Switching three times between a ustekinumab biosimilar and the reference product kept drug exposure and response unchanged

Design

Randomised, double-blind, parallel-group switching study with 28-week run-in

Population

453 randomised adults with moderate-to-severe plaque psoriasis responding to ustekinumab (225 continued, 228 switched)

Primary outcome

AUCtau and Cmax between weeks 52 and 64

Effect

Geometric mean ratio 0.93 (90% CI 0.89 to 0.98) AUCtau; 0.95 (0.90 to 1.00) Cmax

This double-blind trial enrolled 494 people with moderate-to-severe plaque psoriasis. All got reference ustekinumab (45 mg or 90 mg by weight) at weeks 0, 4 and 16. At week 28, 453 people with at least a 50% PASI improvement were randomised: continued reference product at weeks 28, 40 and 52, or alternated between the biosimilar ABP 654 and the reference product (ABP 654 at weeks 28 and 52, reference at week 40).

Between weeks 52 and 64, geometric mean ratios were 0.93 (90% CI 0.89 to 0.98) for AUCtau and 0.95 (90% CI 0.90 to 1.00) for Cmax, both inside the 0.8 to 1.25 similarity margin. Efficacy, antidrug antibodies and adverse events were also similar.

The trial was designed to support a legal interchangeability designation, which is a regulatory step that varies by country, so its practical meaning depends on local rules. For clinicians, it addresses the worry that back-and-forth switching, for example driven by supply or payer changes, might alter exposure or provoke antibodies.

• Reassure patients that, in this trial, repeated switching did not change drug exposure or response.
• Check local regulations on substitution and whether the prescriber must be told.
• Record which product the patient received at each dose so adverse events can be traced.
• Monitor response after any switch as you would after any change in treatment.

Why it matters

It tests the thing pharmacy-led substitution assumes: that multiple switches cause no harm.

Don't overread it

It studied one biosimilar in one indication and was designed for regulatory purposes; it does not apply to other biosimilars.

The statistics, in plain English

The 90% confidence intervals for both pharmacokinetic ratios sit fully within 0.8 to 1.25, the usual margin for similarity. The Cmax upper bound of 1.00 shows no sign of higher peaks after switching. The trial lasted 64 weeks and cannot show effects beyond that.

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