Relevance of structural damage in the sacroiliac joints for the functional status and spinal mobility in patients with axial spondyloarthritis: results from the German Spondyloarthritis Inception Cohort.
ABSTRACT: Functional status and spinal mobility in patients with axial spondyloarthritis (axSpA) are known to be determined both by disease activity and by structural damage in the spine. The impact of structural damage in the sacroiliac joints (SIJ) on physical function and spinal mobility in axSpA has not been studied so far. The objective of the study was to analyze the impact of radiographic sacroiliitis on functional status and spinal mobility in patients with axSpA.In total, 210 patients with axSpA were included in the analysis. Radiographs of SIJ obtained at baseline and after 2 years of follow up were scored by two trained readers according to the modified New York criteria grading system (grade 0-4). The mean of two readers' scores for each joint and a sum score for both SIJ were calculated for each patient giving a sacroiliitis sum score between 0 and 8. The Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI) at baseline and after 2 years were used as outcome measures.Longitudinal mixed model analysis adjusted for structural damage in the spine (modified Stoke Ankylosing Spondylitis Spine Score - mSASSS), disease activity (Bath Ankylosing Spondylitis Disease Activity Index - BASDAI and C-reactive protein level) and gender, revealed an independent association of the sacroiliitis sum score with the BASFI: b = 0.10 (95% CI 0.01-0.19) and the BASMI: b = 0.12 (95% CI 0.03-0.21), respectively, indicating that change by one radiographic sacroiliitis grade in one joint is associated with BASFI/BASMI worsening by 0.10/0.12 points, respectively, independently of disease activity and structural damage in the spine.Structural damage in the SIJ might have an impact on functional status and spinal mobility in axSpA independently of spinal structural damage and disease activity.ClinicalTrials.gov, NCT01277419 . Registered on 14 January 2011.
Project description:OBJECTIVES:To evaluate the efficacy and safety of certolizumab pegol (CZP) after 24 weeks in RAPID-axSpA (NCT01087762), an ongoing Phase 3 trial in patients with axial spondyloarthritis (axSpA), including patients with ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA). METHODS:Patients with active axSpA were randomised 1:1:1 to placebo, CZP 200 mg every 2 weeks (Q2W) or CZP 400 mg every 4 weeks (Q4W). In total 325 patients were randomised. Primary endpoint was ASAS20 (Assessment of SpondyloArthritis international Society 20) response at week 12. Secondary outcomes included change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Metrology Index (BASMI) linear. RESULTS:Baseline disease activity was similar between AS and nr-axSpA. At week 12, ASAS20 response rates were significantly higher in CZP 200 mg Q2W and CZP 400 mg Q4W arms versus placebo (57.7 and 63.6 vs 38.3, p?0.004). At week 24, combined CZP arms showed significant (p<0.001) differences in change from baseline versus placebo in BASFI (-2.28 vs -0.40), BASDAI (-3.05 vs -1.05), and BASMI (-0.52 vs -0.07). Improvements were observed as early as week 1. Similar improvements were reported with CZP versus placebo in both AS and nr-axSpA subpopulations. Adverse events were reported in 70.4% vs 62.6%, and serious adverse events in 4.7% vs 4.7% of All CZP versus placebo groups. No deaths or malignancies were reported. CONCLUSIONS:CZP rapidly reduced the signs and symptoms of axSpA, with no new safety signals observed compared to the safety profile of CZP in RA. Similar improvements were observed across CZP dosing regimens, and in AS and nr-axSpA patients.
Project description:Objectives:To explore the relationship between Vitamin D levels and pain and disease activity in patients with newly diagnosed axial spondyloarthritis (axSpA). Methods:A convenience sample of 131 newly diagnosed axSpA patients and 60 healthy controls was recruited from July 2016 to December 2018. Serum 25-hydroxyvitamin D [25(OH)D] was measured to assess vitamin D levels. Disease activity was assessed by objective indicators [Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), the Bath Ankylosing Spondylitis Metrology Index (BASMI)], patient-reported questionnaires [the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and the Bath Ankylosing Spondylitis Functional Index (BASFI)]. Pain intensity and interference were also assessed. Results:Vitamin D insufficiency [serum 25(OH) D levels<50 nmol/L]was found in 46 (35.1%) and 25 (43.3%) of the axSpA patients and the healthy controls, respectively. Female patients had higher risk (OR:4.928; 95% CI: 1.921-12.642) for vitamin D insufficiency than male patients. Vitamin D was positively correlated with CRP, ESR level, the BASFI, and the BASMI. Logistic regression showed that vitamin D levels were not associated with pain, or disease activity in the newly diagnosed axSpA patients. Gender was the only predictive variable for vitamin D levels. Conclusions:Vitamin D insufficiency was prevalent in both newly diagnosed axSpA patients and healthy controls. There was no association between vitamin D and pain and disease activity in the newly diagnosed axSpA patients. Monitoring vitamin D levels is important and early intervention for vitamin D insufficiency is needed, especially in female patients.
Project description:Previously, many studies have evaluated quality of life (QoL) in patients with ankylosing spondylitis (AS), however, none of them specifically investigated the correlation between pain-related disability measured by Oswestry Disability Index (ODI) and QoL in AS patients. In addition, the correlation between global kyphosis (GK) in lateral plain radiographs and QoL in AS patients remains unclear up to now. Therefore, this study aimed to evaluate QoL and correlation with clinical and radiographic variables in AS patients, especially to figure out the relationship about the pain-specific disability measured by ODI, GK and QoL.From January 2008 to November 2015, two hundred and forty-five consecutive patients with an average age of 36.2 ± 10.9 years (range, 17-66 years) satisfying the Modified New York Criteria for AS from a single institution were enrolled. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI) and Bath Ankylosing Spondylitis Global score (BAS-G) were applied to assess the disease activity, functional status, spinal mobility and overall feeling of AS patients, respectively. ODI was recorded to evaluate low back pain-related disability. QoL was evaluated by the Short Form-36 (SF-36). According to global kyphosis (GK) measured on standing lateral full-spine radiographs, the patients were divided into two groups: mild kyphotic group (GK < 70°,n = 176) and severe kyphotic group (GK ≥ 70°,n = 69).The scores of BASDAI, BASFI, BASMI and ODI had significant negative correlations with all SF-36 subscale scores (P < 0.01). BASFI and BASMI scores of severe kyphotic group were much higher than those of mild kyphotic group, respectively (P = 0.005 and P = 0.001, respectively) and the score of physical function (PF) subscale in severe kyphotic group was significantly higher than that in mild kyphotic group (P = 0.046) as well. Notably, the scores of ODI, BASFI and BASMI were the major predictors of PF subscale score of SF-36.Poor QoL is significantly correlated with high disease activity, poor functional status and decreased spinal mobility in AS. GK is significantly associated with functional status, spinal mobility and QoL in AS patients. ODI, BASFI and BASMI are the major predictors of PF subscale of SF-36.
Project description:Engaging in physical activity (PA) is a key aspect in the management of axial spondyloarthritis (axial SpA), however, its relationship with clinical measures is unknown. Previous research has mainly focused on subjective methods of measuring PA and sedentary behaviour (SB). The aim of this study was to explore the associations between objectively measured PA and SB with clinical measures in people with established axial SpA. Fifty participants were recruited from secondary-care rheumatology outpatient services in Glasgow, UK. Clinical measures collected included; Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Ankylosing Spondylitis Quality of Life (ASQOL) and the Six Minute Walk Test (6MWT). PA and SB were measured using the activPAL3 tri-axial accelerometer. Data from forty-five participants were included (23 males, average age 49?±?12 years). Participants accumulated an average of 93.2?±?41.5 min/day walking with an average of 7200?±?3397 steps/day. The majority of the day (65%) was spent sitting, accumulated in prolonged bouts. Walking time and steps taken/day were associated with better BASFI (r?=?- 0.395, p?=?0.007 and r?=?- 0.404, p?=?0.006), ASQOL (r?=?- 0.375, p?=?0.011 and r?=?- 0.361, p?=?0.015) and 6MWT (r?=?0.396, p?=?0.007 and r?=?0.421, p?=?0.004); while longer walking events were associated with better BASMI (rho?=?- 0.352, p?=?0.018), BASFI (rho?=?- 0.316, p?=?0.034) and 6MWT (rho?=?0.404, p?=?0.006). SB was associated with worse ASQOL (r?=?0.380, p?=?0.010) and 6MWT (6MWT, r?=?- 0.357, p?=?0.016). In people with axial SpA PA is associated with better function, exercise capacity and spinal mobility, while SB is associated with lower exercise capacity and poor quality of life. These findings support the promotion of PA and reduction of SB in people with axial SpA.
Project description:The aim of this study was to investigate the influence of symptom duration on treatment response and on the correlation between improvements in patient reported outcomes (PRO) and objective inflammation in patients with axial spondylarthritis (SpA) treated with etanercept (ETA) or adalimumab (ADA).Data from 112 patients with axial SpA originally enrolled in two randomized controlled clinical trials were pooled and analyzed after one year of treatment with ETA (n?=?66) or ADA (n?=?46). Patients with <4 years and ?4 years of disease were compared for improvement in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Disease Activity Score (ASDAS), C-reactive protein (CRP) and magnetic resonance imaging (MRI) score for sacroiliac joints (SIJ).Patients with <4 years of disease showed a significantly better improvement than longer diseased patients in BASDAI (3.2 (95% confidence interval (CI): 2.7 to 3.7) vs. 1.7 (1.1 to 2.2)), BASFI, BASMI and ASDAS (1.6 (1.4 to 1.8) vs. 0.9 (0.7 to 1.1)). The change in BASDAI showed a significant correlation with the change in SIJ score (Spearman's rank correlation coefficient (rho)?=?0.37, P?=?0.01) and the change in CRP (rho?=?0.45, P?=?0.001) in patients with <4 years of disease. For long diseased patients this correlation was poor and did not achieve statistical significance (rho?=?0.13, P?=?0.46; rho?=?0.22, P?=?0.13 respectively).The low correlation between change of PROs and change of objective signs of inflammation seen in axial SpA patients with longer symptom duration treated with tumor necrosis factor-blocker seems to indicate that inflammation is not the only cause of the patients' symptoms, while inflammation seems to be the major cause in short diseased patients.Clinical Trials.gov NCT00844142 (Trial 1); NCT00235105 (Trial 2).
Project description:Objective: This prospective observational study investigated the efficacy of tumor necrosis factor inhibitors (TNFis) on disease activity, physical functionality, and mobility in patients with ankylosing spondylitis (AS) in a real-world setting. Methods: The Chinese Ankylosing Spondylitis Prospective Imaging Cohort (CASPIC) is an ongoing cohort study. Patients with AS were included to one of two groups: the TNFi user group included those who received TNFi at any time point; the non-TNFi user group included those who did not receive TNFi. Disease activity, physical functionality, and mobility were assessed by AS Disease Activity Scores (ASDAS), Bath AS Functional Index (BASFI), and Bath AS Metrology Index (BASMI), respectively. Results: A total of 804 patients with AS (241 TNFi users and 563 non-TNFi users) were recruited. For TNFi users, 83% received an etanercept biosimilar and 17.0% received adalimumab. Seventy-three TNFi users (30.3%) discontinued TNFis during the follow-up period; the mean duration of TNFi treatment was 6.9 ± 3.2 months. Reductions in ASDAS were significantly greater in TNFi users than in nonusers at 3, 6, and 12 months (differences in ASDAS reduction were 0.61, 0.56, and 0.46 units, respectively, all P < 0.05). Similarly, the improvement in BASFI was significantly greater in users than in nonusers at 3, 6, and 12 months (differences in BASFI improvement: 0.31, 0.75, and 0.74 units, respectively, all P < 0.05). BASMI increased in nonusers at 6 and 12 months (0.27, P = 0.47; 0.66, P < 0.001, respectively), but did not change in users (-0.16 and -0.13, respectively, both P > 0.05). At 12 months, changes in BASMI were significantly greater in nonusers than in users (-0.60, P = 0.47). Conclusion: TNFis are effective against disease activity and improve the physical functionality of patients with AS, even in those who taper or discontinue TNFis. Thus, TNFis may retard the progression of spinal mobility dysfunction in AS patients. TNF may maintain spinal mobility as indicated by the BASMI.
Project description:The effect of cigarette smoking and alcohol consumption on the disease activity and physical functioning in ankylosing spondylitis (AS) is currently understated. Present study aims to investigate the relationship between them. A total of 425 patients with AS were recruited in the study and their smoking and drinking habit were investigated with a semi-quantitative food frequency questionnaire. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Metrology Index (BASMI) were evaluated. Parameters including fingertip-to-floor distance, overall assessment of health, nocturnal pain, total back pain and morning stiffness were analyzed as well. Blood erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were determined. For 118 (27.8%) AS patients with smoking habit, the scorings of BASDAI, BASFI, BASMI and other physical parameters (including fingertip-to-floor, overall assessment of health, nocturnal pain and total back pain) were higher than those in patients without smoking. 101 (23.8%) AS patients with alcohol consumption demonstrated significantly higher scores in BASMI (P < 0.05). In hierarchical multiple regression analysis, the cigarette smoking and alcohol consumption variables contributed to the variance in BASDAI scores, adding an additional 1.6% to the overall R-square, resulting in a final R-square of 5.1%. Smoking has a negative effect on disease activity of patients with AS and the patients' physical functioning. Alcohol consumption would aggravate the overall physical functioning of AS patient. The results indicated the potential benefit of quitting smoking and drinking for AS patients.
Project description:Previous reports of the RAPID-axSpA trial (NCT01087762) described the efficacy and safety of certolizumab pegol (CZP) over 24 weeks in patients with axial spondyloarthritis (SpA), including ankylosing spondylitis (AS) and nonradiographic axial SpA. We report efficacy and safety data up to week 96 of the study.The RAPID-axSpA trial is double-blind and placebo-controlled to week 24, dose-blind to week 48, and open-label to week 204. Outcome variables included Assessment of SpondyloArthritis international Society criteria for 20% and 40% improvement in disease activity (ASAS20/40), ASAS partial remission responses (analyzed by nonresponder imputation), AS Disease Activity Score (ASDAS), ASDAS inactive disease, ASDAS major improvement, Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), and Bath AS Metrology Index (BASMI) linear score (analyzed by the last observation carried forward method). Safety data were collected for patients treated with ?1 dose of CZP.Of the 325 patients who were randomized, 218 received CZP from week 0. Of these, 93% completed week 24, 88% completed week 48, and 80% completed week 96. Improvements in ASAS responses were maintained to week 96 (for ASAS20, 67.4%, 72.0%, and 62.8% at weeks 24, 48, and 96, respectively), as well as improvements in ASDAS, BASDAI (mean score 3.3, 3.1, and 3.0 at weeks 24, 48, and 96, respectively), BASFI, and BASMI linear score. Comparable improvements were observed with both dosing regimens (200 mg every 2 weeks or 400 mg every 4 weeks) and in patients with AS and those with nonradiographic axial SpA. In the safety set, adverse events occurred in 279 patients (88.6%) and serious adverse events in 41 (13.0%). No deaths or malignancies were reported.Clinical improvements to week 24 in both CZP dosing regimens were sustained to week 96. Similar sustained improvements were observed in AS and nonradiographic axial SpA subpopulations. The safety profile was consistent with previous reports from RAPID-axSpA, with no new safety signals observed with longer exposure.
Project description:OBJECTIVE:To investigate whether spinal radiographic progression relates to structural damage at the sacroiliac level in axial spondyloarthritis (axSpA). METHODS:Patients classified as nonradiographic (nr-) and radiographic (r-) axSpA in the Swiss Clinical Quality Management cohort with radiographs performed every 2 years, scored according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), were included. The relationship between classification status and spinal progression during 2 years was investigated using binomial generalized estimating equations models with adjustment for sex, ankylosing spondylitis disease activity score (ASDAS) and tumour necrosis factor inhibitor treatment. Baseline spinal damage was considered an intermediate variable and included in sensitivity analyses. RESULTS:In total, 88 nr-axSpA and 418 r-axSpA patients contributed to data for 725 radiographic intervals. R-axSpA patients were more frequently male, had a longer disease duration and higher structural damage at baseline. Mean (SD) mSASSS change over 2 years was 0.16 (0.62) units in nr-axSpA and 0.92 (2.78) units in r-axSpA, p = 0.01. Nr-axSpA was associated with a significantly lower progression in 2 years (defined as an increase in ?2 mSASSS units) in adjusted analyses (OR 0.33, 95%CI 0.13; 0.83), confirmed with progression defined as the formation of ?1 syndesmophyte. Mediation analyses revealed that sacroiliitis exerted its effect on spinal progression indirectly by being associated with the appearance of a first syndesmophyte (OR 0.09, 95%CI 0.02; 0.36 for nr-axSpA vs r-axSpA). Baseline syndesmophytes were predictors of further progression. CONCLUSION:Spinal structural damage is mainly restricted to patients with r-axSpA, leading to relevant prognostic and therapeutic implications.
Project description:INTRODUCTION:The arthritis-specific Work Productivity Survey (WPS) was developed to evaluate productivity limitations associated with arthritis within and outside the home. There is an unmet need for an instrument assessing similar productivity limitations in axial spondyloarthritis (axSpA), including nonradiographic axSpA and ankylosing spondylitis. Following its validation in rheumatoid and psoriatic arthritis, we aimed to assess psychometric properties of WPS in adult-onset active axSpA in this analysis. METHODS:Psychometric properties were assessed using data from the RAPID-axSpA trial (NCT01087762) in which researchers investigated certolizumab pegol efficacy and safety in axSpA. WPS was completed at baseline and every 4 weeks until week 24. Validity was evaluated at study baseline via known-groups defined by the first and third quartile cutoffs of patient scores to Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), back pain, Bath Ankylosing Spondylitis Functional Index (BASFI), Short Form 36 health survey (SF-36) and Ankylosing Spondylitis Quality of Life Scale (ASQoL). Responsiveness and reliability were assessed by comparing WPS mean changes in ASAS 20% improvement criteria (ASAS20), BASDAI50, ASDAS clinically important improvement/major improvement (CII/MI) and BASFI minimum clinically important difference (MCID) responders versus nonresponders at week 12. All comparisons were conducted on observed cases in the randomized set using a nonparametric bootstrap-t method. RESULTS:The results confirmed the psychometric properties of WPS. AxSpA patients with a worse health state had significantly more days of household work lost, household work with reduced productivity, social activities missed and outside help hired, as well as a higher interference rate of arthritis, than patients with a better health state. Similarly, employed patients with a worse health state had significantly more work days lost or with productivity reduced, and a higher interference of arthritis on work productivity. Similar findings were also observed in the nonradiographic (nr) axSpA and AS subpopulations. The WPS was responsive to clinical changes, with responders reporting larger improvements at week 12 in WPS scores versus nonresponders. Effect sizes in responders were generally moderate to large (standardized response mean >0.5). CONCLUSIONS:These analyses demonstrate that WPS is a valid, responsive and reliable instrument for the measurement of productivity within and outside the home in adult-onset axSpA, as well as the in subpopulations of AS and nr-axSpA.