Ciclesonide | place in therapy review Scope, aims, and objectives Ciclesonide (Alvesco®, ALTANA Pharma AG), an airway-activated inhaled corticosteroid, has been developed for the management of persistent asthma. Its once-daily administration and airway activation may be advantageous in the treatment of asthma. Pharmacologically, the activation of ciclesonide to its active metabolite, desisobutyryl-ciclesonide (des-CIC), by airway esterases is novel. This local activation of drug provides concentrated activity of ciclesonide at the target organ, the lungs, and may decrease the potential for local and systemic adverse effects. Data from phase III clinical trials evaluating ciclesonide in the management of adult and pediatric patients with persistent asthma are available. The purpose of this article is to review the place in therapy of ciclesonide in the management of patients with persistent asthma based on the available clinical evidence. Methods The English language medical literature was reviewed for appropriate articles relating to ciclesonide for the treatment of asthma. The following databases were searched during August 2005 using the search terms “ciclesonide,” “El 876,” “By 90107,” and “Alvesco”: • PubMed, http://www.ncbi.nlm.nih.gov • EMBASE, http://www.datastarweb.com • BIOSIS, http://www.datastarweb.com • York University Centre for Reviews and Dissemination (CRD) databases, http://www.york.ac.uk/inst/crd/crddatabases.htm • National Guideline Clearinghouse, http://www.guideline.gov • Clinical trial registries, http://www.clinicaltrials.gov, http://www.clinicalstudyresults.org • National Coordinating Centre for Health Technology Assessment (NCCHTA), http://www.ncchta.org • Cochrane Database of Systematic Reviews (CDSR), http://www.cochrane.org/index0.htm • National Institute for Health and Clinical Evidence (NICE), http://www.nice.org.uk • Clinical Evidence (BMJ), http://www.clinicalevidence.com No date limitations were placed on the search and only studies in patients with asthma were included. Abstracts from the American Thoracic Society (ATS) (http://www.thoracic.org) and the European Respiratory Society (ERS) meetings (http://www.ersnet.org/ers) for 2002–2005 were also reviewed using the same search terms to identify studies that have not yet been published in full. Numerous guidelines related to asthma management were identified, but only two recent guidelines applicable on a global 234 level were considered relevant for this review. No studies were identified from a review of clinical trials databases. A single Health Technology Assessment of ciclesonide was identified from the York University Centre. The levels of evidence identified from the literature searches are summarized in Table 1. Twenty full papers were identified in the initial search. Records were manually reviewed and 12 papers were excluded: pharmacokinetic (n=5), in vitro (n=1), animal studies (n=2), study other than a large, controlled clinical trial (n=3), or citations that mentioned ciclesonide but did not investigate its clinical use (n=1). Sixty-one abstracts were also reviewed manually. Exclusions included: published in full (n=4), pharmacokinetic (n=5), animal studies (n=6), in vitro (n=10), study other than a large, controlled clinical trial (n=11), and presentation of study results at more than one professional meeting (n=6). The search was updated on February 7 and on June 30, 2006 and 22 new records were identified from the previous search. Eleven records were excluded as they were nonsystematic reviews (n=6), editorials (n=1), in vitro (n=2), small pharmacokinetic study (n=1), or an indication other than asthma (n=1). A systematic review (Dyer et al. 2006) was not included in the evidence base, as it was limited to small phase II studies comparing ciclesonide with other inhaled corticosteroids, rather than more recent larger phase III randomized controlled trials (RCTs). Table 1 | Evidence base included in the review Number of records Full papers Abstracts Category Initial search records excluded records included Additional studies identifieda Search update, new records records excluded records included Level 1 clinical evidence Level 2 clinical evidence Level ≥3 clinical evidence trials other than RCT case reports Economic evidence Total records included 20 12 8 3 22 12 10 2 18 1 1 0 21 61 42 19 3 22 18 4 0 0 27b 0 27 aAdditional studies identified = any relevant study that was picked up from a source other than the main searches, e.g. a reference list. bIncludes several subanalyses from six RCTs. For definitions of levels of evidence see Editorial Information on inside back cover. RCT, randomized controlled trial. © 2006 Core Medical Publishing Limited