title: Alleviating flu-like symptoms with dose titration and analgesics in MS patients on intramuscular interferon beta-1a therapy: a pilot study.
abstract: OBJECTIVE
  To determine the effectiveness of dose titration and choice of analgesic in reducing flu-like side effects of intramuscular interferon beta-1a (i.m. IFNbeta-1a).
  
  
  METHODS
  Patients were randomly assigned to receive weekly i.m. IFNbeta-1a, with or without dose titration, plus acetaminophen or ibuprofen. After 27 patients had been randomized, the original formulation of i.m. IFNbeta-1a became unavailable and the remaining patients used a pre-packaged liquid formulation, necessitating a change in protocol from initially quarter-dose to half-dose titration. Patients scored presence and intensity of muscle aches, chills, and weakness, and measured body temperature; information was recorded in diaries.
  
  
  RESULTS
  Forty-seven patients were enrolled; 36 completed the study. Fifteen patients received full-dose therapy plus acetaminophen, eight patients received quarter-dose titration and acetaminophen, 10 patients received quarter-dose titration and ibuprofen, eight patients received half-dose titration and acetaminophen, and six patients received half-dose titration and ibuprofen. The mean number of acetaminophen doses taken was not statistically different from the mean number of ibuprofen doses taken per patient per week in any dose-titration group over measured time intervals (p > 0.05). Symptom scores from acetaminophen and ibuprofen dose-titration groups were combined and compared with the no-titration group. The proportion of patients with a mean increase of > or = 2 from baseline in flu-like symptom score trended lower in the titrated group compared with the no-titration group at 4 hours and 12-15 hours post-injection; these differences reached statistical significance only during the first 2 weeks of treatment (p = 0.015, quarter-dose vs. no titration).
  
  
  CONCLUSIONS
  This study supports the findings of previous studies demonstrating no difference in the effectiveness of acetaminophen and ibuprofen in controlling flu-like symptoms associated with IFNbeta treatment in patients with relapsing-remitting MS. Trends in this small pilot study suggest that the combination of initial dose titration and analgesic administration is useful for the reduction of flu-like symptoms with IFNbeta-1a therapy.
authors.affiliation: Northridge MS Center, Northridge, CA 91325, USA. dwbnorth@sbcglobal.net
authors.forename: David W
authors.initials: DW
authors.lastname: Brandes
authors.forename: Kim
authors.initials: K
authors.lastname: Bigley
authors.forename: William
authors.initials: W
authors.lastname: Hornstein
authors.forename: Hart
authors.initials: H
authors.lastname: Cohen
authors.forename: William
authors.initials: W
authors.lastname: Au
authors.forename: Richard
authors.initials: R
authors.lastname: Shubin
mesh_terms: D000082:Acetaminophen / Q000627:therapeutic use*; D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000627:therapeutic use*; D007251:Influenza, Human / Q000150:complications / Q000188:drug therapy*; D007273:Injections, Intramuscular; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications*; D010865:Pilot Projects
chemical_list: D000276:Adjuvants, Immunologic; D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen; D016899:Interferon-beta; D007052:Ibuprofen; D000068556:Interferon beta-1a