Baseline increased 18F-fluoride uptake lesions at vertebral corners on positron emission tomography predict new syndesmophyte development in ankylosing spondylitis: a 2-year longitudinal study.

The goal of this study was to demonstrate whether increased 18F-fluoride uptake lesions on positron emission tomography (PET) scan can predict new syndesmophyte development in patients with ankylosing spondylitis (AS). In 12 AS patients, 18F-fluoride PET and magnetic resonance imaging (MRI) was performed at baseline, and radiography was performed at baseline and the 2-year follow-up. The following data were recorded: the presence of increased 18F-fluoride uptake lesions on PET defined as an uptake greater than the uptake in the adjacent normal vertebral body; acute (type A) and advanced (type B) corner inflammatory lesions (CILs) and fat lesions on MRI; and syndesmophytes on radiography. Of 231 anterior vertebral corners without syndesmophyte at baseline, 13 type A CILs (5.5%), 2 type B CILs (0.9%), and 20 fat lesions (8.7%) on MRI and six increased fluoride uptake lesions (2.6%) on PET were observed. At the 2-year follow-up, 16 new syndesmophytes (6.9%) in eight AS patients (66.7%) occurred. New syndesmophytes developed significantly more frequently in anterior vertebral corners with increased 18F-fluoride uptake lesions (50%) or fat lesions (25%) at baseline than in those without such lesions (5.8 and 5.2%; p = 0.005 and p = 0.007, respectively). After adjusting confounding factors, baseline increased 18F-fluoride uptake lesions was independently associated with new syndesmophytes development (OR 13.8, 95% CI 1.5-124.3, p = 0.019). Fat lesions were also associated with new syndesmophytes formation. Our data suggest that 18F-fluoride PET may be applied to identify AS patients with high risk of future syndesmophyte formation.

Compliance and persistence with oral bisphosphonates for the treatment of osteoporosis in female patients with rheumatoid arthritis.

BACKGROUND: Poor adherence with oral bisphosphonates (BPs) can mitigate their therapeutic benefit for osteoporosis and is a significant clinical burden. Most previous studies regarding adherence with oral BPs have focused on postmenopausal osteoporosis, but little attention has been given to patients with rheumatoid arthritis (RA). Thus, we investigated compliance and persistence with oral BPs in the treatment of osteoporosis and analyzed risk factors for poor adherence in female patients with (RA) in real setting. METHODS: This is a retrospective longitudinal study including 396 female patients with RA in whom oral BPs were newly initiated from Aug 2004 to Aug 2014 at a university rheumatology center in South Korea. Compliance was quantified using the 1-year medication possession ratio (MPR), while persistence was defined as duration from the initiation to the end of BPs therapy without interruption exceeding 56 days. Seropositve RA was defined as having a positive test result for the presence of either rheumatoid factor or anti-cyclic citrullinated peptide antibody. RESULTS: Of 396 RA patients, 221 (55.8%) were prescribed risedronate 35 mg weekly; 17 (4.3%) received alendronate 70 mg weekly; and 158 (39.9%) received ibandronate 150 mg monthly. The 1-year MPR was 70.1% and the proportion of RA patients with the 1-year MPR ≥ 0.8 was 60.1%. A total of 274 (69.2%) patients discontinued oral BPs during the study period and persistence with BPs was 63.3% at 1 year, 50.7% at 2 years and 33.3% at 3 years. The most common cause of non-persistence was adverse events (47.5%), followed by poor health literacy (40.5%) and cost (12%). Both compliance and persistence with monthly oral BPs were significantly lower than those with weekly regimens (OR: 2.48, 95% CI: 1.59-3.89, P < 0.001 and HR: 2.19, 95% CI: 1.69-2.83, P < 0.001, respectively). Additionally, patients with seropositive RA showed better compliance and persistence with BPs compared with their seronegative counterparts. CONCLUSIONS: Compliance and persistence with oral BPs in RA patients were suboptimal in real practice, thereby limiting the efficacy of osteoporosis treatment. Extending the dosing interval of BPs may improve medication adherence in RA patients.

Insulin resistance is associated with digital ulcer in patients with systemic sclerosis.

OBJECTIVES: To investigate the relationship between insulin resistance and digital ulcers (DUs) in patients with systemic sclerosis (SSc). METHODS: Using a cross-sectional design, we recruited 73 consecutive female patients with SSc and 109 sex- and age-matched healthy controls in South Korea from July 2014 to June 2015. The magnitude of insulin resistance was measured using the homeostatic model assessment of insulin resistance (HOMA-IR). DUs ever included active and healed DUs and the extent of skin fibrosis was evaluated using the modified Rodnan skin score (MRSS). RESULTS: The HOMA-IR in patients with SSc was significantly higher than that in healthy controls (median 1.18 vs. 0.71, p<0.001). In SSc patients, 7 (9.6%) had active DUs and 14 subjects (19.2%) had healed DUs; thus, DUs ever were observed in 21 cases (28.8%). SSc patients with DUs ever had significantly higher HOMA-IR and MRSS compared with those without this feature (median, 2.05 vs. 0.99, p=0.001 and 14 vs. 9.5, p=0.011, respectively). After adjustment for confounding factors using multivariable logistic regression analyses, the HOMA-IR showed a significant positive association with the presence of DUs ever in patients with SSc (OR=1.43, 95% CI=1.01-2.05, p=0.048). In addition, higher MRSS was significantly correlated with DUs ever (OR=1.11, 95% CI=1.02-1.21, p=0.015). CONCLUSIONS: Insulin resistance was independently associated with the presence of DUs in patients with SSc and may be a potential biomarker for SSc micro-vasculopathy. Moreover, our data also suggest a potential contribution of insulin resistance to the pathogenesis of DUs.

Drug survival and the associated predictors in South Korean patients with rheumatoid arthritis receiving tacrolimus.

BACKGROUND/AIMS: To investigate the drug survival rate of tacrolimus (TAC) and analyze the potential predictors of this rate in patients with rheumatoid arthritis (RA) in routine care. METHODS2018-01-16: In this retrospective longitudinal study, we enrolled 102 RA patients treated with TAC from April 2009 to January 2014 at a tertiary center in South Korea. The causes of TAC discontinuation were classified as lack of efficacy (LOE), adverse events (AEs), and others. The drug survival rate was estimated using the Kaplan-Meier method and the predictors of this rate were identified by Cox-regression analyses. RESULTS: TAC was discontinued in 27 of 102 RA patients (26.5%). The overall 1-, 2-, 3-, and 4-year TAC continuation rates were 81.8%, 78.4%, 74.2%, and 69.1%, respectively and the median follow-up period from the start of TAC was 32.5 months. The number of TAC discontinuations due to LOE, AEs, and others were 15 (55.6%), 11 (40.7 %), and 1 (3.7%), respectively. The baseline high disease activity was a significant risk factor for TAC discontinuation after adjusting for confounding factors (hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.16 to 5.35; p = 0.019). In addition, underlying interstitial lung disease was significantly associated with TAC withdrawal due to AEs (HR, 3.49; 95% CI, 1.06 to 11.46; p = 0.039). CONCLUSIONS: In our study, TAC showed a good overall survival rate in patients with RA in real clinical practice. This suggests that the long-term TAC therapy has a favorable efficacy and safety profile for treating RA.

Male patients with rheumatoid arthritis have an increased risk of osteoporosis: Frequency and risk factors.

Most previous research investigating osteoporosis in rheumatoid arthritis (RA) has focused on female patients and there is a lack of data regarding clinical characteristics of osteoporosis in male patients with RA.The aim of this study was to compare the frequency of osteoporosis between male patients with RA and healthy patients, and to identify the risk factors for osteoporosis and low bone mineral density (BMD) in male patients with RA.We conducted a retrospective, cross-sectional study including 76 South Korean male patients with RA aged over 50 years and 76 age-matched male healthy individuals. BMD was measured at the lumbar spine (L1-4) and left hip (femoral neck and total hip) using dual energy X-ray absorptiometry. Osteoporosis was defined as a T-score of ≤ -2.5 according to the World Health Organization (WHO) classification.The frequency of osteoporosis at either the spine or the hip among male patients with RA was significantly higher than that among controls (22.4% vs 10.5%, P = .049) and RA patients had a significantly lower total hip BMD than healthy individuals (0.92 ±â€Š0.14 vs 0.96 ±â€Š0.1 g/cm, P = .027). For male RA patients, the mean 28-joint Disease Activity Scores using erythrocyte sedimentation rate (DAS28-ESR) and body mass index (BMI) were 3.28 and 22 kg/m, respectively. In multivariable logistic regression models, BMI ≤ 22 kg/m (odds ratio = 3.43, P = .043) and DAS28-ESR > 3.2 (odds ratio = 3.85, P = .032) were independent risk factors for osteoporosis at either site in male patients with RA.Our data demonstrate that male patients with RA had a 2.1 times higher risk for osteoporosis compared with healthy individuals. This suggests that appropriate management of osteoporosis in patients with RA is crucial not only for postmenopausal women but also for men aged over 50 years, especially those with low BMI and higher disease activity.

Relationship between serum adipokine levels and radiographic progression in patients with ankylosing spondylitis: A preliminary 2-year longitudinal study.

The immunomodulatory effects of adipokines have been extensively studied in rheumatic diseases, and there is a paucity of information regarding their effects on bone metabolism.The aim of this study was to investigate the relationships between serum adipokines levels and radiographic progression over 2 years in patients with ankylosing spondylitis (AS).In this preliminary longitudinal study, we prospectively recruited 20 consecutive male patients with AS and 11 gender- and age-matched healthy subjects. At the baseline and 2-year follow-up, serum adiponectin, leptin, resistin, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and Dickkopf-1(DKK-1) levels were measured in AS patients using enzyme-linked immunosorbent assays; these measurements were only performed at the baseline for healthy controls. Radiographic progression was determined as the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) progression of ≥2 by comparing the baseline and 2-year follow-up radiographs.All AS patients were naive to TNF-α blockers at the enrollment and during the 2-year follow-up period and their median disease duration was 51.5 months. At the baseline, the serum resistin, TNF-α, and IL-6 levels were significantly higher in AS patients than in controls. At the 2-year follow-up, the median mSASSS of AS patients was found to be significantly increased from the baseline (8-10.5, P = .001) and 7 (35%) AS patients showed radiographic progression. In AS patients, the leptin and resistin levels were significantly higher at the 2-year follow-up than at the baseline. The baseline resistin levels and changes in leptin levels from the baseline to the 2-year follow-up were significantly higher in AS patients with radiographic progression than in those without radiographic progression (P = .002 and .024, respectively). The baseline resistin levels and the increase in leptin levels during the follow-up period significantly correlated with changes in mSASSS (ρ = 0.528 and 0.559, P = .017 and .01, respectively). No association between changes in serum adipokine levels and disease activity in AS patients was observed.Our findings suggest that leptin and resistin may contribute to the pathogenesis of new bone formation rather than to inflammatory processes and have the potential to be used as biomarkers of the structural outcome of AS.

Vitamin D deficiency is associated with digital ulcer but not with atherosclerosis or arterial stiffness in patients with systemic sclerosis: a pilot study.

The objective of this study was to investigate the association of vitamin D deficiency with digital ulcers (DUs) that result from microvasculopathy, carotid intima-media thickness (CIMT) as surrogate markers of atherosclerosis, and brachial-ankle pulse wave velocity (baPWV) representing arterial stiffness in patients with systemic sclerosis (SSc). In this cross-sectional study, 40 female SSc patients and 80 healthy controls matched for sex, age, and blood sampling season were recruited. Vitamin D deficiency was defined as serum 25-OHD levels <30 ng/mL. "DUs ever" included active and healed DUs. CIMT and carotid plaque were examined using high-resolution ultrasonography, and baPWV was measured using an automatic waveform analyzer. Vitamin D deficiency was more prevalent in SSc patients than in controls (30 vs. 11.3%). Regarding SSc patients, 9 (22.5%) had DUs ever, and the mean CIMT and baPWV were 0.68 mm and 1561.1 cm/s, respectively; carotid plaque was detected in 13 (34.2%) patients. The frequency of DUs ever was significantly higher for SSc patients with vitamin D deficiency than those without this feature (50 vs. 10.7%, p = 0.012), but the median CIMT and baPWV and the frequency of carotid plaque did not differ according to the presence of vitamin D deficiency. Multivariable logistic regression analysis showed that vitamin D deficiency was an independent risk factor for DUs ever (OR = 7.72, p = 0.024). Vitamin D deficiency was associated with DUs, but not with atherosclerosis or arterial stiffness, potentially indicating that vitamin D may have different effects on the microvascular and macrovascular involvement in SSc pathophysiology.

Vitamin D status of patients with early inflammatory arthritis.

The present study aimed to investigate the vitamin D status in patients with early inflammatory arthritis (EIA). We conducted a retrospective study among patients who presented with EIA at the outpatient rheumatology clinic of a tertiary referral center between March 2012 and February 2013. In total, 101 subjects with EIA (≥1 swollen joint and symptom duration of ≤6 months, not explained by another disease) and 101 healthy controls matched for age, sex, and the month of serum vitamin D measurements were enrolled. Serum 25-hydroxy vitamin D (25-OHD) concentrations were assessed by radioimmunoassay. Vitamin D "deficiency" and "severe deficiency" were defined as serum 25-OHD levels <20 and <10 ng/mL, respectively. Among EIA patients, rheumatoid arthritis (RA) was classified according to the 2010 American College of Rheumatology/European League against Rheumatism criteria. Vitamin D deficiency was highly prevalent among EIA patients, but no significant differences in the frequency of vitamin D deficiency of EIA patients and controls were observed (75.2 vs 65.3%, p = 0.106). Additionally, in spring and summer, EIA patients had significantly lower serum 25-OHD concentrations than controls, but the opposite trend was observed in autumn. Among 101 EIA patients, 38 (37.1%) were classified as having RA. Severe vitamin D deficiency in EIA patients was significantly associated with the higher likelihood of being classified as having RA. In conclusion, the frequency of vitamin D deficiency in EIA patients was comparable to that in controls, but severe vitamin D deficiency was associated with the presence of RA among EIA patients.

A study of the reliability and validity of the korean version of the penn alcohol craving scale for alcohol-dependent patients.

OBJECTIVE: The Penn Alcohol Craving Scale (PACS) is a stronger predictor of subsequent drinking and relapse of alcohol dependence that can be administered more quickly and easily than other craving scales. The goal of this study was to develop the Korean version of the Penn Alcohol Craving Scale (PACS-K). METHODS: To examine the psychometric properties of the PACS-K, responses were chosen from 80 patients admitted to a treatment facility for alcohol dependence. RESULTS: The PACS-K possesses good psychometric properties, as assessed by Cronbach's alpha estimates (Cronbach's alpha=0.91). The test-retest reliability of the PACS-K showed high correlation (p<0.01) when the retest interval was 1 day. When the validity of the PACS-K was investigated using correlation analysis with two other craving scales (the Obsessive Compulsive Drinking Scale (OCDS) and the Visual Analogue Scale (VAS), high correlations were obtained between total PACS scores and total OCDS scores, and between total PACS scores and VAS scores (p<0.01, respectively). CONCLUSION: The PACS-K is a reliable and valid measure of alcohol cravings, and it could be useful for predicting which individuals are at risk for subsequent relapse.