Non-radiographic Axial Spondyloarthritis Patients Research Articles

Differences between radiographic and non-radiographic axial spondyloarthritis patients in a Mexican cohort

To compare the demographic, clinical, and laboratory characteristics, disease onset, and clinical features of radiographic axial Spondyloarthritis (r-axSpA) and non-radiographic axial Spondyloarthritis (nr-axSpA) patients. All patients who attended outpatient spondylarthritis (SpA) clinics at Hospital General de Mexico and the Instituto Nacional de la Nutrición from 1998 to 2005 and met the rheumatologist diagnostic criteria for SpA were selected. Then the SpA patients were classified by European Spondyloarthropathy Study Group criteria (ESSG). We selected SpA patients with axial presentation as axial SpA (axSpA), and they were classified as r-axSpA if they met modified New York (mNY) criteria for sacroiliitis and as nr-axSpA if they did not meet mNY criteria; to compared clinical, demographic, and laboratory test between the subgroups. It included 148 SpA patients; 55 (37.2%) patients had r-axSpA, and 70 (47.3%) had nr-axSpA. The nr-axSpA patients had a lower proportion of males (58.6% vs 78.2%, P < 0.05), lower HLA-B27 frequency (54.3%. vs. 92.7%, P < 0.05), were older at disease onset (21 vs 16 years; P < 0.01) and had a higher frequency of infections at disease onset (9.1% vs 32.9, P < 0.05) than r-axSpA. BASFI (2.9 vs 4.8; P < 0.0001), Dougados functional index (7 vs. 14; P < 0.05), and BASDAI (4.1 vs. 5.2; P < 0.001) were lower in patients with nr-axSpA than r-axSpA, respectively. The factors that most influenced the presentation of r-axSpA were history of uveitis (OR 14, 95% CI 2.3–85), HLA-B27 (OR 7.97, 95% CI, 2.96–122), male sex (OR 6.16, 95% CI, 1.47–25.7), axial enthesopathy count (OR 1.17 95% CI, 1.03–1.33). This study provides insight into the differences between nr-axSpA and r-axSpA in Mexico. Patients with r-axSpA were mainly male, with a younger presentation age, a higher prevalence of HLA-B27, more history of uveitis, fewer episodes of dactylitis, more axial enthesopathy, and higher disease activity than nr-axSpA.

Bone metabolism and inflammatory biomarkers in radiographic and non-radiographic axial spondyloarthritis patients: a comprehensive evaluation.

Axial spondyloarthritis (axSpA) is a heterogeneous disease that can be represented by radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA). This study aimed to evaluate the relationship between the markers of inflammation and bone turnover in r-axSpA patients and nr-axSpA patients. A cross-sectional study included 29 r-axSpA patients, 10 nr-axSpA patients, and 20 controls matched for age and sex. Plasma markers related to bone remodeling such as human procollagen type 1 N-terminal propeptide (P1NP), sclerostin, tartrate-resistant acid phosphatase 5b (TRACP5b), receptor activator of nuclear factor kappa B ligand (RANKL), and osteoprotegerin (OPG) were measured by an ELISA kit. A panel of 92 inflammatory molecules was analyzed by proximity extension assay. R-axSpA patients had decreased plasma levels of P1NP, a marker of bone formation, compared to controls. In addition, r-axSpA patients exhibited decreased plasma levels of sclerostin, an anti-anabolic bone hormone, which would not explain the co-existence of decreased plasma P1NP concentration; however, sclerostin levels could also be influenced by inflammatory processes. Plasma markers of osteoclast activity were similar in all groups. Regarding inflammation-related molecules, nr-axSpA patients showed increased levels of serum interleukin 13 (IL13) as compared with both r-axSpA patients and controls, which may participate in the prevention of inflammation. On the other hand, r-axSpA patients had higher levels of pro-inflammatory molecules compared to controls (i.e., IL6, Oncostatin M, and TNF receptor superfamily member 9). Correlation analysis showed that sclerostin was inversely associated with IL6 and Oncostatin M among others. Altogether, different inflammatory profiles may play a role in the development of the skeletal features in axSpA patients particularly related to decreased bone formation. The relationship between sclerostin and inflammation and the protective actions of IL13 could be of relevance in the axSpA pathology, which is a topic for further investigation.

Sonographic Comparison of Neck Extensor Muscle Thickness of Ankylosing Spondylitis and Non-radiographic Axial Spondyloarthritis Patients with Healthy Volunteers

Abstract Introduction This study examines the neck extensor muscle thickness of patients with ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA) by comparing them with healthy volunteers. It also aims to evaluate the relationship between muscle thickness and disease activity, functional parameters, neck disability and quality of life in patients with AxSpA. Method In this cross-sectional study, 30 patients with AS and 30 patients with nr-AxSpA who were admitted to a Physical Medicine and Rehabilitation outpatient clinic were included consecutively. Thirty healthy participants were included as a control group. The thickness of muscles was measured bilaterally by ultrasound and the muscle thickness average was recorded. All patients with axSpA were asked to complete the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath Ankylosing Spondylitis Metrology Index (BASMI), the Ankylosing spondylitis Quality of Life (AsQoL) scale and the Neck Disability Index (NDI). Results Mean patient age was 42.36±10.0 in the AS group, 38.13±7.94 in the nr-axSpA group and 39.06±8.25 in the healthy group. A statistically significant decrease was found in multifidus, semispinalis capitis, semispinalis cervicis and splenius capitis muscle thickness in AS patients compared with the healthy group, and in semispinalis cervicis muscle thickness in nr-axSpA patients compared with the healthy group. However, when trapezius muscle thickness was compared between the groups, no statistical difference was found. There was a significant negative correlation between neck extensor muscle thickness and age, BASDAI, NDI and AsQoL in patients with axSpA. Conclusion The thickness of the neck extensor muscles is decreased in patients with AxSpA compared with healthy individuals, and this situation can be reliably detected by ultrasound.

Exercise capacity in axial spondyloarthritis and associated factors: A cross-sectional controlled study.

To examine the associations between exercise capacity (EC), cardiovascular (CV) risk factors and disease-related variables in axial spondyloarthritis (AxSpA) patients. In this cross-sectional controlled study, CV risk profile data, physical activity, 10-year CV event risk estimated by the Framingham model and Ankylosing Spondylitis Disease Activity Score - C-reactive protein were recorded. A maximal treadmill exercise test by Bruce protocol was administered. Analyses of covariance were performed with adjustments for age, smoking status and physical activity level. Linear regression analysis was performed to study the association between EC and related CV risk factors. Thirty-eight patients and 38 age-gender matched controls were recruited between May and October 2014. Patients had significantly lower EC than controls (MD 2.2; metabolic equivalents 0.91-3.49; P=.001). The difference remained significant after adjustments (P=.001). There were significant correlations between EC and age, 10-year CV event risk, body mass index (BMI) and waist circumference for patients and controls (P<.001 and P<.05, respectively). There was a significant relationship between EC and total cholesterol, triglycerides and heart rate recovery (HRR) in patients (P=.04, P<.001 and P=.006, respectively). High-density lipoprotein - cholesterol was significantly higher, and BMI was significantly lower in nonradiographic AxSpA patients (P=.026 and P=.03 respectively). Age and triglyceride levels were found as the significant predictors for EC in the AxSpa group (for age β=-.105, P=.003; for triglycerides β=-.016 P=.003). Exercise capacity was significantly lower and attenuated HRR was significantly associated with low EC and high 10-year CV event risk in AxSpA patients.

Cross-walk of the Assessment of Spondyloarthritis International Society Health Index and Ankylosing Spondylitis Quality of Life Scores in Ankylosing Spondylitis and Non-radiographic Axial Spondyloarthritis Patients.

IntroductionAxial spondyloarthritis (axSpA) is a chronic rheumatic disease affecting the spine and sacroiliac joints, encompassing both ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA) patients. Patient quality of life (QoL) is assessed using the Ankylosing Spondylitis Quality of Life (ASQoL) (disease-specific measure) and the Assessment of SpondyloArthritis International Society Health Index (ASAS HI) (disease-specific measure). Both ASQoL and ASAS HI have similar parameters and scoring ranges, however, their performance relative to each other is unknown. We conducted a cross-walk analysis of the ASAS HI to the ASQoL in AS and nr-axSpA patients.MethodsA cross-sectional survey using the Adelphi axSpA Disease Specific Programme™, conducted with rheumatologists and their consulting AS and nr-axSpA patients in the United States, was undertaken between Jun and Aug 2018. Rheumatologists provided confirmed diagnoses of AS and nr-axSpA alongside patients’ demographic and clinical characteristics. Patients reported quality-of-life measures using the validated ASAS HI and ASQoL questionnaires. Model performance was assessed by comparing root-mean squared error (RMSE) from tenfold cross-validation to determine the best mapping from ASAS HI to ASQoL, and vice versa. RMSE was calculated overall, and for lower, middle and upper thirds of the predicted scale.ResultsData from 283 AS and 274 nr-axSpA patients were analyzed. Predicting ASAS HI using ASQoL values, the best model was non-parametric local linear regression, with overall RMSE of 1.851. Predicting ASQoL using ASAS HI values, the best model also used non-parametric local-linear regression, with overall RMSE of 2.254. In predicting ASAS HI and ASQoL, models performed better in predicting lower values in the predicted scale (RMSE 1.597, 1.871, 2.871 across thirds for ASAS HI; and 1.719, 2.577, 3.140 for ASQoL).ConclusionsResults present a scoring algorithm for cross-walking the ASAS HI to the ASQoL and vice versa, with the approach enabling comparisons to be made across studies.

Comparing symptoms, treatment patterns, and quality of life of ankylosing spondylitis and non-radiographic axial spondyloarthritis patients in the USA: findings from a patient and rheumatologist Survey

ObjectivesThe aim of this study was to compare the symptoms, treatment patterns, and quality of life (QoL) of ankylosing spondylitis (AS) patients to non-radiographic axial spondyloarthritis (nr-axSpA) patients in the USA.MethodA cross-sectional survey was conducted with rheumatologists and their consulting patients in the USA from June through August 2018. Patients who had a rheumatologist confirmed diagnosis of AS and nr-axSpA were eligible to participate. Patient demographics, symptoms, and medication use were reported by the rheumatologist, while work disability and QoL measures were reported by the patient. Patient demographics, symptoms, QoL and treatment patterns of AS and nr-axSpA patients were compared using parametric tests and non-parametric tests when appropriate.ResultsA total of 515 AS patients and 495 nr-axSpA patients were included in this analysis. A higher proportion of AS patients were male (p < 0.001), older (p = 0.014), and more likely to be prescribed a biologic (p < 0.0001). On average, AS patients experienced slightly more symptoms at diagnosis (p = 0.023); however, nr-axSpA patients were more likely to experience enthesitis (p = 0.048) and synovitis (p = 0.003). Patient reported outcomes such as the ASAS Health Index (p = 0.171), ASQoL (p = 0.296), BASDAI (p = 0.124), and WPAI (p = 0.183) were similar between AS and nr-axSpA patients after adjusting for confounding variables such as medication use.ConclusionsAS and nr-axSpA patients share the same clinical features. The burden of the disease, as assessed by QoL measurements, is also similar in AS and nr-axSpA patients; however, despite these similarities, patients with nr-axSpA are less likely to be treated with a biologic.Key Points• Ankylosing spondylitis and non• radiographic axial spondyloarthritis patients share similar clinical features and burden of disease.• Quality of life is similar among ankylosing spondylitis and non• radiographic axial spondyloarthritis after adjusting for current treatment patterns.

Non-radiographic axial spondyloarthritis in Tunisia: main characteristics and detailed comparison with ankylosing spondylitis.

The aim of the present study is to compare the clinical features, disease activity, and physical impairment between non-radiographic axial spondyloarthritis and ankylosing spondylitis in Tunisian patients. This is a retrospective study conducted in a single rheumatology center in Tunisia. Patients with axial spondyloarthritis fulfilling the 2009 ASAS criteria were included. The various spondyloarthritis-related variables were compared between non-radiographic axial spondyloarthritis and ankylosing spondylitis. p Values below 0.05 were considered statistically significant. Among 200 patients with axial spondyloarthritis, 40 had non-radiographic axial spondyloarthritis and 160 had ankylosing spondylitis. The non-radiographic axial spondyloarthritis patients were more frequently female, were younger, and had shorter disease duration. Patients with non-radiographic axial spondyloarthritis experienced enthesitis more frequently compared with ankylosing spondylitis patients. Psoriasis was more frequent in non-radiographic axial spondyloarthritis group, while inflammatory bowel disease was more frequent in ankylosing spondylitis group. The C-reactive protein level and functional score were significantly higher in patients with ankylosing spondylitis compared with non-radiographic axial spondyloarthritis. Tumor necrosis factor inhibitors were offered significantly more often to the ankylosing spondylitis group. There was no statistically significant difference between the 2 groups in other spondyloarthritis parameters. The non-radiographic axial spondyloarthritis is characterized mainly by a marked female prevalence, a higher enthesitis prevalence, and a better physical function. • Patients with nr-axSpA in Tunisia are more frequently female and have shorter disease duration compared with those with AS. • Peripheral manifestations were similar between nr-axSpA and AS patients except for enthesitis which were more frequent within nr-axSpA patients. • The disease activity is similar between the 2 groups of axSpA but the physical function is better within nr-axSpA patients.

Work disability in non-radiographic axial spondyloarthritis patients before and after start of anti-TNF therapy: a population-based regional cohort study from southern Sweden.

The aim was to assess work-loss days before and after commencement of anti-TNF treatment in patients with non-radiographic axial spondylarthritis (nr-axSpA). Bionaïve nr-axSpA patients (n = 75), aged 17-62 years, fulfilling the Assessment of SpondyloArthritis international Society criteria for axial spondyloarthritis and starting anti-TNF treatment during 2004-11, were retrieved from the observational South Swedish Arthritis Treatment Group study. Patient information was linked to Swedish Social Insurance Agency data on sick leave and disability pension from 1 year before to 2 years after anti-TNF initiation. Matched population references were included for comparison and to adjust for secular trends. The nr-axSpA patients had a median age of 35 years and disease duration of 6 years at the start of treatment. During the 2 years after anti-TNF initiation, mean work-loss days (including both sick leave and disability pension) in the nr-axSpA group decreased significantly from 3.4 to 1.9 times more than among the population references. The effect was seen on sick leave, whereas disability pension levels remained similar in both groups throughout. Anti-TNF therapy in nr-axSpA was associated with a significant and sustained improvement of work disability over 2 years. However, the proportion of work-loss days remained almost twice as high as in the general population at the end of follow-up.

Impact of Certolizumab Pegol on Patient‐Reported Outcomes in Patients With Axial Spondyloarthritis

ObjectivePatient‐reported outcomes (PROs) provide an opportunity to collect important information relating to patient well‐being, which is often difficult for physicians to measure (e.g., quality of life, pain, fatigue, and sleep). Here we evaluate the effects of certolizumab pegol (CZP) on PROs during the 24‐week, double‐blind phase of the RAPID axial spondyloarthritis (SpA) trial, a phase 3 trial of axial SpA patients, including both ankylosing spondylitis (AS) and nonradiographic axial SpA patients.MethodsA total of 325 patients with active axial SpA were randomized 1:1:1 to placebo, CZP 200 mg every 2 weeks, or CZP 400 mg every 4 weeks. The primary end point was the Assessment of SpondyloArthritis International Society criteria for 20% improvement in disease activity response at week 12, and has been reported previously. PROs included total back pain, nocturnal back pain, a daily pain diary, the Sleep Problems Index II (SPI) domain of the Medical Outcomes Study (MOS) Sleep Scale, fatigue, the Ankylosing Spondylitis Quality of Life (ASQOL) measure, and the Short Form 36‐item (SF‐36) health survey physical component summary (PCS), mental component summary (MCS), and domains.ResultsPatients treated with CZP reported significant improvements from week 1 for nocturnal back pain (placebo −0.6, CZP 200 mg every 2 weeks −1.9, and CZP 400 mg every 4 weeks −1.6; P < 0.001) and ASQOL (placebo −1.0, CZP 200 mg every 2 weeks −2.3, and CZP 400 mg every 4 weeks −1.9; P < 0.05) compared with placebo, while significant improvements in total back pain were seen from day 2. Patients treated with both CZP dosing regimens also had significantly greater improvements in fatigue, MOS‐SPI, SF‐36 PCS, MCS, and domains compared with placebo. Improvements were similar in both AS and nonradiographic axial SpA patients.ConclusionBoth CZP dosing schedules rapidly improved patient well‐being, as measured by PROs, including pain, fatigue, sleep, SF‐36, and ASQOL in both AS and nonradiographic axial SpA patients.

Clinical Disease Pattern and Drug Evaluation of Patients with Seronegative Spondyloarthritis at the Outpatient Department

Objective: There are a number of diseases in the spondyloarthritis (SpA) family. In this study, we evaluated the clinical disease pattern and drug use of outpatient department (OPD) patients with SpA. Methods: During a one-month period, we consecutively enrolled 100 patients with SpA. The diagnosis of ankylosing spondylitis (AS) was based on the modified New York criteria and that of psoriatic arthritis (PsA) followed The ClASsification of Psoriatic ARthritis (CASPAR) criteria. The new Assessment of SpondyloArthritis international Society (ASAS) classification criteria were used for the diagnosis of axial or peripheral SpA. Patients’ demographic characteristics, disease activity and laboratory tests were fully assessed. Medications currently used with the SpA family include non-steroidal anti-inflammatory drugs (NSAIDs) and TNF-α blockers. Results: A total of 100 SpA patients were consecutively enrolled in this short-term OPD survey. The male-to-female ratio of the enrolled patients was about 2:1 (66 males, 34 females). The clinical disease patterns of the 100 patients included 69 AS, 15 PsA, 12 non-radiographic axial SpA and 4 peripheral SpA. Uveitis was the most common extraarticular feature. Patients with positive HLA-B27 had higher Bath Ankylosing Spondylitis Functional Index (BASFI) scores, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores and CRP. Male AS patients seemed to have a higher CRP level and more severe sacroiliitis. AS patients receiving anti-TNFa therapy had significantly higher BASFI and BASDAI scores. AS patients had higher BASFI scores, and erythrocyte sedimentation rate (ESR) and CRP levels but no difference in BASDAI scores when compared to non-radiographic axial SpA patients. In terms of NSAIDs use, 45% of patients took cyclooxygenase-2 (COX-2) inhibitors (celecoxib, etoricoxib), 18% preferential COX-2 inhibitors (meloxicam), 30% nonselective NSAIDs (diclofenac, etodolac, naproxen), and 5% of patients used no NSAIDs. Besides, a higher percentage (33%) of our patients with SpA received regular anti-TNFα therapy (etanercept 17, adalimumab 15, golimumab 1). Conclusion: This OPD survey of Taiwan SpA patients disclosed not a small percentage (16%) of Taiwan SpA patients had either axial or peripheral SpA. The lack of significant difference in the BASDAI between AS and axial SpA suggests anti-TNFα therapy is indicated when traditional NSAIDs fail in axial SpA patients.

Bone formation in axial spondyloarthritis.

The success of targeted therapies directed against tumor necrosis factor for patients with spondyloarthritis has shifted the focus of physicians and scientists towards the prevention of structural damage to the involved structures, in particular the sacroiliac joints and the spine, to avoid loss of function and disability. Structural damage to the skeleton as witnessed by radiography mainly consists of new bone formation potentially progressively leading to spine or joint ankylosis. This important long-term outcome parameter has been difficult to study, not alone because the time window for change may be long but also because human tissues with direct translational relevance are rarely available. Data from rodent models have identified growth factor signaling pathways as relevant targets. Both human and animal studies have tried to understand the link between inflammation and new bone formation. At the current moment, most evidence points towards a strong link between both but with the question still lingering about the sequence of events, disease triggers, and the interdependence of both features of disease. New discoveries such as a masterswitch T cell population that carries the IL23 receptor and the analysis of auto-antibodies directed again noggin and sclerostin are contributing to innovative insights into the pathophysiology of disease. Long-term data with tumor necrosis factor (TNF) inhibitors also suggest that some window of opportunity may exist to inhibit structural disease progression. All these data provide support for a further critical analysis of the available datasets and boost research in the field. The introduction of novel disease definitions, in particular the characterization of non-radiographic axial spondyloarthritis patients, will likely be instrumental in our further understanding of structural damage.

FRI0438 Disease management of ankylosing spondylitis and non-radiographic axial spondyloarthritis patients is similar in academic and community practice among 654 surveyed rheumatologists

BackgroundThe Assessment of SpondyloArthritis International Society (ASAS) has recently updated recommendations for the use of anti-TNF in patients (pts) with axial SpondyloArthritis (axSpA), which include ankylosing spondylitis (AS) and non-radiographic...

Serum levels of biomarkers of bone and cartilage destruction and new bone formation in different cohorts of patients with axial spondyloarthritis with and without tumor necrosis factor-alpha blocker treatment

IntroductionRecent data about radiographic progression during treatment with tumor necrosis factor-alpha (TNF-α) blocker agents in patients with ankylosing spondylitis (AS) have prompted an intensive discussion about the link between inflammation/bone destruction and new bone formation and the order of events. Therefore, we analysed parameters of cartilage degradation, neoangiogenesis, and new bone formation in different cohorts of patients with axial spondyloarthritis with and without treatment with TNF-α blocker agents.MethodTNF-α blocker-naïve AS patients were investigated for serum levels of metalloproteinase-3 (MMP-3) (n = 71), vasoendothelial growth factor (VEGF) (n = 50), and bone-specific alkaline phosphatase (BALP) (n = 71) at baseline and after 1 and 2 years. This was compared with 34 adalimumab-treated patients with axial spondyloarthritis (22 AS and 12 non-radiographic axial spondyloarthritis patients) before and after 36 to 52 weeks of treatment.ResultsThere were no significant changes in serum levels of MMP-3 (P > 0.05), VEGF (P > 0.05), and BALP (P > 0.05) in a large cohort of TNF-α blocker-naïve AS patients followed for 2 years. In contrast, adalimumab-treated spondyloarthritis (AS and non-radiographic axial spondyloarthritis) patients had a significant decrease of VEGF (P < 0.001) and MMP-3 (P = 0.022) after 36 to 52 weeks of therapy. Most interestingly, the level of BALP increased significantly after 36 to 52 weeks of therapy (P < 0.001). A decrease in MMP-3 serum levels correlated significantly to an increase of BALP (r = -0.398, P = 0.02). In the case of VEGF, there was a negative correlation without significance (r = -0.214, P > 0.05).ConclusionsRising levels of BALP and the negative correlation between MMP-3 and BALP in spondyloarthritis patients with TNF-α blocker treatment indicate that new bone formation in AS occurs if inflammation is successfully treated and might be part of a healing process.