Molecular Profiling of Axial Spondyloarthritis Patients Reveals an Association between Innate and Adaptive Cell Populations and Therapeutic Response to Tumor Necrosis Factor Inhibitors.

This study aims at identifying molecular biomarkers differentiating responders and non-responders to treatment with Tumor Necrosis Factor inhibitors (TNFi) among patients with axial spondyloarthritis (axSpA). Whole blood mRNA and plasma proteins were measured in a cohort of biologic-naïve axSpA patients (n = 35), pre and post (14 weeks) TNFi treatment with adalimumab. Differential expression analysis was used to identify the most enriched pathways and in predictive models to distinguish responses to TNFi. A treatment-associated signature suggests a reduction in inflammatory activity. We found transcripts and proteins robustly differentially expressed between baseline and week 14 in responders. C-reactive protein (CRP) and Haptoglobin (HP) proteins showed strong and early decrease in the plasma of axSpA patients, while a cluster of apolipoproteins (APOD, APOA2, APOA1) showed increased expression at week 14. Responders to TNFi treatment present higher levels of markers of innate immunity at baseline, and lower levels of adaptive immunity markers, particularly B-cells. A logistic regression model incorporating ASDAS-CRP, gender, and AFF3, the top differentially expressed gene at baseline, enabled an accurate prediction of response to adalimumab in our cohort (AUC = 0.97). In conclusion, innate and adaptive immune cell type composition at baseline may be a major contributor to response to adalimumab in axSpA patients. A model including clinical and gene expression variables should also be considered.

Determinants of health-related quality of life and global functioning and health in axSpA, pSpA, and PsA: results from the ASAS-PerSpA study.

OBJECTIVES: We aim to identify determinants of health-related quality of life (HRQoL) and global functioning and health (GH) in axial spondyloarthritis (axSpA), peripheral spondyloarthritis (pSpA), and psoriatic arthritis (PsA). METHODS: ASAS-perSpA study data were analyzed. Models for the three patient groups were performed separately to explore factors associated with HRQoL and GH, assessed by EQ-5D and ASAS-HI, respectively. RESULTS: The analyses included 4185 patients: 2719 with axSpA, 433 with pSpA, and 1033 with PsA.In axSpA, disease activity (DA) (ß=-0.061), physical function (ß=-0.041), female sex (ß=-0.019), and fibromyalgia (ß=-0.068) were associated with worse HRQoL; age (ß = 0.001) and university education (ß = 0.014) with better HRQoL. In pSpA, DA (ß=-0.04) and physical function (ß=-0.054) were associated with worse HRQoL. In PsA, DA (ß=-0.045), physical function (ß=-0.053), axial disease (ß=-0.041), and female sex (ß=-0.028) were associated with worse HRQoL.In axSpA, DA (ß = 0.889), physical function (ß = 0.887), peripheral disease (ß = 0.564), female sex (ß = 0.812) and fibromyalgia (ß = 1.639) were associated with worse GH; age (ß=-0.013) and university education (ß=-0.274) with better GH. In pSpA, physical function (ß = 1.142), and female sex (ß = 1.060) were associated with worse GH; university education (ß=-0.611) with better GH. In PsA, DA (ß = 0.703), physical function (ß = 1.025), axial involvement (ß = 0.659), female sex (ß = 0.924), and fibromyalgia (ß = 1.387) were associated with worse GH; age (ß=-0.024) and university education (ß=-0.856) with better GH. CONCLUSIONS: DA and physical function are major HRQoL and GH determinants across spondyloarthritis types, and clinical characteristics and sociodemographic factors play an important role, highlighting the importance of a holistic approach for individual patients.

The effects of physical exercise on axial spondyloarthritis - a systematic review.

AIM: To collect and summarize the available scientific evidence that evaluates the effects of physical exercise interventions on axial spondyloarthritis (axSpA). METHODS: A systematic review was conducted in accordance to the guidance of Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) to collect randomized controlled trials on the PubMed, Embase and Web of Science Core Collection databases. The search strategy included terms regarding physical exercise interventions targeted to axSpA participants and all of its variants in multiple combinations adapted to each one of the databases regarding its own special requirements. Several outcomes were defined: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), ASDAS (Ankylosing Spondylitis Disease Activity Score), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), the 36-item short form health survey (SF-36) and the Ankylosing Spondylitis Quality of Life questionnaire (ASQoL). Two independent researchers screened the titles and abstracts followed by full-text analysis when suitable, using EndnoteTM online. Selected articles, according to exclusion/inclusion criteria defined, were submitted to data extraction and bias assessment was performed for each study's outcomes using the Cochrane risk-of-bias tool for randomized trials. RESULTS: A total of 2063 articles were identified through the electronic databases search. After removal of duplicates, 1435 were eligible for screening, of which 45 articles went through full text evaluation. Only 24 articles met the inclusion/exclusion criteria. Physical exercise contributes for a statistically significant improvement of BASDAI in 13 studies, BASFI in 10, BASMI in 6, ASDAS in 3, CRP in 2, ESR in 1, SF-36 in 2 and ASQoL in 3.No major adverse effects were reported and an overall benefit was noted with the implementation of physical exercise as a treatment modality for axSpA. CONCLUSION: Physical exercise seems to be an effective non-pharmacological therapy for axSpA, with positive effects in disease activity, physical function, and quality of life.

ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update.

OBJECTIVES: To update the Assessment of SpondyloArthritis international Society (ASAS)-EULAR recommendations for the management of axial spondyloarthritis (axSpA). METHODS: Following the EULAR Standardised Operating Procedures, two systematic literature reviews were conducted on non-pharmacological and pharmacological treatment of axSpA. In a task force meeting, the evidence was presented, discussed, and overarching principles and recommendations were updated, followed by voting. RESULTS: Five overarching principles and 15 recommendations with a focus on personalised medicine were agreed: eight remained unchanged from the previous recommendations; three with minor edits on nomenclature; two with relevant updates (#9, 12); two newly formulated (#10, 11). The first five recommendations focus on treatment target and monitoring, non-pharmacological management and non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice pharmacological treatment. Recommendations 6-8 deal with analgesics and discourage long-term glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for pure axial involvement. Recommendation 9 describes the indication of biological DMARDs (bDMARDs, that is, tumour necrosis factor inhibitors (TNFi), interleukin-17 inhibitors (IL-17i)) and targeted synthetic DMARDs (tsDMARDs, ie, Janus kinase inhibitors) for patients who have Ankylosing Spondylitis Disease Activity Score ≥2.1 and failed ≥2 NSAIDs and also have either elevated C reactive protein, MRI inflammation of sacroiliac joints or radiographic sacroiliitis. Current practice is to start a TNFi or IL-17i. Recommendation 10 addresses extramusculoskeletal manifestations with TNF monoclonal antibodies preferred for recurrent uveitis or inflammatory bowel disease, and IL-17i for significant psoriasis. Treatment failure should prompt re-evaluation of the diagnosis and consideration of the presence of comorbidities (#11). If active axSpA is confirmed, switching to another b/tsDMARD is recommended (#12). Tapering, rather than immediate discontinuation of a bDMARD, can be considered in patients in sustained remission (#13). The last recommendations (#14, 15) deal with surgery and spinal fractures. CONCLUSIONS: The 2022 ASAS-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA.

Health-related quality of life among spondyloarthritis and chronic low back pain patients: results from a nationwide population-based survey.

PURPOSE: Both spondyloarthritis and chronic low back pain (CLBP) significantly impact health-related quality of life (HRQoL). It is important to clarify whether these disorders have different impacts on the several domains of HRQoL as different mechanisms may necessitate different treatment interventions. Moreover, the factors associated with HRQoL can inform more targeted group interventions to promote HRQoL. METHODS: We used data from EpiReumaPt, a population-based survey conducted from September 2011 to December 2013. HRQoL was assessed with EuroQoL-5-Dimensions (EQ-5D). Spondyloarthritis was diagnosed by expert opinion (rheumatologist) and predefined criteria. CLBP was diagnosed if low back pain was present on the day of the interview and persisted for > 90 days. Univariable and multivariable linear regression analyses compared HRQoL among subjects with spondyloarthritis, CLBP, and no rheumatic diseases. Multivariable linear regression analyses evaluated HRQoL factors in spondyloarthritis and CLBP subjects. RESULTS: We included 92 spondyloarthritis patients, 1376 CLBP patients, and 679 subjects without rheumatic diseases. HRQoL was similarly affected in spondyloarthritis and CLBP (ß = - 0.03, 95% CI [- 0.08; 0.03]) in all EQ5D dimensions. A much lower HRQoL was found in spondyloarthritis and CLBP patients compared with subjects without rheumatic diseases (ß = - 0.14, 95% CI [- 0.19; - 0.10]; ß = - 0.12, 95% CI [- 0.14; - 0.09], respectively). In spondyloarthritis subjects, multimorbidity and active disease were associated with worse HRQoL (ß = - 0.18; 95% CI [- 0.24; 0.03]; ß = - 0.13; 95% CI [- 0.29; - 0.05], respectively), and regular physical exercise was associated with better HRQoL (ß = 0.18; 95% CI [0.10; 0.30]). In CLBP subjects, multimorbidity (ß = - 0.11; 95% CI [- 0.14; - 0.08]), obesity (ß = - 0.04; 95% CI [- 0.08; - 0.01]), and low back pain intensity (ß = - 0.02; 95% CI [- 0.03; - 0.02]) were associated with worse HRQoL, and regular physical exercise (ß = 0.08; 95% CI [0.05; 0.11]) was significantly associated with better HRQoL. CONCLUSION: Spondyloarthritis and CLBP subjects reported similar levels of impairment in the mental, physical, and social domains of HRQoL. Future health plans should address modifiable factors associated with HRQoL in these conditions to achieve better outcomes.

Muscle dysfunction in axial spondylarthritis: the MyoSpA study.

OBJECTIVES: We aimed to investigate muscle physical properties, strength, mass, physical performance, and the prevalence of sarcopenia in patients with axial spondylarthritis (axSpA) compared to the healthy controls (HC). METHODS: We performed a cross-sectional study on 54 participants: 27 patients with axSpA and 27 HC, matched by age, gender, and level of physical activity. Muscle physical properties (stiffness, tone and elasticity), muscle strength (five-times sit-to-stand [5STS] test), muscle mass, physical performance (measured through gait speed) and sarcopenia were compared between the groups. Linear regression models were conducted allowing adjustment for relevant variables. RESULTS: Patients with axSpA (mean age 36.5 (SD 7.5) years, 67% males, mean disease duration 6.5 (3.2) years) had no significant difference in segmental muscle stiffness, tone or elasticity, compared with the HC, despite showing a slight numerically higher lower lumbar (L3-L4) stiffness [median 246.5 (IQR 230.5-286.5) vs. 232.5 (211.0-293.5), p=0.38]. No participants presented sarcopenia. Patients with axSpA, compared to the HC, had lower total strength [B=1.88 (95% CI 0.43;3.33)], as well as lower strength in the upper (B=-17.02 (-27.33;-6.70)] and lower limbs [B=-11.14 (-18.25;-4.04)], independently of muscle physical properties. Patients had also significantly lower gait speed than the HC [B=-0.11 (-0.21;-0.01)], adjusted for muscle mass, strength and muscle physical properties. CONCLUSIONS: Young axSpA patients with a relatively short disease duration presented similar segmental muscle physical properties as the HC and had no sarcopenia. Patients with axSpA had reduced physical performance and lower strength compared to the HC, despite normal muscle mass, suggesting a possible muscle dysfunction. Gait characteristics may be a potential biomarker of interest in axSpA.

The role of muscle in the susceptibility and progression of axial Spondyloarthritis: The MyoSpA Study Protocol.

BACKGROUND: Axial Spondyloarthritis (axSpA) is a chronic, inflammatory rheumatic disease that affects the axial skeleton, causing pain, stiffness, and fatigue. Genetics and environmental factors such as microbiota and microtrauma are known causes of disease susceptibility and progression. Murine models of axSpA found a decisive role for biomechanical stress as an inducer of enthesitis and new bone formation. Here, we hypothesize that muscle properties in axSpA patients are compromised and influenced by genetic background. OBJECTIVES: To improve our current knowledge of axSpA physiopathology, we aim to characterize axial and peripheral muscle properties and identify genetic and protein biomarker that might explain such properties. METHODS: A cross-sectional study will be conducted on 48 participants aged 18-50 years old, involving patients with axSpA (according to ASAS classification criteria, symptoms duration < 10 years) and healthy controls matched by gender, age, and levels of physical activity. We will collect epidemiological and clinical data and perform a detailed, whole body and segmental, myofascial characterization (focusing on multifidus, brachioradialis and the gastrocnemius lateralis) concerning: a) Physical Properties (stiffness, tone and elasticity), assessed by MyotonPRO®; b) Strength, by a dynamometer; c) Mass, by bioimpedance; d) Performance through gait speed and 60-second sit-to-stand test; e) Histological and cellular/ molecular characterization through ultrasound-guided biopsies of multifidus muscle; f) Magnetic Resonance Imaging (MRI) characterization of paravertebral muscles. Furthermore, we will perform an integrated transcriptomics and proteomics analysis of peripheral blood samples. DISCUSSION: The innovative and multidisciplinary approaches of this project rely on the elucidation of myofascial physical properties in axSpA and also on the establishment of a biological signature that relates to specific muscle properties. This hitherto unstudied link between gene/protein signatures and muscle properties may enhance our understanding of axSpA physiopathology and reveal new and useful diagnostic and therapeutic targets.

Identification of clinical phenotypes of peripheral involvement in patients with spondyloarthritis, including psoriatic arthritis: a cluster analysis in the worldwide ASAS-PerSpA study.

OBJECTIVE: To identify clusters of peripheral involvement according to the specific location of peripheral manifestations (ie, arthritis, enthesitis and dactylitis) in patients with spondyloarthritis (SpA) including psoriatic arthritis (PsA), and to evaluate whether these clusters correspond with the clinical diagnosis of a rheumatologist. METHODS: Cross-sectional study with 24 participating countries. Consecutive patients diagnosed by their rheumatologist as PsA, axial SpA or peripheral SpA were enrolled. Four different cluster analyses were conducted: one using information on the specific location from all the peripheral manifestations, and a cluster analysis for each peripheral manifestation, separately. Multiple correspondence analyses and k-means clustering methods were used. Distribution of peripheral manifestations and clinical characteristics were compared across the different clusters. RESULTS: The different cluster analyses performed in the 4465 patients clearly distinguished a predominantly axial phenotype (cluster 1) and a predominantly peripheral phenotype (cluster 2). In the predominantly axial phenotype, hip involvement and lower limb large joint arthritis, heel enthesitis and lack of dactylitis were more prevalent. In the predominantly peripheral phenotype, different subgroups were distinguished based on the type and location of peripheral involvement: a predominantly involvement of upper versus lower limbs joints, a predominantly axial enthesitis versus peripheral enthesitis, and predominantly finger versus toe involvement in dactylitis. A poor agreement between the clusters and the rheumatologist's diagnosis as well as with the classification criteria was found. CONCLUSION: These results suggest the presence of two main phenotypes (predominantly axial and predominantly peripheral) based on the presence and location of the peripheral manifestations.

Direct tissue-sensing reprograms TLR4+ Tfh-like cells inflammatory profile in the joints of rheumatoid arthritis patients.

CD4+ T cells mediate rheumatoid arthritis (RA) pathogenesis through both antibody-dependent and independent mechanisms. It remains unclear how synovial microenvironment impinges on CD4+ T cells pathogenic functions. Here, we identified a TLR4+ follicular helper T (Tfh) cell-like population present in the blood and expanded in synovial fluid. TLR4+ T cells possess a two-pronged pathogenic activity whereby direct TLR4+ engagement by endogenous ligands in the arthritic joint reprograms them from an IL-21 response, known to sponsor antibody production towards an IL-17 inflammatory program recognized to fuel tissue damage. Ex vivo, synovial fluid TLR4+ T cells produced IL-17, but not IL-21. Blocking TLR4 signaling with a specific inhibitor impaired IL-17 production in response to synovial fluid recognition. Mechanistically, we unveiled that T-cell HLA-DR regulates their TLR4 expression. TLR4+ T cells appear to uniquely reconcile an ability to promote systemic antibody production with a local synovial driven tissue damage program.

The Effect of ACTN3 and VDR Polymorphisms on Skeletal Muscle Performance in Axial Spondyloarthropathies.

BACKGROUND: Spondyloarthritis (SpA) are the most common group of chronic inflammatory rheumatic diseases affecting about 1.5% of the adult Caucasian population. Low back pain is the most common symptom. The aetiopathogenesis of SpA is multifactorial, with well-known genetic and environmental contributions. Furthermore, muscle properties might also be involved in the pathophysiological process and these could be modulated by the genetic background. Alpha-actinin-3 (ACTN3) and Vitamin D receptor (VDR) genes are well-known genes related with muscle performance. Our aim was to analyze four SNPs of these genes and to evaluate their influence in axial SpA (axSpA) susceptibility, phenotype and muscle properties. METHODS: We performed a pilot study based on case-control approach involving 56 participants: 28 axSpA patients and 28 healthy controls matched by age, gender and levels of physical activity. Clinical, epidemiological and muscle characterization data-muscle physical properties (stiffness, tone, and elasticity), strength, mass, and performance, were collected. Two different muscles were considered for analysis, the Multifidus and Gastrocnemius. Four SNPs of ACTN3 (rs1815739) and VDR (rs2228570, rs731236, and rs7975232), were selected, analyzed and correlated with clinical, epidemiological and muscle characterization data. RESULTS: In total, 51 individuals (27 axSpA patients and 24 matched controls) were eligible for further genetic analysis, 66.7% being male and with a mean age of 36 years. Muscle physical properties, muscle strength and muscle mass were similar in both groups; however, axSpA patients showed a decrease in muscle performance. None of the studied SNPs were associated with disease susceptibility/phenotype, muscle physical properties, muscle strength or muscle mass. However, ACTN3 rs1815739 and VDR rs2228570 were shown to be associated with muscle performance. CONCLUSION: Our results suggest an association between ACTN3 and VDR polymorphisms and muscle performance in axSpA.

Biologic disease-modifying anti-rheumatic drugs and patient-reported outcomes in axial SpA: a systematic review and a call for action.

This paper is to assess the efficacy of different biologic DMARDs (bDMARDs) on several patient-reported outcomes (PROs) in randomized controlled trials (RCT) in axial spondyloarthritis (axSpA). A systematic literature review (SLR) was performed. MEDLINE (May 1, 2018) was used with the filters "published in the last 10 years" and "humans." The PICO criteria used were Patients: adults with radiographic axSpA (r-axSpA) or non-radiographic axSpA (nr-axSpA); Intervention: any bDMARD; Compararator: placebo (PBO)/any different drug; Outcome: the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), the Ankylosing Spondylitis Quality of Life (ASQoL), the EuroQol-5D (EQ-5D), the Short Form 36 Health Survey physical component summary (SF36-PCS), the Short Form 36 Health Survey mental component summary (SF36-MCS), and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). After screening 84 initial references and manually selecting other 9, 24 publications, assessing TNF inhibitors (TNFi) or IL17A inhibitors (IL17Ai) were selected. Four RCTs quantified the minimal clinical important difference (MCID) between treatment arms. Most of the RCTs compared the mean difference of PROs between different timepoints. Overall, the treatment arm was superior to the comparator. PROs were often underreported or highly heterogeneously presented. MCID was seldom mentioned. There is a need to raise the standard of care on SpA by aiming at remission and PRO associated improvements. In order to achieve this goal, the target must be clearly defined, reported, and tested.

New Insights into Immunological Involvement in Congenital Disorders of Glycosylation (CDG) from a People-Centric Approach.

Congenital disorders of glycosylation (CDG) are rare diseases with variable phenotypes and severity. Immunological involvement remains a largely uncharted topic in CDG, mainly due to lack of robust data. To better characterize immune-related manifestations' prevalence, relevance, and quality-of-life (QoL) impact, we developed electronic questionnaires targeting (1) CDG patients and (2) the general "healthy" population. Two-hundred and nine CDG patients/caregivers and 349 healthy participants were included in this study. PMM2-CDG was the most represented CDG (n = 122/209). About half of these participants (n = 65/122) described relevant infections with a noteworthy prevalence of those affecting the gastrointestinal tract (GI) (63.1%, n = 41/65). Infection burden and QoL impact were shown as infections correlated with more severe clinical phenotypes and with a set of relevant non-immune PMM2-CDG signs. Autoimmune diseases had only a marginal presence in PMM2-CDG (2.5%, n = 3/122), all being GI-related. Allergy prevalence was also low in PMM2-CDG (33%, n = 41/122) except for food allergies (26.8%, n = 11/41, of PMM2-CDG and 10.8%, n = 17/158, of controls). High vaccination compliance with greater perceived ineffectiveness (28.3%, n = 17/60) and more severe adverse reactions were described in PMM2-CDG. This people-centric approach not only confirmed literature findings, but created new insights into immunological involvement in CDG, namely by highlighting the possible link between the immune and GI systems in PMM2-CDG. Finally, our results emphasized the importance of patient/caregiver knowledge and raised several red flags about immunological management.

Effect of biologic disease-modifying anti-rheumatic drugs targeting remission in axial spondyloarthritis: systematic review and meta-analysis.

OBJECTIVES: To assess the efficacy of biologic DMARDs (bDMARDs) in achieving Assessment of Spondyloarthritis International Society partial remission (ASAS-PR) and/or Ankylosing Spondylitis Disease Activity Score inactive disease (ASDAS-ID), as remission-like surrogates, in axial SpA (axSpA). METHODS: Data from randomized controlled trials (RCTs), including long-term extensions, were included. A systematic literature review was performed using the MEDLINE database (first search May 2018, updated February 2020) and PICO criteria according to Patients-adults with radiographic or non-radiographic axSpA; Intervention-any bDMARD; Comparator-placebo and/or any different drug; Outcomes-ASAS-PR and/or ASDAS-ID as primary or secondary endpoints. Meta-analysis was performed after assessment of the homogeneity of study designs, populations and outcomes. RESULTS: After screening 155 references, a total of 22 RCTs and 28 long-term extensions were retrieved. ASAS-PR was the dominant remission-like definition used. Concerning TNF inhibitors, 14/17 RCTs provided evidence of efficacy in reaching remission at different time points: 12, 16, 24 and 28 weeks (ASAS-PR in 16-62% of patients and ASDAS-ID in 24-40% of patients). With a limited number of studies available, IL-17A inhibitors exhibited remission rates of 15-21% for ASAS-PR and 11-16% for ASDAS-ID at week 16. A meta-analysis regarding ASAS-PR was performed considering RCTs with a similar duration (12, 16 or 24 weeks). The relative risk for achieving remission was 3.864 (95% CI 2.937, 5.085). CONCLUSION: bDMARDs have a clear impact in axSpA remission evaluated by ASAS-PR. Nevertheless, these data show an unmet need for improved reporting of remission-like outcomes.

GO-DACT: a phase 3b randomised, double-blind, placebo-controlled trial of GOlimumab plus methotrexate (MTX) versus placebo plus MTX in improving DACTylitis in MTX-naive patients with psoriatic arthritis.

OBJECTIVES: To assess the efficacy of golimumab in combination with methotrexate (MTX) versus MTX monotherapy in psoriatic arthritis (PsA) dactylitis. METHODS: Multicentre, investigator-initiated, randomised, double-blind, placebo-controlled, parallel-design phase 3b trial in 11 Portuguese rheumatology centres. Patients with PsA along with active dactylitis and naive to MTX and biologic disease-modifying antirheumatic drugs (bDMARDs) were randomly assigned to golimumab or placebo, both in combination with MTX. The primary endpoint was Dactylitis Severity Score (DSS) change from baseline to week 24. Key secondary endpoints included DSS and Leeds Dactylitis Index (LDI) response, and changes from baseline in the LDI and MRI dactylitis score. Analysis was by intention-to-treat for the primary endpoint. RESULTS: Twenty-one patients received golimumab plus MTX and 23 MTX monotherapy for 24 weeks. One patient from each arm discontinued. Patient inclusion was halted at 50% planned recruitment due to a favourable interim analysis. Median baseline DSS was 6 in both arms. By week 24, patients treated with golimumab plus MTX exhibited significantly greater improvements in DSS relative to MTX monotherapy (median change of 5 vs 2 points, respectively; p=0.026). In the golimumab plus MTX arm, significantly higher proportions of patients achieved at least 50% or 70% improvement in DSS and 20%, 50% or 70% improvement in LDI in comparison to MTX monotherapy. CONCLUSIONS: The combination of golimumab and MTX as first-line bDMARD therapy is superior to MTX monotherapy for the treatment of PsA dactylitis. TRIAL REGISTRATION NUMBER: NCT02065713.

Muscle Evaluation in Axial Spondyloarthritis-The Evidence for Sarcopenia.

Sarcopenia is a syndrome defined as a progressive and generalized skeletal muscle disorder associated with an increased likelihood of adverse outcomes such as falls, fractures, physical disability, and death. The actual definition of sarcopenia is based on a reduction in the values of three parameters: strength, muscle mass quantity or quality, and physical performance (the determinant of severity). Muscle wasting is a common feature in several chronic diseases, such as spondyloarthritis (SpA), and significantly increases patient morbidity and mortality. Although there has been huge progress in this field over recent years, the absence of a clear definition and clear diagnostic criteria of sarcopenia has resulted in inconsistent information regarding muscle-involvement in SpA. Thus, the aim of this review is to collect relevant evidence on muscular changes occurring during the disease process from the published literature, according to the recommended tools for sarcopenia evaluation proposed by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2). In addition, data from histological, electromyography, and biochemical muscle analyses of SpA patients are also reviewed. Overall, a reduction in muscle strength with a systemic decrease in lean mass seems to be associated with a gait speed compromise. This information is usually fragmented, with no studies considering the three parameters together. This paper represents a call-to-action for the design of new studies in the future.

Translation, cross-cultural adaptation and validation of the Osteoarthritis Quality of Life (OAQoL) questionnaire for use in Portugal.

Osteoarthritis (OA) is the most prevalent rheumatic disease and is a leading cause of decreased quality of life (QoL). The OA Quality of Life questionnaire (OAQoL) is an OA-specific patient-reported outcome measures. The aim of this study was to translate and validate the original UK English version of the Osteoarthritis Quality of Life (OAQoL) questionnaire into European Portuguese. The translation of the questionnaire was carried out according to a dual panel methodology (bilingual panel followed by lay panel). This was followed by cognitive debriefing interviews (CDIs) with OA patients to assess comprehension and relevance of the translated questionnaire. Finally, a validation survey was conducted to assess its psychometric properties. The Portuguese OAQoL, a comparator scale (the Nottingham Health Profile-NHP) as well as questions relating to demographic and disease information were administered to OA patients. A sub-sample of patients also completed the Portuguese OAQoL two weeks later, to assess test-retest reliability. The internal consistency, construct validity and known group validity (according to perceived OA severity) of the scale was also assessed. Both the bilingual and lay panels consisted of five individuals and no major difficulties relating to the translation process were identified. A total of ten patients with OA participated in the CDIs. The mean time to complete the questionnaire was 5 min. These interviews revealed that the Portuguese version of the OAQoL was clear, relevant and easy to complete. Finally, 53 OA patients (44 females; mean age of 67.6 years) completed the validation survey. Cronbach's alpha coefficient was 0.87, demonstrating high internal consistency. Test-retest reliability, assessed by Spearman's rank correlation coefficient, was 0.86. Moderate correlations were found with the majority of the NHP sections, providing evidence of construct validity. Significant differences in OAQoL scores were found between patients who differed according to their perceived OA severity, providing evidence of known group validity. The Portuguese version of the OAQoL is a valid and reliable questionnaire that can be used to assess QoL in OA, both in clinical practice and for research purposes.

Prognostic factors for recovery and non-recovery in patients with non-specific neck pain: a protocol for a systematic literature review.

INTRODUCTION: Neck pain is a common musculoskeletal disorder worldwide. It can result in significant disability and impaired quality of life. More than 50% of patients with neck pain still report symptoms 1 year later despite receiving different forms of non-pharmacological and pharmacological treatment. Identifying patient characteristics that are modifiable or predict recovery and non-recovery for an individual patient might identify ways of improving outcomes. This systematic review aims to comprehensively summarise the existing evidence regarding baseline patient characteristics associated with recovery and non-recovery, as defined by measures of pain intensity, disability and global perceived improvement. METHODS AND ANALYSIS: Six electronic databases, PubMed, CINAHL, PEDro Database, EMBASE, Cochrane Library and Web of Science, will be searched, with terms related to the review question such as neck pain, prognostic or predictive research, from inception to 28 September of 2018. Studies will be included if they have investigated an association between patient characteristics and outcomes, with at least one follow-up time point. Two independent reviewers will screen the titles and abstracts followed by a full-text review to assess papers regarding their eligibility. Data from included papers will be extracted using standardised forms, including study and participants' characteristics, outcomes, prognostic factors and effect size of the association. The risk of bias of each study will be assessed using the Quality in Prognostic Studies tool. A narrative synthesis will be conducted considering the strength, consistency of results and the methodological quality. ETHICS AND DISSEMINATION: This systematic review does not require ethical approval. The results will be disseminated through publication in a peer-review journal, as a chapter of a doctoral thesis and through presentations at national and international conferences. PROSPERO REGISTRATION NUMBER: CRD42018091183.

Translation and cross-cultural adaptation of the ASAS Health Index and ASAS Environmental Factors Item Set into European Portuguese Language.

OBJECTIVE: There is a lack of outcome measures to assess the impact of axial spondyloarthritis (axSpA) on health, function and quality of life. The Assessment of SpondyloArthritis International Society (ASAS) group developed the ASAS Health Index (ASAS-HI) and the ASAS Environmental Factors Item Set (ASAS-EF) to measure functioning and health across all aspects of health that are typically affected and relevant for patients with axSpA, based on the International Classification of Functioning, Disability and Health (ICF). The aim of this paper was to describe the translation and cross-cultural adaptation of both questionnaires into European Portuguese among patients with radiographic and non-radiographic axial SpA (nr-axSpA) and test the conceptual equivalence of the translated version in the Portuguese context. MATERIAL AND METHODS: The ASAS-HI and ASAS-EF were firstly translated into European Portuguese and then back-translated into English, following forward-backward procedure. After the review of the Portuguese version by an expert committee, the field test with cognitive debriefing involved a sample of 10 axSpA patients with different gender, age, disease duration, and educational background. RESULTS: Minor difficulties arose from the translation process of the ASAS-HI. The EF Item Set offered more difficulties indicating that concepts underlying the contextual factors may be more culture-dependent. A total of 10 patients with axSpA [8 males, mean age of 41.4 (±13.7)] participated in the field test. Cognitive debriefing showed that items of the ASAS-HI and EF Item Set of the Portuguese version are clear, relevant, understandable and easy to complete. As a result of cognitive debriefing, the wording of four items had to be changed to avoid misunderstandings or unintended interpretations, and a new response option "not applicable" was added to two items of the ASAS-HI to improve appropriateness. CONCLUSIONS: The resulting Portuguese version of the ASAS-HI and ASAS-EF showed acceptable linguistic validity and has potential for use in both clinical practice and research settings. Nevertheless, before European Portuguese versions can be fully implemented, its psychometric properties (validity and reliability) need to be evaluated.

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.