International Journal of Nephrology and Renovascular Disease
Background: Anemia is prevalent among patients with chronic kidney disease (CKD), yet current evi... more Background: Anemia is prevalent among patients with chronic kidney disease (CKD), yet current evidence indicates that treatment may not adhere to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. We aimed to document the management of patients with non-dialysis-dependent (NDD)-CKD receiving erythropoiesis-stimulating agent (ESA) therapy in Europe. Methods: This retrospective, observational study extracted information from medical records in Germany, Spain, and the UK. Eligible patients were adults with NDD-CKD stages 3b-5 who initiated ESA therapy for anemia between January and December 2015. Anemia was defined as hemoglobin (Hb) <13.0 g/dL (males) or <12.0 g/dL (females). Data regarding ESA treatment, treatment response, concomitant iron therapy and blood transfusions were extracted up to 24 months post-ESA initiation, and data on CKD progression until abstraction date. Results: Eight hundred and forty-eight medical records were abstracted. Approximately 40% received no iron therapy prior to ESA initiation. At ESA initiation, mean ± standard deviation Hb level was 9.8 ± 1.0 g/dL. Most patients received darbepoetin alfa, and switching between ESAs was rare (8.5% of patients). Concomitant intravenous and oral iron therapy was prescribed for 36% and 42% of patients, respectively, during initial ESA therapy. Mean Hb levels reached the target level (10-12 g/dL) within 3-6 months of ESA initiation. Hb, transferrin saturation, and ferritin levels were infrequently monitored from 3 months post-ESA initiation. Rates of blood transfusion, dialysis, and diagnosis of end-stage renal disease were 16.4%, 19.3%, and 24.6%, respectively. Rates of kidney transplant and death were 4.8% and 8.8%, respectively. Conclusion: Among ESA-treated patients, ESA initiation was in accordance with KDIGO guidelines, but subsequent monitoring of Hb and iron deficiency were suboptimal.
Objective: To understand prevalence, severity, impact, and treatment of vasomotor symptoms associ... more Objective: To understand prevalence, severity, impact, and treatment of vasomotor symptoms associated with menopause, using cross-sectional survey data. Methods: This online, two-part survey was conducted in East Asia among women 40-65 years recruited from established online panels (Edelman, Beijing; Hankook Research, Seoul; Rakuten Insight, Taipei) using stratified sampling. Part I collected demographics/disease characteristics, including menopausal status and vasomotor symptom severity. Women with moderate-to-severe vasomotor symptoms completed Part II, including clinical characteristics, health-related quality of life, and healthcare-seeking behavior. Primary endpoints included vasomotor symptom prevalence and severity and proportions of women eligible and willing to take hormone therapy. Results are presented for each of the three online panels separately and as a pooled total. All analyses are descriptive with no formal hypothesis testing across groups. Results: Numbers of peri...
d GlaxoSmithKline, USA e Fourth Hurdle Consulting, UK Introduction: Large scale surveys in Europe... more d GlaxoSmithKline, USA e Fourth Hurdle Consulting, UK Introduction: Large scale surveys in Europe (AIRE), Asia Pacific (AIRIAP), and Latin America (AIRLA) showed that current levels of asthma control fall short of guideline-defined goals. Aims: This analysis determines the relationship between level of asthma control and use of unscheduled healthcare resources in 26 countries across the regions. Subjects and methods: Responses of patients aged ≥12 years included in the three surveys were mapped to the five items of the Asthma Control Test (ACT TM ). Unscheduled healthcare resources used by patients (inpatient stay, ER visit, unscheduled primary care) were analysed for patients with not well controlled (NWC) asthma (derived ACT TM score <20) and well controlled asthma (derived ACT TM score 20-25). Results: 6329 patients from 26 countries were included in the three surveys, with derived ACT TM scores evaluable for 5888 patients (93%). Approximately half of the patients (3072, 52%) had NWC asthma, with only 341 (6%) achieving the best possible derived ACT TM score (25). Over the previous year, 52% patients with NWC asthma (derived ACT TM score <20) reported use of any unscheduled healthcare resources compared with 29% of those with WC asthma (derived ACT TM score 20-25). Similarly more than twice as many patients reported ER visit/inpatient stay comparing NWC and WC asthma patients (34% and 14% respectively). Patients with a derived ACT TM score 5-14 (poorly controlled asthma) were more than three times as likely to report anER visit/inpatient stay compared with those with WC asthma, 47% and 14% respectively). Conclusions: NWC asthma in Europe, Asia Pacific and Latin America is associated with considerable use of unscheduled healthcare resource use. Management regimens that result in WC asthma may reduce the requirement for unscheduled healthcare and direct cost of the disease.
Background and Aims Among patients with CKD, prevalence of anaemia increases with CKD severity,1 ... more Background and Aims Among patients with CKD, prevalence of anaemia increases with CKD severity,1 and is accompanied by elevated risk of hospitalisation and mortality.2 Treatment options include iron therapy and ESAs; international guidelines recommend initiating ESA therapy when haemoglobin (Hb) declines <10 g/dL, and to monitor Hb and iron status every 3 months during ESA treatment.3 This study aimed to describe the routine clinical management of patients with NDD-CKD and anaemia following ESA initiation, in Germany, Spain and the UK. Method This was a non-interventional, retrospective cohort study of adults with NDD-CKD stages 3b–5 (as defined in KDIGO 2012 guidelines)1 diagnosed with anaemia (Hb <13.0 g/dL [males] or <12.0 g/dL [females]), who began ESA treatment 01 Jan 2015–31 Dec 2015 inclusive. Data for ≤24 months after ESA initiation were extracted from medical records: patient characteristics; anaemia diagnosis and treatment (including iron and ESA use); Hb, serum f...
RATIONALE: To evaluate the efficacy of omalizumab (Xolair| a monoclonal anti-immunoglobulin E ant... more RATIONALE: To evaluate the efficacy of omalizumab (Xolair| a monoclonal anti-immunoglobulin E antibody, for reducing the rate of asthmadeterioration related incidents (ADRIs) in patients with poorly controlled allergic asthma. METHODS: In a 52-week, open-label study, 312 patients (aged 12-75 yrs) receiving _>400 mcg/d (pediatric) or _>800 mcg/d (adult) inhaled beclomethasone dipropionate or equivalent for poorly controlled, moderate-to-severe allergic asthma were randomized (2:1) to current asthma therapy (CAT) with or without subcutaneous omalizumab (at least 0.016 mg/kg/IgE [IU/mL) per 4 wks). The primary efficacy variable was the annualized rate of ADRIs, ie, >1 of the following events due to asthma: course of oral steroids or antibiotics, missed school/work attendance, unscheduled physician visit, or emergency room visit/hospitalization. RESULTS: Baseline characteristics were comparable for the two groups (omalizumab, n=206; CAT alone, n=106), with 99% of patients being treated according to GINA step 3/4. Among evaluable patients, treatment with omalizumab significantly reduced the mean rate of ADRIs vs CAT alone (4.92 and 9.76 per patient-year, respectively; p<0.001). The percentage of patients who remained ADRl-free was increased for omalizumab-treated patients vs CAT alone (36% [69/191] and 20% [18/89], respectively; p=0.008). These results were paralleled by significantly improved lung function and fewer exacerbations for those treated with omalizumab, which proved safe and well tolerated. The findings of this naturalistic study indicate that add-on therapy with omalizumab is effective in reducing the rate of ADRIs in patients with moderate-to-severe allergic asthma who remain poorly controlled despite conventional treatment.
RATIONALE: Patients with severe asthma are at high risk of asthma exacerbations. This pooled anal... more RATIONALE: Patients with severe asthma are at high risk of asthma exacerbations. This pooled analysis was conducted to assess the efficacy of add-on therapy with omalizumab (Xolair ® ), an anti-IgE monoclonal antibody, on asthma exacerbation rates in patients with severe persistent asthma according to the GINA 2002 classification. METHODS: Data were pooled from 7 controlled trials that evaluated the clinical profile of omalizumab in patients with IgE-mediated asthma. Omalizumab was added to current asthma therapy and compared with placebo (in 5 double-blind studies) or with current asthma therapy alone (in 2 open-label studies). The rate of asthma exacerbations was assessed in all studies. Using the Poisson regression model, results were calculated as the ratio of treatment effect (omalizumab:control) on the standardized exacerbation rate per year. The studies included 4308 patients (2511 treated with omalizumab), 93% of whom had severe persistent asthma according to the GINA 2002 classification. Pooled analysis showed that omalizumab significantly reduced the annualized rate of asthma exacerbations by 38% (0.910 vs 1.474 [treatment group difference 0.564] rate ratio 0.617; p<0.0001 vs control). Analysis of demographic subgroups showed that the efficacy of omalizumab on asthma exacerbations was apparent irrespective of patient age, gender, baseline serum IgE (split by median) or dosing schedule. CONCLUSIONS: Omalizumab significantly reduces asthma exacerbations and is highly efficacious as an add-on treatment to concomitant asthma therapy in patients with severe persistent asthma.
Omalizumab, a humanised anti-immunoglobulin E monoclonal antibody for treatment of uncontrolled m... more Omalizumab, a humanised anti-immunoglobulin E monoclonal antibody for treatment of uncontrolled moderate-to-severe or severe persistent allergic asthma, was developed as a lyophilised powder for reconstitution. A liquid formulation in pre-filled syringes has now been developed. The purpose of this study was to assess the immunogenicity and safety of this liquid formulation. In this multinational, open-label, single-arm study, patients (≥12 years) with moderate-to-severe allergic asthma were treated for 24 weeks with the liquid formulation of omalizumab (75 or 150 mg in a pre-filled syringe) at 2 or 4 week intervals. Immunogenicity was assessed by measurement of human anti-therapeutic antibody (ATA) levels. Safety was assessed by monitoring adverse events (AEs), haematology, blood chemistry, urine analysis and vital signs. A total of 155 patients were enrolled in the study. No patient had a confirmed positive ATA test result. Most frequent individual AEs were asthma (17.4%), sinusitis (17.4%) and upper respiratory tract infection (11.6%). Fourteen patients (9.0%) had serious AEs and there was one death (not treatment related). There were no cases of anaphylaxis according to Sampson criteria. Most patients remained within normal ranges for haematology and biochemistry laboratory variables. Omalizumab in pre-filled syringes was not associated with immunogenicity. This novel formulation, which does not require reconstitution, had a safety profile consistent with the lyophilised formulation. A limitation of this study is that efficacy of omalizumab in the treatment of asthma was not specifically addressed herein. Clinicaltrials.gov identifier: NCT00500539.
Background: Since initial registration, the omalizumab clinical trial database has expanded consi... more Background: Since initial registration, the omalizumab clinical trial database has expanded considerably, with a doubling of patients exposed in the clinical trial environment. Previous pooled data (2003) from phase I to III studies of omalizumab showed a numeric imbalance in malignancies arising in omalizumab recipients (0.5%) compared with control subjects (0.2%). The previous analysis was based on limited available data, warranting further investigation. Objective: We sought to examine the incidence of malignancy using comprehensive pooled data from clinical trials of omalizumab-treated patients. Methods: This pooled analysis included data from 67 phase I to IV clinical trials. The prespecified primary analysis assessed the incidence of primary malignancy in 32 randomized, doubleblind, placebo-controlled (RDBPC) trials. Results: There were 11,459 unique patients in all clinical trials (7,789 received omalizumab). The primary analysis identified malignancies in 25 patients (RDBPC trials): 14 in 4,254 omalizumab-treated patients and 11 in 3,178 placebo-treated patients. Incidence rates per 1,000 patient-years of observation time for omalizumab-and placebo-treated patients were 4.14 (95% CI, 2.26-6.94) and 4.45 (95% CI, 2.22-7.94), respectively; the corresponding rate ratio was 0.93 (95% CI, 0.39-2.27). Primary malignancies were of varying histologic type and occurred in a number of different organ systems; no cluster of histologies was identified. Conclusions: In this pooled analysis no association was observed between omalizumab treatment and risk of malignancy in RDBPC trials; the rate ratio was below unity. The data suggest that a causal relationship between omalizumab therapy and malignancy is unlikely. (J Allergy Clin Immunol 2012;nnn:nnnnnn.
International Journal of Nephrology and Renovascular Disease
Background: Anemia is prevalent among patients with chronic kidney disease (CKD), yet current evi... more Background: Anemia is prevalent among patients with chronic kidney disease (CKD), yet current evidence indicates that treatment may not adhere to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. We aimed to document the management of patients with non-dialysis-dependent (NDD)-CKD receiving erythropoiesis-stimulating agent (ESA) therapy in Europe. Methods: This retrospective, observational study extracted information from medical records in Germany, Spain, and the UK. Eligible patients were adults with NDD-CKD stages 3b-5 who initiated ESA therapy for anemia between January and December 2015. Anemia was defined as hemoglobin (Hb) <13.0 g/dL (males) or <12.0 g/dL (females). Data regarding ESA treatment, treatment response, concomitant iron therapy and blood transfusions were extracted up to 24 months post-ESA initiation, and data on CKD progression until abstraction date. Results: Eight hundred and forty-eight medical records were abstracted. Approximately 40% received no iron therapy prior to ESA initiation. At ESA initiation, mean ± standard deviation Hb level was 9.8 ± 1.0 g/dL. Most patients received darbepoetin alfa, and switching between ESAs was rare (8.5% of patients). Concomitant intravenous and oral iron therapy was prescribed for 36% and 42% of patients, respectively, during initial ESA therapy. Mean Hb levels reached the target level (10-12 g/dL) within 3-6 months of ESA initiation. Hb, transferrin saturation, and ferritin levels were infrequently monitored from 3 months post-ESA initiation. Rates of blood transfusion, dialysis, and diagnosis of end-stage renal disease were 16.4%, 19.3%, and 24.6%, respectively. Rates of kidney transplant and death were 4.8% and 8.8%, respectively. Conclusion: Among ESA-treated patients, ESA initiation was in accordance with KDIGO guidelines, but subsequent monitoring of Hb and iron deficiency were suboptimal.
Objective: To understand prevalence, severity, impact, and treatment of vasomotor symptoms associ... more Objective: To understand prevalence, severity, impact, and treatment of vasomotor symptoms associated with menopause, using cross-sectional survey data. Methods: This online, two-part survey was conducted in East Asia among women 40-65 years recruited from established online panels (Edelman, Beijing; Hankook Research, Seoul; Rakuten Insight, Taipei) using stratified sampling. Part I collected demographics/disease characteristics, including menopausal status and vasomotor symptom severity. Women with moderate-to-severe vasomotor symptoms completed Part II, including clinical characteristics, health-related quality of life, and healthcare-seeking behavior. Primary endpoints included vasomotor symptom prevalence and severity and proportions of women eligible and willing to take hormone therapy. Results are presented for each of the three online panels separately and as a pooled total. All analyses are descriptive with no formal hypothesis testing across groups. Results: Numbers of peri...
d GlaxoSmithKline, USA e Fourth Hurdle Consulting, UK Introduction: Large scale surveys in Europe... more d GlaxoSmithKline, USA e Fourth Hurdle Consulting, UK Introduction: Large scale surveys in Europe (AIRE), Asia Pacific (AIRIAP), and Latin America (AIRLA) showed that current levels of asthma control fall short of guideline-defined goals. Aims: This analysis determines the relationship between level of asthma control and use of unscheduled healthcare resources in 26 countries across the regions. Subjects and methods: Responses of patients aged ≥12 years included in the three surveys were mapped to the five items of the Asthma Control Test (ACT TM ). Unscheduled healthcare resources used by patients (inpatient stay, ER visit, unscheduled primary care) were analysed for patients with not well controlled (NWC) asthma (derived ACT TM score <20) and well controlled asthma (derived ACT TM score 20-25). Results: 6329 patients from 26 countries were included in the three surveys, with derived ACT TM scores evaluable for 5888 patients (93%). Approximately half of the patients (3072, 52%) had NWC asthma, with only 341 (6%) achieving the best possible derived ACT TM score (25). Over the previous year, 52% patients with NWC asthma (derived ACT TM score <20) reported use of any unscheduled healthcare resources compared with 29% of those with WC asthma (derived ACT TM score 20-25). Similarly more than twice as many patients reported ER visit/inpatient stay comparing NWC and WC asthma patients (34% and 14% respectively). Patients with a derived ACT TM score 5-14 (poorly controlled asthma) were more than three times as likely to report anER visit/inpatient stay compared with those with WC asthma, 47% and 14% respectively). Conclusions: NWC asthma in Europe, Asia Pacific and Latin America is associated with considerable use of unscheduled healthcare resource use. Management regimens that result in WC asthma may reduce the requirement for unscheduled healthcare and direct cost of the disease.
Background and Aims Among patients with CKD, prevalence of anaemia increases with CKD severity,1 ... more Background and Aims Among patients with CKD, prevalence of anaemia increases with CKD severity,1 and is accompanied by elevated risk of hospitalisation and mortality.2 Treatment options include iron therapy and ESAs; international guidelines recommend initiating ESA therapy when haemoglobin (Hb) declines <10 g/dL, and to monitor Hb and iron status every 3 months during ESA treatment.3 This study aimed to describe the routine clinical management of patients with NDD-CKD and anaemia following ESA initiation, in Germany, Spain and the UK. Method This was a non-interventional, retrospective cohort study of adults with NDD-CKD stages 3b–5 (as defined in KDIGO 2012 guidelines)1 diagnosed with anaemia (Hb <13.0 g/dL [males] or <12.0 g/dL [females]), who began ESA treatment 01 Jan 2015–31 Dec 2015 inclusive. Data for ≤24 months after ESA initiation were extracted from medical records: patient characteristics; anaemia diagnosis and treatment (including iron and ESA use); Hb, serum f...
RATIONALE: To evaluate the efficacy of omalizumab (Xolair| a monoclonal anti-immunoglobulin E ant... more RATIONALE: To evaluate the efficacy of omalizumab (Xolair| a monoclonal anti-immunoglobulin E antibody, for reducing the rate of asthmadeterioration related incidents (ADRIs) in patients with poorly controlled allergic asthma. METHODS: In a 52-week, open-label study, 312 patients (aged 12-75 yrs) receiving _>400 mcg/d (pediatric) or _>800 mcg/d (adult) inhaled beclomethasone dipropionate or equivalent for poorly controlled, moderate-to-severe allergic asthma were randomized (2:1) to current asthma therapy (CAT) with or without subcutaneous omalizumab (at least 0.016 mg/kg/IgE [IU/mL) per 4 wks). The primary efficacy variable was the annualized rate of ADRIs, ie, >1 of the following events due to asthma: course of oral steroids or antibiotics, missed school/work attendance, unscheduled physician visit, or emergency room visit/hospitalization. RESULTS: Baseline characteristics were comparable for the two groups (omalizumab, n=206; CAT alone, n=106), with 99% of patients being treated according to GINA step 3/4. Among evaluable patients, treatment with omalizumab significantly reduced the mean rate of ADRIs vs CAT alone (4.92 and 9.76 per patient-year, respectively; p<0.001). The percentage of patients who remained ADRl-free was increased for omalizumab-treated patients vs CAT alone (36% [69/191] and 20% [18/89], respectively; p=0.008). These results were paralleled by significantly improved lung function and fewer exacerbations for those treated with omalizumab, which proved safe and well tolerated. The findings of this naturalistic study indicate that add-on therapy with omalizumab is effective in reducing the rate of ADRIs in patients with moderate-to-severe allergic asthma who remain poorly controlled despite conventional treatment.
RATIONALE: Patients with severe asthma are at high risk of asthma exacerbations. This pooled anal... more RATIONALE: Patients with severe asthma are at high risk of asthma exacerbations. This pooled analysis was conducted to assess the efficacy of add-on therapy with omalizumab (Xolair ® ), an anti-IgE monoclonal antibody, on asthma exacerbation rates in patients with severe persistent asthma according to the GINA 2002 classification. METHODS: Data were pooled from 7 controlled trials that evaluated the clinical profile of omalizumab in patients with IgE-mediated asthma. Omalizumab was added to current asthma therapy and compared with placebo (in 5 double-blind studies) or with current asthma therapy alone (in 2 open-label studies). The rate of asthma exacerbations was assessed in all studies. Using the Poisson regression model, results were calculated as the ratio of treatment effect (omalizumab:control) on the standardized exacerbation rate per year. The studies included 4308 patients (2511 treated with omalizumab), 93% of whom had severe persistent asthma according to the GINA 2002 classification. Pooled analysis showed that omalizumab significantly reduced the annualized rate of asthma exacerbations by 38% (0.910 vs 1.474 [treatment group difference 0.564] rate ratio 0.617; p<0.0001 vs control). Analysis of demographic subgroups showed that the efficacy of omalizumab on asthma exacerbations was apparent irrespective of patient age, gender, baseline serum IgE (split by median) or dosing schedule. CONCLUSIONS: Omalizumab significantly reduces asthma exacerbations and is highly efficacious as an add-on treatment to concomitant asthma therapy in patients with severe persistent asthma.
Omalizumab, a humanised anti-immunoglobulin E monoclonal antibody for treatment of uncontrolled m... more Omalizumab, a humanised anti-immunoglobulin E monoclonal antibody for treatment of uncontrolled moderate-to-severe or severe persistent allergic asthma, was developed as a lyophilised powder for reconstitution. A liquid formulation in pre-filled syringes has now been developed. The purpose of this study was to assess the immunogenicity and safety of this liquid formulation. In this multinational, open-label, single-arm study, patients (≥12 years) with moderate-to-severe allergic asthma were treated for 24 weeks with the liquid formulation of omalizumab (75 or 150 mg in a pre-filled syringe) at 2 or 4 week intervals. Immunogenicity was assessed by measurement of human anti-therapeutic antibody (ATA) levels. Safety was assessed by monitoring adverse events (AEs), haematology, blood chemistry, urine analysis and vital signs. A total of 155 patients were enrolled in the study. No patient had a confirmed positive ATA test result. Most frequent individual AEs were asthma (17.4%), sinusitis (17.4%) and upper respiratory tract infection (11.6%). Fourteen patients (9.0%) had serious AEs and there was one death (not treatment related). There were no cases of anaphylaxis according to Sampson criteria. Most patients remained within normal ranges for haematology and biochemistry laboratory variables. Omalizumab in pre-filled syringes was not associated with immunogenicity. This novel formulation, which does not require reconstitution, had a safety profile consistent with the lyophilised formulation. A limitation of this study is that efficacy of omalizumab in the treatment of asthma was not specifically addressed herein. Clinicaltrials.gov identifier: NCT00500539.
Background: Since initial registration, the omalizumab clinical trial database has expanded consi... more Background: Since initial registration, the omalizumab clinical trial database has expanded considerably, with a doubling of patients exposed in the clinical trial environment. Previous pooled data (2003) from phase I to III studies of omalizumab showed a numeric imbalance in malignancies arising in omalizumab recipients (0.5%) compared with control subjects (0.2%). The previous analysis was based on limited available data, warranting further investigation. Objective: We sought to examine the incidence of malignancy using comprehensive pooled data from clinical trials of omalizumab-treated patients. Methods: This pooled analysis included data from 67 phase I to IV clinical trials. The prespecified primary analysis assessed the incidence of primary malignancy in 32 randomized, doubleblind, placebo-controlled (RDBPC) trials. Results: There were 11,459 unique patients in all clinical trials (7,789 received omalizumab). The primary analysis identified malignancies in 25 patients (RDBPC trials): 14 in 4,254 omalizumab-treated patients and 11 in 3,178 placebo-treated patients. Incidence rates per 1,000 patient-years of observation time for omalizumab-and placebo-treated patients were 4.14 (95% CI, 2.26-6.94) and 4.45 (95% CI, 2.22-7.94), respectively; the corresponding rate ratio was 0.93 (95% CI, 0.39-2.27). Primary malignancies were of varying histologic type and occurred in a number of different organ systems; no cluster of histologies was identified. Conclusions: In this pooled analysis no association was observed between omalizumab treatment and risk of malignancy in RDBPC trials; the rate ratio was below unity. The data suggest that a causal relationship between omalizumab therapy and malignancy is unlikely. (J Allergy Clin Immunol 2012;nnn:nnnnnn.
Uploads
Papers by Martin Blogg