Repeated switching between biosimilar ABP 654 and reference ustekinumab in patients with moderate-to-severe plaque psoriasis: a randomized, double-blinded clinical trial to support interchangeability

Abstract Background ABP 654 is a biosimilar to ustekinumab reference product (RP). It is approved for the treatment of patients with moderate-to-severe plaque psoriasis and other autoimmune disorders. Objectives To demonstrate the interchangeability of ABP 654 and ustekinumab RP following multiple switches. Methods In this randomized, double-blinded study that evaluated pharmacokinetics (PK), efficacy, immunogenicity, and safety, patients with moderate-to-severe plaque psoriasis received a subcutaneous injection of ustekinumab RP 45 mg or 90 mg (baseline body weight ≤100 kg or >100 kg, respectively) on day 1 (week 0), week 4, and week 16 (Run-in Period). At week 28, patients with a 50% improvement in Psoriasis Area and Severity Index (PASI) or better response were randomized in a 1:1 ratio to the Continued-Use group or Switching group. Those in the Continued-Use group received ustekinumab RP at the same dose as in the Run-in Period at weeks 28, 40, and 52, while the Switching group received ABP 654 at week 28, ustekinumab RP at week 40, and ABP 654 at week 52. The primary endpoints were area under the curve over the dosing interval (AUCtau) and maximum concentration (Cmax) between weeks 52 and 64. Secondary endpoints included time to maximum concentration between weeks 52 and 64, trough concentration at steady state between weeks 28 and 52, PASI percent improvement from baseline at week 64, PASI 75 and PASI 100 responses at week 64, incidence of antidrug antibodies (ADAs), and incidence and severity of adverse events (AEs). Results Of the 494 enrolled patients, 453 successfully completed the Run-in period and were randomized to the Continued-Use (n = 225) or Switching (n = 228) groups. The point estimates and 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) for AUCtau and Cmax between weeks 52 and 64 were 0.93 (0.89, 0.98) and 0.95 (0.90, 1.00), respectively. As both 90% CIs fell within the prespecified similarity margin of 0.8 to 1.25, PK similarity was demonstrated between the Switching and Continued-Use groups. In addition, efficacy, incidence of ADAs, and AEs were also similar between the groups. Conclusion These results support interchangeability of ABP 654 and ustekinumab RP.