Factors associated with early-onset intracranial aneurysms in patients with autosomal dominant polycystic kidney disease.

BACKGROUND: Recently, the importance of attribute-based medicine has been emphasized. The effects of early-onset intracranial aneurysms on patients can be significant and long-lasting. Herein, we compared the factors associated with intracranial aneurysms in patients with autosomal dominant polycystic kidney disease (ADPKD) according to age categories (≥ 50 years, < 50 years). METHODS: We included 519 ADPKD patients, with a median age of 44 years, estimated glomerular filtration rate of 54.5 mL/min/1.73 m2, and total follow-up duration of 3104 patient-years. Logistic regression analyses were performed to determine factors associated with intracranial aneurysms. RESULTS: Regarding the presence of intracranial aneurysm, significant interactions were identified between the age category (age ≥ 50 years), female sex (P = 0.0027 for the interaction) and hypertension (P = 0.0074 for the interaction). Female sex and hypertension were associated with intracranial aneurysm risk factors only in patients aged ≥ 50 years. The presence of intracranial aneurysm was significantly associated with chronic kidney disease (CKD) stages 4-5 (odds ratio [OR] = 3.87, P = 0.0007) and family history of intracranial aneurysm or subarachnoid hemorrhage (OR = 2.30, P = 0.0217) in patients aged < 50 years. For patients aged ≥ 50 years, in addition to the abovementioned factors [OR = 2.38, P = 0.0355 for CKD stages 4-5; OR = 3.49, P = 0.0094 for family history of intracranial aneurysm or subarachnoid hemorrhage], female sex (OR = 4.51, P = 0.0005), and hypertension (OR = 5.89, P = 0.0012) were also associated with intracranial aneurysm. CONCLUSION: Kidney dysfunction and family history of intracranial aneurysm or subarachnoid hemorrhage are risk factors for early-onset intracranial aneurysm. Patients aged < 50 years with a family history of intracranial aneurysm or subarachnoid hemorrhage or with CKD stages 4-5 may be at an increased risk of early-onset intracranial aneurysm.

Immediate drop of urine osmolality upon tolvaptan initiation predicts impact on renal prognosis in patients with ADPKD.

BACKGROUND AND HYPOTHESIS: Tolvaptan, a vasopressin V2 receptor antagonist, is used for treating autosomal dominant polycystic kidney disease (ADPKD). We focused on changes in urinary osmolality (U-Osm) after tolvaptan initiation to determine whether they were associated with the therapeutic response to tolvaptan. METHODS: This was a single-centre, prospective, observational cohort study. Seventy-two patients with ADPKD who received tolvaptan were recruited. We analysed the relationship between changes in U-Osm and annual estimated glomerular filtration rate (eGFR) in terms of renal prognostic value using univariable and multivariable linear regression analyses. RESULTS: The mean value of U-Osm immediately before tolvaptan initiation was 351.8 ± 142.2 mosm/kg H2O, which decreased to 97.6 ± 23.8 mosm/kg H2O in the evening. The decrease in U-Osm was maintained in the outpatient clinic 1 month later. However, the values of U-Osm showed higher variability (160.2 ± 83.8 mosm/kg H2O) than did those in the first evening of tolvaptan administration. Multivariate analysis revealed that the baseline eGFR, baseline urinary protein, and U-Osm change in the evening of the day of admission (initial U-Osm drop) were significantly correlated with the subsequent annual change in eGFR. CONCLUSIONS: U-Osm can be measured easily and rapidly, and U-Osm change within a short time after tolvaptan initiation may be a useful index for the renal prognosis in actual clinical practice.

Duration of sweat cyclophosphamide excretion in patients undergoing a conditioning regimen of high-dose cyclophosphamide for hematopoietic stem-cell transplantation.

PURPOSE: To investigate the duration of cyclophosphamide (CPA) excretion in the sweat after administration when receiving high-dose CPA therapy as a conditioning regimen for hematopoietic stem-cell transplantation (HSCT). METHODS: Shirts and pillowcases samples (changed once a day) from 12 patients, categorized as groups 1 (n = 6), 2 (n = 4), and 3 (n = 2), receiving high-dose CPA therapy were collected, sealed, stored at 4°C, and mailed to an analytical facility for CPA estimation using LC-MS/MS. CPA was administered intravenously at a dose of 60 mg/kg on days 1, 2 (closed-system delivery for group 3), and samples were collected during days 1-4 (groups 1,3) or days 1-9 (group 2). RESULTS: CPA was detected in all 126 shirts and pillowcases. In 9 patients, excluding 1 patient who had fever during the study period and group 3 patients, the mean (range) rate of CPA excretion in sweat was 0.03% (0.01-0.12%). The mean CPA excretion in 9 patients adjusted for body weight was 19.9 µg/kg on day 1 and 0.3 µg/kg on day 4. CONCLUSIONS: This study showed that CPA was excreted for an extended duration in the patient's sweat, receiving a high-dose CPA therapy as a conditioning regimen against HSCT.

Machine learning for morbid glomerular hypertrophy.

A practical research method integrating data-driven machine learning with conventional model-driven statistics is sought after in medicine. Although glomerular hypertrophy (or a large renal corpuscle) on renal biopsy has pathophysiological implications, it is often misdiagnosed as adaptive/compensatory hypertrophy. Using a generative machine learning method, we aimed to explore the factors associated with a maximal glomerular diameter of ≥ 242.3 µm. Using the frequency-of-usage variable ranking in generative models, we defined the machine learning scores with symbolic regression via genetic programming (SR via GP). We compared important variables selected by SR with those selected by a point-biserial correlation coefficient using multivariable logistic and linear regressions to validate discriminatory ability, goodness-of-fit, and collinearity. Body mass index, complement component C3, serum total protein, arteriolosclerosis, C-reactive protein, and the Oxford E1 score were ranked among the top 10 variables with high machine learning scores using SR via GP, while the estimated glomerular filtration rate was ranked 46 among the 60 variables. In multivariable analyses, the R2 value was higher (0.61 vs. 0.45), and the corrected Akaike Information Criterion value was lower (402.7 vs. 417.2) with variables selected with SR than those selected with point-biserial r. There were two variables with variance inflation factors higher than 5 in those using point-biserial r and none in SR. Data-driven machine learning models may be useful in identifying significant and insignificant correlated factors. Our method may be generalized to other medical research due to the procedural simplicity of using top-ranked variables selected by machine learning.

Impact of kidney function and kidney volume on intracranial aneurysms in patients with autosomal dominant polycystic kidney disease.

Presently, only personal or family history of intracranial aneurysm/subarachnoid hemorrhage (IA/SAH) has been established as a risk factor for IA in autosomal dominant polycystic kidney disease (ADPKD). This study aimed to verify the association between kidney function/volume and IAs in patients with ADPKD. This study included 519 patients with ADPKD. At baseline IA screening, the median age and estimated glomerular filtration rate were 44 years and 54.5 mL/min/1.73 m2, respectively. Family IA/SAH history was confirmed in 18.1% of the patients, and 54.3% of the patients had hypertension. The IA point prevalence was 12.5%. During clinical follow up of 3104 patient-years, de novo IA was detected in 29 patients (0.93% patient-years). The IA period prevalence was 18.1% (median age, 60 years). Multivariable logistic regression demonstrated that total kidney volume (TKV) ≥ 1000 mL (odds ratio [OR] = 2.81), height-adjusted TKV ≥ 500 mL (OR = 2.81), Mayo imaging classification Class 1D-1E (OR = 2.52), and chronic kidney disease stages 3-5 (OR = 2.31) were significantly associated with IA formation. IAs in patients with ADPKD may be associated not only with general risk factors for IAs but also with declining kidney function and increased KV. Kidney disease progression may contribute to effective IA screening and treatment planning in patients with ADPKD.

Germline Mutations for Kidney Volume in ADPKD.

Introduction: Valid prediction models or predictors of disease progression in children and young patients with autosomal dominant polycystic kidney disease (ADPKD) are lacking. Although total kidney volume (TKV) and Mayo imaging classification are generally used to predict disease progression in patients with ADPKD, it remains unclear whether germline mutation types are associated with these factors. We therefore investigated the association between mutation type and TKV and Mayo imaging classification among patients with ADPKD. Methods: A total of 129 patients with ADPKD who underwent genetic analyses were enrolled in the study. The associations between the severity of PKD (TKV ≥ 1000 ml and Mayo classes 1C-1E) and the PKD1 mutation types (nonsense mutation, frameshift or splicing mutation, and substitution) were evaluated. Results: Among the mutation types, only PKD1 splicing/frameshift mutation had significant associations with TKV ≥ 1000 ml in sex-adjusted and multivariable logistic analyses. Similarly, only the PKD1 splicing/frameshift mutation was significantly associated with Mayo 1C-1E in sex-adjusted and multivariable logistic analyses. PKD1 nonsense mutation, PKD1 substitution, or PKD1 mutation position had no significant association with TKV ≥ 1000 ml or Mayo 1C-1E. Conclusion: Kidney cyst severity differs according to the mutation types in PKD1. Patients with PKD1 splicing mutations or PKD1 frameshift mutations are associated with TKV ≥ 1000 ml or Mayo 1C-1E. Detailed assessment of mutation types may be useful for predicting renal prognosis in patients with ADPKD and may especially contribute to the care of a high-risk group of children with ADPKD.

Initial decline in eGFR to predict tolvaptan response in autosomal-dominant polycystic kidney disease.

BACKGROUND: Tolvaptan, a vasopressin V2 receptor antagonist, is used to treat autosomal-dominant polycystic kidney disease (ADPKD). Although tolvaptan curbs disease progression, a few reports have examined factors related to treatment response. The estimated glomerular filtration rate (eGFR) decreases soon after tolvaptan is initiated. We investigated whether initial eGFR decline affects renal prognosis of patients. METHODS: This was a single-center, retrospective observational cohort study. Eighty-three patients with ADPKD who initiated tolvaptan were selected. We analyzed the relationship of the initial eGFR change with clinical parameters and analyzed the annual eGFR change in terms of renal prognostic value using univariable and multivariable linear regression analyses. RESULTS: The initial eGFR change was - 4.6 ± 8.0%/month. The initial eGFR change correlated significantly with the annual eGFR change in multivariable analysis, suggesting that the larger decline in the initial eGFR change, the better the renal prognosis. Furthermore, the change in fractional excretion (FE) of free water (FEH2O) correlated positively with initial eGFR change. FEH2O and urea nitrogen FE (FEUN) increased significantly; however, sodium FE (FENa) level remained unchanged. In approximately half of the patients, FENa unexpectedly decreased. CONCLUSIONS: The initial eGFR decline might be caused by suppressing glomerular hyperfiltration, due to the pharmacological effect of tolvaptan, and/or by reducing renal plasma flow, due to potential volume depletion. The initial eGFR change reflects the tolvaptan effect, can be easily evaluated in clinical practice, and may be useful as one of the clinical indicator for predicting renal prognosis in patients under tolvaptan.

Slowly Progressive Male Alport Syndrome Evaluated by Serial Biopsy: Importance of Type IV Collagen Staining.

A slowly progressive middle-aged man initially diagnosed with thin basement membrane nephropathy based on extensive thinning of the glomerular basement membrane (GBM) was subsequently diagnosed with Alport syndrome (AS) by a serial renal biopsy eight years later. The ultrastructural analysis of the second biopsy indicated thickening and wrinkling with mild reticulation in the GBM, consistent with AS. However, a retrospective analysis of the first biopsy revealed mild attenuation of type IV collagen α5 chain staining, suggesting a potential diagnosis of AS, despite the lack of ultrastructural features of AS. We herein report the clinical usefulness of type IV collagen staining in the early diagnosis of AS.

Successful Treatment with Belimumab in a Patient with Refractory Systemic Lupus Erythematosus after Initiation of Hemodialysis: Considering the Synergistic Effect of Belimumab and Immunological Burn-Out Phenomenon in End-Stage Renal Disease Patients on Hemodialysis.

BACKGROUND: In patients with systemic lupus erythematosus (SLE), disease activity can persist even after initiating dialysis. However, guidelines for the treatment of patients with SLE after dialysis is initiated have not yet been established. CASE PRESENTATION: We describe the case of a 54-year-old Japanese woman who was diagnosed with SLE at age 12, progressed to end-stage renal disease (ESRD), and initiated hemodialysis for lupus nephritis. However, SLE activity persisted after hemodialysis. Cyclophosphamide and mycophenolate mofetil were administered in addition to prednisolone and immunoadsorption, but this treatment strategy was limited by side effects. The patient was subsequently treated with belimumab, and the activity of SLE decreased rapidly. CONCLUSIONS: ESRD patients with SLE show no significant decrease in transitional B cells and have elevated levels of B-cell activating factor (BAFF). Both transitional B cells and BAFF are important therapeutic targets for belimumab, indicating that patients with ESRD may benefit from belimumab therapy. However, the effects of belimumab may be potentiated in patients with uremia, who may be more susceptible to adverse events such as infections. Patients with SLE who receive belimumab after initiation of hemodialysis therefore require careful follow-up. Here, we report the first case of belimumab administration in a patient with SLE after initiation of hemodialysis.

Urinary Aquaporin 2 as a Potential Indicator Predicting Tolvaptan Response in Patients With ADPKD.

INTRODUCTION: Tolvaptan is used to treat autosomal dominant polycystic kidney disease (ADPKD) because it inhibits binding of the antidiuretic hormone vasopressin to the vasopressin V2 receptor (V2R), which suppresses the insertion of preformed water channel aquaporin 2 (AQP2) molecules in the luminal membrane of the collecting duct cells. METHODS: This single-center, prospective observational cohort study investigated whether decreased AQP2 elimination in urine affects the renal prognosis of patients who received tolvaptan. We selected 92 patients with ADPKD who were administered tolvaptan in our hospital. We evaluated correlations between changes in urinary AQP2 (U-AQP2) and clinical parameters and the annual change in total kidney volume (TKV) and estimated glomerular filtration rate (eGFR) as renal prognostic factors using univariable and multivariable multiple regression analyses. RESULTS: The observation period was 2.4 ± 1.5 years. U-AQP2 per milligram of urinary creatinine (U-AQP2/Cr) decreased from 67.8 ± 50.6 to 20.7 ± 15.1 fmol/mg urinary creatinine after 1 month of tolvaptan treatment. This initial change in U-AQP2/Cr was correlated with high baseline U-AQP2/Cr, low baseline eGFR, and a large initial change in eGFR (baseline to 1 month). The initial change in U-AQP2/Cr (baseline to 1 month) was strongly correlated with the annual change in TKV and eGFR in multivariable analysis. CONCLUSION: Initial decrease in U-AQP2/Cr in the first month of treatment reflects the pharmacologic effect of tolvaptan and could be an indicator of renal prognosis during tolvaptan treatment.

Lupus Nephritis and Hydroxychloroquine-Associated Zebra Bodies: Not Just in Fabry Disease.

Zebra bodies in kidney biopsy specimens are widely accepted as a specific feature of Fabry disease but they can also be present in a drug-induced mimic of Fabry disease, phospholipidosis. Chloroquine and hydroxychloroquine may both induce zebra body formation and kidney phospholipidosis. However, the frequency and clinical significance of such changes remain unknown. We report 5 serial kidney biopsy cases diagnosed as lupus nephritis during hydroxychloroquine administration. All 5 patients exhibited a few, but varying amounts, of zebra bodies in glomerular intrinsic cells, that is, podocytes, parietal epithelial cells, mesangial cells, and endothelial cells. Most of the zebra bodies detected were subtle, though certainly recognizable; these zebra bodies were much smaller than those observed in Fabry disease. Zebra bodies were not observed in patients with lupus nephritis in the absence of chloroquine or hydroxychloroquine administration. All patients with lupus nephritis who received hydroxychloroquine achieved complete remission during continuous use of hydroxychloroquine, though kidney toxicity of drug-induced phospholipidosis might be masked by immunosuppression. Based on this small series of cases, we speculate that the hydroxychloroquine-associated manifestation of zebra bodies and phospholipidosis in the kidney may be frequent phenomena and may have only a subclinical influence on kidney function, at least in the short term.

Predicting liver cyst severity by mutations in patients with autosomal-dominant polycystic kidney disease.

BACKGROUND: Most patients with autosomal-dominant polycystic kidney disease (ADPKD) develop liver cysts and polycystic liver disease as they age. To date, no simple clinical indicator has been confirmed to predict polycystic liver disease exacerbation. Furthermore, the effect of the type and location of mutation on disease progression of polycystic liver disease remains unclear. Here, we aimed to establish a simple liver cyst indicator for clinical practice and investigate whether gene mutations determined liver phenotype in patients with autosomal-dominant polycystic kidney disease. METHODS: In total, 129 patients with ADPKD were enrolled and liver cyst indicators were assessed based on mutation type (truncating mutation: nonsense, frameshift, and splicing mutation; non-truncating mutation: substitution) and mutation position. Liver cyst severity was determined using Gigot and Drenth classifications, based on their number, maximum diameter, and area ratio with the liver. RESULTS: We observed an overall prevalence of 62.8% for polycystic liver disease. Patients with PKD1 nonsense mutations, a type of PKD1 truncating mutation, exhibited more severe liver disease phenotypes than those without the mutation. We identified maximum diameter as a potential liver cyst indicator. Moreover, a subgroup analysis that included a PKD1 nonsense mutation cohort revealed that genetic mutations located closer to the 5' end of PKD1 were associated with a maximum diameter index value ≥ 6 cm. CONCLUSION: PKD1 nonsense mutations were associated with liver cyst severity, which along with maximum diameter index as a simple clinical indicator for liver cysts, may improve the treatment of polycystic liver disease associated with ADPKD.

Impact of visceral fat area in patients with chronic kidney disease.

Longitudinal studies evaluating the association between visceral fat area (VFA) and kidney function decline in patients with chronic kidney disease (CKD) are limited, and little is known about VFA interactions contributing to the kidney prognosis (e.g. interactions between VFA ≥ 100 cm2 and age, sex, and CKD category). In this study, we stratified patients with CKD according to VFA category, as well as age, sex, CKD category, hyperglycemia, and diabetes mellitus, and determined the ability of obesity-related indicators (body mass index, waist circumference, subcutaneous fat area, visceral-to-subcutaneous fat ratio) to predict the renal prognosis. Kidney outcomes (≥ 50% estimated glomerular filtration rate decline or end-stage kidney disease) were examined in 200 patients with CKD (median follow-up, 12.3 years). On multivariable Cox analysis, an increase in VFA (10-cm2 increase) was significantly associated with kidney outcomes in the entire cohort, and VFA was significantly associated with kidney disease progression even in the VFA < 100 cm2 sub-cohort. Interestingly, the hazard ratio (HR) was higher for VFA (10-cm2 increase) than for the VFA ≥ 100 cm2 sub-cohort (HR 1.33 vs. 1.07). Overall, VFA was found to be the most versatile obesity-related indicator associated with kidney disease progression. VFA was associated with the primary outcome in the sub-cohorts of CKD stages 1-2, hyperglycemia, and diabetes mellitus. A high VFA was a significant kidney prognostic factor in the entire CKD cohort, with greater significance in patients with VFA < 100 cm2 than in patients with VFA ≥ 100 cm2. Our results may provide new insights into strategies for treating CKD.

Treatment practices and costs among patients with psoriatic arthritis: A Japanese hospital claims database analysis.

OBJECTIVE: Assess patient characteristics, real-world treatment patterns, and health care resource utilization (HCRU) among patients with psoriatic arthritis (PsA) in Japan. METHODS: Patients diagnosed with PsA from April 2009 through July 2017 were identified from the Medical Data Vision database. Patient characteristics, treatment patterns, and HCRU were evaluated for these patients. RESULTS: A total of 639 patients met inclusion criteria and were included in the analysis for patients with a PsA diagnosis. Over 12 months following diagnosis, patients received oral NSAIDs (61.7%), conventional synthetic disease-modifying antirheumatic drugs (DMARDs) (55.1%), corticosteroids (35.1%), topical NSAIDs (34.0%), adalimumab (14.7%), infliximab (9.7%), secukinumab (5.0%), ustekinumab (4.5%), ixekizumab (1.6%), and golimumab (1.6%). A total of 227 (35.5%) patients initiated biologic DMARDs (bDMARDs) over the median 25.2 months of study follow-up. Compared with the overall group of patients diagnosed with PsA, patients who initiated bDMARDs had higher median total per-patient health care costs ($27,772 vs. $11,316), lower median per-patient hospitalization costs ($31,164 vs. $39,359), and fewer median hospital days per admission (8.0 vs. 12.0 days). CONCLUSION: This study presents knowledge of the current state of patient characteristics, treatment patterns, HCRU, and costs among patients with PsA in Japan. Considering the relatively recent guideline recommendations, the preliminary treatment patterns suggest physicians may be following treatment guidelines.

Dose-Dependent Effect of Tolvaptan on Renal Prognosis in Patients with Autosomal Dominant Polycystic Kidney Disease.

This is the first report to describe dose dependency in the effects of tolvaptan treatment for autosomal dominant polycystic kidney disease.The weight-adjusted average daily dose of tolvaptan was found to be a factor that significantly affected the change in eGFR.If a patient shows tolerance, increasing the tolvaptan dose to the maximum should be considered.

Maximum Carotid Intima-Media Thickness in Association with Renal Outcomes.

AIM: We aimed to examine the association between the maximum intima-media thickness of the carotid artery (Max IMT) and renal prognosis, considering their potential interaction with age. METHODS: Survival analyses were performed in 112 patients with chronic kidney disease (CKD), to assess renal prognosis, with the endpoint defined as a ≥ 30% decline in estimated glomerular filtration rate (eGFR) or end-stage renal disease. RESULTS: During a median follow-up of 12.5 years, 44 participants reached the study endpoint. The major determinant of Max IMT was the maximum IMT of the internal carotid artery (Max ICA-IMT), which was the distribution ratio of 50.0% of Max IMT. Kaplan-Meier analyses showed that Max IMT ≥ 1.5 mm was significantly associated with renal prognosis when age and eGFR were matched. On multivariate Cox regression analysis, Max IMT was significantly associated with the renal outcomes and had a significant interaction with the age categories (≥ 65 years or ＜65 years) (P=0.0153 for interaction). A 1-mm increase in Max IMT was significantly associated with disease progression in the sub-cohort ＜65 years age-category, but not in the ≥ 65 years age-category; similarly the hazard ratio (HR) in the ＜65 years age-category was higher than in the ≥ 65 years age-category (HR: 2.52 vs. 0.95). Comparable results were obtained for Max ICA-IMT, Max bulb-IMT, but not for Max common carotid artery-IMT. CONCLUSIONS: A higher Max IMT was a significant renal prognosis factor in patients with CKD aged ＜65 years. Our results may provide new insights into treating CKD.

Assessment of discordance of treatment satisfaction between patients with rheumatoid arthritis in low disease activity or in remission and their treating physicians: A cross-sectional survey.

OBJECTIVES: To assess discordance in overall treatment satisfaction between patients with rheumatoid arthritis (RA) and their physicians. METHODS: This was a multicenter, cross-sectional, observational study of patients with RA (in low disease activity or remission) and their board-certified treating physicians in Japan; 202 patient-physician pairs were analyzed. Treatment satisfaction and perceptions were assessed using a structured questionnaire. RESULTS: Using a two-level ('satisfied' or 'unsatisfied') assessment of satisfaction, 195 patients (96.5%) and 190 physicians (94.1%) answered 'satisfied' with a high level of concordance (184 pairs, 91.1%). Using a four-level assessment, the ratio of 'satisfied' to 'somewhat satisfied' was higher in patients (66.3%/30.2%) than physicians (43.6%/50.5%). Satisfaction with treatment outcomes (e.g. joint conditions, subjective symptoms) was generally high in patients and physicians; relatively less satisfaction was reported for medication cost, especially among patients. Shared treatment decision-making was reported in ≥96% of patient-physician pairs. The most common 'most important' treatment target differed between patients ('Have a social life without worrying about RA') and physicians ('Prevent joint damage, deformity, and joint swelling'). CONCLUSIONS: Treatment satisfaction and concordance were high between patients in low activity/remission and physicians. Some differences between patients and physicians were reported in satisfaction for specific treatment outcomes and important treatment targets.

Treatment patterns and health care resource utilization among Japanese patients with ankylosing spondylitis: A hospital claims database analysis.

OBJECTIVES: To understand the current state of treatment patterns and health care resource utilization among patients in Japan with ankylosing spondylitis (AS) managed in the real-world setting. METHODS: Patient records from the Medical Data Vision database were analyzed to identify patients with ICD-10 AS from April 2009 through July 2017. Measures evaluated included demographic, clinical, and other characteristics at diagnosis; treatment patterns; health care resource utilization; and costs. RESULTS: Four hundred and seventeen patients met the study's inclusion criteria. Treatments observed during the first year after the initial AS diagnosis included nonsteroidal anti-inflammatory drugs (79.6%), corticosteroids (39.3%), methotrexate (22.3%), sulfasalazine (16.8%), adalimumab (14.2%), and infliximab (12.2%). At any time during the mean 33 months of study follow-up, biologic disease-modifying antirheumatic drugs (bDMARDs) were initiated by 115 patients. During the study follow-up, patients who initiated bDMARDs had higher median total per-patient annual health care costs ($26,937 vs $15,323), lower median per-patient hospitalization costs ($29,817 vs. $39,509), and fewer median hospital days per admission (7.0 vs. 11.0 days) compared with the overall group of patients diagnosed with AS. CONCLUSION: This database study provides knowledge of patient characteristics, treatment patterns, HCRU, and costs for patients with AS in Japan. The study outcomes demonstrate a need for increased awareness of proper AS management.