Dose Escalation of IL-17A Inhibitors for Psoriasis Effective, Though Risks Remain

Off-label dose escalation of 2 interleukin (IL)-17A inhibitors, secukinumab and ixekizumab, may improve outcomes in certain cases among patients with psoriasis, but new findings suggest the benefits should be weighed against costs and risks.1

These findings and others regarding off-label adjustments to using ixekizumab and secukinumab among individuals living with psoriasis resulted from a recent letter to the editor authored in part by Jashin J. Wu, MD, from the Department of Dermatology at the University of Miami Miller School of Medicine.

Wu and coauthors highlighted that despite the well-known efficacy of IL-17A inhibitors in treating moderate-to-severe plaque psoriasis, many individuals need off-label dosing adjustments. Such shifts can include reduction, escalation, or interruption of medications.

“To evaluate the efficacy and safety of such regimens, a search of PubMed, Cochrane Library, Ovid MEDLINE and Embase was conducted for randomized controlled trials published between January 1, 2014 and December 6, 2024, assessing off-label dosing regimens in adults with moderate-to-severe psoriasis,” the investigative team wrote.1

Review Details and Conclusions

The investigators noted that the escalation of biologic use is sometimes considered by clinicians to improve one's response in psoriasis, but evidence suggests this strategy should be implemented selectively. For secukinumab, dose intensification from every 4 weeks (Q4W) to every 2 weeks (Q2W) is not routinely advised unless those on the medication weigh ≥90 kg.2

Among those showing only partial improvement in their disease (PASI ≥75 but <90), a shift to Q2W led to a modest 7%–10% PASI-90 rate increase compared with Q4W, though this difference did not reach statistical significance. In additional data highlighted by the team, patients ≥90 kg saw more substantial benefits as a result of this strategy.

Escalation of one's ixekizumab dose during maintenance was shown in additional findings highlighted by Wu et al to yield greater advantages, with PASI-90 being observed in 79.5% of those on Q2W dosing versus 65.2% on Q4W (P< .001). Other data explored by the investigators suggested that dose de-escalation strategies, aimed at drug cost reduction or side effect limits, carry the risk of diminished effectiveness among patients.

Specifically, the research team pointed to findings showing that among secukinumab-treated individuals who had already reached PASI ≥90, maintenance at Q4W preserved higher PASI-90 rates (85.7%) as opposed to Q6W (74.9%) by the 52-week mark (OR 1.91, 95% CI 1.44–2.55). Similarly, the team pointed to findings showing that extending dosing to Q12W led to a 35% reduction in sPGA 0/1 rates at the 60-week mark relative to Q4W.

In pooled analyses from the UNCOVER trials, data also suggested that during induction, sPGA 0/1 responses were more robust with Q2W dosing compared to Q4W at the 12-week mark (81.8% versus 75%, P< .001). Although some maintained adequate disease control with the diminished dosing, overall patterns suggested that less frequent administration of this drug would compromise outcomes. As such, Wu and coauthors highlighted the importance of individualizing such decisions.

The investigators pointed to additional data indicating that continuous therapy generally provides the most stable disease control, adding that despite this conclusion, treatment interruption does not always lead to irreversible loss of efficacy. IL-17A inhibitors are known to have a moderate relapse timeline, allowing certain patients to remain clear for months without treatment. Although not all individuals with psoriasis regain their initial level of improvement, many do, supporting the feasibility of temporary treatment pauses when clinically necessary. Additional data was noted as necessary to clarify whether reintroducing loading doses at the time of re-treatment improves outcomes, as study designs have differed.

Lastly, Wu and colleagues highlighted the central concern of safety with both escalation and de-escalation. Notably, the investigative team pointed to the consistent dose-dependent increase in serious adverse events that was observed with secukinumab and ixekizumab. However, they added that prior data suggest common mild infections with higher dosing. Anti-drug antibodies (ADA) are another concern. The team noted that this may be impacted by treatment interruption. In secukinumab retreatment-as-needed studies, ADA formation took place in 2 subjects on continuous therapy and a single patient on intermittent therapy, with neutralizing antibodies (nAbs) observed in 1 patient from each cohort. In the ixekizumab UNCOVER-1 and -2 extension trials, investigators had observed ADA in 19% of individuals on continuous treatment and 22.5% of those retreated after interruption, with nAbs present in 2 subjects from the re-treatment cohort.

“This study is limited by cross-trial comparisons, restricted generalizability due to selective trial populations and analysis of dose adjustments in patients meeting prespecified responses,” the team concluded.1 “Brodalumab and bimekizumab were excluded to maintain focus, as including all IL-17 inhibitors would significantly broaden the review and reduce the depth of analysis.”

References

1. Kim D, Babaei N, Cervantes M, Wu JJ. Off-label biologic regimens of IL-17A inhibitors for psoriasis. J Eur Acad Dermatol Venereol. https://doi.org/10.1111/jdv.70039. Accessed September 15, 2025.

2. Reich K, Puig L, Orsenigo R, et al. Secukinumab dosing optimization in patients with moderate-to-severe plaque psoriasis: results from the randomized, open-label OPTIMISE study. Br J Dermatol. 2020 Feb;182(2):304-315. doi: 10.1111/bjd.18143. Epub 2019 Sep 8. PMID: 31102257. Accessed September 15, 2025.