title: Randomized Crossover Comparison of Injection Site Pain with 40 mg/0.4 or 0.8 mL Formulations of Adalimumab in Patients with Rheumatoid Arthritis.
abstract: BACKGROUND
  Adalimumab, an anti-tumor necrosis factor antibody, is currently available in a 40 mg/0.8 mL formulation. The objective of this analysis was to evaluate injection site-related pain, safety, and tolerability of a 40 mg/0.4 mL formulation of adalimumab that had fewer excipients, a smaller volume, and a delivery presentation with a smaller gauge needle, versus the current 40 mg/0.8 mL formulation in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  Two identically designed, phase 2, randomized, single-blind, two-period crossover studies were conducted in Belgium and the Czech Republic (Study 1) and Australia, Canada, and Germany (Study 2). In both studies, adults with RA [biologic-naive or current users of 40 mg/0.8 mL adalimumab with an average injection site-related pain rating ≥3 cm on a visual analog scale (VAS; 0-10 cm)] were randomized to receive 40 mg/0.8 mL or 40 mg/0.4 mL adalimumab at visit 1. After 1-2 weeks (depending on patient medication schedule), patients received the other formulation at visit 2. A pain VAS [McGill Pain Questionnaire (MPQ-SF)] and the Draize scale were evaluated immediately after injection and 15 min postinjection. The primary endpoint was immediate pain after injection.
  
  
  RESULTS
  64 and 61 patients were randomized in Studies 1 and 2, respectively. Both studies found a clinically relevant and statistically significant lower immediate pain after injection for the 40 mg/0.4 mL versus the 40 mg/0.8 mL formulation. The mean difference on the VAS for the pooled data (-2.48 cm) was also clinically relevant. Most other endpoints in both studies favored the 40 mg/0.4 mL formulation, and its tolerability and safety profile were consistent with 40 mg/0.8 mL adalimumab.
  
  
  CONCLUSIONS
  A 40 mg/0.4 mL adalimumab formulation was well tolerated and associated with less injection site-related pain than the 40 mg/0.8 mL adalimumab formulation.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier, NCT01561313 and NCT01502423.
  
  
  BACKGROUND
  AbbVie.
authors.affiliation: Department of Medicine, University of Queensland Rheumatology Research Unit Sunshine Coast, Queensland, Australia. drpnash@tpg.com.au.
authors.forename: Peter
authors.initials: P
authors.lastname: Nash
authors.affiliation: Department of Rheumatology, ReumaClinic Genk, Genk, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Vanhoof
authors.affiliation: Department of Medicine, Monash University, Cabrini Health, Malvern, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hall
authors.affiliation: Immunology Clinical Development, AbbVie, North Chicago, IL, USA.
authors.forename: Udayasankar
authors.initials: U
authors.lastname: Arulmani
authors.affiliation: Biotherapeutics, Global Medical Affairs, AbbVie, Lake Bluff, IL, USA.
authors.forename: Rita
authors.initials: R
authors.lastname: Tarzynski-Potempa
authors.affiliation: Data and Statistical Sciences, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Unnebrink
authors.affiliation: Immunology Clinical Development, AbbVie, North Chicago, IL, USA.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Payne
authors.affiliation: Department of Medicine, McMaster University, Ontario, Canada.
authors.forename: Alfred
authors.initials: A
authors.lastname: Cividino
keywords: Injections; Pain; Quality of life; Rheumatoid arthritis; Tumor necrosis factor inhibitors