ORIGINAL RESEARCH ![](https://assets.reachrx.ai/images/10.1007%E2%98%8Ds13555-025-01544-6/_page_0_Picture_2.jpeg) # **Effcacy and Safety of Risankizumab in Genital or Scalp Psoriasis in the UnlIMMited Phase 4 Randomized Clinical Trial at Week 16** Eingun James Song · Benjamin Ehst · Brad Glick · George Michael Lewitt · Phoebe Rich · Navid Ezra · Jerry Bagel · Toni Anschutz · Brenton Bialik · Chenyang Duan · Doug Ashley · Manish Patel · Greg St. John · Arathi R. Setty · Lindsay Ackerman Received: July 25, 2025 / Accepted: September 5, 2025 © AbbVie Inc., and The Authors 2025 ## ABSTRACT *Introduction***:** Psoriasis (PsO) in the genital and scalp areas is associated with increased patient burden and impact on quality of life. Effective treatments for PsO in these highimpact areas are essential, though patients are frequently excluded from both biologic clinical **Prior Presentation:** Parts of this work were presented at the Society for Investigative Dermatology, May 7–10, 2025; San Diego, CA, USA: Song EJ et al. 2025. Safety and effcacy of risankizumab in genital and scalp psoriasis in the UnlIMMited phase 4 randomized clinical trial at week 16. **Supplementary Information** The online version contains supplementary material available at [https://doi.org/10.1007/s13555-025-01544-6.](https://doi.org/10.1007/s13555-025-01544-6) E. J. Song (\*) Frontier Dermatology, Mill Creek, WA, USA e-mail: esong812@gmail.com B. Ehst Oregon Medical Research Center, Portland, OR, USA B. Glick GSI Clinical Research, LLC, Miami, FL, USA G. M. Lewitt Illinois Dermatology Institute, DeNova Research, Chicago, IL, USA P. Rich Oregon Dermatology and Research Center, Portland, OR, USA trials and treatment because of their often low overall affected body surface area (BSA) despite the disproportionate impact of PsO on their quality of life. Recent guidance also considers these patients as candidates for advanced therapies. Here, we compare the effcacy and safety of risankizumab, an interleukin-23 inhibitor approved for the treatment of moderate-tosevere plaque psoriasis, versus placebo in the treatment of PsO in the genital or scalp region. *Methods***:** UnlIMMited (NCT05969223) is an ongoing phase 4, multicenter, randomized, double-blind, placebo-controlled study for adult patients with moderate-to-severe genital or scalp PsO in patients with < 10% BSA or ≥ 10% BSA involvement. Two parallel studies were conducted with study-G assessing genital PsO and study-S assessing scalp PsO. Patients N. Ezra California Dermatology Institute and Clinical Trials Research Institute, Thousand Oaks, CA, USA J. Bagel Psoriasis Treatment Center of New Jersey, East Windsor, NJ, USA T. Anschutz · B. Bialik · C. Duan · D. Ashley · M. Patel · G. St. John · A. R. Setty AbbVie Inc., North Chicago, IL, USA L. Ackerman Medical Dermatology Specialists, US Dermatology Partners, Phoenix, AZ, USA were randomized 1:1 within each study to receive either 150 mg risankizumab or placebo at weeks 0 and 4. The primary endpoints for the studies were the achievement of static Physician's Global Assessment – Genital (sPGA-G) 0/1 for study-G and scalp Investigator Global Assessment (IGA) 0/1 for study-S, both assessed at week 16. Secondary endpoints are also reported at week 16 in each study assessing skin clearance, symptom resolution, and impact on quality of life. Safety was reported through the frst 16 weeks. *Results***:** At week 16, in both studies, a signifcantly higher proportion of patients receiving risankizumab achieved the primary endpoints compared with placebo. In study-G, 69.1% of patients receiving risankizumab versus 13.0% of patients receiving placebo achieved sPGA-G 0/1 (*P* < 0.0001). In study-S, 60.8% of patients receiving risankizumab versus 13.0% of patients receiving placebo achieved scalp IGA 0/1 (*P*<0.0001). No new safety signals were identifed. *Conclusion***:** These results demonstrate that risankizumab is effective in the treatment of genital and scalp psoriasis at week 16, with no new safety signals identifed. *Trial Registration Number***:** ClinicalTrials.gov identifer NCT05969223. **Keywords:** Risankizumab; Genital psoriasis; Scalp psoriasis; IL-23 inhibitor; Effcacy; Safety ### **Key Summary Points** #### *Why carry out this study?* Psoriasis in the genital region or the scalp is associated with high patient burden and reduced quality of life but often remains untreated with systemic agents. Here we assess the effcacy and safety of risankizumab, an interleukin-23 inhibitor, for the treatment of genital or scalp psoriasis. #### *What was learned fom this study?* At week 16, a signifcantly higher proportion of patients with genital psoriasis receiving risankizumab achieved the primary endpoint of static Physician's Global Assessment – Genital 0/1 compared to those receiving placebo. Similarly, a signifcantly higher proportion of patients receiving risankizumab achieved scalp Investigator Global Assessment 0/1, the primary endpoint, compared to those receiving placebo at week 16. Risankizumab is an effective treatment for genital and scalp psoriasis with patients reporting symptom resolution and improved quality of life, and no new safety signals were identifed. ## INTRODUCTION Psoriasis (PsO) is a chronic infammatory skin disease that typically presents with erythematous scaly plaques that can often be itchy and painful. PsO can affect virtually any area of the body, including high-impact areas such as the genitals and scalp. While estimates differ, approximately 14–63% of patients with PsO have genital involvement and 43–65% have scalp involvement with frequency increasing with the duration of PsO [\[1–](#page-13-0)[10\]](#page-13-1). However, rates may be underreported as a result of patient embarrassment or lack of awareness [\[6,](#page-13-2) [11](#page-13-3)]. While patients with genital or scalp involvement may have a low affected body surface area (BSA), the impact on quality of life can still be high because of the sensitivity and visibility of the affected areas [[12](#page-13-4)[–15\]](#page-13-5). Patients with genital PsO also report lower sexual frequency and function [[13](#page-13-6)]. Furthermore, development of genital or scalp PsO is associated with an increased risk of psoriatic arthritis [[14,](#page-13-7) [16](#page-13-8)]. Treatment in these areas is challenging as a result of both patient dissatisfaction with applying topical treatments that can be cosmetically unacceptable and the increased risk for topical drug absorption from the genital region, which can potentially lead to more side effects [[14](#page-13-7)]. In addition, ultraviolet therapy is not suitable for the genital skin because of the higher risk of burning or the scalp because of poor penetration [\[14](#page-13-7)]. As a result of these treatment challenges, a large proportion of patients with genital or scalp PsO report not receiving any treatment, highlighting an unmet need in this patient population [\[14\]](#page-13-7). Risankizumab selectively binds the p19 subunit of interleukin-23 with high binding affnity and is approved for multiple indications including adults with moderate-to-severe plaque psoriasis [\[17\]](#page-13-9). Risankizumab has previously reported high effcacy compared with ustekinumab [\[17](#page-13-9)], adalimumab [[18](#page-14-0)], secukinumab [[19\]](#page-14-1), and apremilast [[20](#page-14-2)]. Additionally, risankizumab has demonstrated effcacy in diffcult to treat areas such as the nails, scalp, and palms and in the condition palmoplantar pustulosis [[20–](#page-14-2)[22\]](#page-14-3). Furthermore, risankizumab has demonstrated a favorable long-term safety profle for patients with moderate-to-severe psoriasis [[23](#page-14-4)]. Multiple studies have also reported on the effectiveness of risankizumab in real-world settings [\[24](#page-14-5)[–26\]](#page-14-6). Here we assess the efficacy and safety of risankizumab in the UnlIMMited phase 4 clinical trial for the treatment of adults with genital and/ or scalp psoriasis after 16 weeks of treatment. ## METHODS #### **Study Design** UnlIMMited (NCT05969223) is an on-going phase 4, multicenter, randomized, doubleblind, placebo-controlled trial examining the effcacy and safety of risankizumab on patients with moderate-to-severe genital PsO (study-G) or moderate-to-severe scalp PsO (study-S). This study was conducted across 38 sites in the USA, in a combination of dermatology practices and clinical research centers. The study includes a 30-day screening period, followed by a 16-week double-blind, placebo-controlled treatment period (period A), a 36-week openlabel period (period B), and an 8-week follow up period (Fig. [1\)](#page-3-0). In period A, patients were randomized 1:1 within each study to receive blinded subcutaneous 150 mg risankizumab or placebo at week 0 and 4 at the study site. Patients were randomized using an interactive response technology system at the screening visit. Randomization was stratifed by weight (≤ 100 kg vs > 100 kg) and the number of prior biologic therapies for psoriasis (0 vs ≥ 1). Beginning at week 16, all patients received open-label 150 mg risankizumab every 12 weeks with the last dose occurring at week 40. Results presented here are assessed through the end of period A (week 16). #### **Ethical Approval** Study approval was obtained from local ethics committees (Advarra, reference numbers available in the supplementary materials), and the patients provided written informed consent for participation in the study and publication of ![](https://assets.reachrx.ai/images/10.1007%E2%98%8Ds13555-025-01544-6/_page_3_Figure_1.jpeg) Fig. 1 UnlIMMited study design. *BSA* body surface area, *IGA* Investigator Global Assessment, *IL* interleukin, *PBO* placebo, *PsO* psoriasis, *PSSI* Psoriasis Scalp Severity Index, study data. The study was conducted in accordance with the International Conference on Harmonisation, Good Clinical Practice Guidelines, and the Declaration of Helsinki 1964 and its later amendments. ### **Patients** The UnlIMMited study enrolled adults≥18 years of age with stable moderate-to-severe plaque PsO diagnosed ≥ 6 months prior to the baseline visit with an affected BSA ≥ 1% and an overall static Physician's Global Assessment (sPGA) score of ≥ 3 at baseline. At least 60% of patients within each study presented a baseline affected BSA≥10%. Eligible patients also had inadequate control and/or intolerance to topical treatment, phototherapy, and/or systemic therapy. For study-G eligibility, an sPGA-Genital (sPGA-G) score ≥ 3 at baseline was needed. For study-S, inclusion required a Psoriasis Scalp Severity Index (PSSI) score ≥ 12, scalp Investigator Global Assessment (IGA) score≥3, and ≥30% of *RZB* risankizumab, *sPGA-G* static Physician's Global Assessment – Genital the scalp affected at baseline. Patients meeting requirements for both studies were randomly assigned for treatment to one study. ### **Assessments** The primary endpoints were the achievement of an sPGA-G score of 0 or 1 at week 16 for study-G and a scalp IGA 0 or 1 at week 16 for study-S. The following ranked secondary effcacy endpoints were assessed in study-G at week 16: achievement of sPGA-G score of 0, Dermatology Life Quality Index (DLQI) score of 0 or 1, ≥ 4 point improvement from baseline (clinically meaningful improvement) in genital PsO itch assessed by numerical rating scale (NRS using a 0 [no] to 10 [worst imaginable] scale) for patients with a baseline score ≥ 4, and Genital Psoriasis – Sexual Frequency Questionnaire [[27\]](#page-14-7) (GenPs-SFQ) item 2 score of 0 or 1 (genital PsO rarely or never limiting sexual activity) among patients with a baseline score≥2. The following ranked secondary effcacy endpoints were assessed in study-S at week 16: achievement of ≥90% reduction in PSSI (PSSI 90), achievement of PSSI 75, change from baseline in Psoriasis Symptom Scale (PSS), achievement of PSSI 100, and achievement of PSS score of 0. Additional endpoints reported at week 16 for study-G included sPGA 0/1, sPGA 0, and ≥2 point improvement in Patient's Global Assessment of Genital Psoriasis (PatGA)-Genital for patients with a baseline score≥2. Percent change from baseline and change from baseline for Genital Psoriasis Symptom Scale [\[28\]](#page-14-8) (GPSS) total score, Hospital Anxiety and Depression Scale – Anxiety (HADS-A), and HADS – Depression (HADS-D) score are also reported. Mean percent change from baseline, when reported, was calculated for patients with a nonmissing baseline score>0. Additional endpoints for study-S reported at week 16 included DLQI score of 0/1, PSS score of 0/1, scalp IGA 0, sPGA 0, and sPGA 0/1. A ≥ 4 point reduction from baseline scalp itch NRS among patients with a baseline score ≥ 4, percent change from baseline and change from baseline for PSSI, scalp itch NRS, HADS-A, and HADS-D are also reported. Safety was assessed by adverse events (AEs), vital signs, physical examinations, ECGs, and clinical laboratory evaluations throughout the study. ### **Statistical Analysis** Effcacy analyses were conducted on the intentto-treat population. A hierarchical testing strategy was used to control overall type 1 error for primary and ranked secondary endpoints. Primary and categorical secondary endpoints for each study were analyzed using Cochran–Mantel–Haenszel test. Missing data for categorical endpoints was handled using non-responder imputation, i.e., subjects with missing data will be imputed as non-responders. The number of missing data points is provided in Supplemental Table 1. Continuous endpoints were analyzed using mixed-effect model repeated measurement method (MMRM), adjusting for the fxed effects of treatment, actual values of stratifcation factors at baseline, baseline value, visit and treatment by visit interaction as covariates. MMRM was also used to handle missing data for continuous endpoints. A sample size of *N*=100 for both studies was calculated to provide more than 90% power to detect the treatment difference between risankizumab and placebo, using a chi-square test with a two-sided signifcance level of 0.05. # RESULTS ### **Patient Demographics and Baseline Disease Characteristics** A total of 109 patients were enrolled in study-G and 105 patients were enrolled in study-S. In study-G, 54 patients received at least one dose of risankizumab and 54 received at least one dose of placebo (Supplementary Fig. 1). In study-S, 51 patients randomized to risankizumab received at least one dose 54 received at least one dose of placebo (Supplementary Fig. 2). Within study-G, demographics and baseline disease characteristics were generally similar between treatment groups (Table [1\)](#page-5-0). Patients randomized to receive risankizumab were less likely to be female (29.1% vs 40.7%), slightly less likely to have prior non-biologic systemic exposure for PsO (14.5% vs 18.5%), and more likely to have an sPGA-G of 3 (69.1% vs 55.6%) (Table [1\)](#page-5-0). In study-S, patient demographics were generally balanced between treatment groups; however, patients randomized to receive risankizumab had a longer duration of psoriasis (Table [2\)](#page-6-0). ## **Primary Endpoints** A signifcantly higher proportion of patients receiving risankizumab, compared with those receiving placebo, achieved the primary endpoints in both studies (Fig. [2](#page-7-0)). In study-G, 69.1% (38/55) of patients receiving risankizumab versus 13.0% (7/54) of patients receiving placebo achieved sPGA-G 0/1 at week 16 (*P* < 0.0001; Fig. [2](#page-7-0)). In study-S, 60.8% (31/51) of patients receiving risankizumab versus 13.0% (7/54) of patients receiving placebo achieved scalp IGA 0/1 at week 16 (*P* < 0.0001; Fig. [2](#page-7-0)). | | RZB (N=55) | PBO (N=54) | | |-----------------------------------------------------------|-------------|-------------|--| | Sex, n (%) | | | | | Female | 16 (29.1) | 22 (40.7) | | | Male | 39 (70.9) | 32 (59.3) | | | Age, years, mean (SD) | 45.3 (15.0) | 46.3 (15.7) | | | Ethnicity, n (%) | | | | | Hispanic or Latino | 15 (27.3) | 17 (31.5) | | | Not Hispanic or Latino | 40 (72.7) | 37 (68.5) | | | Race, n (%) | | | | | American Indian or Alaska Native | 0 | 0 | | | Asian | 3 (5.5) | 1 (1.9) | | | Black or African American | 0 | 2 (3.7) | | | Native Hawaiian or other Pacifc Islander | 2 (3.6) | 0 | | | Multiple | 2 (3.6) | 1 (1.9) | | | White | 48 (87.3) | 50 (92.6) | | | Body mass index (kg/m2
), n (%) | | | | | <25 | 10 (18.2) | 11 (20.8) | | | ≥25 to <30 | 17 (30.9) | 13 (24.5) | | | ≥30 | 28 (50.9) | 29 (54.7) | | | Afected body surface area, mean (SD) | 16.4 (18.3) | 18.0 (17.0) | | | <10%, n (%) | 22 (40.0) | 18 (33.3) | | | ≥10%, n (%) | 33 (60.0) | 36 (66.7) | | | Duration of disease, years, mean (SD) | 16.3 (12.6) | 16.0 (14.9) | | | Prior biologic exposure, n (%) | 15 (27.3) | 13 (24.1) | | | Prior non-biologic systemic exposure for psoriasis, n (%) | 8 (14.5) | 10 (18.5) | | | DLQI, mean (SD) | 13.1 (7.8) | 14.5 (8.2) | | | sPGA categories, n (%) | | | | | 3 | 45 (81.8) | 43 (79.6) | | | 4 | 10 (18.2) | 11 (20.4) | | | sPGA-G categories, n (%) | | | | | 3 | 38 (69.1) | 30 (55.6) | | | ≥4 | 17 (30.9) | 24 (44.4) | | | GenPs-SFQ item 2, mean (SD) | 2.0 (1.6) | 2.0 (1.7) | | | Genital psoriasis itch NRS, mean (SD) | 6.0 (2.7) | 6.4 (2.6) | | | PatGA-genital, mean (SD) | 3.5 (1.1) | 3.7 (1.1) | | Table 1 Study-G patient demographics and baseline characteristics *DLQI* Dermatology Life Quality Index, *GenPs-SFQ* Genital Psoriasis – Sexual Frequency Questionnaire item 2, *NRS* numerical rating scale, *PBO* placebo, *RZB* risankizumab, *sPGA* static Physician's Global Assessment, *sPGA-G* static Physician's Global Assessment – Genital | | RZB (N=51) | PBO (N=54) | | |-----------------------------------------------------------|-------------|-------------|--| | Sex, n (%) | | | | | Female | 24 (47.1) | 22 (40.7) | | | Male | 27 (52.9) | 32 (59.3) | | | Age, years, mean (SD) | 46.0 (14.8) | 46.7 (14.2) | | | Ethnicity, n (%) | | | | | Hispanic or Latino | 12 (23.5) | 26 (48.1) | | | Not Hispanic or Latino | 39 (76.5) | 28 (51.9) | | | Race, n (%) | | | | | American Indian or Alaska Native | 0 | 1 (1.9) | | | Asian | 2 (3.9) | 3 (5.7) | | | Black or African American | 4 (7.8) | 4 (7.5) | | | Native Hawaiian or other Pacifc Islander | 0 | 0 | | | Multiple | 1 (2.0) | 2 (3.8) | | | White | 44 (86.3) | 43 (81.1) | | | Body mass index (kg/m2
), n (%) | | | | | <25 | 8 (15.7) | 12 (22.2) | | | ≥25 to <30 | 19 (37.3) | 12 (22.2) | | | ≥30 | 24 (47.1) | 30 (55.6) | | | Afected body surface area, mean (SD) | 16.4 (16.1) | 17.2 (17.6) | | | <10%, n (%) | 20 (39.2) | 20 (37.0) | | | ≥10%, n (%) | 31 (60.8) | 34 (63.0) | | | Duration of disease, years, mean (SD) | 16.0 (13.3) | 14.8 (13.8) | | | Prior biologic exposure, n (%) | 20 (39.2) | 19 (35.2) | | | Prior non-biologic systemic exposure for psoriasis, n (%) | 9 (17.6) | 7 (13.0) | | | DLQI, mean (SD) | 13.4 (7.4) | 13.1 (7.6) | | | sPGA categories, n (%) | | | | | 3 | 38 (74.5) | 42 (77.8) | | | 4 | 13 (25.5) | 12 (22.2) | | | Scalp IGA, n (%) | | | | | 3 | 36 (70.6) | 42 (77.8) | | | 4 | 15 (29.4) | 12 (22.2) | | | Baseline PSSI, mean (SD) | 35.1 (15.0) | 32.5 (14.9) | | | Baseline PSS, mean (SD) | 9.0 (3.9) | 9.4 (4.3) | | | Scalp itch NRS, mean (SD) | 7.4 (2.0) | 7.1 (2.7) | | Table 2 Study-S patient demographics and baseline characteristics *DLQI* Dermatology Life Quality Index, *IGA* Investigator Global Assessment, *PBO* placebo, *NRS* numerical rating scale, *PSS* Psoriasis Symptom Score, *PSSI* Psoriasis Scalp Severity Index, *RZB* risankizumab, *sPGA* static Physician's Global Assessment ![](https://assets.reachrx.ai/images/10.1007%E2%98%8Ds13555-025-01544-6/_page_7_Figure_1.jpeg) Fig. 2 Achievement of primary endpoints in study-G and study-S. \*\*\**P*<0.001. *IGA* Investigator Global Assessment, *PBO* placebo, *RZB* risankizumab, *sPGA-G* static Physician's Global Assessment – Genital #### **Study‑G Ranked Secondary and Additional Endpoints** A significantly higher proportion of patients receiving risankizumab, compared with those receiving placebo, achieved all ranked secondary endpoints of sPGA-G 0, DLQI 0/1, clinically meaningful improvement in genital itch from baseline, and GenPs-SFQ item 2 0/1 at week 16 (*P*<0.0001; Fig. [3\)](#page-8-0). For the additional endpoints, a numerically higher proportion of patients receiving risankizumab, compared with placebo, also achieved sPGA 0/1, sPGA 0, and ≥2 point improvement in PatGA-genital at week 16 (Fig. [3](#page-8-0)). Patients receiving risankizumab versus placebo also reported numerically greater improvements from baseline scores in GPSS total score (26.5 vs 1.0), HADS-A score (2.3 vs 1.3), and HADS-D score (1.6 vs 0.6) at week 16. These Changes represent percent improvement from baseline of 58.1% vs −14.1% for GPSS total score, 36.2% vs 10.9% for HADS-A, and 34.0% vs −7.1% for HADS-D score at week 16 for patients receiving risankizumab versus placebo, respectively. ### **Study‑S Ranked and Additional Secondary Endpoints** A significantly higher proportion of patients receiving risankizumab, compared with those receiving placebo, achieved the frst four ranked secondary endpoints of PSSI 90, PSSI 75, PSSI 100, and a signifcantly improved change from baseline in PSS at week 16 (*P* < 0.0001; Fig. [4](#page-9-0)). The third ranked endpoint, change from baseline in PSS, was − 6.0 for patients receiving risankizumab versus − 1.0 for patients receiving placebo at week 16 (*P*<0.0001). For the ffth ranked endpoint, a numerically higher proportion of patients with risankizumab achieved PSS 0 (*P*=0.0539) compared with placebo at week 16 (Fig. [4](#page-9-0)). For the additional endpoints, a numerically higher proportion of patients with risankizumab achieved ≥ 4 point improvement from baseline scalp itch, DLQI 0/1, PSS 0/1, scalp IGA 0, sPGA 0, and sPGA 0/1, compared to placebo at week 16 (Fig. [4\)](#page-9-0). Patients receiving risankizumab versus placebo also reported numerically greater improvements from baseline scores in PSSI (28.3 vs 10.6), scalp itch NRS (4.1 vs 1.2), HADS-A score (1.8 vs 0.3), and HADS-D score (1.8 vs 0.3) at week 16. These results represent percent improvement from baseline of 79.7% vs 23.9% for PSSI, 54.6% vs 13.3% for scalp itch NRS, 29.3% vs − 4.1% for HADS-A, and 34.0% vs − 3.9% for HADS-D at week 16 for patients receiving risankizumab versus placebo, respectively. ![](https://assets.reachrx.ai/images/10.1007%E2%98%8Ds13555-025-01544-6/_page_8_Figure_1.jpeg) **Fig. 3** Study-G ranked secondary and additional endpoints at week 16. \*\*\*P < 0.001; +++ nominal P < 0.001. Numbers at the bottom of each bar represent *n*. ^a ≥ 4 point improvement from baseline in genital PsO itch assessed by NRS for patients with a baseline score ≥ 4 (RZB N=41, PBO N=45), ^bfor patients with a baseline score ≥ 2 at baseline (RZB N=31, PBO N=32), ^c ≥ 2 point improvement from baseline in PatGA-Genital for patients with a #### Safety Through the first 16 weeks for both study-G and study-S, risankizumab was generally well tolerated and no new safety signals were identified (Table 3). In study-G, 35.2% of patients receiving risankizumab and 31.5% of patients receiving placebo reported an AE (Table 3). According to the investigators, 9.3% of patients receiving risankizumab and 1.9% of patients receiving placebo had an AE that was related to the study treatment (Table 3). In study-S, 25.5% of patients receiving risankizumab and 27.8% of patients receiving placebo reported an AE (Table 3). For patients receiving risankizumab and 27.8% of patients receiving risankizumab and 27.8% of patients receiving risankizumab and 27.8% of patients receiving risankizumab and 27.8% of patients receiving risankizumab and 27.8% of patients receiving risankizumab and 27.8% of patients receiving risankizumab and 27.8% of patients receiving risankizumab and 27.8% of patients receiving risankizumab and 27.8% of patients receiving risankizumab receiving risankizumab, 3.9% were related to the study treatment per the investigators and 0% were reported for patients receiving placebo (Table 3). The most baseline score $\geq 2$ (RZB N=46, PBO N=48). *DLQI* Dermatology Life Quality Index, GenPs-SFQ Genital Psoriasis – Sexual Frequency Questionnaire item 2, NRS numerical rating scale, *PatGA* genital Patient's Global Assessment of Genital Psoriasis, *PBO* placebo, *RZB* risankizumab, *sPGA* static Physician's Global Assessment, *sPGA-G* static Physician's Global Assessment – Genital commonly reported AE for patients receiving risankizumab was upper respiratory tract infection in both study-G (n=4, 7.4%) and study-S (n=3, 5.9%). In study-G, no serious AEs were identified for patients receiving risankizumab (Table 3). In study-S one serious AE was reported, a small bowel obstruction that was considered not related to the study treatment according to the investigator. No AEs leading to the discontinuation of the study drug, deaths, serious infections, malignancies, serious hypersensitivity reaction, extended major adverse cardiovascular events, adjudicated anaphylactic reactions, or suicidal ideation or behavior were reported in either study-G or study-S for patients receiving risankizumab through the first 16 weeks of treatment (Table 3). ![](https://assets.reachrx.ai/images/10.1007%E2%98%8Ds13555-025-01544-6/_page_9_Figure_1.jpeg) Fig. 4 Study-S ranked secondary and additional endpoints at week 16. \*\*\**P*<0.001; ++ nominal *P*<0.01; +++nominal *P*<0.001. Numbers at the bottom of each bar represent *n*. a≥4 point improvement from baseline in scalp PsO itch assessed by NRS for patients with a baseline score≥4 (RZB *N*=40, PBO *N*=45). *DLQI* Dermatology Life Quality Index, *IGA* Investigator Global Assessment, *NRS* numerical rating scale, *PBO* placebo, *PSS* Psoriasis Symptom Score, *PSSI* Psoriasis Scalp Severity Index, *RZB* risankizumab, *sPGA* static physician's global assessment One hepatic event (increased gamma-glutamyl transferase, GGT) in a patient with a baseline elevated GGT was reported in study-G and one hepatic event (hepatic steatosis) was reported in study-S for a patient receiving risankizumab. Neither was considered related to the study treatment according to the investigator (Table [3\)](#page-10-0). # DISCUSSION Genital and scalp psoriasis are considered highimpact areas that can result in a signifcant burden on the patient's quality of life, even in cases with a low affected BSA [\[12–](#page-13-4)[15](#page-13-5)]. Diagnosis and treatment of genital and scalp PsO can also be challenging. For example, genital PsO is often underreported and underdiagnosed as patients may be embarrassed to address their concerns with their clinician, and clinicians may not be asking patients to undress completely for exams. Many treatment options are also diffcult to use in the genital or scalp region [\[13](#page-13-6), [14](#page-13-7)]. The International Psoriasis Council recategorized PsO severity to emphasize that patients with special area involvement are eligible for treatments with systemic drugs, such as biologics, irrespective of affected BSA [\[29\]](#page-14-9). In the UnlIMMited study, a significantly higher proportion of patients receiving risankizumab met the study's primary endpoints at week 16 in both study-G (sPGA-G 0/1) and study-S (scalp IGA 0/1) compared with patients receiving placebo. A signifcantly higher proportion of patients receiving risankizumab also met all the ranked secondary endpoints for study-G (sPGA-G 0, DLQI 0/1, clinically meaningful improvement in genital itch, and GenPs-SFQ 0/1) at week 16. Similarly for study-S, a signifcantly higher proportion of patients #### Table 3 Safety events through week 16 | | Study-G | | Study-S | | |---------------------------------------------------------|------------|------------|------------|------------| | | RZB (N=54) | PBO (N=54) | RZB (N=51) | PBO (N=54) | | Any AE | 19 (35.2) | 17 (31.5) | 13 (25.5) | 15 (27.8) | | AE related to study treatment according to investigator | 5 (9.3) | 1 (1.9) | 2 (3.9) | 0 | | Serious AE | 0 | 1 (1.9) | 1 (2.0)a | 1 (1.9) | | AE leading to discontinuation of study treatment | 0 | 0 | 0 | 0 | | Deaths | 0 | 0 | 0 | 0 | | Serious infections | 0 | 0 | 0 | 0 | | Malignancies | 0 | 0 | 0 | 0 | | Serious hypersensitivity reactions | 0 | 0 | 0 | 0 | | Extended MACE | 0 | 0 | 0 | 1 (1.9) | | Adjudicated anaphylactic reaction | 0 | 0 | 0 | 0 | | Hepatic events | 1 (1.9)b | 1 (1.9) | 1 (2.0)c | 0 | | Injection site reactions | 1 (1.9) | 0 | 0 | 0 | | Suicidal ideation or behavior | 0 | 0 | 0 | 0 | Safety results are reported for patients who received at least one dose of their study drug *AE* adverse event, *MACE* major cardiovascular events, *PBO* placebo, *RZB* risankizumab a Small bowel obstruction, not related to study treatment according to investigator b Increased gamma-glutamyl transferase, not related to study treatment according to investigator c Hepatic steatosis, not related to study treatment according to investigator receiving risankizumab, compared to placebo, achieved the ranked secondary endpoints of PSSI 90, PSSI 75, change from baseline PSS, and PSSI 100. A numerically higher proportion of patients receiving risankizumab compared to placebo achieved PSS 0, the last ranked endpoint. Through the frst 16 weeks of treatment, no new safety signals were identified, and safety was consistent with previous risankizumab studies [[23\]](#page-14-4). Defning treatment outcomes for patients beyond skin clearance will allow physicians to more fully understand their patient's quality of life and identify the best treatment options for their patients. Itch is one of the most impactful symptoms reported by patients with genital PsO, which can lead to scratching and further exacerbation of their disease (Koebner phenomenon) [\[30\]](#page-14-10). Itch has a signifcant impact on the patient's daily activities and sleep [[31\]](#page-14-11). Patients with genital PsO also experience signifcantly higher rates of sexual function impairments including reduced sexual desire, avoidance of sexual relationships, and a lower frequency of intercourse, which is reported as a major concern among patients [\[27](#page-14-7), [30](#page-14-10)]. In this study, we attempt to directly assess the impact on quality of life beyond skin clearance by including clinically meaningful improvement in genital itch (≥4 point reduction from baseline), GenPs-SFQ item 2 which measures sexual activity frequency, and incorporating the patient's own view of their disease severity using the PatGA-genital (a substantial improvement is reported as≥2 point improvement from baseline) [[30](#page-14-10)]. Similarly, patients with scalp PsO report physical and social distress associated with the symptoms and visibility of their PsO [\[32\]](#page-14-12). Scalp itch is often considered one of the most disruptive symptoms to patients, but they frequently complain of pain and burning as well [[32](#page-14-12), [33](#page-14-13)]. Signs such as skin redness and fakiness, which could be mistaken for dandruff, but can also contribute to patient burden [\[32\]](#page-14-12). The UnlIMMited study addresses these additional concerns by reporting ≥ 4 point improvement in scalp itch from baseline, and PSS which assesses four symptoms (itching, pain, burning, and stinging) and three signs (redness, scaling, and cracking) [[32](#page-14-12)[–34](#page-14-14)]. Dedicated studies evaluating treatments for genital and scalp psoriasis, which are distinct from post hoc analysis of moderate-to-severe plaque PsO studies, are limited. Here, we present two dedicated placebo-controlled studies for moderate-to-severe genital and scalp PsO, supporting the use of risankizumab in these high-impact areas. These studies add to the positive data that was demonstrated in other highimpact manifestations of PsO such as non-pustular palmoplantar PsO in the IMMprint study, and high-impact body regions of the scalp, nails, and palmoplantar PsO in the post hoc data from the LIMMitless studies [[35](#page-14-15)[–37\]](#page-14-16). A limitation of this study is that patients enrolled may not refect the overall population of patients with PsO. In an effort to better refect the general population, this study enrolled patients with both high and low affected BSA. Patients meeting inclusion criteria for both genital and scalp psoriasis were randomized to either study-G or study-S. Concurrent high-impact areas were not assessed. While the enrolled patient number is lower, this study was suffciently powered to detect differences between patients receiving risankizumab and placebo. Additionally, the results reported here are through week 16; the continued study through week 52 will provide longer-term effcacy and safety. # CONCLUSION Risankizumab is effective for the treatment of genital and scalp PsO, and no new safety signals were identifed. These results provide additional evidence for the effcacy and safety of risankizumab for the treatment of PsO, including in hard to treat, high-impact areas. # ACKNOWLEDGEMENTS AbbVie and authors thank all the trial investigators and the patients who participated in this clinical trial *Medical Writing and Editorial Assistance.* Medical writing support was provided by Trisha Rettig PhD and editorial support was provided by Angela T. Hasdell both employees of and funded by AbbVie. *Author Contributions.* All authors had access to relevant data for this publication. Toni Anschutz, Brenton Bialik, Manish Patel, Greg St. John, Arathi R Setty, and Doug Ashley contributed to conceptualization. Formal analysis was conducted by Chenyang Duan. Investigation was conducted by Eingun James Song, Benjamin Ehst, Brad Glick, George Michael Lewitt, Phoebe Rich, Navid Ezra, Jerry Bagel, and Lindsay Ackerman. All authors contributed to the writing of this manuscript. *Funding.* AbbVie funded this study and the journal's rapid service fee and also participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. No honoraria or payments were made for authorship. *Data Availability.* AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual, and trial-level data (analysis data sets), as well as other information (e.g., protocols, clinical study reports, or analysis plans), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. These clinical trial data can be requested by any qualifed researchers who engage in rigorous, independent, scientific research, and will be provided following review and approval of a research proposal, Statistical Analysis Plan (SAP), and execution of a Data Sharing Agreement (DSA). Data requests can be submitted at any time after approval in the US and Europe and after acceptance of this manuscript for publication. The data will be accessible for 12 months, with possible extensions considered. For more information on the process or to submit a request, visit the following link: [https://vivli.](https://vivli.org/ourmember/abbvie/) [org/ourmember/abbvie/](https://vivli.org/ourmember/abbvie/) then select "Home". ### *Declarations* *Confict of Interest.* Eingun James Song is a consultant, promotional speaker and/or investigator for AbbVie, Alphyn, Alumis, Amgen, Apogee, Bristol Myers Squibb, CorEvitas, Dermavant, Dermbiont, Galderma, Incyte, Johnson & Johnson, Lilly, LEO, Moon Lake, Novartis, Organon, Ortho dermatologics, Pfze, Regeneron, Sanof, SUN Pharma, UCB, Veradermics, Takeda, Target Registry Timber. Lindsay Ackerman has been an consultant, speaker, and/ or investigator for AbbVie, Amgen, ArGEN-X, Artacus, AstraZeneca, Biofronterra, Bristol Myers Squibb, Castle, ChemoCentryx, Corevitas (Corrona), DermTech, Eli Lilly, Helsinn Incyte, Janssen, Kyowa Kirin, Mindera, Novartis, Sanof, Sun, Timber, Trevi, and UCB. Benjamin Ehst is a speaker, adviser and/or clinical study investigator for AbbVie, Acelyrin, Allakos, Alumis, Amgen, Apogee, Arcutis, Bristol Myers Squibb, Celldex, Concert, Dermavant, Eli Lilly, Evelo Biosciences, Evommune, Incyte, Janssen, LEO, Merck, Navigator Medicines, Novartis, Pfzer, Takeda, Regeneron, Sanof, Sun Pharma, UCB, and Ventyx. Phoebe Rich has served on advisory boards for Alumis, Oruka, and Veradermics and as an investigator for Abbvie, Afasigma, Allakos, Amgen, Arcutis, Aslan, Bristol-Myers-Squibb, Dermavant, Dermbiont, Dermira, EliLilly, Galderma, Hallux, Incyte, Janssen, Leo, Moberg, Pfzer, Sun, Technoderma, Teva, UCB, and Veradermics. Jerry Bagel has received research funds from Amgen, Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, CorEvitas (Corrona) Psoriasis Registry, Dermavant, Dermira/ UCB, Eli Lilly, Glenmark, Janssen Biotech, Kadmon, Leo Pharma, Lycera, Menlo Therapeutics, Novartis, Pfzer, Regeneron, Sun Pharma, Taro, and Valeant; has served as a consultant for AbbVie, Amgen, Celgene, Eli Lilly, Janssen Biotech, Novartis, Sun Pharma, and Valeant; and has served as a speaker for AbbVie, Celgene, Eli Lilly, Janssen Biotech, and Novartis. George Michael Lewitt is a consultant, promotional speaker, and/or investigator for AbbVie, Amgen, Arcutis, Bristol Meyers Squibb, Dermavant, Galderma Laboratories, Incyte, Janssen, Lilly, Novan, Novartis, Orthodermatologics, Pfzer, Sanof, Sun Pharma, UCB, and the CorEvitas PsO and AD registries. Navid Ezra is a speaker, adviser and/or clinical study investigator for AbbVie, Alumis, Amgen, Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, ChemoCentryx, Dermavant, Eli Lilly, Incyte, Janssen, LEO, Merck, Novartis, Ortho Dermatologics, Pfzer, Takeda, Regeneron, Sanof, Sun Pharma, UCB and the CorEvitas registries. Brad Glick is an advisory board member, consultant, speaker and/or investigator for and received honoraria or grants from Amgen, AbbVie, AstraZeneca, Almirall, Acrutis, Bausch Health/Valeant, OrthoDermatologics, Boehringer Ingelheim, Bristol Myers Squibb, Brickell Biotech, Cara Therapeutics, ChemoCentryx, Dermavant, Dermira, Eli Lilly, EPI/Novan Pharmaceuticals, Incyte, Janssen Pharmaceuticals, LEO Pharma, Galderma, Nimbus Lakshmi, Inc, Novartis Pharmaceutical Corporation, Sun Pharma, Pfzer, Sanof, Regeneron, UCB Biopharmaceuticals and the CorEvitas AD, CorEvitas PSO and PROSE Registries. Dr. Glick is a shareholder of Top MD, LLC. Toni Anschutz, Brenton Bialik, Greg St. John, Arathi Setty, Chenyang Duan, Manish Patel, and Doug Ashley are full time employees of AbbVie receiving a salary and may hold stock and/or stock options. *Ethical Approval.* Study approval was obtained from local ethics committees (Advarra, reference numbers available in the supplementary materials), and the patients provided written informed consent for participation in the study and publication of study data. The study was conducted in accordance with the International Conference on Harmonisation, Good Clinical Practice Guidelines, and the Declaration of Helsinki 1964 and its later amendments. *Open Access.* This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativeco](http://creativecommons.org/licenses/by-nc/4.0/) [mmons.org/licenses/by-nc/4.0/.](http://creativecommons.org/licenses/by-nc/4.0/) # REFERENCES - 1. Smith RL, Warren RB, Eyre S, et al. Polymorphisms in the IL-12beta and IL-23R genes are associated with psoriasis of early onset in a UK cohort. J Invest Dermatol. 2008;128(5):1325–7. - 2. Zhang M, Carter C, Olson WH, et al. Patient preference for dosing frequency based on prior biologic experience. J Drugs Dermatol. 2017;16(3):220–6. - 3. Larsabal M, Ly S, Sbidian E, et al. GENIPSO: a French prospective study assessing instantaneous prevalence, clinical features and impact on quality of life of genital psoriasis among patients consulting for psoriasis. Br J Dermatol. 2019;180(3):647–56. - 4. Augustin M, Sommer R, Kirsten N, et al. Topology of psoriasis in routine care: results from highresolution analysis of 2009 patients. Br J Dermatol. 2019;181(2):358–65. - 5. Egeberg A, See K, Garrelts A, Burge R. Epidemiology of psoriasis in hard-to-treat body locations: data from the Danish skin cohort. BMC Dermatol. 2020;20(1):3. - 6. Merola JF, Li T, Li WQ, Cho E, Qureshi AA. Prevalence of psoriasis phenotypes among men and women in the USA. Clin Exp Dermatol. 2016;41(5):486–9. - 7. Meeuwis KAP, Potts Bleakman A, van de Kerkhof PCM, et al. Prevalence of genital psoriasis in patients with psoriasis. J Dermatol Treat. 2018;29(8):754–60. - 8. Chan CS, Van Voorhees AS, Lebwohl MG, et al. Treatment of severe scalp psoriasis: from the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol. 2009;60(6):962–71. - 9. National Psoriasis Foundation. Genital Psoriasis Quick Guide. . Accessed 5 June 25. - 10. National Psoriasis Foundation. Scalp Psoriasis Quick Guide. . Accessed 5 June 25. - 11. Meeuwis KA, de Hullu JA, IntHout J, et al. Genital psoriasis awareness program: physical and psychological care for patients with genital psoriasis. Acta Derm Venereol. 2015;95(2):211–6. - 12. Zampieron A, Buja A, Fusco M, et al. Quality of life in patients with scalp psoriasis. G Ital Dermatol Venereol. 2015;150(3):309–16. - 13. Ryan C, Sadlier M, De Vol E, et al. Genital psoriasis is associated with signifcant impairment in quality of life and sexual functioning. J Am Acad Dermatol. 2015;72(6):978–83. - 14. Merola JF, Qureshi A, Husni ME. Underdiagnosed and undertreated psoriasis: nuances of treating psoriasis affecting the scalp, face, intertriginous areas, genitals, hands, feet, and nails. Dermatol Ther. 2018;31(3):e12589. - 15. Strober B, Callis DK, Mark L, et al. Impact of psoriasis disease severity and special area involvement on patient-reported outcomes in the real world: an analysis from the CorEvitas psoriasis registry. J Dermatol Treat. 2024;35(1):2287401. - 16. Amorim GM, Radichewski V, Sponholz ML, Carneiro S. P82 Are nail, scalp and intergluteal cleft psoriasis really risk factors for psoriatic arthritis or are we just repeating previous studies? Br J Dermatol. 2024;191(Suppl\_3). [https://doi.org/10.1093/](https://doi.org/10.1093/bjd/ljae360.112) [bjd/ljae360.112](https://doi.org/10.1093/bjd/ljae360.112) - 17. Gordon KB, Strober B, Lebwohl M, et al. Effcacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials. Lancet. 2018;392(10148):650–61. - 18. Reich K, Gooderham M, Thaçi D, et al. Risankizumab compared with adalimumab in patients with moderate-to-severe plaque psoriasis (IMMvent): a randomised, double-blind, activecomparator-controlled phase 3 trial. Lancet. 2019;394(10198):576–86. - 19. Warren RB, Blauvelt A, Poulin Y, et al. Effcacy and safety of risankizumab vs. secukinumab in patients with moderate-to-severe plaque psoriasis (IMMerge): results from a phase III, randomized, open-label, effcacy-assessor-blinded clinical trial. Br J Dermatol. 2021;184(1):50–9. - 20. Stein Gold LF, Bagel J, Tyring SK, et al. Comparison of risankizumab and apremilast for the treatment of adults with moderate plaque psoriasis eligible for systemic therapy: results from a randomized, open-label, assessor-blinded phase IV study (IMMpulse). Br J Dermatol. 2023;189(5):540–52. - 21. Orsini D, Gargiulo L, Ibba L, et al. Effectiveness of risankizumab in plaque psoriasis with involvement of diffcult-to-treat areas: a real-world experience from two referral centers. J Dermatol Treat. 2023;34(1):2220849. - 22. Okubo Y, Murakami M, Kobayashi S, et al. Risankizumab in Japanese patients with moderate-tosevere palmoplantar pustulosis: results from the randomized, phase 3 JumPPP study. J Dermatol. 2025;52(4):593–602. - 23. Gordon KB, Lebwohl M, Papp KA, et al. Long-term safety of risankizumab from 17 clinical trials in patients with moderate-to-severe plaque psoriasis. Br J Dermatol. 2022;186(3):466–75. - 24. Megna M, Cinelli E, Gallo L, Camela E, Ruggiero A, Fabbrocini G. Risankizumab in real life: preliminary results of effcacy and safety in psoriasis during a 16-week period. Arch Dermatol Res. 2022;314(6):619–23. - 25. Megna M, Tommasino N, Potestio L, et al. Realworld practice indirect comparison between guselkumab, risankizumab, and tildrakizumab: results from an Italian 28-week retrospective study. J Dermatol Treat. 2022;33(6):2813–20. - 26. Strober B, Patel M, Kaldas MI, et al. Real-world skin clearance and quality of life with risankizumab in patients with psoriasis with moderate skin involvement and those eligible for systemic therapy per International Psoriasis Council classifcation. Dermatol Ther (Heidelb). 2025;15(9):2409–21. - 27. Gottlieb AB, Kirby B, Ryan C, et al. The development of the GenPs-SFQ to assess the impact of genital psoriasis on sexual health. Dermatol Ther (Heidelb). 2018;8(1):33–44. - 28. Gottlieb AB, Kirby B, Ryan C, et al. The development of a patient-reported outcome measure for assessment of genital psoriasis symptoms: the genital psoriasis symptoms scale (GPSS). Dermatol Ther (Heidelb). 2018;8(1):45–56. - 29. International Psoriasis Council. Recategorization of Psoriasis Severity. [https://psoriasiscouncil.org/](https://psoriasiscouncil.org/education/disease-severity/) [education/disease-severity/](https://psoriasiscouncil.org/education/disease-severity/). Accessed 5 Dec. - 30. Yang EJ, Beck KM, Sanchez IM, Koo J, Liao W. The impact of genital psoriasis on quality of life: a systematic review. Psoriasis (Auckl). 2018;8:41–7. - 31. National Psoriasis Foundation. Impact of Pain and Itch USA 2024. [https://www.psoriasis.org/advance/](https://www.psoriasis.org/advance/impact-of-pain-and-itch) [impact-of-pain-and-itch.](https://www.psoriasis.org/advance/impact-of-pain-and-itch) Accessed 5 Dec. - 32. Mosca M, Hong J, Hadeler E, Brownstone N, Bhutani T, Liao W. Scalp psoriasis: a literature review of effective therapies and updated recommendations for practical management. Dermatol Ther (Heidelb). 2021;11(3):769–97. - 33. Wang Y, Coyne K, Sofen H, et al. Qualitative analysis and reproducibility assessment of the Scalp Itch Numeric Rating Scale among patients with moderate to severe plaque psoriasis of the scalp. J Dermatol Treat. 2019;30(8):775–83. - 34. Blakely K, Gooderham M. Management of scalp psoriasis: current perspectives. Psoriasis (Auckl). 2016;6:33–40. - 35. Lebwohl M, Bukhalo M, Stein Gold L, et al. A randomized phase 3b study evaluating the safety and effcacy of risankizumab in adult patients with moderate-to-severe plaque psoriasis with nonpustular palmoplantar involvement. J Am Acad Dermatol. 2024;91(6):1150–7. - 36. Strober B, Bachelez H, Crowley J, et al. Effcacy of long-term risankizumab treatment for moderateto-severe plaque psoriasis: subgroup analyses by baseline characteristics and psoriatic disease manifestations through 256 weeks (LIMMitless trial). J Eur Acad Dermatol Venereol. 2024;38(5):864–72. - 37. Gold LS, Tyring SK, Hong HC, et al. 50251 effcacy of risankizumab versus apremilast among patients with scalp or nail psoriasis from the phase 4 IMMpulse study. J Am Acad Dermatol. 2024;91(3):AB38. **Publisher's Note** Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affliations.