The impact of adoption of a new urate-lowering agent on trends in utilization and cost in practice.

OBJECTIVES: Changes in treatment choice of therapy and size of treated population that can lead to under- or overestimate of payer's budget are less likely to be reassured after reimbursement adoption of a new drug. The aim of this study was to evaluate the effects of febuxostat introduction and the modifications in its insurance coverage on the utilization and expenditure of urate-lowering therapy (ULT). METHODS: Electronic medical records for adults patients prescribed any ULT during 2010-2015 was derived from the largest medical organization in Taiwan. Aggregated estimates of ULT use and costs were assessed per 3-month and per patient per month (PPPM). Factors associated with total ULT expenditure were assessed using a time series design with factored Autoregressive Integrated Moving Average (ARIMA) models. RESULTS: ULT prevalent users increased 34.1% from 2010 to 2015 and a 123% increase in total ULT expenditure. Numbers on allopurinol and sulfinpyrazone both declined 31%, and on benzbromarone and febuxostat gradually increased to 38.21% and 22.89% of all users in 2015. Insurance payments PPPM ($4.44 to $9.22) and total monthly ULT cost ($32,946 to $ 85,732) growth more than doubled in 6 years, trend changes generated mostly by individuals switching to febuxostat. CONCLUSIONS: ULT use moved to favor benzbromarone and febuxostat; greater expensive uptake for febuxostat led to a rapid rise in ULT cost. Marginal values of increasing access to febuxostat for asymptomatic hyperuricemia should be focus on future studies to facilitate drug prices negotiation and ensure appropriate ULT use.

Adherence to long-term use of renin-angiotensin II-aldosterone system inhibitors in children with chronic kidney disease.

BACKGROUND: Although renin-angiotensin II-aldosterone system inhibitor (RASI) use for renal protection is well-documented, adherence to RASI therapy in the pediatric population is unclear. This study aimed to evaluate patient characteristics associated with adherence to chronic RASI use in patients with childhood chronic kidney disease (CKD). METHODS: Childhood CKD was identified using ICD-9 codes in the population-based, Taiwan national health insurance research database between 1997 and 2011. Patients continuously receiving RASIs for ≥3 months without interruption > 30 days after CKD diagnosis were defined as incident users. Medication adherence was measured as the proportion of days covered (PDC) by RASI prescription refills during the study period. Multivariate logistic regression was employed to assess the odds for adherence (PDC ≥80%) to RASI refills. RESULTS: Of 1271 incident users of RASI chronic therapy, 16.9% (n = 215) had PDC ≥80%. Compared to the group with PDC < 80%, patients in the high adherence group more often had proteinuria (aOR [adjusted odds ratio]1.93; 95%CI [confidence interval], 1.18-3.17), anemia (aOR, 1.76; 95% CI, 1.20-2.58), and time to start of chronic use > 2 years (aOR, 1.12; 95%CI, 1.06-1.19). Odds of being non-adherent were increased by hypertension and older ages (comparing to < 4 years) at start of chronic use, 9-12 years (aOR, 0.38; 95%CI, 0.17-0.82), 13-17 years (aOR, 0.45; 95%CI, 0.22-0.93),≥18 years (aOR, 0.34; 95%CI 0.16-0.72) and males (aOR, 0.68; 95%CI, 0.49-0.94). CONCLUSIONS: The rate of RASI prescription refilling adherence was relatively low and associated with CKD-specific comorbid conditions. This study identifies factors associated with low adherence and highlights the need to identify those who should be targeted for intervention to achieve better blood pressure control, preventing CKD progression.

Impact of drug price adjustments on utilization of and expenditures on angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in Taiwan.

BACKGROUND: A previous study has suggested that drug price adjustments allow physicians in Taiwan to gain greater profit by prescribing generic drugs. To better understand the effect of price adjustments on physician choice, this study used renin-angiotensin drugs (including angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin receptor blockers [ARBs]) to examine the impact of price adjustments on utilization of and expenditures on patented and off-patent drugs with the same therapeutic indication. METHODS: Using the Taiwan's Longitudinal Health Insurance Database (2005), we identified 147,157 patients received ACEIs and/or ARBs between 1997 and 2008. The annual incident and prevalent users of ACEIs, ARBs and overall renin-angiotensin drugs were examined. Box-Tiao intervention analysis was applied to assess the impact of price adjustments on monthly utilization of and expenditures on these drugs. ACEIs were divided into patented and off-patent drugs, off-patent ACEIs were further divided into original brands and generics, and subgroup analyses were performed. RESULTS: The number of incident renin-angiotensin drug users decreased over the study period. The number of prevalent ARB users increased and exceeded the cumulative number of first-time renin-angiotensin drug users starting on ARBs, implying that some patients switched from ACEIs to ARBs. After price adjustments, long term trend increases in utilization were observed for patented ACEIs and ARBs; a long-term trend decrease was observed for off-patent ACEIs; long-term trend change was not significant for overall renin-angiotensin drugs. Significant long-term trend increases in expenditures were observed for patented ACEIs after price adjustment in 2007 (200.9%, p = 0.0088) and in ARBs after price adjustments in 2001 (173.4%, p < 0.0001) and 2007 (146.3%, p < 0.0001). A significant long-term trend decrease in expenditures was observed for off-patent ACEIs after 2004 price adjustment (-156.9%, p < 0.0001). Expenditures on overall renin-angiotensin drugs showed long-term trend increases after price adjustments in 2001 (72.2%, p < 0.0001) and 2007 (133.4%, p < 0.0001). CONCLUSIONS: Price adjustments did not achieve long-term cost savings for overall renin-angiotensin drugs. Possible switching from ACEIs to ARBs within individuals is evident. Policy makers should reconsider the appropriateness of the current adjustment strategies applied to patented and off-patent drugs.

Treatment of pediatric idiopathic pulmonary hemosiderosis with low-dose cyclophosphamide.

OBJECTIVE: To report the safety and efficacy of long-term, low-dose cyclophosphamide therapy in a child with idiopathic pulmonary hemosiderosis (IPH). CASE SUMMARY: A 7-year-old boy diagnosed with IPH 4 years previously was initially prescribed prednisolone. Because he only had a transient response to prednisolone, oral cyclophosphamide 2 mg/kg/d was later added. A dramatic improvement was noted during the subsequent follow-up. One year after cyclophosphamide therapy, the patient suddenly developed thrombocytopenia (platelet count 75 x 10(3)/mm(3)), with the platelet count decreasing to 10 x 10(3)/mm(3) over the following 10 months. Cyclophosphamide was tapered to an alternating daily dosage of 1 mg/kg. The tapering resulted in a subsequent increase in the platelet count, which was maintained between 20 and 50 x 10(3)/mm(3) without occurrence of petechiae or spontaneous bleeding. Under this reduced dosing regimen, the disease has remained in remission for >1 year. DISCUSSION: Due to the low prevalence of IPH, only limited data document the safety and efficacy of immunosuppressive therapy in treating this disease. Although our patient showed a good response to low-dose cyclophosphamide, he developed thrombocytopenia with its use. The mechanism is unclear, but it may be similar to that of high-dose cyclophosphamide-induced myelosuppression. Due to the development of thrombocytopenia, the use of cyclophosphamide was maintained under a reduced dosing regimen. The benefit of long-term immunosuppressive therapy is controversial, and more clinical evidence is required to support its continued usage. CONCLUSIONS: Long-term, low-dose cyclophosphamide is effective in treating childhood IPH, but caution should be exercised due to the possible development of thrombocytopenia. Periodic monitoring of the platelet count in long-term treatment is recommended.

Detecting drug-drug interactions in medication profiles of psychiatric inpatients: a two-stage approach.

A two-stage evaluation methodology was developed to detect drug-drug interactions (D-DIs) of moderate and major severity in a psychiatric inpatient population. During a 3-month study period, the medication orders prescribed for 152 psychiatric inpatients in two psychiatric wards of a medical center were examined. A primary assessment of patients' reactions due to drug interactions was carried out by physicians who were provided with pertinent drug interaction monographs. A secondary assessment was performed by a three-member committee using explicit criteria to decide which reactions were actual D-DIs. Potential moderate or major severity D-DIs were identified in 79 (52.0%) of the 152 patients. A total of 130 potential interactions were detected in 339 (63.1%) of the 537 medication profiles. Actual D-DIs were seen in two patients (1.3%) who were prescribed trazodone with chlorpromazine and doxepin with paroxetine, respectively. The discrepancy between incidences of potential and actual D-DIs suggests that the method was sensitive in the detection and prudent in the assessment of D-DIs.