Therapeutic potential of spironolactone in ankylosing spondylitis patients: Relation to disease activity and functional status

Aim of the workSpironolactone with its anti-inflammatory and immunomodulatory properties due to inhibition of nuclear factor kappa B could have a therapeutic potential in ankylosing spondylitis (AS). The aim was to study the impact of spironolactone in active AS patients with an inadequate response to synthetic disease modifying antirheumatic drugs (sDMARDs).Patients and methodsSixty AS patients were randomized to receive 24 weeks of treatment with spironolactone (n = 30, 2 mg/kg/day) or placebo (n = 30) as an adjunct to existing stables DMARDs. Therapy results evaluated by assessment of inflammatory measures erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath AS disease activity index (BASDAI), AS disease activity score (ASDAS) and Bath AS functional index (BASFI), and proinflammatory cytokines (TNF-α,IL-6 and IL-1). Endothelial progenitor cells (EPCs), flow-mediated dilatation (FMD), oxidative measures (TBARS and serum nitrite) were assessed as surrogates for cardiovascular endpoints.ResultsAfter 24 weeks: inflammatory and disease activity measures ESR, CRP, ASDAS, BASDAI, and BASFI (All p < 0.001) were significantly reduced after treatment with spironolactone but did not show significant change in the placebo group (p > 0.05). Proinflammatory cytokines, TNF-α and IL-6, significantly reduced after treatment (both p < 0.001) in spironolactone arm. After 24 weeks treatment, surrogates of vascular function including EPCs, FMD and oxidative measures significantly improved in spironolactone treated patients.ConclusionSpironolactone in AS inhibits the proinflammatory cytokines and has antioxidative action, improves ESR and CRP with improvement in inflammatory disease activity. It reduces nitrite and improves EPC population with resultant improvement of endothelial dysfunction. Spironolactone has anti-inflammatory, immunomodulatory and vasculoprotective potential in AS.     

Association of macroscopic gut inflammation with disease activity, functional status and quality of life in ankylosing spondylitis

The aim of this cross-sectional study was to evaluate the frequency of intestinal inflammation and its association with disease activity, functional status and quality of life in patients with ankylosing spondylitis (AS). A total of 25 patients with AS had undergone ileocolonoscopy and concomitant histological study. Clinical and demographical parameters, BASDAI, BASFI, and SF-36 scores were compared between patients with and without macroscopic gut inflammation (MGI). Colonoscopic study revealed MGI in 9 patients and macroscopically normal gut mucosa in 16 patients. On histological examination, of 25 patients 20 had gut inflammation, mostly in ileum. BASDAI score was higher (P < 0.05), SF-36 pain and physical scores, and chest expansion measurement were lower (P = 0.00, P = 0.01, P = 0.01), duration of morning stiffness was longer (P = 0.01) in patients with MGI. Serum C-reactive protein, erytrocyte sedimentation rate levels were similar between groups (P > 0.05). There is high prevalence of histological gut inflammation in AS patients. More active disease should suggest gut inflammation in AS patients.     

A longitudinal study of disease activity and functional status in a hospital cohort of patients with ankylosing spondylitis

OBJECTIVE: To evaluate changes in functional status and disease activity and their determinants in patients with ankylosing spondylitis (AS) attending hospital, using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI). METHODS: Patients completed BASDAI and BASFI questionnaires annually from 1996 to 2001. Demographic and clinical data were collected. The mean first and last recorded scores were compared. The change per year and area under the curve per year for the BASDAI and BASFI were calculated. Relationships between demographic, clinical and longitudinal BASDAI/BASFI data were examined. Subgroup analyses were performed using the cross-sectional and longitudinal data. RESULTS: Two hundred and seventy-nine BASDAI and 322 BASFI questionnaires were analysed. The BASFI increased [mean change 6.15, 95% confidence interval (CI) 1.9, 10.3, P = 0.005] but the BASDAI did not (mean change 0.87, 95% CI -3.96, 5.7, P = 0.71). First recorded scores were the best predictors of the cumulative scores per year. Patients with peripheral joint (P = 0.01) and hip (P<0.001) disease had higher mean BASFI scores. Males (P<0.001) and patients with spinal disease alone (P = 0.0014), iritis (P = 0.005) and late-onset AS (P = 0.002) became more functionally impaired over time. CONCLUSIONS: Disease activity in this AS cohort remained relatively constant but there was functional decline. Initial BASDAI/FI can predict a severe disease course. PJD patients with peripheral joint disease were more functionally impaired, but deteriorated less than spinal disease alone patients. Iritis and late onset disease may be severity markers for functional impairment.     

强直性脊柱炎新的疾病活动性指数在中国患者中的应用价值研究

目的 验证新的强直性脊柱炎(AS)疾病活动性指数(ASDAS)在中国的AS患者中的辨别能力,评估其临床应用价值.方法 本研究共纳入AS患者129例,分别为参加依那西普临床试验的活动期AS患者(87例)和使用类克治疗的AS患者(42例).分别以4个ASDAS、毕氏AS疾病活动指数(BASDA1)及患者总体评价来评价患者的疾病活动性水平和治疗效果.计算标准化的均数差(SMD)分析指标的辨别能力,运用Pearson相关分析.两独立样本t检验与一元线性回归进行统计学处理.结果 无论是基线水平还是治疗6周后的变化程度,4个新的ASDAS均与患者总体评价(r=0.56～0.74)、红细胞沉降率(ESR)(r=0.50～0.80)及C反应蛋白(CRP)(r=0.50～0.69)有较好的相关性.4个ASDAS对AS患者的疾病活动性水平及治疗前后病情变化程度的辨别能力均优于BASDA1、患者总体评价、ESR和CRP.4个ASDAS之间差异无统计学意义.结论 新的ASDAS用于评价我国AS患者的疾病活动性和药物疗效有较高的辨别能力,值得临床推广和应用.     

Serum IL-6 level as a marker of disease activity in ankylosing spondylitis patients with pure axial involvement

BackgroundThe assessment of disease activity in patients with ankylosing spondylitis (AS) continues to be a challenging issue. The currently available markers like C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) show poor correlation with clinical disease activity.ObjectivesTo compare serum IL-6 and hs-CRP levels between patients with AS with pure axial involvement and healthy controls; and to correlate them with Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI) and Bath ankylosing spondylitis metrology index (BASMI).MethodsSixty-two consecutive patients of AS with pure axial involvement satisfying the modified New York criteria and 60 age-matched healthy controls were recruited. In all patients, Bath indices were measured and fasting venous blood samples for serum IL-6 and hs-CRP levels were obtained. Comparison of median of serum IL-6 and hs-CRP levels was done between cases and healthy controls and levels also correlated with Bath indices by appropriate statistical methods.ResultsThe median serum IL-6 and hs-CRP levels were significantly higher in cases as compared to healthy controls (p = 0.001). Serum IL-6 levels correlated significantly with BASDAI and BASFI (r = 0.61, p = 0.001 and r = 0.27, p = 0.032 respectively) but no correlation was found with BASMI (r = −0.08, p = 0.53). Serum hs-CRP did not correlate with Bath indices except BASMI (r = 0.28, p = 0.03).ConclusionSerum IL-6 levels can be reliably used as an aid in monitoring of disease activity in AS patients with pure axial involvement.     

Quality of life in patients with ankylosing spondylitis: relationships with spinal mobility, disease activity and functional status

The aim of this study was to evaluate quality of life (QOL) in patients with ankylosing spondylitis (AS) and to determine the relationships between QOL and clinical variables including spinal mobility, disease activity and functional status. Forty-eight adult patients who fulfilled the modified New York criteria for AS were included in the study. After detailed physical examination, disease-specific instruments: the Bath ankylosing spondylitis disease activity index (BASDAI) and the Bath ankylosing spondylitis functional index (BASFI) were applied. QOL was assessed using short form-36 (SF-36). The mean age of the patients was 37.0 ± 9.7 years and the mean duration of symptoms was 11.7 ± 8.4 years. Most affected domains of SF-36 were bodily pain, vitality, and physical role, respectively. No significant correlations were found between SF-36 subgroup scores and chest expansion, wall–tragus distance, chin–sternum distance, and floor–finger tip distance. Only modified Schober correlated with two SF-36 domains: physical role and bodily pain. BASDAI and BASFI scores had significant negative correlations with all SF-36 domains except for general health. Identification of QOL in patients with AS is very important in evaluation of illness-related sufferings and development of new management strategies.     

Relationship between psychological status and disease activity and quality of life in ankylosing spondylitis

Our aim in this study was to compare the depression and anxiety risk in patients with AS and healthy controls and also to determine the relationship between disease activity, quality of life and psychological well-being. Two hundred and forty-three patients with ankylosing spondylitis (AS) and 118 age-, sex- and education-matched healthy controls were enroled into the study. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Functional Index, and Metrology Index, Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S), Hospital Anxiety and Depression Scale (HADS) including depression subscale (HADS-D) and anxiety subscale (HADS-A), Ankylosing Spondylitis Quality of Life (ASQoL) Scale, duration of morning stiffness, pain-visual analogue scale (VAS), patient and physician??s global assessment of disease activity (100?mm VAS) were used to assess clinical and psychological status. Patients had similar HADS-D but higher HADS-A than healthy controls. Patients with high risk for depression and anxiety had higher scores in BASDAI, BASFI and also poorer scores in VAS pain, patient global assessment, physician global assessment, HAQ-S and ASQoL. There was a negative correlation of HADS-D and HADS-A scores with educational level of the patients. Higher scores in HADS-D and HADS-A indicated poorer functional outcome and quality of life. Multivariate logistic regression analysis revealed that the HADS-D (OR?=?6.84), HAQ-S (OR?=?1.76), VAS pain score (OR?=?1.03) and ESR (OR?=?1.02) were independent risk factors for higher anxiety scores whereas HADS-A (OR?=?1.36) and ASQoL (OR?=?1.24) were independent risk factors for higher depression scores. The psychological status had close interaction with disease activity and quality of life in patients with AS.     

Discrimination ability of ASDAS estimating disease activity status in patients with ankylosing spondylitis

Objectives: To investigate discrimination ability of the Assessment of Spondyloarthritis International Society (ASAS) endorsed disease activity score (ASDAS) versions evaluating low and high disease activity in an unselected group of patients with ankylosing spondylitis (AS). Methods: Patients consecutively included into the joint database of five university hospitals were analyzed for low or high disease activity according to different criteria. Standardized mean differences (SMD) for two ASDAS versions were evaluated. Results: The ASDAS versions (back pain, morning stiffness, patient global pain, pain/swelling of peripheral joints, plus either erythrocyte sedimentation rate or C‐reactive protein) discriminated high and low disease activity in subgroups according to Bath Ankylosing Spondylitis Disease Activity Score (BASDAI) and ASAS remission/partial remission criteria. ASDAS versions were also not influenced by peripheral arthritis and correlated well with other outcome measurements and acute‐phase reactants. The ASDAS versions performed better than patient‐reported measures or acute‐phase reactants discriminating high and low disease activity status. Conclusion: Both ASDAS versions, consisting of both patient‐reported data and acute‐phase reactants, performed well in discriminating low and high disease activity. Further longitudinal data may better estimate the usefulness of ASDAS to assess disease activity subgroups and treatment response.     

Vitamin D status in ankylosing spondylitis patients: Relation to bone health,disease activity,functional status,spine mobility and enthesitis

Aim of the workTo evaluate serum levels of vitamin D in ankylosing spondylitis (AS) patients in relation to bone mineral density, bone metabolism, and disease activity, functional status, spine mobility and extent of enthesitis.Patients and methodsSixty AS patients and 60 controls were included. Bath AS disease activity index (BASDAI), functional index (BASFI), metrology index (BASMI), AS disease activity score (ASDAS), and Maastricht AS enthesitis score (MASES) were assessed. Serum levels of vitamin D3, carboxy-terminal telopeptide of type-I collagen (CTX-1), alkaline phosphatase (ALP) and bone alkaline phosphatase (bALP) were measured. Dual-energy X-ray absorptiometry (DXA) was assessed.ResultsPatients mean age was 31.7 ± 9.1 years, disease duration 7.8 ± 4.4 years and were 46 males and 14 females. The mean BASDAI was 3.9 ± 1.02, ASDAS 2.7 ± 0.98, BASFI 3.6 ± 2.1, BASMI 4.5 ± 1.6 and MASES 4.4 ± 3.2. Patients had significantly (p = 0.001) lower levels of vitamin D (13 ± 7.8 vs 29.9 ± 9.5 ng/mL) and higher CTX-1 (547.5 ± 130.1 vs 230.1 ± 34.9 pg/mL), ALP (195.8 ± 100.8 vs 120.8 ± 10 IU/L) and bALP (48.4 ± 7.3 vs 21.03 ± 3.2 IU/L) compared to controls. Vitamin D significantly correlated with BMD (p = 0.04), inversely with CTX-1 (r = −0.22,p < 0.001), ALP (r = −0.03,p = 0.005), bALP (r = -0.22,p = 0.049), BASDAI (r = −0.57,p < 0.001), ASDAS (r =−0.37,p = 0.04), BASMI (r = −0.18,p = 0.03), MASES (r = −0.03,p = 0.008) and sacroiliitis grading (r = −2.4,p < 0.001). Vitamin D deficiency was associated with peripheral joints affection, enthesitis and not receiving sulfasalazine.ConclusionSerum vitamin D levels were decreased in patients with AS and were more deficient in relation to disease activity and bone turnover. Vitamin D may play a role in the pathogenesis and progression of AS in Egyptian patients which should be more comprehensively investigated.     

Evaluation of clinical activity and functional impairment in smokers with ankylosing spondylitis

Background Ankylosing spondylitis (AS), a rheumatic disease, incapacitates human beings during the most productive stage of their lives, causes functional disturbances, and thus affects both patients and their relatives. Disease activity, functional impairment, and efficacy of treatment are affected by various environmental and genetic factors, one of which is smoking. We investigated smokings effect on clinical activity and functional impairment in AS.Patients and methods Forty-eight patients with back pain and limited movements, diagnosed with AS based on clinical, radiological, and laboratory examinations and referred to the Trakya University School of Medicine Physical Medicine and Rehabilitation Department in Turkey were included in this study. Disease activity was evaluated with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and functional impairment with the Bath Ankylosing Spondylitis Functional Index (BASFI). The Mann-Whitney U test was used to determine relationships between smoking and physical findings, laboratory results, and BASDAI and BASFI scores.Results Twenty-four patients were smokers. They had significantly higher BASDAI and BASFI scores and significantly lower forced vital capacity values than nonsmokers (P=0.000, P=0.002, and P=0.001, respectively) (Mann-Whitney U test).Conclusion Smoking is associated with poor clinical aspect and functional impairment in AS. The underlying mechanism can be the physical incapacity caused by smoking.     

肺炎支原体感染与强直性脊柱炎活动性的研究

目的 研究成人强直性脊柱炎(AS)患者肺炎支原体(MP)感染与疾病活动性的关系.方法 选取我院门诊AS患者66例;对照组选取类风湿关节炎(RA)31例,骨关节炎(OA)25例,健康人群(NC)36名.根据抗肺炎支原体抗体(anti-MP IgM)将AS患者分成MP感染组和非MP感染组,比较和分析4周以内上呼吸道感染史、白细胞、疾病活动指数(BASDAI)、红细胞沉降率(ESR)、C反应蛋白(CRP)、免疫球蛋白以及骶髂关节损害程度、脊柱活动度(Schober测量和胸廓活动度).结果 66例AS患者抗MP抗体检测发现,阳性检出率为52%(34/66),与RA(6%)、OA(4%)、NC(11%)比较,差异有统计学意义(P＜0.01).MP感染组的疾病活动也显著高于非MP感染组,其中BASDAI(4.0±1.1对3.0±1.9,P=0.017),ESR[(44±32)mm/1 h对(28±23)mm/1 h,P=0.029],CRP[(40±38)mg/L对(22±21)mg/L,P=0.025],血清总IgG水平[(18±3)g/L对(16±5)g/L,P=0.027],但与总IgA和IgM无关.两组的骶髂关节分级、Schober测量和胸廓扩张度差异无统计学意义.抗MP抗体阳性的AS患者中只有44%出现呼吸道症状,但有呼吸道症状的AS患者中,71%的患者抗MP抗体阳性,与无呼吸道症状组比较,差异具有统计学意义(P=0.027).结论 AS患者的MP感染与疾病的活动性密切相关,可能是AS发病的主要诱发因素.     

Disease and psychological status in ankylosing spondylitis

OBJECTIVES: Psychological factors may be important in the assessment and management of ankylosing spondylitis (AS). Our primary objective was to describe associations between disease and psychological status in AS, using AS-specific assessment tools and questionnaires. Our secondary objectives were to identify patient subgroups based on such associations and to determine the stability of the measures over time. METHODS: A total of 110 patients were assessed at 6-monthly intervals up to four times using tools to measure disease [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Metrology Index (BASMI)], psychological [Hospital Anxiety and Depression Questionnaire (HADS), Health Locus of Control-Form C Questionnaire (HLC-C)] and generic health [Short form (SF)-36] status. RESULTS: Eighty-nine participants completed all four assessments. Throughout the study, BASDAI, BASFI and BASMI scores correlated significantly with anxiety, depression, internality and health status, but not with levels of belief in chance or powerful others. Clinically anxious or depressed subgroups had significantly worse BASDAI and BASFI, but not BASMI, scores. BASMI scores were the least closely linked to psychological status. Mean scores for disease, psychological and health status were clinically stable over the 18 months period. CONCLUSIONS: Disease status scores in AS correlated significantly with anxiety, depression, internality and health status. Interpretation of AS disease scores should take an account of psychological status and the choice of measures used. These findings have important potential applications in AS management and monitoring, including the identification of patients for biological therapies.     

Juvenile-onset ankylosing spondylitis is associated with worse functional outcomes than adult-onset ankylosing spondylitis

OBJECTIVE: To compare functional outcome of patients with juvenile-onset ankylosing spondylitis (JoAS; defined as AS with symptom onset before 16 years of age) with that of patients with adult-onset AS (AoAS) and to identify variables associated with a poor functional outcome of JoAS. METHODS: A cross-sectional study was performed of 326 JoAS patients who participated in a postal survey conducted by the Spondylitis Association of America. This cohort was compared with 2,021 AoAS patients who participated in the same survey. Simple and multiple logistic regression analyses were performed to identify differences with respect to clinical features, demographic features, and functional outcome (defined by the Bath Ankylosing Spondylitis Functional Index [BASFI]) between the 2 groups. A validation cohort of 255 AS patients was also surveyed. RESULTS: The mean +/- SD BASFI score (controlled for disease duration) for JoAS was 51.3 +/- 1.5 compared with 46.4 +/- 0.6 for AoAS (P < 0.0001). Multiple logistic regression identified only age (P < 0.0001) and income status (P < 0.0001) as factors associated with functional impairment. CONCLUSION: It appears that JoAS is a progressive disease and is associated with significant delay in diagnosis and worse functional outcome compared with AoAS. Furthermore, women do worse than men with JoAS. This would argue for the importance of early diagnosis and treatment of AS, particularly in the subgroup of patients with JoAS.