Search

Predicting radiographic progression is vital for assessing the prognosis of patients with radiographic axial spondyloarthritis, and C-reactive protein (CRP) may be a valuable biomarker for this purpose. This study aimed to investigate the relationship between changes in the CRP level and spinal radiographic progression in patients with radiographic axial spondyloarthritis who were initially treated with non-biologics.Patients with radiographic axial spondyloarthritis who were followed up for 18 years at a single center and initially treated with nonsteroidal anti-inflammatory drugs and/or conventional disease-modifying antirheumatic drugs for 3 months were included. Patients with a CRP level of0.8 mg/dL or 50% of the baseline CRP at 3 months were assigned to the controlled CRP group (n = 351), and the remaining patients were assigned to the uncontrolled CRP group (n = 452). A generalized estimating equation was used to analyze the differences in the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) between the 2 groups.The increase in the mSASSS was slower in the controlled CRP group than in the uncontrolled CRP group (interaction term β = -.499, 95% confidence interval -0.699 to -0.300).Controlled CRP achieved in response to initial treatment with non-biologic agents for 3 months was significantly associated with a slower rate of spinal radiographic change in patients with radiographic axial spondyloarthritis. The CRP level at 3 months after initial non-biologic treatment is a good predictor of radiographic progression.

Background Although nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment for ankylosing spondylitis (AS), their effect on kidney function remains unclear. This longitudinal study investigated the correlation between long-term NSAID use and kidney function in patients with AS using electronic medical records. Methods The electronic medical records of 1,280 patients with AS collected from a single center between January 2001 and December 2018 were reviewed. The Assessment of Spondyloarthritis International Society (ASAS) NSAID Intake Score was used to determine the cumulative dose of all NSAIDs prescribed for a different time intervals. Each ASAS NSAID Intake Score was obtained for intervals of 6 months, 1 year, 2 years, 3 years, 5 years, and 10 years. The correlation between the ASAS NSAID Intake Score and final estimated glomerular filtration rate (eGFR) for each interval was investigated. Results The mean ASAS Intake Scores for 6-month, 1-year, 2-year, 3-year, 5-year, and 10-year intervals were 55.30, 49.28, 44.84, 44.14, 44.61, and 41.17, respectively. At each interval, the pearson correlation coefficients were − 0.018 (95% CI: -0.031 ‒ -0.006, p = 0.004), -0.021 (95% CI: -0.039 ‒ -0.004, p = 0.018), -0.045 (95% CI: -0.071 ‒ -0.019, p = 0.001), -0.069 (95% CI: -0.102 ‒ -0.037, p

This retrospective study evaluated the electronic medical records of patients with ankylosing spondylitis (AS) between January 2001 and December 2018 to determine the relationship between serum alkaline phosphatase (ALP) levels and radiographic changes over time. Longitudinal data including serum ALP levels were imputed by linear interpolation at 3-month intervals. Among the serum ALP levels for 8 years prior to modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) measurement, the serum ALP level having the highest beta coefficient with the mSASSS was selected. Linear mixed models with the selected serum ALP levels, mSASSS, and clinical variables were investigated. We included 1122 patients, with a mean follow-up period of 8.20 (standard deviation: 2.85) years. The serum ALP level from 5 years and 3 months prior showed the highest beta coefficient with the mSASSS. In the linear mixed model, the serum ALP level 5 years and 3 months before radiographic changes was significantly associated with the mSASSS (β = 0.021, 95% confidence interval: 0.017–0.025, p < 0.001). Serum ALP levels measured approximately 5 years before may be a surrogate marker for predicting spinal radiographic changes. Long-term prospective clinical and experimental studies of > 5 years are required for biomarker discovery or therapeutic research on AS radiographic progression.

ObjectiveTo determine the relationship between inflammation and radiographic progression over time in patients with ankylosing spondylitis (AS) attaining a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) of < 4 during tumor necrosis factor inhibitor (TNFi) treatment.MethodsMedical records data of patients with AS with BASDAI scores of < 4 during TNFi treatment were analyzed at 6-month intervals from January 2001 to December 2018. To determine the relationship between the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and C-reactive protein (CRP) over time, we fitted linear mixed models with mSASSS as the response variable, baseline mSASSS and the cumulative sum of CRP with different lag times (6, 12, 18, 24, 30, and 36 months) as fixed effects, and patients as random effects. Associations between mSASSS and the cumulative sum of CRP, or the lag times with the highest beta coefficients, were further investigated with linear mixed models that included additional clinical variables.ResultsA total of 2956 intervals were obtained from 333 patients. Among different lag times, the cumulative sum of log CRP in the previous 18 to 36 months associated with mSASSS showed significant beta coefficients. In the final linear mixed model, the cumulative sum of log CRP in the previous 24 months was significantly associated with mSASSS at 24 months (β 0.04, 95% CI 0.01-0.07,P= 0.004).ConclusionRemnant inflammation correlates with radiographic progression, even in patients attaining a BASDAI of < 4 during TNFi treatment. CRP is a surrogate marker for radiographic progression despite clinical improvement with TNFi treatment.

ObjectivesTo identify clinical and genetic factors associated with severe radiographic damage in patients with ankylosing spondylitis (AS).MethodsWe newly generated genome-wide single nucleotide polymorphism data (833K) for 444 patients with AS. The severity of radiographic damage was assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). To identify clinical and genetic factors associated with severe radiographic damage, multiple linear regression analyses were performed. Human AS-osteoprogenitor and control-osteoprogenitor cells were used for functional validation.ResultsThe significant clinical factors of final mSASSS were baseline mSASSS (β=0.796, p=3.22×10−75), peripheral joint arthritis (β=−0.246, p=6.85×10−6), uveitis (β=0.157, p=1.95×10−3), and smoking (β=0.130, p=2.72×10−2) after adjusting for sex, age and disease duration. After adjusting significant clinical factors, theRyanodine receptor 3(RYR3) gene was associated with severe radiographic damage (p=1.00×10−6). For pathway analysis, the PI3K-Akt signalling pathway was associated with severe radiographic damage in AS (p=2.21×10−4, false discovery rate=0.040). Treatment with rhodamine B, a ligand of RYR3, dose-dependently induced matrix mineralisation of AS osteoprogenitors. However, the rhodamine B-induced accelerated matrix mineralisation was not definitive in control osteoprogenitors. Knockdown of RYR3 inhibited matrix mineralisation in SaOS2 cell lines.ConclusionsThis study identified clinical and genetic factors that contributed to better understanding of the pathogenesis and biology associated with radiographic damage in AS.

Background/Aims: Biologics are very effective drugs for patients with ankylosing spondylitis (AS). However, there are patients who are not responding to biologics. This study aimed to evaluate the level of tumor necrosis factor α (TNF-α), inter leukin (IL)-23, and IL-17 from synovial fluid in patients with AS and rheumatoid arthritis (RA) and differences of the level of those cytokines according to drugs. Methods: Synovial fluid was obtained from 34 patients (42 samples) with AS and 45 patients (47 samples) with RA with active arthritis of the knee, and the cytokine levels were measured. The differences in the levels between patients treated with and without biologics (biologics and non-biologics groups, respectively) were an alyzed in AS and RA. The correlations between cytokines were examined in the non-biologics and biologics groups. Results: The TNF-α level in AS was significantly lower than that in RA (p = 0.016). The IL-17 and IL-23 levels were not different between AS and RA (p = 0.409 and p = 0.562, respectively). In AS and RA, TNF-α, IL-17, and IL-23 showed good correla tion among each other in the non-biologics group. However, there was no signifi cant correlation in biologics group. In some patients in the AS group, the IL-17 or IL-23 level was markedly elevated in the biologics group. Conclusions: Treatment with biologics affects the cytokine profile in inflamma tory synovial fluid in patients with both AS and RA. Furthermore, IL-23 and IL-17 cytokine might be an important factor in some patients who are unresponsive to biologics in AS.

Objectives: To determine the relationship between inflammation and radiographic progression over time in patients in clinical remission for ankylosing spondylitis (AS) after tumor necrosis factor inhibitor (TNFi) treatment.Method: Medical records data of AS patients with Bath Ankylosing Spondylitis Disease Activity Index scores Results: A total of 2,956 intervals were obtained from 333 patients. Among different lag times, the cumulative sum of log CRP in the previous 18–36 months and mSASSS showed significant beta coefficients. In the final linear mixed model that included clinical variables, the cumulative sum of log CRP in the previous 24 months was significantly associated with mSASSS at 24 months (β=0.043, 95% CI: 0.014–0.071, p=0.004). Conclusion: Remnant inflammation correlates with radiographic progression even in patients in clinical remission with TNFi treatment. CRP is a surrogate marker for radiographic progression despite clinical improvement with TNFi treatment.

Aim This study investigated the use of fat fraction (FF) measurements in the sacroiliac (SI) joint to determine radiologic progression in patients with spondyloarthritis (SpA). Method A total of 138 patients who underwent pelvic magnetic resonance imaging (MRI) between September 2014 and March 2015 were retrospectively evaluated. The FF based upon fat deposition (%) using fat signaling on T1 and T2 weighted images in the sacroiliac joint was quantified using a 6-echo variant of the modified Dixon technique. We defined the normal bone marrow as normal FF, bone marrow edema as active inflammatory FF, and fat metaplasia as post-inflammatory FF. Results The mean FF of normal marrow was 52.0% ± 10.4% and 50.5% ± 10.1% in the left and right SI joints, respectively. The mean FF of post-inflammatory fat deposition was 81.9% ± 9.7% and 82.3% ± 9.6% in the left and right SI joints, respectively. The mean FF of active inflammatory fat deposition was 15.8% ± 5.9% and 13.5% ± 6.7% in the left and right SI joints, respectively. In multiple linear regression, post-inflammatory FF was found to be significantly associated with radiologic progression, such as symptom duration, SI joint grade, and modified Stoke Ankylosing Spondylitis Spine Score. Conclusion Post-inflammatory FF indicates the chronicity of SpA. Evaluating FF using MRI in the SI joint will help to determine radiologic progression.

To identify predictors of low health-related quality of life (HRQoL) and depression in ankylosing spondylitis (AS) patients with a focus on gender differences. We conducted a cross-sectional cohort study. Both AS-related clinical data and contextual factors were obtained. HRQoL and depressive mood were assessed by EuroQol-5 dimension (EQ-5D) and the Center for Epidemiological Studies Depression Scale (CES-D), respectively. Gender-stratified multivariable logistic regression analyses were performed. Among 211 patients, 161 were males. Males had similar disease activity and higher radiographic damage compared with females. There was no significant difference in EQ-5D index score between genders. CES-D score was higher in females. Higher ASDAS-C-reactive protein (CRP) was associated with low HRQoL in both males (Odds ratio [OR] 4.25, 95% confidence interval [CI] 2.42–7.46) and females (OR 2.94, 95% CI 1.02–8.48). Being employed was associated with decreased possibility of having low HRQoL in males (OR 0.39, 95% CI 0.16–0.95). Regarding depression, higher ASDAS-CRP (OR 1.87, 95% CI 1.03–3.40), current smoking (OR 2.98, 95% CI 1.09–8.15), and being employed (OR 0.17, 95% CI 0.06–0.46) were associated with depression in males. For females, living with a partner was related to depression (OR 0.08, 95% CI 0.01–0.93). AS patients with high disease activity are likely to be suffering from low HRQoL. Both disease-related factors and contextual factors were associated with depression, and predictors showed some differences between genders. Awareness of gender differences in comprehensive assessment can lead us to better personalized management in AS patients.

Background The purpose of this study was to determine the prevalence of high disease activity as measured using the Ankylosing Spondylitis Disease Activity Score (ASDAS) in ankylosing spondylitis (AS) patients who nonetheless have low Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores after anti-tumor necrosis factor (TNF) treatment. Its clinical impact on anti-TNF survival was also investigated. Methods We conducted a single-centre retrospective cohort study of AS patients having low BASDAI scores ( Results Among 116 AS patients with low BASDAI scores after 3 months of anti-TNF treatment, 38.8% were grouped into the high-ASDAS group. The high-ASDAS group tended to have greater disease activity after 9 months of treatment (BASDAI 2.9 ± 1.1 vs. 2.3 ± 1.4, p=0.007; ASDAS-CRP 1.8 ± 0.6 vs. 1.5 ± 0.7, p=0.079; proportion of high ASDAS-CRP 27.8% vs. 13.8%, p=0.094) and greater risk of discontinuing anti-TNF treatment due to lack/loss of efficacy than the low-ASDAS group (p=0.011). Conclusions A relatively high proportion of AS patients with low BASDAI scores had high ASDAS-CRP. These low-BASDAI/high-ASDAS-CRP patients also had a greater risk for discontinuation of anti-TNF treatment due to low/lack of efficacy than the low-ASDAS group. The use of the ASDAS-CRP alone or in addition to the BASDAI may improve the assessment of AS patients treated with anti-TNF agents.

Resume Objectif Evaluer l’influence des inhibiteurs du facteur de necrose tumorale (TNF) sur la progression radiographique chez les patients atteints de spondylarthrite ankylosante (SpA). Methodes Au total 610 patients ont ete recrutes et repartis dans deux groupes : patients naifs d’anti-TNF et patients exposes aux anti-TNF. Nous avons ensuite analyse la progression radiographique rachidienne. Des analyses univariees et multivariees ont ete realisees afin d’identifier des facteurs predictifs de la progression radiographique, evaluee par le Stokes AS Spinal Score modifie (mSASSS). Comme il s’agissait d’une etude observationnelle, les patients n’ont pas ete randomises dans le bras de traitement et les scores de propension ont egalement ete apparies selon l’âge, le sexe et la CRP a l’inclusion. Le modele d’equation d’estimation generalisee a ete applique aux echantillons apres appariement. Les eventuels facteurs parasites ont ete inclus dans le modele. Resultats La concordance entre les deux lecteurs etait excellente. Sur les 610 patients atteints de SPA, 341 n’avaient jamais recu d’anti-TNF. Il n’y avait pas de difference significative de progression radiographique (moyenne ± ET) entre les groupes (4,73 ± 1,01 et 6,14 ± 2,00, p = 0,54), meme apres ajustement selon les facteurs parasites (âge, sexe, duree de la maladie, tabagisme, concentration de la CRP, prise d’AINS et score mSASSS a l’inclusion). Les scores de propension ont ete apparies pour confirmer l’effet des anti-TNF sur la progression radiographique. Meme apres ajustement en fonction de l’exposition aux anti-TNF, le resultat n’etait pas significatif ; l’Odd Ratio (OR) de la progression avec prise d’anti-TNF etait de 0,69 (p = 0,41 ; intervalle de confiance [IC] 95 % : 0,29–1,63). Conclusion Les donnees de notre registre indiquent que les anti-TNF sont restes sans effets sur la progression radiographique chez les patients atteints de SPA sur une periode de cinq ans.

ObjectivesTumour necrosis factor inhibitors (TNFis) have been suggested to slow radiographic progression in patients with ankylosing spondylitis. However, limitations such as variations in disease activity, complex drug administration and short follow-up duration make it difficult to determine the effect of TNFis on radiographic progression. The aim of the study was to investigate whether long-term treatment with TNFis can reduce radiographic progression in patients with ankylosing spondylitis using 18-year longitudinal real-world data.MethodsThis retrospective study was conducted between January 2001 and December 2018 at a single centre. Among the 1280 patients whose electronic medical records were reviewed, data of 595 patients exposed to TNFis at least once were included. Among them, time intervals of TNFi exposure or non-exposure were determined in 338 patients (‘on the TNFis’ or ‘off the TNFis’ intervals, respectively). The difference in the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) change rate between ‘on the TNFis’ and ‘off the TNFis’ intervals was investigated.ResultsWe obtained 2364 intervals of 338 patients (1281 ‘on the TNFis’ and 1083 ‘off the TNFis’ intervals). In the marginal structural model for inverse probability of treatment weighting, the change rate of mSASSS significantly decreased with the use of TNFis (β=−0.112, p=0.004), and the adjusted mSASSS changes were 0.848 and 0.960 per year during ‘on the TNFis’ and ‘off the TNFis’ intervals, respectively.ConclusionCompared with treatment without TNFis, treatment with TNFis slowed radiologic progression significantly.

We thank Zhang et al 1 for their interest in our study, titled “Tumour necrosis factor inhibitors slow radiographic progression in patients with ankylosing spondylitis: 18-year real-world evidence.” We investigated long-term observational data using advanced statistical methods to determine whether changes in radiographic progression are affected by tumour necrosis factor inhibitors (TNFi) in patients with ankylosing spondylitis (AS).2 However, our study did not consider the risk of osteoporosis or vertebral fractures while evaluating the effects of TNFi. There are several studies on bone mineral density (BMD) in patients with AS. Compared with the general population, patients with AS have a lower BMD.3–5 …

To evaluate differences in radiographic progression between adult-onset ankylosing spondylitis (AoAS) and juvenile-onset ankylosing spondylitis (JoAS).A total of 533 patients (418 patients with AoAS and 115 patients with JoAS) from the Observation Study of Korean spondyloArthropathy Registry (OSKAR) cohort were enrolled. All baseline OSKAR data were analysed in relation to disease onset and radiographic progression was analysed between the groups over 5 years. The modified Stoke AS Spinal Score (mSASSS) were used by two experienced radiologists. Clinical data were collected to investigate the associations between clinical factors and radiographic progression. Radiographic scores were compared using analysis of covariance model after adjusting for confounding factors.Inter-reader reliability for baseline mSASSS was very good. Inter-reader reliability for the changes in the mSASSS was also good. A significant difference in baseline mSASSS (mean ± SD) unit was detected between the AoAS and JoAS groups (18.1±17.4 vs. 14.3±13.8, p=0.015). We assessed the change in mSASSS to confirm whether age at onset affected radiographic progression. A simple comparison revealed a significant difference between changes on the mSASSS (mean ± SEM) between the JoAS and AoAS groups (1.75±0.71 vs. 3.77±0.56, p0.001). After adjusting for multiple comparisons, change on the mSASSS remained lower in patients with JoAS than those with AoAS (0.28±1.33 vs. 4.08±0.62, p=0.016).Patients with JoAS had slower radiographic spinal damage progression over 5 years than those with AoAS.

Objective To evaluate the influence of tumor necrosis factor (TNF) blocker on the radiographic progression in ankylosing spondylitis (AS) patients. Methods A total of 610 patients were recruited. We stratified two groups (TNF blocker naive and exposure patients). After then, we analyzed the radiographic spinal progression. Univariable and multivariable analyses were performed to identify predictors associated with radiographic progression, which was assessed by the modified Stokes AS Spinal Score (mSASSS). As this was an observational study, the patients were not randomized to the treatment arm. Therefore, propensity score matching was also done with age, gender, and the baseline CRP. The generalized estimating equation model was performed in the post-matched samples. Potential confounders were included in the model. Results Agreements between the two readers were excellent. Of the 610 patients with AS, 341 patients did not have any exposure to TNF blocker. The radiographic progression (mean ± SEM) was not significantly different between groups (4.73 ± 1.01, and 6.14 ± 2.00, P = 0.54) in spite of adjusting for confounding factors (age, gender, disease duration, smoking, CRP level, NSAID intake, and baseline mSASSS). Propensity score matching was done to confirm the effect of TNF blockers on radiographic progression. Even after adjusting for the TNF blocker exposure, the result still remained not significant with an OR for progression while taking TNF blocker of 0.69 ( P = 0.41; 95% CI: 0.29⿿1.63). Conclusion Our registry data showed that TNF blocker failed to affect the radiographic progression over 5 years in AS patients.