Dual blockade of interleukin-17A and interleukin-17F as a therapeutic strategy for liver fibrosis: Investigating the potential effect and mechanism of brodalumab.

Liver fibrosis is a terminal manifestation of various chronic liver diseases. There are no drugs that can reverse the condition. Recently, the importance of interleukin-17 (IL17) in the pathophysiology has been revealed and has attracted attention as a therapeutic target. We aimed to reveal the roles of IL17A and IL17F in liver fibrosis, and to validate the potential of their dual blockade as therapeutic strategy. First, we retrospectively reviewed the longitudinal change of FIB-4 index, a clinical indicator of liver fibrosis, among psoriasis patients treated by brodalumab, which blocks IL17 receptor A (IL17RA). Next, we examined anti-fibrotic efficacy of anti-IL17RA antibody (Ab) in two murine liver fibrosis models by histopathological investigation and real-time reverse transcription polymerase chain reaction (RT-PCR). Finally, we analyzed the effect of IL17A and IL17F upon human hepatic stellate cells with RNA sequencing, real-time RT-PCR, western blotting, chromatin immunoprecipitation, and flow cytometry. Clinical data showed that FIB-4 index significantly decreased among psoriasis patients treated by brodalumab. In vivo studies additionally demonstrated that anti-IL17RA Ab ameliorates liver fibrosis induced by tetrachloride and methionine-choline deficient diet. Furthermore, in vitro experiments revealed that both IL17A and IL17F enhance cell-surface expression of transforming growth factor-ß receptor II and promote pro-fibrotic gene expression via the JUN pathway in human hepatic stellate cells. Our insights suggest that IL17A and IL17F share their pro-fibrotic function in the context of liver fibrosis, and moreover, dual blockade of IL17A and IL17F by anti-IL17RA Ab would be a promising strategy for the management of liver fibrosis.

Vaccination recommendations for adults receiving biologics and oral therapies for psoriasis and psoriatic arthritis: Delphi consensus from the medical board of the National Psoriasis Foundation.

BACKGROUND: For psoriatic patients who need to receive nonlive or live vaccines, evidence-based recommendations are needed regarding whether to pause or continue systemic therapies for psoriasis and/or psoriatic arthritis. OBJECTIVE: To evaluate literature regarding vaccine efficacy and safety and to generate consensus-based recommendations for adults receiving systemic therapies for psoriasis and/or psoriatic arthritis receiving nonlive or live vaccines. METHODS: Using a modified Delphi process, 22 consensus statements were developed by the National Psoriasis Foundation Medical Board and COVID-19 Task Force, and infectious disease experts. RESULTS: Key recommendations include continuing most oral and biologic therapies without modification for patients receiving nonlive vaccines; consider interruption of methotrexate for nonlive vaccines. For patients receiving live vaccines, discontinue most oral and biologic medications before and after administration of live vaccine. Specific recommendations include discontinuing most biologic therapies, except for abatacept, for 2-3 half-lives before live vaccine administration and deferring next dose 2-4 weeks after live vaccination. LIMITATIONS: Studies regarding infection rates after vaccination are lacking. CONCLUSION: Interruption of antipsoriatic oral and biologic therapies is generally not necessary for patients receiving nonlive vaccines. Temporary interruption of oral and biologic therapies before and after administration of live vaccines is recommended in most cases.

Paradoxical psoriasis induced by IL-17 inhibitors: a case series of patients with axial spondyloarthritis and a systematic literature review.

Following the market authorization of interleukin (IL)-17 inhibitors, a growing number of cases of IL-17 inhibitor-induced paradoxical psoriasis (PsO) have been reported. Our objectives were to present two cases of IL-17 inhibitor-induced paradoxical PsO and to systematically review the literature for similar cases, summarizing and presenting the relevant data. A systematic literature review of previously presented cases of paradoxical PsO induced by IL-17 inhibitors was conducted. We presented two patients with axial spondyloarthritis (axSpA) and paradoxical PsO induced by secukinumab (SEC). One patient's psoriatic lesions responded well to adjuvant topical treatment, while the other patient required a combination of topical treatment and cyclosporine Α for successful treatment. SEC was continued in both cases. We also identified 35 patients with IL-17 inhibitor-induced paradoxical PsO in the literature review. The most frequent types of paradoxical PsO were palmoplantar pustular and plaque PsO, while the median latency period was 11 weeks. Approximately one-third of patients continued IL-17 inhibitor treatment with adjunctive therapy, primarily topical, which produced satisfactory results in most patients. Almost two-thirds of the patients discontinued the IL-17 inhibitor, with the majority of patients switching to another biological agent with a different mechanism of action or initiating other systemic antipsoriatic treatments, resulting in mainly satisfactory outcomes. Therefore, paradoxical PsO induced by IL-17 inhibitors appears to respond well in both patients who continue IL-17 inhibitors with adjunctive treatment and those who discontinue IL-17 inhibitors while switching to a different class of biological agent or initiating other systemic antipsoriatic treatments.

Brodalumab for moderate-severe hidradenitis suppurativa: An open-label multicentric cohort study in real clinical practice.

INTRODUCTION: The use of biological therapy is becoming increasingly common in patients with hidradenitis suppurativa (HS). Levels of serum TNF-alfa and IL17 support the role of an immune system dysregulation in the pathogenesis of HS. Brodalumab targets the receptor A of IL-17, thus having a promising role in the treatment of HS. MATERIAL AND METHODS: A multicenter retrospective observational open-label study was conducted in two tertiary hospitals. Adults with moderate to severe HS under treatment with brodalumab 210 mg at week 0, 1, 2 and then every 2 weeks were included and assessed at weeks 0 and 16 which was the median follow-up time. Demographic and disease-related variables as well as response parameters (HiSCR and IHS4) and safety data were recorded and analysed. RESULTS: A total of 16 patients (75% males) were included in our study. 50% of patients presented an inflammatory phenotype and mean BMI was 28.37. HiSCR was achieved in 50% of patients and mean IHS4 decreased from 24.13 to 16.81 (p = 0.002). No differences were found between those who achieved HiSCR and those who did not. Grade 2 adverse events were reported in three patients with no fatal outcomes and treatment discontinuation was advised in four patients. CONCLUSIONS: Brodalumab seems to be effective and safe in patients with moderate to severe HS, even in those that did not respond to adalimumab, which, at the moment, is the only widely approved biologic for this indication. Thus, it stands as an interesting option for the treatment of HS.

No Evidence of Gut Microbiota Alteration in Psoriasis Patients Switching to Brodalumab after Loss of TNFα Inhibition Effect.

Biological agents used to treat severe psoriasis may alter the gut microbiota, though current knowledge is limited. This study examines whether switching from TNFα inhibitors, from which patients had reduced or lost effect, to brodalumab, an IL-17 inhibitor, affects the gut microbiota in patients with psoriasis and how these changes correlate with the clinical variables of psoriasis severity and depressive symptoms. Fecal samples from patients were collected before the treatment switch and 12 weeks after the switch and were analyzed for the microbiota composition using next-generation sequencing targeting the V3-V5 region of the 16S rRNA gene, followed by bioinformatics analysis. No significant changes in overall gut microbiota composition were observed after the treatment switch, although individual variations in the Firmicutes/Bacteroidetes ratio were noted, and no significant correlations with clinical variables were found. These findings suggest that short-term changes in gut microbiota in patients with psoriasis are limited and that dysbiosis may be influenced by the interplay of various microbial populations rather than specific taxa. This study provides a foundation for further research into the effects of biological treatments on the gut microbiota in patients with psoriasis.

Brodalumab, an anti-interleukin-17 receptor A monoclonal antibody, in axial spondyloarthritis: 68-week results from a phase 3 study.

OBJECTIVE: To evaluate the long-term efficacy and safety of brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, in patients with axial spondyloarthritis (axSpA). METHODS: Patients receiving subcutaneous brodalumab 210 mg during the 16-week double-blind period of this multicentre, phase 3 study conducted across Japan, Korea and Taiwan continued the same during the 52-week open-label extension, whereas patients receiving placebo switched to brodalumab 210 mg at week 16. Efficacy [Assessment of SpondyloArthritis International Society (ASAS) 40 and ASAS 20 response rates; change from baseline in AS Disease Activity Score using CRP (ASDAS-CRP)] and safety were evaluated. RESULTS: Overall, 145 patients (brodalumab, n = 77; placebo, n = 68) received brodalumab during the open-label extension. ASAS 40 response rates (95% CI) of 56.3% (44.7%, 67.3%) and 57.4% (44.1%, 70.0%) were achieved in the brodalumab and placebo groups, respectively, at week 68. ASAS 20 response rates (95% CI) achieved at week 68 in both treatment groups were similar [brodalumab, 71.3% (60.0%, 80.8%); placebo, 78.7% (66.3%, 88.1%)]. The least squares mean change (95% CI) in ASDAS-CRP at week 68 suggested a clinically important improvement (change, ≥1.1) in both treatment groups [brodalumab, -1.528 (-1.737, -1.319); placebo, -1.586 (-1.815, -1.357)]. The exposure-adjusted event rates (per 100 patient-years) for treatment-emergent adverse events (TEAEs) and drug-related TEAEs were 255.9 and 147.9, respectively; nasopharyngitis (35.6) and upper respiratory tract infection (14.7) were the most common TEAEs. CONCLUSIONS: Brodalumab demonstrated sustained efficacy and a consistent safety profile in patients with axSpA over 68 weeks. STUDY REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02985983.

Anti-Interleukin-17s for successful management of pustular psoriasis.

Generalised pustular psoriasis (GPP) and acrodermatitis continua of Hallopeau (ACH) are two rare entities included in the spectrum of pustular psoriasis (PP). Due to the lack of randomised controlled clinical trials and standardized guidelines, their treatment remains a challenge for clinicians. Thus, herein we report our centre experience with the successful use of interleukin (IL)-17 inhibitors in three patients affected by PP. We also provide a brief overview of the current knowledge concerning the role of IL-17 in PP pathogenesis and of the use of IL-17 inhibitors in the treatment of PP. Based on our experience, anti-IL-17 molecules may represent a valuable therapeutical option for patients affected by different PP subtypes.

Effectiveness and safety of brodalumab in the treatment of plaque, scalp and palmoplantar psoriasis: A multicentre retrospective study in a Spanish population.

BACKGROUND AND OBJECTIVE: The data in clinical practice regarding the effectiveness and safety of brodalumab in psoriasis are scarce, especially at scalp and palmoplantar locations. The main objective was the percentage of patients achieving absolute PASI ≤3/ ≤1/ =0 for plaque psoriasis and the percentage of patients achieving an IGA 0-1/IGA 0 for the special locations at Week 52 of treatment. PATIENTS AND METHODS: Observational retrospective multicentre study in 28 Spanish Hospitals that included adult patients with plaque psoriasis treated with brodalumab, from September 2018 until March 2021. RESULTS: A total of 200 patients were included. The mean baseline PASI was 10.97 (±6.28) with a mean basal scalp (n = 58) and palmoplantar (n = 40) IGA of 2.10 (±0.97) and 2.15 (±1.26), respectively. At Week 52, 93.98%/75.90%/68.67% of patients reached an absolute PASI ≤3/ ≤1/ =0 in plaque psoriasis (n = 83), with a percentage of patients achieving scalp (n = 27) and palmoplantar (n = 19) IGA 0-1/IGA 0 of 96.3%/88.9% and 100%/88.9%, respectively. Fifteen per cent of patients reported any adverse events with candidiasis being the most reported (6%), but only 6% of the adverse events required the withdrawal. CONCLUSIONS: Brodalumab demonstrated high PASI and IGA responses and was well tolerated in clinical practice in plaque, scalp and palmoplantar psoriasis.

Brodalumab-Induced Eczematous Reactions in Psoriasis Patients: Management With Switching to Risankizumab.

Biological treatments targeting IL-17 are highly efficacious with rapid onset of action in psoriasis. Cutaneous adverse events are associated with different biological treatments, including paradoxical psoriasis and eczematous reactions. Brodalumab was previously suggested as an alternative treatment option in psoriasis patients who developed dermatitis or paradoxical psoriasis while on a biologic. Here we report three psoriasis patients who developed brodalumab induced eczematous reaction with complete clearance after switching to risankizumab. Early recognition is crucial for appropriate management. We propose switching patients with psoriasis who develop severe eczematous reaction while on a biologic targeting IL-17 to an IL 23 inhibitor due to efficacy in psoriasis and rarely reported eczematous reaction.

Brodalumab for Plaque Psoriasis: A Canadian Real-World Experience at 2-Years Post-Launch.

BACKGROUND: There is limited real-life evidence with brodalumab in patients with plaque psoriasis in Canada. OBJECTIVES: To examine real-world effectiveness of brodalumab in Canadian routine care with a focus on clinician and patient-reported outcomes, as well as measuring continuation rates and persistency. METHODS: Retrospective analysis was conducted on data collected through the brodalumab patient support program (PSP) in Canada for patients initiating brodalumab between June 2018 (PSP launch)- June 2020 with a minimum of 16 weeks follow-up from first dose. Effectiveness was assessed by improvements in PASI, BSA and DLQI; continuation rates and persistency on therapy were reported. RESULTS: Overall, 864 patients (male, 59%; median age, 52 years) were included in the analysis. In a subset of patients with both baseline and follow-up scores, statistically significant improvements were observed: PASI improved from 13.9 to 1.8, BSA improved from 16.6% to 2.5% and DLQI improved from 16.2 to 2.9. Brodalumab demonstrated high continuation rates (89.9%), with similar rates in biologic-naïve and biologic-experienced patients (92.1% and 88.6%, respectively) and in patients who received secukinumab or ixekizumab as their most recent biologic therapy (89.0% and 86.2%, respectively). Persistence at 6, 12, and 18 months was 82.0%, 69.9%, and 63.4%, respectively. CONCLUSIONS: The effectiveness of brodalumab was demonstrated in this Canadian routine care study, with significant improvements in disease severity and patient-reported outcomes. High continuation rates were achieved; including in patients previously treated with IL-17A inhibitors. Future studies will provide further evidence of brodalumab's benefits for the management of plaque psoriasis in the real-world setting.

Inhibiting IL-17A and IL-17F in Rheumatic Disease: Therapeutics Help to Elucidate Disease Mechanisms.

PURPOSE OF REVIEW: Psoriatic arthritis and ankylosing spondylitis belong to a family of rheumatological diseases that lead to painful joint inflammation that impacts on patient function and quality of life. Recent studies have shown that the pro-inflammatory cytokine IL-17 is involved in the inflammatory joint changes in spondyloarthritides. We will review the pathophysiology of IL-17 and review the biological therapies targeting IL-17. RECENT FINDINGS: IL-17 is produced and released from T cells and is dependent on multiple upstream cytokines, which include IL-23. There are six members of the IL-17 family that are secreted from multiple populations of T cells. The initial biologic medications have been developed against IL-17A, which is the best-studied member of this family. These medications appear to be effective in controlling joint inflammation, improving patient quality of life, and are generally well tolerated. More recently, medications have been developed that target both IL-17A and IL-17F. In addition, brodalumab, an antibody targeting the IL-17 receptor, has had a resurgence after initial concerns for an increased risk of suicide. IL-17 is an inflammatory cytokine that is critical in the pathobiology of axial spondyloarthritides. Recent biological therapies targeting IL-17A are effective and well tolerated in patients with axial spondyloarthritis. Specific targeting of the Il-17A/F heterodimer is also effective and provides another viable option in the clinician's armamentarium.

Treatments and outcomes of generalized pustular psoriasis: A cohort of 1516 patients in a nationwide inpatient database in Japan.

BACKGROUND: Because generalized pustular psoriasis (GPP) is rare, there are few studies reporting treatments and outcomes for large numbers of patients. OBJECTIVE: To report treatments and outcomes in a large cohort of patients hospitalized with GPP. METHODS: Using a Japanese national inpatient database, we identified 1516 patients with GPP who required hospitalization between July 2010 and March 2019. We categorized patients into 3 medication groups: biologics (294 patients), oral agents without biologics (948 patients), and systemic corticosteroids only (274 patients). We investigated their characteristics, treatments, and outcomes. RESULTS: Mean age was 66 years (interquartile range: 52-77 years). Fifty patients (3.3%) were admitted to the intensive care unit, 125 (8.2%) required blood pressure support, and 63 (4.2%) died. Patients who received biologics were younger and had fewer comorbidities. In-hospital mortality was lower in the biologics group (1.0% [biologics group] vs 3.7% [oral-agents group] vs 9.1% [corticosteroids-only group]; P < .001) as was morbidity (5.4% vs 8.2% vs 12%, respectively; P = .02). Among those who received biologics, IL-17 inhibitor use increased over time, with in-hospital mortality and morbidity comparable to those of tumor necrosis factor inhibitors. LIMITATIONS: Retrospective study design. Some patients received multiple medications. CONCLUSION: Biologic treatments showed favorable outcomes compared with other treatments.

Real world experience of brodalumab treatment in patients with moderate-to-severe plaque psoriasis in the Greek population: Results from an interim analysis of the BrIDGE study.

Brodalumab's clinical efficacy and favorable safety profile have been demonstrated during controlled clinical trials, but real-world data remain scarce. BrIDGE, an ongoing 104 week, observational, prospective, multicenter study conducted in Greece, enrolled moderate-to-severe plaque psoriasis patients, with body surface area (BSA) > 10 or psoriasis area severity index score (PASI) > 10 and dermatology life quality index (DLQI) > 10, based on European consensus, initiating brodalumab treatment as per routine clinical practice. This interim analysis includes evaluations 12-16 weeks following treatment initiation. Key efficacy endpoints included proportion of patients achieving static Physician's Global Assessment (sPGA) score of "clear/almost clear" (0/1) and a reduction ≥75%, 90%, 100% from baseline in PASI (PASI75, PASI90, and PASI100) at weeks 12-16. Other endpoints included time to achieve PASI100, changes in self-reported DLQI and psoriasis symptom inventory (PSI) at weeks 12-16. From 200 patients (mean age 51.4 years, 70% male, mean disease duration 13.8 years) enrolled, 72.8% achieved sPGA of 0/1, whereas 70.2%, 47.5%, and 32.0% achieved corresponding PASI75, PASI90, and PASI100 responses following 12-16 weeks of brodalumab treatment, according to the "as-observed" analysis. The mean time to achieve PASI100 was 13.7 ± 1.2 weeks for the 32% who achieved PASI100. Concurrent decreases in mean DLQI and PSI were observed. Furthermore, 90% adherence to brodalumab was noted and nine adverse events were reported. Brodalumab confers substantial clinical improvements short-term as reflected by high levels of skin clearance in moderate-to-severe plaque psoriasis patients within 12-16 weeks of treatment under everyday clinical conditions, followed by improvements in symptoms and quality of life and a favorable safety profile.

Clinical evidence on the use of brodalumab for the treatment of psoriasis in Greece: Experience from clinical practice of four tertiary hospitals.

Despite brodalumad demonstrated efficacy in clinical trials, real-world data reflecting clinical benefits in unselected patient populations treated in routine clinical practice are limited. Thus, we performed a longitudinal, retrospective, real-world analysis assessing the long-term clinical benefits of patients with moderate-to-severe psoriasis treated with brodalumab in Greece in the long term (up to 24 months). Main efficacy assessments included changes from baseline in the psoriasis area and severity index (PASI) and proportions of patients achieving at least 50%, 75%, 90% and 100% reduction from baseline in PASI scores (PASI50, PASI75, PASI90 and PASI100) at different timepoints up to 24 months. Other endpoints included changes in the dermatology life quality index (DLQI) and body surface area (BSA) involvement. Data from medical records of 180 patients with moderate-to-severe psoriasis treated with brodalumab for up to 24 months were assessed. Following treatment, mean [standard deviation (SD)] PASI scores were decreased across all visits compared to baseline (p < 0.001). The proportion of patients achieving PASI50, PASI75, PASI90 or PASI100 were high as early as at month 1 and consistently tended to increase over time, mainly during the first 6 months. Improvements on disease severity were further reflected by reductions from baseline on BSA scores across all visits (p < 0.001). Concurrent improvements on DLQI scores were observed across all visits (p < 0.001). This retrospective analysis provides real-world evidence supporting the long-term efficacy profile of brodalumab in Greek patients with moderate-to-severe psoriasis treated in standard clinical practice, which is characterized by a rapid onset of action generally sustained over time.

Ixekizumab and brodalumab indirect comparison in the treatment of moderate to severe psoriasis: Results from an Italian single-center retrospective study in a real-life setting.

Eleven biologic drugs are currently approved for psoriasis management. Real-life studies are needed to guide clinicians in choosing a tailored-tail therapy. The aim of our retrospective study is to indirectly compare the efficacy and safety of ixekizumab and brodalumab in psoriasis patients. A single-centre real-life retrospective study was performed enrolling moderate-to-severe psoriatic patients under biologic treatment with ixekizumab or brodalumab. For each patient, clinical and demographic data were collected and the effectiveness and safety of brodalumab and ixekizumab treatment were evaluated at weeks 4, 12, and 24. Psoriasis Area Severity Index (PASI) and Body Surface Area (BSA) were used for psoriasis severity. A total of 139 patients were included in the study: 98(70.5%) and 41(29.5%) patients received ixekizumab and brodalumab, respectively. Mean PASI and BSA significantly reduced at each follow up for both ixekizumab and brodalumab groups. Even if ixekizumab reached higher rates of PASI90 and PASI100 than brodalumab (PASI90: 43.8% vs. 39.0% PASI100: 20.4% vs. 17.1% at week4 and PASI90: 83.6% vs. 75.6% PASI100: 71.5% vs. 60.9% at week24), these results were not statistically significant. Adverse events, mainly mild, were registered in 25.5% of ixekizumab and 26.8% of brodalumab group, respectively. Discontinuation rate was higher for brodalumab (17.1% vs. 9.1%), without statistical significance. Our study showed comparable efficacy and safety for ixekizumab and brodalumab.

Brodalumab Is Associated with High Rates of Complete Clearance and Quality of Life Improvement: A Subgroup Analysis of Patients with Psoriasis and Concomitant Psoriatic Arthritis.

BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory disease associated with psoriasis that significantly impairs physical function and quality of life (QoL). Prompt therapeutic intervention is crucial for limiting PsA progression and preventing disability. OBJECTIVES: The aim of this study was to compare the efficacy of brodalumab versus ustekin-umab and the impact on QoL in patients with moderate-to-severe plaque psoriasis, by concomitant PsA status. METHODS: This post hoc analysis of pooled data from the phase 3 AMAGINE-2 and -3 trials evaluated complete skin clearance (100% improvement of Psoriasis Area and Severity Index [PASI 100]), improvement in symptom severity (Psoriasis Symptom Inventory [PSI] response), and QoL (Dermatology Life Quality Index [DLQI] score of 0/1) by concomitant PsA status. A competing risk model assessed cumulative incidence over 52 weeks with outcomes of PASI 100 or inadequate response. RESULTS: This analysis included 929 patients with moderate-to-severe psoriasis. Concomitant PsA was present in 79/339 (23%) and 110/590 (19%) patients receiving brodalumab 210 mg and ustekinumab, respectively. At Week 52, odds ratios (ORs) (95% confidence intervals [CIs]) for complete clearance with brodalumab versus ustekin-umab were 3.15 (1.52-6.55, p = 0.0015) in patients with concomitant PsA and 3.05 (2.19-4.26, p < 0.0001) in patients without concomitant PsA. Corresponding Week 52 ORs (95% CIs) for DLQI 0/1 with brodalumab versus ustekinumab were 2.05 (1.07-3.90, p = 0.0277) and 1.83 (1.32-2.53, p = 0.0002); Week 52 ORs (95% CIs) for PSI ≤8 with brodalumab versus ustekinumab were 3.42 (1.43-8.18, p = 0.0036) and 1.40 (1.01-1.95, p = 0.0434). The 52-week cumulative incidence of patients achieving PASI 100 was significantly higher for brodalumab versus ustekinumab in patients with concomitant PsA (p = 0.0001) and in those without concomitant PsA (p < 0.0001). CONCLUSIONS: Treatment with brodalumab rapidly results in high levels of complete and sustained skin clearance and greater cumulative treatment benefit in patients with moderate-to-severe psoriasis versus ustekinumab, regardless of concomitant PsA status.

A case of inflammatory linear verrucous epidermal nevus successfully treated with Brodalumab.

Inflammatory linear verrucous epidermal nevus (ILVEN) is a rare type of epidermal nevus, commonly arising in childhood. We present a case of a 13-year-old female with Blaschkoid psoriasiform plaques extending from her left foot to the scalp, sparing the right side of the body. While treatment options historically show variable success, we trialed an IL-17a receptor inhibitor as studies have shown increased levels of IL-17 receptor expression in ILVEN keratinocytes. At both 3 and 6 months after treatment initiation there was found to be significant improvement. We propose brodalumab as an effective treatment option for widespread ILVEN.

Treatment Outcomes of IL-17 Inhibitors in Hidradenitis Suppurativa: A Systematic Review.

The IL-17 pathway is a potential therapeutic target shown to be implicated in hidradenitis suppurativa (HS), however, it remains unclear whether evidence from mechanistic studies may translate into clinical practice. This systematic review summarizes available treatment outcomes of IL-17 inhibitors in patients with HS. Embase, MEDLINE, PubMed, and clinicaltrials.gov were comprehensively searched on February 26, 2021 to include 16 original studies representing 128 patients with HS (mean age: 36.5 years; age range: 21-47 years; male: 50.0%). Treatment outcomes were reported for the following biologics: secukinumab (n = 105), brodalumab (n = 22), and ixekizumab (n = 1). Patients were classified as responders or non-responders according to achievement of a positive response/improvement based on criteria established for each included study. For secukinumab 57.1% (n = 60/105) of patients were responders in a mean response period of 16.2 weeks and 42.9% (n = 45/105) were non-responders; for brodalumab, 100.0% (n = 22/22) of patients were responders within 4.4 weeks; and the one patient treated with ixekizumab was a responder within 10 weeks. In conclusion, IL-17 inhibitors may serve as an effective therapeutic target in approximately two-thirds of patients with HS and can be considered in those who are refractory to other treatment modalities. We also stress the importance of consistent outcome measures to enhance evidence synthesis, decrease reporting bias, provide potential for future meta-analysis, and ultimately improve clinical outcomes for patients with HS.

Epithelialized tunnels are a source of inflammation in hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic, painful, and burdensome inflammatory disease manifesting in nodules and abscesses, with progression to chronically draining tunnels in later-stage disease. OBJECTIVE: We sought to determine whether HS tunnels are immunologically active participants in disease activity. METHODS: Skin biopsy specimens were obtained by using ultrasound guidance in untreated patients with HS and those enrolled in an open-label study of brodalumab (ClinicalTrials.gov identifier NCT03960268) for patients with moderate-to-severe HS. RESULTS: Immunohistochemistry of HS biopsy specimens demonstrated that the epithelialized HS tunnels recapitulate the psoriasiform epidermal hyperplasia morphology of the overlying epidermis, displaying molecular inflammation, including S100A7 (psoriasin) positivity, as well as features of epidermal skin, including loricrin, filaggrin, lipocalin-2, and Melan-A positive cells. Tunnels were associated with increased infiltration of T cells, dendritic cells, and neutrophils; formation of neutrophil extracellular traps, and increased expression of psoriasiform proinflammatory cytokines. Unsupervised hierarchical clustering demonstrated a separation of HS samples based on the presence or absence of tunnels. Tunnels isolated by microdissection had higher levels of epithelium-derived inflammatory cytokines compared with the overlying epidermis and healthy controls. Clinically, the size and draining of the tunnels were decreased with treatment with the IL-17RA antagonist brodalumab. CONCLUSION: These data suggest that tunnels are a source of inflammation in HS.

IL-17A inhibitors in patients with chronic plaque psoriasis and history of malignancy: A case series with systematic literature review.

The treatment of moderate to severe plaque psoriasis in patients with history of malignancy is challenging. To review the studies reporting the experience with IL-17A inhibitors in patients with psoriasis and history of malignancy; secondly, to investigate cancer recurrence in a series of patients with a prior malignancy and plaque psoriasis treated with IL-17A inhibitors. A systematic literature review and an observational retrospective analysis of patients with history of malignancy and plaque psoriasis treated with IL-17A inhibitors was performed. About 5 original articles out of 601 were retrieved, reporting a total of 10 patients with a median age of 59 years, interquartile range (IQR) 50-63. Seven patients were treated with secukinumab, one with ixekizumab and two with both sequentially. Although the stage ranged from in situ to IV stage, most of the cases were early-stage neoplasm. The IL-17A inhibitor was initiated after a median of 10 months, interquartile range (IQR) 5-30 (range 0-144) from the diagnosis of malignancy. In addition, a series of 12 patients with history of malignancy were identified from the University Hospital of Verona, including 9 cases with cancer in clinical remission and 3 with advanced disease at time of initiating IL-17 inhibitor. No malignancy recurrence was reported within a median of 12 (IQR 6-23) and 46 (IQR 36-48) months follow up in case series from literature and our experience, respectively. Data on use of IL-17A inhibitors in patients with chronic plaque psoriasis and history of malignancy are limited. Registries and proactive pharmacovigilance activities are needed to guide clinical practice.