John S Bradley1, Ralph E Kauffman2, Dainius A Balis3, Ciaran M Duffy4, Peter G Gerbino5, Samuel D Maldonado3, Gary J Noel6. 1. University of California, San Diego School of Medicine and Rady Children's Hospital San Diego, San Diego, California; jbradley@rchsd.org. 2. Children's Mercy Hospitals and Clinics and University of Missouri at Kansas City, Kansas City, Missouri; 3. Janssen Research and Development, LLC, Raritan, New Jersey; 4. Children's Hospital of Eastern Ontario and University of Ottawa, Ottawa, Ontario, Canada; 5. Community Hospital of the Monterey Peninsula; Monterey, California; and. 6. Janssen Research and Development, LLC, Raritan, New Jersey;Weill Cornell Medical College, New York, New York.
Abstract
BACKGROUND: Safety concerns for fluoroquinolones exist from animal studies demonstrating cartilage injury in weight-bearing joints, dependent on dose and duration of therapy. For children treated with levofloxacin or comparator in randomized, prospective, comparative studies for acute otitis media and community-acquired pneumonia, this 5-year follow-up safety study was designed to assess the presence/absence of cartilage injury. METHODS: Children enrolled in treatment studies were also enrolled in a 1-year follow-up safety study, which; focused on musculoskeletal adverse events (MSAE). Those with persisting MSAEs, protocol-defined musculoskeletal disorders, or of concern to the Data Safety and Monitoring Committee were requested to enroll in four additional years of follow-up, the subject of this report. RESULTS: Of the 2233 subjects participating in the 12-month follow-up study, 124 of 1340 (9%) of the levofloxacin subjects, and 83 of 893 (9%) of the comparator subjects were continued for 5-year posttreatment assessment. From children identified with an MSAE during years 2 through 5 posttreatment, the number that were "possibly related" to drug therapy was equal for both arms: 1 of 1340 for levofloxacin and 1 of 893 for comparator. Of all cases of MSAE assessed by the Data Safety and Monitoring Committee at 5 years' posttreatment, no case was assessed as "likely related" to study drug. CONCLUSIONS: With no clinically detectable difference between levofloxacin- and comparator-treated children in MSAEs presenting between 1 and 5 years in these safety studies, risks of cartilage injury with levofloxacin appear to be uncommon, are clinically undetectable during 5 years, or are reversible.
BACKGROUND: Safety concerns for fluoroquinolones exist from animal studies demonstrating cartilage injury in weight-bearing joints, dependent on dose and duration of therapy. For children treated with levofloxacin or comparator in randomized, prospective, comparative studies for acute otitis media and community-acquired pneumonia, this 5-year follow-up safety study was designed to assess the presence/absence of cartilage injury. METHODS:Children enrolled in treatment studies were also enrolled in a 1-year follow-up safety study, which; focused on musculoskeletal adverse events (MSAE). Those with persisting MSAEs, protocol-defined musculoskeletal disorders, or of concern to the Data Safety and Monitoring Committee were requested to enroll in four additional years of follow-up, the subject of this report. RESULTS: Of the 2233 subjects participating in the 12-month follow-up study, 124 of 1340 (9%) of the levofloxacin subjects, and 83 of 893 (9%) of the comparator subjects were continued for 5-year posttreatment assessment. From children identified with an MSAE during years 2 through 5 posttreatment, the number that were "possibly related" to drug therapy was equal for both arms: 1 of 1340 for levofloxacin and 1 of 893 for comparator. Of all cases of MSAE assessed by the Data Safety and Monitoring Committee at 5 years' posttreatment, no case was assessed as "likely related" to study drug. CONCLUSIONS: With no clinically detectable difference between levofloxacin- and comparator-treated children in MSAEs presenting between 1 and 5 years in these safety studies, risks of cartilage injury with levofloxacin appear to be uncommon, are clinically undetectable during 5 years, or are reversible.
Authors: Payam Nahid; Sundari R Mase; Giovanni Battista Migliori; Giovanni Sotgiu; Graham H Bothamley; Jan L Brozek; Adithya Cattamanchi; J Peter Cegielski; Lisa Chen; Charles L Daley; Tracy L Dalton; Raquel Duarte; Federica Fregonese; C Robert Horsburgh; Faiz Ahmad Khan; Fayez Kheir; Zhiyi Lan; Alfred Lardizabal; Michael Lauzardo; Joan M Mangan; Suzanne M Marks; Lindsay McKenna; Dick Menzies; Carole D Mitnick; Diana M Nilsen; Farah Parvez; Charles A Peloquin; Ann Raftery; H Simon Schaaf; Neha S Shah; Jeffrey R Starke; John W Wilson; Jonathan M Wortham; Terence Chorba; Barbara Seaworth Journal: Am J Respir Crit Care Med Date: 2019-11-15 Impact factor: 21.405
Authors: Payam Nahid; Susan E Dorman; Narges Alipanah; Pennan M Barry; Jan L Brozek; Adithya Cattamanchi; Lelia H Chaisson; Richard E Chaisson; Charles L Daley; Malgosia Grzemska; Julie M Higashi; Christine S Ho; Philip C Hopewell; Salmaan A Keshavjee; Christian Lienhardt; Richard Menzies; Cynthia Merrifield; Masahiro Narita; Rick O'Brien; Charles A Peloquin; Ann Raftery; Jussi Saukkonen; H Simon Schaaf; Giovanni Sotgiu; Jeffrey R Starke; Giovanni Battista Migliori; Andrew Vernon Journal: Clin Infect Dis Date: 2016-08-10 Impact factor: 9.079
Authors: Sarah Alexander; Brian T Fisher; Aditya H Gaur; Christopher C Dvorak; Doojduen Villa Luna; Ha Dang; Lu Chen; Michael Green; Michael L Nieder; Beth Fisher; L Charles Bailey; John Wiernikowski; Lillian Sung Journal: JAMA Date: 2018-09-11 Impact factor: 56.272