Kooperativer Bibliotheksverbund

In: Current Medical Research and Opinion, Informa UK Limited, Vol. 32, No. 11 ( 2016-11-01), p. 1789-1795

Type of Medium: Online Resource

ISSN: 0300-7995 , 1473-4877

URL: Article

DOI: 10.1080/03007995.2016.1211516

Language: English

Publisher: Informa UK Limited

Publication Date: 2016

detail.hit.zdb_id: 2034331-0

In: Therapeutic Advances in Respiratory Disease, SAGE Publications, Vol. 11, No. 5 ( 2017-05), p. 193-209

Abstract: Chronic airway infection with Pseudomonas aeruginosa is a major cause of increased morbidity and mortality in patients with cystic fibrosis (CF). The development and widespread use of nebulized antibacterial therapies, including tobramycin inhalation solution (TIS), has led to improvements in lung function and quality of life. However, the use of nebulizers is associated with various challenges, including extended administration times and the need for frequent device cleaning and disinfection. Multiple therapies are required for patients with CF, which poses a considerable burden to patients, and adherence to the recommended treatments remains a challenge. Tobramycin inhalation powder (TIP), delivered via the T-326 Inhaler, has been shown to have similar clinical efficacy and safety as compared to TIS, with improved patient convenience, satisfaction, and treatment adherence. Long-term safety studies have shown that TIP was well tolerated with no unexpected adverse events in patients with CF. This review of the TIP pivotal and postmarketing studies reinforces the well-established efficacy and safety profile of TIP and its ease of use.

Type of Medium: Online Resource

ISSN: 1753-4666 , 1753-4666

URL: Article

DOI: 10.1177/1753465817691239

Language: English

Publisher: SAGE Publications

Publication Date: 2017

detail.hit.zdb_id: 2387506-9

In: Pediatric Pulmonology, Wiley, Vol. 51, No. 11 ( 2016-11), p. 1159-1167

Type of Medium: Online Resource

ISSN: 8755-6863

URL: Issue

URL: Article

DOI: 10.1002/ppul.v51.11

DOI: 10.1002/ppul.23451

Language: English

Publisher: Wiley

Publication Date: 2016

detail.hit.zdb_id: 1491904-7

In: American Journal of Hematology, Wiley, Vol. 96, No. 4 ( 2021-04), p. 404-417

Abstract: Sickle cell disease (SCD) is a genetic disorder, characterized by hemolytic anemia and vaso‐occlusive crises (VOCs). Data on the global SCD impact on quality of life (QoL) from the patient viewpoint are limited. The international Sickle Cell World Assessment Survey (SWAY) aimed to provide insights into patient‐reported impact of SCD on QoL. This cross‐sectional survey of SCD patients enrolled by healthcare professionals and advocacy groups assessed disease impact on daily life, education and work, symptoms, treatment goals, and disease management. Opinions were captured using a Likert scale of 1‐7 for some questions; 5‐7 indicated “high severity/impact.” Two thousand one hundred and forty five patients (mean age 24.7 years [standard deviation (SD) = 13.1], 39% ≤18 years, 52% female) were surveyed from 16 countries (six geographical regions). A substantial proportion of patients reported that SCD caused a high negative impact on emotions (60%) and school achievement (51%) and a reduction in work hours (53%). A mean of 5.3 VOCs (SD = 6.8) was reported over the 12 months prior to survey (median 3.0 [interquartile range 2.0‐6.0] ); 24% were managed at home and 76% required healthcare services. Other than VOCs, fatigue was the most commonly reported symptom in the month before survey (65%), graded “high severity” by 67% of patients. Depression and anxiety were reported by 39% and 38% of patients, respectively. The most common patient treatment goal was improving QoL (55%). Findings from SWAY reaffirm that SCD confers a significant burden on patients, epitomized by the high impact on patientsʼ QoL and emotional wellbeing, and the high prevalence of self‐reported VOCs and other symptoms.

Type of Medium: Online Resource

ISSN: 0361-8609 , 1096-8652

URL: Issue

URL: Article

DOI: 10.1002/ajh.v96.4

DOI: 10.1002/ajh.26063

Language: English

Publisher: Wiley

Publication Date: 2021

detail.hit.zdb_id: 1492749-4

In: Clinical Drug Investigation, Springer Science and Business Media LLC, Vol. 37, No. 8 ( 2017-8), p. 795-805

Type of Medium: Online Resource

ISSN: 1173-2563 , 1179-1918

URL: Article

DOI: 10.1007/s40261-017-0537-9

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2017

detail.hit.zdb_id: 2043793-6

SSG: 15,3

In: Therapeutic Advances in Respiratory Disease, SAGE Publications, Vol. 11, No. 7 ( 2017-07), p. 249-260

Abstract: This study assessed the ease of use of tobramycin inhalation powder (TIP) administered via T-326 inhaler versus tobramycin inhalation solution (TIS) and colistimethate sodium (COLI), both administered via nebulizers, for the treatment of chronic pulmonary Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF). Methods: A real-world, open-label, crossover, interventional phase IV study was conducted in CF patients aged ⩾6 years with forced expiratory volume in 1 second (FEV 1 ) ⩾25% to ⩽90% predicted. Patients were assigned to one of the three treatment arms in Cycle 1; all patients received TIP in Cycle 2. Each cycle consisted of 28 days on and 28 days off the treatment. Results: A total of 60 patients [mean (standard deviation) age, 27.6 (8.4) years] were allocated to three treatment arms [TIS/TIP ( n = 14); COLI/TIP ( n = 28); TIP/TIP ( n = 18)] in Cycle 1. The mean total administration time, which included device setup and cleaning, in Cycle 1 versus Cycle 2 for TIS/TIP, COLI/TIP, and TIP/TIP arms were 37.0 versus 5.0 min, 16.4 versus 3.8 min, and 4.2 versus 3.4 min, respectively. The difference in mean total administration time was significantly shorter in Cycle 2 than in Cycle 1 for TIS/TIP ( p = 0.0112) and COLI/TIP ( p = 0.0016) arms. Overall, 12 patients were found to have contaminated devices across the two treatment cycles. In the TIP/TIP arm, no contamination of the T-326 inhaler was observed in either cycle. Treatment satisfaction, assessed by the Treatment Satisfaction Questionnaire for Medication and ACCEPT® questionnaire, was better overall for TIP compared with TIS and COLI. There were no unexpected adverse events and most were mild or moderate in intensity. Conclusion: The T-326 inhaler used to deliver TIP was easy to use, required shorter total administration time, and was much less frequently contaminated than the nebulizers. The safety findings observed for TIP were generally consistent with its established safety profile.

Type of Medium: Online Resource

ISSN: 1753-4666 , 1753-4666

URL: Article

DOI: 10.1177/1753465817710596

Language: English

Publisher: SAGE Publications

Publication Date: 2017

detail.hit.zdb_id: 2387506-9

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 1018-1018

Abstract: Background: Sickle cell disease (SCD) is an inherited genetic disorder that results in the formation of sickle hemoglobin (HbS). HbS polymerizes when deoxygenated, deforming erythrocytes and leading to chronic hemolysis, anemia and vaso-occlusion. Sickle cell nephropathy (SCN) is the term used to describe the renal complications of SCD. Renal vaso-occlusion and hemolysis contribute to the manifestations of SCN which include hyperfiltration and progressive renal impairment. Chronic kidney disease (CKD) is diagnosed if abnormalities in kidney structure or function are present for 〉 3 months. The prevalence of CKD in patients with SCD increases with age, and ~12% of patients progress to end-stage renal disease (Gosmanova et al. J Investig Med 2014; Powars et al. Medicine 2005). There are no treatments approved for CKD caused by SCD. Standard of care (SoC) typically consists of angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs) and/or hydroxyurea (HU). Evidence for the clinical effectiveness of ARBs and ACE inhibitors has been generated mainly from trials in other causes of kidney disease or short-term studies in SCD. P-selectin contributes to vaso-occlusion by mediating adhesion of sickled erythrocytes and leukocytes to the endothelium. Crizanlizumab is a humanized monoclonal antibody that binds to P-selectin with high affinity and specificity. In SUSTAIN, crizanlizumab significantly reduced the median annual rate of vaso-occlusive crises compared with placebo (Ataga et al. N Engl J Med 2017). Preclinical data show P-selectin expression in the kidneys and upregulation in response to renal ischemia-reperfusion injury (Singbartl et al. FASEB J 2000; Zizzi et al. J Pediatr Surg 1997). Crizanlizumab may have a beneficial effect in patients with SCD and CKD by blocking P-selectin-mediated multicellular adhesion, reducing the effects of vaso-occlusion in the renal vasculature and slowing the decline in renal function. The aim of the STEADFAST study is to determine if crizanlizumab can slow the progression of CKD due to SCD (EUDRACT no. 2018-003608-38). Methods: Approximately 170 patients aged ≥16 years with CKD due to SCD will be enrolled. Eligible patients will have HbSS or HbSβ0-thalassemia genotypes, an estimated glomerular filtration rate (eGFR) ≥45 to ≤120 mL/min/1.73 m2, an albumin-to-creatinine ratio (ACR) ≥100 to 〈 2000 mg/g and be receiving SoC (which includes HU, ACE inhibitors and/or ARBs) for SCD and/or CKD. Patients must have been receiving SoC for ≥6 months and plan to continue at the same dose and schedule until study end. Exclusion criteria include history of stem cell transplant, chronic red blood cell transfusion therapy, acute kidney injury (AKI) within 3 months of study entry, and patients undergoing hemodialysis. Patients will be randomized to receive crizanlizumab 5.0 mg/kg plus SoC or SoC alone. Patients in the combination arm will receive crizanlizumab 5.0 mg/kg by IV infusion over 30 minutes on day 1 of week 1, followed by a second dose 2 weeks later, after which it will be administered every 4 weeks. The total treatment period is 12 months. Primary endpoint: proportion of patients with a ≥30% decrease from baseline in ACR at 12 months, based on the intent-to-treat population. A logistic regression model including treatment effects and stratification factors will be utilized and the test (based on the log-odds ratio estimated by the model) will be carried out at the 1-sided significance level of 0.025. Secondary endpoints include mean change in ACR from baseline to 3, 6, 9, and 12 months, proportion of patients with ≥30% decrease in ACR at 6 months, proportion of patients with ≥20% improvement of protein-to-creatinine ratio (PCR) at 12 months, percentage change in eGFR from baseline to 3, 6, 9, and 12 months, and the proportion of patients with progression of CKD (based on decline in eGFR category accompanied by a ≥25% drop in eGFR from baseline) from baseline to 12 months. Exploratory endpoints include improvement in renal and cardiac biomarkers at 3, 6, 9, and 12 months and tricuspid regurgitation velocity (TRV) 〈 2.5 m/s at 12 months among patients with abnormal TRV at baseline. Conclusion: CKD is a common complication of SCD. The STEADFAST study will evaluate whether crizanlizumab, in combination with SoC, can reduce albuminuria and slow CKD progression, thus providing evidence of a reno-protective effect of crizanlizumab. Figure Disclosures Ataga: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Emmaus Life Sciences: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bioverativ: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Modus Therapeutics: Honoraria. Saraf:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding. Derebail:RTI: Honoraria; Novartis: Consultancy; Retrophin: Consultancy. Sharpe:Novartis: Consultancy. Inati:Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novonordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Research Funding; Global Blood Therapeutics: Research Funding. Lebensburger:Pfizer: Research Funding; Novartis: Consultancy. DeBonnett:Novartis Pharmaceuticals Corporation: Employment. Zhang:Novartis: Employment. Bartolucci:Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; HEMANEXT: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; AddMedica: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-124823

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 2289-2289

Abstract: Background: Sickle cell disease (SCD) is characterized by the presence of sickle hemoglobin (HbS), chronic hemolysis, recurrent pain episodes called vaso-occlusive crises (VOCs), multiorgan dysfunction and early death. VOCs decrease quality of life, are the main cause of healthcare encounters in SCD, and increase the risk of death. New therapies that reduce SCD hospitalizations are desirable given the potential to impact healthcare utilization, but also to reduce disease burden and decrease mortality and morbidity. The SUSTAIN study (Ataga et al. NEJM 2017), was a Phase 2, multicenter, randomized, placebo-controlled, double-blind, 12-month study to assess safety and efficacy of crizanlizumab (2.5 and 5 mg/kg) with or without hydroxyurea therapy, in patients with SCD and a history of 2-10 VOCs in the previous 12 months (NCT01895361). The primary efficacy endpoint was annual rate of SCD-related pain crises (VOCs) leading to healthcare visit. The key secondary endpoint was annual rate of days hospitalized, regardless of cause. There was a statistically significant 45.3% reduction in median annual rate of VOCs leading to healthcare visit with crizanlizumab 5 mg/kg compared with placebo (1.63 vs 2.98 VOCs/year, P=0.01). There was a 41.8% reduction in median rate of days hospitalized with crizanlizumab 5 mg/kg compared with placebo (4.00 vs 6.87 days/year). Although this difference was not statistically significant (P=0.45), it appears to be clinically relevant. Methods: A post-hoc analysis of the SUSTAIN data was performed to better characterize the difference in the annual rate of days hospitalized between the crizanlizumab 5 mg/kg and placebo arms, and to compare the distribution of hospitalizations and time to first hospitalization. Results: As illustrated in Figure 1, a greater proportion of patients in the crizanlizumab arm (46%) were not hospitalized during the trial period (up to end of treatment) than in the placebo arm (35%). Correspondingly, the percentage of patients with ≥1 hospitalization was lower in the crizanlizumab (54%) than the placebo arm (65%). In addition, a trend for delayed time to first hospitalization shown in Figure 1 was further explored with a Kaplan-Meier (KM) analysis (Figure 2). Figure 2 shows clear separation of the curves, evident from Month 1 of treatment. The median time to first hospitalization was greater with crizanlizumab 5 mg/kg than with placebo (6.3 vs 3.2 months; hazard ratio [HR] 0.683 [95% CI 0.437-1.066] ). The apparent improvement in time to first hospitalization is consistent with previously published SUSTAIN results regarding median time to first VOC leading to healthcare visit. Patients treated with crizanlizumab 5 mg/kg were found to experience a longer median time to first VOC leading to healthcare visit than patients on placebo (4.07 vs 1.38 months; HR 0.50 [95% CI 0.33-0.74]). Conclusions: The primary SUSTAIN results showed that crizanlizumab reduced VOCs leading to a healthcare visit. This analysis demonstrates additional positive trends associated with crizanlizumab treatment compared to placebo, regarding the percentage of patients with no hospitalizations and a delayed time to first hospitalization. Together, these findings provide further evidence that crizanlizumab may have a beneficial impact on reducing hospitalizations. Disclosures Ataga: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Emmaus Life Sciences: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bioverativ: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Modus Therapeutics: Honoraria. Kutlar:Micelle Biopharma: Other: DSMB Chair; Novartis: Consultancy; Global Blood Therapeutics, Inc. (GBT): Research Funding; Novo Nordisk: Research Funding; Bluebird Bio: Other: DSMB Member. DeBonnett:Novartis Pharmaceuticals Corporation: Employment. Lincy:NOVARTIS PHARMA AG: Employment. Kanter:Novartis: Consultancy, Honoraria; Imara: Consultancy; Sangamo: Consultancy, Honoraria; Modus: Consultancy, Honoraria; Guidepoint Global: Consultancy; GLG: Consultancy; Cowen: Consultancy; Jeffries: Consultancy; Medscape: Honoraria; Rockpointe: Honoraria; Peerview: Honoraria; SCDAA: Membership on an entity's Board of Directors or advisory committees; NHLBI: Membership on an entity's Board of Directors or advisory committees; bluebird bio, Inc.: Consultancy.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-125868

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 3026-3026

Abstract: Background: SCD is an inherited blood disorder that for many patients (pts) has a high clinical burden, results in poor quality of life (QoL), and reduces life expectancy. Gaining a deeper understanding of pt and HCP experiences of SCD is important to improve pt management. Aims: SWAY was a cross-sectional survey that assessed pt and HCP experiences of SCD. Here we focus on the experiences of HCPs from various regions on SCD symptoms and complications, impact of SCD on QoL, treatment goals and treatment satisfaction. Methods: SWAY was developed by international SCD expert physicians, pt advocates and Novartis. HCPs completed the survey between Apr and Oct 2019. Eligible HCPs had qualified in their primary specialty by 2014 and were managing ≥10 SCD pts at the time of survey (≥5 pts per HCP in Canada; ≥2 pts in the Netherlands). Responses to questions on how much SCD impacts pt QoL, and on HCP treatment satisfaction, were ranked on a Likert scale (1-7, where 1=not at all/strongly dissatisfied, 7=a great deal/strongly satisfied; 5-7 indicated high impact/satisfaction). The data reflect only the experiences of the surveyed HCPs in each region (recruited by Adelphi Real World fieldwork). A limitation is that Asia and South America (SA) were represented by single countries (India and Brazil, respectively). Results: SWAY was completed by 365 HCPs from 6 regions (Table). In all regions HCPs recognized the prevalence of acute and chronic pain, however acute pain was reported less frequently by HCPs in Africa than in other regions (Table). Acute chest syndrome and joint issues were among the top 5 most frequently mentioned complications by HCPs in all regions. Globally, HCPs recognized the high impact of SCD symptoms and complications on pt QoL and the high negative impact of SCD on pt emotional wellbeing (Likert score 5-7 reported by 79-100% and 71-97%, respectively). Fewer HCPs in the Middle East (ME) reported a high impact of SCD on physical and sexual activity, compared with HCPs in other regions. Around 40% of HCPs in the ME and Asia thought SCD has a high impact on daily activities, compared with 79-90% of HCPs in other regions. In Asia, fewer HCPs reported that SCD has a high impact on pts' education and ability to maintain a job compared with HCPs in other regions (Figure). Hydroxyurea (HU) was among the top 3 most common therapies ever initiated and was the therapy most likely to be initiated in any age group by HCPs in almost all regions. In Africa, the most common therapy ever initiated and the therapy most likely to be initiated in any age group was opioids (Table). Fewer HCPs in North America (NA; 32%) and SA (27%) were highly satisfied with current SCD treatments, compared with HCPs in other regions (46-72%). The main reason for dissatisfaction was limited treatment options in all regions except Asia, where HCPs said they were unable to reach their treatment goals with current therapies. Improving pts' QoL was among the top 3 treatment goals for 51-84% of HCPs across all regions. For HCPs in NA and the ME, the most important goal when treating vaso-occlusive crises was to improve QoL; in SA, Europe and Asia it was to avoid organ damage; and in Africa it was to eliminate pain completely. Discussion: The top 5 most frequent SCD symptoms and complications that HCPs reported were similar across all regions. There were regional differences in HCP experiences of how SCD impacts aspects of pts' daily life, with fewer HCPs in the ME reporting a high impact on physical and sexual activity, and fewer HCPs in Asia and the ME reporting a high impact on daily activities compared with other regions. This may be due to cultural variations, with pts in these regions being less comfortable discussing these topics with HCPs. There was a difference in the reported impact of SCD on school and work between HCPs in Asia and other regions, which could be due to varying expectations regarding school/work productivity. HU was one of the top 3 most common treatments ever initiated by HCPs for pts of any age, except in Africa, which may be due to an educational knowledge gap about HU, high cost, or poor access in this region. HCPs in almost all regions, except Asia, were dissatisfied with current SCD treatments because of limited therapeutic options, indicating a global unmet need for additional treatment choices. Improving QoL was the most important treatment goal for HCPs in all regions, demonstrating the high negative impact that SCD has on pt QoL and the ongoing need for methods to address this. Figure 1 Figure 1. Disclosures Osunkwo: Novartis Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; FORMA Therapeutics: Consultancy; Global Blood Therapeutics: Consultancy, Speakers Bureau; Chiesi: Consultancy; Acceleron: Consultancy; Cyclerion: Consultancy; Emmaus: Consultancy. Minniti: Roche: Consultancy, Honoraria; NovoNordisk: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; GBT: Consultancy, Research Funding. Nur: Roche: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Research Funding, Speakers Bureau. Nero: Global Blood Therapeutics: Consultancy; Editas Medicine: Consultancy; bluebird bio: Consultancy; Novartis: Consultancy. Colombatti: Global Blood Therapeutics: Research Funding; Addmedica: Consultancy; Forma Therapeutics: Consultancy; Novartis: Consultancy; NovoNordisk: Consultancy; BlueBirdBio: Consultancy; Global Blood Therapeutics: Consultancy; BlueBirdBio: Research Funding. de Montalembert: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Addmedica: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; bluebird bio: Membership on an entity's Board of Directors or advisory committees; Vertex: Membership on an entity's Board of Directors or advisory committees. Abboud: Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Research Support and Advisory Board, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Other: Reserach support and advisory board , Research Funding; GBT: Other: Research Support, Research Funding; Vertex Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: DSMB. Arlet: Addmedica: Research Funding; Pfizer: Honoraria; Novartis company: Consultancy, Honoraria, Research Funding. Jastaniah: Novartis: Consultancy, Honoraria, Research Funding. Pita: GLOBAL ALLIANCE OF SCD: Membership on an entity's Board of Directors or advisory committees; LUA VERMELHA SCD ASSOCIATION: Membership on an entity's Board of Directors or advisory committees. Francis-Gibson: Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Sickle Cell Disease Association of America: Current Employment; ASH: Membership on an entity's Board of Directors or advisory committees; Alliance for Regenerative Medicine Foundation for Cell and Gene Medicine: Membership on an entity's Board of Directors or advisory committees; Global Alliance of SCD Organizations: Membership on an entity's Board of Directors or advisory committees. Trimnell: Novartis: Consultancy; Cyclerion: Consultancy; Global Blood Therapeutics: Consultancy. DeBonnett: Novartis Pharmaceuticals Corporation: Current Employment. Bailey: Novartis Pharmaceuticals: Other: I am an employee of Adelphi Real World, which received payment from Novartis Pharmaceuticals for this research. Rajkovic-Hooley: Novartis Pharmaceuticals: Other: I am an employee of Adelphi Real World, which received payment from Novartis Pharmaceuticals for this research. James: GBT: Honoraria; Novartis: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-145409

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 4180-4180

Abstract: Background: VOCs are the hallmark of SCD and can lead to serious complications and organ damage. P-selectin, a cell adhesion protein, plays a central role in the multicellular interactions that can lead to VOCs. Crizanlizumab, a first-in-class humanized monoclonal antibody that targets P-selectin, is approved in several regions to prevent/reduce VOC burden for patients (pts) with SCD aged ≥16 years. Pts in some countries can obtain early access to crizanlizumab before health authority approval via a MAP (NCT03720626); first pt enrolled in June 2018. Aim: To describe the proportions of pts with 0 home- or 0 healthcare-managed VOCs after 6 months of treatment with crizanlizumab in the MAP (in countries where publication of these data is allowed). Methods: The MAP was designed to provide access to crizanlizumab for SCD pts with serious or life-threatening disease for which no comparable or satisfactory alternative to crizanlizumab was available as treatment in their country. Other eligibility criteria included: aged 16-70 years (18-70 years in Italy); history of VOCs as assessed by the treating physician (including recurrent VOCs while receiving hydroxyurea [HU], L-glutamine or other therapies); and not eligible for a crizanlizumab clinical trial. At baseline, treating physicians were asked about their pts' disease burden in the 12 months prior to requesting access to crizanlizumab (eg frequency of home- or healthcare-managed VOCs and opioid use for VOC management). The proportions of pts with 0 home- or 0 healthcare-managed VOCs after 6 months of treatment with crizanlizumab are described overall and stratified by SCD ge notype and history of HU use. Results: Treating physicians made requests for initial access to crizanlizumab for 146 pts eligible for this analysis. Most of these pts were from Brazil (n=105; 72%), with the remainder residing in Italy, Spain, Israel, Canada, Portugal and Switzerland. Of the 144 pts with baseline data (missing, n=2), 142 (99%) had ≥1 home-managed VOC (median [interquartile range; IQR] of 6 [4‒8.5] VOCs) and 137 (95%) had ≥1 healthcare-managed VOC (median [IQR] of 3 [2‒5] VOCs) in the 12 months before entry into the MAP. Opioids were taken for VOC management by 92% of pts in the 12 months prior to baseline (n=132/144); the most common was morphine (n=57/132; 43%). As of June 2021, 102 of the 146 pts with initial requests had received crizanlizumab for ≥6 months and had resupply requests submitted by their physicians. For these 102 pts, median (IQR) age was 33 (25-40) years, 62% were female, 47% were of African American ethnicity, the genotype was HbSS in 79%, and a history of HU use was reported in 45% of these pts. Eleven pts (5%) discontinued crizanlizumab during the 6 months of treatment reported in this analysis. Of the 102 pts with data available 6 months post-crizanlizumab initiation, 46 (45%) reported 0 home-managed VOCs (median [IQR] of 1 [0‒2] VOC) and 62 (61%) reported 0 healthcare-managed VOCs (median [IQR] of 0 [0‒1] VOCs) during this time period. The proportions of pts with 0 home- or 0 healthcare-managed VOCs after 6 months of treatment with crizanlizumab stratified by SCD genotype and history of HU use are shown in Figure 1. Clinicians participating in the MAP anecdotally reported improvement in certain clinical complications (eg leg ulcers and priapism), reduced frequency of hospitalizations, shorter lengths of hospital stay and reduced use of opioids in some pts after crizanlizumab treatment. Adverse events were consistent with those reported in other crizanlizumab studies. Limitations: The difference in time periods for which data are available (ie 12 months for baseline data vs 6 months for post-treatment initiation data) precludes a comparison of data pre- and post-initiation of crizanlizumab in this analysis. Information about HU use was not provided for all pts, therefore the proportion of pts with a history of HU use in this analysis could be higher than reported. Conclusion: Pts participating in the crizanlizumab MAP had a high burden of home- and healthcare-managed VOCs at baseline despite many pts reporting a history of HU use; almost all required opioids for VOC management. Findings from this analysis looking at the proportion of pts with 0 home- or 0 healthcare-managed VOCs after 6 months of treatment with crizanlizumab are promising, although additional data with ≥12 months of exposure are required to compare VOC burden on treatment with that reported here at baseline. Figure 1 Figure 1. Disclosures Cançado: Novartis: Consultancy. Colombatti: NovoNordisk: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; bluebird bio: Membership on an entity's Board of Directors or advisory committees, Research Funding; Forma Therapeutics: Membership on an entity's Board of Directors or advisory committees. Quarta: Novartis: Membership on an entity's Board of Directors or advisory committees, Other: collaboration relationships for Advisory boards, Webinar events, editorial projects; Speaker at conferences; Celgene: Other: collaboration relationships for Advisory boards, Webinar events, editorial projects; Sanofi - Genzyme: Membership on an entity's Board of Directors or advisory committees, Other: collaboration relationships for Advisory boards, Webinar events, editorial projects; Speaker at conferences; Blue Bird Bio: Other: collaboration relationships for Advisory boards, Webinar events, editorial projects; Takeda: Other: collaboration relationships for Advisory boards, Webinar events, editorial projects; speaker at conferences; Bristol Meyer Squibb: Membership on an entity's Board of Directors or advisory committees, Other: Speaker at conferences. DeBonnett: Novartis Pharmaceuticals Corporation: Current Employment. Soliman: Novartis: Current Employment. Sarkar: Novartis: Current Employment. Pinto: Novartis: Consultancy; Global Blood therapeutics (GBT): Consultancy; EMS, Brazil: Consultancy.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-152407

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7