Evaluating Risankizumab’s Long-Term Effects in Psoriasis Using Optical Coherence Tomography

Abstract

Introduction

Psoriasis is a chronic inflammatory disease associated with multiple systemic comorbidities and reduced quality of life. Risankizumab, an interleukin (IL)-23 inhibitor, has demonstrated efficacy in achieving rapid and sustained skin clearance in moderate-to-severe psoriasis. However, its impact on chronic subclinical inflammation is less understood. Conventional clinical assessments like Psoriasis Area and Severity Index (PASI), Investigator’s Global Assessment (IGA), and Body Surface Area (BSA) focus on evaluating visible symptoms and are limited in capturing underlying disease activity. Optical coherence tomography (OCT), a non-invasive imaging modality, offers real-time assessment of structural and vascular changes, providing valuable insights beyond the skin surface.

Methods

This sub-analysis of a prospective, single-center exploratory study included 22 patients with moderate-to-severe psoriasis treated with risankizumab. Clinical assessments (PASI, IGA, BSA) were conducted at baseline and weeks 2, 4, 16, 28, 40, and 52. OCT imaging performed at baseline and weeks 4, 16, and 52 evaluated epidermal thickness and vascular parameters (e.g., vessel density and diameter) in lesional and perilesional skin.

Results

By week 16, mean (95% confidence interval [CI]) PASI score decreased from 16.3 (11.6–21.1) at baseline to 3.5 (1.8–5.2), and BSA involvement from 24.7% (16.1–33.3) to 5.2% (1.9–8.4) (both p < 0.001). By week 52, 86.7%, 73.3%, and 40.0% of patients achieved PASI 75, 90, and 100, respectively, and 93.3% achieved IGA 0/1. OCT showed lesional reductions in epidermal thickness (− 37.4%), vessel density (− 26.6% Δ area under the curve [AUC]), and vessel diameter (− 59.5% ΔAUC) over the 52-week period. Notably, vascular changes also occurred in uninvolved perilesional skin.

Conclusion

Risankizumab improved both clinical and OCT parameters over 52 weeks, emphasizing the importance of long-term therapy with benefits extending beyond visible improvement. OCT emerged as a valuable tool for assessing deep (vascular) treatment response, thereby supporting a more comprehensive understanding of therapeutic outcomes in psoriasis.

Supplementary Information

The online version contains supplementary material available at 10.1007/s13555-025-01637-2.

Key Summary Points

Why carry out this study?

Psoriasis is a chronic inflammatory skin condition characterized by keratinocyte hyperproliferation, immune cell infiltration, and vascular remodeling driven by pro-angiogenic factors, contributing to persistent inflammation and disease chronicity.

Conventional clinical tools for assessing disease severity, such as the Psoriasis Area and Severity Index (PASI), Investigator’s Global Assessment (IGA), and Body Surface Area (BSA), primarily evaluate visible symptoms but fail to capture deeper, subclinical inflammation, underscoring the need for more advanced assessment methods.

This sub-analysis aimed to investigate the effects of interleukin (IL)-23 inhibition with risankizumab on both clinical outcomes and subclinical (vascular) changes in moderate-to-severe psoriasis, using optical coherence tomography (OCT) to objectively quantify epidermal thickness and—enabled by the novel application of vascular imaging—a range of vascular parameters over a 52-week treatment period.

What was learned from the study?

Treatment with risankizumab led to substantial improvement in PASI, IGA, and BSA scores, along with progressive changes in skin vascularization and reduction of lesional epidermal thickness over 52 weeks.

The findings highlight that treatment with risankizumab extends beyond surface-level improvements, addressing subclinical parameters and supporting the need for long-term maintenance of treatment response to promote deeper disease remission.

By visualizing subclinical parameters such as vascular remodeling relevant to disease chronicity, OCT may support future efforts to define tissue-level disease dynamics and treatment-related changes in psoriasis.

Introduction

Psoriasis is a chronic inflammatory skin disease with diverse clinical manifestations, the most common being plaque psoriasis, which typically affects the scalp, trunk, knees, and elbows [1, 2]. Beyond skin manifestations, psoriasis is associated with multiple systemic comorbidities, including rheumatological, cardiovascular, metabolic, and hepatic disorders [3, 4]. In addition to the physical burden, psoriasis impacts mental health and significantly diminishes quality of life [5–7].

At the tissue level, psoriatic plaques are characterized by keratinocyte hyperproliferation, immune cell infiltration, and prominent vascular remodeling—features that collectively contribute to epidermal thickening and the formation of erythematous, scaly lesions [8]. While psoriasis is primarily a T cell-driven disease, growing evidence highlights the critical role of papillary dermal vascular abnormalities in both initiation and persistence [8–10]. The psoriatic inflammatory milieu promotes the expression of pro-angiogenic mediators, particularly vascular endothelial growth factor A (VEGF-A), which is largely secreted by activated keratinocytes [9, 10]. VEGF-A drives endothelial cell migration and proliferation, initiating angiogenesis in the superficial papillary dermis and contributing to vascular changes such as increased vascular density, capillary dilation, tortuosity, increased permeability, and elongation [8]. Remarkably, these abnormalities can be long-lasting and may persist beyond clinical resolution, indicating ongoing subclinical inflammation potentially contributing to faster disease recurrence [10]. Consequently, normalization of psoriatic vasculature may represent an important therapeutic target for achieving sustained disease control.

Several cytokines are central to the inflammatory processes underlying psoriasis, including interleukin (IL)-17, IL-22, IL-23, IL-36, interferon-γ (IFNγ), and tumor necrosis factor alpha (TNFα) [1, 10]. Among these, IL-23 has emerged as one of the key drivers of chronic inflammation. It promotes the differentiation, activation, and survival of T helper 17 (Th17) cells and innate immune cells, which are a major source of pro-inflammatory cytokines such as IL-17 and IL-22 [11–13]. In addition, IL-23 was shown to interfere with regulatory and tissue-resident memory T cells and disrupt the balance between pro- and anti-inflammatory T cell responses [14, 15]. Through intracellular signaling via the Tyk2-Jak2-STAT3-pathway, IL-23 induces the expression of pro-inflammatory mediators that stimulate keratinocyte proliferation, endothelial activation, and immune cell recruitment [1]. Given its central role in these pathological processes, IL-23 represents an important therapeutic target in moderate-to-severe psoriasis.

The biologic agent risankizumab is a monoclonal antibody that selectively inhibits IL-23 by binding to its p19 subunit [16]. Clinical trials have demonstrated significant efficacy with risankizumab in patients with moderate-to-severe plaque psoriasis, including rapid and sustained skin clearance, superiority to placebo and other therapies, improved quality of life, and a tolerable safety profile [17–25]. Importantly, its efficacy remains consistent over nearly 6 years of continuous treatment, with high rates of complete clearance at weeks 52 and 304 [21, 22, 26, 27]. This suggests that therapeutic benefits are sustained with risankizumab even in the absence of visible clinical symptoms. However, reliable biomarkers for remission and deeper therapeutic responses, especially those related to vascular remodeling, remain unknown.

Scoring systems currently used to assess psoriasis severity in clinical practice and research include the Psoriasis Area and Severity Index (PASI), the Investigator’s Global Assessment (IGA), and the Body Surface Area (BSA), which rely primarily on visual evaluation by the investigator, making them prone to bias and limiting their objectivity [28, 29]. Additionally, these methods fail to capture deeper inflammatory processes integral to the pathophysiology of psoriasis, such as vascular remodeling [1, 2], underscoring the need for more comprehensive and objective assessment techniques. Optical coherence tomography (OCT) is a non-invasive imaging modality that provides high-resolution, real-time images of tissues using low-coherence interferometry [30]. OCT is widely used in ophthalmology and is increasingly employed in dermato-oncology for diagnosis, disease evaluation, and treatment monitoring of non-melanoma skin cancers to assess vascularization and tissue microstructure [30–35]. More recently, OCT has become a valuable tool for evaluating psoriatic lesions, partly due to the similarities between the angiogenic mechanisms involved in tumor biology and those present in chronic inflammation [30, 31, 36–39]. OCT enables quantification of parameters such as epidermal thickness, vascular plexus depth, and vessel density and diameter, providing objective insights into structural and vascular changes that indicate inflammation [40, 41].

This sub-analysis of a prospective study aims to pivotally evaluate the therapeutic effects of risankizumab in patients with moderate-to-severe psoriasis over a 52-week period, combining conventional clinical scoring (i.e., PASI, IGA, and BSA) with dynamic OCT (including vascular imaging) as an innovative imaging tool. By quantifying changes in epidermal thickness and vascularization, these analyses provide deeper insights into the therapeutic impact of risankizumab on visible and subclinical aspects of psoriatic inflammation. This approach has the potential to advance the understanding of disease dynamics and treatment-related remission.

Methods

Study Design and Participants

This is a sub-analysis of a prospective, single-center, long-term study conducted at the Institute and Comprehensive Center for Inflammation Medicine at the University of Lübeck in Lübeck, Germany. The results presented here derive from data collected over 52 weeks. Eligible patients were adults aged ≥ 18 years with a diagnosis of moderate-to-severe psoriasis initiating treatment with risankizumab. The treatment decision was made before and independently of study participation. Participants were enrolled between June 19, 2020 and July 18, 2022. All participants provided written informed consent prior to enrollment and after the decision to initiate risankizumab treatment had been made. Throughout the study, patients were treated according to routine care.

Ethical Approval

Ethical approval for the study was granted by the local ethics committee of the University of Lübeck for prospective inclusion of the patients (old ethics file number #20-170A, new file number #2023-800) and for the subsequent analysis (#22-133). All individuals provided written informed consent upfront for inclusion in the study. The study was conducted in accordance with the Declaration of Helsinki.

Clinical Assessments

Patient demographics were documented at study entry (baseline, week 0). Clinical evaluations were performed at weeks 0, 2, 4, 16, 28, 40, and 52 and included PASI, IGA, and BSA scoring. Clinical treatment response was evaluated based on absolute PASI and BSA scores, the proportions of patients achieving ≥ 75%, ≥ 90%, and 100% improvement in PASI (PASI 75/90/100), respectively, as well as the proportion of patients reaching an IGA score of 0 or 1 (IGA 0/1). Dermatoscopic imaging was performed for illustrative purposes at weeks 0, 4, 16, and 52 to document visual changes in psoriatic lesions throughout the study. Imaging was carried out at both lesional and perilesional (clinically uninvolved) skin sites.

OCT Measurements

OCT imaging was performed at weeks 0, 4, 16, and 52 to assess structural and vascular changes in psoriatic lesions (Fig. 1). The clinically approved VivoSight Dx OCT scanner, version 4.16 (Michelson Diagnostics Ltd., Maidstone, Kent, UK), was used, following the previously described protocol [40]. Four parameters were analyzed: (1) epidermal thickness, defined as the maximum thickness of the epidermis calculated as a mean from three image stacks; (2) plexus depth, measured as the depth of the top of the superficial plexus, at which vessel density reaches 50% of its maximum; (3) vessel density, and (4) vessel diameter, both measured at 0.05-mm intervals over a depth of 2 mm, with shown images corresponding to the depth of the superficial plexus. OCT imaging was conducted at both lesional and perilesional skin sites.

Fig. 1.

Study design illustrating the inclusion of patients with moderate-to-severe psoriasis treated with risankizumab, along with scheduled time points for clinical assessments and OCT imaging. OCT measurements included epidermal thickness, plexus depth, vessel density, and vessel diameter in psoriatic lesions and perilesional sites. OCT optical coherence tomography

Objectives

The primary objective of this analysis was to assess changes in epidermal thickness at lesional and perilesional sites over 52 weeks of risankizumab treatment. Additional objectives were to evaluate changes in plexus depth, vessel density, and vessel diameter at lesional and perilesional sites at week 16 and week 52. Clinical outcomes, including changes in PASI and BSA scores at week 16, along with the proportion of patients achieving PASI 75, PASI 90, PASI 100, and IGA 0/1 by week 52, were also examined.

Statistical Analysis

Statistical analyses were performed using GraphPad Prism version 10.4.1 (GraphPad Software, San Diego, CA, USA). Data were calculated as means with standard deviation (SD) or 95% confidence interval (CI). This was an exploratory analysis that was not powered for formal hypothesis testing. Clinical outcomes were reported as observed. The Wilcoxon test was used to compare absolute PASI and BSA scores at week 16 to baseline. Differences in epidermal thickness between baseline and week 52 were analyzed with the Mann–Whitney U test. OCT quantifications of vascular parameters were conducted using the VivoSight analysis software VivoTools v1.3.1 (Michelson Diagnostics Ltd., Maidstone, Kent, UK). For vessel density and diameter, the area under the curve (AUC) was calculated to evaluate differences between time points.

Results

Patient Cohort

The study included 22 patients with moderate-to-severe psoriasis (Fig. 1). Patient demographics and baseline characteristics were generally consistent with the overall moderate-to-severe psoriasis population, although female patients (13.6%) were slightly underrepresented (Table 1). The mean (SD) age was 46.6 (14.8) years. The mean (SD) BMI was 31.1 (5.4) kg/m², and 40.9% of patients were current smokers and 31.8% former smokers. Comorbid psoriatic arthritis was present in 27.3% of the cohort, and 68.2% of patients had nail psoriasis. Of the 22 patients, 11 (50.0%) were biologic-naïve, while 5 (22.7%) had received one prior biologic, 5 (22.7%) had received two, and one (4.5%) had been pre-treated with more than two. Among those with previous biologic exposure, IL-17 inhibitors were the most common (8/22 patients; 36.4%), followed by TNFα inhibitors (7/22; 31.8%), IL-12/IL-23 inhibitors (2/22; 9.1%), and a single case (1/22; 4.5%) of IL-23 inhibition (tildrakizumab). Mean (SD) PASI score was 16.3 (10.6), mean (SD) BSA involvement was 24.7% (19.4%), and mean (SD) IGA score was 3.2 (0.6) at baseline.

Table 1.

Patient demographics and baseline characteristics

Characteristics	N = 22
Age, years, mean (SD)	46.6 (14.8)
Sex, n (%)
Male	19 (86.4)
Female	3 (13.6)
BMI, kg/m2, mean (SD)	31.1 (5.4)
Smoking status, n (%)
Current smoker	9 (40.9)
Former smoker	7 (31.8)
Never smoked	6 (27.3)
Psoriatic arthritis, n (%)	6 (27.3)
Nail psoriasis, n (%)	15 (68.2)
Prior biologic therapy
Number of pre-treatments, n (%)
0	11 (50.0)
1	5 (22.7)
2	5 (22.7)
> 2	1 (4.5)
Biologic class, n (%)
IL-17 inhibitor	8 (36.4)
IL-23 inhibitor	1 (4.5)
IL-12/IL-23 inhibitor	2 (9.1)
TNFα inhibitor	7 (31.8)
Clinical scores at baseline
PASI, mean (SD)	16.3 (10.6)
BSA involvement, %, mean (SD)	24.7 (19.4)
IGA, mean (SD)	3.2 (0.6)

BMI body mass index, BSA Body Surface Area, IGA Investigator’s Global Assessment, IL Interleukin, PASI Psoriasis Area and Surface Index, SD standard deviation, TNFα tumor necrosis factor alpha

Clinical Outcomes

Treatment with risankizumab significantly decreased the mean (95% CI) absolute PASI score from 16.3 (11.6–21.1) to 3.5 (1.8–5.2; p < 0.001) by week 16 (Fig. 2a). Similarly, 59.1% (13/22) of patients achieved PASI 75 and 27.3% (6/22) reached PASI 90 (Fig. 2b). By week 52, the proportion of patients achieving PASI 75, PASI 90, and PASI 100 increased to 86.7% (13/15), 73.3% (11/15), and 40.0% (6/15), respectively (as observed analysis; Fig. 2b). Similarly, 68.4% (13/19) of patients reached IGA 0/1 by week 16 and 93.3% (14/15) by week 52 (Fig. 2c). Moreover, mean (95% CI) BSA involvement significantly lowered from 24.7% (16.1–33.3) to 5.2% (1.9–8.4; p < 0.001) by week 16 (Fig. 2d). Visual improvements in skin appearance were evident over the 52-week treatment period (Fig. 2e), demonstrating notable resolution of psoriatic lesions along with clinical response.

Fig. 2.

Clinical efficacy of risankizumab treatment over a 52-week period: a absolute PASI response presented as individual values with the mean, b relative PASI 75, PASI 90, and PASI 100 response, c relative IGA 0/1 response, d absolute BSA response presented as individual values with the mean, e representative dermatoscope images of the clinical presentation. BSA Body Surface Area, IGA Investigator’s Global Assessment, PASI Psoriasis Area and Severity Index

OCT Outcomes

Consistent with clinical outcomes, risankizumab treatment was also associated with structural and vascular changes, as assessed by OCT vascular imaging. At lesional sites, epidermal thickness decreased from a mean (SD) of 572.4 (116.2) µm at baseline to 358.6 (247.3) µm at week 52, reflecting a reduction of 213.8 µm (− 37.4%; p < 0.0001) over 52 weeks (Fig. 3a, b). In contrast, perilesional sites showed an increase of 78.7 µm (+ 73.9%; p = 0.01) in epidermal thickness, rising from a mean (SD) of 106.5 (95.7) µm at baseline to 185.2 (197.7) µm at week 52 (Fig. 3c, d). Between week 16 and week 52, plexus depth at lesional sites decreased by 75.5 µm (− 22.7%) (Supplementary Material). A similar, though less pronounced, reduction was observed in perilesional areas, with a decrease of 50.1 µm (−14.5%) between week 16 and week 52 (Supplementary Material), suggesting a reorganization of the vascular architecture in psoriatic lesions and the surrounding skin. It is important to note that the measurement of plexus depth is inherently dependent on epidermal thickness. At early time points (weeks 0 and 4), plexus depth was likely underestimated due to the markedly thickened epidermis in lesional skin of patients with psoriasis at the beginning of the study (572.4 µm in lesional vs. 213.8 µm in perilesional skin), which impairs OCT to accurately capture the underlying vasculature. Thus, it is likely that the plexus depth at lesional sites also decreased continuously over the study period, as observed for epidermal thickness. Notably, OCT findings indicated that risankizumab treatment impacted both lesional and perilesional skin, with vessel density and diameter in lesional areas approaching those of perilesional skin over the 52-week period (Fig. 4a). Vessel density at lesional sites decreased by 26.6% (ΔAUC from maximum) from week 0 to week 52 (Fig. 4b), similar to the 36.0% (ΔAUC) reduction observed in perilesional sites (Fig. 4c). When comparing the ΔAUC for vessel density between week 16 and week 52, lesional sites showed a 15.9% reduction, while perilesional sites exhibited a decrease of 32.4% (Fig. 4d). Vessel diameter declined by 59.5% (ΔAUC) from week 0 to week 52 at lesional sites (Fig. 4e), while perilesional sites exhibited a reduction of 39.8% (ΔAUC) (Fig. 4f). Analysis of the ΔAUC for vessel diameter from week 16 to week 52 revealed a 49.4% decline at lesional and 37.7% decline at perilesional sites (Fig. 4g). Together, these results suggest that risankizumab is associated with measurable changes in vascular characteristics in psoriatic skin and that OCT is a useful tool for the objective quantification of these effects.

Fig. 3.

Changes in epidermal thickness during 52 weeks of risankizumab treatment: a representative OCT images of lesional skin showing epidermal thickness in a biologic-naïve and a biologic-experienced patient, b absolute epidermal thickness in lesional skin presented as means ± SD, c representative OCT images of perilesional skin showing epidermal thickness in a biologic-naïve and a biologic-experienced patient, d absolute epidermal thickness in perilesional skin presented as means ± SD. OCT optical coherence tomography, SD standard deviation

Fig. 4.

Changes in vessel density and diameter during 52 weeks of risankizumab treatment: a representative OCT images of lesional and perilesional skin showing vascularization without (upper row) and with (lower two rows) visualization of the overlying skin in a biologic-naïve patient, b vessel density in lesional skin, c vessel density in perilesional skin, d comparison of vessel density in lesional vs. perilesional skin at week 16 and week 52, e vessel diameter in lesional skin, f vessel diameter in perilesional skin, g comparison of vessel diameter in lesional vs. perilesional skin at week 16 and week 52. All values are presented as means ± 95% CI. AUC area under the curve, CI confidence interval, OCT optical coherence tomography

Discussion

Plaque psoriasis is a multifactorial inflammatory skin disease characterized by visible, sharply demarcated, erythematous, and scaly lesions [1]. While these visible skin manifestations are key clinical markers, accumulating evidence highlights the importance of persistent subclinical inflammation and vascular remodeling in driving disease chronicity and relapse [8–10]. Achieving deep remission, encompassed by clinical and subclinical resolution, has therefore become a meaningful therapeutic goal. Our study showed that IL-23 inhibition with risankizumab improved both visible and non-visible parameters in patients with moderate-to-severe psoriasis, and that OCT provided precise evaluation of tissue changes extending beyond the skin surface.

IL-23 is a central cytokine in the pathogenesis of psoriasis, driving downstream inflammatory effects [11–13]. As a selective IL-23 inhibitor, risankizumab has previously demonstrated high efficacy and durability in clinical trials, with responses maintained over multiple years [16, 26]. This makes risankizumab a well-suited candidate for investigating deep tissue-level responses. In this sub-analysis, clinical outcomes, as measured by PASI, IGA, and BSA, improved rapidly within the first 16 weeks and remained stable throughout the treatment period, consistent with previous studies [23–25, 27]. Notably, OCT outcomes revealed ongoing reductions in lesional epidermal thickness and progressive changes in vascular parameters over the 52-week period of risankizumab treatment. These findings suggest that IL-23 inhibition with risankizumab promotes continuous tissue remodeling beyond resolution of visible surface-level symptoms, underlining the potential to induce deeper remission, which may be relevant for long-term disease control.

Conventional clinical assessments, such as PASI, show interobserver variability and limited sensitivity to subtle changes in disease activity [28, 29, 42], as they primarily evaluate surface-level skin characteristics rather than underlying pathological processes [43]. These limitations become particularly relevant with highly effective treatments like risankizumab, which can achieve near-complete (PASI 90) or complete (PASI 100) skin clearance by week 52 [21, 22, 26, 27]. As a result, there is an increasing need for more sensitive and objective methods capable of capturing continuous changes beneath clinically resolved skin. With the ability to image up to 2 mm below the skin surface while preserving the necessary resolution to evaluate fine structural and vascular changes, OCT provides valuable insights into the underlying pathophysiological tissue remodeling of psoriasis without the need for invasive procedures like skin biopsies [43–45]. The integration of artificial intelligence (AI)-based image analysis further enhances precision and reproducibility of OCT by enabling objective quantification of key vascular parameters such as vessel diameter, vessel density, and plexus depth. In our analysis, OCT results revealed continued improvements in lesional epidermal thickness and changes in vascular parameters in patients with psoriasis treated with risankizumab, even when clinical scores like PASI and BSA had plateaued. These findings highlight the potential of OCT to provide deeper insight into tissue-level remission and therapeutic response in psoriasis. Notably, subclinical improvements have also been reported in patients with psoriasis receiving biologic therapies with distinct mechanisms of action, such as IL-17 inhibitors [46]. High-resolution imaging techniques, including OCT and line-field confocal OCT (LC-OCT), have been employed in this context to visualize changes in epidermal morphology, dermal vascular remodeling, and the distribution of inflammatory cells during IL-17 inhibition [47, 48]. These studies suggest that OCT can characterize tissue-level treatment responses across different biologic classes, supporting its broader applicability in therapeutic monitoring.

The gradual reduction in epidermal thickness in lesional skin during risankizumab treatment likely has immunological, vascular, and functional relevance. As the predominant cell type in the epidermis, keratinocytes play a central role in psoriasis by producing pro-angiogenic mediators such as VEGF-A, which contribute to vascular remodeling and growth and local inflammation [8–10]. A thinner epidermis may therefore reduce the overall production of these factors, supporting the resolution of the inflammatory microenvironment. Additionally, a thickened epidermis has been linked to increased numbers of tissue-resident memory T (TRM) cells, which are key contributors to inflammation and disease recurrence [49, 50]. Indeed, psoriatic skin is particularly enriched in TRM cells [51]. Consequently, a thinner epidermal layer may provide less architectural space and fewer survival signals for these TRM cells, potentially reducing their persistence and pathogenic activity. Therefore, reduction of epidermal thickness may not only reflect therapeutic response but also contribute to the establishment of a more durable remission.

Psoriatic lesions exhibit notable alterations in the dermal microvasculature, including increased vascular density, capillary dilation, and displacement of the superficial vascular plexus closer to the epidermis [8, 37, 39–41, 52, 53]. These vascular changes, particularly the vessel dilation, contribute to increased local blood flow, which may underlie the elevated skin temperature and persistent erythema observed in psoriatic lesions [54]. Notably, similar vascular alterations, such as enhanced cutaneous blood flow, have also been described in perilesional, clinically uninvolved skin areas [8, 55], highlighting the systemic nature of psoriasis. Beyond their morphological impact, vascular changes driven by VEGF-A and other pro-angiogenic factors amplify chronic inflammation by stimulating keratinocyte proliferation, facilitating immune cell recruitment, and preceding the characteristic epidermal hyperplasia in psoriatic lesions [8–10, 55–57]. This underscores the importance of vascular remodeling as a clinical marker for disease activity in psoriasis. Importantly, the relevance of vascular pathology in psoriasis may extend beyond the skin. Psoriasis is associated with an increased risk for cardiovascular comorbidities like coronary artery disease, with shared inflammatory pathways including TNFα and IFNγ that contribute to immune cell infiltration and inflammation in both cutaneous and vascular tissues [4, 10]. Previous studies have shown that improving endothelial cell function in blood vessels of peripheral organs like the lung or adipose tissue can reduce overall inflammation and cardiovascular risk [58–60]. Whether similar effects can be achieved through remodeling of the skin vasculature remains to be determined. However, in our study, IL-23 inhibition with risankizumab was associated with vascular changes not only in lesional but also in perilesional skin, reinforcing previous observations that its therapeutic effects may extend beyond visible plaques.

This study has several notable strengths, including the use of a novel, non-invasive imaging modality, OCT, to evaluate tissue-level remission in patients with moderate-to-severe psoriasis treated with risankizumab. One of the key challenges of non-invasive imaging techniques is balancing resolution with imaging depth, and OCT may provide the right balance between those parameters, offering deeper tissue penetration than confocal microscopy while maintaining higher resolution than ultrasound or magnetic resonance imaging (MRI) [44]. OCT is a rapid, user-friendly technique for assessing structural and vascular changes in psoriatic lesions that extend beyond what clinical scores capture. By combining OCT measurements with PASI, IGA, and BSA scoring, this analysis aimed to ensure a comprehensive evaluation of treatment response, addressing both visible symptoms and subclinical changes. Furthermore, the study duration allowed for the evaluation of both early (week 16) and sustained (week 52) therapeutic effects, offering valuable insights into the long-term benefits of risankizumab therapy.

However, the study also has limitations. A limitation to consider is the technical constraints of OCT, including difficulties in accurately capturing vascular parameters at early time points (weeks 0–4) due to epidermal thickening and hyperkeratotic scales in severely inflamed psoriatic lesions. Psoriatic plaques may have an epidermal thickness several times greater than that of uninvolved or treated skin [61], which can affect the accurate visualization of underlying blood vessels, potentially leading to an underestimation of certain vascular parameters like plexus depth. In addition, OCT captures only a relatively small area of the skin at a time, which could limit the representativeness of the measurements, as disease activity may vary across different body regions. Imaging larger skin areas would provide a more comprehensive assessment of psoriasis disease activity. Furthermore, the lack of standardized imaging protocols and variability between different devices may affect consistency and reproducibility across studies. Another limitation is the study design and the relatively small sample size of 22 patients, reducing the generalizability of the findings to broader populations with psoriasis. The absence of a control group limits the ability to attribute the observed effects on epidermal thickness and vascular parameters specifically to risankizumab, and confounding factors may have contributed to the results. Future controlled studies could aim to validate these findings and verify treatment-specific effects.

Conclusion

The findings of this sub-analysis suggest that IL-23 inhibition with risankizumab not only resolves visible symptoms of psoriasis but also targets deeper, subclinical processes, as revealed by OCT. This supports the value of complementing conventional clinical assessments with imaging tools capable of capturing structural and vascular changes beneath the surface. Looking ahead, AI-driven analysis, greater imaging depth, and combination of OCT with complementary modalities such as confocal microscopy may further refine our understanding of deep disease activity and treatment-related responses. Standardizing OCT protocols and validating findings in larger, more diverse patient cohorts with suitable control groups will be essential steps toward broader clinical applicability of OCT in monitoring therapeutic response and improving patient care.

Supplementary Information

Below is the link to the electronic supplementary material.

Author Contributions

All authors made a significant contribution to the work reported. Linh Ha-Wissel and Diamant Thaçi contributed to the study’s conception and design, as well as to the development of the methodology. Linh Ha-Wissel, Evelyn Gaffal, and Diamant Thaçi contributed to data acquisition (acquired and managed patients, provided facilities, etc.). Henner Zirpel, Linh Ha-Wissel, Sarah Hobelsberger, Lena Pommerien, Stefan Beissert, Ruth Bauer, and Kristina Lohmann analyzed and interpreted the data (e.g., performed statistical analyses). Jenia Neumeister and all other authors critically reviewed and commented on the drafts of the manuscript, approved the final version of it, and agreed to submit the manuscript to this journal.

Funding

This work has been financially supported by the Cluster of Excellence “Precision Medicine in Chronic Inflammation” (EXC2167/1) from the Deutsche Forschungsgemeinschaft (DFG). AbbVie supported this analysis and participated in the interpretation of data, review, and approval of the publication and funded the journal fees, including the journal’s Rapid Service fee. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship.

Data Availability

The data that support the findings of this study are available from the corresponding author upon request.

Declarations

Conflict of Interest

Henner Zirpel is a salaried employee of Almirall Hermal GmbH, Reinbeck, Germany, and has received support for meeting attendance and/or travel from Pfizer, UCB Pharma, Almirall, Janssen, and TriNetX. Linh Ha-Wissel has received support for meeting attendance and travel from AbbVie. Sarah Hobelsberger reported clinical trial support from Almirall and Pierre Fabre, advisor’s honoraria from Almirall, AbbVie, and Bristol Myers Squibb, speaker’s honoraria from Almirall, UCB, Bristol Myers Squibb, and AbbVie, and travel support from UCB, Janssen Cilag, Almirall, Novartis, Lilly, LEO Pharma, and AbbVie. Stefan Beissert has served as consultant/advisor for AbbVie Deutschland GmbH & Co, Actelion Pharmaceuticals GmbH, Almirall-Hermal GmbH, Amgen GmbH, Celgene GmbH, Galderma Laboratorium GmbH, Janssen Cilag GmbH, Leo Pharma GmbH, Lilly Deutschland GmbH, Menlo Therapeutics, MSD Sharp & Dohme GmbH, Novartis Pharma GmbH, Pfizer Pharma GmbH, Sanofi-Aventis Deutschland GmbH, UCB Pharma GmbH. He has received speaker’s honoraria from Novartis Pharma GmbH, AbbVie Deutschland GmbH & Co, MSD, Pfizer, Janssen-Cilag, Roche-Posay, Actelion, GSK, Bristol Myers Squibb, Celgene GmbH, Almirall-Hermal GmbH, Hexal-Sandoz, Sanofi-Aventis Deutschland GmbH. Evelyn Gaffal has served as an investigator and/or consultant/advisor for AbbVie, Almirall, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen Cilag, LEO Pharma, Novartis, Sanofi, and UCB. She has received grants from Almirall and Sanofi. Ruth Bauer, Jenia Neumeister, and Kristina Lohmann are salaried employees of AbbVie Deutschland GmbH & Co. KG and may own stock/options. Diamant Thaçi has served as an investigator and/or consultant/advisor for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Galderma, Incyte, Janssen-Cilag, Kyowa Kirin, LEO Pharma, La Roche Possay, New Bridge, Novartis, Regeneron, Sandoz, Sanofi, Samsung, Pfizer, Target-RWE Solution, UCB, and Vichy. He has received grants from AbbVie, LEO Pharma, and Novartis. Lena Pommerien has nothing to declare.

Ethical Approval

Ethical approval for the study was granted through the local ethics committee of the University of Lübeck for prospective inclusion of the patients (old ethics file number #20-170A, new file number #2023-800) and for the subsequent analysis (#22-133). All individuals provided written informed consent upfront for inclusion in the study. The study was conducted in accordance with the Declaration of Helsinki.