title: Factors influencing secondary non-response to botulinum toxin type A injections in cervical dystonia.
abstract: BACKGROUND
  The development of secondary non-response (SNR) to botulinum neurotoxin type-A (BoNT-A) is considered a key issue in the management of cervical dystonia (CD). This case-controlled study was performed to systematically identify factors influencing SNR during BoNT-A therapy.
  
  
  METHODS
  This was a retrospective, international, non-interventional study of CD patients. Patients with SNR were matched with up to three responder patients (control) on the basis of duration of therapy and number of injection cycles. Factors influencing the development of SNR were screened using a univariate logistic regression model and confirmed using a multivariate conditional logistic regression model.
  
  
  RESULTS
  216 patients were enrolled, and 201 (SNR = 52; responder = 149) were matched and subdivided into blocks (doublets, triplets or quadruplets). At baseline, a significantly higher proportion of SNR patients had received previous or concomitant therapies (p = 0.038) and surgery for CD (p = 0.007) compared with controls. Although disease severity at onset was similar between groups, a significantly higher proportion of SNR patients experienced severe CD at the time of SNR compared with controls at the last documented visit. Multivariate analyses identified five factors that were significantly associated in predicting SNR (odds ratio [OR] > 1 indicated higher chances for being SNR): previous surgical procedure for CD (OR 9.8, p = 0.013), previous BoNT-A related severe adverse event (AE) (OR 5.6 p = 0.027), physical therapy (OR 4.6, p = 0.028), neuroleptic use (OR 3.3, p = 0.019) and average BoNT-A dose (OR 2.7, p = 0.010).
  
  
  CONCLUSIONS
  These findings suggest that SNR may not reflect true pharmacological resistance to BoNT-A therapy, but may be related to underlying disease severity.
authors.affiliation: Neurological Clinical Research Unit and Clinical Pharmacology Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Portugal. Electronic address: joaquimjferreiras@gmail.com.
authors.forename: Joaquim J
authors.initials: JJ
authors.lastname: Ferreira
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Colosimo
authors.affiliation: Chulalongkorn Center of Excellence on Parkinson's Disease and Related Disorders, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
authors.forename: Roongroj
authors.initials: R
authors.lastname: Bhidayasiri
authors.affiliation: Neurology Service, Institut Cliníc de Neurosciències (ICN), CIBERNED, Hospital Clinic of Barcelona, Barcelona, Spain.
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Marti
authors.affiliation: Global Medical Affairs, Ipsen Pharma, Boulogne-Billancourt, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Maisonobe
authors.affiliation: Global Medical Affairs, Ipsen Pharma, Boulogne-Billancourt, France.
authors.forename: Savary
authors.initials: S
authors.lastname: Om
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D038622:Internationality; D008297:Male; D008875:Middle Aged; D009465:Neuromuscular Agents / Q000008:administration & dosage*; D012189:Retrospective Studies; D014103:Torticollis / Q000175:diagnosis* / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A
keywords: Botulinum toxin; Cervical dystonia; Secondary non-response