Factors Associated with Poor Mental Health in Patients with Axial Spondyloarthritis: Results from the International Map of Axial Spondyloarthritis (IMAS).

BACKGROUND: This study aims to assess the prevalence of poor mental health in axial spondyloarthritis (axSpA) and its associated factors in a large sample of patients from the International Map of Axial Spondyloarthritis (IMAS) study from around the globe. METHODS: IMAS is a cross-sectional online survey (2017-2022) that includes 5557 unselected patients with axSpA worldwide. Mental health was evaluated by the 12-item General Health Questionnaire (GHQ-12) and the cut-off point for poor mental health was set at 3. Logistic regression analysis was used to evaluate relationships between the investigated factors and poor mental health (GHQ-12≥3) in patients with axSpA (n=4335). RESULTS: Of 5351 patients, the mean of GHQ-12 was 4.7 and 59.4% were having poor mental health, being 69.9% in South Africa, 63.7% in Latin America, 60.8% in Europe, 54.3% in North America and 51.8% in Asia. Overall, 40.5% and 37.2% of patients experienced anxiety and depression. The factors associated with poor mental health were younger age (OR=0.99), female gender (OR=1.16), being on sick leave or unemployed (OR=1.63), non-physical activity (OR=1.22), smoking (OR=1.20), higher Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] (OR=1.42), functional limitation (OR=1.02) and shorter symptoms duration (OR=0.98). CONCLUSIONS: Globally, 6 in 10 patients with axSpA had poor mental health, with a higher proportion in South Africa and lower in Asia. The factors associated with poor mental health include domains such as younger age, female gender, employment difficulties, harmful habits, disease burden and symptom duration. A holistic management approach to axSpA should encompass both physical and mental health.

Natural language processing to identify and characterize spondyloarthritis in clinical practice.

OBJECTIVE: This study aims to use a novel technology based on natural language processing (NLP) to extract clinical information from electronic health records (EHRs) to characterise the clinical profile of patients diagnosed with spondyloarthritis (SpA) at a large-scale hospital. METHODS: An observational, retrospective analysis was conducted on EHR data from all patients with SpA (including psoriatic arthritis (PsA)) at Hospital Universitario La Paz, between 2020 and 2022. Data were collected using Savana Manager, an NLP-based system, enabling the extraction of information from unstructured, free-text EHRs. Variables analysed included demographic data, SpA subtypes, comorbidities and treatments. The performance of the technology in detecting SpA clinical entities was evaluated through precision, recall and F-1 score metrics. RESULTS: From a hospital population of 639 474 patients, 4337 (0.7%) patients had a diagnosis of SpA or their subtypes in their EHR. The population predominantly comprised men (55.3%) with a mean age of 50.9 years. Peripheral SpA (including PsA) was reported in 31.6%, axial SpA in 20.9%, both axial and peripheral SpA in 3.7%, while 43.7% of patients did not have the SpA subtype reported. Common comorbidities included hypertension (25.0%), dyslipidaemia (22.2%) and diabetes mellitus (15.5%). The use of conventional disease-modifying antirheumatic drugs (csDMARDs) and biological DMARDs (bDMARDs) was documented, with methotrexate (25.3% of patients) being the most used csDMARDs and adalimumab (10.6% of patients) the most used bDMARD. The NLP technology demonstrated high precision and recall, with all the assessed F-1 score values over 0.80, indicating reliable data extraction. CONCLUSION: The application of NLP technology facilitated the characterisation of the SpA patient profile, including demographics, clinical features, comorbidities and treatments. This study supports the utility of NLP in enhancing the understanding of SpA and suggests its potential for improving patient management by extracting meaningful information from unstructured EHR data.

Effect of Secukinumab Versus Adalimumab Biosimilar on Radiographic Progression in Patients With Radiographic Axial Spondyloarthritis: Results From a Head-to-Head Randomized Phase IIIb Study.

OBJECTIVE: Spinal radiographic progression is an important outcome in radiographic axial spondyloarthritis (SpA). The objective of the phase IIIb SURPASS study was to compare spinal radiographic progression in patients with radiographic axial SpA treated with secukinumab (interleukin-17A inhibitor) versus adalimumab biosimilar (Sandoz adalimumab [SDZ-ADL]; tumor necrosis factor inhibitor). METHODS: Biologic-naive patients with active radiographic axial SpA, at high risk of radiographic progression (high-sensitivity C-reactive protein [hsCRP] ≥5 mg/L and/or ≥1 syndesmophyte[s] on spinal radiographs), were randomized (1:1:1) to secukinumab (150/300 mg) or SDZ-ADL (40 mg). The proportion of patients with no radiographic progression (change from baseline [CFB] in modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS] ≤0.5) on secukinumab versus SDZ-ADL at week 104 (primary endpoint), mean CFB-mSASSS, proportion of patients with ≥1 syndesmophyte(s) at baseline with no new syndesmophyte(s), and safety were evaluated. RESULTS: Overall, 859 patients (78.5% male, mSASSS 16.6, Bath Ankylosing Spondylitis Disease Activity Index 7.1, hsCRP 20.4 mg/L, and 73.0% with ≥1 syndesmophyte[s]) received secukinumab 150 mg (n = 287), secukinumab 300 mg (n = 286), or SDZ-ADL (n = 286). At week 104, the proportion of patients with no radiographic progression was 66.1%, 66.9%, and 65.6% (P = not significant, both secukinumab doses) and mean CFB-mSASSS was 0.54, 0.55, and 0.72 in secukinumab 150 mg, secukinumab 300 mg, and SDZ-ADL arms, respectively. Overall, 56.9%, 53.8%, and 53.3% of patients on secukinumab 150 mg, secukinumab 300 mg, and SDZ-ADL, respectively, with ≥1 syndesmophyte(s) at baseline did not develop new syndesmophyte(s) by week 104. There were no unexpected safety findings. CONCLUSION: Spinal radiographic progression over two years was low with no significant difference between secukinumab and SDZ-ADL arms. The safety of both treatments was consistent with previous reports.

Sacroiliac radiographic progression over 10 years in axSpA: data from the DESIR inception cohort.

OBJECTIVES: To evaluate sacroiliac radiographic progression over a 10-year follow-up and determine the baseline factors associated with such progression in patients with recent-onset axial spondyloarthritis (axSpA, <3 years). METHODS: This analysis was performed in the DESIR cohort (NCT01648907). The radiographic status of the patients (radiographic axSpA (r-axSpA) vs non-radiographic axSpA (nr-axSpA)) was based on the modified New York (mNY) criteria. Information on mNY criteria on the pelvic radiographs was obtained in four reading waves over a 10-year period. Images were blinded and centrally read by 3 trained readers. The % of mNY net progressors (ie, number of 'progressors' minus number of 'regressors' divided by the total number of patients) was assessed in completers (ie, pelvic radiographs at baseline and 10 years). The yearly likelihood of mNY+ was estimated using an integrated analysis (ie, including all patients with at least one available mNY score ('intention-to-follow' population) using a generalised estimating equations model and time-varying tumour necrosis factor (TNF) use as a confounder. Baseline predictors of mNY+ during 10 years were evaluated. RESULTS: Completers included 294 patients, while intention-to-follow included 659 participants. In the completers, the net % progression (from nr-axSpA to r-axSpA) was 5.8%. In the intention-to-follow population, the probability of being mNY+ was estimated to increase 0.87% (95% CI 0.56 to 1.19) per year (ie, 8.7% after 10 years) while when introducing TNF inhibitors (TNFi) as a time-varying covariate, the probability was 0.45% (95% CI 0.09 to 0.81) (ie, 4.5% after 10 years). Baseline bone marrow oedema (BME) on MRI of the sacroiliac joints (SIJ) was associated with being mNY+ over time OR 6.2 (95% CI 5.3 to 7.2) and OR 3.1 (95% CI 2.4 to 3.9) in HLA-B27+ and HLA-B27-, respectively). Male sex, symptom duration >1.5 years, Axial Spondyloarthritis Disease Activity Score ≥2.1 and smoking (only in HLA-B27 positives) were also associated with being mNY+ over 10 years. BME was not found to be a mediator of the HLA-B27 effect on mNY+ at 10 years. CONCLUSIONS: The yearly likelihood of switching from nr-axSpA to r-axSpA in patients after 10 years of follow-up was low, and even lower when considering TNFi use.

Magnetic resonance imaging characteristics in patients with psoriatic arthritis and axial manifestations from the MAXIMISE cohort.

OBJECTIVE: The current analysis of the MAXIMISE trial was conducted to investigate the presence of post-inflammatory and degenerative spinal changes and inflammatory changes in spinal processes identified in baseline MRIs and their potential for predicting differential treatment effects in a cohort of PsA patients with axial manifestations. METHODS: Baseline spinal MRIs from the MAXIMISE trial were re-read to identify additional inflammatory (spinal process), post-inflammatory, and degenerative changes, and investigate the differential treatment effect of these imaging features using logistic regression modelling. RESULTS: In addition to bone marrow oedema assessed at primary analysis, spinal process inflammation and post-inflammatory changes evaluated by FAt Spondyloarthritis Spine Score were documented in 11.1% and 20.2% patients, respectively. At least one type of degenerative change was noted in 64% patients, with Pfirrmann grade ≥3 (51.1%) being the most common. Combining primary and re-read MRI findings, 67.1% of patients presented with inflammatory or post-inflammatory changes while 21.2% had degenerative changes alone. Although not statistically significant, post-inflammatory changes were associated with a trend for better efficacy outcomes in terms of ASAS20, ASAS40 and BASDAI50 responses; a trend for worse outcomes was observed in the presence of degenerative changes. CONCLUSION: The current analysis revealed the occurrence of additional inflammatory and post-inflammatory changes suggestive of axial PsA (axPsA) and a trend for better clinical outcomes for patients treated with secukinumab. These results elucidate the imaging characteristics and improve our current understanding of axPsA thereby supporting the interpretation of future trials. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02721966.

The paradigm of IL-23-independent production of IL-17F and IL-17A and their role in chronic inflammatory diseases.

Interleukin-17 family (IL-17s) comprises six structurally related members (IL-17A to IL-17F); sequence homology is highest between IL-17A and IL-17F, displaying certain overlapping functions. In general, IL-17A and IL-17F play important roles in chronic inflammation and autoimmunity, controlling bacterial and fungal infections, and signaling mainly through activation of the nuclear factor-kappa B (NF-κB) pathway. The role of IL-17A and IL-17F has been established in chronic immune-mediated inflammatory diseases (IMIDs), such as psoriasis (PsO), psoriatic arthritis (PsA), axial spondylarthritis (axSpA), hidradenitis suppurativa (HS), inflammatory bowel disease (IBD), multiple sclerosis (MS), and asthma. CD4+ helper T cells (Th17) activated by IL-23 are well-studied sources of IL-17A and IL-17F. However, other cellular subtypes can also produce IL-17A and IL-17F, including gamma delta (γδ) T cells, alpha beta (αß) T cells, type 3 innate lymphoid cells (ILC3), natural killer T cells (NKT), or mucosal associated invariant T cells (MAIT). Interestingly, the production of IL-17A and IL-17F by innate and innate-like lymphocytes can take place in an IL-23 independent manner in addition to IL-23 classical pathway. This would explain the limitations of the inhibition of IL-23 in the treatment of patients with certain rheumatic immune-mediated conditions such as axSpA. Despite their coincident functions, IL-17A and IL-17F contribute independently to chronic tissue inflammation having somehow non-redundant roles. Although IL-17A has been more widely studied, both IL-17A and IL-17F are overexpressed in PsO, PsA, axSpA and HS. Therefore, dual inhibition of IL-17A and IL-17F could provide better outcomes than IL-23 or IL-17A blockade.

Serum leptin concentration is associated with the attainment of clinical outcomes in patients with axial spondyloarthritis treated with TNF inhibitors.

OBJECTIVES: To analyse the influence of adipokines on attaining the clinical outcomes in patients with axial spondyloarthritis (axSpA) treated with TNF inhibitors (TNFi), and then, to investigate the association of patients' characteristics and adipokine concentrations. METHODS: This was a longitudinal study including 110 patients with axSpA who were initiated at TNFi and were followed-up for 6 months (m). Disease activity was assessed by Ankylosing Spondylitis Disease Activity Score (ASDAS) at baseline and at 6 m of treatment. Clinical outcomes at 6 m of treatment were defined as remission (ASDAS <1.3) and the attainment of low disease activity (LDA; ASDAS<2.1). Leptin and adiponectin concentrations were measured in serum samples collected at baseline and after 6 m. RESULTS: Both leptin and adiponectin were constitutively elevated in female axSpA patients. At time of TNFi initiation, leptin concentrations were higher in patients with high body mass index (overweight or obese). On the contrary, adiponectin was higher in normalweight patients. After 6 m of TNFi treatment, 24% of patients attained remission. They had significant lower leptin concentration at baseline compared with patients who did not attain remission. Furthermore, this difference remained significant after 6 m of treatment meaning that TNFi did not modify adipokine concentration. Similar results were found considering LDA as the clinical outcome, obtained in 48% of the patients. CONCLUSIONS: The present study showed that low leptin concentrations were associated with attaining clinical outcomes in axSpA patients treated with TNFi. In addition, since leptin secretion by white adipocytes is enhanced during obesity and considering that TNFi do not seem to modulate its expression, obese patients should be encouraged to decrease BMI to attain a successful therapy.

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.

Does gender influence outcome measures similarly in patients with spondyloarthritis? Results from the ASAS-perSpA study.

OBJECTIVES: To investigate the influence of gender on disease outcomes in patients with spondyloarthritis (SpA), including across SpA subtypes. METHODS: Data from 4185 patients of 23 countries with a diagnosis of axial SpA (axSpA), peripheral SpA (pSpA) or psoriatic arthritis (PsA) from the Assessment of SpondyloArthritis International Society (ASAS)-perSpA study were analysed. Associations between gender and disease activity (Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Score (BASDAI), C-reactive protein (CRP)), function (Bath Ankylosing Spondylitis Functional Index (BASFI)) and overall health (ASAS Health Index (ASAS HI), European Quality of Life Five Dimension (EQ-5D)) outcomes were investigated. Multilevel multivariable linear mixed models adjusted for relevant confounders (and stratified by disease subtype in case of a relevant interaction) were used. RESULTS: In total, 65%, 10% and 25% of patients had axSpA, pSpA and PsA, respectively. axSpA was more frequent in males (68%), whereas pSpA and PsA were more frequent in females (53% and 52%, respectively). A significant interaction between gender and disease subtype was found for ASDAS, BASDAI and BASFI. While being female independently contributed to higher BASDAI across the three disease subtypes (with varying magnitude), female gender was only associated with higher ASDAS in pSpA (ß (95% CI): 0.36 (0.15 to 0.58)) and PsA (0.25 (0.12 to 0.38)) but not in axSpA (0.016 (-0.07 to 0.11)). No associations were observed between gender and CRP levels. Female gender was associated with higher ASAS HI and EQ-5D, without differences across disease subtype. CONCLUSION: Female gender is associated with less favourable outcome measures across the SpA spectrum. However, while female gender influences BASDAI across the three subtypes, ASDAS is associated with gender only in pSpA and PsA but not in axSpA. Therefore, ASDAS is an appropriate instrument both for females and males with axSpA.

Sustained low disease activity measured by ASDAS slow radiographic spinal progression in axial spondyloarthritis patients treated with TNF-inhibitors: data from REGISPONSERBIO.

BACKGROUND: To evaluate the influence of the disease activity on radiographic progression in axial spondyloarthritis (axSpA) patients treated with TNF inhibitors (TNFi). METHODS: The study included 101 axSpA patients from the Spanish Register of Biological Therapy in Spondyloarthritides (REGISPONSERBIO), which had clinical data and radiographic assessment available. Patients were classified into 2 groups based on the duration of TNFi treatment at baseline: (i) long-term treatment (≥4 years) and (ii) no long-term treatment (< 4 years). Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. Disease activity differences between patients' groups at each time point were assessed using a linear mixed-effect model. RESULTS: Radiographic progression was defined as an increase in ≥2 mSASSS units. At inclusion, approximately half of the patients (45.5%) were receiving long-term treatment with TNFi (≥4 years). In this group of subjects, a significant difference in averaged Ankylosing Spondylitis disease Activity Score (ASDAS) across follow-up was found between progressors and non-progressors (2.33 vs 1.76, p=0.027, respectively). In patients not under long-term TNFi treatment (54.5%) though, no significant ASDAS differences were observed between progressors and non-progressors until the third year of follow-up. Furthermore, no significant differences were found in progression status, when disease activity was measured by Bath Ankylosing spondylitis Disease Activity Index (BASDAI) and C reactive protein (CRP). CONCLUSIONS: Patients on long-term TNFi treatment with a mean sustained low disease activity measures by ASDAS presented lower radiographic progression than those with active disease.

Poor health and functioning in patients with axial spondyloarthritis during the COVID-19 pandemic and lockdown: REUMAVID study (phase 1).

AIM: To evaluate the overall health and functioning in patients with axial spondyloarthritis (axSpA) and related factors affecting these during the COVID-19 pandemic and lockdown measures. METHODS: Data from 587 axSpA patients participating in the first phase (April-July 2020) of the REUMAVID study who completed the ASAS Health Index (ASAS-HI) were analysed. REUMAVID is a cross-sectional study that collects data through an online survey to assess the impact of the COVID-19 pandemic on patients with rheumatic and musculoskeletal diseases across seven European countries. Poor health was defined as ASAS-HI ⩾ 12. The World Health Organization Five well-being index, self-perceived health status and change in health status during COVID-19 pandemic were evaluated as secondary outcomes. Logistic regression models were used to identify the factors associated with poor health. RESULTS: According to the ASAS-HI, 147 (25.0%) patients reported poor health. Pain and moving around were the main affected categories. In addition, 14.0% reported their self-perceived health status as 'bad' or 'very bad' and 46.8% as worse than before the pandemic. In the multivariate analysis, smoking (OR = 1.98), diabetes (OR = 4.89) and taking painkillers (OR = 2.82) or corticosteroids use (OR = 2.20) were significantly associated with poor health, while engaging in physical activity (OR = 0.54) and being actively employed (OR = 0.48) were inversely associated with this. CONCLUSIONS: During the first wave of the COVID-19 pandemic, one in four axSpA patients reported poor health and functioning, while the self-perceived health status of almost half of these patients worsened. Nonsmoking, physical activity and being employed were associated with better outcomes.

Association between HLA-B27 and peripheral spondyloarthritis phenotype: results from the ASAS perSpA study.

OBJECTIVE: To analyse the influence of HLA-B27 in the phenotypical expression of peripheral spondyloarthritis (pSpA). METHOD: This is an observational cross-sectional study using data from the Assessment of SpondyloArthritis international Society perSpA registry, including all patients with an available HLA-B27 test result and with a diagnosis of pSpA or psoriatic arthritis (PsA) as per rheumatologist's judgement. Demographic and clinical data, presence of extra musculoskeletal manifestations (EMM) and fibromyalgia were the variables included in a simple and multiple logistic regression model to assess their association to HLA-B27 positivity. RESULTS: From the 4465 patients included in the registry, 790 were classified as having either pSpA or PsA and had the HLA-B27 typing available. HLA-B27-positive patients presented a male predominance, had an earlier disease onset and a shorter diagnostic delay compared with the negatives. HLA-B27-positive patients presented a higher frequency of axial involvement, radiographic sacroiliitis, enthesitis and uveitis. Also, root joint involvement, poliarticular joint patern and tarsitis were significantly higher within HLA-B27-positive patients. Furthermore, we did not observe any association between the presence of HLA-B27 and peripheral joint damage, dactylitis, other EMM (psoriasis, inflammatory bowel disease) or fibromyalgia.The multivariable analysis confirmed the independent association of HLA-B27 positivity with male sex, an earlier onset of the disease, the presence of axial involvement, tarsitis and uveitis. SUMMARY: In summary, the presence of HLA-B27 in pSpA patients was associated with earlier disease onset and higher axial involvement, tarsitis and uveitis, but not with other EMM, fibromyalgia or peripheral structural damage.

Comparison of long-term efficacy between biological agents following tumor necrosis factor inhibitor failure in patients with rheumatoid arthritis: a prospective cohort study.

BACKGROUND: Currently, there is contradictory evidence regarding the best strategy to follow after discontinuation of a first biological agent in patients with rheumatoid arthritis (RA). We aimed to compare the long-term efficacy of switching to a second tumor necrosis factor inhibitor (TNFi) versus biopharmaceuticals with other mechanisms of action (non-TNFi) in patients with RA who previously failed a first TNFi. METHODS: This prospective cohort study analyzed data from 127 patients who discontinued a previous TNFi between 1999 and 2016. Disease activity was assessed at baseline and at 6, 12, and 24 months (m-6, m-12, m-24) after switching. Primary outcome was the proportion of patients achieving good/moderate EULAR response (E-resp). Factors associated with clinical outcomes were assessed using univariate and multivariate logistic regression models. RESULTS: Seventy-seven (61%) patients received a second TNFi and 50 (39%) switched to a non-TNFi. At m-6 and m-12, no differences were observed between groups; nevertheless, at m-24, the proportion of patients with E-resp was higher in the non-TNFi group (49% TNFi group versus 77% non-TNFi group; p = 0.002). In regression models, switching to a non-TNFi was significantly associated with E-resp at m-24 (odds ratio = 3.21; p = 0.01). When assessing the response to the second biological agent based on the reason for discontinuation of the first TNFi, similar results were obtained; at m-24, patients who discontinued the first TNFi due to inefficacy (either primary or secondary) experienced a better E-resp if they had switched to a non-TNFi (primary inefficacy: 52% TNFi group versus 79% non-TNFi group, p = 0.09; secondary inefficacy: 50% versus 76%, p = 0.03). CONCLUSION: In our cohort of RA patients who discontinued a first TNFi, those who switched to a non-TNFi were three times more likely to attain a sustained clinical response, regardless of whether they had discontinued the first biologic due to a primary or secondary inefficacy.

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.

Axial spondyloarthritis.

Axial spondyloarthritis (axSpA) encompasses both radiographic and non-radiographic axSpA. It is a chronic inflammatory disease with a predilection for involving the axial skeleton. The most common presenting symptoms are chronic back pain and spinal stiffness but peripheral and extra-musculoskeletal manifestations occur also frequently. The diagnosis of axSpA relies on the recognition of a clinical pattern of the disease, based on clinical, laboratory and imaging features. The Assessment in SpondyloArthritis international Society classification criteria for axSpA are valid and well implemented for research purposes. Sustained disease activity, measured by validated tools such as the Ankylosing Spondylitis Disease Activity Score, leads to irreversible structural damage and poor functioning and therefore should be abrogated. As part of the management algorithm, non-steroidal anti-inflammatory drugs remain as the first line of pharmacological treatment besides physiotherapy. As a second line, tumour necrosis factor inhibitor and interleukin-17 inhibitor are available but recently Janus kinase inhibitors have also shown efficacy in improving symptoms of the disease.

Ixekizumab improves spinal pain, function, fatigue, stiffness, and sleep in radiographic axial Spondyloarthritis: COAST-V/W 52-week results.

BACKGROUND: This analysis assessed improvements in patients with radiographic axial spondyloarthritis (r-axSpA) treated with ixekizumab in the Assessment of Spondyloarthritis International Society (ASAS) treatment response domains and additional patient-reported outcomes at 1 year of treatment. METHODS: COAST-V and COAST-W were 52-week, phase 3, randomized controlled trials evaluating the efficacy and safety of ixekizumab in biologic disease-modifying antirheumatic drug (bDMARD)-naïve and tumor necrosis factor inhibitor (TNFi)-experienced patients with radiographic spondyloarthritis, respectively. Patients were treated with 80-mg ixekizumab either every 2 weeks or every 4 weeks. Patient-reported outcomes included Patient Global Disease Activity, Spinal Pain, stiffness as measured by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Questions 5 and 6, function as measured by the Bath Ankylosing Spondylitis Functional Index, fatigue as measured by the Fatigue Numeric Rating Scale and BASDAI question 1, Spinal Pain at Night, and sleep quality as measured by the Jenkins Sleep Evaluation Questionnaire. Mixed-effects models for repeated measures were used to analyze changes from baseline in patient-reported outcomes from weeks 1 to 16, and descriptive statistics were reported from weeks 20 to 52. Analysis of covariance with Scheffé's method was used for the ASAS response association analyses. RESULTS: This study assessed 341 bDMARD-naïve and 316 TNFi-experienced patients in the placebo-controlled blinded treatment dosing period (weeks 1-16) as well as 329 bDMARD-naïve and 281 TNFi-experienced patients in the dose double-blind extended treatment period (weeks 20-52). bDMARD-naïve or TNFi-experienced patients treated with ixekizumab every 2 weeks and every 4 weeks reported improvements in patient global disease activity, spinal pain, function, stiffness, fatigue, spinal pain at night, and sleep quality through week 52. Greater correlations with improvements in all response domains were seen when comparing ASAS40 responders to ASAS20 non-responders (p < 0.001), with up to 10.5-fold greater improvements observed in ASAS40 responses compared with ASAS20 non-responders. Function and fatigue demonstrated the highest values. CONCLUSIONS: Ixekizumab-treated bDMARD-naïve and TNFi-experienced patients with radiographic axial spondyloarthritis achieving ASAS40 reported sustained and consistent improvement in all ASAS response domains and other patient-reported outcomes though week 52, with spinal pain, function, and stiffness as major drivers of the response. TRIAL REGISTRATION: NCT02696785 and NCT02696798 , March 2, 2016.

Comparative results of the implementation in daily practice of an evaluation checklist for patients with axial spondyloarthritis and psoriatic arthritis.

OBJECTIVE: To analyse and compare changes in the collection of clinical variables after the implementation in daily practice of an evaluation checklist for patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). METHODS: An observational study was performed based on medical records review. The number and type of variables of the evaluation checklist in the medical records were collected. The first review was made before the implementation of the checklist, and the second one 6 months after the implementation (in different patients). A descriptive and bivariate analysis was carried out. RESULTS: Six hospitals and 11 rheumatologists participated. A total of 83 and 68 medical records were reviewed before and after the implementation of the checklist. After the implementation, in the axSpA patients, a significant increase was recorded in alcohol consumption, diarrhoea or IBD and urethritis, diabetes mellitus, hyperlipidaemia, depression, obesity or gout/hyperuricaemia, weight, height, blood pressure, patient and physician global assessments of disease activity, BASDAI and DAS28. And, in the PsA patients, alcohol consumption, hypertension, diabetes mellitus, hyperlipidaemia, disease, gout/hyperuricaemia, thoracic expansion, cervical rotation, weight, height, blood pressure, patient and physician global assessments of disease, ASDAS, BASDAI, and BASFI were recorded. In general, there was a trend towards greater recording in axSpA compared with PsA. CONCLUSIONS: The implementation of a specific checklist in daily practice improves the evaluation of patients with axSpA and PsA. More efforts are necessary to continue improving the evaluation of patients with axSpA, but especially of those with PsA.

BAFF predicts immunogenicity in older patients with rheumatoid arthritis treated with TNF inhibitors.

Immunogenicity related to treatment with TNF inhibitors (TNFi) is one of the causes for the decreased attainment of clinical response in patients with rheumatoid arthritis (RA). The B-cell activating factor (BAFF) may be playing a role in the development of immunogenicity. The objective of this study was to analyse the association of baseline concentration of serum B-cell activating factor (BAFF) with immunogenicity after 6 months of TNFi treatment. A total of 127 patients with RA starting a TNFi (infliximab, adalimumab, certolizumab pegol or golimumab) were followed-up for 6 months. Serum samples were obtained at baseline and at 6 months and anti-drug antibody (ADA) and BAFF concentrations were measured. Logistic regression models were employed in order to analyse the association between BAFF concentrations and immunogenicity. Receiver operating characteristic analysis was performed to determine the BAFF concentrations with a greater likelihood of showing immunogenicity association. At 6 months, 31 patients (24%) developed ADA. A significant interaction between the age and baseline BAFF concentration was found for the development of ADA (Wald chi-square value = 5.30; p = 0.02); therefore, subsequent results were stratified according to mean age (≤ / > 55 years). Baseline serum BAFF concentration was independently associated with ADA development only in patients over 55 years (OR = 1.51; 95% CI 1.03-2.21). Baseline serum BAFF ≥ 1034 pg/mL predicted the presence of ADA at 6 months (AUC = 0.81; 95% confidence interval (CI) 0.69-0.93; p = 0.001; positive likelihood ratio = 3.7). In conclusion, our results suggest that the association of BAFF concentration and immunogenicity depends on the patient's age. Baseline serum BAFF concentration predicts the presence of ADA within 6 months of TNFi therapy in older patients with RA.

Assessment of impact of the COVID-19 pandemic from the perspective of patients with rheumatic and musculoskeletal diseases in Europe: results from the REUMAVID study (phase 1).

AIM: To assess the impact of the COVID-19 pandemic on patients with rheumatic and musculoskeletal diseases (RMDs). METHODS: REUMAVID is a cross-sectional study using an online survey developed by an international multidisciplinary patient-led collaboration across seven European countries targeting unselected patients with RMDs. Healthcare access, daily activities, disease activity and function, well-being (WHO Five Well-Being Index (WHO-5)), health status, anxiety/depression (Hospital Anxiety and Depression Scale (HADS)) and access to information were evaluated. Data were collected in April-July 2020 (first phase). RESULTS: Data from the first phase included 1800 patients with 15 different RMDs (37.2% axial spondyloarthritis, 29.2% rheumatoid arthritis, 17.2% osteoarthritis and others). Mean age was 53, 80% female and 49% had undertaken university studies. During the beginning of the pandemic, 58.4% had their rheumatology appointment cancelled and 45.6% reported not having received any information relating to the possible impact of SARS-CoV-2 infection in their RMDs, with the main source being patient organisations (27.6%).Regarding habits, 24.6% increased smoking, 18.2% raised their alcohol consumption, and 45.6% were unable to continue exercising. Self-reported disease activity was high (5.3±2.7) and 75.6% reported elevated pain. Half the patients (49.0%) reported poor well-being (WHO-5) and 46.6% that their health had changed for the worse during lockdown. According to HADS, 57.3% were at risk of anxiety and 45.9% of depression. CONCLUSION: Throughout the first wave of the COVID-19 pandemic, patients with RMDs have experienced disruption in access to healthcare services, poor lifestyle habits and negative effects on their overall health, well-being and mental health. Furthermore, information on COVID-19 has not reached patients appropriately.

Prevalence and distribution of peripheral musculoskeletal manifestations in spondyloarthritis including psoriatic arthritis: results of the worldwide, cross-sectional ASAS-PerSpA study.

OBJECTIVES: To characterise peripheral musculoskeletal involvement in patients with spondyloarthritis (SpA) including psoriatic arthritis (PsA), across the world. METHODS: Cross-sectional study with 24 participating countries. Patients with a diagnosis of axial SpA (axSpA), peripheral SpA (pSpA) or PsA according to their rheumatologist were included. The investigators were asked which diagnosis out of a list of six (axSpA, PsA, pSpA, inflammatory bowel disease-associated SpA, reactive arthritis or juvenile SpA (Juv-SpA)) fitted the patient best. Peripheral manifestations (ie, peripheral joint disease, enthesitis, dactylitis and root joint disease), their localisation and treatments were evaluated. RESULTS: A total of 4465 patients were included (61% men, mean age 44.5 years) from four geographic areas: Latin America (n=538), Europe plus North America (n=1677), Asia (n=975) and the Middle East plus North Africa (n=1275). Of those, 78% had ever suffered from at least one peripheral musculoskeletal manifestation; 57% had peripheral joint disease, 44% had enthesitis and 15% had dactylitis. Latin American had far more often peripheral joint disease (80%) than patients from other areas. Patients with PsA had predominantly upper limb and small joint involvement (52%).Hip and shoulder involvement was found in 34% of patients. The prevalence of enthesitis ranged between 41% in patients with axSpA and 65% in patients with Juv-SpA. Dactylitis was most frequent among patients with PsA (37%). CONCLUSION: These results suggest that all peripheral features can be found in all subtypes of SpA, and that differences are quantitative rather than qualitative. In a high proportion of patients, axial and peripheral manifestations coincided. These findings reconfirm SpA clinical subtypes are descendants of the same underlying disease, called SpA.