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Vitiligo is a chronic depigmenting disorder that significantly impacts the quality of life of patients. Though there have been significant advancements in targeted therapies in skin diseases such as psoriasis or eczema, the progress in the treatment of vitiligo has been slow, with minimal studies assessing the effect of biologics, though there has been recent evidence of the effectiveness of JAK inhibition. This paper reviews the published case reports and studies for the use of systemic targeted therapies including biologics and JAK inhibitors in vitiligo. [ABSTRACT FROM AUTHOR]

Introduction: The efficacy and safety of tildrakizumab for the treatment of plaque psoriasis were demonstrated by randomized clinical studies, but the reappraisal of prolonged experiences in the clinical practice helps to optimize the use of this biologic drug. The aim of this study was to evaluate the long-term efficacy of tildrakizumab in patients with moderate-to-severe psoriasis in the real world. Methods: This is a long-term retrospective observational study in a real-life setting. Overall, 136 adult patients with moderate-to-severe plaque psoriasis and treated with tildrakizumab were included. Results: One hundred percent reduction of Psoriasis Area Severity Index (PASI100) was reached by 21.7% of patients at 4 weeks of therapy and by 51.2% at week 16, and the proportion of patients with this improvement was between 66.9% and 64.5% from 36 weeks to 3 years. The mean PASI of the cohort progressively improved from 12.6 at baseline to 1.8 at week 36 and was stable at 1 year, 2 years and 3 years. We could not confirm a previous observation that patients naïve to biologic had a better response, but we observed that those with a short history of psoriasis had a higher probability of 90% PASI reduction (PASI90) or PASI 100 within 36 weeks, suggesting that early treatment could be useful. Conclusion: This long-term observation in the real life of patients with moderate-to-severe plaque psoriasis receiving tildrakizumab 100 mg showed that PASI100 can be obtained in a high proportion of patients by week 36 and be maintained for up to 3 years. [ABSTRACT FROM AUTHOR]

Background/Objectives: Psoriasis (PsO) is a chronic inflammatory skin disease that severely impacts patients' quality of life (QoL). Its global prevalence is about 2%, with significant regional variations. PsO manifests in the form of erythematous and scaly plaques, causing intense pruritus and discomfort and limiting daily activities. The condition often includes comorbidities such as psoriatic arthritis, cardiovascular diseases, and metabolic syndrome, further deteriorating QoL. Psychological well-being is notably affected, with high levels of depression and anxiety due to the visible lesions, leading to social stigma and isolation. QoL indexes like WHO-QoL and SF-36 assess various well-being aspects, while patient-reported outcomes (PROs) provide a comprehensive understanding of PsO's impact. However, there are no universally shared PROs in outpatient practice to fully understand the impact of the disease and associated therapies. This study aims to evaluate differences between DLQI and WHO-5 in adult patients with moderate-to-severe PsO treated with tildrakizumab 100 mg or 200 mg. Methods: The study was conducted at the University Hospital of Siena, Italy, from May 2023 to April 2024. Data from 15 patients treated with tildrakizumab 200 mg and 15 patients treated with tildrakizumab 100 mg, observed for at least 28 weeks, were recorded. Demographic data, PASI, DLQI, and WHO-5 scores were analyzed. Patients in the 100 mg group (G100) were selected to match the demographic characteristics of the 200 mg group (G200). Reduction rates of DLQI and WHO-5 were assessed at baseline values and after 4, 16, and 28 weeks. Results: Both groups experienced improvements in QoL. The group treated with 200 mg showed more pronounced and rapid reductions in DLQI and WHO-5 scores compared to the 100 mg group. WHO-5 demonstrated faster improvements in overall well-being than DLQI, indicating its greater sensitivity to changes in mental well-being and overall QoL. No differences in adverse events were observed between the two groups, with no major adverse events reported. Conclusions: In our study, WHO-5 proved more sensitive than DLQI in capturing well-being changes in PsO patients treated with tildrakizumab. However, a combined use of both WHO-5 and DLQI questionnaires should be encouraged in clinical practice. Furthermore, this study confirmed the superior QoL improvement associated with tildrakizumab 200 mg compared to 100 mg. Future research should explore the long-term impact on QoL and comparative effectiveness among other biologic therapies in diverse patient populations. [ABSTRACT FROM AUTHOR]

Purpose of the article: Interleukin-23 inhibitors, such as tildrakizumab, have emerged as safe and effective options for the management of psoriasis. Yet their efficacy in elderly patients (aged 65years or more), particularly in those with difficult-to-treat areas involvement, remains insufficiently explored. We conducted this real-life retrospective multicentric observational study to assess the effectiveness of tildrakizumab in elderly patients with moderate-to-severe psoriasis, with involvement of difficult-totreat areas. Materials and methods: We enrolled forty-nine patients aged 65years old or more (mean age 73.1±6.0), all treated with tildrakizumab for at least 28weeks. The effectiveness of tildrakizumab was assessed by Static Physician’s Global Assessment of Genitalia (sPGA-G), fingernail-PGA (f-PGA), palmoplantar PGA (pp-PGA), scalp-specific PGA (sc-PGA), and Psoriasis Area and Severity Index (PASI) scores. Results: Significant improvements in PASI scores were observed within 28weeks of treatment, with 77.5%, 60%, and 45.2% of patients achieving PASI75, PASI90, and PASI100, respectively. The mean PASI decreased significantly from baseline (13.6±9.9) to 1.3±1.7 at week 28. More than 90% of patients had clear sPGA-G and pp-PGA scores and over 70% had clear f-PGA and sc-PGA scores after 28weeks. Conclusions: Our findings suggest that tildrakizumab could be a valuable option for the treatment of elderly patients, including those with difficult-to-treat areas involvement. [ABSTRACT FROM AUTHOR]

Purpose: Tildrakizumab is a selective inhibitor of IL-23 approved for the treatment of moderate-tosevere plaque psoriasis in two dosages. We conducted a 16-week multicenter retrospective study to compare the effectiveness and safety of tildrakizumab 200mg versus tildrakizumab 100mg in patients with a high disease burden or high body weight. Materials and methods: Our retrospective study included 134 patients treated with tildrakizumab 200mg and 364 patients treated with tildrakizumab 100mg from 28 Italian Dermatology Units affected by moderate-to-severe plaque psoriasis. The patients had a body weight above 90kg or a high disease burden (Psoriasis Area and Severity Index [PASI]≥16 or the involvement of difficult-to-treat areas). We evaluated the effectiveness of tildrakizumab at the week-16 visit in terms of PASI90, PASI100 and absolute PASI ≤ 2. Results: After 16weeks of treatment with tildrakizumab 200mg, PASI90 was reached by 57.5% of patients and PASI100 by 39.6% of patients. At the same time point, 34.3% and 24.2% of patients treated with tildrakizumab 100mg achieved PASI90 and PASI100, respectively. Conclusions: Our data suggest that tildrakizumab 200mg has better effectiveness than tildrakizumab 100mg in patients with a body weight ≥ 90kg and a high disease burden. [ABSTRACT FROM AUTHOR]

Detecting the association of genetic variants to the response of biological therapy represents an important advance in developing a personalized therapy. The aim of this work was to study the association of polymorphisms with an optimal response to tildrakizumab in patients with psoriasis in a real‐life clinical practice. Ninety patients with plaque psoriasis recruited from—Spanish hospitals receiving tildrakizumab for at least 24 weeks were genotyped for 180 polymorphisms. Optimal response to tildrakizumab was evaluated by absolute PASI ≤1 at 6 and 12 months. Polymorphisms corrected for weight and disease duration with an FDR <0.15 were included in a multiple regression model. Sixty three percent of patients achieved an absolute PASI ≤1 at 6 months, while 71% did so after 12 months. Disease duration (>27 years) and weight (>76 kg) were associated with treatment response; after correcting by these factors, no association (FDR >0.15) was found for any polymorphism and response to tildrakizumab at 6 months. The analysis at 12 months identified the genotype GG for rs610604 (TNFAIP3), CT for rs9373839 (ATG5), and delCTGT/delCTGT for rs72167053 (PDE4D) as risk factors to not achieve an optimal response (PASI ≤1), while CT for rs708567 (IL17RC) was protective, independently of weight and disease duration (FDR <0.15). The final multivariable model at 12 months showed an AUC of 0.90 (95% CI 0.82 to −0.98). We identified a set of polymorphisms that could be helpful to identify psoriatic patients with an optimal response to tildrakizumab at 12 months in real‐world practice conditions. [ABSTRACT FROM AUTHOR]

Background: Tildrakizumab, the IL-23 inhibitor, is used to treat plaque psoriasis and psoriatic arthritis. Many studies have reported adverse drug reactions (ADRs) associated with Tildrakizumab. Objective: The aim of this study was to describe ADRs associated with Tildrakizumab monotherapy by mining data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: The signals of Tildrakizumab-associated ADRs were quantified using disproportionality analyses such as the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multiitem gamma Poisson shrinker (MGPS) algorithms. Results: A total of 10,530,937 reports of ADRs were collected from the FAERS database, of which 1,177 reports were identified with tildrakizumab as the "primary suspect (PS)". Tildrakizumab-induced ADRs occurred against 27 system organ classes (SOCs). A total of 32 significant disproportionality Preferred Terms (PTs) conformed to the algorithms. Unexpected significant ADRs such as coronavirus infection, herpes simplex, diverticulitis, atrial fibrillation and aortic valve incompetence were also possible. The median time to onset of Tildrakizumabassociated ADRs was 194 days (interquartile range [IQR] 84-329 days), with the majority occurring, within the first 1 and 3 months after initiation of Tildrakizumab. Conclusion: This study identified a potential signal for new ADRs with Tildrakizumab, which might provide important support for clinical monitoring and risk prediction. [ABSTRACT FROM AUTHOR]

Tildrakizumab is a humanised IgG1/k-type monoclonal antibody that targets the p19 protein subunit of IL23. Despite its effectiveness and safety have been widely reported by clinical trials and real-life experiences, data regarding its use on patients who previously failed anti-IL17 (brodalumab, ixekizumab, bimekizumab and/or secukinumab) are scant. Therefore, further studies on this topic would be beneficial for clinicians in guiding the selection of biologic shifting, considering that anti-IL23, − 12/23, and -IL17 partially share their therapeutic targets. In this context, we performed a 28-week, single-center, real-life, retrospective study, with the aim of assessing the efficacy and safety of tildrakizumab in patients who previously failed anti-IL17, also focusing the attention on psoriasis located in difficult-to-treat areas (scalp, palms or soles, fingernails, genitals). A total of 23 patients (12 male, 52.2%; mean age 52.8 ± 12.4 years) were enrolled. Of these, 11 (47.8%) failed secukinumab, 7 (30.4%) ixekizumab, 3 (13.0%) brodalumab, 1 (4.3%) both secukinumab and ixekizumab and 1 (4.3%) bimekizumab. At baseline, mean PASI and BSA were 12.8 ± 5.9 and 18.7 ± 9.6, respectively. At W16 PASI75 and PASI90 response were achieved by 15 (65.2%), and 9 (39.1%) patients, respectively, whereas 19 (82.6%) and 13 (56.6%) subjects reached these scores at W28. One (4.3%) case of primary inefficacy and 1 (4.3%) case of secondary inefficacy were assessed. Finally, no severe adverse events were collected. Tildrakizumab seems to be a valuable option in selected patients with psoriasis unresponsive to anti-IL17, suggesting that prior exposure to biological therapies seem not directly affect its effectiveness. [ABSTRACT FROM AUTHOR]

Introduction: Plaque psoriasis is a chronic condition that may impact patients' work productivity. Tildrakizumab, an interleukin-23 p19 inhibitor, is approved for treatment of moderate-to-severe plaque psoriasis in adults. However, the effect of tildrakizumab treatment on work productivity in patients with psoriasis is not well characterized. Methods: In this multicenter, open-label, uncontrolled phase 4 study (NCT03718299), patients with moderate-to-severe plaque psoriasis received tildrakizumab 100 mg at week 0, week 4, and every 12 weeks thereafter through week 52. Patients completed the Work Productivity and Activity Impairment Questionnaire: Psoriasis (WPAI:PSO) at baseline and every 12 weeks from week 16 through week 64. The following four domains of the WPAI:PSO were examined: absenteeism (percentage of time missed from work due to psoriasis), presenteeism (percentage reduction of productivity while at work due to psoriasis), total activity impairment (percentage impairment in activities other than work due to psoriasis), and total work productivity impairment (total percentage of work impairment from both absenteeism and presenteeism due to psoriasis). Missing data were not imputed. Results: Of the 55 patients enrolled, 31 patients completed all domains of the WPAI:PSO at week 64. From baseline to week 64, respectively, mean ± standard deviation (SD) scores improved for presenteeism (20.5 ± 21.7 to 2.6 ± 5.8; P < 0.001), total activity impairment (29.5 ± 26.6 to 4.4 ± 9.4; P < 0.001), and total work productivity impairment (20.9 ± 22.2 to 2.6 ± 5.8; P < 0.001). The mean ± SD score for absenteeism decreased from 1.1 ± 5.7 at baseline to 0.0 ± 0.0 at week 64, but this change was not statistically significant. Conclusion: Tildrakizumab treatment mitigated work productivity loss due to psoriasis as measured by the presenteeism, total activity impairment, and total work productivity impairment domains of the WPAI:PSO. Trial Registration: ClinicalTrials.gov identifier, NCT03718299. [ABSTRACT FROM AUTHOR]

Copyright of Remedia is the property of Medical Tribune CZ, s.r.o. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: As a form of precision medicine, this study aimed to investigate the specific patient population that would derive the greatest benefit from tildrakizumab, as well as the mechanism of action and efficacy of tildrakizumab in reducing the occurrence of psoriatic arthritis (PsA). Methods: To achieve this, amulti-center, prospective cohort study was conducted, involving a population of 246 psoriasis patients who had not received any systemic therapy or topical finger therapy between January 2020 and April 2023. Two independent clinicians, who were blinded to the study, analyzed nailfold capillary (NFC) abnormalities, such as nailfold bleeding (NFB) and enlarged capillaries, as well as the incidence of new PsA. Additionally, the factors that determined the response of psoriasis after seven months of tildrakizumab treatment were examined. The study also examined the quantity and role of regulatory T cells (Tregs) and T helper 17 cells both pre- and post-treatment. Results: The severity of psoriasis, as measured by the Psoriasis Area and Severity Index (PASI), was found to be more pronounced in the tildrakizumab group (n=20) in comparison to the topical group (n=226). At 7months after tildrakizumab treatment, multivariate analysis showed that those 65 years and older had a significantly better response to treatment in those achieved PASI clear or PASI 2 or less (Likelihood ratio (LR) 16.15, p<0.0001; LR 6. 16, p=0.01). Tildrakizumab improved the number and function of Tregs, which had been reduced by aging. Tildrakizumab demonstrated significant efficacy in improving various pathological factors associated with PsA. These factors include the reduction of NFB, enlargement of capillaries, and inhibition of PsA progression. The hazard ratio for progression to PsA was found to be 0.06 (95% confidence interval: 0.0007-0.46, p=0.007), indicating a substantial reduction in the risk of developing PsA. Discussion: Tildrakizumab's effectiveness in improving skin lesions can be attributed to its ability to enhance the number and function of Tregs, which are known to decline with age. Furthermore, the drug's positive impact on NFB activity and capillary enlargement, both of which are recognized as risk factors for PsA, further contribute to its inhibitory effect on PsA progression. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory skin disease characterized by plaque formation. Interleukin (IL)‐23 is upregulated in psoriatic lesions and is thought to be a major regulator of the Th17 pathway in psoriasis pathogenesis. Three monoclonal antibodies targeting the IL‐23p19 subunit, guselkumab, tildrakizumab, and risankizumab, have been approved for psoriasis therapy. The balance between cytokines IL‐23 and IL‐12 can affect antitumor and pro‐tumor immune activities, and patients with psoriasis may have higher rates of cancer than the general population. Moreover, a chronic inflammatory state typical of psoriasis may induce protumorigenic effects, however, the potential risk of malignancy in patients taking these drugs remains largely unknown. This study investigated the occurrence of malignancies as suspected adverse reactions (SARs) potentially associated with IL‐23 inhibitors by analyzing real‐world data from the European EudraVigilance database. Although indicatory, these real‐world data seem to confirm the potential association between the IL‐23 inhibitors risankizumab and tildrakizumab, and the occurrence of SARs linked to cancer in patients with psoriasis and, according to a gender perspective, they show that this relationship is asymmetrically distributed between women and men, with a clear prevalence of oncologic SARs in men. [ABSTRACT FROM AUTHOR]

The treatment of hidradenitis suppurativa (HS) has always been a real challenge for dermatologists; to date, the only biologic drugs approved for HS are adalimumab, an anti-tumor necrosis factor (TNF)-α drug, authorized in 2015, and secukinumab, recently licensed. The management of this condition is challenging as the available treatments show variable results, and the course of the condition is often chronic-recurrent; therefore, it will be necessary for the future to identify new therapeutic targets for HS. In recent years, studies have focused on the development towards new therapeutic targets. The purpose of our review was to perform a comprehensive literature review of real-life data on anti-IL23 (guselkumab, tildrakizumab, and risankizumab) in HS to summarize the existing evidence on the efficacy and safety of these drugs. We selected 64 articles, among which 32 had the characteristics that we were looking for in our review. To date, the positive data expressed in real-life experiences contrast with the three existing Phase 2 studies conducted so far, where it seems that these drugs may be useful only for a subgroup of patients with HS whose features need to be elucidated. Data from Phase 3 studies and other real-life experiences, perhaps more detailed and with higher numbers, will certainly be needed to fully understand the efficacy and safety of this class of drugs. [ABSTRACT FROM AUTHOR]

The approved biologics targeting interleukin (IL)-23 p19 for the treatment of moderate-to-severe plaque psoriasis, including guselkumab, tildrakizumab, and risankizumab, have generally favorable safety profiles. The aim of the current review is to describe in detail the safety of these selective inhibitors. A literature search was performed using PubMed from inception to 1 November 2022, to identify clinical trials and real-world evidence publications using the keywords "guselkumab," "tildrakizumab," and "risankizumab." Overall, the most common adverse events (AEs) associated with IL-23 p19 inhibitors in clinical trials were nasopharyngitis, headache, and upper respiratory tract infections. Rates of serious AEs and AEs of interest, including serious infections, nonmelanoma skin cancer (NMSC), malignancies excluding NMSC, major adverse cardiovascular events, and serious hypersensitivity reactions, were not increased with long-term use in clinical trials. Selectively targeting IL-23 p19 was also not associated with elevated risk of opportunistic infections, tuberculosis reactivation, oral candidiasis, or inflammatory bowel disease. Results from real-world studies were similar, supporting the safe long-term use of these biologics in a wider population of patients with psoriasis, including older patients, patients for whom multiple biologics failed, and those with comorbidities such as obesity, metabolic syndrome, cardiovascular disease, dyslipidemia, diabetes, hypertension, and psoriatic arthritis. This review is limited by the lack of direct comparisons among therapeutic agents due to differences among study designs and safety data reporting methods. In conclusion, the favorable safety profiles of IL-23 p19 inhibitors support their long-term use in the management of patients with moderate-to-severe psoriasis. [ABSTRACT FROM AUTHOR]

Copyright of Remedia is the property of Medical Tribune CZ, s.r.o. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Plaque psoriasis and hidradenitis suppurativa are chronic inflammatory skin conditions with common pathogenetic pathways. Methods: We report the case of a 38-year-old man with 15-year history of psoriasis and hidradenitis suppurativa successfully treated with tildrakizumab for both conditions. After treatment failure to adalimumab, secukinumab, and guselkumab, tildrakizumab therapy was initiated and resulted in complete remission of psoriasis and the achievement of hidradenitis suppurativa clinical response after 40 weeks, without reporting adverse events. These responses were maintained at week 52. Conclusion: Tildrakizumab may be an effective and safe therapeutic option for concomitant psoriasis and hidradenitis suppurativa. [ABSTRACT FROM AUTHOR]

Nowadays, the biological equipment available for the treatment of moderate-to-severe psoriasis is plenty. Anti-interleukin-23 represents the latest class of biologic approved for the management of moderate-to-severe psoriasis. Their efficacy and safety have been assessed through two major sources: clinical trials (CTs) and real-world experiences data (RWE). Notably, the two sources differ from one another, but together, they complement information and current knowledge on both efficacy and safety of biological therapy. We carry out a review on CTs and RWE reports on the latest group of biological approved for moderate-to-severe psoriasis: anti-IL23 (guselkumab, risankizumab, and tildrakizumab). [ABSTRACT FROM AUTHOR]

Background/Objectives: For patients with vulvovaginal lichen planus (VLP), there exists limited data on the comparison between patient quality of life treated with topical and/or systemic treatments. We characterised the treatment outcomes of VLP using the vulvar quality of life index (VQLI) comparing women treated with systemic immunosuppression, including humanised interleukin‐23 monoclonal antibody tildrakizumab, to those treated with topical corticosteroids alone. Methods: A retrospective cohort study is reported from a dermatology practice in Sydney, Australia. Electronic medical records for adult women with a diagnosis of VLP were reviewed identifying 112 subjects. VQLI scores in four domains (symptoms, activities of daily living, anxiety and sexual function) were compared between women able to maintain remission of disease with topical monotherapy to those with recalcitrant disease requiring treatment with conventional systemic immunosuppressants and for those not responding to this treatment, tildrakizumab. Results: At baseline women requiring tildrakizumab treatment had the highest total VQLI score (24.6), whilst women whose disease was maintained on topical treatment had the lowest (19.2). Women treated whilst on tildrakizumab had significant reduced total mean VQLI scores (13.32, 95% CI 8.61–18.01) than when treated with other Systemic (22.00, 95% CI 16.52–27.53; p < 0.001) or topical (21.71, 95% CI 16.13–26.32; p < 0.01). Women treated with tildrakizumab demonstrated statistically significant decreases in mean VQLI scores in all four domains of the VQLI compared to previous scores when on other systemic treatments. Conclusion: We report the largest cohort study to date of adult women with VLP evaluating treatment responses to topical and systemic agents using the VQLI. In women whose VLP did not improve with conventional systemic immunosuppressants, tildrakizumab resulted in statistically significant decrease in mean VQLI scores in all 4 domains, highlighting tildrakizumab as an alternative treatment for VLP. [ABSTRACT FROM AUTHOR]

Tildrakizumab is a humanized IgG1κ monoclonal antibody that selectively targets the p19 subunit of interleukin IL-23, thereby inhibiting the IL-23/IL-17 axis, which is primarily implicated in the immunopathogenesis of psoriasis. Tildrakizumab is approved for the treatment of moderate-to-severe plaque-type psoriasis in adults based on the evidence of two randomized and controlled phase-III clinical trials (reSURFACE 1 and reSURFACE 2). Here, we report our real-life experience treating 53 psoriatic patients (19 female and 34 male) who were administered tildrakizumab every 12 weeks and received follow-ups over 52 weeks. Descriptive and inferential statistical analyses were performed, in particular the Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI) and, if applicable, the Nail Psoriasis Severity Index (NAPSI) and Palmoplantar Psoriasis Physician Global Assessment (PPPGA). These were assessed at baseline and after different timepoints (weeks) during the follow-up period. We described and evaluated demographical and epidemiological characteristics in our cohort group, focusing on comorbidities. In this group, 35.9% of patients were female and 64.1% were male, with 47.1% being smokers and with a mean age of 51.2 years. A total of 37.7% of these patients was affected by scalp psoriasis; regarding comorbidities, hypertension was the most frequent (32.5%), followed by psoriatic arthritis (PsA) (18.60%) and diabetes (13.9%). At week 52, 93%, 90.2% and 77% of patients achieved a PASI reduction ≥75% (PASI 75), PASI 90 and PASI 100, respectively. In addition, NAPSI, PPPGA and DLQI scores were significantly reduced by week 52. In our cohort of complex psoriasis patients, disease remission began at the end of the fourth week of treatment and remained constant from week 16 to week 52. [ABSTRACT FROM AUTHOR]

Background: IL-23 inhibitors are the latest class of biologic drugs approved for moderate-to-severe psoriasis. Objectives: to investigate real-life safety and efficacy of tildrakizumab. Methods: demographic data, medical history, psoriasis disease history, PASI, DLQI, BSA, NAPSI were recorded at weeks 0, 12, 24, 36. Results: PASI, BSA, DLQI and NAPSI all decreased rapidly during the 36 week follow-up period. PASI score reduced from 12.28 to 4.65 by week 12, followed by a further decrease to 1.18 at week 36 Multiple logistic regression showed that smoking, BMI ≥30, ≥3 comorbidities, previous systemic traditional or biologic drugs, psoriatic arthritis nor difficult-to-treat areas influenced the reduction of PASI and NAPSI scores during treatment with tildrakizumab (P >.05). Conclusions: we assessed a good performance of tildrakizumab in patients with multiple comorbidities, multi-failure, elderly patients, and in subjects with psoriatic arthritis. [ABSTRACT FROM AUTHOR]

Background: Tildrakizumab, an anti-IL-23, showed promising efficacy and safety profiles in two randomized clinical-trials (reSURFACE-1 and reSURFACE-2), comparing tildrakizumab superiority to placebo and etanercept. Due to its recent availability in clinical-practice, real-life data are still limited. Objective: To assess the efficacy and safety of tildrakizumab in a real-world-practice in patients suffering from moderate-to-severe psoriasis. Methods: A 52-week observational retrospective study enrolled patients suffering from moderate-to-severe plaque-psoriasis, starting tildrakizumab treatment. Results: A total of 42 patients were included in the study. Mean PASI showed a significant reduction at each follow-up (p< 0.001), reducing from 13.5± 5.9 at baseline, 2.8± 3.8 at week-28, resulting stable up to week-52. High rates of patients reached both PASI90 and PASI100 responses at both week 16 (PASI90: 52.4%, PASI100: 33.3%) and week 28 (PASI90: 76.1%, PASI100: 61.9%), maintaining these up to week 52 (PASI90: 73.8%, PASI100: 59.5%). The impact of treatment on patient's quality of life has been evaluated with DLQI, which showed a significant reduction during follow-ups. Conclusion: Our data confirm tildrakizumab as an effective and generally safe treatment for the management of moderate-to-severe psoriasis, with high rates of both PASI90 and PASI100 responses, and very few reported adverse events, up to 52 weeks of follow-up. [ABSTRACT FROM AUTHOR]

The introduction of biologic drugs revolutionized the management of moderate-to-severe forms of psoriasis. However, safety concerns still remain, particularly on patient affected by opportunistic infections. In this scenario, the safety of biologic drugs in patient with HBV infection is debated. Globally, screening for hepatitis before starting biological treatment is mandatory as well as a referral to an infectivologist and eventual prophylactic management should be evaluated case by case, also considering risk factors. On the one hand, the use of anti-Tumor Necrosis Factor seems to increase the risk of HBV reactivation, conversely, the use of recently approved classes of biologics [anti-interleukin (IL) 17 and anti-IL23] seems to have a lower risk of HBV reactivation. However, the evidence on the safety of anti-IL23 drugs in patients affected by HBV is scant, particularly for patients undergoing treatment with tildrakizumab. Herein, we report the first case of a female patient affected by moderate-to-severe psoriasis and with chronic HBV infection undergoing prophylaxis, successfully treated with tildrakizumab without reporting hepatitis reactivation. Even if limited, our case seems to confirm available evidence about the safety of anti-IL23, particularly tildrakizumab, on patients with chronic HBV infection undergoing prophylaxis. [ABSTRACT FROM AUTHOR]

Five-year tildrakizumab safety data have been reported as exposure-adjusted incidence rates (EAIRs) of patients with events per 100 patient-years (PYs) of exposure. To present 5-year safety data from reSURFACE 1/2 phase 3 trials as EAIRs of events per 100 PYs of exposure, and the number needed to harm (NNH) for one adverse event of special interest (AESI) to occur. Pooled analysis from two randomized controlled trials in patients with moderate-to-severe plaque psoriasis (n = 1800). PSOLAR registry was used as safety reference data for NNH estimation. Rates of AESI with tildrakizumab were comparable with rates reported in PSOLAR. The NNH for one-year severe infection occurrence was 412 with tildrakizumab 200 mg, and negative for tildrakizumab 100 mg due to lower rates in reSURFACE trials; the NNH for malignancy was 990 for one year with tildrakizumab 100 mg (negative for tildrakizumab 200 mg); and the NNH for major adverse cardiovascular events was 355 for one year with tildrakizumab 200 mg (negative for tildrakizumab 100 mg). Tildrakizumab demonstrated a favorable safety profile over 5 years with low rates of AESI, comparable to those of the PSOLAR. Consequently, the NNH for AESI with tildrakizumab were very high or negative due to lower event rates for tildrakizumab. [ABSTRACT FROM AUTHOR]

Tildrakizumab is an anti–interleukin-23 p19 monoclonal antibody approved for the treatment of adults with moderate-to-severe plaque psoriasis. Little real-world evidence is available regarding the effects of tildrakizumab on patients' health-related quality of life (HRQoL) and patient-reported symptoms. This real-world study of tildrakizumab evaluated changes in HRQoL and clinical symptoms in patients with psoriasis. In this Week (W)28 interim analysis of a 64-week Phase 4 study (NCT03718299), patients received tildrakizumab 100 mg at W0, W4, and every 12 weeks thereafter. Endpoints were improvement from baseline in Psychological General Well-Being Index (PGWBI), Dermatology Life Quality Index (DLQI), and Itch-, Pain-, and Scaling-Numerical Rating Scale scores through W28. Of 55 patients enrolled, 53 were assessed at W28. Mean (standard deviation [SD]) total PGWBI score improved from baseline to W28 (change, 3.7 [12.4]; p =.033), as did the positive well-being (1.0 [2.9]; p =.018) and general health (1.5 [2.2]; p <.001) domain scores. Mean (SD) DLQI score improved by −3.9 (4.3) at W4 and by −7.6 (5.1) at W28 (p <.001). Patient-reported symptoms improved starting at W4 (p <.001). Tildrakizumab treatment improved HRQoL and patient-reported symptoms in patients with psoriasis in a real-world setting. Clinical trial registration: [ABSTRACT FROM AUTHOR]

Clinical trials have shown promising results for interleukin-23 inhibitors in the treatment of psoriasis. The drugs have been used in clinical practice since 2017. To investigate the drug survival and effectiveness of interleukin-23 inhibitors in the treatment of psoriasis and psoriatic arthritis (PsA) in a real-world setting. The study was a retrospective analysis of patients treated with either guselkumab, tildrakizumab, or risankizumab at the Department of Dermatology, Aarhus University Hospital, during the period from June 11 2018, to July 14 2021. A total of 80 patients were included. During the study, 19 patients discontinued treatment with an interleukin-23 inhibitor, and mean treatment duration (SD) was 61.4 weeks (43.7). Seventy-six patients (95%) had previous use of ≥1 biologic. One-year drug survival was 81.0%. Among patients, 64.3% achieved a Psoriasis Area and Severity Index (PASI) ≤ 2 at weeks 12–17; 61.3%, at weeks 40–60. There was no statistically significant difference between the drugs regarding the chance of achieving PASI ≤ 2 (p>.05). Twenty-two patients (27.5%) had PsA. Among these, 40.9% and 36.4% achieved complete remission and partial remission, respectively. Interleukin-23 inhibitors appear to have high and similar drug survival and effectiveness in patients with difficult-to-treat psoriasis and PsA. [ABSTRACT FROM AUTHOR]

The evidence on treating older patients with psoriasis with modern biologics is scarce. This study compared the efficacy and safety of tildrakizumab among younger and older patients with psoriasis (<65/≥65 years) in a post hoc analysis of 2 phase III trials (reSURFACE1/2, n=1,862). Tildrakizumab 100 mg/200 mg was administered at weeks 0/4/every 12 weeks thereafter. At week 28, patients with ≥75% improvement in baseline Psoriasis Area and Severity Index (PASI75) in reSURFACE1 were re-randomized to the same tildrakizumab dose or placebo; in reSURFACE2, PASI75 responders to 200 mg were re-randomized to tildrakizumab 100 mg or 200 mg; PASI75 responders to 100 mg maintained their dose. At weeks 64/52 (reSURFACE1/2), PASI50 responders entered an extension period (weeks 256/244). Outcomes were proportion of patients with PASI<3, Dermatology Life Quality Index (DLQI) 0/1, comorbidities, comedication, and side-effects. The proportion of patients with a PASI<3 was similar and maintained (tildrakizumab 100 mg and 200 mg, week 244: 83.3% and 84.1%/92.3% and 100.0%); DLQI 0/1 proportions at week 52 were 66.8% and 72.0%/68.3% and 81.3%. Comorbidity and comedication were more common in older patients. The safety profile of tildrakizumab appeared favourable in both groups. Tildrakizumab in patients ≥65 years appears effective and safe in longterm psoriasis management. These findings might assist treatment selection and overcome treatment reluctance. [ABSTRACT FROM AUTHOR]

Background: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis characterised by musculoskeletal and extra‐articular manifestations, most notably psoriasis. While the underlying pathogenetic mechanisms are not yet fully understood, a central role has been identified for the IL‐23/IL‐17 pathway. Objectives: We briefly describe the role of IL‐23 in the pathogenesis of PsA and go on to describe the available anti‐IL‐23 agents and their place in the management of PsA. Methods: This is a narrative review of the current literature, focussing on the results of the phase 3 studies in PsA for the IL‐12/23 p40 inhibitor ustekinumab and the more recent IL‐23 p19 inhibitors guselkumab, risankizumab and tildrakizumab. Results: IL‐23 triggers expression of IL‐17 and other effector cytokines in a variety of cells, leading to tissue inflammation and injury. Targeting IL‐23, particularly with p19 inhibitors, appears to be an effective and safe strategy for multiple clinical domains in PsA, most notably the skin, with some differences in efficacy emerging between these agents. Conclusion: The development of IL‐23 inhibitors represents a significant advance in the management of psoriatic disease. In the absence of head‐to‐head studies, future data emerging from real‐world experiences of individual IL‐23 p19 inhibitors will help inform the use of these agents in relation to other biologics in PsA. [ABSTRACT FROM AUTHOR]

Introduction: As with most medicines historically, clinicians prescribing tildrakizumab have relied on information derived from registration studies undertaken in a prospective controlled clinical trial setting. More recently, clinicians, policymakers, and commissioners increasingly rely on real-world data to inform both policy and practice. Methods: A retrospective real-world data study was undertaken at four specialist dermatology departments in the United Kingdom. All adult patients treated with tildrakizumab for moderate-to-severe plaque psoriasis were included, with data being collected for 122 patients. Results: Psoriatic patients on tildrakizumab tended to be overweight (median body mass index of 32 (range 19–59) (n = 61); 26/68 (38%) < 90 kg, 32/68 (47%) between 90 and 120 kg, and 10/68 (15%) > 120 kg). The study population had high levels of comorbidities (83/116, 72%), multiple special sites (39/117, 33%), and histories of biological treatments (81/100, 81%). Most patients (61/80, 76%) initiated on tildrakizumab were switched from another biological treatment. Tildrakizumab was effective, with 91/122 (75%) patients remaining on treatment for the duration of the study—a median of 12 months per patient (range 1–29 months)—and achieving a change in median Psoriasis Area and Severity Index (PASI) from 12 to 0.35 and in Dermatology Life Quality Index (DLQI) from 20 to 0. The response rate was 57/66 (86%) when tildrakizumab was used as the first- or second-line biologic compared to 19/31 (61%) when used as the third- to seventh-line. Thirty-three (78.6%) patients over 90 kg of weight received the 200-mg dose of tildrakizumab. All but one (n = 8) patient with body weight over 120 kg maintained response over time. There was one treatment discontinuation; a patient who had a local sensitivity reaction. Conclusions: In UK clinical practice, tildrakizumab was well tolerated and effective at doses of 100 mg or 200 mg in a range of patient phenotypes. [ABSTRACT FROM AUTHOR]

Introduction: Tildrakizumab (TIL), a monoclonal antibody that selectively targets interleukin-23p19, has been approved for the treatment of moderate-to-severe plaque psoriasis. According to the European Medicines Agency Summary of Product Characteristics, the recommended dose is 100 mg, but a 200 mg dose can be used in patients with certain characteristics, such as a high disease burden or body weight (BW) ≥ 90 kg. Fixed one-dose biological therapies tend to become less effective in patients with high BW. This post-hoc study describes the long-term efficacy of TIL across different BWs in pivotal clinical trials. Methods: A 5-year pooled analysis of two double-blind, randomised, controlled phase III trials—reSURFACE 1 and 2—was performed. Efficacy measures were the proportions of the patients with an absolute Psoriasis Area and Severity Index (PASI) of < 3 and < 1 and a Dermatology Life Quality Index (DLQI) of 0/1. The study population included patients randomised to TIL 100 mg or TIL 200 mg who received ≥ 1 TIL dose up to week 12 (part 1 of the trial) or up to week 28 (part 2) and patients who were responders (≥ 75% improvement in PASI) to TIL 100 or TIL 200 mg at week 28 and who were maintained on the same dose up to week 244. Efficacy was evaluated by analysing BW subgroups at weeks 28, 52 and 244. Missing data were analysed using multiple imputation. Safety was assessed in the all-patients-as-treated population. Results: The proportions of TIL-treated patients with PASI < 3 and < 1 (up to week 244) and DLQI 0/1 (up to week 52) were similar for patients with BW < 90 or ≥ 90 kg, regardless of dose. Patients ≥ 120 kg had greater efficacy outcomes at the 200 mg dose. Safety outcomes were similar regardless of treatment dose and weight (< 120/≥ 120 kg). Conclusion: In patients with BW ≥ 120 kg, TIL 200 mg is more efficacious than TIL 100 mg, with similar favourable safety profiles obtained regardless of dose and BW group. Trial registration: ClinicalTrials.gov NCT01722331 (reSURFACE 1) and NCT01729754 (reSURFACE 2). [ABSTRACT FROM AUTHOR]

Background: Absolute Psoriasis Area and Severity Index (PASI) is a key endpoint in psoriasis management. Petto et al. [Pharm Stat. 2019;18(1):4–21] developed a statistical method to estimate the proportion of patients reaching absolute PASI response given baseline PASI score and proportion of patients achieving relative improvements at predefined time points. Objectives: To test this method on clinical data from two phase 3 tildrakizumab trials (reSURFACE 1/2) comparing estimated absolute PASI ≤1/≤2/≤3/≤5 responses with reference responses from clinical databases. Methods: Reference PASI responses of ≤1/≤2/≤3/≤5 were extracted from clinical databases. Estimation of absolute PASI ≤1/≤2/≤3/≤5 response rates at week (W) 12 and W28 by treatment and trial were performed. Differences between estimated and reference responses were analysed. Bland-Atman limits of agreement and Passing-Bablok regression to assess variations between estimated and reference responses were performed. Results: Differences between estimated and reference absolute PASI ≤1/≤2/≤3/≤5 responses at W12 and W28 by treatment and trial were of little clinical relevance with an overall mean difference in PASI response proportion of −2.2% (e.g., for the tildrakizumab 100-mg arm, original proportions of patients achieving PASI of ≤1/≤2/≤3/≤5 at W28 were 38.5%/52.2%/63.5%/73.9% and 39.8%/54.8%/63.6%/76.9% [reSURFACE 1 and 2, respectively] vs. estimated proportions of 33.2%/49.8%/62.5%/78.3% and 34.3%/51.6%/64.5%/79.9%). Limits of agreement were −7.1% to 1.4% at W12 and –6.8% to 4.3% at W28. Scatterplots revealed linearity that stood the cusum test in Passing-Bablok regression with slope 1.14 (95% confidence intervals: 1.06 to 1.20). Conclusion: Good estimates of absolute PASI response rates were achieved with the application of the statistical method to tildrakizumab data reported in the phase 3 studies, in particular in the verum study arms. Our data support the method provided by Petto et al. [2019] to estimate proportions of psoriasis patients reaching absolute PASI value thresholds using relative PASI improvements. [ABSTRACT FROM AUTHOR]

Introduction: Tildrakizumab 200 mg/2 mL pre-filled syringe is a new preparation of tildrakizumab that is developed to facilitate patients' compliance. This phase I clinical trial compares the local tolerability, safety, and subjects' preferred method of administration of tildrakizumab when administered as a new single 200 mg/2 mL subcutaneous injection or as two 100 mg/1 mL subcutaneous injections in healthy subjects. Methods: Visual analogue scores were used to self-assess injection site pain immediately (< 1 min) after each administration and at 1 h and 48 h after each administration. Treatment injection site reactions were assessed at 1 h and 48 h after each administration. Treatment safety was monitored throughout the study period. Subjects' preferred method of administration was assessed 4 weeks after the last administration (day 56). Results: No statistically significant difference in visual analogue scores and injection site reactions was detected between the two treatments. Treatment-emergent adverse events were mild, and there were no deaths or serious adverse events. Most subjects (61.5%) preferred the treatment when administered as a single 200 mg/2 mL subcutaneous injection rather than as two 100 mg/mL subcutaneous injections. Conclusions: Administration of 200 mg tildrakizumab as a single 2 mL subcutaneous injection was safe, well tolerated, and preferred over two separate 100 mg/1 mL subcutaneous injections by healthy subjects. Eudract No. 2020-000183-37. [ABSTRACT FROM AUTHOR]

Guselkumab, tildrakizumab, and risankizumab, acting on interleukin(IL)23 axis, have been recently approved for psoriasis management. However, real-life data regarding their comparison are scant. The aim of our real life study was to perform an indirect efficacy and safety comparison among anti-IL23s, particularly focusing on difficult-to-treat areas. A 2-year single-center retrospective observational study was performed enrolling moderate-to-severe psoriasis patients treated with anti-IL23. For each patient, clinical and demographical data were collected at baseline and at week4, week16, and week28. PASI, BSA, NAPSI, and specific BSA regarding difficult to treat areas were evaluated. One hundred and fifty patients were included in the study: 63 (42%) received guselkumab, 21 (14%) tildrakizumab, and 66 (44%) risankizumab. The three groups were comparable for age, sex, and disease severity, only differing for psoriasis duration, psoriatic arthritis prevalence (higher in guselkumab), and previous systemic treatment failure (lower for tildrakizumab). Mean PASI and BSA significantly reduced from baseline up to week 28 without significant differences among the 3 drugs (reduction of 95–97.3% for PASI and 94.8–96.7% for BSA). No significant differences were registered for PASI75, 90, or 100 responses, in particular, PASI100 was reached by 73.4–85% of patients. As regards difficult-to-treat areas, all the drugs displayed a high efficacy, with significant differences registered only for the rapidity of action on palmoplantar psoriasis. Our 28-weeks study demonstrated a comparable efficacy and safety profile for all anti-IL23, with guselkumab and risankizumab appearing slightly faster than tildrakizumab particularly on palmoplantar lesions in the short-term. The interleukins (IL) 23/17 axis seems to play a key role in psoriasis management. Guselkumab, tildrakizumab, and risankizumab, selectively blocking the IL23 signaling, have been recently approved for psoriasis management. Real-world data regarding different anti-IL23 comparisons are scant. Our 28-weeks study showed that there were not any significant differences in terms of efficacy and safety between each anti-IL-23 apart from palmoplantar area where guselkumab and risankizumab showed higher efficacy. Globally risankizumab and guselkumab appeared slightly faster than tildrakizumab. Guselkumab, tildrakizumab, and risankizumab are valid weapons for psoriasis management, also for difficult-to-treat areas (scalp, nails, genitalia, lower limbs, and palmo-plantar area). [ABSTRACT FROM AUTHOR]

Interleukin (IL)-23 inhibitors, guselkumab, risankizumab, and tildrakizumab, represent the latest class of biologics approved for the treatment of moderate-to-severe psoriasis. Since their approval numerous real-life studies were published on anti-IL-23 use in routine clinical practice. Indeed, real-life data are important to improve the dermatological decision-making process, including patients who are typically excluded from clinical trials, such as subjects suffering from several comorbidities, subjects on polypharmacy, as well as multifailure patients. Herein, we performed a comprehensive literature review about real-life data available on guselkumab, risankizumab, and tildrakizumab. Real-life data of anti-IL-23 seem to confirm the promising results of IL-23 shown by clinical trials, highlighting the efficacy and safety profiles of this new class of biologics also in clinical practice. [ABSTRACT FROM AUTHOR]

Successful treatment has been described with the TNF- inhibitors adalimumab and infliximab6 as well as the Janus kinase inhibitor tofacitinib.5 Unsuccessful treatment has been reported with tildrakizumab and secukinumab.7,8 The effectiveness of tildrakizumab in our cases implicates IL23 and the TH17 axis in the pathogenesis of GA in at least our patient and underlines the likely heterogeneity in the immune mechanisms involved in the pathogenesis of GA. Granuloma annulare skin profile shows activation of T-helper cell type 1, T-helper cell type 2, and Janus kinase pathways. Keywords: granuloma annulare; granulomatous; necrobiotic; tildrakizumab EN granuloma annulare granulomatous necrobiotic tildrakizumab e285 e288 4 08/17/22 20220801 NES 220801 INTRODUCTION Granuloma annulare (GA) is a non-infectious granulomatous and necrobiotic skin disease with a relative predilection for females.1 It classically presents with one or more localized annular erythematous papules. [Extracted from the article]

Background: After registration of drugs, evidence about efficacy and safety is solely based on data of phase 2/3 clinical trial programs. A major drawback is the selection of patients following inclusion/exclusion criteria. There is a considerable time and knowledge gap between study and registry data that evaluate real-world evidence (RWE). To close this gap, prospective cohort data are helpful. Objectives: Soon after tildrakizumab, an interleukin 23p19-inhibitor, was registered for moderate-to-severe plaque psoriasis, a prospective single-center cohort study was established to evaluate efficacy and safety of tildrakizumab in daily practice. Methods: Following approval of tildrakizumab, patients with moderate-to-severe plaque psoriasis eligible for systemic treatment were included into the Kiel Tildra Cohort (KTC) and followed using routine assessments of efficacy, psoriasis area and severity index (PASI), body surface area (BSA), dermatology life quality index (DLQI), itch (visual analog scale), and safety. Data of the KTC were compared to the respective phase 3 clinical trials. Results: The KTC included 150 patients differing substantially from those in the trial program. There was a high rate of previous systemic (87.3%) and biologic (31.8%) therapy and of comorbidity in the KTC as compared to the phase 3 studies. Due to the best practice approach, baseline PASI was lower in the KTC, but DLQI was similar in both groups. At the time of this analysis, 126 patients completed week 28, 92 patients week 52, and 58 patients week 76, respectively. There was a constant improvement in PASI, BSA, DLQI, and itch from baseline until week 76. There was no clinically meaningful laboratory abnormality. Conclusions: Patients treated in routine practice with tildrakizumab differed substantially from the phase 3 studies. Despite systemic pre-treatment and increased comorbidity, tildrakizumab showed comparable efficacy and safety in the KTC. Prospective cohort studies are a suitable tool to generate RWE before registry data become available. [ABSTRACT FROM AUTHOR]

New biologic agents targeting interleukin (IL)23/T‐helper17 axis, such as tildrakizumab, have been developed for the treatment of plaque psoriasis. To analyze the efficacy and safety of tildrakizumab in a real life setting of patients affected by moderate‐to‐severe psoriasis over a 28‐week treatment period. A multicentric retrospective study was conducted in patients who initiated tildrakizumab between February 2020 and March 2021. Psoriasis Area and Severity Index—PASI was measured at baseline and after 4, 16 and 28 weeks. The percentage change in PASI value from baseline to the considered time‐points, proportion of patients with absolute PASI <3 at week 28 and the percentages of achieving a PASI75 or PASI90 response were assessed. Data about potential safety issues and adverse events (AEs) were collected. Statistical analysis were performed for establish clinical efficacy and for variables predicting clinical response. Fifty nine patients with psoriasis were included. Overall mean PASI percentage reduction was of 88% from baseline to week 28 and 47 out of 59 patients (79.7%) at week 28 had an absolute PASI <3. PASI75 and PASI90 responses at week 28 were achieved by 48 (81.40%) patients and 38 (64.4.0%) patients, respectively. No substantial associations between gender, body mass index ‐ BMI, PASI at baseline and prior exposition to biological therapies and the efficacy endpoints were retrieved. No serious safety issues or discontinuations related to adverse events were reported. In our real‐life study, tildrakizumab showed high efficacy and a favorable safety profile, regardless of patient‐ and disease‐related factors. [ABSTRACT FROM AUTHOR]

Tildrakizumab, an IL-23 inhibitor, is effective and safe for the improvement of moderate-to-severe chronic plaque psoriasis. However, little evidence is available on the use of this biologic in psoriasis in difficult-to-treat locations. In this retrospective analysis, we treated patients with 100 mg tildrakizumab at Day 0, after 4 weeks and every 12 weeks thereafter. Disease severity and treatment response was assessed by the Psoriasis Area and Severity Index (PASI), the static Physician's Global Assessment of Genitalia (sPGA-G), the Psoriasis Scalp Severity Index (PSSI), Nail Psoriasis Severity Index (NAPSI) and the Palmoplantar Psoriasis Area and Severity Index (ppPASI) at baseline and after 4, 12 and 28 weeks. We followed 18 patients (mean age 49.1 ± 12.7 years, 61.1% male) with psoriasis localized to the genital region (N = 7), scalp (N = 6), nails (N = 5) and palmar/plantar areas (N = 7). PASI score decreased from 11.5 at baseline to 3.1 and 2.4 at 12 and 28 weeks. Tildrakizumab treatment decreased sPGA-G (3.3 to 0.2), PSSI (36.2 to 2.7), NAPSI (48.4 to 15.7) and ppPASI (5.3 to 0) from baseline to 28 weeks, respectively. Data from this real-life retrospective analysis shows that tildrakizumab is an effective option for the management of psoriasis in difficult-to-treat areas. [ABSTRACT FROM AUTHOR]

To evaluate whether early Psoriasis Area Severity Index (PASI) improvements can predict week 28 tildrakizumab responders and nonresponders. Psoriasis patients pooled from two tildrakizumab phase 3 trials randomized to receive tildrakizumab 100 mg at weeks 0, 4, 16, and 28 were included. Patients were grouped by week 28 PASI responses (<50, 50–74, 75–89, and 90–100). PASI improvements from baseline at weeks 4 and 16 were analyzed for each response group. Of 575 patients included, 8.3%, 14.3%, 23.8%, and 53.6%, respectively, achieved PASI <50, 50–74, 75–89, and 90–100 at week 28. Of patients with PASI <50 at week 16, 85% did not achieve PASI ≥75 at week 28 (nonresponders). Rapid response, defined as PASI ≥50 at week 4 (after a single tildrakizumab dose), was observed in 41% of patients. Of these patients, 87% were week 28 responders (PASI ≥75); 67% were 'super responders' (PASI 90–100). Among week 28 responders and super responders, 45% and 50% achieved PASI ≥50 at week 4, respectively. Tildrakizumab week 28 nonresponders can be identified by week 16 PASI response. PASI improvements as early as week 4 can predict patients' week 28 PASI improvement status. [ABSTRACT FROM AUTHOR]

This review article aims to compare global dermatologic organizations and the clinical practice guidelines available for the use of interleukin (IL)-23 inhibitors in the treatment of psoriasis. A literature review encompassing systemic therapies for the treatment of psoriasis was conducted. Guidelines from the American Academy of Dermatology (AAD)-National Psoriasis Foundation (NPF), the National Institute for Health and Care Excellence (NICE), and the British Association of Dermatologists (BAD) served as the main comparators in this review. Of the American and European guidelines available for use of IL-23 inhibitors, several organizations are in agreement regarding the dosage and indications of guselkumab, tildrakizumab, and risankizumab. However, there are differences as well as insufficient recommendations concerning laboratory monitoring and screenings as well as contraindications to therapy. IL-23 inhibitors are safe and efficacious therapeutic options for patients with psoriasis and should be considered as a potential first-line therapy alone or in combination with topical medications, phototherapy, and other systemic non-biologic agents. Consideration should be given to the evidence-based guidelines of global dermatologic organizations to help guide therapeutic decisions. [ABSTRACT FROM AUTHOR]

Vulvovaginal lichen planus (VLP) is a chronic inflammatory dermatosis affecting the genital skin and mucosa that can have a profound negative impact on patient quality of life. Up to 43% of women with VLP require systemic immunosuppression to achieve disease remission, and some individuals prove to be highly treatment resistant. We present a case series of 24 women with severe VLP who successfully achieved remission using off‐label treatment with the interleukin‐23 (IL‐23) monoclonal antibody blocker tildrakizumab, and highlight tildrakizumab as a treatment for women with recalcitrant VLP who have failed more conservative treatments. [ABSTRACT FROM AUTHOR]

Copyright of Turkderm - Turkish Archives of Dermatology & Venereology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In Western countries, the number of individuals suffering from an autoimmune condition is constantly growing and often patients suffering from autoimmune disease are susceptible to developing a second autoimmune disorder. We report a case of an adult female patient affected by psoriasis vulgaris and treated with tildrakizumab, a humanized monoclonal antibody targeting interleukin‐23, who later developed chronic spontaneous urticaria and started omalizumab, a humanized antibody to IgE, showing a favorable outcome. We speculate that the two combined therapies have restored the cytokine balance bringing it toward tolerance and remission of the two pathologies. It is conceivable that tildrakizumab may have a synergic action with omalizumab in the treatment of urticaria in patients affected by both psoriasis and urticaria. Our case and the study of the mechanisms of action of the two drugs suggest how the two therapies can act with an interlocking mechanism in achieving the final therapeutic effect. [ABSTRACT FROM AUTHOR]

To evaluate the relative cost-effectiveness of tildrakizumab and other biologic and targeted systemic treatments compared with a mix of topical therapies, phototherapies, and other conventional systemic therapies as first-line treatment for moderate-to-severe plaque psoriasis from a United States payer's perspective. A Markov model consisting of health states based on Psoriasis Area Severity Index (PASI) response rate categories and death was developed. The probabilities of achieving PASI responses were derived from a network meta-analysis based on published efficacy data. Health care costs and effectiveness measured in quality-adjusted life-years (QALYs) were estimated. Incremental costs per QALY gained of each biologic/targeted first-line treatment versus a mix of conventional treatments were compared to provide relative cost-effectiveness among biologic and targeted first-line treatments. Over 10 years, the incremental cost per QALY gained compared with a mix of topical therapies, phototherapies, and other oral systemic therapies was lowest for brodalumab, infliximab, apremilast, and tildrakizumab, followed by secukinumab, ixekizumab, guselkumab, adalimumab, ustekinumab, and etanercept. The position of tildrakizumab relative to the other treatments remained the same across multiple scenarios. Tildrakizumab is among the most cost-effective first-line therapies for moderate-to-severe plaque psoriasis and is more cost-effective than secukinumab, ixekizumab, guselkumab, adalimumab, ustekinumab, and etanercept. [ABSTRACT FROM AUTHOR]

It is unclear whether primary efficacy outcomes in plaque psoriasis clinical trials represent residual disease during treatment. To evaluate supplementing dichotomous efficacy with residual disease activity. This post hoc analysis used pooled, patient-level data after tildrakizumab 100 mg (N = 616) or placebo (N = 309) treatment from reSURFACE 1/2 (NCT01722331/NCT01729754) phase 3 clinical trials of patients with moderate to severe plaque psoriasis. Median baseline Psoriasis Area and Severity Index (PASI) was 17.9 for patients receiving tildrakizumab 100 mg. At Week 12, median PASI was 2.9, whereas dichotomous PASI 90 response rate was 36.9%, and absolute PASI <5.0, <3.0, and <1.0 were 64.0%, 50.8%, and 23.3%, respectively. At Week 28, median PASI was 1.7, whereas PASI 90 response rate was 51.9%, and absolute PASI <5.0, <3.0, and <1.0 were 75.3%, 62.8%, and 38.0%, respectively. Dermatology Life Quality Index and PASI scores were correlated through Week 28 (r = 0.51, p ≤.0001). Disease activity was more reliably estimated by PASI scores than percentage PASI improvement; this may partially explain efficacy disparities between clinical trials and practice. These results suggest supplementing dichotomous PASI improvement with PASI scores and consideration of patient treatment goals could facilitate clinical decisions. [ABSTRACT FROM AUTHOR]

Erythrodermic psoriasis (EP), clinically defined as prominent erythema and scaling affecting almost the entire skin surface, is a severe form and a rare variant of psoriasis. The treatment may require hospital admission with monitoring of vital signs and use of immunosuppressive drugs. Newer biological drugs, including anti-TNF, anti-IL-17, and anti-IL-23 agents, even if not specifically developed for the treatment of erythrodermic psoriasis, have been used successfully in single cases or in small case series. Tildrakizumab is an IgG1? monoclonal antibody that selectively binds to the p19 subunit thus inhibiting the interaction of interleukin 23 (IL-23) with its receptor and suppressing the release of IL-23 mediated proinflammatory cytokines. We present a case of EP in an obese man (Body mass index 35.2) successfully and safely treated with Tildrakizumab. [ABSTRACT FROM AUTHOR]

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Nail psoriasis significantly impacts quality of life and is notoriously difficult to treat. Tildrakizumab, an IL‐23 inhibitor, has shown significant clinical improvement in the treatment of moderate‐to‐severe chronic plaque psoriasis. We report 2 cases of treatment resistant nail psoriasis which showed marked improvement with the use of off‐label tildrakizumab. The dosing regimen utilised was consistent with that used to treat chronic plaque psoriasis, with 100 mg subcutaneously at Day 0 and Week 4, and maintenance dosing of 100 mg every 12 weeks thereafter. Significant improvement at 6 and 12 months, as per the modified Nail Psoriasis Severity Index (mNAPSI) and Dermatology Life Quality Index (DLQI), was seen. There have been no tildrakizumab related side effects observed to date. Tildrakizumab appears to be an effective option in managing treatment resistant nail psoriasis. [ABSTRACT FROM AUTHOR]

The three part, double‐blind, randomized, controlled reSURFACE 1 trial and extension study (NCT01722331) evaluated efficacy and safety of tildrakizumab in adults with moderate to severe plaque psoriasis. Patients with ≥50% improvement from baseline in Psoriasis Area and Severity Index (PASI 50) following treatment with tildrakizumab 100 mg (TIL100) or 200 mg (TIL200) could enter the optional long‐term extension study and continue treatment at the same dose for an additional 192 weeks. This subgroup analysis assessed the long‐term efficacy and safety of tildrakizumab treatment for Japanese patients enrolled in reSURFACE 1 for up to 5 years of treatment. The primary efficacy outcomes were the proportions of patients who maintained PASI 75 and Physician Global Assessment (PGA) clear or minimal with ≥2‐grade reduction from baseline (PGA 0/1) from base study week 64 to extension week 192. Secondary outcomes were the proportion of patients who maintained PASI 90/100 from base study week 64 to extension week 192. Adverse events (AEs) were monitored throughout the study and for up to 20 weeks after the last study visit. Of the 120 Japanese patients who entered the reSURFACE 1 extension study, 43 (79.6%) patients receiving tildrakizumab 100 mg and 58 (87.9%) patients receiving tildrakizumab 200 mg completed the extension study. Of all Japanese patients with PASI 75/90/100 and PGA 0/1 at week 64, 85%/88% receiving TIL100/TIL200 maintained PASI 75, 70%/96% maintained PASI 90, 63%/67% maintained PASI 100, and 68%/72% maintained PGA 0/1 at extension week 192. AEs led to discontinuation in 1.7 patients per 100 patient‐years (P100PY) receiving tildrakizumab 100 mg and 0.8 P100PY receiving tildrakizumab 200 mg. Incidences of severe infections, malignancies, confirmed major adverse cardiac events, and hypersensitivity reactions were low in both treatment groups. Through 5 years of treatment, tildrakizumab maintained efficacy and was well tolerated with low rates of AEs of special interest. [ABSTRACT FROM AUTHOR]

Tildrakizumab is a high‐affinity, humanized immunoglobulin G1κ, anti‐interleukin‐23p19 monoclonal antibody recently approved in Japan for treatment of plaque psoriasis. We report results from Japanese patients treated with tildrakizumab in the multinational, randomized, double‐blind, placebo‐controlled reSURFACE 1 study (clinicaltrials.gov NCT01722331). Adults with moderate to severe plaque psoriasis were randomized (2:2:1) to receive subcutaneous tildrakizumab 100 or 200 mg or placebo every 12 weeks. Placebo recipients were rerandomized to tildrakizumab 100 or 200 mg at week 12. The global study coprimary endpoints were the proportions of patients achieving 75% improvement from baseline Psoriasis Area and Severity Index (PASI 75) and Physician Global Assessment (PGA) response (0/1 with ≥2 grade reduction from baseline) at week 12. Analyses included 158 Japanese patients randomized to tildrakizumab 100 (n = 64) or 200 mg (n = 62) or placebo (n = 32). Japanese patients had higher mean baseline body surface area involvement and PASI versus all reSURFACE 1 patients. At week 12, significantly more Japanese patients receiving tildrakizumab 100 and 200 mg versus placebo achieved PASI 75 (54.7% and 54.8% vs 6.3%, respectively, both nominal p < 0.001) and PGA 0/1 response (54.7% and 56.5% vs 9.4%, respectively, both nominal P < 0.001). Response rates increased over time with maximal efficacy after 22‐28 weeks; >80% of patients achieving PASI 75 or PASI 90 at week 28 and continuing tildrakizumab treatment at the same dose maintained response at week 64. From baseline to week 28, absolute PASI decreased from >12 in all patients to ≤2 in >40% and ≤3 in >50% of patients receiving tildrakizumab. Tildrakizumab was generally well tolerated with an adverse event profile similar to that of placebo. Tildrakizumab treatment was associated with durable efficacy in Japanese patients with moderate to severe plaque psoriasis despite greater baseline disease severity versus the global reSURFACE 1 population. [ABSTRACT FROM AUTHOR]

Guselkumab is a subcutaneously administered human monoclonal antibody, selectively blocking IL-23 through binding to its p19 subunit. It was initially approved for the treatment of patients with moderate-to-severe plaque-psoriasis who are candidates for systemic therapy or phototherapy. Pubmed and Embase databases were searched for publications, using the following search terms: psoriasis, psoriatic arthritis, guselkumab, risankizumab, tildrakizumab, p19, interleukin 23, guidelines, treatment recommendations, DISCOVER, ECLIPSE, and VOYAGE. Accumulating evidence suggests that the IL-23/Th17 pathway is important in the pathogenesis of both psoriasis and psoriatic arthritis. Following a successful development program in psoriasis, guselkumab was evaluated for its efficacy and safety in psoriatic arthritis in a comprehensive clinical trial program, comprising one phase-2 study and two phase-3 studies (DISCOVER-1 and −2). Complementary data on pharmacokinetics and safety exist from pre-clinical experiments and pooled analyses from two long-term studies in psoriasis (VOYAGE-1 and −2). Based on the DISCOVER-1 and −2 data, guselkumab was approved by the FDA for the treatment of active psoriatic arthritis in 2020. Guselkumab is the first selective IL-23 inhibitor approved to treat adults with active psoriatic arthritis, broadening therapeutic options in the field through a novel mode of action. [ABSTRACT FROM AUTHOR]