OBJECTIVE: To investigate the clinical response at week 52 in patients with ankylosing spondylitis (AS) who received secukinumab 300 vs 150 mg after inadequate response to 150 mg at week 16.
METHODS: ASLeap (NCT03350815) was a randomized, double-blind, parallel-group, multicentre, phase 4 trial. After 16 weeks of open-label secukinumab 150 mg (Treatment Period 1), patients who did not achieve inactive disease (Ankylosing Spondylitis Disease Activity Score [ASDAS] <1.3) at both Weeks 12 and 16 were considered to have an inadequate response and were randomized 1:1 to receive secukinumab 300 or 150 mg every 4 weeks until week 52 (Treatment Period 2). The primary efficacy variable was achievement of ASDAS <1.3 at week 52 using week 16 as baseline. Safety was evaluated by the incidence of treatment-emergent adverse events through week 52.
RESULTS: Of 322 patients treated with secukinumab in Treatment Period 1, 207 (64.3%) had inadequate response. Similar proportions of patients with inadequate response randomized to secukinumab 300 mg (n = 101) and 150 mg (n = 105) in Treatment Period 2 completed the study (83.8% and 84.3%, respectively). At week 52, 8.8% and 6.7% of patients receiving secukinumab 300 and 150 mg, respectively, achieved ASDAS <1.3. The incidence of treatment-emergent adverse events was similar in both groups through week 52. No new safety signals were observed.
CONCLUSIONS: Patients with AS who did not achieve ASDAS <1.3 after receiving secukinumab 150 mg for 16 weeks experienced similar clinical response and safety through week 52 regardless of dose escalation.
BACKGROUND: ClinicalTrials.gov, NCT03350815.

OBJECTIVE: To develop a CT-based scoring system for assessment of hip arthropathy in AS.
METHODS: All AS patients were prospectively recruited, consented, and underwent whole-body stereoradiographs and pelvis CT, which were assessed by two independent radiologists. Stereoradiographs were assessed according to Kellgreen-Lawrence and BASRI-h. For the Hip arthropathy CT score in AS (HACTSAS), joints were divided into 7 segments and scored for joint space, osteophytes, subchondral cysts/erosions. Patients were clinically assessed for range of motion (ROM), pain, and clinical scores (BASMI, BASFI, ASQol, BASDAI and ASDAS). Radiological scores correlations with clinical parameters were compared. ROM sensitivity and specificity for hip arthropathy (BASRI-h ≥ 2) were calculated.
RESULTS: Sample included 112 patients, with 36/112 females and 76/112 males. Average age was 51.0 ± 11.2 years and mean duration of AS was 20.9 ± 9.6 years. ICC for HACTSAS, Kellgreen-Lawrence and BASRI-h were 0.89, 0.89 and 0.82 respectively. HACTSAS showed moderate absolute correlation with ROM (ρ=-0.41) and BASMI (ρ = 0.45), and weak with pain (ρ = 0.18) and BASFI (ρ = 0.25). BASRI-h and Kellgreen-Lawrence exhibited moderate correlation with ROM (ρ=-0.44 and ρ=-0.40, respectively), weak with pain (ρ=-.27and ρ=-0.23, respectively) and BASFI (ρ=-0.16 and ρ=-0.18, respectively), but only weak with BASMI (ρ=-0.34 and ρ=-0.36, respectively). Internal rotation <15°, abduction <31°, and intermalleolar distance <75cm were, respectively, 73%, 70% and 73% sensitivity and 81%, 65% and 68% specific for hip arthropathy.
CONCLUSIONS: HACTSAS exhibited higher correlation with BASMI and BASFI when compared with BASRI-h, but less correlation with pain and ROM. Internal rotation was the best clinical discriminator for hip arthropathy.

暂无摘要。

UNASSIGNED: Ankylosing spondylitis (AS), an autoimmune disease, often leads to lower cervical spine fractures, with the potential for severe spinal nerve damage even from low-energy injuries. The optimal treatment approach remains debated.
UNASSIGNED: A retrospective study involved 17 AS patients with lower cervical spine fractures who received anterior cervical fixation. Most presented cervicothoracic or thoracolumbar kyphosis, with 11 exhibiting neurological deficits. Patient characteristics, clinical data, visual analog scale (VAS), complications, and nerve recovery were analyzed.
UNASSIGNED: No postoperative neurological deterioration occurred. All cases experienced complete fusion of fractures during the follow-up period. Preoperative VAS significantly decreased at 3 days and 3 months post-surgery. Of the 11 patients with preoperative neurological deficits, approximately 54.5% showed improvement post-surgery. No complications were reported, such as esophageal fistula, wound infection, or fixation failure.
UNASSIGNED: Anterior internal fixation is a possible treatment for AS-related lower cervical fractures. This approach ensures satisfactory spinal stability and neurological recovery with proper cranial traction and external fixation post-surgery. Our findings demonstrate that this surgical method is safe and effective.

OBJECTIVE: Our aim in this study is to compare patients with ankylosing spondylitis (AS), a rheumatologic disease that can cause eye involvement and the normal population in terms of orbital Doppler findings, which is an inexpensive and easily applicable method that can be used in early diagnosis and follow-up.
METHODS: The study was planned prospectively. The data of patients with AS were compared to those of age- and gender-matched healthy volunteers. A total of 42 participants, 23 (54.8%) males and 19 (45.2%) females, with a mean age of 42.4±12.6 years were included in the study. In addition to demographic information, such as age and gender, the diameter, peak systolic velocity, end-diastolic velocity, mean velocity, resistive index, pulsatility index, and blood flow volumes of the central retinal artery of the left eye were measured using spectral Doppler ultrasonography.
RESULTS: According to the comparison of the patients with and without AS according to orbital Doppler ultrasonography findings, the mean velocity, resistive index, and volume measurements of the patients with AS were significantly higher than those without AS (p=0.028, p=0.039, and p=0.038, respectively). However, in the subgroup analysis of the AS group, the Doppler findings did not significantly differ between the patients with and without anterior uveitis.
CONCLUSIONS: In the patient group with AS, independent of anterior uveitis (AU), there was a difference in Doppler parameters and therefore in ophthalmic vasculature. In patients with AS, orbital vascularity changes can be detected with orbital Doppler US before clinical signs appear.

UNASSIGNED: Current observational investigations hint at a potential linkage between ankylosing spondylitis and cardiovascular wellness. However, the nature of this causality remains to be elucidated. Consequently, this study is designed to evaluate the causal interconnection between ankylosing spondylitis and cardiovascular-related conditions utilizing a bidirectional two-sample Mendelian Randomization (MR) methodology.
UNASSIGNED: In this study, we conducted Mendelian randomization (MR) analyses using genome-wide association study (GWAS) data. The fixed-effects inverse variance weighted (IVW) model was used as the primary analysis method, and MR-Egger regression and the weighted median method were employed as supplementary approaches. Horizontal pleiotropy and heterogeneity were evaluated using various statistical tests, including MR-PRESSO global test, MR-Egger intercept, and Cochran\'s Q test.
UNASSIGNED: The MR result demonstrated an increased risk of heart failure in individuals with ankylosing spondylitis (OR: 1.0132, 95% CI = 1.0043-1.0221, p = 0.003). The MR analysis results did not demonstrate a causal relationship between ankylosing spondylitis and other cardiovascular diseases, such as atrial fibrillation, coronary artery disease, ischemic stroke, myocardial infarction, and valvular heart disease (all p > 0.05). No evidence of reverse causality was found between ankylosing spondylitis and mentioned cardiovascular diseases in reverse MR analyses. Sensitivity analysis verified the reliability of the results.
UNASSIGNED: Our MR study indicates a relationship between ankylosing spondylitis and an increased risk of heart failure. Further research is needed to confirm these findings and elucidate the underlying mechanisms involved.

UNASSIGNED: Accumulating evidence suggests that patients with ankylosing spondylitis (AS) have an elevated risk for cardiovascular disease (CVD) and cardiovascular death, however, whether AS has causal effects on the risk of CVD is unclear.Two-sample Mendelian randomization (MR) was utilizedto examine the probable causal link between them.
UNASSIGNED: Summary statistics from publicly released genome-wide association studies (GWAS) was used to perform MR analyses. Genetically predicted AS was selected as the exposure variable from published GWAS meta-analyses. CVD was adopted as the outcome variable. The inverse variant weighted method was employed to obtain the casual estimates. The robustness of the results was also examined by evaluating the pleiotropy and heterogeneity of single-nucleotide polymorphisms.
UNASSIGNED: According to MR analyses, genetic susceptibility to AS was associated with a high risk of heart failure and ischemic stroke, while negativelygenetic susceptibility was found between AS and peripheral atherosclerosis. No statistical relationship was found between AS and venous thromboembolism, atrial fibrillation, coronary atherosclerosis, and valvular heart disease. Sensitivity analysis showed no evidence of horizontal pleiotropy or heterogeneity.
UNASSIGNED: The present study suggests that AS exerts causal effects on the risk of CVD, including heart failure, ischemic stroke, and peripheral atherosclerosis.

Clinical data on the use of tumour necrosis factor inhibitors (TNFi) in late-onset ankylosing spondylitis (LoAS) are limited. The present study aimed to evaluate efficacy, safety, and treatment adherence associated with the initial use of TNFi therapy in biologic naive patients diagnosed with LoAS. Patients whose age of onset was ≥ 45 years and < 45 years were classified as having LoAS and YoAS, respectively, based on the age of symptom onset. There were 2573 patients with YoAS and 281 LoAS. Baseline disease activity measures were similar between the groups. No significant differences were seen between the two groups in response to treatment and in remaining on the first TNFi at 6, 12 and 24 months. In the LoAS group, the analysis showed that TNFi discontinuation was linked to VAS pain score (HR 1.04; 95% CI 1.01-1.06). Patient groups had similar rates of adverse events (YoAS: 8.7% vs. LoAS: 11.7%). In both biologic naive LoAS and YoAS patients, the study showed that the initial TNFi therapy was equally effective and safe.

BACKGROUND: Interleukin-17A (IL-17A) plays a crucial role in the pathogenesis of ankylosing spondylitis (AS), although not all patients respond to traditional IL-17A antibody treatments. QX002N injection, as a new monoclonal antibody targeting IL-17A, has shown potential in treating AS, offering a new treatment option for patients who do not respond well to existing therapies.
METHODS: A randomized, open, parallel, single-center, phase I study was conducted to assess the pharmacokinetics, safety, and immunogenicity of single doses of QX002N injection administered intravenously (IV) or subcutaneously (SC) to healthy Chinese volunteers. Blood samples were collected at specified time intervals, and then serum concentrations of QX002N were analyzed by enzyme-linked immunosorbent assay.
RESULTS: Pharmacokinetic analysis of the drug concentration-time data showed that the mean maximum observed serum QX002N concentration (Cmax) was 110 and 33.9 µg/ml, respectively. The average area under the drug concentration-time curves from 0 to the time of the last quantifiable concentration (AUClast) were 52,656 and 36,269 µg·h/ml, respectively and the average area under the drug concentration-time curves from 0 to infinity (AUCinf) were 54,867 and 38,194 µg·h/ml, respectively. The absolute bioavailability of QX002N after SC injection was 69.6%.
CONCLUSIONS: Immunogenicity was assessed and all the subjects in this study were Anti-drug antibody (ADA)-negative, which means no subjects appeared to develop immunogenicity to QX002N. All the results testify to the safety of QX002N injection, which is satisfactory after IV or SC dosing in healthy subjects.
BACKGROUND: www.chinadrugtirals.org.cn , CTR20220430.

OBJECTIVE: Immune checkpoints have emerged as promising therapeutic targets for autoimmune diseases. However, the specific roles of immune checkpoints in the pathophysiology of ankylosing spondylitis (AS) remain unclear.
METHODS: Hip ligament samples were obtained from two patient groups: those with AS and femoral head deformity, and those with femoral head necrosis but without AS, undergoing hip arthroplasty. Label-Free Quantification (LFQ) Protein Park Analysis was used to identify the protein composition of the ligaments. Peripheral blood samples of 104 AS patients from public database were used to validate the expression of key proteins. KEGG, GO, and GSVA were employed to explore potential pathways regulated by immune checkpoints in AS progression. xCell was used to calculate cell infiltration levels, LASSO regression was applied to select key cells, and the correlation between immune checkpoints and immune cells was analyzed. Drug sensitivity analysis was conducted to identify potential therapeutic drugs targeting immune checkpoints in AS. The expression of key genes was validated through immunohistochemistry (IHC).
RESULTS: HLA-DMB and HLA-DPA1 were downregulated in the ligaments of AS and this has been validated through peripheral blood datasets and IHC. Significant differences in expression were observed in CD8 + Tcm, CD8 + T cells, CD8 + Tem, osteoblasts, Th1 cells, and CD8 + naive T cells in AS. The infiltration levels of CD8 + Tcm and CD8 + naive T cells were significantly positively correlated with the expression levels of HLA-DMB and HLA-DPA1. Immune cell selection using LASSO regression showed good predictive ability for AS, with AUC values of 0.98, 0.81, and 0.75 for the three prediction models, respectively. Furthermore, this study found that HLA-DMB and HLA-DPA1 are involved in Th17 cell differentiation, and both Th17 cell differentiation and the NF-kappa B signaling pathway are activated in the AS group. Drug sensitivity analysis showed that AS patients are more sensitive to drugs such as doramapimod and GSK269962A.
CONCLUSIONS: Immune checkpoints and immune cells could serve as avenues for exploring diagnostic and therapeutic strategies for AS.