title: Patient adherence to and tolerability of self-administered interferon β-1a using an electronic autoinjection device: a multicentre, open-label, phase IV study.
abstract: BACKGROUND
  Achieving good adherence to self-injected treatments for multiple sclerosis can be difficult. Injection devices may help to overcome some of the injection-related barriers to adherence that can be experienced by patients. We sought to assess short-term adherence to, and tolerability of, interferon (IFN) β-1a administered via electronic autoinjection device in patients with relapsing-remitting multiple sclerosis (RRMS).
  
  
  METHODS
  BRIDGE (RebiSmart to self-inject Rebif serum-free formulation in a multidose cartridge) was a 12-week, multicentre, open-label, single-arm, observational, Phase IV study in which patients self-administered IFN β-1a (titrated to 44 μg), subcutaneously (sc), three times weekly, via electronic autoinjection device. Patients were assessed at baseline and 4-weekly intervals to Week 12 or early termination (ET) for: physical examinations; diary card completion (baseline, Weeks 4, 8 only); neurological examinations (baseline, Week 12/ET only); MS Treatment Concern Questionnaire (MSTCQ; Weeks 4, 8, 12 only); Convenience Questionnaire (Week 12 only); Hospital Anxiety and Depression Scale (HADS); and Paced Auditory Serial Addition Task (PASAT; baseline only). Adherence was defined as administration of ≥ 80% of scheduled injections, recorded by the autoinjection device.
  
  
  RESULTS
  Overall, 88.2% (105/119; intent-to-treat population) of patients were adherent; 67.2% (80/119) administered all scheduled injections. Medical reasons accounted for 35.6% (31/87) of missed injections, forgetfulness for 20.6% (18/87). Adherence did not correlate with baseline Expanded Disability Status Scale (P = 0.821) or PASAT (P = 0.952) scores, or pre-study therapy (P = 0.303). No significant changes (baseline-Week 12) in mean HADS depression (P = 0.482) or anxiety (P = 0.156) scores were observed. 'Overall convenience' was the most important reported benefit of the autoinjection device. Device features associated with handling and ease of use were highly rated. Mean MSTCQ scores for 'flu-like' symptoms (P = 0.022) and global side effects (P = 0.002) significantly improved from Week 4-12. Mean MSTCQ scores for pain at injection site and injection pain increased from Week 4-12 (P < 0.001). Adverse events were mild/moderate. No new safety signals were identified.
  
  
  CONCLUSIONS
  Convenience and ease of use of the autoinjection device may improve adherence and, therefore, outcomes, in patients with RRMS receiving sc IFN β-1a.
  
  
  BACKGROUND
  EU Clinical Trials Register (EU-CTR; http://www.clinicaltrialsregister.eu): 2009-013333-24.
authors.affiliation: Department of Neuroscience and Imaging, University "G, d'Annunzio", Via dei Vestini 31, 66100 Chieti, Italy. a.lugaresi@unich.it
authors.forename: Alessandra
authors.initials: A
authors.lastname: Lugaresi
authors.forename: Ciro
authors.initials: C
authors.lastname: Florio
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Brescia-Morra
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cottone
authors.forename: Paolo
authors.initials: P
authors.lastname: Bellantonio
authors.forename: Marinella
authors.initials: M
authors.lastname: Clerico
authors.forename: Diego
authors.initials: D
authors.lastname: Centonze
authors.forename: Antonio
authors.initials: A
authors.lastname: Uccelli
authors.forename: Maria
authors.initials: M
authors.lastname: di Ioia
authors.forename: Giovanna
authors.initials: G
authors.lastname: De Luca
authors.forename: Andrea
authors.initials: A
authors.lastname: Marcellusi
authors.forename: Andrea
authors.initials: A
authors.lastname: Paolillo
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D004185:Disability Evaluation; D016503:Drug Delivery Systems; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D007279:Injections, Subcutaneous; D016899:Interferon-beta / Q000008:administration & dosage*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000523:psychology*; D010147:Pain Measurement; D010349:Patient Compliance / Q000523:psychology*; D012646:Self Administration; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007155:Immunologic Factors; D016899:Interferon-beta