Comparative efficacy of tyrosine kinase inhibitor treatments in the third-line setting, for chronic-phase chronic myelogenous leukemia after failure of second-generation tyrosine kinase inhibitors.

We compared the efficacy of ponatinib and second-generation tyrosine kinase inhibitors (2G-TKIs: bosutinib, dasatinib, and nilotinib) in chronic phase CML resistant/intolerant to ≥1 prior 2G-TKI. Estimated probabilities of CCyR with 2G-TKI ranged from 22% to 26%, compared with 60% (95% CrI 52-68%) with ponatinib. The estimated probability of ponatinib providing higher response rate than all other included treatments was 99% (CCyR) and 97% (MCyR). Use of further 2G-TKI may provide limited benefit in CP-CML patients resistant/intolerant to prior 2G-TKI treatment. Compared with 2G-TKIs, ponatinib is estimated to provide substantially higher probability of achieving CCyR and MCyR; safety was not compared.

Modelled evaluation of multi-component meningococcal vaccine (Bexsero®) for the prevention of invasive meningococcal disease in infants and adolescents in the UK.

Neisseria meningitidis is the main cause of bacterial meningitis and sepsis in the UK, and can potentially be lethal or cause long-term sequelae. Bexsero® (4CMenB) is a new multi-component vaccine approved by the European Commission for use in individuals aged ⩾2 months. A theoretical transmission model was constructed to assess the long-term effectiveness of Bexsero compared to standard care. The model was populated with UK-specific demographic data and calibrated to ensure that the transmission dynamics of meningococcal disease in the UK were adequately simulated. The model showed the best strategy to be a routine vaccination programme at ages 2, 3, 4, 12 months and 14 years combined with a 5-year catch-up programme in toddlers aged 12-24 months and adolescents aged 15-18 years. This would lead to a 94% reduction in meningococcal cases or 150 000 cases and 15 000 deaths over a 100-year time-frame.

Use of rhDNase therapy and costs of respiratory-related care in patients with cystic fibrosis.

OBJECTIVE: To assess the relationship between level of use of recombinant deoxyribonuclease I (rhDNase) therapy and costs of respiratory-related care in patients with cystic fibrosis. DESIGN: Retrospective, cohort study using healthcare claims data from a large New England health insurer. PATIENTS: All cystic fibrosis patients five years of age and older who began therapy with rhDNase in 1994 (the year it was first marketed in the US). Healthcare claims were compiled for six months prior to first receipt of rhDNase (pretreatment) and for 30 months subsequently (follow-up). Patients were stratified according to their level of rhDNase use during follow-up, based on whether it was above or below the median number of therapy days for the sample. MAIN OUTCOME MEASURES: Costs of rhDNase, all antibiotics, and all respiratory-related outpatient (physician, home health, hospital outpatient) and inpatient care were included. All costs were expressed on an annualized basis. RESULTS: Twenty-four patients with cystic fibrosis who began treatment with rhDNase in 1994 met all entry criteria; the median number of therapy days over a 30-month period was 355. Among patients with low (i.e., below the median) rhDNase use (n = 12), mean +/- SD annualized costs of respiratory-related care increased by almost $17,000 between pretreatment and follow-up, from $29,251 +/- $37,919 to $46,109 +/- $40,944. Among high-use patients (n = 12), costs decreased by approximately $2500, from $37,178 +/- $48,476 to $34,592 +/- $22,591. The change in both groups was accounted for primarily by a change in the number of respiratory-related hospitalizations. CONCLUSIONS: Prolonged use of rhDNase may reduce costs of respiratory-related care in patients with cystic fibrosis; further study is required, however, to confirm these findings.

Management of otitis media among children in a large health insurance plan.

BACKGROUND: Otitis media is one of the most common office diagnoses among children in the US and the leading reason for the use of antimicrobials in pediatric practice. We undertook this study to characterize medical and surgical management of otitis media. METHODS: Using claims data from a large New England health insurer, we identified all children <10 years of age who had one or more episodes of acute otitis media between July, 1995, and June, 1996, and examined patterns of treatment for this condition. RESULTS: Study subjects (n = 22,004) averaged 2.9 physician office visits for management of otitis media; among children <2 years of age, one-fourth had 6 or more such visits. Amoxicillin was prescribed as initial therapy in more than one-half (56.6%) of all episodes of acute otitis media, followed by cephalosporins (18.3%), trimethoprim-sulfamethoxazole (12.3%), macrolides (6.4%) and amoxicillin-clavulanate (6.0%). Over multiple episodes, however, use of amoxicillin declined by about 50%. Antimicrobial prophylaxis was received by 7.3% of all study subjects for a mean of 61.3 days; the incidence of breakthrough episodes of acute otitis media during prophylaxis varied according to the antimicrobial used (13.9, 12.3 and 19.5% for amoxicillin, trimethoprim-sulfamethoxazole and sulfisoxazole, respectively). Surgical procedures related to otitis media were performed on 3.8% of all study subjects, including 4.6% of children <2 years of age. CONCLUSIONS: The health care burden of otitis media is large, particularly in the first 2 years of life.