title: Postmarketing Safety Profile of Subcutaneous Interferon Beta-1a Given 3 Times Weekly: A Retrospective Administrative Claims Analysis.
abstract: BACKGROUND
  Health insurance administrative claims databases represent a valuable source of information regarding the safety profile of marketed products as used in actual clinical practice in a broader range of patients than that assessed in clinical trials. Interferon beta-1a administered subcutaneously 3 times weekly (IFN β-1a SC tiw), which was approved in 2002 by the FDA for the treatment of relapsing-remitting multiple sclerosis (MS), has over a decade of postmarketing experience. To date, however, its postmarketing safety profile has not been described using a real-world evidence source such as administrative claims data.
  
  
  OBJECTIVE
  To describe the safety profile of IFN β-1a SC tiw as presented in its U.S. prescribing information (PI) for patients with MS initiating IFN β-1a SC tiw therapy using data from U.S. health care administrative claims databases.
  
  
  METHODS
  This study featured an observational and retrospective "new start" cohort design using data from the Truven MarketScan Commercial and Medicare Supplemental health care administrative claims databases. Patients were eligible for inclusion if they were aged ≥ 18 years; had ≥ 1 diagnosis for MS recorded between January 1, 2006, and December 31, 2012; had ≥ 2 prescriptions for IFN β-1a SC tiw; and had ≥ 90 days of continuous eligibility pre-index date and ≥ 180 days of continuous eligibility post-index date. Patients with a prescription for IFN β-1a SC tiw without a MS diagnosis were excluded. Patients were followed from first prescription for IFN β-1a SC tiw (index date) until date of therapy switch or discontinuation, end of insurance eligibility, or end of observation period. Adverse events (AEs) examined were those listed in the Warnings and Precautions, Adverse Reactions, and Postmarketing Experience sections of the 2014 U.S. PI. Outcomes of interest were identified at the Medical Dictionary for Regulatory Activities (version 17.1) Preferred Term level and then coded to the corresponding ICD-9-CM criteria. Descriptive analyses of patient demographic, health status, health care utilization, and adherence status were performed, and incidence rates (IRs) per 100 person-years of labeled AEs with corresponding 95% CIs were calculated. The IR calculation was based on events that presented after therapy initiation and that were not present in the 90-day pre-index period.
  
  
  RESULTS
  The top 6 AEs included influenza-like symptoms (IR = 15.65, 95% CI = 14.96-16.36); malaise (IR = 15.33, 95% CI = 14.65-16.04; fatigue (IR = 15.02, 95% CI = 14.35-15.72); abdominal pain (IR = 10.18, 95% CI = 9.67-10.70); chest pain (IR = 8.48, 95% CI = 8.03-8.95); and depression (IR = 7.75, 95% CI = 7.32-8.20). In contrast, the 6 lowest IRs were for maculo-papular rash (IR = 0.01, 95% CI = 0.00-0.04; injection-site necrosis (IR = 0.01, 95% CI = 0.00-0.03); erythema multiforme (IR = 0.01, 95% CI = 0.00-0.04); hypoesthesia (IR = 0.00, 95% CI = 0.00-0.02); Stevens-Johnson Syndrome (IR = 0.00, 95% CI = 0.00-0.02); and xerophthalmia (IR = 0.00, 95% CI = 0.00-0.02).
  
  
  CONCLUSIONS
  Study results show strong convergence between the real-world safety profile of IFN β-1a SC tiw and its U.S. label. Our findings demonstrate the value of using real-world evidence obtained from administrative claims to complement clinical trial and postmarketing surveillance data in order to characterize the safety profile of established products, such as IFN β-1a SC tiw, in the postmarketing context.
authors.affiliation: Merck KGaA, Frankfurter Straße 250, Darmstadt, Germany 64293. florent-frederic.richy@merckgroup.com.
authors.forename: Meredith Y
authors.initials: MY
authors.lastname: Smith
authors.forename: Meritxell
authors.initials: M
authors.lastname: Sabidó-Espin
authors.forename: Anton
authors.initials: A
authors.lastname: Trochanov
authors.forename: Mark
authors.initials: M
authors.lastname: Samuelson
authors.forename: Sandra
authors.initials: S
authors.lastname: Guedes
authors.forename: Frank A
authors.initials: FA
authors.lastname: Corvino
authors.forename: Florent F
authors.initials: FF
authors.lastname: Richy
mesh_terms: D000328:Adult; D016208:Databases, Factual; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000453:epidemiology*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects*; D007279:Injections, Subcutaneous; D007345:Insurance Claim Review; D007356:Insurance, Pharmaceutical Services; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D006278:Medicare; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D061214:Patient Safety; D011358:Product Surveillance, Postmarketing; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D007155:Immunologic Factors; D016898:Interferon-alpha