P031 Systematic-analysis of injection-site pain from administration of subcutaneous adalimumab biosimilar FKB327 versus the adalimumab reference product humira via different methods

Abstract

BACKGROUND: FKB327 is a proposed biosimilar of the adalimumab reference product (RP). Several studies in both healthy volunteers and patients with active rheumatoid arthritis (RA) were undertaken, the results of which have been reported elsewhere. The formulation excipients of the biosimilar product differ from that of the RP, and different injection-site pain with subcutaneous injection has been reported. The current meta-analysis examines pooled data from these studies in relation to the amount of injection-site pain resulting from using prefilled syringes (PFS) versus auto-injectors (AI) versus regular syringes (RS) and the proposed biosimilar, FKB327, versus the RP. METHODS: Data from 4 studies, FKB327-001, -002, -003, and -004, were pooled in an effort to compare injection-site pain upon subcutaneous administration of FKB327 versus the RP (citrate-containing formulation of the RP (40 mg/0.8 mL). Study FKB327-001, in healthy volunteers (n = 180), involved a single subcutaneous dose of either FKB327 or the RP. Study FKB327-004 was a similar study in healthy Japanese volunteers (n = 130). Study FKB327-002 was a randomized (FKB327 with RS or the RP), double-blind, multiple-dose study in patients with active RA. This was followed by Study FKB327-003, in which patients were rerandomized to receive either FKB327-PFS or the RP in the randomization phase, followed by an open-label extension phase of the study, in which AI was introduced. As patients were continued on treatment or switched during the course of the FKB327-002 and -003 studies, the injection-site pain was assessed at the first dosing occasion of FKB327 or the RP (n = 691). Data from all 4 studies were examined by meta-analysis of the visual analog scale (VAS) using a 100-mm horizontal scale for FKB327 versus the RP and for comparison of AI, PFS, and RS. RESULTS: Data were analyzed from a total of 2007 assessments in 1,001 subjects. A linear mixed model of the VAS in mm for the RP versus FKB327 across all 4 studies showed a 12.6-point improvement in the score for FKB327 versus the RP (95% confidence interval [CI], –14.3 to –10.8; P < 0.001). For the AI and PFS used for FKB327 administration, AI showed a 1.7-point improvement in VAS compared with PFS (95% CI, –3.3 to –0.1; P = 0.035). Gender, age, body weight, and population (healthy subject or patient) were not identified for differences in injection-site pain. CONCLUSION(S): FKB327 showed a significant advantage in terms of injection-site pain compared with the RP, as well as lack of inferiority for both AI and PFS versus RS.