To be or not to B27 positive: implications for the phenotypes of axial spondyloarthritis outcomes. Data from a large multiracial cohort from the Brazilian Registry of Spondyloarthritis.

BACKGROUND: There is a remarkable variability in the frequency of HLA-B27 positivity in patients with spondyloarthritis (SpA), which may be associated with different clinical presentations worldwide. However, there is a lack of data considering ethnicity and sex on the evaluation of the main clinical and prognostic outcomes in mixed-race populations. The aim of this study was to evaluate the frequency of HLA-B27 and its correlation with disease parameters in a large population of patients from the Brazilian Registry of Spondyloarthritis (RBE). METHODS: The RBE is a multicenter, observational, prospective cohort that enrolled patients with SpA from 46 centers representing all five geographic regions of Brazil. The inclusion criteria were as follow: (1) diagnosis of axSpA by an expert rheumatologist; (2) age ≥18 years; (3) classification according to ASAS axial. The following data were collected via a standardized protocol: demographic data, disease parameters and treatment historical. RESULTS: A total of 1096 patients were included, with 73.4% HLA-B27 positivity and a mean age of 44.4 (±13.2) years. Positive HLA-B27 was significantly associated with male sex, earlier age at disease onset and diagnosis, uveitis, and family history of SpA. Conversely, negative HLA-B27 was associated with psoriasis, higher peripheral involvement and disease activity, worse quality of life and mobility. CONCLUSIONS: Our data showed that HLA-B27 positivity was associated with a classic axSpA pattern quite similar to that of Caucasian axSpA patients around the world. Furthermore, its absence was associated with peripheral manifestations and worse outcomes, suggesting a relevant phenotypic difference in a highly miscegenated population.

Effectiveness and safety of secukinumab in ankylosing spondylitis and psoriatic arthritis: a 52-week real-life study in an Italian cohort.

BACKGROUND: Secukinumab has shown high efficacy in randomized controlled trials in both ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Here, we investigated its real-life effectiveness and tolerability in a cohort of AS and PsA patients. METHODS: We retrospectively analyzed medical records of outpatients with AS or PsA treated with secukinumab between December 2017 and December 2019. ASDAS-CRP and DAS28-CRP scores were used to measure axial and peripheral disease activity in AS and PsA, respectively. Data were collected at baseline and after 8, 24, and 52 weeks of treatment. RESULTS: Eighty-five adult patients with active disease (29 with AS and 56 with PsA; 23 males and 62 females) were treated. Overall, mean disease duration was 6.7 years and biologic-naïve patients were 85%. Significant reductions in ASDAS-CRP and DAS28-CRP were observed at all time-points. Body weight (in AS) and disease activity status at baseline (particularly in PsA) significantly affected disease activity changes. ASDAS-defined inactive disease and DAS28-defined remission were achieved in comparable proportions between AS and PsA patients, at both 24 weeks (45% and 46%) and 52 weeks (65.5% and 68%, respectively); male sex was found an independent predictor of positive response (OR 5.16, P = 0.027). After 52 weeks, achievement of at least low disease activity and drug retention were observed in 75% of patients. Secukinumab was well-tolerated and only mild injection-site reactions were recorded in 4 patients. CONCLUSION: In a real-world setting, secukinumab confirmed great effectiveness and safety in both AS and PsA patients. The influence of gender on treatment response deserves further attention.

Effectiveness and safety of secukinumab in ankylosing spondylitis and psoriatic arthritis: a 52-week real-life study in an Italian cohort

Abstract Background Secukinumab has shown high efficacy in randomized controlled trials in both ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Here, we investigated its real-life effectiveness and tolerability in a cohort of AS and PsA patients. Methods We retrospectively analyzed medical records of outpatients with AS or PsA treated with secukinumab between December 2017 and December 2019. ASDAS-CRP and DAS28-CRP scores were used to measure axial and peripheral disease activity in AS and PsA, respectively. Data were collected at baseline and after 8, 24, and 52 weeks of treatment. Results Eighty-five adult patients with active disease (29 with AS and 56 with PsA; 23 males and 62 females) were treated. Overall, mean disease duration was 6.7 years and biologic-naïve patients were 85%. Significant reductions in ASDAS-CRP and DAS28-CRP were observed at all time-points. Body weight (in AS) and disease activity status at baseline (particularly in PsA) significantly affected disease activity changes. ASDAS-defined inactive disease and DAS28-defined remission were achieved in comparable proportions between AS and PsA patients, at both 24 weeks (45% and 46%) and 52 weeks (65.5% and 68%, respectively); male sex was found an independent predictor of positive response (OR 5.16, P = 0.027). After 52 weeks, achievement of at least low disease activity and drug retention were observed in 75% of patients. Secukinumab was well-tolerated and only mild injection-site reactions were recorded in 4 patients. Conclusion In a real-world setting, secukinumab confirmed great effectiveness and safety in both AS and PsA patients. The influence of gender on treatment response deserves further attention.

Disease activity indexes might not capture the same disease aspects in males and females with ankylosing spondylitis: A real-world nationwide analysis.

Background: To evaluate gender differences in disease activity and health status (HS) in patients with radiographic axial spondyloarthritis (r-axSpA)/ankylosing spondylitis (AS). Methods: Ancillary analysis of the MIDAS study, an observational, non-interventional, cross-sectional and retrospective multicenter nationwide study to assess disease activity and its relationship with HS in clinical practice. Adult patients with AS diagnosis, fulfilling ASAS and modified New York criteria, treated for ≥3 months upon study inclusion according to clinical practice were included. The primary outcome was "disease control" assessed by the percentage of patients in remission and low disease activity (BASDAI and ASDAS-CRP scores). HS was evaluated using the ASAS health index (ASAS-HI). Patients' responses and characteristics were analyzed by gender. Results: We analyzed 313 patients with AS, 237 (75.7%) males and 76 (24.3%) females. A total of 202 (64.5%) patients had adequate disease control (BASDAI < 4); 69.2% of males [mean (SD) BASDAI 2.9 (2.1)] and 50.0% of females [mean (SD) BASDAI 3.8 (2.4); p = 0.01]. According to ASDAS-CRP, 57.5% of patients were adequately controlled (ASDAS-ID +ASDAS-LDA); 138 (58.2%) males and 42 (55.3%) females. The mean (SD) ASDAS-CRP was 1.9 (1.1); being 1.9 (1.0) in males and 2.0 (1.1) in females. Overall, the impact of AS on HS was low to moderate [mean (SD) ASAS-HI 5.8 (4.4)]; being 5.5 (4.4) for males and 6.8 (4.2) for females (p = 0.02). Conclusion: This study showed a higher proportion of females with AS and active disease using the BASDAI definition. When using the ASDAS-CRP definition these differences by gender were less pronounced. The impact of disease activity on HS appears to be higher in females than males.

The relationship between CRP gene polymorphism (rs2794521, rs3091244), ASDAS-CRP and ASDAS-ESR in ankylosing spondylitis.

Background: We aimed to investigate the haplotypes and alleles of two variants (rs2794521 and rs3091244) in AS patients and to examine their relationship with ASDAS-CRP and ASDAS-ESR values.Methods: We evaluated 160 AS patients diagnosed according to the ASAS criteria. ASDAS-CRP and ASDAS-ESR values were calculated. ESR and CRP were examined. The restriction fragment length polymorphism (RFLP) method was used for detecting the rs2794521 and rs3091244 regions on the CRP gene.Results: As a result of the evaluation of rs2794521 gene polymorphism using PCR, TT, TC and CC genotypes were observed in 90, 81 and 9 individuals, respectively. As a result of the evaluation of rs3091244 gene polymorphism, CC, AC and TT genotypes were observed in 104, 51 and 5 individuals, respectively. T allele and C allele were found in rs2794521 gene by 75% and 25%, respectively. In addition, T allele, C allele and A allele were found in rs3091244 gene by 80%, 17% and 3%, respectively. With the help of regression equation, ASDAS-CRP level was 0.34 units higher in cases with rs3091244 C allele than cases without rs3091244 C alleles.Conclusion: CRP rs3091244 C allele may be associated with the increased relative risk for ASDAS-CRP.

Validity and reliability of the Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in patients with axial spondyloarthritis (axSpA) in Singapore.

INTRODUCTION: The Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) are commonly used instruments for measuring disease activity. However, few studies have assessed their psychometric properties in patients with axial spondyloarthritis (axSpA). We aimed to assess the validity and reliability of ASDAS-CRP and BASDAI in patients with axSpA in Singapore. METHODS: Cross-sectional data from 280 patients with axSpA from a dedicated axSpA clinic in a Singapore tertiary referral hospital from 2011 to 2019 were used. Internal consistency was assessed using Cronbach's alpha. Construct validity was assessed through 12 a priori hypotheses by correlation of overall ASDAS-CRP and BASDAI score with other patient-reported outcomes measures (PROMs). Structural validity was evaluated via confirmatory factor analysis using maximum-likelihood method, where Comparative Fit Index (CFI) >0.95, Tucker-Lewis Index (TLI) >0.95, Root Mean Square Error of Approximation (RMSEA) <0.06 and Standardized Root Mean Residuals (SRMR) <0.08 were indicative of good fit. RESULTS: Among 280 patients (78.2% Male; 92.5% Chinese), ASDAS-CRP showed poor internal consistency of 0.33, while BASDAI showed high internal consistency of 0.87. Convergent and divergent construct validity were demonstrated by fulfillment of 11 out of 12 a priori hypotheses when ASDAS-CRP and BASDAI were compared with other PROMs. Our proposed ASDAS-CRP and BASDAI model showed good fit for a 1-factor structure respectively (CFI = 0.993, TLI = 0.984, RMSEA = 0.036, SRMR = 0.026 for ASDAS-CRP; CFI = 0.993, TLI = 0.985, RMSEA = 0.057, SRMR = 0.022 for BASDAI), demonstrating structural validity. CONCLUSION: This study supports the use of both ASDAS-CRP and BASDAI in measuring disease activity in patients with axSpA in Singapore.

Disease Activity and Patient-Reported Health Measures in Relation to Cytokine Levels in Ankylosing Spondylitis.

INTRODUCTION: Ankylosing spondylitis (AS) is a lifelong condition where spinal inflammation causes chronic back pain and restriction of spinal function. While proinflammatory cytokines participate in the disease process, their relation with disease activity, spinal function, and quality of life is less well understood. METHODS: Cross-sectional study of serum levels of four inflammatory cytokines (IL-6, TNF, IL-23, and IL-17A) in AS patients not on biologics. Disease characteristics and simultaneous spinal function tests and patient-reported health measures (Bath Functional Index (BASFI), Dougados Functional Index (DFI), Modified Health Assessment Questionnaire (MHAQ), and routine laboratory parameters were recorded. The composite ASDAS-CRP score was used to classify disease activity as absent, low, or high. RESULTS: In 164 AS patients (age 46 years, 70.1% males, 90.9% HLAB27 positive, ASDAS-CRP 1.8), disease activity was classified as inactive in 14%, low in 54%, and high in 31%. ASDAS-CRP correlated well with MHAQ, DFI, BASFI, and spinal mobility across patients with low and high disease activity (all p < 0.05). Cytokine levels did not correlate with ASDAS-CRP, ESR, BASFI, or spinal mobility scores and were comparable between patients with no, low, or high disease activity regardless of gender or disease duration (all p > 0.2). CONCLUSIONS: A large proportion of AS not on biologics have active disease far into the disease course. This impacts negatively on quality of life, work ability, and spinal mobility. Serum cytokine levels are poor markers for these central disease features in AS management. FUNDING: Abbott Norway AS and Arthritis Foundation of Western Australia.