Identification of the first signs or symptoms in different spondyloarthritis subtypes and their association with HLA-B27: data from REGISPONSER and RESPONDIA registries.

OBJECTIVE: To describe and analyse the initial symptoms attributable to patients with spondyloarthritis (SpA) and their association with HLA-B27 status. METHODS: This was an observational, cross-sectional and multicentre study with patients who fulfilled the European Spondyloarthropathy Study Group criteria for SpA from the Registry of Spondyloarthritis of Spanish Rheumatology (REGISPONSER) and Ibero-American Registry of Spondyloarthropathies (RESPONDIA) united registries. Differences in the first sign(s) or symptom(s) were compared across diagnoses and between HLA-B27 status. The diagnostic delay between patients who start the disease with musculoskeletal manifestations (MMs) and extra-MMs (EMMs) was compared. RESULTS: A total of 4067 patients were included (2208 from REGISPONSER and 1859 from RESPONDIA) (ankylosing spondylitis (AS): 68.3%, psoriatic arthritis (PsA): 19.9%, undifferentiated SpA: 11.8%). Overall, 3624 (89.1%) patients initiated the disease with MMs and 443 (10.9%) with EMMs. Low back pain (61.7%) and lower-limb arthritis (38.5%) were the most frequent initial symptoms. In AS patients, the absence of HLA-B27 seems to be related to an increase in the probability of starting the disease with cervical pain and peripheral manifestations. In PsA, the onset of arthritis and psoriasis was more prevalent in HLA-B27-negative patients, while initiation with axial manifestations was more predominant in HLA-B27-positive patients. The diagnostic delay was longer in patients with initial MMs than in those with EMMs (7.2 (34.8) vs 4.5 (7.6) years, respectively). CONCLUSION: In this SpA population, MMs were the most prevalent initial symptoms, with differences across diagnoses and depending on the presence of the HLA-B27 antigen.

Differences between early vs. late-onset of psoriatic arthritis: Data from the RESPONDIA and REGISPONSER registries.

OBJECTIVES: The objective was to evaluate the association between the age at onset of psoriatic arthritis (PsA) symptoms with the characteristics and burden of the disease. METHODS: This was an observational and cross-sectional study that included a subgroup of 231 patients with PsA with < 10 years of disease duration from the REGISPONSER and RESPONDIA registries. Patients were divided into two groups according to the age of PsA symptom onset (early onset: ≤ 40-years-old and late onset: ≥ 60-years-old). The characteristics and burden of the disease were compared between the two groups, and multivariate logistic regression was performed to determine the factors independently associated with late-onset PsA. RESULTS: Patients from the early-onset group showed a significantly lower prevalence of males [94 (62.3%) vs. 38 (86.4%)] and a higher prevalence of enthesitis [44 (24.6%) vs. 5 (9.8%)] and sacroiliitis [30 (16.8%) vs. 4 (7.7%)]. Additionally, the early-onset group showed lower scores on the BASFI [2.2 (2.2) vs. 3.3 (2.5)] and minor structural damage (BASRI) in both the spine [1.6 (2) vs. 2.9 (3)] and whole axial skeleton (total BASRI) [1.9 (2.4) vs. 3.4 (3.4)]. In contrast, no statistically significant differences were found between the groups in disease activity evaluated by the BASDAI and ASDAS. Logistic regression analysis showed that late-onset PsA was independently associated with being male (OR 4.4, 95% CI: 1.3, 16.3), greater structural damage (total BASRI) (OR 3.3, 95% CI: 1.3, 8.1), a higher frequency of arthritis in the upper limbs (OR 2.8, 95% CI: 1, 7.7), and greater loss of function (BASFI) (OR 1.3, 95% CI: 1, 1.6). CONCLUSIONS: Patients with late-onset PsA showed different clinical characteristics and greater disease severity than those with early-onset PsA.

Achilles enthesitis on physical examination leads to worse outcomes after 2 years of follow up in patients with ankylosing spondylitis from REGISPONSER-AS registry.

BACKGROUND: Enthesitis represents one of the most important peripheral musculoskeletal manifestations in patients with axial spondyloarthritis (axSpA). However, studies specifically evaluating Achilles tendon enthesitis and its impact over time are scarce. The objectives of this study were to evaluate the impact of Achilles' tendon enthesitis found at baseline during physical examination on the outcome measures after 2 years of follow-up in patients with ankylosing spondylitis (AS). METHODS: This was an observational and prospective study conducted during 2 years of follow-up in the REGISPONSER-AS registry. Linear regression models adjusted for age, body mass index (BMI), and anti-TNF intake were conducted to evaluate the association between the presence of Achilles enthesitis at baseline and the patient-reported outcome (PRO) scores at baseline. The impact of this feature on PROs over 2 years of follow-up was evaluated using mixed models for repeated measures adjusted for age, BMI, and anti-TNF intake. RESULTS: Among the 749 patients included, 46 patients (6.1%) showed Achilles' tendon enthesitis during physical examination at the baseline study visit. Patients with Achilles enthesitis had an increase in the global VAS score, BASDAI, mBASDAI, ASDAS-CRP, and BASFI scores in comparison with patients without this feature. In addition, the mean global VAS, BASDAI, and ASDAS-CRP scores were significantly higher among patients with Achilles enthesitis over the 2 years of follow-up after adjusting for age, BMI, and current anti-TNF intake. The percentage of patients achieving ASDAS low disease activity (ASDAS < 2.1) after 2 years of follow-up was 15.9% and 31.5% for patients with and without Achilles enthesitis, respectively (p = 0.030). CONCLUSIONS: In patients with AS, the presence of Achilles' tendon enthesitis was associated with worse scores on the outcome measures after 2 years of follow-up, leading to a lower probability of achieving low disease activity.

Impact of the number of comorbidities on the outcome measures and on the retention rate of the first anti-TNF in patients with Ankylosing Spondylitis. Two-year follow-up in REGISPONSER-AS.

OBJECTIVES: To evaluate the impact of the number of comorbidities on the outcome measures after two years of follow-up in patients with Ankylosing Spondylitis (AS) and to determine whether the number of comorbidities influences the retention rate of the first anti-TNF. METHODS: This was an observational and prospective study conducted during 2 years of follow-up in the REGISPONSER-AS registry. The patients were divided into three groups according to the number of comorbidities at baseline (0, 1 or ≥2). Linear regression models adjusted for disease duration, age, sex and smoking were constructed to evaluate the association between the number of comorbidities and the Patient Reported Outcomes (PRO) scores. The impact of the number of comorbidities on PROs over two years of follow-up was evaluated using mixed models for repeated measures adjusted for disease duration, age, sex and smoking. Finally, the retention rate of the first anti-TNF antibody across the three groups was evaluated using a log-rank test. RESULTS: Patients with two or more comorbidities showed higher scores at baseline and during the two years of follow-up for the Global VAS, BASDAI, ASDAS, and BASFI and worse scores for the physical component of the SF12. A higher probability of discontinuation of the first anti-TNF was found in patients with 2 or more comorbidities compared with the patients in the other groups (38.2% vs. 26.6% vs. 25.4% for ≥2 comorbidities, 0 and 1 comorbidity, respectively), although these differences were not significant (log-rank test: p-value = 0.180). CONCLUSION: In patients with AS, the presence of 2 or more comorbidities was associated with worse scores on the outcome measures test after two years of follow-up and a greater tendency of discontinuation for the first anti-TNF.

ASAS Health Index in patients with spondyloarthritis and its association with disease activity and disease burden including fibromyalgia.

OBJECTIVES: To evaluate the association of the Assessment of Spondyloarthritis international Society Health Index (ASAS-HI) with disease activity and disease burden in patients with spondyloarthritis (SpA). METHODS: Observational, cross-sectional and single-centre study from the Córdoba AxSpA Task force, Registry and Outcomes (CASTRO). Scores related to disease activity (BASDAI and ASDAS), functionality (BASFI), structural damage, mobility, health and the presence of concomitant fibromyalgia (FM) were obtained from all patients. ASAS-HI score was considered the main outcome. Pearson's r statistic, Student's t test, and univariate and multivariate linear regressions were performed to assess the association between the ASAS-HI score and the studied covariates. RESULTS: A total of 126 SpA patients were included. The mean ASAS-HI score was 4.6±3.9, showing a "strong" positive linear correlation (r>0.60) with the BASDAI and BASFI and a "moderate" positive linear correlation (r=0.40 to 0.60) with the global VAS and ASDAS. Patients with FM showed a significantly higher ASAS-HI score than patients without FM (9.5±3.2 vs. 3.7±3.4, respectively, p<0.01). Multiple linear regression showed that 57.4% of the ASAS-HI variability (R2=0.574) was explained by the presence of concomitant FM (ß=2.23, 95% CI 0.73 to 3.80, p=0.004), higher scores on the BASDAI (ß=0.62, 95% CI 0.25 to 0.97, p=0.001) and BASFI (ß=0.57, 95% CI 0.26 to 0.88, p=0.001). CONCLUSIONS: The impairment of health in patients with SpA was mainly associated with high disease activity, worsening functionality and with the presence of a possible concomitant FM. Therefore, in patients with high ASAS-HI scores we must evaluate the presence of concomitant FM.

Complement component 3 as biomarker of disease activity and cardiometabolic risk factor in rheumatoid arthritis and spondyloarthritis.

OBJECTIVE: To analyze the relationship between complement component 3 (C3) and the prevalence of cardiometabolic risk factors and disease activity in the rheumatic diseases having the highest rates of cardiovascular morbidity and mortality: rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). METHODS: This is a cross-sectional study including 200 RA, 80 PsA, 150 axSpA patients and 100 healthy donors. The prevalence of cardiometabolic risk factors [obesity, insulin resistance, type 2 diabetes mellitus, hyperlipidemia, apolipoprotein B/apolipoprotein A (apoB/apoA) and atherogenic risks and hypertension] was analyzed. Serum complement C3 levels, inflammatory markers and disease activity were evaluated. Cluster analysis was performed to identify different phenotypes. Receiver operating characteristic (ROC) curve analysis to assess the accuracy of complement C3 as biomarker of insulin resistance and disease activity was carried out. RESULTS: Levels of complement C3, significantly elevated in RA, axSpA and PsA patients, were associated with the prevalence of cardiometabolic risk factors. Hard clustering analysis identified two distinctive phenotypes of patients depending on the complement C3 levels and insulin sensitivity state. Patients from cluster 1, characterized by high levels of complement C3 displayed increased prevalence of cardiometabolic risk factors and high disease activity. ROC curve analysis showed that non-obesity related complement C3 levels allowed to identify insulin resistant patients. CONCLUSIONS: Complement C3 is associated with the concomitant increased prevalence of cardiometabolic risk factors in rheumatoid arthritis and spondyloarthritis. Thus, complement C3 should be considered a useful marker of insulin resistance and disease activity in these rheumatic disorders.