[Hypogonadism in men with inflammatory joint diseases: Frequency and clinical characteristics].

AIM: To study the frequency of hypogonadism (HG) in men with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) and to evaluate the impact of HG on the course of RA and and concomitant diseases. MATERIALS AND METHODS: A single-stage continuous study included 170 men with RA, 57 men with AS and 85 men with PsA, who were hospitalized at the Nasonova Research Institute of Rheumatology. Patients were assessed for total testosterone (ТS) levels and subsequently divided into subgroups with normal (>12 nmol/l) and reduced levels. An intergroup comparison was carried out on the main indicators used in clinical rheumatological practice to assess the stage, activity and other medical and demographic characteristics of rheumatic disease, as well as on concomitant conditions. The second stage of the study involved a pairwise intergroup comparison among patients with HG with RA, AS and PsA. RESULTS: The incidence of ТS deficiency among patients with RA was 24.1%, among patients with AS - 17.5%, and with PsA - 31.8%. In patients with RA, HG was associated with a significantly higher mean body mass index, higher fasting blood glucose and uric acid, higher erythrocyte sedimentation rate and anemia. Patients with AS with HG had significantly lower hemoglobin levels and more frequent anemia, as well as higher levels of C-reactive protein and erythrocyte sedimentation rate. In PsA, older age was observed in the androgen deficiency group, as well as higher body mass index and fasting glucose levels; obesity was more common. An intergroup comparison of quantitative and qualitative indicators between patients with androgen deficiency in all three rheumatic diseases (RDs) did not reveal significant differences in the average concentrations of ТS, luteinizing hormone, sex hormone binding globulin, experience of RD, laboratory markers of inflammatory activity, as well as glucose and uric acid. A similar incidence of diabetes mellitus, obesity and anemia was noted for all three nosologies. CONCLUSION: ТS levels and the presence of HG were not associated with the stage and activity of RD, but ТS deficiency was accompanied by higher laboratory indicators of inflammatory activity, lower hemoglobin values, and metabolic disorders. Patients with HG, regardless of nosology, had similar levels of sex hormones and indicators reflecting RD and concomitant conditions.

Bone mineral density, bone metabolism-related factors, and microRNA-218 are correlated with disease activities in Chinese ankylosing spondylitis patients.

OBJECTIVE: To investigate bone mineral density (BMD), bone metabolism-related factors, and microRNA-218 in Chinese ankylosing spondylitis (AS) patients and to identify their correlation with disease activities and the treatment with TNF-α inhibitors. METHODS: A total of 89 AS patients were enrolled in the study. Patients' information and laboratory examination results were collected. BMD of the anteroposterior lumbar spine (L2-L4), left femoral neck, and whole body were measured and T-scores were calculated. MicroRNA-218 was extracted from PBMCs of AS patients and detected by RT-PCR. Bone metabolism-related factors were detected using protein chips and flow cytometer. RESULTS: Out of 86 patients undergoing whole-body BMD measurement, 14 had osteopenia and 72 had normal BMD without osteoporosis or high BMD. Compared with short- (disease duration ≤3 years) and long-term groups (disease duration ≥10 years), medium-term group (disease duration ranges from 3 to 10 years) showed lowest BMD. Patients with onset age ≤20 years old had significantly lower BMD than the other groups (p < 0.05). The BMD of femoral neck had negative correlation with CRP (p < 0.05) and no correlation with BASDAI or ESR. Both whole-body BMD and femoral neck BMD were negatively correlated with BASMI (p < 0.05). Dickkopf-1 (DKK-1), platelet-derived growth factor-BB (PDGF-BB), and receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) were significantly increased, while Osteopontin (OPN) was significantly decreased in AS patients. Expression of microRNA-218 in PBMC of AS patients was low and was positively correlated with BASMI (p < 0.05), but it was not correlated with the duration of disease, age of onset, BASDAI, ESR, or BMD. CONCLUSION: Loss of bone mass mainly occurred at the inflammatory sites in AS patients, depending on the severity of inflammation. The alleviation of inflammation can improve loss of bone mass and bone metabolism disorders. Anti-inflammatory treatment is critical for the treatment of secondary osteoporosis caused by AS.

Disease modification in ankylosing spondylitis with TNF inhibitors: spotlight on early phase clinical trials.

INTRODUCTION: Ankylosing spondylitis (AS) is a chronic inflammatory disease whose main hallmark is involvement of the axial skeleton. Non-steroidal anti-inflammatory drugs (NSAIDs) are the first line treatment; however, their use is limited because of side effects. Tumor necrosis factor inhibitors (TNFi) are a safe and effective therapy, and they have been approved for the management of AS. AREAS COVERED: This is a review of the efficacy of TNFi in disease modification in AS. It is focused on results from early-phase clinical trials; however, it also discusses the most relevant findings in order to optimize anti-TNF treatment. A literature search was done using PubMed, Medline, Embase, Google Scholar, and Cochrane library, looking for scientific publications from inception to August 2021. Further information was retrieved from ClinicalTrial.gov and Clinicaltrialsregister.eu. EXPERT OPINION: TNFi have demonstrated short- and long-term improvements in all aspects of disease activity, as well as physical function in patients with AS. They have drastically revolutionized the management of the disease; and even though new drugs have become available in the market, TNFi has not been displaced for the treatment of AS, and still constitute the best alternative when NSAIDs are no-longer an option.

Anterior uveitis in patients with spondyloarthritis treated with secukinumab or tumour necrosis factor inhibitors in routine care: does the choice of biological therapy matter?

BACKGROUND: The effect of interleukin 17-inhibitors on anterior uveitis (AU) in spondyloarthritis (SpA) is poorly understood. This study aimed to compare the risk of AU during treatment with secukinumab versus tumour necrosis factor inhibitors (TNFi). METHODS: Patients with SpA starting secukinumab or a TNFi 2015 through 2018 were identified in the Swedish Rheumatology Quality Register. Occurrence of AU was identified based on diagnosis codes in outpatient ophthalmology care in the National Patient Register. The main outcomes were crude rates of AU-diagnoses per 100 patient-years, and adjusted HRs for AU, during treatment, in patients without AU during the year before treatment start (in order to reduce confounding by indication). HRs were adjusted for age, sex, history of AU and patient global assessment of disease activity. RESULTS: Based on 4851 treatment starts (456 secukinumab; 4395 any TNFi), the rate of AU-diagnoses per 100 patient-years was 6.8 (95% CI 5.2 to 8.7) for secukinumab. Among the TNFi, the rate varied from 2.9 (95% CI 2.1 to 3.7) for infliximab and 4.0 (95% CI 3.3 to 4.9) for adalimumab to 7.5 (95% CI 6.7 to 8.4) for etanercept. The adjusted HRs for first AU (adalimumab as reference) were: secukinumab 2.32 (95% CI 1.16 to 4.63), infliximab 0.99 (95% CI 0.49 to 1.96), etanercept 1.82 (95% CI 1.13 to 2.93), golimumab 1.59 (95% CI 0.90 to 2.80) and certolizumab 1.12 (95% CI 0.44 to 2.83). Sensitivity analyses confirmed the pattern of higher AU rates with secukinumab and etanercept versus monoclonal TNFi. CONCLUSION: As used in clinical practice in SpA, secukinumab appears to be associated with a higher risk of AU, compared with the monoclonal TNFi and a similar risk compared with etanercept.

SNP-adjacent super enhancer network mediates enhanced osteogenic differentiation of MSCs in ankylosing spondylitis.

Ankylosing spondylitis (AS) is a rheumatic disease with pathological osteogenesis that causes bony ankylosis and even deformity over time. Mesenchymal stem cells (MSCs) are multipotent stem cells that are the main source of osteoblasts. We previously demonstrated that enhanced osteogenic differentiation of MSCs from AS patients (ASMSCs) is related to pathological osteogenesis in AS. However, the more concrete mechanism needs further exploration. Super enhancers (SEs) are dense clusters of stitched enhancers that control cell identity determination and disease development. Single-nucleotide polymorphisms (SNPs) regulate the formation and interaction of SEs and denote genes accounting for AS susceptibility. Via integrative analysis of multiomic data, including histone 3 lysine 27 acetylation (H3K27ac), chromatin immunoprecipitation sequencing (ChIP-seq), SNPs and RNA sequencing (RNA-seq) data, we discovered a transcription network mediated by AS SNP-adjacent SEs (SASEs) in ASMSCs and identified key genes, such as Toll-like receptor 4 (TLR4), interleukin 18 receptor 1 (IL18R1), insulin-like growth factor binding protein 4 (IGFBP4), transportin 1 (TNPO1) and proprotein convertase subtilisin/kexin type 5 (PCSK5), which are pivotal in osteogenesis and AS pathogenesis. The SASE-regulated network modulates the enhanced osteogenic differentiation of ASMSCs by synergistically activating the PI3K-Akt, NF-kappaB and Hippo signaling pathways. Our results emphasize the crucial role of the SASE-regulated network in pathological osteogenesis in AS, and the preferential inhibition of ASMSC osteogenic differentiation by JQ1 indicates that SEs may be attractive targets in future treatment for new bone formation in AS.

Is fibromyalgia frequency increasing in axial spondyloarthritis? Association with fibromyalgia and biological therapies.

Fibromyalgia (FM) is known a common painful syndrome and its frequency is increased in inflammatory rheumatic diseases. We aimed to assess FM frequency in axial spondyloarthritis (AxSpA) patients and age- and sex-matched healthy controls with the 2011 ACR FM criteria. We evaluated the association between receiving biologic disease-modifying antirheumatoid drugs (bDMARD) and presence of FM. 127 patients with Ax-SpA and 73 age- and sex-matched controls were included. Individuals were assessed according to modified 2011 ACR diagnostic criteria for FM. The pain was evaluated by visual analog scale (VAS). Disease activity was assessed by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activation Score (ASDAS). Spinal limitation, quality of life, and functionality were assessed. Drug therapies were noted. AxSpA and control group had similar FM rates. 43 (33.9%) patients in AxSpA group and 22 (30.1%) patients in control group had FM diagnosis (p = 0.589). Age, gender, BMI, and CRP values were similar in the AxSpA patients with and without FM, while global VAS and ASDAS scores were higher in patients with FM. Biologic DMARD use was higher in the AxSpA patients with FM; however, the difference was not statistically significant. In conclusion, FM frequency does not increase in AxSpA patients as compared to healthy controls. FM awareness is one of the key points to determine the appropriate treatment due to the influence on disease activity.

Effects of exercise programmes on pain, disease activity and function in ankylosing spondylitis: A meta-analysis of randomized controlled trials.

BACKGROUND: To evaluate the effects of exercise programmes on pain, function and disease activity in patients with ankylosing spondylitis (AS). MATERIALS AND METHODS: We searched PubMed, Embase, CNKI and Wanfang from inception to February 2020. Randomized controlled trials comparing exercises with nonexercise interventions in AS patients were applied. Studies that assessed the visual analogue scale (VAS) pain score, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were included. Outcomes of home-based exercise intervention were also reported independently. RESULTS: Ten studies met the inclusion criteria in all, including 534 patients (278 exercise, 256 control). Compared with the nonexercise group, exercise group had statistically significant improvements in pain (weighted mean difference [WMD]: -1.02 [95% CI: -1.50 to -0.55]) (I2 : 31%, P <.0001), BASDAI (WMD: -0.85 [95% CI: -1.09 to -0.61]) (I2 : 20%, P <.00001), and BASFI (WMD: -0.66 [95% CI: -0.95 to -0.38]) (I2 : 0%, P <.00001), but not in CRP and ESR. What's more, home-based exercise programmes had positive impacts on BASFI, BASDAI and pain. CONCLUSIONS: For patients with AS, exercise programmes improve pain, function and disease activity. To confirm the results, more well-designed randomized controlled trials with large number of patients are required.

Drug-neutralizing Antibodies against TNF-α blockers as Biomarkers of Therapy Effect Evaluation.

INTRODUCTION: TNF-α blocker therapy is part of the treatment with biologics used in the management of inflammatory joint diseases. In recent years, drug-induced neutralizing antibodies have been shown to have a negative effect on the course of the disease process. AIM: To investigate drug-induced neutralizing antibodies against TNF-α blocking drugs used in patients with inflammatory joint diseases and their effect on the clinical course of the disease. MATERIALS AND METHODS: The study included 121 (56.8%) patients with rheumatoid arthritis, 50 (23.5%) patients with ankylosing spondylitis, 42 (19.7%) patients with psoriatic arthritis, and 31 sex and age-matched healthy controls. The patients were monitored at 0, 6, 12, and 24 months after initiation of TNF-α blocker treatment. The demographic data, vital signs and the parameters of inflammatory activity (C-reactive protein, erythrocyte sedimentation rate, and disease activity indices) were analyzed in all patients. Drug-induced anti-TNF-α blockers antibodies (adalimumab and etanercept) were analyzed using ELISA. Statistical analysis was performed with SPSS v. 24. RESULTS: Drug-induced neutralizing antibodies against adalimumab were obtained in 11.57% of patients at 6 month, in 17.64% at 12 month, and in 24.8% at 24 month. Drug-induced neutralizing antibodies to etanercept were not demonstrated in patients followed up at 6 months, at 7.77% at 12 months, and at 9.63% at 24 months. Between the presence of neutralizing antibodies to blockers of TNF-α and indices available for disease activity, there is a strong positive correlation and Pearson Correlation = 0.701, p=0.001. Patients with poor clinical response and available antibodies against adalimumab at 12 months were 82.36% and patients treated with etanercept 71.42%. The difference between the two groups was non-significant (U = 0.527, p> 0.05). Patients with poor clinical response and available anti-adalimumab antibodies at 24 month were 75%, and in patients treated with etanercept - 87.50%, the difference between the two groups not being able to reach significance (U = 0.623, p> 0.05). CONCLUSION: Drug-induced neutralizing antibodies against TNF-α blockers (adalimumab and etanercept) have a negative effect on the course of inflammatory joint disease and can be used as reliable biomarker to assess the effect of the treatment with these drugs.

Spinal mobility in the cervical and lumbar spine correlates with magnetic resonance imaging findings for inflammatory and structural changes in patients with active ankylosing spondylitis.

OBJECTIVES: We aimed to assess relationships between single Bath Ankylosing Spondylitis Metrology Index (BASMI) components and corresponding spinal segment magnetic resonance images (MRI) in anti-tumour-necrosis-factor-treated AS patients. METHODS: Using available MRI and BASMI data from the GO-RAISE trial (n=91 patients), MRI scores for active inflammatory (ASspiMRI-a) and chronic structural (ASspiMRI-c) changes in cervical and lumbar spine segments were compared with BASMI cervical (cervical-rotation [CR] angle, tragus-to-wall [TTW] distance) and lumbar (lumbar flexion [LF], lateral-lumbar-flexion [LLF]) spine component scores (linear definition). Generalised linear models were employed to assess relationships between BASMI components and ASspiMRI-a/ASspiMRI-c measurements at baseline and for week-14 (golimumab/placebo groups) and week-104 (all golimumab-treated) change scores. RESULTS: Baseline lumbar ASspiMRI-a scores correlated with LF and LLF (ß=0.231 and 0.238, respectively; both p<0.01), while this was less prominent for ASspiMRI-c scores and LLF (ß=0.142, p=0.04). A significant but weak correlation was found between changes from baseline to week 104 in cervical spine ASspiMRI-c score and TTW distance among all treated patients (ß=0.161, p=0.003). CONCLUSIONS: Detailed assessments indicated baseline spinal mobility impairment in patients with active AS correlated weakly with MRI-detected lumbar spinal inflammation; correlations with chronic, structural damage/changes were very weak. Improved, less variable MRI and spinal metrology assessments are needed for future clinical research.

Eligibility criteria for biologic disease-modifying antirheumatic drugs in axial spondyloarthritis: going beyond BASDAI.

OBJECTIVES: To compare definitions of high disease activity of the Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in selecting patients for treatment with biologic disease-modifying antirheumatic drugs (bDMARDs). METHODS: Patients from Rheumatic Diseases Portuguese Register (Reuma.pt) with a clinical diagnosis of axial spondyloarthritis (axSpA) were included. Four subgroups (cross-tabulation between ASDAS (≥2.1) and BASDAI (≥4) definitions of high disease activity) were compared regarding baseline characteristics and response to bDMARDs at 3 and 6 months estimated in multivariable regression models. RESULTS: Of the 594 patients included, the majority (82%) had both BASDAI≥4 and ASDAS ≥2.1. The frequency of ASDAS ≥2.1, if BASDAI<4 was much larger than the opposite (ie, ASDAS <2.1, if BASDAI≥4): 62% vs 0.8%. Compared to patients fulfilling both definitions, those with ASDAS ≥2.1 only were more likely to be male (77% vs 51%), human leucocyte antigen B27 positive (79% vs 65%) and have a higher C reactive protein (2.9 (SD 3.5) vs 2.1 (2.9)). Among bDMARD-treated patients (n=359), responses across subgroups were globally overlapping, except for the most 'stringent' outcomes. Patients captured only by ASDAS responded better compared to patients fulfilling both definitions (eg, ASDAS inactive disease at 3 months: 61% vs 25% and at 6 months: 42% vs 25%). CONCLUSION: The ASDAS definition of high disease activity is more inclusive than the BASDAI definition in selecting patients with axSpA for bDMARD treatment. The additionally 'captured' patients respond better and have higher likelihood of predictors thereof. These results support using ASDAS≥2.1 as a criterion for treatment decisions.

Longitudinal associations between depressive symptoms and clinical factors in ankylosing spondylitis patients: analysis from an observational cohort.

OBJECTIVES: Although cross-sectional studies have shown that ankylosing spondylitis-specific factors correlate with depressive symptom severity, the association of these factors over time is unresolved. We examined the demographic and clinical factors associated with longitudinal depressive symptom severity in AS patients. METHODS: We analyzed sociodemographic, clinical, behavioral and medication data from 991 patients from the Prospective Study of Outcomes in Ankylosing spondylitis cohort, and measured depression severity with the Center for Epidemiological Studies Depression (CES-D) Scale administered at approximately 6-month visit intervals. Multivariable longitudinal negative binomial regression models were conducted using generalized estimating equation modeling to assess the demographic, clinical, and medication-related factors associated with depression severity by CES-D scores over time. RESULTS: The median baseline CES-D score (possible range 0-60) was 10.0 (interquartile range = 5, 17). In longitudinal multivariable analyses, higher CES-D scores were associated with longitudinal smoking, greater functional impairment, greater disease activity, self-reported depression, and poor global health scores. Marital status (e.g., being married) was associated with lower CES-D. Adjusted mean CES-D scores in our model decreased over time, with a significant interaction between time and gender observed. CONCLUSION: This study identified longitudinal clinical factors such as greater disease activity, greater functional impairment, and poor global health to be associated with longitudinal depression severity. These factors are potentially modifiable and may help manage depressive symptoms in AS.

Cerebral hemodynamics in patients with ankylosing spondylitis.

OBJECTIVE: The aim of this study was to assess the cerebral blood flow velocity as a marker by using transcranial Doppler (TCD) ultrasonography in patients with ankylosing spondylitis (AS). METHODS: A total of 30 AS patients aged 20 to 50 were enrolled in the AS group (male/female: 4/26, mean age: 34.7 ± 5.9) consecutively. The control group (non-AS group; male/female: 4/26, mean age: 32.3 ± 4.7) consisted of 30 age- and sex-matched, randomly selected patients without AS who had other diagnoses such as fibromyalgia and did not have risk factors for atherosclerosis. Bilateral middle cerebral artery (MCA) peak-systolic, end-diastolic, and mean blood flow velocities, Gosling's pulsatility index values, and Pourcelot's resistance index values were recorded with TCD by a neurosonologist blinded to the AS and control groups. RESULTS: The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels and cerebral blood flow velocities of bilateral MCA were significantly higher in the AS group than in the control group. CONCLUSIONS: This study highlights that the increased cerebral blood flow is indirectly associated with atherosclerosis regarding persistent inflammation in patients with AS.

Associated factors with adherence to standard exercise therapy and health-related quality of life in Chinese patients with ankylosing spondylitis.

Objectives: The aim of this study is to assess the current situations of standard exercise treatment and predictors of non-standard exercise in Chinese patients with ankylosing spondylitis (AS). An analysis of the effect of standard exercise on health-related quality of life (HR-QoL) was also conducted.Methods: In the cross-sectional study, a total of 259 AS patients were constantly invited to participate in this study and complete the questionnaire under the researchers' supervision in a clinical setting including sociodemographic variables, clinical variables, psychological variables, and HR-QoL. Data were analyzed by Mann-Whitney U test, Chi-square test as well as multivariable analysis of Binary Stepwise Logistic Regression.Results: The data showed that just 20.5% of them could complete the standard exercise. Exercise adherence was associated with employment, educational level, marital status, place of residence, treatment of Tumor Necrosis Factor-α inhibitor, knowledge about exercise, disease duration, clinical variables, and anxiety. The HR-QoL in the group of standard exercise was better than that in the non-standard exercise group. Logistic Regression Analysis showed that lower educational level, less knowledge about benefits of exercise treatment and higher score of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were the independent risk factors of exercise treatment non-adherence.Conclusion: AS patients educated less than 9 years or with higher BASDAI score were more likely not to adhere to standard exercise treatment. Non-adherence to exercise treatment among AS patients is exceedingly common, particularly in patients without knowledge about benefits of exercise treatment. Standard exercise treatment can also improve HR-QoL of AS patients.

Impact of Comorbidity on Physical Function in Patients With Ankylosing Spondylitis and Psoriatic Arthritis Attending Rheumatology Clinics: Results From a Cross-Sectional Study.

OBJECTIVE: To evaluate the impact of comorbidities on physical function in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA). METHODS: This was a cross-sectional analysis of the baseline visit from the Cardiovascular in Rheumatology study. Multivariate models with physical function as the dependent variable (Bath Ankylosing Spondylitis Functional Index and Health Assessment Questionnaire for AS and PsA, respectively) were performed. Independent variables were a proxy for the Charlson Comorbidity Index (CCIp; range 0-27), sociodemographic data, disease activity (erythrocyte sedimentation rate [ESR] and Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] in AS; Disease Activity Score in 28 joints [DAS28] using the ESR in PsA), disease duration, radiographic damage, and treatments. Results were reported as beta coefficients, 95% confidence intervals (95% CIs), and P values. RESULTS: We included 738 patients with AS and 721 with PsA; 21% of patients had >1 comorbidity. Comorbidity burden (CCIp) was independently associated with worse adjusted physical function in patients with PsA (ß = 0.11). Also, female sex (ß = 0.14), disease duration (ß = 0.01), disease activity (DAS28-ESR; ß = 0.19), and the use of nonsteroidal antiinflammatory drugs (ß = 0.09), glucocorticoids (ß = 0.11), and biologics (ß = 0.15) were associated with worse function in patients with PsA. A higher education level was associated with less disability (ß = -0.14). In patients with AS, age (ß = 0.03), disease activity (BASDAI; ß = 0.81), radiographic damage (ß = 0.61), and the use of biologics (ß = 0.51) were independently associated with worse function on multivariate analyses, but CCIp was not. CONCLUSION: The presence of comorbidities in patients with PsA is independently associated with worse physical function. The detection and control of the comorbidities may yield an integral management of the disease.

Demographic and clinical differences between ankylosing spondylitis and non-radiographic axial spondyloarthritis: results from a multicentre retrospective study in the Lazio region of Italy.

OBJECTIVES: Axial spondyloarthritides (axSpA) are a group of disorders that share similar pathogenetic mechanisms and clinical picture. The aim of this retrospective multicentric study was to evaluate demographic and clinical differences between ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA) patients. METHODS: Patients from 7 rheumatological centres in the Lazio region of Italy were included from January 1st, 2010 to April 1st, 2018, if they had undergone pelvic and/or spine radiographs or magnetic resonance imaging (MRI). Images were evaluated by one experienced radiologist in each centre who already had the clinical suspicion of axSpA. Clinical and therapeutic data were collected at the last observation visit. Categorical variables were presented with percentages and analysed by Chi squared test. Continuous variables were expressed as mean ± standard deviation and compared using the parametric unpaired t-test or the non-parametric Mann-Whitney U-test, when appropriate. p-values <0.05 were considered significant. RESULTS: 210 axSpA patients were included: 65.2% with AS and 34.7% with nr-axSpA. When comparing the two groups, AS patients had longer disease duration, were older, were more frequently males, had a greater diagnostic delay and a higher body mass index than the nr-axSpA patients (p<0.0001, p<0.0001, p=0.003 p=0.007, and p=0.04, respectively). The peripheral joints of the nr-axSpA patients were more frequently involved, had higher frequency of inflammatory bowel disease, higher C-reactive protein levels and lower frequency of HLA-B27 positivity (p=0.005, p=0.007, p=0.01, and p=0.01, respectively). TNF inhibitors were used in 87.8% patients with AS and 78.3% with nr-axSpA (p=0.04). More fat metaplasia was observed on MRI in the nr-axSpA group than in the AS group at sacroiliac joints (p=0.003), and more backfills were detected in the AS group on spine-MRI (p=0.003). Spine-bone marrow oedema was more prevalent in AS than in nr-axSpA (p=0.04), and more sclerosis and backfill were found in AS (p=0.003 and p=0.01, respectively). CONCLUSIONS: In clinical practice, distinctive features in AS and nr-axSpA patients emerged. Imaging is crucial in guiding the choice of treatment in order to control disease activity and inflammation.

Cardiovascular Disease in Spondyloarthritides.

The spondyloarthritides are a group of chronic systemic inflammatory joint diseases, the main types being ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Evidence accumulating during the last decades suggests that patients with AS or PsA carry an increased risk for cardiovascular disease and cardiovascular death. This risk appears to be mediated by systemic inflammation over and above classical cardiovascular risk factors. The excess cardiovascular risk in those patients has been formally acknowledged by scientific organizations, which have called physicians' attention to the matter. The application by Rheumatologists of new effective anti-rheumatic treatments and treat-to-target strategies seems to benefit patients from a cardiovascular point of view, as well. However, more data are needed in order to verify whether anti-rheumatic treatments do have an effect on cardiovascular risk and whether there are differences among them in this regard. Most importantly, a higher level of awareness of the cardiovascular risk is needed among patients and healthcare providers, better tools to recognize at-risk patients and, ultimately, commitment to address in parallel both the musculoskeletal and the cardiovascular aspect of the disease.

Serum Uric Acid Shows Inverted "U" Type Correlation with Osteoporosis in Chinese Ankylosing Spondylitis Patients: A Retrospective Study.

BACKGROUND This study was to investigate the correlation between osteoporosis and serum uric acid in ankylosing spondylitis (AS) patients, and to further identify potential factors that might be associated with osteoporosis in AS patients. MATERIAL AND METHODS We included 182 AS patients, consisted of 143 male patients and 39 female patients, who visited our hospital from January 1, 2014 to December 31, 2018. We used dual-energy x-ray absorptiometry to measure bone mineral density (BMD) of orthotopic lumbar vertebrae in patients with AS. The gender, age, disease duration, BMD, T-score, Z-score, uric acid, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), blood platelet (PLT), and status of treatment with biologics of the patients were collected. Then, the Spearman correlation coefficient and multivariate liner regression analysis were applied to identify the relationship between the factors and BMD, T-score, and Z-score in AS patients. RESULTS Male AS patients between the ages of 16 and 30 years old had a higher risk of osteoporosis (P<0.05). AS patients with uric acid value between 300-360 µmol/L had the highest BMD, T-score, and Z-score. The BMD had a positive correlation with age and disease duration (P<0.01) while had a negative correlation with PLT (P<0.05). BMD in AS patients with elevated ESR was significantly (P<0.05) lower than in AS patients with normal ESR. There were no significant differences in BMD between AS patients with elevated CRP and the patients with normal CRP and PLT. Treatment with TNFi (tumor necrosis factor alpha inhibitor) did not improve BMD in AS patients. CONCLUSIONS The relationship between uric acid and BMD in AS patients was observed as inverted "U"-type. Keeping uric acid within 300-360 µmol/L might be helpful in preventing AS patients from developing osteoporosis.

Efficacy of wIRA in the treatment of sacroiliitis in male patients with ankylosing spondylitis and its effect on serum VEGF levels.

BACKGROUND: This study aimed to assess the efficacy of water-filtered infrared A (wIRA) in sacroiliitis in male patients with ankylosing spondylitis (AS) and the effect of wIRA therapy on serum vascular endothelial growth factor (VEGF). METHODS: One hundred twenty male AS patients with active sacroiliitis were randomly divided into wIRA group and control group. wIRA treatment was performed twice daily for 5 consecutive days with 24-h interval before switching the treatment (crossover design). Bath ankylosing spondylitis disease activity index (BASDAI) scores, pain visual analogue scale (VAS), and morning stiffness VAS were recorded prior to and after each treatment period. Additionally, C-reactive protein (CRP), serum VEGF, and resistance index (RI) of sacroiliac joints detected by ultrasonography were recorded at baseline and after the first and second treatment period, respectively. The efficacy was examined by using repeated measures analysis of variance (ANOVA). RESULTS: BASDAI, pain VAS, and morning stiffness VAS scores decreased significantly (P < 0.001) after wIRA treatment and no-wIRA treatment (control group), and the difference between the two groups was significant (P < 0.001). CRP declined and RI increased during the wIRA treatment as compared with the no-wIRA treatment (P < 0.001). The increase in RI was associated with improvement of pain VAS scores (P = 0.018), while serum VEGF was unaffected by the treatment. CONCLUSIONS: wIRA treatment achieved symptom and pain relief for AS patients with active sacroiliitis. wIRA treatment also improved RI revealed by ultrasonography, and this effect was associated with improved pain VAS scores.

Disease Activity, Occupational Participation, and Quality of Life for Individuals with and without Severe Fatigue in Ankylosing Spondylitis.

BACKGROUND: Fatigue is one of the most frequently reported symptoms by individuals with ankylosing spondylitis. However, it is often overlooked clinically and in research. Literature researching the impact of severe fatigue on occupational participation in ankylosing spondylitis is limited. Therefore, the aim of this research was to explore the impact of severe fatigue on occupational participation, disease activity, and quality of life in people with AS. METHODS: A sequential exploratory mixed method study design was used in this study. Self-reported questionnaires gathered quantitative data which were analysed with descriptive and inferential statistics. Qualitative data were generated through semistructured interviews and analysed using a content analysis approach. RESULTS: Fifty individuals with AS completed all study questionnaires. Participants had a mean age of 46.5 years; 72% were men with a mean disease duration of 14.5 years. High fatigue was reported by 38% of participants using the Multidimensional Assessment of Fatigue (MAF). Fatigue was significantly associated with lower occupational participation (p = 0.018), higher disease activity (p < 0.001), higher pain (p < 0.001), reduced physical capacity (p = 0.018), lower quality of life (p < 0.001), and lower global well-being (p < 0.001). There were significant differences between those with low and high fatigue levels for occupational participation (p = 0.007), disease activity (p < 0.001), physical capacity (p = 0.015), pain (p < 0.001), and quality of life (p < 0.001). Participants discussed the impact of fatigue on productivity and leisure. They also discussed a range of strategies for managing their fatigue but reported a lack of education from health professionals on managing this symptom. CONCLUSION: Severe fatigue is a prevalent symptom for individuals with ankylosing spondylitis and results in reduced occupational participation in productivity and leisure. Early fatigue management interventions may reduce the occupational participation impact of this symptom for individuals with ankylosing spondylitis.

Risk of Developing Additional Immune-Mediated Manifestations: A Retrospective Matched Cohort Study.

INTRODUCTION: Immune-mediated inflammatory diseases (IMIDs) cause significant impairment in quality of life. Although they share similar genetic factors, environmental precipitants, and pathophysiological mechanisms, there is little evidence on the risk of developing subsequent IMIDs after an initial IMID diagnosis. We sought to assess the risk of developing subsequent IMIDs among patients diagnosed with an initial IMID. METHODS: This retrospective matched cohort study used a large US commercial health insurance claims database (01/01/2006-09/30/2015). The risks of developing secondary IMIDs among patients aged 18-64 years with a diagnosis of one of nine IMIDs of interest (ankylosing spondylitis, celiac disease, hidradenitis suppurativa [HS], inflammatory bowel disease, lupus, psoriatic arthritis [PsA], psoriasis, rheumatoid arthritis, and uveitis) as identified from diagnosis codes on medical claims were compared with up to 1000 matched controls without the primary IMID using Cox proportional hazards models. RESULTS: Across the nine IMIDs of interest, there were 398,935 unique case patients matched to 256,795,796 non-unique control patients. Case patients with an initial IMID had higher risks of developing each, any one, and any two of the other eight secondary IMIDs compared to their matched controls. Hazard ratios [95% confidence intervals] for the risk of developing any one secondary IMID ranged from 5.4 [5.0, 5.8] (initial IMID: HS) to 62.2 [59.9, 64.6] (initial IMID: PsA), and hazard ratios for developing any two secondary IMIDs ranged from 3.0 [2.3, 3.8] (HS) to 75.2 [69.3, 81.7] (PsA). CONCLUSIONS: This study demonstrates that the risk of developing a second IMID is significantly higher for individuals who have already experienced a first IMID in a large and contemporary US claims database. Certain pairs of IMIDs co-occur more frequently than others. The risk of developing subsequent IMIDs may be an important consideration for clinicians when selecting treatment strategies. FUNDING: Abbvie.