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Randomized Crossover Comparison of Injection Site Pain with 40 mg/0.4 or 0.8 mL Formulations of Adalimumab in Patients with Rheumatoid Arthritis - PubMed

Randomized Crossover Comparison of Injection Site Pain with 40 mg/0.4 or 0.8 mL Formulations of Adalimumab in Patients with Rheumatoid Arthritis

Peter Nash et al. Rheumatol Ther. 2016 Dec.

Abstract

Introduction: 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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov identifier, NCT01561313 and NCT01502423.

Funding: AbbVie.

Keywords: Injections; Pain; Quality of life; Rheumatoid arthritis; Tumor necrosis factor inhibitors.

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Figures

Fig. 1
Fig. 1

Study design. aDependent on patient’s prescribed on-label dosing schedule

Fig. 2
Fig. 2

Patient disposition. cITT crossover intent-to-treat

Fig. 3
Fig. 3

Parameters assessed in the cITT population immediately after injection. Injection site pain for pooled data, Study 1, and Study 2 (i); present pain intensity in Study 1 and Study 2 (ii); and MPQ-SF total pain, sensory dimension, and affective dimension scores of pain experience scores in Study 1 and Study 2 (iii). cITT crossover intent-to-treat, MPQ-SF short-form McGill Pain Questionnaire, SD standard deviation, VAS visual analog scale. a P < 0.001. b P = 0.001. c P = 0.009

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