CCL19-CCR7-dependent reverse transendothelial migration of myeloid cells clears Chlamydia muridarum from the arterial intima.

Regions of the normal arterial intima predisposed to atherosclerosis are sites of ongoing monocyte trafficking and also contain resident myeloid cells with features of dendritic cells. However, the pathophysiological roles of these cells are poorly understood. Here we found that intimal myeloid cells underwent reverse transendothelial migration (RTM) into the arterial circulation after systemic stimulation of pattern-recognition receptors (PRRs). This process was dependent on expression of the chemokine receptor CCR7 and its ligand CCL19 by intimal myeloid cells. In mice infected with the intracellular pathogen Chlamydia muridarum, blood monocytes disseminated infection to the intima. Subsequent CCL19-CCR7-dependent RTM was critical for the clearance of intimal C. muridarum. This process was inhibited by hypercholesterolemia. Thus, RTM protects the normal arterial intima, and compromised RTM during atherogenesis might contribute to the intracellular retention of pathogens in atherosclerotic lesions.

Cutting Edge: Negative Regulation of Inflammasome Activation by TRAF1 Can Limit Gout.

Secretion of IL-1ß, a potent cytokine that plays a key role in gout pathogenesis, is regulated by inflammasomes. TRAF1 has been linked to heightened risk to inflammatory arthritis. In this article, we show that TRAF1 negatively regulates inflammasome activation to limit caspase-1 and IL-1ß secretion in human and mouse macrophages. TRAF1 reduces linear ubiquitination and subsequent oligomerization of the adapter protein, ASC. i.p. injection of monosodium urate crystals resulted in increased inflammatory cell infiltrates and IL-1ß production in Traf1 knockout mice compared with wild type littermates. In a model of monosodium urate crystal-induced gout, Traf1 knockout mice exhibited more swelling in the knee joints, increased infiltration of inflammatory cells, and higher expression of proinflammatory cytokines. In summary, this study identifies TRAF1 as a key regulator of IL-1ß production and a potential therapeutic target for inflammasome-driven diseases such as gout.

Third and Fourth Vaccine Doses Broaden and Prolong Immunity to SARS-CoV-2 in Adult Patients with Immune-Mediated Inflammatory Diseases.

Previous studies have reported impaired humoral responses after SARS-CoV-2 mRNA vaccination in patients with immune-mediated inflammatory diseases (IMIDs), particularly those treated with anti-TNF biologics. We previously reported that IMID patients diagnosed with inflammatory bowel disease, psoriasis, psoriatic arthritis, ankylosing spondylitis, or rheumatoid arthritis exhibited greater waning of Ab and T cell responses than healthy control subjects after SARS-CoV-2 vaccine dose 2. Fewer data are available on the effects of third and fourth doses. This observational cohort study collected plasma and PBMCs from healthy control subjects and untreated or treated patients with IMIDs prevaccination and after one to four doses of SARS-CoV-2 mRNA vaccine (BNT162b2 or mRNA-1273). SARS-CoV-2-specific Ab levels, neutralization, and T cell cytokine release were measured against wild-type and Omicron BA.1 and BA.5 variants of concern. Third vaccine doses substantially restored and prolonged Ab and T cell responses in patients with IMIDs and broadened responses against variants of concern. Fourth-dose effects were subtle but also prolonged Ab responses. However, patients with IMIDs treated with anti-TNF, especially patients with inflammatory bowel disease, exhibited lower Ab responses even after the fourth dose. Although T cell IFN-γ responses were maximal after one dose, IL-2 and IL-4 production increased with successive doses, and early production of these cytokines was predictive of neutralization responses at 3-4 mo postvaccination. Our study demonstrates that third and fourth doses of the SARS-CoV-2 mRNA vaccines sustain and broaden immune responses to SARS-CoV-2, supporting the recommendation for three- and four-dose vaccination regimens in patients with IMIDs.

Goodbye to the term 'ankylosing spondylitis', hello 'axial spondyloarthritis': time to embrace the ASAS-defined nomenclature.

Ankylosing spondylitis (AS) is the historic term used for decades for the HLA-B27-associated inflammatory disease affecting mainly the sacroiliac joints (SIJ) and spine. Classification criteria for AS have radiographic sacroiliitis as a dominant characteristic. However, with the availability of MRI of SIJ, it could be demonstrated that the disease starts long before definite SIJ changes become visible on radiographs. The Assessment of SpondyloArthritis international Society, representing a worldwide group of experts reached consensus on changes in the nomenclature pertaining to axial spondyloarthritis (axSpA), such as the terminology of diagnosis and of assessment of disease activity tools. These are important changes in the field, as experts in axSpA are now in agreement that the term axSpA is the overall term for the disease. A further differentiation, of which radiographic versus non-radiographic is only one aspect, may be relevant for research purposes. Another important decision was that the terms AS and radiographic axSpA (r-axSpA) can be used interchangeably, but that the preferred term is r-axSpA. Based on the decision that axSpA is the correct terminology, a proposal was made to officially change the meaning of the ASDAS acronym to 'Axial Spondyloarthritis Disease Activity Score'. In addition, for simplification it was proposed that the term ASDAS (instead of ASDAS-CRP) should be preferred and applied to the ASDAS calculated with C reactive protein (CRP). It is hoped that these changes will be used consequently for education, in textbooks, manuscripts and presentations.

Proteomic and genomic profiling of plasma exosomes from patients with ankylosing spondylitis.

INTRODUCTION: Recent advances in understanding the biology of ankylosing spondylitis (AS) using innovative genomic and proteomic approaches offer the opportunity to address current challenges in AS diagnosis and management. Altered expression of genes, microRNAs (miRNAs) or proteins may contribute to immune dysregulation and may play a significant role in the onset and persistence of inflammation in AS. The ability of exosomes to transport miRNAs across cells and alter the phenotype of recipient cells has implicated exosomes in perpetuating inflammation in AS. This study reports the first proteomic and miRNA profiling of plasma-derived exosomes in AS using comprehensive computational biology analysis. METHODS: Plasma samples from patients with AS and healthy controls (HC) were isolated via ultracentrifugation and subjected to extracellular vesicle flow cytometry analysis to characterise exosome surface markers by a multiplex immunocapture assay. Cytokine profiling of plasma-derived exosomes and cell culture supernatants was performed. Next-generation sequencing was used to identify miRNA populations in exosomes enriched from plasma fractions. CD4+ T cells were sorted, and the frequency and proliferation of CD4+ T-cell subsets were analysed after treatment with AS-exosomes using flow cytometry. RESULTS: The expression of exosome marker proteins CD63 and CD81 was elevated in the patients with AS compared with HC (q<0.05). Cytokine profiling in plasma-derived AS-exosomes demonstrated downregulation of interleukin (IL)-8 and IL-10 (q<0.05). AS-exosomes cocultured with HC CD4+ T cells induced significant upregulation of IFNα2 and IL-33 (q<0.05). Exosomes from patients with AS inhibited the proliferation of regulatory T cells (Treg), suggesting a mechanism for chronically activated T cells in this disease. Culture of CD4+ T cells from healthy individuals in the presence of AS-exosomes reduced the proliferation of FOXP3+ Treg cells and decreased the frequency of FOXP3+IRF4+ Treg cells. miRNA sequencing identified 24 differentially expressed miRNAs found in circulating exosomes of patients with AS compared with HC; 22 of which were upregulated and 2 were downregulated. CONCLUSIONS: Individuals with AS have different immunological and genetic profiles, as determined by evaluating the exosomes of these patients. The inhibitory effect of exosomes on Treg in AS suggests a mechanism contributing to chronically activated T cells in this disease.

Incidence and predictors of demyelinating disease in spondyloarthritis: data from a longitudinal cohort study.

OBJECTIVES: To investigate the incidence of demyelinating disease (DD) among spondyloarthritis (SpA) patients and identify risk factors that predict DD in this patient population. METHODS: Axial SpA (axSpA) and psoriatic arthritis (PsA) patients were identified from a longitudinal cohort database. Each group was analysed according to the presence or absence of DD. Incidence rates (IR) of DD were obtained with competing risk analysis. Cox regression analysis with Fine and Grey's method was used to evaluate predictors of DD development. RESULTS: Among 2260 patients with follow-up data, we identified 18 DD events corresponding to an average IR of 31 per 100 000 persons per year for SpA. The IR of DD at 20 years was higher in axSpA than in PsA (1.30% vs 0.13%, p= 0.01). The risk factors retained in the best predictive model for DD development included ever- (versus never-) smoking (HR 2.918, 95% CI 1.037-8.214, p= 0.0426), axSpA (versus PsA) (HR 8.790, 95% CI 1.242-62.182, p= 0.0294), and presence (versus absence) of IBD (HR 5.698, 95% CI 2.083-15.589, p= 0.0007). History of TNFi therapy was not a predictor of DD. CONCLUSION: The overall incidence of DD in this SpA cohort was low. Incident DD was higher in axSpA than in PsA. A diagnosis of axSpA, the presence of IBD, and ever-smoking predicted the development of DD. History of TNFi use was not found to be a predictor of DD in this cohort.

Isolated axial disease in psoriatic arthritis and ankylosing spondylitis with psoriasis.

OBJECTIVES: To compare isolated axial psoriatic arthritis (PsA), axial PsA with peripheral involvement and isolated axial ankylosing spondylitis (AS) with psoriasis. To evaluate predictors for developing peripheral disease from isolated axial PsA over time. METHODS: Two PsA and AS cohorts identified patients with PsA with axial disease and isolated axial patients with AS with psoriasis. Logistic regression compared isolated axial PsA to axial PsA with peripheral involvement and isolated axial AS with psoriasis. Cox proportional hazards model evaluated predictors for developing peripheral disease from isolated axial PsA. RESULTS: Of 1576 patients with PsA, 2.03% had isolated axial disease and 29.38% had axial and peripheral disease. human leucocyte antigen HLA-B*27 positivity (OR 25.00, 95% CI 3.03 to 206.11) and lower Health Assessment Questionnaire scores (OR 0.004, 95% CI 0.00 to 0.28) were associated with isolated axial disease. HLA-B*27 also predicted peripheral disease development over time (HR 7.54, 95% CI 1.79 to 31.77). Of 1688 patients with AS, 4.86% had isolated axial disease with psoriasis. Isolated axial patients with PsA were older at diagnosis (OR 1.06, 95% CI 1.01 to 1.13), more likely to have nail lesions (OR 12.37, 95% CI 2.22 to 69.07) and less likely to have inflammatory back pain (OR 0.12, 95% CI 0.02 to 0.61) compared with patients with isolated axial AS with psoriasis. CONCLUSIONS: Isolated axial PsA and AS with psoriasis are uncommon. HLA-B*27 positivity is associated with isolated axial PsA and may identify those who develop peripheral disease over time. Isolated axial PsA is associated with better functional status. Isolated axial PsA appears clinically distinct from isolated axial AS with psoriasis.

Efficacy and safety of upadacitinib for active ankylosing spondylitis refractory to biological therapy: a double-blind, randomised, placebo-controlled phase 3 trial.

OBJECTIVES: To evaluate the efficacy and safety of upadacitinib, a Janus kinase inhibitor, in patients with active ankylosing spondylitis (AS) with an inadequate response (IR) to biological disease-modifying antirheumatic drugs (bDMARDs). METHODS: Adults with active AS who met modified New York criteria and had an IR to one or two bDMARDs (tumour necrosis factor or interleukin-17 inhibitors) were randomised 1:1 to oral upadacitinib 15 mg once daily or placebo. The primary endpoint was Assessment of SpondyloArthritis international Society 40 (ASAS40) response at week 14. Sequentially tested secondary endpoints included Ankylosing Spondylitis Disease Activity score, Spondyloarthritis Research Consortium of Canada MRI spine inflammation score, total back pain, nocturnal back pain, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index and Maastricht Ankylosing Spondylitis Enthesitis Score. Results are reported from the 14-week double-blind treatment period. RESULTS: A total of 420 patients with active AS were randomised (upadacitinib 15 mg, n=211; placebo, n=209). Significantly more patients achieved the primary endpoint of ASAS40 at week 14 with upadacitinib vs placebo (45% vs 18%; p<0.0001). Statistically significant improvements were observed with upadacitinib vs placebo for all multiplicity-controlled secondary endpoints (p<0.0001). Adverse events were reported for 41% of upadacitinib-treated and 37% of placebo-treated patients through week 14. No events of malignancy, major adverse cardiovascular events, venous thromboembolism or deaths were reported with upadacitinib. CONCLUSION: Upadacitinib 15 mg was significantly more effective than placebo over 14 weeks of treatment in bDMARD-IR patients with active AS. No new safety risks were identified with upadacitinib. TRIAL REGISTRATION NUMBER: NCT04169373.

Characteristics of patients with axial spondyloarthritis by geographic regions: PROOF multicountry observational study baseline results.

OBJECTIVES: To compare demographic and clinical characteristics of patients with axial SpA (axSpA) across geographic regions. METHODS: Patients With Axial Spondyloarthritis: Multicountry Registry of Clinical Characteristics (PROOF) is an observational study that enrolled recently diagnosed (≤1 year) axSpA patients fulfilling the Assessment of SpondyloArthritis international Society classification criteria from rheumatology clinical practices in 29 countries across six geographic regions. Demographics and disease-related parameters were collected. Here we present baseline data for patients who were classified as radiographic axSpA (r-axSpA) or non-radiographic axSpA (nr-axSpA) confirmed by central reading. RESULTS: Of the 2170 patients enrolled, 1553 were classified based on central evaluation of sacroiliac radiographs [r-axSpA: 1023 (66%); nr-axSpA: 530 (34%)]. Patients with nr-axSpA had a significantly higher occurrence of enthesitis (40% vs 33%), psoriasis (10% vs 5%) and IBD (4% vs 2%) vs r-axSpA patients. Significant differences in axSpA characteristics were observed between geographic regions. The highest occurrence of peripheral arthritis (60%), enthesitis (52%) and dactylitis (12%) was in Latin America, and the lowest was in Canada (9%, 9% and 2%, respectively). The occurrence of uveitis and psoriasis was highest in Canada (18% and 14%, respectively) and lowest in China (6% and <1%, respectively). IBD was highest in Arabia (21%), and no cases were observed in China. In multivariable analysis adjusted for factors potentially affecting peripheral and extramusculoskeletal manifestations, geographic regions still exhibited significant differences in frequencies of uveitis (P < 0.01), psoriasis (P < 0.0001) and peripheral arthritis (P < 0.0001). CONCLUSION: The multinational PROOF study of axSpA patients showed significant regional differences in peripheral and extramusculoskeletal manifestations of SpA, which could be considered in management guidelines and clinical trials.

Is axial psoriatic arthritis distinct from ankylosing spondylitis with and without concomitant psoriasis?

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.

Abnormal Low-Frequency Oscillations Reflect Trait-Like Pain Ratings in Chronic Pain Patients Revealed through a Machine Learning Approach.

Measures of moment-to-moment fluctuations in brain activity of an individual at rest have been shown to be a sensitive and reliable metric for studying pathological brain mechanisms across various chronic pain patient populations. However, the relationship between pathological brain activity and clinical symptoms are not well defined. Therefore, we used regional BOLD signal variability/amplitude of low-frequency oscillations (LFOs) to identify functional brain abnormalities in the dynamic pain connectome in chronic pain patients that are related to chronic pain characteristics (i.e., pain intensity). Moreover, we examined whether there were sex-specific attributes of these functional brain abnormalities and whether functional brain abnormalities in patients is related to pain intensity characteristics on different time scales. We acquired resting-state functional MRI and quantified frequency-specific regional LFOs in chronic pain patients with ankylosing spondylitis. We found that patients exhibit frequency-specific aberrations in LFOs. Specifically, lower-frequency (slow-5) abnormalities were restricted to the ascending pain pathway (thalamus and S1), whereas higher-frequency abnormalities also included the default mode (i.e., posterior cingulate cortex; slow-3, slow-4) and salience (i.e., mid-cingulate cortex) networks (slow-4). Using a machine learning approach, we found that these abnormalities, in particular within higher frequencies (slow-3), can be used to make generalizable inferences about patients' average pain ratings (trait-like pain) but not current (i.e., state-like) pain levels. Furthermore, we identified sex differences in LFOs in patients that were not present in healthy controls. These novel findings reveal mechanistic brain abnormalities underlying the longer-lasting symptoms (trait pain intensity) in chronic pain.SIGNIFICANCE STATEMENT Measures of moment-to-moment fluctuations in brain activity of an individual at rest have been shown to be a reliable metric for studying functional brain associated with chronic pain. The current results demonstrate that dysfunction in these intrinsic fluctuations/oscillations in the ascending pain pathway, default mode network, and salience network during resting state display sex differences and can be used to make inferences about trait-like pain intensity ratings in chronic pain patients. These results provide robust and generalizable implications for investigating brain mechanisms associated with longer-lasting/trait-like chronic pain symptoms.

The ties that bind: skin, gut and spondyloarthritis.

PURPOSE OF REVIEW: This article aims to review recent literature linking epithelial barrier inflammation and arthritis in spondyloarthritis (SpA), with a critical view on how they are bound by genetic, immunological and environmental ties. RECENT FINDINGS: The epithelia-joint axis has become an intense area of both basic and clinical SpA research. The penultimate goal is to understand the immunopathologic links between epithelial inflammation and arthritis in SpA. Inflammatory bowel disease (IBD) and psoriasis (PsO) have strong links to SpA at several levels. Clinically, there is a strong association of IBD, PsO and SpA. Genetically, there are many shared risk factors; however, there are also distinct differences in the genetics of the respective diseases. Immunologically, type 3 immunity, especially interleukin (IL)-17 and IL-23 dysregulation, has been shown to play a central role in IBD, PsO and SpA. Environmentally, a microbial dysbiosis has been noted in each of these diseases, but whether the microbial signature is similar between diseases is not clear, nor is the effect of dysbiosis on the immune response known. SUMMARY: It will be crucial to determine whether the relationship between epithelia inflammation and SpA is truly causal for both the understanding of pathogenesis and for future treatment strategies.

Efficacy and safety of continuing versus withdrawing adalimumab therapy in maintaining remission in patients with non-radiographic axial spondyloarthritis (ABILITY-3): a multicentre, randomised, double-blind study.

BACKGROUND: Success of treatment withdrawal in patients with non-radiographic axial spondyloarthritis who are in remission remains unknown. The ABILITY-3 study explored the ability to withdraw adalimumab treatment in patients with non-radiographic axial spondyloarthritis who achieved sustained clinical remission after open-label treatment with adalimumab. METHODS: ABILITY-3 was a multicentre, two-period study done in 107 sites in 20 countries. We enrolled adult patients (≥18 years) diagnosed with non-radiographic axial spondyloarthritis, fulfilling Assessment of SpondyloArthritis international Society classification criteria but not the modified New York radiologic criterion, who had objective evidence of active inflammation, active disease, and inadequate response to at least two non-steroidal anti-inflammatory drugs. Patients who achieved Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease (<1·3) with open-label adalimumab (40 mg subcutaneously every other week for 28 weeks) at weeks 16, 20, 24, and 28 were randomly assigned (1:1) using an interactive voice or web response system to 40-week, double-blind treatment with adalimumab (continuation) or placebo (withdrawal). The primary efficacy endpoint was the proportion of patients who did not experience a flare (defined as ASDAS ≥2·1 at two consecutive visits) during the double-blind period. Patients who flared were rescued with open-label adalimumab. This study is registered with ClinicalTrials.gov, number NCT01808118. FINDINGS: Between June 27, 2013, and October 22, 2015, 673 patients were enrolled to the study. The trial completed on April 14, 2017. Of 673 enrolled patients, 305 (45%) achieved sustained remission and were randomly assigned to double-blind treatment (152 patients to adalimumab and 153 to placebo). A greater proportion of patients continuing adalimumab than those receiving placebo did not experience a flare (107 [70%] of 152 patients vs 72 [47%] of 153 patients; p<0·0001) up to and including week 68. Among 673 patients receiving adalimumab at any time, 516 (77%) patients reported an adverse event and 28 (4%) experienced a serious adverse event. The most common adverse events in both the adalimumab and placebo groups were nasopharyngitis (25 [16%] vs 20 [13%]), upper respiratory tract infection (20 [13%] vs 12 [8%]), and worsening of axial spondyloarthritis (ten [7%] vs 21 [14%]). INTERPRETATION: In patients with active non-radiographic axial spondyloarthritis who achieved sustained remission with adalimumab, continued therapy was associated with significantly fewer patients flaring than was treatment withdrawal. FUNDING: AbbVie.

Integrin and transcriptomic profiles identify a distinctive synovial CD8+ T cell subpopulation in spondyloarthritis.

OBJECTIVES: Current evidence suggests that immune events in the gut may impact joint inflammation in ankylosing spondylitis (AS) but the expression of gut-related trafficking molecules in the inflammed joint is poorly characterised. We aimed to (1) assess differential expression patterns of trafficking molecules between patients and controls, (2) generate joint-specific cellular signatures and (3) obtain transcriptomic profiles of noteworthy cell subpopulations. METHODS: Male subjects under 40 years of age fulfilling the mNY criteria were recruited. The following cells were surface stained using a 36-marker mass cytometry antibody panel: (1) peripheral blood mononuclear cells from AS patients, and healthy controls; (2) synovial fluid mononuclear cells from AS and rheumatoid arthritis (RA) patients. Additionally, RNA-seq was performed on CD8+ T cell subpopulations from the synovial fluid (SF). RESULTS: Mature CD8+ T cells were enriched in AS SF, with a distinct pattern of integrin expression (ß7, CD103, CD29 and CD49a). RNA-seq analysis of SF-derived CD103+CD49a+CD8+ T cells revealed elevated TNFAIP3, GZMB, PRF1 and IL-10. CONCLUSIONS: We have identified a novel integrin-expressing mature CD8+ T cell population (CD49a+CD103+ß7+CD29+) that appears to be more prevalent in AS SF than RA SF. These cells seem to possess dual cytotoxic and regulatory profiles which may play a role in AS pathogenesis.

Measurement properties of the ASAS Health Index: results of a global study in patients with axial and peripheral spondyloarthritis.

OBJECTIVES: To evaluate construct validity, interpretability, reliability and responsiveness as well as determination of cut-off points for good and poor health within the original English version and the 18 translations of the disease-specific Assessment of Spondyloarthritis international Society Health Index (ASAS HI) in 23 countries worldwide in patients with spondyloarthritis (SpA). METHODS: A representative sample of patients with SpA fulfilling the ASAS classification criteria for axial (axSpA) or peripheral SpA was used. The construct validity of the ASAS HI was tested using Spearman correlation with several standard health outcomes for axSpA. Test-retest reliability was assessed by intraclass correlation coefficients (ICCs) in patients with stable disease (interval 4-7 days). In patients who required an escalation of therapy because of high disease activity, responsiveness was tested after 2-24weeks using standardised response mean (SRM). RESULTS: Among the 1548 patients, 64.9% were men, with a mean (SD) age 42.0 (13.4) years. Construct validity ranged from low (age: 0.10) to high (Bath AnkylosingSpondylitisFunctioning Index: 0.71). Internal consistency was high (Cronbach's α of 0.93). The reliability among 578 patients was good (ICC=0.87 (95% CI 0.84 to 0.89)). Responsiveness among 246 patients was moderate-large (SRM=-0.44 for non-steroidal anti-inflammatory drugs, -0.69 for conventional synthetic disease-modifying antirheumatic drug and -0.85 for tumour necrosis factor inhibitor). The smallest detectable change was 3.0. Values ≤5.0 have balanced specificity to distinguish good health as opposed to moderate health, and values ≥12.0 are specific to represent poor health as opposed to moderate health. CONCLUSIONS: The ASAS HI proved to be valid, reliable and responsive. It can be used to evaluate the impact of SpA and its treatment on functioning and health. Furthermore, comparison of disease impact between populations is possible.

Treating axial spondyloarthritis and peripheral spondyloarthritis, especially psoriatic arthritis, to target: 2017 update of recommendations by an international task force.

Therapeutic targets have been defined for axial and peripheral spondyloarthritis (SpA) in 2012, but the evidence for these recommendations was only of indirect nature. These recommendations were re-evaluated in light of new insights. Based on the results of a systematic literature review and expert opinion, a task force of rheumatologists, dermatologists, patients and a health professional developed an update of the 2012 recommendations. These underwent intensive discussions, on site voting and subsequent anonymous electronic voting on levels of agreement with each item. A set of 5 overarching principles and 11 recommendations were developed and voted on. Some items were present in the previous recommendations, while others were significantly changed or newly formulated. The 2017 task force arrived at a single set of recommendations for axial and peripheral SpA, including psoriatic arthritis (PsA). The most exhaustive discussions related to whether PsA should be assessed using unidimensional composite scores for its different domains or multidimensional scores that comprise multiple domains. This question was not resolved and constitutes an important research agenda. There was broad agreement, now better supported by data than in 2012, that remission/inactive disease and, alternatively, low/minimal disease activity are the principal targets for the treatment of PsA. As instruments to assess the patients on the path to the target, the Ankylosing Spondylitis Disease Activity Score (ASDAS) for axial SpA and the Disease Activity index for PSoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA) for PsA were recommended, although not supported by all. Shared decision-making between the clinician and the patient was seen as pivotal to the process. The task force defined the treatment target for SpA as remission or low disease activity and developed a large research agenda to further advance the field.

2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis.

To update and integrate the recommendations for ankylosing spondylitis and the recommendations for the use of tumour necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA) into one set applicable to the full spectrum of patients with axSpA. Following the latest version of the European League Against Rheumatism (EULAR) Standardised Operating Procedures, two systematic literature reviews first collected the evidence regarding all treatment options (pharmacological and non-pharmacological) that were published since 2009. After a discussion of the results in the steering group and presentation to the task force, overarching principles and recommendations were formulated, and consensus was obtained by informal voting. A total of 5 overarching principles and 13 recommendations were agreed on. The first three recommendations deal with personalised medicine including treatment target and monitoring. Recommendation 4 covers non-pharmacological management. Recommendation 5 describes the central role of non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice drug treatment. Recommendations 6-8 define the rather modest role of analgesics, and disprove glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for axSpA patents with predominant axial involvement. Recommendation 9 refers to biological DMARDs (bDMARDs) including TNFi and IL-17 inhibitors (IL-17i) for patients with high disease activity despite the use (or intolerance/contraindication) of at least two NSAIDs. In addition, they should either have an elevated C reactive protein and/or definite inflammation on MRI and/or radiographic evidence of sacroiliitis. Current practice is to start with a TNFi. Switching to another TNFi or an IL-17i is recommended in case TNFi fails (recommendation 10). Tapering, but not stopping a bDMARD, can be considered in patients in sustained remission (recommendation 11). The final two recommendations (12, 13) deal with surgery and spinal fractures. The 2016 Assessment of SpondyloArthritis international Society-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA.