No Efficacy Loss After Multiple Ustekinumab Biosimilar Switches in Psoriasis

Patients with moderate-to-severe plaque psoriasis who were switched from reference ustekinumab to a first biosimilar and then to a second maintained durable disease control with no serious adverse events, according to real-world data presented at the American Academy of Dermatology (AAD) 2026 Annual Meeting.

The study, an ambispective cohort analysis from the University of Lübeck in Germany, followed 39 patients across 4 time points, from initial biologic induction through 2 sequential biosimilar transitions. As health systems move toward biosimilar-first prescribing, investigators aimed to assess if patients could be switched multiple times without losing the clinical ground gained on the originator.

Study Design

Patients were initially treated with reference ustekinumab (T1), then transitioned to a first biosimilar (Biosimilar A; T2) and subsequently to a second biosimilar (Biosimilar B; T3–T4). Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index and body surface area were assessed at each time point. Laboratory markers and adverse events were also reviewed throughout. Statistical comparisons used Wilcoxon signed-rank tests for paired data.

The cohort had a mean age of approximately 44 years; two-thirds were male, and just over a quarter carried a concurrent diagnosis of psoriatic arthritis. The majority had prior systemic therapy experience, most commonly methotrexate, fumaric acid esters, and phototherapy, underscoring a population with established, often refractory disease.

Outcomes Across Time Points

Reference ustekinumab induction produced a striking reduction in PASI, from a mean of 11.3 at baseline to 1.2 after induction, a change that was highly statistically significant. Crucially, PASI remained essentially flat across both subsequent biosimilar transitions. The small numerical increase observed at T4 (mean 1.6 vs 1.2 at T3) was statistically significant in a paired test, but investigators noted that absolute values remained clinically low throughout, with a median PASI at or near 0.6 from T2 onward.

Safety and Laboratory Findings

No serious adverse events were identified during the biosimilar phases. Mild-to-moderate infections were the most commonly recorded clinical events, occurring in 7 patients between T2 and T3, and 4 patients between T3 and T4. Minor psoriasis worsening—defined as PASI below 5—was noted in 2 patients at each of the final 2 intervals; of these, one required dose escalation from 45 mg to 90 mg, and one was eventually switched to tildrakizumab 200 mg. One patient developed enthesitis that resolved with physiotherapy alone. A lentigo maligna was detected and surgically removed in one patient between T3 and T4; this lesion had been identified and monitored before the biosimilar transition began.

Laboratory monitoring showed stability across all measured parameters from T2 through T4. Liver enzyme (ALT/GPT) levels declined significantly between T1 and T2, then held steady. The neutrophil-to-lymphocyte ratio, a proxy for systemic inflammatory activity, fell significantly from T1 to T3 and remained stable thereafter, suggesting that the anti-inflammatory effect of ustekinumab was preserved across both switches.

Implications for Clinical Practice

The findings directly address a practical question facing dermatologists and payers alike: whether health systems can carry out nonmedical switching across multiple biosimilar generations without jeopardizing patient outcomes. The data presented here suggest the answer is yes, at least in the medium term and within this cohort.

Investigators were careful to acknowledge limitations. The ambispective design—retrospective through the first switch, prospective thereafter—introduces potential for selection bias. The sample of 39 patients limits statistical power, and the absence of a concurrent control group means confounders cannot be fully excluded. Follow-up after the second switch was also limited; longer-term durability data would strengthen the case further.

Nonetheless, the authors concluded that sequential switching between ustekinumab biosimilars appears to be a viable, cost-effective strategy that does not compromise efficacy or safety. As biosimilar pipelines for IL-12/23 blockade continue to expand, these real-world data add important evidence to complement the controlled trial literature on individual switches.

Reference

1. De Luca DA, Papara C, Pommerien L, Hawro T, Thaçi D. Sequential switching between ustekinumab biosimilars in psoriasis: real-world evidence of clinical interchangeability. Presented at the American Academy of Dermatology Annual Meeting; Poster 72304.