Tyrosine Kinase in Pediatric Growth

The use of tyrosine kinase inhibitor (TKI) therapy has become more common in pediatric patients in the last few years. This trend is likely to continue as more TKIs are approved and the list of conditions for which TKIs have clinical utility expands. Imatinib (Gleevec™) is a tyrosine kinase inhibitor that is specifically indicated for Philadelphia positive chronic myelogenous leukemia (PHÆCML). Dasatinib (Sprycel™) and nilotinib (Tasigna™) are TKIs indicated for CML patients who are no longer benefitting from, or did not tolerate, other treatments including imatinib. OBJECTIVE:The objective of this study was to determine whether there is evidence of growth retardation as an adverse drug experience for TKIs. METHODS:The FDA Adverse Event Reporting System (FAERS) was reviewed for currently posted data from 4th quarter 2012 until 1st quarter 2014 for individuals ≤ 18 years of age. The most recent update of the FAERs data was in October of 2014. These are sponsor, patient and physician reported events. A search for approximate matches to the drug names using the generalized Levenshtein edit distance using the R and SAS™ 9.3 was used to search for patterns in the adverse experiences. These AEs were grouped by Preferred Term(PT), and the ranking of growth related AEs was conducted relative to other PTs. RESULTS:Of 574 self-reported adverse experiences reported for imatinib from 2012-2014, there were 12 (2.1%) cases of growth retardation. Growth retardation was the 5th most commonly occurring AE. Of 594 self-reported adverse experiences for dasatinib from 2012-2104, no cases of growth retardation occurred. Likewise, of 25 self-reported AEs for nilotinib, none were growth related. CONCLUSION:There appears to be some evidence of growth retardation in imatinib patients, and none for dasatinib patients. Not enough AEs have yet been reported for nilotinib to judge whether growth is also retarded in these patients

Tyrosine Kinase in Pediatric Growth

The use of tyrosine kinase inhibitor (TKI) therapy has become more common in pediatric patients in the last few years. This trend is likely to continue as more TKIs are approved and the list of conditions for which TKIs have clinical utility expands. Imatinib (Gleevec™) is a tyrosine kinase inhibitor that is specifically indicated for Philadelphia positive chronic myelogenous leukemia (PHÆCML). Dasatinib (Sprycel™) and nilotinib (Tasigna™) are TKIs indicated for CML patients who are no longer benefitting from, or did not tolerate, other treatments including imatinib. OBJECTIVE:The objective of this study was to determine whether there is evidence of growth retardation as an adverse drug experience for TKIs. METHODS:The FDA Adverse Event Reporting System (FAERS) was reviewed for currently posted data from 4th quarter 2012 until 1st quarter 2014 for individuals ≤ 18 years of age. The most recent update of the FAERs data was in October of 2014. These are sponsor, patient and physician reported events. A search for approximate matches to the drug names using the generalized Levenshtein edit distance using the R and SAS™ 9.3 was used to search for patterns in the adverse experiences. These AEs were grouped by Preferred Term(PT), and the ranking of growth related AEs was conducted relative to other PTs. RESULTS:Of 574 self-reported adverse experiences reported for imatinib from 2012-2014, there were 12 (2.1%) cases of growth retardation. Growth retardation was the 5th most commonly occurring AE. Of 594 self-reported adverse experiences for dasatinib from 2012-2104, no cases of growth retardation occurred. Likewise, of 25 self-reported AEs for nilotinib, none were growth related. CONCLUSION:There appears to be some evidence of growth retardation in imatinib patients, and none for dasatinib patients. Not enough AEs have yet been reported for nilotinib to judge whether growth is also retarded in these patients

Evolution of Interventional Vancomycin Trials in Light of New Antibiotic Development in the USA, 1999–2012

Use of vancomycin has increased following the emergence of resistant Gram-positive bacterial infections. Investigation into recent vancomycin clinical studies provides insight into the optimal use of vancomycin and the development of novel antibiotics for the treatment of resistant infections. Interventional vancomycin trials registered in ClinicalTrials.gov from January 1999 to December 2012 were identified. Trial trends and characteristics were evaluated in the context of vancomycin use and new antibiotic development. Overall, 122 interventional vancomycin trials were identified, with a significant increase in the number of registered trials per year (P \u3c 0.001). The top three indications studied were skin and soft-tissue infections (28.7%), Clostridium difficile infections (13.1%) and surgical prophylaxis (12.3%). Trials testing vancomycin as an experimental agent differed from trials using vancomycin as an active comparator. Experimental agent trials commonly investigated new formulations, dosing regimen optimisation and combination therapy, which were less likely to be in phase 2 or 3 (25% vs. 70%; P \u3c 0.001), adopt a randomisation procedure (70% vs. 98%; P \u3c 0.001), report results (15% vs. 35%; P = 0.02) or be funded by industry (8% vs. 76%; P \u3c 0.001). Active comparator trials mainly focused on monotherapy, which led to six FDA-approved drug products and ten investigational new drugs in late-phase development. This study demonstrated a significant increase in interventional vancomycin trials and its recent success, which resulted in several novel agents against resistant Gram-positive bacteria. Further studies are warranted to determine how these agents can best be incorporated within clinical practice

Evolution of Interventional Vancomycin Trials in Light of New Antibiotic Development in the USA, 1999–2012

Use of vancomycin has increased following the emergence of resistant Gram-positive bacterial infections. Investigation into recent vancomycin clinical studies provides insight into the optimal use of vancomycin and the development of novel antibiotics for the treatment of resistant infections. Interventional vancomycin trials registered in ClinicalTrials.gov from January 1999 to December 2012 were identified. Trial trends and characteristics were evaluated in the context of vancomycin use and new antibiotic development. Overall, 122 interventional vancomycin trials were identified, with a significant increase in the number of registered trials per year (P \u3c 0.001). The top three indications studied were skin and soft-tissue infections (28.7%), Clostridium difficile infections (13.1%) and surgical prophylaxis (12.3%). Trials testing vancomycin as an experimental agent differed from trials using vancomycin as an active comparator. Experimental agent trials commonly investigated new formulations, dosing regimen optimisation and combination therapy, which were less likely to be in phase 2 or 3 (25% vs. 70%; P \u3c 0.001), adopt a randomisation procedure (70% vs. 98%; P \u3c 0.001), report results (15% vs. 35%; P = 0.02) or be funded by industry (8% vs. 76%; P \u3c 0.001). Active comparator trials mainly focused on monotherapy, which led to six FDA-approved drug products and ten investigational new drugs in late-phase development. This study demonstrated a significant increase in interventional vancomycin trials and its recent success, which resulted in several novel agents against resistant Gram-positive bacteria. Further studies are warranted to determine how these agents can best be incorporated within clinical practice

Vaccination Patterns Among Pediatric Cancer Patients Treated with Vancomycin

Background: The improvement in survival among children diagnosed with malignancy over the past two decades has been a remarkable achievement. As a consequence of therapy most of these patients are immunocompromised and therefore at high risk of infections. Vaccination is important to prevent infectious diseases, especially for patients who will become vulnerable to infections. Methods: A multicenter retrospective study of patients from birth to 18 years who received ≥ 2 does of IV vancomycin between 01/2006 and 12/2012 was preformed using an EMR database. Cancer diagnoses were identified via validated hospital registry. These data could not be analyzed prior to September 8 due to time constrains for consultation with the data architect. Statistical analysis was performed in SASTM version 9.3 and R. Results: There were 259 cancer and 4727 cancer-free patients who received vancomycin over the study period. Of these, there were a total of 19 vaccinations among 9 patients with cancer and 3070 vaccinations for 1169 cancer-free patients. Patients with cancer were vaccinated less frequently than cancer-free patients (3.4% vs 24.7%,

Vaccination Patterns Among Pediatric Cancer Patients Treated with Vancomycin

Background: The improvement in survival among children diagnosed with malignancy over the past two decades has been a remarkable achievement. As a consequence of therapy most of these patients are immunocompromised and therefore at high risk of infections. Vaccination is important to prevent infectious diseases, especially for patients who will become vulnerable to infections. Methods: A multicenter retrospective study of patients from birth to 18 years who received ≥ 2 does of IV vancomycin between 01/2006 and 12/2012 was preformed using an EMR database. Cancer diagnoses were identified via validated hospital registry. These data could not be analyzed prior to September 8 due to time constrains for consultation with the data architect. Statistical analysis was performed in SASTM version 9.3 and R. Results: There were 259 cancer and 4727 cancer-free patients who received vancomycin over the study period. Of these, there were a total of 19 vaccinations among 9 patients with cancer and 3070 vaccinations for 1169 cancer-free patients. Patients with cancer were vaccinated less frequently than cancer-free patients (3.4% vs 24.7%,