Alhossan A.,King Saud University |
Alhossan A.,University of Arizona |
Lee C.S.,Oregon Health And Science University |
MacDonald K.,Matrix45 |
Abraham I.,University of Arizona
Journal of Allergy and Clinical Immunology: In Practice | Year: 2017
Background: After the approval of omalizumab for severe allergic asthma, a total of 25 studies have evaluated the effectiveness of omalizumab under "real-life" conditions of heterogeneity in patients, clinicians, sites, and treatment patterns. Objective: We conducted a meta-analysis to evaluate the effectiveness of omalizumab focusing on treatment response, lung function, quality of life, symptom control, corticosteroid use, and exacerbations and hospitalizations at 4-6, 12, and 24 months. Methods: We searched PubMed and Embase for real-life studies on omalizumab in severe asthma published up to 2015. Three effect size types were extracted: single-point proportions; mean ± SD of change relative to baseline as raw numbers and standardized as Cohen's d; and changes in proportions of patients as relative risk. Random-effects meta-analyses were performed to account for within- and between-study heterogeneity. Studies were weighted by the DerSimonian and Laird method. Results: Per data available at the 3 time points, omalizumab therapy was consistently associated with large proportions of patients classified as "good" to "excellent" treatment responders (Global Evaluation of Treatment Effectiveness scale); improvements in forced expiratory volume in 1 second, quality of life (Asthma-related Quality-of-Life Questionnaire scale), and asthma symptom control (Asthma Control Test scale); reductions in oral and inhaled corticosteroid (ICS) use; and reductions in exacerbations and hospitalizations. Conclusions: This meta-analysis of noncontrolled studies documents the real-life pharmacotherapeutic effectiveness of omalizumab, as add-on treatment to ICS ± long-acting β2-agonists agents, in improving outcomes in patients with severe allergic asthma under conditions of heterogeneity in patients, clinicians, sites, and treatment patterns. The results mirror, complement, and extend the efficacy data from randomized controlled trials. © 2017 American Academy of Allergy, Asthma & Immunology.
Rakic J.-M.,University of Liège |
Leys A.,Leuven University Eye Hospital |
Brie H.,Novartis |
Denhaerynck K.,Matrix45 |
And 6 more authors.
Clinical Ophthalmology | Year: 2013
Introduction: The aim of this study was to examine ranibizumab treatment patterns in "real-world" practice and clinical settings, as well as to assess quality of life outcomes over a 24-month period. Materials and methods: This was a prospective, observational, multicenter, open-label study of 0.5 mg of ranibizumab administered intravitreally. Patients were followed over 24 ± 3 months with intermediate data points at 6 ± 2 months and 12 ± 2 months, and a limited data point at 2.5 ± 1 month that coincided with the end of the loading phase. Outcomes included visual acuity (Early Treatment Diabetic Retinopathy Study), visual function (National Eye Institute Visual Function Questionnaire-25 [NEI VFQ-25]), quality of life (Health Utilities Index Mark III [HUI3]), and safety. Results: A total of 267 patients with wet age-related macular degeneration (mean ± standard deviation [SD] age = 78.5 ± 7.3 years; 62.4% were female; 34.5% with dual eye involvement; 74.9% were treatment-naïve) were treated (309 eyes were treated). The mean ± SD Early Treatment Diabetic Retinopathy Study score at baseline was 56.3 ± 14.3 letters. The mean ± SD number of injections over 24 months was 7.6 ± 4.1, including 2.5 ± 0.7 and 5.9 ± 3.6 during the loading and maintenance phases, respectively, with corresponding treatment intervals of 4.8 ± 1.4 weeks and 11.5 ± 9.5 weeks, respectively. Improvements in visual acuity over baseline were reached at 2.5 months and maintained at 6 months (both P < 0.0001). The mean visual acuity increase over baseline at 12 months was not significant (P = 0.08); the decline over baseline at 24 months statistically significant (P = 0.02). Overall, 94.3% of patients showed stable or improved disease at 6 months and 81.5% of patients showed stable or improved disease at 24 months. At 6 months, improvements over baseline were significant for VFQ-25 (P = 0.03) and HUI3 (P = 0.02), but not at 12 months and 24 months. Improvements in VFQ-25 and HUI3 were maintained at 24 months in 38% and 34% of patients, respectively. In total 78 serious adverse events were reported in 40 patients and 77 nonserious adverse events in 34 patients. Nine serious adverse events and nine nonserious adverse events in 14 patients were suspected to be related to ranibizumab treatment. Conclusion: The "real-world" clinical effectiveness of ranibizumab was evidenced by the initial improvements over baseline in visual acuity and quality of life, as well as the maintenance of these outcomes at baseline levels at 24 months, and this was observed under variable treatment conditions. The findings underscore the need for individualized treatment with regular monitoring to achieve optimal vision and quality of life outcomes. © 2013 Rakic et al.
PubMed | University of Oregon, Matrix45 and University of Arizona
Type: Journal Article | Journal: Allergy | Year: 2016
We reviewed 24 real-life effectiveness studies of omalizumab in the treatment of severe allergic asthma that included 4117 unique patients from 32 countries with significant heterogeneity in patients, clinicians and settings. The evidence underscores the short- and long-term benefit of anti-IgE therapy in terms of the following: improving lung function; achieving asthma control and reducing symptomatology, severe exacerbations and associated work/school days lost; reducing healthcare resource utilizations, in particular hospitalizations, hospital lengths of stay and accident specialist or emergency department visits; reducing or discontinuing other asthma medications; and improving quality of life - thus confirming, complementing and extending evidence from randomized trials. Thus, omalizumab therapy is associated with signal improvements across the full objective and subjective burden of illness chain of severe allergic asthma. Benefits of omalizumab may extend up to 2-4 years, and the majority of omalizumab-treated patients may benefit for many years. Omalizumab has positive short- and long-term safety profiles similar to what is known from randomized clinical trials. Initiated patients should be monitored for treatment response at 16 weeks. Those showing positive response at that time are highly likely to show sustained treatment response and benefit in terms of clinical, quality of life and health resource utilization outcomes.
PubMed | Institute Multidisciplinaire dOncologie, University of Barcelona, Matrix45, Medizinische Abteilung I Onkologie und Haematologie and 2 more.
Type: Journal Article | Journal: Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer | Year: 2015
The purpose of this study is to examine the real-world treatment patterns and outcomes of chemotherapy-induced (febrile) neutropenia (chemotherapy-induced (CIN)/febrile neutropenia (FN)) prophylaxis with biosimilar filgrastim (Zarzio).MONITOR-GCSF is an international (12 countries), multi-center (140), prospective (max. six cycles), observational, open-label, pharmaco-epidemiologic study of cancer patients (n=1447) treated with myelosuppressive chemotherapy across a total of 6,213 cycles and receiving prophylaxis with Zarzio. Data were analyzed using both the patient and cycle as unit of analysis.Most (72.3 %) received primary prophylaxis; dosed mainly (53.2 %) at 30 MIU but differentiated by weight, chemotoxicity, and tumor type; and mainly (53.2 %) initiated in the 24-72h post-chemotherapy window but differentiated by prophylaxis type, tumor type, and chemotoxicity and for modal/median duration of 5 days. Relative to European Organisation for Research and Treatment of Cancer (EORTC) guidelines, 56.6 % were correctly prophylacted, 17.4 % under-prophylacted, and 26.0 % over-prophylacted. The following incidence rates were recorded: CIN grade 4 13.2 % of patients and 3.9 % of cycles, FN 5.9 % of patients and 1.4 % of cycles, CIN/FN-related hospitalizations 6.1 % of patients and 1.5 % of cycles, CIN/FN-related chemotherapy disturbances 9.5 % of patients and 2.8 % of cycles, and composite outcomes index 22.3 % of patients and 6.7 % of cycles. Rates varied by type of prophylaxis and tumor, chemotoxicity, initiation day, and prophylaxis duration. There were 1834 musculoskeletal events with 24.7 % of patients reporting bone pain of any grade (mostly mild to moderate), and 148 adverse drug reactions, including 4 serious, were recorded in 76 patients.The clinical and safety outcomes are well within the range of historically reported data for originator filgrastim underscoring the clinical effectiveness and safety of biosimilar filgrastim in daily clinical practice.
PubMed | Institute Multidisciplinaire dOncologie, Wilhelminen Cancer Research Institute, Matrix45, University of Basel and 4 more.
Type: | Journal: Journal of geriatric oncology | Year: 2016
Myelotoxic chemotherapy is associated with chemotherapy-induced (febrile) neutropenia (CIN/FN). The MONITOR-GCSF study evaluated biosimilar filgrastim (Zarzio) prophylaxis patterns, associated outcomes, and determinants. We performed stratified analyses comparing elderly and non-elderly patients.Comparative (elderly/non-elderly) analysis of demographics and clinical status, prophylaxis, associated CIN/FN outcomes (CIN grade 4 [CIN4], FN, CIN/FN-related hospitalizations and chemodisturbances, composite), and, per hierarchical modeling, determinants thereof evaluated at the patient- and cycle-level.There were no significant differences between both cohorts in prophylaxis initiation/duration and associated outcomes, but proportionately more elderly patients were correctly-prophylacted and fewer over-prophylacted. Common determinants of poor CIN/FN outcomes included concomitant antibiotic prophylaxis, impaired performance status, and any grade CIN in a previous cycle, whereas common determinants of good outcomes included over-prophylaxis and prophylaxis initiation within 24-72h. In the elderly, female gender, liver/renal/cardiovascular disease, secondary prophylaxis, and under-prophylaxis were associated with poorer outcomes. In the non-elderly, CIN4 at baseline or in a prior cycle was associated with poorer CIN/FN outcomes, and higher biosimilar filgrastim dose and, perhaps counter-intuitively, under-prophylaxis with better outcomes.Adequate GCSF support is essential for all patients, but especially for elderly patients with serious chronic disease, certainly, if concomitant antibiotic prophylaxis is indicated and if a CIN4 episode occurred in a prior cycle. The potential impact of impaired performance status, especially ECOG2 at chemotherapy start or a worsening to such during chemotherapy; under-prophylaxis, including inadequate secondary prophylaxis, should be considered in elderly patients. Timely GCSF initiation and over-prophylaxis is associated with lower rates of adverse CIN/FN events in elderly and non-elderly patients, and should be further evaluated in prospective randomized trials.
Sun D.,University of Arizona |
Andayani T.M.,Gadjah Mada University |
Altyar A.,University of Arizona |
Altyar A.,King Abdulaziz University |
And 2 more authors.
Clinical Therapeutics | Year: 2015
Purpose The objectives of this study were to simulate for the European Union G5 countries the potential cost savings of converting patients from originator granulocyte colony-stimulating factor (G-CSF) filgrastim and pegfilgrastim to a biosimilar filgrastim, to evaluate how reallocating these savings could increase patient access to antineoplastic therapy, and to estimate the number of patients needed to convert to provide antineoplastic treatment to one patient. Methods Three models were built: (1) to estimate the costs of using originator G-CSFs and the savings generated from switching to a biosimilar G-CSF, (2) to estimate the incremental number of patients who could be provided antineoplastic therapy - rituximab or trastuzumab - in a hypothetical panel of 10,000 patients with cancer, and (3) to calculate the number of patients needed to convert to provide access to anticancer therapy. Scenarios were developed in which the rate of conversion was varied to estimate the effect on total cost savings. This study took the perspective of the payer in the European Union. Findings The savings associated with the biosimilar filgrastim over the originator filgrastim ranged from €785 (day 4) to €2747 (day 14) and increased with longer duration of therapy. By contrast, the savings associated with the biosimilar filgrastim over pegfilgrastim decreased over time, ranging from €6199 (day 4) to €471 (day 14). In a hypothetical panel of 10,000 patients with cancer, the savings associated with the biosimilar filgrastim over the originator filgrastim and the expanded access to antineoplastic therapy improved over time, irrespective of conversion rates. Conversely, in the same hypothetical panel, the savings associated with the biosimilar filgrastim over pegfilgrastim reduced over time, irrespective of conversion rates, along with the expanded access to antineoplastic treatment. Under conversion of the originator filgrastim to the biosimilar filgrastim, the number needed to convert to expand access to rituximab ranged from 4 to 14 patients, and the number needed to convert to expand access to trastuzumab ranged from 11 to 38 patients. Under conversion of pegfilgrastim to the biosimilar filgrastim, the number needed to convert to expand access to rituximab ranged from 2 to 24 patients, and the number needed to convert to expand access to trastuzumab ranged from 5 to 63 patients. Implications Use of biosimilar G-CSFs for supportive cancer care could yield potential cost savings and improve patient access to antineoplastic therapy in a budget neutral way - a financial effect with an ethical perspective.
Olvey E.L.,University of Arizona |
MacDonald K.,Matrix45 |
Abraham I.,University of Arizona
Pharmaceuticals Policy and Law | Year: 2012
Recent health care legislation in the United States has turned considerable focus to comparative effectiveness research (CER) domestically, though it has been a topic of discussion internationally for many years. Without a fully comprehensive and consistent definition of CER developed, much uncertainty and confusion surrounds its utilization. In addition, contention exists regarding the incorporation of cost and economic considerations as a component of CER. This discussion includes various suggested definitions of CER, methodological considerations, legislation and utilization, and the role of cost-effectiveness evaluations in CER. © 2012 - Network of Centres for Study of Pharmaceutical Law. All rights reserved.
Abraham I.,University of Arizona |
Tharmarajah S.,University of Arizona |
Expert Opinion on Drug Safety | Year: 2013
Introduction: A 'biosimilar', or 'similar biological medicinal product', is a biologic agent that is similar in terms of quality, safety and efficacy to an authorized reference biological medicine. Since the expiration of the filgrastim patent in Europe, three agents have received marketing authorization from the EMA: Tevagrastim, Zarzio and Nivestim. Tevagrastim has also been approved as a biologic by the FDA as tbo-filgrastim. Areas covered: Using the EMA dossiers (all three agents), the FDA dossier (Tevagrastim), and journal publications, this article reviews clinical safety data for these products with emphasis on serious/severe adverse events and special consideration of immunogenicity, bone pain, splenomegaly, allergic reactions, acute respiratory distress syndrome and mortality. Expert opinion: All three agents have similar safety profiles. None were statistically higher on safety parameters to what is known about originator filgrastim (Neupogen). What is known about filgrastim in general regarding safety can be extended to biosimilar filgrastim. Safety profiles may become more differentiated once long-term product-specific safety data are available. Large-sample, long-term, observational studies of real-world practice will provide the heterogeneity and statistical power to demonstrate product-specific safety profiles. Current evidence indicates that statistically no one product is less and no one product is more safe. © 2013 Informa UK, Ltd.
Abraham I.,University of Arizona |
Han L.,University of Arizona |
Sun D.,University of Arizona |
Macdonald K.,Matrix45 |
Aapro M.,Institute Multidisciplinaire dOncologie
Future Oncology | Year: 2014
Aim: We simulated the budget impact of biosimilar erythropoiesis- stimulating agent (ESA) in EU G5 countries. Materials & methods: Three models were built to estimate the number of patients who could be provided with antineoplastic therapy with rituximab, bevacizumab or trastuzumab from cost savings of biosimilar erythropoietin use in a hypothetical panel of 100,000 patients. The associated number of patients needed to convert to biosimilar ESA to provide such treatments was also calculated. Results: Under fixed dosing, the savings from 100% conversion were €110,592,159, translating into an additional 9770 rituximab, 3912 bevacizumab, or 3713 trastuzumab treatments. Under weight-based dosing, the savings from 100% conversion were €146,170,333, corresponding to an additional 12,913 rituximab, 5171 bevacizumab or 4908 trastuzumab treatments. The number of patients needed to convert ranged from four to 51. Conclusion: Using biosimilar ESA for supportive cancer care yields significant savings and increases accessibility to primary antineoplastic therapy in a budget neutral way. © 2014 Future Medicine Ltd.
PubMed | Institute Multidisciplinaire dOncologie, University of Barcelona, Medizinische Abteilung I Oncology and Hematology, Matrix45 and 3 more.
Type: Journal Article | Journal: Annals of oncology : official journal of the European Society for Medical Oncology | Year: 2016
Risk models of chemotherapy-induced (CIN) and febrile neutropenia (FN) have to date focused on determinants measured at the start of chemotherapy. We extended this static approach with a dynamic approach of CIN/FN risk modeling at the start of each cycle.We applied predictive modeling using multivariate logistic regression to identify determinants of CIN/FN episodes and related hospitalizations and chemotherapy disturbances (CIN/FN consequences) in analyses at the patient (ever during the whole period of chemotherapy) and cycle-level (during a given chemotherapy cycle). Statistical dependence of cycle data being nested under patients was managed using generalized estimation equations. Predictive performance of each model was evaluated using bootstrapped c concordance statistics.Static patient-level risk models of ever experiencing CIN/FN adverse events and consequences during a planned chemotherapy regimen included predictors related to history, risk factors, and prophylaxis initiation and intensity. Dynamic cycle-level risk models of experiencing CIN/FN adverse events and consequences in an upcoming cycle included predictors related to history, risk factors, and prophylaxis initiation and intensity; as well as prophylaxis duration, CIN/FN in prior cycle, and treatment center characteristics.These real-world evidence models provide clinicians with the ability to anticipate CIN/FN adverse events and their consequences at the start of a chemotherapy line (static models); and, innovatively, to assess risk of CIN/FN adverse events and their consequences at the start of each cycle (dynamic models). This enables individualized patient treatment and is consistent with the EORTC recommendation to re-appraise CIN/FN risk at the start of each cycle. Prophylaxis intensity (under-, correctly-, or over-prophylacted relative to current EORTC guidelines) is a major determinant. Under-prophylaxis is clinically unsafe. Over-prophylaxis of patients administered chemotherapy with intermediate or low myelotoxicity levels may be beneficial, both in patients with and without risk factors, and must be validated in future studies.