The Effect of Alcohol Consumption on Clinical Outcomes and Structural Damage in Patients with Axial Spondyloarthritis: A Systematic Literature Review and Meta-Analysis.

OBJECTIVE: To systematically review the effects of alcohol consumption (AC) on disease-specific outcomes in axial spondyloarthritis (axSpA). METHODS: A systematic review of observational studies on axSpA and AC was conducted. Multiple electronic databases were searched for keywords. Two investigators reviewed articles to assess for inclusion eligibility. The Joanna Briggs Institute Critical Appraisal checklist was employed to evaluate the risk of bias. Standardized mean differences (SMD) were used to synthesize the data and I² was used to ascertain heterogeneity. Spinal pain, disease activity as measured by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS), and spinal radiographic progression based on the modified Stokes Ankylosing Spondylitis Spinal Score (mSASSS) were examined as outcomes. RESULTS: Search strategy identified 703 records; 13 articles were assessed for eligibility. Five studies (n = 3858) were included. Compared to non-consumers, axSpA patients who consumed alcohol had lower BASDAI (SMD -0.19, 95% CI -0.37 to -0.02, I²=72.5%) and lower spinal pain (SMD -0.17, 95% CI -0.24 to -0.09, I² = 0%). No significant difference was found for ASDAS (SMD -0.19, 95% CI -0.39 to 0.00, I² = 36%). One cohort study on the spinal radiographic progression indicated greater radiographic progression among consumers (SMD 0.35, 95% CI 0.08 to 0.62). CONCLUSION: AC appears to be associated with lower disease activity and spinal pain. However, these findings may reflect confounding by sex and smoking. Further longitudinal cohort studies with standardized measures for AC are warranted to assess the direction of alcohol's effect on structural damage progression.

Enhanced Type 1 Interferon Signature in Axial Spondyloarthritis Patients Unresponsive to Secukinumab Treatment.

OBJECTIVE: Axial spondyloarthritis (axSpA) is an inflammatory disease in which overactive interleukin (IL)-17A-producing cells are implicated in a central role. Therapeutically, biologics that target IL-17A, such as secukinumab, have demonstrated improved clinical outcomes. Despite this translational success, there is a gap in understanding why some patients with axSpA do not respond to IL-17A-blocking therapy. Our study aims to discriminate immune profiles between secukinumab responders (SEC-R) and nonresponders (SEC-NR). METHODS: Peripheral blood mononuclear cells were collected from 30 patients with axSpA before and 24 weeks after secukinumab treatment. Frequency of CD4+ subsets were compared between SEC-R and SEC-NR using flow cytometry. Mature CD45RO+CD45RA-CD4+ T cells were fluorescent-activated cell sorting sorted, and RNA was measured using NanoString analysis. RESULTS: SEC-NR had an increased frequency of IL-17A-producing RORγt+CD4+ T cells compared to healthy controls before secukinumab treatment (P < 0.01). SEC-NR had a significant increase of CXCR3+ CD4+ T cells before secukinumab treatment compared to SEC-R (P < 0.01). Differentially expressed gene analysis revealed up-regulation of type 1 interferon (IFN)-regulated genes in SEC-NR patients compared to SEC-R patients after receiving the biologic. SEC-R patients had an up-regulated cytotoxic CD4+ T cell gene signature before receiving secukinumab treatment compared to SEC-NR patients. CONCLUSION: The increased frequency of IL-17A-producing cells in SEC-NR patients suggests a larger inflammatory burden than SEC-R patients. With treatment, SEC-NR patients have a more pronounced type 1 IFN signature than SEC-R patients, suggesting a mechanism contributing to this larger inflammatory burden. The results point toward more immune heterogeneity in axSpA than has been recognized and highlights the need for precision therapeutics in this disease.

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.

Radiographic Progression in Sacroiliac Joints in Patients With Axial Spondyloarthritis: Results From a Five-Year International Observational Study.

OBJECTIVE: To evaluate progression from nonradiographic (nr-) to radiographic axial spondyloarthritis (r-axSpA) over 5 years in patients with recently diagnosed (≤1 year) axSpA fulfilling the Assessment of SpondyloArthritis international Society (ASAS) classification criteria. METHODS: A prospsective, observational study (Patients with Axial Spondyloarthritis: Multi-Country Registry of Clinical Characteristics) was conducted in rheumatology practices in 29 countries. Baseline and follow-up radiographs of sacroiliac joints were centrally evaluated by three readers according to the grading system of the modified New York criteria for patients initially classified as nr-axSpA. Radiographic progression from nr-axSpA to r-axSpA was evaluated by Kaplan-Meier analysis. Cox proportional regression analyses for progression from nr-axSpA to r-axSpA were also conducted. RESULTS: Among 2,165 patients with axSpA, 1,612 (74%) were classified as having r-axSpA (1,050 [65%]) or nr-axSpA (562 [35%]) by central reading. Of 246 patients with nr-axSpA (mean [SD] symptom duration: 4.4 [6.2] years) who had at least one follow-up sacroiliac joint radiograph, progression from nr-axSpA to r-axSpA at any follow-up visit was observed in 40 patients (16%) over 5 years. Mean time to radiographic progression was 2.4 years (ranging from 0.9 to 5.1 years). Progression to r-axSpA was associated with male sex (hazard ratio [HR] 3.16 [95% CI 1.22-8.17]), fulfillment of the imaging arm of the ASAS classification criteria (HR 6.64 [1.37-32.25]), and good response to nonsteroidal anti-inflammatory drugs (HR 4.66 [1.23-17.71]). CONCLUSION: 16% of patients with nr-axSpA progressed to r-axSpA within 5 years. Male sex, fulfillment of the imaging arm of the ASAS criteria, and good response to nonsteroidal anti-inflammatory drugs were predictors of radiographic progression in patients with recently diagnosed axSpA.

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.

Efficacy and safety of upadacitinib in patients with ankylosing spondylitis refractory to biologic therapy: 1-year results from the open-label extension of a phase III study.

BACKGROUND: Upadacitinib, a Janus kinase inhibitor, has demonstrated efficacy and an acceptable safety profile in patients with ankylosing spondylitis (AS) in the phase III SELECT-AXIS programs. We report the 1-year efficacy and safety in patients with AS and an inadequate response to biologic disease-modifying antirheumatic drugs (bDMARD-IR) from the SELECT-AXIS 2 study. METHODS: Patients ≥ 18 years with active AS who met the modified New York criteria for AS and were bDMARD-IR received double-blind upadacitinib 15 mg once daily (QD) or placebo for 14 weeks. Patients who completed 14 weeks could enter an open-label extension and receive upadacitinib 15 mg QD for up to 2 years. Efficacy endpoints included the percentage of patients achieving ≥ 40% improvement in Assessment of SpondyloArthritis international Society response (ASAS40), Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity (LDA), and ASDAS inactive disease (ID); and change from baseline in total and nocturnal back pain, and Bath Ankylosing Spondylitis Functional Index (BASFI). Subgroup analyses (bDMARD lack of efficacy versus intolerance, and prior tumor necrosis factor inhibitor [TNFi] versus interleukin-17 inhibitor [IL-17i] exposure) were conducted. Binary and continuous efficacy endpoints were assessed using non-responder imputation with multiple imputation (NRI-MI) and as observed (AO) analyses; and mixed-effects model repeated measures (MMRM) and AO, respectively. Safety was assessed based on adverse events. Data through week 52 are reported. RESULTS: Of 420 randomized patients, 366 (continuous upadacitinib: n = 181; placebo to upadacitinib: n = 185) completed 52 weeks of treatment. At week 52, in the continuous upadacitinib and placebo to upadacitinib groups, ASAS40, ASDAS LDA, and ASDAS ID were achieved by 66% and 65%, 57% and 55%, and 26% and 25% (all NRI-MI); and change from baseline in total back pain, nocturnal back pain, and BASFI was -4.5 and -4.3, -4.6 and -4.4, and -3.6 and -3.5 (all MMRM), respectively. No new safety risks were identified. Subgroup analyses were consistent with the overall study population. CONCLUSIONS: Upadacitinib 15 mg QD demonstrated sustained improvement up to 52 weeks in bDMARD-IR patients with AS. Efficacy was generally similar in patients with lack of efficacy versus intolerance to bDMARDs and prior TNFi versus IL-17i exposure. TRIAL REGISTRATION: NCT02049138.

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.

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.

Biology and therapeutic potential of mesenchymal stem cell extracellular vesicles in axial spondyloarthritis.

Axial spondyloarthritis (AxSpA) is a chronic, inflammatory, autoimmune disease that predominantly affects the joints of the spine, causes chronic pain, and, in advanced stages, may result in spinal fusion. Recent developments in understanding the immunomodulatory and tissue-differentiating properties of mesenchymal stem cell (MSC) therapy have raised the possibility of applying such treatment to AxSpA. The therapeutic effectiveness of MSCs has been shown in numerous studies spanning a range of diseases. Several studies have been conducted examining acellular therapy based on MSC secretome. Extracellular vesicles (EVs) generated by MSCs have been proven to reproduce the impact of MSCs on target cells. These EVs are associated with immunological regulation, tissue remodeling, and cellular homeostasis. EVs' biological effects rely on their cargo, with microRNAs (miRNAs) integrated into EVs playing a particularly important role in gene expression regulation. In this article, we will discuss the impact of MSCs and EVs generated by MSCs on target cells and how these may be used as unique treatment strategies for AxSpA.

Sustained low functional impairment in axial spondyloarthritis (axSpA): which are the primary outcomes that should be targeted to achieve this?

OBJECTIVES: To (i) determine whether sustained disease activity states, as measured by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS), impact function, and (ii) evaluate characteristics predicting sustained low functional impairment in a prospective axial spondyloarthritis (axSpA) cohort. METHODS: Biologic Treatment Registry Across Canada (BioTRAC) was a multi-center, prospective registry that collected real-world data on axSpA patients receiving infliximab or golimumab between 2006 and 2017. Generalized estimating equations (GEE) were used to test baseline characteristics, treatment, and duration (at 6 and 12 months vs. only at 6 or 12 months vs. neither) of low BASDAI (< 3), ASDAS-inactive disease (ID)(< 1.3), and ASDAS-low disease activity (LDA) in predicting sustained low Bath Ankylosing Spondylitis Functional Index (BASFI)(< 3) between 12 and 18 months. The adjusted impact of achieving low disease state at 6 and/or 12 months on BASFI at 18 months was analyzed by generalized linear models. RESULTS: Eight hundred ten patients were enrolled. 33.7%, 13.4%, and 24.7% achieved sustained low BASDAI, ASDAS-ID, and ASDAS-LDA, respectively. In univariable GEE of baseline variables, age and baseline BASDAI, BASFI, and ASDAS significantly predicted sustained low BASFI. In multivariable GEE, sustained low BASDAI (p < 0.001), low BASDAI only at 6 or 12 months (p = 0.001), and baseline BASFI (p < 0.001) were the only predictors of sustained low BASFI. Sustained ASDAS-ID (p = 0.040) and ASDAS-LDA (p < 0.001) were also predictors when forced into the model. Similar results were obtained when evaluating the BASFI score at 18 months. CONCLUSION: Sustained BASDAI < 3 may be a valid and feasible target for a treat-to-target strategy in axSpA having function as treatment goal.

Can we characterize A-P/IAP behavioural phenotypes in people with chronic pain?

Two behavioural phenotypes in healthy people have been delineated based on their intrinsic attention to pain (IAP) and whether their reaction times (RT) during a cognitively-demanding task are slower (P-type) or faster (A-type) during experimental pain. These behavioural phenotypes were not previously studied in chronic pain populations to avoid using experimental pain in a chronic pain context. Since pain rumination (PR) may serve as a supplement to IAP without needing noxious stimuli, we attempted to delineate A-P/IAP behavioural phenotypes in people with chronic pain and determined if PR can supplement IAP. Behavioural data acquired in 43 healthy controls (HCs) and 43 age-/sex-matched people with chronic pain associated with ankylosing spondylitis (AS) was retrospectively analyzed. A-P behavioural phenotypes were based on RT differences between pain and no-pain trials of a numeric interference task. IAP was quantified based on scores representing reported attention towards or mind-wandering away from experimental pain. PR was quantified using the pain catastrophizing scale, rumination subscale. The variability in RT was higher during no-pain trials in the AS group than HCs but was not significantly different in pain trials. There were no group differences in task RTs in no-pain and pain trials, IAP or PR scores. IAP and PR scores were marginally significantly positively correlated in the AS group. RT differences and variability were not significantly correlated with IAP or PR scores. Thus, we propose that experimental pain in the A-P/IAP protocols can confound testing in chronic pain populations, but that PR could be a supplement to IAP to quantify attention to pain.

Real-World Retention and Clinical Effectiveness of Secukinumab for Axial Spondyloarthritis: Results From the Canadian Spondyloarthritis Research Network.

OBJECTIVE: Axial spondyloarthritis (axSpA) is a chronic, immune-mediated, inflammatory condition consisting of 2 clinical subsets: nonradiographic axSpA and ankylosing spondylitis, the latter having an estimated prevalence of 0.2% to 1% in Canada. Secukinumab (SEC) received Health Canada approval in 2016 for the treatment of adults with axSpA who have responded inadequately to conventional treatment, and has demonstrated efficacy and safety through extensive clinical trials. However, there is limited evidence on its real-world use in Canada. The objective of this study was to use the Canadian Spondyloarthritis (CanSpA) Research Network to describe real-world retention and effectiveness of SEC in the Canadian axSpA population. METHODS: This was an observational cohort study of Canadian patients with axSpA aged 18 to 65 years within the CanSpA network who had received treatment with SEC. Patients were indexed on the first date of SEC initiation. Retention and clinical effectiveness were assessed at 12 months postindex. Clinical effectiveness was measured as the proportion in remission and change in disease activity using multiple clinical indices. RESULTS: A total of 146 patients were included. Overall retention was estimated at 62.9%. Low disease activity (ie, Bath Ankylosing Spondylitis Disease Activity Index < 4) was achieved in 29.2% of patients, and 2% had achieved remission based on the Ankylosing Spondylitis Disease Activity Score. Bath Ankylosing Spondylitis Metrology Index scores improved by more than 60% from baseline to 12 months. CONCLUSION: The results of this real-world study of Canadian patients with axSpA, one of the first of its kind, support the effectiveness of SEC for treatment of axSpA. The CanSpA network presents an opportunity to continue building and improving the real-world evidence base for treatment of Canadian patients with spondyloarthritis.

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.

Work-Related Issues and Physical and Psychological Burden in Canadian Patients With Axial Spondyloarthritis: Results From the International Map of Axial Spondyloarthritis.

OBJECTIVE: To identify factors associated with work-related issues in Canadian patients with axial spondyloarthritis. METHODS: Data from 542 Canadian patients who participated in the International Map of Axial Spondyloarthritis online survey were analyzed. Participants who were employed, unemployed, or on short-term disability were included in this analysis. Regression analysis was used to study the association between work-related issues, disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), and psychological distress (12-item General Health Questionnaire [GHQ-12]). RESULTS: The mean age of surveyed participants was 44.3 (SD 13.9) years, 81% were university educated, and 52.6% employed. A substantial proportion had high disease activity (BASDAI ≥ 4, 72.1%) and psychological distress (GHQ-12 ≥ 3, 53.1%); 81% had work-related issues. This study analyzed responses from a subset of participants who were either employed, unemployed, or on short-term disability (n = 339). Ninety percent of this subset reported at least 1 work-related issue in the year before questionnaire completion, with the most frequent being absenteeism (49.3%) and missing work for healthcare provider visits (42.5%). Factoring in disability benefits eliminated the association between work-related issues and disease activity for all variables except fatigue (r = 0.217; P = 0.03) and discomfort (r = 0.196; P = 0.047). Difficulty fulfilling working hours (ß 2.342, 95% CI 1.413-3.272) and effect on professional advancement (ß 1.426, 95% CI 0.355-2.497) were associated with psychological distress. In the presence of disability benefits, only the effect on professional advancement remained (ß 2.304, 95% CI 0.082-4.527). CONCLUSION: Work-related issues are associated with worse patient-reported outcomes, both physical and psychological.

Real-World Retention and Clinical Effectiveness of Secukinumab for Psoriatic Arthritis: Results From the Canadian Spondyloarthritis Research Network.

OBJECTIVE: Psoriatic arthritis (PsA) is an immune-mediated disease characterized by pain, stiffness, and swelling of peripheral joints, with an estimated prevalence in Canada of 0.45%. Treatment aims to minimize disease activity, reduce progression of damage, and improve quality of life. Secukinumab (SEC) is a biologic disease-modifying antirheumatic drug (bDMARD) that has demonstrated efficacy and safety for PsA in clinical trials; however, there is limited real-world evidence on its use in Canada. The objective of this study was to use the Canadian Spondyloarthritis (CanSpA) Research Network to describe real-world retention and effectiveness of SEC among Canadian patients with PsA. METHODS: This was an observational cohort study of Canadian patients with PsA, 18 to 65 years of age, who attended a clinic of the CanSpA network and received treatment with SEC. Patients were indexed on the date they first initiated SEC. Retention was assessed at 12 months postindex. Clinical effectiveness was measured as the proportion of patients in remission and change in disease activity from baseline to 12 months using several clinical indices. RESULTS: In total, 213 patients were included. Overall retention was estimated at 73.6% at 12 months (81.8% for bDMARD- or targeted synthetic DMARD-naïve patients). Out of 110 patients, 17 (15.5%) were in remission based on the Disease Activity Index in Psoriatic Arthritis in 28 joints, and 10 out of 70 patients (14.3%) were in remission based on the Psoriatic Arthritis Disease Activity Score at 12 months. The Psoriasis Area and Severity Index improved by 65.8%; the tender joint count in 68 joints and the swollen joint count in 66 joints improved by 65.5% and 73.7%, respectively. CONCLUSION: This is the first nationwide study that we know of to describe real-world use of SEC in Canada for PsA, and the results support its effectiveness in a Canadian real-world setting. The CanSpA network represents a unique opportunity to build and improve the real-world evidence base for SpA treatment in Canada.

Platelet-Derived Growth Factor B Is a Key Element in the Pathological Bone Formation of Ankylosing Spondylitis.

Enthesophyte formation plays a crucial role in the development of spinal ankylosis in ankylosing spondylitis (AS). We aimed to investigate the role of platelet-derived growth factor B (PDGFB) in enthesophyte formation of AS using in vitro and in vivo models and to determine the association between PDGFB and spinal progression in AS. Serum PDGFB levels were measured in AS patients and healthy controls (HC). Human entheseal tissues attached to facet joints or spinous processes were harvested at the time of surgery and investigated for bone-forming activity. The impact of a pharmacological agonist and antagonist of platelet-derived growth factor B receptor (PDGFRB) were investigated respectively in curdlan-treated SKG mice. PDGFB levels were elevated in AS sera and correlated with radiographic progression of AS in the spine. Mature osteoclasts secreting PDGFB proteins were increased in the AS group compared with HC and were observed in bony ankylosis tissues of AS. Expression of PDGFRB was significantly elevated in the spinous enthesis and facet joints of AS compared with controls. Moreover, recombinant PDGFB treatment accelerated bone mineralization of enthesis cells, which was pronounced in AS, whereas PDGFRB inhibition efficiently reduced the PDGFB-induced bone mineralization. Also, PDGFRB inhibition attenuated the severity of arthritis and enthesophyte formation at the joints of curdlan-treated SKG mice. This study suggests that regulating PDGFB/PDGFRB signaling could be a novel therapeutic strategy to block key pathophysiological processes of AS. © 2022 American Society for Bone and Mineral Research (ASBMR).

A Hidden Markov Model reveals magnetoencephalography spectral frequency-specific abnormalities of brain state power and phase-coupling in neuropathic pain.

Neuronal populations in the brain are engaged in a temporally coordinated manner at rest. Here we show that spontaneous transitions between large-scale resting-state networks are altered in chronic neuropathic pain. We applied an approach based on the Hidden Markov Model to magnetoencephalography data to describe how the brain moves from one activity state to another. This identified 12 fast transient (~80 ms) brain states including the sensorimotor, ascending nociceptive pathway, salience, visual, and default mode networks. Compared to healthy controls, we found that people with neuropathic pain exhibited abnormal alpha power in the right ascending nociceptive pathway state, but higher power and coherence in the sensorimotor network state in the beta band, and shorter time intervals between visits of the sensorimotor network, indicating more active time in this state. Conversely, the neuropathic pain group showed lower coherence and spent less time in the frontal attentional state. Therefore, this study reveals a temporal imbalance and dysregulation of spectral frequency-specific brain microstates in patients with neuropathic pain. These findings can potentially impact the development of a mechanism-based therapeutic approach by identifying brain targets to stimulate using neuromodulation to modify abnormal activity and to restore effective neuronal synchrony between brain states.

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.