PARIS — Doses of interleukin (IL)-17 and IL-23 inhibitors were safely reduced in people with plaque psoriasis who had “very stable low disease activity”; it was reported during a late-breaking news session last week at the European Academy of Dermatology and Venereology (EADV) 2025 Congress.

“We showed a stepwise dose reduction of IL-17 and IL-23 inhibitors is noninferior to usual care regarding persistent flares,” said Juul van den Reek, MD, of Radboud University Medical Center in Nijmegen, Netherlands, who presented the first results from the BeNeBio study.

Moreover, a “substantial portion of patients was able to achieve successful dose reduction after 18 months” with IL-23 inhibitors, which were seemingly “a bit more taperable than IL-17 inhibitors,” van den Reek added.

Study Background and Design

BeNeBio was conducted to see if dose reduction of biologics was feasible for people with plaque psoriasis who had attained and maintained a low disease state.

“We have a lot of biologics to choose from for psoriasis, and in the last few years, we’ve got these very effective and safe IL-17 and IL-23 inhibitors,” van den Reek noted. “On the one hand, we have these very effective drugs, but on the other side, we expose patients lifelong to these agents, and these agents come with high costs, therefore limiting accessibility in parts of the world.”

The study, designed as a noninferiority trial, was conducted at 19 hospitals in Netherlands and Belgium and enrolled 244 adult patients with plaque psoriasis. For inclusion, patients must have been treated with an IL-17 or IL-23 inhibitor for at least 6 months, have a Psoriasis Area and Severity Index (PASI) score ≤ 5 for at least 6 months, and must have a Dermatology Life Quality Index (DLQI) score ≤ 5.

Recruited patients were randomly allocated (2:1) to a dose reduction (n = 164) or usual care (n = 80) group. Those in the first group underwent a two-phased reduction in their doses (first to 67%, then 50% of their standard dose), while those in the usual care group continued taking the standard doses of their medications. Follow-up occurred every 3 months over an 18-month period.

Patients in the dose reduction group only stepped down to the lower doses of their medications if their PASI and DLQI scores remained low. When necessary, the previous effective dose was reinstated.

The dose reduction intervals depended on the biologic. For short-dosing drugs, such as the IL-17 inhibitor secukinumab (Cosentyx), dosing intervals were prolonged from every 4 weeks to every 6 weeks, and then to every 8 weeks. The long-interval drugs were initially administered every 12 weeks, followed by every 18 weeks and then 24 weeks, van den Reek explained.

Baseline characteristics were similar between the study groups. The mean age was 49 years in the dose reduction group (65% men; PASI scores, 0.0; DLQI scores, 0.0) and 54 years in the usual care group (71% men; PASI scores, 0.1; DLQI scores, 0.0). Overall, 14% had concomitant psoriatic arthritis, and 47% had never been treated with a biologic.

Approximately half of the study population was given an IL-17 inhibitor: 25% were on ixekizumab (Taltz), 14% on secukinumab, 6% on brodalumab (Kyntheum), and 1% on bimekizumab (Bimzelx). The other half was given an IL-23 inhibitor: 30% on guselkumab (Tremfya), 21% on risankizumab (Skyrizi), and 3% on tildrakizumab (Ilumya and others).

Primary Outcomes and Safety

The primary outcome was the difference between the groups in the cumulative incidence of patients who had persistent flares defined as a PASI score > 5 for 3 months or more.

The incidence of persistent flares was 2.1% in the dose reduction group and 1.5% in the usual care group. Regardless of the analysis performed — per protocol last observation carried forward, intention-to-treat last observation carried forward, or intention to treat with imputation of missing values — the difference between the two groups was well below the noninferiority threshold of 15% (0.62%, 1.16%, and 1.91%) that had been set and thus showed that dose reduction was indeed noninferior to usual care.

Dose reduction was successful in 75% of patients at 18 months, meaning they were on a low dose and had low disease activity. Looking at the drug classes separately, van den Reek reported that 86% of those on an IL-23 inhibitor and 61% on an IL-17 inhibitor had a successful dose reduction.

“PASI and DLQI course remains very low in both dose reduction and in the usual care group,” she said, noting “We found no safety signals related to dose reduction.”

Three patients (1.3 cases per 100 observation years) in the dose reduction group and none in the usual care group were diagnosed with new-onset psoriatic arthritis. Worsening of preexisting psoriatic arthritis occurred in 3.4% of the dose reduction group and 5.8% of the usual care group.

Practical Questions

Session Co-chair Johann Bauer, MD, of EB-Haus Austria and the University of Salzburg, Salzburg, Austria, asked, “Does it make sense to measure drug levels in these studies? And how can you be sure that the patients act per protocol?”

Drug levels had been measured, van den Reek confirmed, but those data were still being evaluated. Also, pharmacologic analysis, including the antidrug antibody development, and cost-effectiveness analyses are still to be determined and will follow soon.

van den Reek was also asked about the practicalities of reducing the dose to 67% and whether, considering the high proportion of people that were able to do this, would it not make sense to just skip this step altogether?

She responded it “was a possibility” that the step could be skipped but that it might be “too quick” for some patients to just drop to 50% of the standard dose.

“What we found in the study was that in the patients that were successful after 18 months, one third was still on the first step that could not further lower the dose or had to go back because 50% of the dose was too low,” she said. Two thirds, however, were at 50% of the dose.

As for the practicalities of dropping the doses, van den Reek said a prior implementation study had been done to look at how best to undertake dose reduction of tumor necrosis factor inhibitors. “We made leaflets for the patients with the exact intervals for each biologic,” she said, adding it takes time to talk to the patient and explain everything, but it gives a lot back.

The BeNeBio study was funded by ZonMw (the Netherlands Organisation for Health Research and Development) and the Belgian Health Care Knowledge Centre through its BeNeFIT (Belgium-Netherlands Funding of International Trials) program. van den Reekreported that her institution has received funding for research from AbbVie, Celgene, Almirall, and Janssen. She also acknowledged receiving speaking fees from or attending advisory boards on behalf of AbbVie, Janssen, Zoetis, Bristol Myers Squibb, Almirall, LEO Pharma, Novartis, UCB, and Eli Lilly and Company and received reimbursement for attending or chairing a symposium from Janssen, Pfizer, Celgene, and AbbVie.

Sara Freeman is a freelance medical journalist based in London, England.