Philip Robinson

Omalizumab-induced decrease of FcɛRI expression in patients with severe allergic asthma

BACKGROUNDnIt is documented that omalizumab treatment reduces the cell surface expression of immunoglobulin E high-affinity receptor (FcɛRI) on several cell types. This has not been investigated in patients with uncontrolled severe persistent allergic asthma.nnnMETHODSnIn a double-blind, randomized, placebo-controlled study, patients with severe allergic asthma uncontrolled by high dose inhaled corticosteroids and long-acting β(2)-agonist received either omalizumab (n = 20) or placebo (n = 11) over 16 weeks at appropriate doses and frequencies. Baseline and end of study (week 16) FcɛRI expression on basophils and plasmacytoid dendritic cells was determined by flow cytometry for the primary endpoint. Secondary efficacy endpoints included asthma control and lung function as part of an initial investigation into the use of FcɛRI expression as a marker of response.nnnRESULTSnIn the omalizumab group, and with respect to placebo, FcɛRI expression was significantly reduced at end of study on basophils (-82.6%, p < 0.01) and plasmacytoid dendritic cells (-44.2%, p = 0.029). FcɛRI expression reduction was not found to be correlated with clinical response.nnnCONCLUSIONSnLong-term omalizumab treatment induced reduction of FcɛRI expression on circulating basophils and plasmacytoid dendritic cells. These changes were not associated with those of clinical features related to severe asthma, which does not support further investigation into its use as a predictive marker of response.nnnTRIAL REGISTRATIONnThe study was registered with ClinicalTrials.gov (identifier: NCT00454051) and the European Clinical Trials Database, EudraCT (identifier: 2006-003591-35).

Adherence to anti-inflammatory treatment for asthma in clinical practice in France

OBJECTIVESnThis study evaluated adherence to anti-inflammatory controller medication for asthma in a French population.nnnMETHODSnThis was an observational cohort study that employed data from the health insurance database for the Aquitaine region of France. Eligible subjects were aged between 15 and 45 years and had > or = 1 reimbursement claim for anti-inflammatory controller medication between December 1, 2003, and December 31, 2003. Data were collected from June 1, 2003, to May 28, 2005. New users were defined as those having no reimbursement claim for any asthma controller medication in the 6 months preceding the index date; all others were considered previous users. All subjects were followed for 17 months. Continuous multiple-interval measures of medication availability and medication gaps, treatment persistence, and time to first renewal were calculated for users of inhaled corticosteroids (ICS) alone, users of ICS combined with a long-acting beta2-agonist (LABA) in a single inhaler (ICS/LABA) or in separate inhalers (ICS + LABA), and users of oral leukotriene antagonists.nnnRESULTSnThe study population contained 12,502 new and previous users of anti-inflammatory controller medication for asthma. Their mean (SD) age was 32.0 (8.9) years and 58.3% were female. Previous users had better adherence to treatment than new users with respect to all measures. Adherence was best in previous users of leukotriene antagonists. However, only 40.2% of previous users of leukotriene antagonists had sufficient medication (95% CI, 37.6-42.9), compared with 56.8% of previous users of ICS + LABA (95% CI, 50.7-62.8), 65.5% of previous users of ICS only (95% CI, 63.1-67.9), and 69.8% of previous users of ICS/LABA (95% CI, 68.2-71.4). The rate of persistence over a 1-year period was 44.3% for previous users of leukotriene antagonists (95% CI, 41.7-46.8), compared with 27.1% for previous users of ICS only (95% CI, 25.1-29.1), 32.1% for previous users of ICS/LABA (95% CI, 30.5-33.6), and 44.1% for previous users of ICS + LABA (95% CI, 38.2-50.0).nnnCONCLUSIONnAdherence to treatment was poor (< or = 44%) in these users of anti-inflammatory controller medications for asthma.

Impact of a public media event on the use of statins in the French population

BACKGROUNDnIn February 2013, a retired French professor of medicine published a book denying the benefits of statins for cardiovascular prevention. The book was the subject of extensive media coverage and multiple public discussions and debate.nnnAIMSnTo investigate the impact of this media event on use of statins among regular users.nnnMETHODSnThis repeated cohort study used the French claims database sample Échantillon généraliste des bénéficiaires to identify regular statin users and quantify the number who discontinued statins after February 2013, compared to discontinuation patterns in previous years (2011 and 2012). Discontinuation was defined as a gap of at least 2months without statin exposure.nnnRESULTSnIn 2013, 30,725 regular statin users were identified; 29,517 in 2012 and 28,272 in 2011. Statin discontinuation at 9-month follow-up in 2013 was 11.9% (95% confidence interval [CI] 11.5-12.2), compared with 8.5% (95% CI 8.2-8.8) in 2012 and 8.5% (95% CI 8.2-8.8) in 2011. Discontinuation varied according to cardiovascular risk: 19.4% (95% CI 18.2-20.6) in low risk, 11.6% (95% CI 11.1-12.0) in moderate risk, and 7.4% (95% CI 6.8-8.1) in high risk for the 2013 cohort. These discontinuation rates were, respectively, 1.53 (95% CI 1.36-1.72), 1.40 (95% CI 1.31-1.49), and 1.25 (95% CI 1.08-1.46)xa0times higher in 2013 than in 2012 for low risk, moderate risk, or high risk patients.nnnCONCLUSIONSnThe rate of statin discontinuation, overall and in each cardiovascular risk group, was greater in 2013 after the media event than in previous years. The clinical impact of the increased discontinuation could be important.

Concordance between prescriber- and patient-reported previous medical history and NSAID indication in the CADEUS cohort.

Various data sources may be used in pharmacoepidemiological studies. When they cannot be obtained from valid databases, medical data must be obtained from physicians or patients. In the CADEUS study, both patients and their prescribers reported medical data allowing investigation of the concordance between these sources.

The EULEV cohort study: rates of and factors associated with continuation of levetiracetam after 1 year

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECTnLevetiracetam has shown good safety/tolerability and efficacy in regulatory trials. This was confirmed in observational investigations performed soon after marketing by using continuation or retention rates as a composite measure. When an anti-epileptic drug first becomes available; however, there is evidence of channelling to more severe patients than thereafter.nnnWHAT THIS STUDY ADDSnThis study was performed several years after marketing of levetiracetam and found high rates of continuation. It also further explores this measure by determining the continuation in the absence of initiation of additional anti-epileptic drugs.nnnAIMSnTo investigate real-life effectiveness of levetiracetam in patients initiating treatment in a stable market situation.nnnMETHODSnEpileptic adults who had initiated levetiracetam between 1 January and 31 August in 2005 or 2006 were included and followed for 1 year by hospital or nonhospital neurologists practising in France. One-year continuation rates were estimated using Kaplan-Meier analysis. Among those still treated at end of study, treatment goals were investigated. Factors associated with discontinuation were investigated using Cox proportional hazards regression.nnnRESULTSnA total of 794 subjects were included in the cohort, and 753 subjects were followed up and included in the analysis. Among these, mean (SD) age was 42.6 (±17.0) years, 51.1% were female, 76.6% had partial epilepsy, 93.5% had seizures in the 6 months preceding levetiracetam initiation and 82.9% had at least one concomitant anti-epileptic drug when starting levetiracetam. One-year levetiracetam continuation rate was 83.5% (95% confidence interval, 80.5-86.0%). Of the 579 patients still using levetiracetam at end of study, 46.8% were seizure free during the last 6 months, and 24% were on levetiracetam monotherapy. Reasons for discontinuation (n= 122) were adverse events (45%), lack of efficacy (38%) or both (9%). Levetiracetam discontinuation was most strongly associated with previous exposure to more than four anti-epileptic drugs, whereas continuation was most strongly associated with presence of seizure-related falls in the 6 months preceding levetiracetam initiation.nnnCONCLUSIONSnThis population-based cohort study in a stable market situation found a high 1 year levetiracetam continuation rate compared with previous studies done sooner after market introduction.

Comparative effectiveness of recommended versus less intensive drug combinations in secondary prevention of acute coronary syndrome

The secondary prevention treatment for acute coronary syndrome (ACS) is based on the combined use of drugs from four therapeutic classes (beta‐blockers, antiplatelet agents, statins, and angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers). The objective of this study was to compare the long‐term effectiveness of the recommended therapeutic combination with those of incomplete combinations in secondary prevention of ACS.

Real-life patterns of use and effectiveness of bortezomib: the VESUVE cohort study.

Abstract In response to a regulatory request for real-life data on patterns of use and survival outcomes, 793 patients initiating bortezomib for multiple myeloma in France (May 2004–April 2006) were included in this observational study. Data were collected from medical files and patients were followed for 2 years, with vital status collected after 3 years. In total 779 patients were analyzed: 83.1% had immunoglobulin G (IgG) or IgA M-component, mean age was 65.7 years and 46.5% were female. Bortezomib was initiated as third-or-later line in 82.0%. For 75.9%, the starting dose was 1.3 mg/m2; 42.6% had bortezomib alone, 54.0% with dexamethasone. The mean number of bortezomib cycles was 5.0. Three-year overall survival from bortezomib initiation was 31.4% (95% confidence interval, CI [28.1; 34.7]) and median overall survival was 19.6 months. Two-year progression-free survival was 12.0% (95% CI [9.8; 14.4]), and median progression-free survival was 7.2 months. Overall best response was 44.0%. Survival outcomes during real-life use of bortezomib were within the range of those reported in clinical trials.

Patterns and effectiveness of bortezomib use according to age in the VESUVE cohort

Abstract Therapeutical options for older multiple myeloma patients have been improved with the advent of new drugs, yet there is a lack of observational data for such patients. To address this issue, an age-stratified analysis of the VESUVE cohort of bortezomib users was performed. Among the 779 patients included in the analysis, 358 (46%) were agedu2009≤u200965 years, 282 (36%) were between 65–75 years and 139 (18%) were more than 75 years old. There were few significant differences in treatment parameters across age groups; notably, older patients received a lower dose of bortezomib and more frequently experienced general or administration site conditions, metabolism or nutrition disorders and cardiac disorders. Overall best response rate and progression-free survival were similar across age groups. Taken together, these results indicate that older patients do benefit from bortezomib and that tailored treatment in real-life clinical practice does not compromise effectiveness.

Continuation rates of levetiracetam in children from the EULEVp cohort study

BACKGROUNDnSince indication extension to children data regarding the effectiveness of levetiracetam in paediatric patients remains limited.nnnAIMSnInvestigate the real-life effectiveness of levetiracetam in paediatric patients.nnnMETHODSnEpileptic children (<16 years) who had initiated levetiracetam between 1 October 2006 and 31 March 2007 were included and followed for 1 year by hospital or non-hospital neurologists practising in France.nnnRESULTSnAmong the 156 identified children, 147 were analysed: 51.7% were female, and mean (SD) age was 9.2 years (4.2). Most patients had either partial symptomatic (30.6%) or partial cryptogenic (26.5%) epilepsy, 92.5% experienced seizures during the 6 months preceding levetiracetam initiation, and 19.2% were on levetiracetam alone at initiation. One-year levetiracetam continuation rate was estimated to be 72.0% (95%CI [63.8; 78.6]). Of the 104 children continuing levetiracetam treatment at end of study, 31.7% were seizure-free during the last six months of follow-up, and 23.1% on levetiracetam alone. Discontinuation of levetiracetam (n = 41) was mainly for insufficient efficacy (58.5% of those concerned).nnnCONCLUSIONSnIn real-life clinical practice important treatment retention and non-negligible reduction of seizure frequency may be expected.

Real‐life patterns of use, safety and effectiveness of sunitinib in first‐line therapy of metastatic renal cell carcinoma: the SANTORIN cohort study

To investigate sunitinib in the real‐life first‐line treatment of metastatic renal cell carcinoma (mRCC).