higher tender joint count (p<0.01), swollen joint count (SJC) (p<0.001) and C reactive protein (CRP) (p<0.01) than non-dactylitic PsA. Dactylitis was more prevalent in toes (146/214 (68.2%)) than fingers (68/214 (31.8%)); 'hot' dactylitis was more prevalent than 'cold' (83.6% vs 16.4%). Ultrasound (US) synovitis and erosions were significantly more prevalent in dactylitic PsA (p<0.001 and p<0.001, respectively). Exclusion of dactylitis in dactylitic PsA confirmed significantly greater SJC (3 vs 1, p=0.002), US synovitis (GS ≥2: 20.6% vs 16.1%, p<0.001, or PD ≥1: 5.1% vs 3.3%, p<0.001) and erosions (1.1% vs 0.5% joints, p=0.008; 26.1% vs 12.8% patients, p=0.035%) than non-dactylitic PsA. Synovitis (GS ≥2 and/or PD ≥1) occurred in 53.7% of dactylitis. No substantial differences were observed for US enthesitis. CONCLUSION: Dactylitis signifies a more severe disease phenotype independently associated with an increased disease burden with greater SJC, CRP, US-detected synovitis and bone erosions in DMARD-naive early PsA and may be a useful discriminator for early risk stratification.
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Antirreumáticos , Artrite Psoriásica , Entesopatia , Sinovite , Antirreumáticos/uso terapêutico , Artrite Psoriásica/complicações , Artrite Psoriásica/diagnóstico por imagem , Artrite Psoriásica/tratamento farmacológico , Proteína C-Reativa , Entesopatia/diagnóstico por imagem , Entesopatia/etiologia , Humanos , Fenótipo , Índice de Gravidade de Doença , Sinovite/diagnóstico por imagem , Sinovite/tratamento farmacológico , Sinovite/etiologia , UltrassonografiaRESUMO
This review highlights the molecular and cellular mechanisms underlying psoriatic inflammation with an emphasis on recent developments which may impact on treatment approaches for this chronic disease. We consider both the skin and the musculoskeletal compartment and how different manifestations of psoriatic inflammation are linked. This review brings a focus to the importance of inflammatory feedback loops that exist in the initiation and chronic stages of the condition, and how close interaction between the epidermis and both innate and adaptive immune compartments drives psoriatic inflammation. Furthermore, we highlight work done on biomarkers to predict the outcome of therapy as well as the transition from psoriasis to psoriatic arthritis.
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Artrite Psoriásica , Psoríase , Artrite Psoriásica/genética , Humanos , Inflamação , PeleRESUMO
BACKGROUND: Many patients with psoriatic arthritis have an inadequate response to tumor necrosis factor (TNF) inhibitors. Guselkumab, a specific inhibitor of interleukin-23 (IL-23) via IL-23 p19 subunit binding, significantly improved psoriatic arthritis signs and symptoms with an acceptable safety profile in a phase 2 trial. METHODS: This multicentre, double-blind, randomised, placebo-controlled, phase 3 trial was done at 86 sites in 13 countries across Asia, Australasia, Europe, and North America and enrolled adults with active psoriatic arthritis (at least three swollen and three tender joints; and C-reactive protein ≥0·3 mg/dL) despite standard therapies. Eligibility criteria included inadequate response to or intolerance of standard treatment, including at least 4 months of apremilast, at least 3 months of non-biologic disease-modifying antirheumatic drugs (DMARDs), or at least 4 weeks of non-steroidal anti-inflammatory drugs for psoriatic arthritis. About 30% of study participants could have previously received one or two TNF inhibitors. Patients were randomly assigned (1:1:1, computer-generated permuted blocks; stratified by baseline DMARD and previous TNF inhibitor use) to subcutaneous guselkumab 100 mg every 4 weeks; guselkumab 100 mg at weeks 0, 4, then every 8 weeks; or matching placebo. The primary endpoint was American College of Rheumatology 20% improvement (ACR20) at week 24 in all patients per assigned treatment group using non-responder imputation. Safety was assessed in all patients per treatment received. This trial is registered at ClinicalTrials.gov, NCT03162796 (active, not recruiting). FINDINGS: From Aug 28, 2017, to Aug 17, 2018, we screened 624 patients, of whom 381 were randomly assigned and treated with guselkumab every 4 weeks (n=128), guselkumab every 8 weeks (n=127), or placebo (n=126). 362 patients continued study treatment up to week 24. The primary endpoint was met: ACR20 at week 24 was achieved by significantly greater proportions of patients in the guselkumab every 4 weeks group (76 [59%] of 128 [95% CI 50-68]) and every 8 weeks group (66 [52%] of 127 [43-61]) than in the placebo group (28 [22%] of 126 [15-30]), with percentage differences versus placebo of 37% (95% CI 26-48) for the every 4 weeks group and 30% (19-41) for the every 8 weeks group (both p<0·0001). Serious adverse events up to week 24 occurred in no patients receiving guselkumab every 4 weeks, four (3%) patients receiving guselkumab every 8 weeks, and five (4%) patients receiving placebo. Up to week 24, one patient in the placebo group died from cardiac failure and two had serious infections; no guselkumab-treated patient died or had serious infections. INTERPRETATION: Guselkumab demonstrated a favourable benefit-risk profile and might be an effective treatment option for patients with active psoriatic arthritis. FUNDING: Janssen Research and Development.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
OBJECTIVE: To compare the efficacy and safety of brodalumab, an interleukin-17 receptor subunit A inhibitor, with placebo, in patients with psoriatic arthritis (PsA). METHODS: Adult patients with active PsA and inadequate response to, or intolerance to, conventional treatment were enrolled into two phase III studies (NCT02029495 and NCT02024646) and randomised 1:1:1 to receive subcutaneous brodalumab 140 mg or 210 mg or placebo at weeks 0, 1 and every 2 weeks up to 24 weeks. About 30% of patients had prior use of biologics. The primary endpoint for both studies was the American College of Rheumatology 20 (ACR20) response at week 16. RESULTS: 962 patients were randomised across the studies prior to early termination due to sponsor decision. The primary endpoint was met in both studies. Based on comparable design and eligibility criteria, data from both studies were pooled. Significantly more patients achieved ACR20 at week 16 in both brodalumab treatment groups (45.8% and 47.9% for 140 mg and 210 mg, respectively) versus placebo (20.9%) (p<0.0001). Similar results were observed at week 24. Significantly higher proportions of patients receiving brodalumab achieved ACR50/70, Psoriasis Area and Severity Index 75/90/100 and resolution of dactylitis and enthesitis versus placebo (p<0.01). Adverse event rates were similar across treatments at week 16 (54.4%, 51.6% and 54.5% for placebo, brodalumab 140 mg and 210 mg, respectively). No new safety signals were reported. CONCLUSION: Brodalumab was associated with rapid and significant improvements in signs and symptoms of PsA versus placebo. Brodalumab was well tolerated, with a safety profile consistent with other interleukin-17 inhibitors.
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Anticorpos Monoclonais Humanizados/administração & dosagem , Artrite Psoriásica/tratamento farmacológico , Receptores de Interleucina-17/antagonistas & inibidores , Adolescente , Adulto , Artrite Psoriásica/imunologia , Método Duplo-Cego , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: There are few papers concerning ethnic differences in disease expression in PsA, which may be influenced by a number of genetic, lifestyle and cultural factors. This article aims to compare clinical and radiographic phenotypes in people of South Asian (SA) and North European (NE) origin with a diagnosis of PsA. METHODS: This was a cross-sectional observational study recruiting patients of SA and NE origin from two hospitals in a well-defined area in the North of England. RESULTS: A total of 58 SA and 48 NE patients were recruited. SA patients had a more severe clinical phenotype with more tender (median 5 vs 2) and swollen (median 1 vs 0) joints, more severe enthesitis (median 3 vs 1.5), more patients with dactylitis (24% vs 8%), more severe skin disease (median PASI 2.2 vs 1) and worse disease activity as measured by the composite Psoriatic Arthritis Disease Activity Score (mean 4.5 vs 3.6). With regards to patient-completed measures, SA patients had worse impact with poorer quality of life and function (mean HAQ 0.9 vs 0.6; mean PsAQoL 10.8 vs 6.2; mean 36-item short form physical component score 33.5 vs 38.9). No significant differences in current MTX and biologics use were found. CONCLUSIONS: SA patients had a worse clinical phenotype and worse impact of disease than NE patients. Further studies are needed to confirm and explore the reasons behind these differences.
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Artrite Psoriásica/diagnóstico , Entesopatia/diagnóstico , Inflamação/diagnóstico , Qualidade de Vida , Adulto , Artrite Psoriásica/diagnóstico por imagem , Artrite Psoriásica/etnologia , Estudos Transversais , Progressão da Doença , Inglaterra , Entesopatia/diagnóstico por imagem , Entesopatia/etnologia , Feminino , Humanos , Inflamação/diagnóstico por imagem , Inflamação/etnologia , Masculino , Pessoa de Meia-Idade , Radiografia , Índice de Gravidade de DoençaRESUMO
The aim of this guideline is to provide an update on evidence-based recommendations for treatment of adult patients with PsA. The previous BSR guidelines for PsA were published in 2012 and since that time, there have been many new advanced therapies licensed for PsA. This update will provide practical guidance for clinicians on the optimal selection of advanced therapies taking into account different domains of PsA (arthritis, enthesitis, dactylitis, axial disease and psoriasis) and key associated comorbidities. It will also update guidance on treatment strategy including the use of a treat-to-target approach. The guideline will be developed using the methods and processes outlined in Creating Clinical Guidelines: Our Protocol. (1) This development process to produce guidance, advice and recommendations for practice has National Institute for Health and Care Excellence (NICE) accreditation.
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Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Humanos , Reumatologia/normas , Resultado do TratamentoRESUMO
OBJECTIVES: To examine which composite measures are most sensitive to change when measuring psoriatic arthritis (PsA) disease activity, analyses compared the responsiveness of composite measures used in a 48-week randomized, controlled trial of MTX and etanercept in patients with PsA. METHODS: The trial randomised 851 patients to receive weekly: MTX (20 mg/week), etanercept (50 mg/week) or MTX plus etanercept. Dichotomous composite measures examined included ACR 20/50/70 responses, minimal disease activity (MDA) and very low disease activity (VLDA). Continuous composite measures examined included Disease Activity Score (28 joints) using CRP (DAS28-CRP), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Disease Activity for Psoriatic Arthritis (DAPSA) and Psoriatic Arthritis Disease Activity Score (PASDAS). RESULTS: At week 24, etanercept-treated groups were significantly more effective than MTX monotherapy to achieve ACR 20 (primary end point) and MDA (key secondary end point). When examining score changes from baseline at week 24 across the five continuous composite measures, PASDAS demonstrated relatively greater changes in the etanercept-treated groups compared with MTX monotherapy and had the largest effect size and standardized response. Joint count changes drove overall score changes at week 24 from baseline in all the continuous composite measures except for PASDAS, which was driven by the Physician and Patient Global Assessments. CONCLUSION: PASDAS was the most sensitive continuous composite measure examined with results that mirrored the protocol-defined primary and key secondary outcomes. Composite measures with multiple domains, such as PASDAS, may better quantify change in PsA disease burden. TRAIL REGISTRATION: https://ClinicalTrials.gov, number NCT02376790.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Etanercepte/uso terapêutico , Metotrexato/uso terapêutico , Avaliação de Resultados da Assistência ao Paciente , Administração Oral , Proteína C-Reativa/análise , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
BACKGROUND/AIMS: Design of clinical trials requires careful decision-making across several dimensions, including endpoints, eligibility criteria, and subgroup enrichment. Clinical trial simulation can be an informative tool in trial design, providing empirical evidence by which to evaluate and compare the results of hypothetical trials with varying designs. We introduce a novel simulation-based approach using observational data to inform the design of a future pragmatic trial. METHODS: We utilize propensity score-adjusted models to simulate hypothetical trials under alternative endpoints and enrollment criteria. We apply our approach to the design of pragmatic trials in psoriatic arthritis, using observational data embedded within the Tight Control of Inflammation in Early Psoriatic Arthritis study to simulate hypothetical open-label trials comparing treatment with tumor necrosis factor-α inhibitors to methotrexate. We first validate our simulations of a trial with traditional enrollment criteria and endpoints against a recently published trial. Next, we compare simulated treatment effects in patient populations defined by traditional and broadened enrollment criteria, where the latter is consistent with a future pragmatic trial. In each trial, we also consider five candidate primary endpoints. RESULTS: Our results highlight how changes in the enrolled population and primary endpoints may qualitatively alter study findings and the ability to detect heterogeneous treatment effects between clinical subgroups. For treatments of interest in the study of psoriatic arthritis, broadened enrollment criteria led to diluted estimated treatment effects. Endpoints with greater responsiveness to treatment compared with a traditionally used endpoint were identified. These considerations, among others, are important for designing a future pragmatic trial aimed at having high external validity with relevance for real-world clinical practice. CONCLUSION: Observational data may be leveraged to inform design decisions in pragmatic trials. Our approach may be generalized to the study of other conditions where existing trial data are limited or do not generalize well to real-world clinical practice, but where observational data are available.