Ying-Chou Chen

Cumulative immunosuppressant exposure is associated with diversified cancer risk among 14 832 patients with systemic lupus erythematosus: a nested case–control study

Objectives. Immunosuppressive therapy is necessary to alter the natural course of SLE. However, immunosuppressant‐related cancer risk is a major concern. The aim of this study was to determine whether immunosuppressant use is associated with cancer risk in SLE. Methods. We designed a retrospective nested case‐control study within an SLE population based on the National Health Insurance Research Database in Taiwan. We screened 14 842 patients with SLE from 2001 to 2013 and compared patients with SLE complicated by later cancer with patients with SLE but without cancer. The cumulative dose of immunosuppressants was calculated from the SLE diagnosis date to the occurrence of cancer. The immunosuppressants of interest were AZA, CYC, MTX, HCQ and systemic glucocorticoids. Adjusted odds ratios (ORs) for cancer were calculated in conditional Cox regression models after propensity score matching. Results. The top five types of cancers were breast (16.9%), haematological (11.7%), colorectal (11.0%), lung (10.6%) and hepatobiliary (10.4%) cancers. After matching, this study included 330 cancer patients and 1320 matched cancer‐free patients. The adjusted analyses showed an association of a higher cumulative CYC dose (OR = 1.09, 95% CI: 1.04, 1.13) and lower HCQ dose (OR = 0.93, 95% CI: 0.90, 0.97) with cancer risk in comparison with the controls. Conclusion. Diverse cancer risks are associated with different immunosuppressants in patients with SLE. CYC increases the risk of cancer, and HCQ decreases this risk in SLE patients, both in a dose‐dependent manner.

Adherence to anti-osteoporotic regimens in a Southern Taiwanese population treated according to guidelines: a hospital-based study.

This study was designed to investigate adherence to anti‐osteoporotic regimens in a population following therapeutic guidelines; and to assess whether this experience differs from that in other administrative surveys.

Preliminary study of a traditional Chinese medicine formula in systemic lupus erythematosus patients to taper steroid dose and prevent disease flare-up

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease. Prolonged complete remission is rare. Most patients with SLE need long‐term treatment with glucocorticoid and immunomodulators. However, side effects because of the above medications are common. We evaluated the effect of adding‐on Dan‐Chi‐Liu‐Wei combination (DCLWC) on SLE patients with conventional therapy in tapering steroid and preventing disease flare‐up. This was a double‐blind and randomized controlled trial. Sixty‐six SLE patients were recruited into this study and 53 patients who fulfilled the 1997 revised criteria for the classification of SLE with an SLE disease activity index (SLEDAI) score of 2–12 and a steroid (measured with prednisolone) daily dose of less than 20 mg/d were enrolled. The patients were randomized into either an experimental or control group. We checked the urine analysis, hemogram, liver function, renal function, C3, C4, erythrocyte sedimentation rate, and anti‐dsDNA, evaluated the SLEDAI score, and recorded the steroid dose at 0 months, 3 months, and 6 months, respectively. After 6 months of study, the C4 and blood urea nitrogen level revealed a statistically significant difference in either group. There was a tendency toward a decreased SLEDAI score in the experimental group (p = 0.083) but not in the control group (p = 0.867). The steroid dose was not statistically significant in either group. Renal function and liver function revealed no statistically significant statistics changes in either group. Adding‐on DCLWC to conventional therapy for the treatment of SLE was safe and might have a borderline effect in decreasing disease activity, but it was not possible to taper the dosage of steroid after 6 months of clinical trial. Therefore, a long‐term follow‐up and a large‐scale study are necessary to confirm the effect of DCLWC.

Association of tri-nucleotide (CAG and GGC) repeat polymorphism of androgen receptor gene in Taiwanese women with refractory or remission rheumatoid arthritis

We investigated the relationship between CAG and GGC repeat polymorphism of the androgen receptor (AR) gene and rheumatoid arthritis (RA) in female patients with different disease subtypes. This case-control study enrolled 215 women in three groups: RA patients refractory to standardized therapy (n = 51); RA patients at complete remission phase (n = 60); and healthy controls (n = 104). CAG and GGC repeat lengths were determined by automated fluorescence-based DNA fragment-sizing method. Demographic data, allele lengths, allele distribution, and zygosity status of CAG/GGC repeats were assessed for the three groups. Refractory RA patients tend to have a significantly younger onset age of RA and more elevated erythrocyte sedimentation rates than do remission RA patients. Mean and median values of CAG and GGC repeat lengths are similar in both RA and control patients. However, RA patients harboring any long CAG alleles with more than 23 repeats had an increased risk of a refractory course, whereas differences in risk were not observed between these patients and RA subtypes harboring any long GGC alleles with more than 16 repeats. In addition, the homozygous frequency of CAG but not GGC alleles was lower in refractory RA than in remission RA patients or in controls (p = 0.042). Neither CAG nor GGC repeat lengths had a significant relationship with rheumatoid factor reactivity. Our observations indicate that short CAG repeats of the AR gene with higher transactivation activity may have protective effects against refractory course of RA development and that homozygous frequency of CAG alleles may be involved in the disease remission subtype. In contrast, lack of association of GGC polymorphism and RA was also observed. Together, these data imply that CAG but not GGC alleles in the AR polymorphism may play an important role in modulating the disease pattern of RA among Taiwanese women.

Can lumbar spine bone mineral density predict readmission in denosumab-treated patients with chronic kidney disease?

This study investigated whether bone mineral density (BMD) affects readmission risk in patients with chronic kidney diseases (CKD) who received denosumab therapy. The study design was a retrospective case review of patients with CKD. Baseline age, sex, and body mass index were recorded for all patients included in the study. All comorbidities were recorded. All subjects underwent dual energy X-ray absorptiometry assay of the lumbar spine and right hip for BMD. The primary outcome was readmission. Predictive variables were categorized and compared between readmitted and non-readmitted patients. Logistic regression was used for multivariable analysis. A total of 121 patients with CKD who received denosumab therapy were enrolled. Of these, 29 were readmitted within 2 years, and 92 had no readmission. The lumbar BMD differed between the readmission (−2.94±0.68) and non-readmission (−2.09±1.48) groups. The readmission group had a lower T score than the non-readmission group. When adjusted for potential confounding factors, a decreased lumbar BMD had a higher readmission risk. When the cut-off points determined by receiver operating characteristic curve analysis were applied, the most precise point was set at a T score of −3. Osteoporosis in patients with CKD is associated with a high risk of readmission; the best predictor after denosumab therapy was the lumbar spine T score. A lower T score (especially if <−3) was associated with a higher probability of fracture readmission. It is essential to optimize primary and secondary prevention in these patients to improve their quality of life.

Predictor of Hand Radiological Progression in Patients With Rheumatoid Arthritis Receiving Tnf Antagonist Therapy by Change in Grayscale Synovitis—a Preliminary Study

ObjectivesThis prospective study aimed to compare synovial ultrasound scores to conventional measures (DAS28, CRP levels) in predicting radiographic progression in patients with rheumatoid arthritis under TNF antagonist therapy. MethodsPatients with RA who received TNF antagonist therapy were enrolled, all of whom underwent clinical, laboratory, and ultrasonographic assessments with grayscale and power Doppler assessments of bilateral elbows (anterior and posterior recess), wrists (dorsal, palmar, and ulnar aspects), second and third MCP joints (dorsal and palmar recess), and PIP II and III (dorsal and palmar) at baseline and at 1, 3 months. Hand radiographic damage was evaluated using van der Heijde modified Total Sharp Score (TSS) at baseline and 12 months. ResultsThirty-two patients (384 joints, 832 synovial sites) continued the same treatment regimen for 12 months and completed the study, 41.6% of whom showed radiographic progression during the study period. Baseline DAS28 (P = 0.123), CRP level (P = 0.177), grayscale synovitis (P = 0.092), and power Doppler synovitis (P = 0.120) could not predict radiological damage in the TNF antagonist therapy group. However, &Dgr;TSS was significantly related to changes in grayscale synovitis between baseline and 1 month (P = 0.011), but not at 3 months (P = 0.591), and was not related to changes in the power Doppler score at 1 (P = 0.634) and 3 months (P = 0.298). ConclusionsOur data confirm that delayed improvement in grayscale synovitis between baseline and 1 month more accurately reflects 1-year radiological damage than conventional measures such as DAS28 score and CRP level. Therefore, we recommend serial ultrasound follow-up of patients with RA receiving TNF antagonist therapy.

Urinary UMOD Excretion and Chronic Kidney Disease in Gout Patients: Cross-Sectional Case–Control Study

Patients with gout often have concurrent chronic kidney disease (CKD); the relationship between the two conditions is still unclear. Previous studies have identified an association between low level of urinary uromodulin (UMOD) and CKD within the setting of diabetes and lupus. The aim of this study was to examine the association between urinary UMOD excretion and CKD in patients with gout. A total of 53 Taiwanese gout patients with stable disease activity were enrolled. Patients were divided into a CKD group (n = 25) and a non-CKD group (n = 28). Using Pearson correlation analysis, urinary UMOD excretion was positively correlated with estimated glomerular filtration rate (Ha: ρ > 0, p = 0.004). Using multivariate analysis, patients with CKD and gout were associated with lower urinary UMOD excretion than those who have gout alone [odds ratio (95% CI): 0.826 (0.694–0.985), p < 0.001]. Patients with CKD and gout were also more likely to be older (p < 0.001) and have higher uric acid levels (p < 0.001). This study implicates that UMOD might play a role in the relationship between gout and CKD. Further studies with animal models of gout and CKD would be recommended.

The Diagnostic Value of Anti-CCP and Rheumatoid Factor for Patients with Refractory Rheumatoid Arthritis (RA) and RA in Remission

To compare the diagnostic value of antibodies to cyclic citrullinated peptides (anti-CCP) and rheumatoid factor (RF) for patients with refractory rheumatoid arthritis (RA) and RA in remission. Methods. A total of one hundred and forty three participants were enrolled: fifty one patients with RA refractory to standard methotrexate therapy, group I (Gr I, refractory RA); forty three RA patients in complete remission status for at least 3 months, group II (Gr II, RA in remission); and forty nine community-based healthy controls, group III (Gr III). Levels of anti-CCP and RF were measured for all of the subjects. The sensitivity and specificity of both tests were determined via these subjects. The receiver operating characteristic (ROC) analysis was used to display the pairs of sensitivity and specificity for different cut off points of anti-CCP and RF. False negative rate and the complementary diagnostic effect of both assays were also calculated and compared. Results. The sensitivity of anti-CCP and RF for Gr I were 84% and 78%, and 74% and 67% for Gr II, respectively. The specificity of anti-CCP and RF was 98% and 92% respectively. The ROC analysis disclosed that anti-CCP, compared to RF, provided the best combination of sensitivity and specificity for detecting either groups of RA. In addition, anti-CCP provided better complementary diagnostic effect for our RA patients when the results of opposite tests were negative (33% vs 11% in Gr I, and 29% vs 9% in Gr II) (p＜0.001). Conclusion. The detection of anti-CCP in the diagnosis of patients with refractory RA and RA in remission showed higher sensitivity and specificity than RF assay.

Inpatients with Allopurinol Hypersensitivity Syndrome: Experiences at a Medical Center in Southern Taiwan

Allopurinol is considered an effective and safe uric-acid lowering drug but occasional severe allopurinol hypersensitivity syndrome (AHS) may develop. Reviewing the records of 22 inpatients with AHS at our hospital, impaired renal function and old age seem to play an important role in the development of AHS. Three cases developed AHS with elevation of total 1gE level only 5-10 minutes after taking 100mg of allopurinol. This finding seems to imply that type I hypersensitivity could play a part in the development of AHS. One patient experienced 5 episodes of AHS due to the ignorance of AHS history at other hospitals or drug stores, which could be avoided by giving these patients Medic-Alert bracelets, noting the history of AHS. Twelve cases (54.5%) received allopurinol because of asymptomatic hyperuricemia, which is a common practice in Southern Taiwan but not an established indication for starting allopurinol. The chances of developing AHS could be lowered if the clinicians follow the proper indications for the use of allopurinol. We suggest that allopurinol should be prescribed in cases that exhibit proper indications. And the dosage for patients with impaired renal function and/or older age should be adjusted.

Adherence to hydroxychloroquine improves long-term survival of patients with systemic lupus erythematosus

Objectives HCQ, which is known to decrease SLE activity, may have a protective effect on survival, but this has not been proven in Asia. This study aimed to determine whether HCQ treatment is associated with increased survival in patients with SLE. Methods We designed this prospective SLE cohort study using data from the Taiwan National Health Insurance Research Database. The participants were divided into HCQ and control groups according to whether HCQ was prescribed during the first year after an SLE diagnosis. The primary outcome was mortality 1 year after inclusion. In the subgroup analysis, these participants were divided based on medication possession ratio (MPR) in the first year into non-users, MPR <40%, 40% ⩽ MPR < 80% and MPR ⩾80% subgroups to explore the relationship between survival and HCQ adherence. Results A total of 12 443 patients were eligible for the analysis. After propensity score matching, we included 2287 patients in each group. During a mean follow-up of 7.6 years, there were 169 events in the HCQ group (7.4%) and 248 events in the control group (10.8%). The risk of mortality in the HCQ group was lower than that in the control group (hazard ratio = 0.68; 95% CI: 0.56, 0.82). The subgroup analysis revealed that the survival protective effect was associated with HCQ adherence. Conclusion Patients with SLE who received HCQ had lower mortality rates due to any cause than those who did not. The survival benefit could be augmented by HCQ adherence.