Long-Term Durability of Bimekizumab Over 4 Years Highlighted in Psoriasis

New long-term data on long-term bimekizumab use in psoriasis suggest sustained efficacy through 4 years of therapy, with investigators additionally observing molecular findings explaining the medication’s prolonged disease control.1

James G. Krueger, MD, PhD, of the Centre for Clinical and Translational Science at The Rockefeller University, led a team of investigators in authoring these data. The investigative team noted prior clinical results had already demonstrated durable responses through 3 years of use, including successful maintenance with every-8-week dosing following the initial period of bimekizumab use.

Krueger et al noted the relatively slow return of psoriasis activity following treatment withdrawal had previously led to comparisons to response patterns observed with interleukin (IL)-23 inhibitors. This prompted inquiries regarding whether dual inhibition of IL-17A and IL-17F may also influence pathogenic tissue-resident memory T (TRM) cells believed to impact disease persistence and relapse.

In Krueger and coauthors’ analyses, these earlier data were extended by assessing long-term clinical outcomes, withdrawal and re-treatment responses. Additionally, transcriptomic data were evaluated to further characterize the biologic mechanisms linked with sustained remission.

“Here, we extend clinical observations to report [bimekizumab] response durability over 4 years, alongside response to treatment withdrawal and retreatment,” Krueger and coauthors wrote.1

Study Design Details

The investigative team pooled results from individuals who had been randomized to bimekizumab in the phase 3 feeder studies BE VIVID, BE READY, and BE SURE, as well as the open-label extension study BE BRIGHT. In their primary analyses, Krueger and colleagues focused on participants who attained complete clearance of their skin, defined as 100% Psoriasis Area and Severity Index improvement (PASI 100), by the 16-week mark.

Maintenance of response through 4 years via multiple efficacy thresholds was evaluated by the team, with thresholds including PASI 100, PASI 90, PASI 75, and lower absolute PASI scores. Treatment outcomes were assessed by Krueger et al among those treated with 320-mg bimekizumab every 4 weeks or every 8 weeks. These subjects included those transitioned to the approved maintenance approach of every-8-week dosing following Week 16.

Modified non-responder imputation methods were implemented to address missing data, classifying individuals who discontinued because of treatment-related adverse events (TEAEs) or lack of efficacy as non-responders for later assessments. Additionally, the investigators looked into “continuous response maintenance,” defined as maintaining higher disease control levels across visits while allowing for limited fluctuations in response.

Under these criteria, remission at the time of treatment referred to maintaining PASI 100 with occasional dips no lower than PASI 90, whereas “high disease control” described sustained PASI 90 with limited drops to PASI 75. Among individuals who attained complete clearance of skin at the 16-week mark, remained on blinded bimekizumab treatment, and subsequently entered the BE BRIGHT extension study, the investigators noted 73.0% maintained PASI 100 at the end of the fourth year via modified non-responder imputation analysis.

Additional data drawn from BE READY assessed durability following withdrawal of medication use. In that analysis, the investigators noted Week-16 PASI 90 responders had been re-randomized either to continued bimekizumab or placebo. The team implemented Kaplan-Meier analyses for the purposes of estimating time to loss of PASI responses after cessation, including loss of PASI 100, PASI 90, and PASI 75.

Outside of clinical outcomes, Krueger and coauthors performed single-cell RNA sequencing analyses via 3 independent lesional psoriasis biopsy datasets, in addition to bulk RNA sequencing in a phase 2a study. These analyses identified a subgroup of TRM cells in psoriatic lesions expressing IL-17A and/or IL-17F that were shown to be largely absent in those witth healthy skin. The investigators suggested these cells could represent a pathogenic TRM population involved in chronic inflammation and relapse.

The transcriptomic analyses also identified pro-survival signaling pathways within lesional TRM cells. Notably, IL-7R expression was found to be higher among IL-17F–positive TRM cells than among IL-17A–positive cells. The team further noted the reversal of these prosurvival molecular signatures, in addition to broader TRM-linked gene expression patterns, following bimekizumab over 8 weeks corresponding to 2 doses.

“Normalization of pathogenic TRM cells with BKZ may be linked to the long-term durability of the high level of response observed over 4 years,” the investigators concluded.1

Taken together, the findings suggest dual IL-17A and IL-17F inhibition may contribute not only to robust skin clearance, but also to longer-term disease control through potential effects on pathogenic immune memory pathways in psoriasis.

References

1. Krueger JG, Cutcutache I, Warren RB, et al. Bimekizumab long-term response in psoriasis: Mechanistic insights into efficacy level and durability. J Allergy Clin Immunol. 2026 Apr;157(4):905-916. doi: 10.1016/j.jaci.2025.12.1013. Epub 2026 Jan 22. PMID: 41580158.

2. Adams R, Maroof A, Griffiths M, et al. Bimekizumab, a Novel Humanized IgG1 Antibody That Neutralizes Both IL-17A and IL-17F. Front Immunol. 2020 Aug 21;11:1894. doi: 10.3389/fimmu.2020.01894. PMID: 32973785; PMCID: PMC7473305.