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Background: Ixekizumab, an interleukin-17A (IL-17A) inhibitor used in psoriasis treatment, has been linked to drug-induced interstitial lung disease (DI-ILD). The pathophysiological mechanisms and histopathological features of this adverse effect remain poorly documented. Case Presentation: A 69-year-old male with familial psoriasis developed respiratory symptoms after 18 months of ixekizumab therapy. His medical history included mild smoking-related interstitial pneumonia and chronic obstructive pulmonary disease. One month after treatment, he presented with cough and dyspnea. High-resolution chest CT showed bilateral ground-glass opacities, accompanied by elevated Krebs von den Lungen-6 and surfactant protein-D levels. Transbronchial lung cryobiopsy (TBLC) revealed a fibrotic non-specific interstitial pneumonia pattern with granulomatous changes. Immunohistochemical analysis demonstrated a predominance of CD4-positive cells and IL-17A-positive lymphocytes, suggesting Th17 cell involvement in the pathogenesis. The patient's condition improved following ixekizumab discontinuation. Conclusions: This case identifies distinct histopathological features in ixekizumab-induced DI-ILD, particularly the presence of granulomatous changes and Th17 cell involvement. The findings suggest that IL-17A inhibition may trigger pulmonary inflammation through Th17 cell function dysregulation. This observation supports the importance of careful pulmonary monitoring in patients receiving biologic therapies for psoriasis, particularly those with pre-existing lung conditions. TBLC may contribute to understanding the pathogenesis of this drug-induced complication. [ABSTRACT FROM AUTHOR]

Background: This safety analysis investigates treatment-emergent mucosal/cutaneous Candida infections in patients treated with ixekizumab (IXE), an anti-interleukin-17A monoclonal antibody, across the approved indications: psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA). Research design and methods: Safety data were pooled from 25 clinical studies. Incidence rates (IRs) are expressed as per 100 patient-years (PY), using the entire duration of exposure. Results: Candida infections had an IR of 1.9 per 100 PY in patients with PsO (N = 6892; total PY = 18025.7), 2.0 per 100 PY in patients with PsA (N = 1401; total PY = 2247.7), and 1.2 per 100 PY in patients with axSpA (N = 932; total PY = 2097.7). The majority of treatment-emergent Candida infections were: (i) experienced only once by patients (IR = 1.3;IR = 1.6;IR = 1.0), (ii) mild/moderate in severity (IR = 0.8/0.9;IR = 1.5/0.4;IR = 0.8/0.5) as opposed to severe (IR = 0.0; IR = 0.0; IR = 0.0), (iii) oral Candida or genital Candida (IR = 0.9/0.6;IR = 1.0/0.7;IR = 0.4/0.6), (iv) marked as recovered/resolved during the studies (89.3%;93.8%;90.3%), (v) not leading to IXE discontinuation (0.0%;0.0%;0.1% discontinued), (vi) managed with topical (34.7%;22.2%;11.5%) or no anti-fungal medications (63.5%;77.8%;80.8%) as opposed to systemic therapies (1.5%;0.0%;7.7%), (vii) typically resolved before next visit. Conclusions: This integrated safety analysis shows that the risk of developing Candida infections is low with IXE, and the severity is mild-to-moderate in most instances across the approved IXE indications. Trial registration: A comprehensive list of the clinical trials and their registration numbers is reported in Table S1 of the supplemental material. Plain Language Summary: Ixekizumab (IXE) is a drug approved for the treatment of psoriasis, psoriatic arthritis, and axial spondyloarthritis. IXE belongs to the class of molecules that blocks a protein called interleukin-17A. Since interleukin-17A is involved in the defense against fungi, the clinical use of this class of drug has the potential to increase the risk of developing fungal infections, such as Candida infections. Therefore, researchers collected safety data from 25 clinical studies comprising 9225 adult patients treated with IXE: 6892 with psoriasis, 1401 with psoriatic arthritis, and 932 with axial spondyloarthritis. Researchers looked at the rate of new cases of Candida infections, the so-called incidence rate, and found that 1.9 per 100 patient-years experienced at least 1 Candida infection in the psoriasis group, 2.0 per 100 patient-years in the psoriatic arthritis group, and 1.2 per 100 patient-years in the axial spondyloarthritis group. Across indications, the majority of Candida infections (i) were experienced only once by patients, (ii) were mild or moderate in severity, (iii) involved infections caused by superficial skin fungus in the mouth or genitals, (iv) were considered recovered/resolved during the studies, (v) did not lead to IXE discontinuation, (vi) were managed with topical anti-fungal medications or no medications, and (vii) were typically resolved before next visit. In conclusion, this safety analysis shows that the risk of developing Candida infections is low with IXE, and the severity is mild-to-moderate in most instances across the approved IXE indications. [ABSTRACT FROM AUTHOR]

The application of interleukin-17 (IL-17) inhibitors, including secukinumab, ixekizumab, brodalumab, and bimekizumab, are associated with elevated risk of candidiasis. These medications interfere with the IL-17 pathway, which is essential for maintaining mucosal barriers and coordinating the immune response against Candida species. The observational data and clinical trials demonstrate the increased incidence of candidiasis in individuals treated with IL-17 inhibitors. Brodalumab and bimekizumab pose a greater risk than secukinumab in eliciting candidiasis, whereas the data regarding ixekizumab are equivocal. Higher doses and prolonged treatment duration of IL-17 inhibitors increase the risk of candidiasis by compromising the immune response against Candida species. Prior to prescribing IL-17 inhibitors, healthcare professionals should comprehensively evaluate patients' medical histories and assess their risk factors. Patients should be educated on the signs and symptoms of candidiasis to facilitate early detection and intervention. Future research should focus on identifying the risk factors associated with candidiasis in patients receiving IL-17 inhibitors. Prospective studies and long-term surveillance are required to explore the impact of specific inhibitors on the incidence and severity of candidiasis and to evaluate the effectiveness of combination therapies, such as concurrent use of IL-17 inhibitors and prophylactic antifungal agents. [ABSTRACT FROM AUTHOR]

Objective: To estimate the cost-effectiveness of a treatment-pathway initiated with bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F and IL-17A, in patients with axial spondyloarthritis (axSpA) compared with IL-17Ai's, ixekizumab, and secukinumab, from the NHS Scotland perspective. Methods: The axSpA treatment-pathway was modeled using a decision tree followed by a lifetime Markov model. The pathway included first- and second-line biologic disease-modifying antirheumatic drugs (bDMARD), followed by best supportive care (bDMARD, nonbiologic). Bimekizumab followed by any bDMARD ("BKZ") was compared with IL-17Ai's: secukinumab 150 mg followed by a blend ("SEC") of dose up-titration to secukinumab 300 mg and any bDMARD, or ixekizumab followed by any bDMARD ("IXE"). Transition to the next therapy was triggered by Bath Ankylosing Spondylitis Disease Activity Index-50% (BASDAI50) non-response or any-cause discontinuation. A published network meta-analysis provided efficacy data. EuroQoL-5-dimensions utilities were derived by mapping from Ankylosing Spondylitis Disease Activity Score. Costs included disease management (linked to functional limitations), biologics acquisition (list prices), administration and monitoring (NHS 2021/22). Discounting was 3.5%/year. Probabilistic results from patients with non-radiographic axSpA and ankylosing spondylitis were averaged to reflect the axSpA disease spectrum. Scenario and sensitivity analyses were performed. Results: The incremental cost-effectiveness ratio (ICER) of BKZ was £24,801/quality-adjusted life-year (QALY) vs. SEC (95% credible interval £24,163–£25,895). BKZ had similar costs (Δ -£385 [−£15,239–£14,468]) and QALYs (Δ 0.039 [−0.748–0.825]) to IXE, with £1,523 (£862–£2,222) net monetary benefit. Conclusions remained unchanged in most scenarios. Results' drivers included BASDAI50 response rate and disease management cost. Limitations: Results were based on list prices. Data concerning up-titration to secukinumab 300 mg was scarce. Conclusions: The bimekizumab treatment-pathway represents a cost-effective option across the axSpA disease spectrum in Scotland. Bimekizumab is cost-effective compared to a secukinumab-pathway that includes dose up-titration, and has similar costs and QALYs to an ixekizumab-pathway. [ABSTRACT FROM AUTHOR]

Available network meta-analyses (NMAs) comparing the efficacy of biologics in nail psoriasis (NP) have not included recently approved biologics such as bimekizumab nor have they provided comparisons up to 1 year. We conducted two NMAs that update and extend results from a previous NMA comparing biologics for achieving complete resolution of NP. Bayesian NMAs were performed using a generalized linear model with a logit link to model the binary outcome of nail clearance at weeks 24–28 and 48–52. For the NMA at weeks 24–28, which included seven biologics and placebo, the absolute probability of achieving complete resolution of NP was highest for ixekizumab (46.4%; 95% credibility interval [CrI] 35.2–58.0), followed by brodalumab (37.1%; 95% CrI 17.1–62.2) and bimekizumab (30.3%; 95% CrI 12.7–53.9). For the NMA at weeks 48–52, which included six biologics, the absolute probability was highest for ixekizumab (77.2%; 95% CrI 51.1–93.4), followed by adalimumab (75.6%; 95% CrI 61.5–87.3) and brodalumab (71.9%; 95% CrI 38.4–93.2). Among biologics included in these two NMAs, ixekizumab has the highest absolute probability of achieving complete resolution of NP. Results may help to inform treatment decisions for patients with NP. [ABSTRACT FROM AUTHOR]

Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A approved for the treatment of moderate-to-severe plaque psoriasis. The objective of this study was to describe the real-world long-term effectiveness of ixekizumab in patients with plaque psoriasis in Italy. A retrospective study was conducted in patients affected by moderate-to-severe plaque psoriasis who were continuously treated with ixekizumab for at least 12 months. Patient data was obtained at 4-weeks, 12-weeks and 6-, 12-, 18- and 24-months after baseline (June 2017 and September 2019) from 10 sites. Results were analyzed by complete case approach, with sensitivity analysis performed to evaluate the impact of missing data. A total of 198 patients were enrolled in the study. At Month 24, 94.3% of patients achieved PASI75 response, while 85.1 and 71.8% achieved PASI90 and PASI100, respectively; and 91.1% of the patients achieved absolute PASI score ≤2. Patients experienced psoriasis improvement at 4 weeks after starting treatment, and improvement was maintained with continued ixekizumab use. The quality of life of patients also improved significantly starting at Week 12, with sustained effect in the long term. This 24-month observational cohort study confirmed that ixekizumab is effective in the long-term management of patients with moderate-to-severe plaque psoriasis. [ABSTRACT FROM AUTHOR]

Background: Lichen planopilaris (LPP) is a lymphocytic primary cicatricial alopecia characterized by perifollicular erythema, follicular hyperkeratosis and scaring, resulting in permanent hair loss. Current treatment modalities, both topical and systemic, fail to achieve satisfactory and consistent results. As therapies fail to halt the inflammatory process, patients with LPP may face long-term disfigurement and significant psychological burden. Purpose: To initiate an efficacious targeted therapy with good tolerability and low side effect profile that will allow hair regrowth and prevent the development to disfiguring alopecia. Materials and methods: Here, we report on a case of rare LPP in a linear distribution (LLPP) involving the scalp and forehead failing to achieve satisfactory results with continued hair loss with multiple previous treatments. Results: Complete hair regrowth was achieved 12 weeks after treatment with an anti-psoriatic, anti-interleukin (IL)-17A/F antibody (Taltz, Ixekizumab, Lilly). Patient continued to display sustained efficacy with no reported side effects until 12 months on treatment. Conclusions: The present case underlines the viability of Ixekizumab as a possible first-line, targeted therapy for LPP and its variants with sustained efficacy. Multicenter trials are warranted to confirm the benefit of Ixekizumab as a successful targeted biologic treatment option for LPP and LLPP. [ABSTRACT FROM AUTHOR]

Head-to-head comparisons through randomized controlled trials (RCTs) provide high-quality evidence to inform healthcare decisions. In their absence, indirect comparisons are often performed; however, evidence is limited on how valid matching-adjusted indirect comparison (MAIC)–based comparative efficacy estimates are vs. RCT-based estimates. Compare MAIC and RCT results of guselkumab vs. secukinumab and ixekizumab to provide insight into the validity of results generated using MAIC methods. Previously reported results from MAICs of guselkumab vs. secukinumab and ixekizumab were compared with results from ECLIPSE and IXORA-R RCTs based on risk differences between Psoriasis Area and Severity Index (PASI) 90 response rates. Risk difference (95% confidence interval) in PASI 90 response rates at week 48 for guselkumab vs. secukinumab was 14.4% (9.4%; 19.4%) in ECLIPSE and 9.4% (4.7%; 14.0%) in the MAIC. The risk difference at week 24 for guselkumab vs. ixekizumab was 0.0% (−5.4%; 5.4%) in IXORA-R and 0.7% (−5.1%; 6.4%) in the MAIC. Comparative efficacy results were consistent between MAICs and RCTs of guselkumab vs. secukinumab and ixekizumab. This analysis demonstrates that MAIC methods can provide valid relative treatment effect estimates when direct comparisons are lacking, particularly when trials with similar designs and patient populations inform the analysis. [ABSTRACT FROM AUTHOR]

To describe the results of a structured literature review of real-world outcomes with ixekizumab in patients with psoriasis (PsO) and/or psoriatic arthritis (PsA). Literature databases, conference proceedings and additional sources were searched for relevant publications. Real-world studies of ≥25 ixekizumab-treated patients with PsO and/or PsA were included. Data on clinical effectiveness, treatment persistence/patterns, economic outcomes, patient-reported outcomes (PROs) and safety were extracted. Fifty-one publications were included. Most studies focused on patients with PsO, and the number of publications with a focus on PROs was low. Studies of treatment patterns found that in general, ixekizumab had similar or better persistence versus other biologics, and rates or risk of switching similar to or less than comparator drugs. Adherence to ixekizumab was high, and patients were less likely to discontinue ixekizumab than other biologics. Ixekizumab was effective in the real world, with a safety profile consistent with that reported in clinical trials. Real-world use of ixekizumab in PsO and PsA is effective and safe, with generally high treatment persistence and adherence. Further work is required to determine the impact of ixekizumab on PROs in PsO, and to gather more data on real-world use of ixekizumab in PsA. [ABSTRACT FROM AUTHOR]

Off-label uses of biologics in the treatment of psoriasis are usually implemented in limited-resource settings and studies regarding their response profiles are limited. This was a retrospective study performed in moderate-to-severe plaque-type psoriasis patients who had been treated with either secukinumab, ixekizumab or brodalumab at a university hospital in Thailand between 1 January 2017 and 1 April 2021. A total of 142 patients were included in the data analysis consisting of three groups of 48 patients, 86 patients, and 8 patients treated by secukinumab, ixekizumab, and brodalumab, respectively. Patients were then classified into five groups according to the dosing pattern they received; on-label, off-label with induction, off-label with specific pattern, off-label with irregular dosing interval <8 weeks and >8 weeks. Considering both secukinumab and ixekizumab, the adjusted hazard ratios (95%CI) for complete skin clearance of the four off-label regimens were 2.2(0.9–5.2), 1.9 (0.9–3.9), 1.0 (0.4–2.2), and 1.6 (0.7–3.6), compared to on-label regimen, respectively. In each biologic drug, almost all off-label dosing regimens demonstrated higher adjusted hazard ratios compared to on-label regimen. Off-label, patient-oriented regimens could be a promising choice of IL-17 inhibitors for administration in special settings. Off-label regimens are not inferior in terms of skin clearance to an on-label regimen in the efficacy of psoriasis treatment of secukinumab and ixekizumab but do cause more flares. The decision to use off-label regimens must account for the benefits and associated risks. [ABSTRACT FROM AUTHOR]

Psoriasis is an inflammatory, chronic and immune-mediated disease that can affect the skin and joints. Pro-inflammatory cytokines have a dominant role in the pathogenesis of this heterogeneous disease in which the IL-23/IL-17 axis plays a crucial role. The IL-17 family is involved in numerous processes such as immune defense, intestinal disorders and diseases of the central nervous system. In psoriasis, in particular, many cytokines belonging to the IL-17 family are involved in the inflammatory cascade underlying the disease. The knowledge of the mechanisms and pathways behind psoriasis is crucial for the development of new target therapies. We focused on IL-17 biology in order to understand why biological drugs against this cytokine are an effective treatment for moderate to severe psoriasis. Clinical trials results of ixekizumab, brodalumab, secukinumab and bimekizumab have been presented. Il-17 inhibitors are a very fast and effective treatment against psoriasis; however, fungal infections can occur during their use, due to IL-17 biological functions. Therefore, it should be mandatory to choose the right patients to treat with these monoclonal antibodies in order to have a tailored target therapy for each patient. [ABSTRACT FROM AUTHOR]

Real-world data on the use of interleukin-17 (IL-17) inhibitors for the treatment of psoriasis are limited. To evaluate and compare the efficacy, safety, and drug survival of IL-17 inhibitors. This retrospective study analyzed the BIOREP registry data of patients treated with at least one IL-17 inhibitor (secukinumab, ixekizumab, and brodalumab). In total, 949 patients were included. The improvement in PASI score was significant for all drugs, and the proportion of patients achieving PASI 75, 90, and 100 after both 3 and 24 months of therapy was highest for brodalumab, followed by ixekizumab and secukinumab. The Dermatology Life Quality Index score decreased to ˂3 after 3 months and to ˂2 after 24 months of therapy for all inhibitors. Loss of effectiveness was the major reason for discontinuation in 17.2% of patients, followed by adverse events in 3.2% of patients. The drug survival probability was the highest for brodalumab, followed by ixekizumab and secukinumab. Negative predictors for treatment discontinuation were obesity and the number of treatment lines, whereas a positive predictor was the presence of concomitant psoriatic arthritis; sex had no influence. This real-life study demonstrated the effectiveness and good safety profile of all currently available IL-17 inhibitors. [ABSTRACT FROM AUTHOR]

As aberrant IL-17 signaling plays a critical role in the pathogenesis of psoriasis, biologic agents targeting this pathway have become an important weapon against this disease. Some biologic agents such as IL-17 inhibitors (secukinumab and ixekizumab) and the IL-17 receptor (IL17R) inhibitor (brodalumab) are relatively safe, tolerable and efficacious drugs. Nevertheless, side effects of IL-17 pathway inhibition occur. This review focuses on the dermatological manifestations linked to these treatments. Paradoxical psoriasis and atopic-like eczema may be the most common cutaneous adverse events, while manifestations such as neutrophilic dermatoses, hypersensitivity reactions, lichenoid eruptions, vasculitides, bullous diseases, lupus-like reactions, pigmentation disorders, adnexal diseases and granulomatous dermatoses have been described less frequently. [ABSTRACT FROM AUTHOR]

Psoriasis, psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) are chronic inflammatory diseases that often affect women of childbearing age. Detailed information about pregnancy and related outcomes across these indications in patients exposed to ixekizumab is lacking. To evaluate pregnancy outcomes after maternal or paternal exposure to ixekizumab in patients with psoriasis, PsA, or axSpA. Pregnancy cases from clinical trials and post-marketing reports, associated with either maternal or paternal exposure to ixekizumab cumulatively through 22 March 2019, were identified in the Eli Lilly Global Safety Database and described separately. One hundred and ninety-three ixekizumab-exposed pregnancies were identified. Maternal exposure occurred in 51.3% of pregnancies (clinical trials: n = 58; post-marketing: n = 41). The majority of paternal exposure pregnancies occurred in clinical trials (91 of 94). Live births were reported for 53.8 and 61.1% of known outcomes in maternal exposure pregnancies during clinical trials and post-marketing surveillance, respectively. No congenital malformations resulting from maternal exposure were reported in clinical trials: one case, not causally related to ixekizumab therapy, was recorded in the post-marketing setting. This integrated safety analysis provides relevant information for clinicians treating patients with psoriasis, PsA, or axSpA with ixekizumab. No new safety signals were identified in patients receiving ixekizumab. [ABSTRACT FROM AUTHOR]

To assess treatment patterns of Ixekizumab (IXE) and evaluate the speed of onset and long-term clinical and quality-of-life outcomes among a subset of patients who switched from adalimumab (ADA) and secukinumab (SEC) to IXE in a real-world setting. A retrospective chart review study was conducted at a single US dermatology referral center. 153 patients were included in the study, 69.3% of patients were biologic-experienced. ADA was the most commonly used biologic prior to IXE initiation. 66.7% of patients remained on IXE at the study end. 47.7% of patients received concomitant methotrexate, and usage decreased consistently after 1 month. IXE treatment duration was longer among patients who were early responders (achieved sPGA (0,1) at 1 month) vs. non-early responders. 69.4% and 43.3% of patients who switched from ADA and SEC to IXE achieved sPGA (0,1) by week 4, respectively. Patients who switched to IXE, specifically from ADA or SEC, had rapid treatment response as well as desirable long-term outcomes. IXE persistence was longer among early responders than non-early responders. Concomitant usage of methotrexate prior to switching to IXE and as a concomitant bridging treatment was reduced after IXE initiation while the proportion of patients achieving treatment targets remained high. [ABSTRACT FROM AUTHOR]

Nail psoriasis (NP) is common and of high importance in patients with psoriasis. Complete resolution of NP at week 24‒26 is an unambiguous nail outcome accessible for indirect treatment comparison of biologics. To evaluate the comparative efficacy of approved biologics in achieving complete resolution of NP at week 24‒26. A network meta-analysis (NMA) was conducted to indirectly compare the efficacy of six biologics in achieving complete resolution of NP at week 24‒26 in patients with moderate-to-severe psoriasis and concomitant NP. Complete resolution of NP was defined as a score of zero on the Nail Psoriasis Severity Index (NAPSI), modified NAPSI (mNAPSI) or Physician's Global Assessment of Fingernails (PGA-F). The probability of achieving complete resolution of NP was highest for ixekizumab (46.5%; 95% credibility interval [CrI] 35.1‒58.0; Surface Under the Cumulative RAnking curve [SUCRA] 97%), followed by brodalumab (37.0%; 17.0‒61.0; 79%), adalimumab (28.3%; 24.4‒32.4; 62%), guselkumab (27.7%; 21.1‒35.1; 58%), ustekinumab (20.8%; 10.2‒35.2; 37%), and infliximab (0.8%; 0.0‒8.9; 17%). In patients with moderate-to-severe psoriasis and concomitant NP, ixekizumab has the greatest likelihood among approved biologics of achieving complete resolution of NP at week 24‒26. Findings should be interpreted carefully because of inherent study limitations. [ABSTRACT FROM AUTHOR]

There is limited real-world evidence on using ixekizumab in psoriasis patients. Therefore, we characterized patients with psoriasis initiating ixekizumab and report 6-month changes in disease and patient-reported outcomes. Adult patients with psoriasis who initiated ixekizumab and completed a 6-month follow-up visit were enrolled from the Corrona Psoriasis Registry. Disease characteristics and outcomes were assessed at ixekizumab initiation. Outcomes included the mean 6-month change in Psoriasis Area and Severity Index (PASI), body surface area (BSA), Investigator Global Assessment (IGA), and IGA*BSA. From baseline to follow-up in all patients (n = 136), means decreased for IGA*BSA (−45.5) and BSA (−12.4), and a higher % achieved an absolute PASI ≤ 5 (84.6%), BSA 0–3 (72.1%), and IGA 0/1 (50.7%). Within stratified groups, means decreased for PASI <12 for IGA*BSA (−21.1) and BSA (−6.3); PASI≥12 for IGA*BSA (−94.8) and BSA (−24.6); weight <100 kg for IGA*BSA (−45.1) and BSA (−12.4); weight ≥100 kg for IGA*BSA (−46.2) and BSA (−12.3); concomitant PsA for IGA*BSA (−56.0) and BSA (−15.3); and in no concomitant PsA for IGA*BSA (−36.9) and BSA (−10.0). We provide real-world evidence on the benefits of ixekizumab for treating psoriasis, regardless of baseline disease severity, weight, or concomitant PsA. [ABSTRACT FROM AUTHOR]

Psoriasis in pediatric patients is uncommon and the management of moderate-to-severe cases can be challenging. We report the case of a 17-year-old girl who presented with severe plaque psoriasis unresponsive to UVB phototherapy. The Psoriasis Area Severity Index (PASI) was 18 and the Dermatology Life Quality Index was 24. We decided to prescribe ixekizumab, observing complete skin clearance after only 8 weeks. The patient is still on treatment with no reported adverse events after two years. [ABSTRACT FROM AUTHOR]

Data on real-world experiences for patients treated with ixekizumab is currently limited. Describe characteristics of ixekizumab-treated psoriasis patients and provide evidence of clinical outcomes using disease severity scores Body Surface Area (BSA) and Psoriasis Area and Severity Index (PASI) in the real world. Chart review was performed for adult patients treated with ixekizumab at a single Canadian dermatology clinic (February 2017–August 2018). The cohort was stratified into responders (patients who remained on ixekizumab) and non-responders (patients who discontinued ixekizumab). Subgroup analyses were performed for responders to assess clinical improvement stratified by previous biologic exposure. Thirty-eight patients were included (mean observational time 32 weeks). At baseline, mean PASI and BSA were 10.8 and 11.6%, respectively. Mean changes in PASI and BSA were –7.8 and –6.7%, respectively, at week 4. PASI 100 was achieved in 70% of patients. Significant differences in mean change of BSA were seen between bio-naïve and bio-experienced patients. This analysis represents the first investigation of early clinical outcomes in a small cohort of Canadian patients treated with ixekizumab. Overall, complete and rapid skin clearance was observed. Future studies including more patients and longer follow-up time are crucial to confirm these findings. [ABSTRACT FROM AUTHOR]

Factors beyond the Psoriasis Area and Severity Index (PASI) contribute to disease severity in psoriasis and potentially affect treatment responses. This subset analysis of data from two phase 3 clinical studies assessed baseline parameters in patients with different degrees of psoriasis severity in order to determine treatment responses to ixekizumab and safety outcomes. This study used integrated data from the UNCOVER-2 and -3 trials involving 2709 patients with chronic plaque psoriasis to assess the efficacy and safety of ixekizumab in three subgroups of patients, defined by PASI > 15 (group 1), PASI > 15 and history of ≥3 non-biologic systemic therapies (group 2), or PASI = 12-15 (group 3). In groups 1 and 2, additional baseline features were identified that could influence treatment responses, including age at disease onset, Dermatology Life Quality Index, and work productivity. Irrespective of subgroup, ixekizumab demonstrated high PASI responses at weeks 12 and 60, which were evident as early as week 2. Adverse events did not differ across subgroups. Our data support the efficacy, early onset of action, and maintained response of ixekizumab as observed in previous trials, and highlight the complexity of comprehensively defining disease severity in psoriasis. [ABSTRACT FROM AUTHOR]

It is challenging to select the most appropriate biologic treatment for patients with moderate-to-severe plaque psoriasis. To compare speed of onset and level of skin improvement between the interleukin (IL)-17A antagonist ixekizumab and the IL-23 p19 inhibitors guselkumab, tildrakizumab, and risankizumab in patients with moderate-to-severe plaque psoriasis. Using data from controlled clinical trials, both adjusted indirect comparisons (AICs) and matching adjusted indirect comparisons (MAICs) were performed to determine the risk difference (RD) between ixekizumab and each IL-23 p19 inhibitor for the proportion of patients with ≥75%/90%/100% improvement compared with baseline in Psoriasis Area and Severity Index (PASI 75/90/100) up to week 12. Placebo, etanercept, or ustekinumab were used as the comparator bridge. In all (M)AICs, RDs generally significantly favored ixekizumab over guselkumab (placebo bridge), tildrakizumab (placebo or etanercept bridge), and risankizumab (placebo or ustekinumab bridge) from the earliest assessment time (≥ week 2) to week 12 when considering PASI 75/90/100 responses. Ixekizumab provides a faster onset of effect and earlier clinical benefits than guselkumab, tildrakizumab, or risankizumab in patients with moderate-to-severe psoriasis, as reflected by higher levels of skin improvement than with these IL-23 p19 inhibitors up to week 12. [ABSTRACT FROM AUTHOR]

IL-17 inhibitors, including secukinumab, brodalumab, and ixekizumab, have been U.S. Food and Drug Administration (FDA) approved for the treatment of psoriasis. In addition to psoriasis, IL-17 has been implicated in the pathophysiology of other inflammatory skin conditions. This review aims to synthesize and interpret the literature evaluating the off-label dermatologic uses of IL-17 inhibitors. We performed searches in PubMed and ClinicalTrials.gov for clinical trials, observational studies, case series, and case reports evaluating non-psoriatic uses of the three IL-17 inhibitors. Studies evaluated the efficacy of IL-17 inhibitors for the following conditions: hidradenitis suppurativa (HS), pityriasis rubra pilaris (PRP), Behçet's disease, alopecia areata, and allergic contact dermatitis. Based on the available literature, secukinumab appears to be a potential treatment for HS, PRP, and Behçet's disease, while ixekizumab appears to be a potential treatment for HS and PRP. However, more clinical trials data are needed to adequately assess the safety and efficacy of IL-17 inhibitors for the treatment of these conditions. [ABSTRACT FROM AUTHOR]

To compare long-term healthcare resource utilization (HCRU) and costs among patients who initiated ixekizumab (IXE) or adalimumab (ADA) for treatment of psoriasis in the United States. Adult patients with psoriasis who had ≥1 claim for IXE or ADA were identified from IBM MarketScan claims databases prior to the COVID-19 pandemic (1 March 2016–31 October 2019). The index date was the date of first claim for the index drug of interest. Inverse probability of treatment weighting was employed to balance treatment cohorts. All-cause and psoriasis-related HCRU and costs were examined for 24 months of follow-up. Costs were reported as per patient per month. Costs of psoriasis-related biologics were adjusted using published Institute for Clinical and Economic Review (ICER) discount factors. Index drug costs were adjusted for adherence and ICER discount rates. The analyses included 407 IXE and 2,702 ADA users. IXE users had significantly higher inpatient admission rate (all-cause HCRU: 14.9% vs. 11.0%; p =0.012) and greater mean length of stay per admission (days, 6.6 vs. 4.1; p =0.004) than ADA users. ICER-adjusted costs were significantly higher in IXE than ADA users (all-cause costs: $4,132 vs. $3,610; p <0.001; psoriasis-related costs $3,077 vs. $2,700; p <0.001). After adjusting for ICER and adherence, IXE and ADA drug costs were comparable ($3,636 vs. $3,677; p =0.714). Study relied on administrative claims data, subjected to data coding limitations and data entry errors. Rebates, patient assistance programs, and commission to wholesalers are not always captured in claims. Adjustment made by ICER discount factors may lead to double-discounting if the discounts have been applied in claim payments. All-cause HCRU was higher in IXE than ADA users. Healthcare costs were also higher in IXE than ADA users after ICER adjustment, over 24 months. Cost differences were largely driven by higher treatment adherence associated with IXE. Index drug costs were comparable after ICER and adherence adjustments. [ABSTRACT FROM AUTHOR]

Biologic switching is common in psoriasis patients with non-response to or adverse events under therapy with a biologic. However, evidence on efficacy of switching between newly approved biologics of similar mode of action is scarce. The objective was to assess the efficacy of treating psoriasis patients with an IL-17-receptor A antagonist after failure of any IL-17A antagonist and to identify predictors of treatment response. A retrospective multicenter chart review on psoriasis patients who received brodalumab after failure of ixekizumab or secukinumab therapy was conducted in five German University Medical centers. Overall, 23 patients were identified. PASI75 response to brodalumab was reached by 47.8% (11/23) of all patients at week 12 and at week 24. 3 patients experienced mild adverse events which did not lead to drug discontinuation. Brodalumab appears to be an efficacious and safe treatment option in psoriasis patients with prior exposure to IL-17A antagonists. [ABSTRACT FROM AUTHOR]

Axial spondyloarthritis (axSpA) is an inflammatory arthritis which affects primarily the entheses of the spine and sacroiliac joints with peripheral joint synovitis and extra-articular manifestations. In 2017, the first IL-17A inhibitor (IL-17Ai) secukinumab was approved for the treatment of radiographic axSpA not responding adequately to conventional therapies, and this was followed in 2019 by a second IL-17Ai, ixekizumab. These agents represent the first alternative class of biological treatments after the TNF inhibitor which dominated the therapeutic landscape of axSpA for over a decade. This review discusses the role of IL-17Ais in the treatment in axSpA focusing on the newest IL-17Ai ixekizumab. It provides a detailed overview of the drug pharmacodynamic, pharmacokinetics, and clinical trial data, including areas of future research needed in the post-marketing era. Early trials of ixekizumab for axSpA have shown encouraging results and an acceptable safety profile. Future phase IV trials should focus on direct head-to-head comparisons between ixekizumab and other biologic drugs, and stratify patients according to important disease characteristics known to affect treatment response including sex, HLA-B27 status, presence of MRI bone marrow edema at baseline, disease duration and any extra-articular manifestations. [ABSTRACT FROM AUTHOR]

Objectives: To describe ixekizumab treatment patterns, all-cause healthcare utilization, and costs among psoriasis patients. Methods: Adults diagnosed with psoriasis having ≥1 ixekizumab claim were selected from MarketScan® databases between March 01, 2016 and July 31, 2017. Patients were continuously enrolled for ≥6 months prior and ≥3 months after the index date (first ixekizumab claim) and followed until inpatient death, end of enrollment, or end of data. Treatment patterns included persistence, switching, and re-initiation. All-cause utilization and costs were reported per-patient-per-month (PPPM). Results: 801 patients (mean age 49 years; 55.8% male; median follow-up 201 days) were included. Among all patients, 87.4% were persistent (mean (median) duration 86 (75) days) Of the 12.6% of patients who discontinued ixekizumab, 11.9% re-initiated and 6.9% switched treatments. Mean (median) time to switching was 208 (206) days. Mean number of all-cause inpatient admissions and physician office visits PPPM were 0.01 and 0.72, respectively. Mean total cost PPPM was $8,371, of which pharmacy comprised $7,792. Ixekizumab costs, $7,079, occurred primarily during induction and were paid predominantly by health plans ($6,810 [96.2%]). Conclusion: Most (87.4%) ixekizumab users remained persistent during follow-up. Pharmacy was the primary driver of total healthcare costs, with the majority covered by health plans and <4% as patient out-of-pocket expense. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a chronic inflammatory skin disease that has been associated with a significantly higher risk of herpes zoster (HZ). Several newer biologics such as secukinumab, ixekizumab, and brodalumab inhibit IL-17 and have been highly effective for treatment of psoriasis. However, adverse events related to the immunosuppressive properties of these biologics have been observed. Methods: This review aims to synthesize and evaluate the literature investigating the risk of HZ in patients treated with IL-17 inhibitors, with a focus on psoriasis patients. We performed searches using the PubMED database with the following search terms: 'psoriasis,' 'herpes zoster,' 'secukinumab,' 'ixekizumab,' 'brodalumab,' 'IL-17,' 'anti-IL-17,' and 'safety.' Clinical trials, cohort studies, review articles, and meta-analyses were evaluated. Results: Studies did not detect a higher risk of HZ infections in psoriasis patients treated with IL-17 inhibitors when compared to those treated with placebo or other therapies. Studies of IL-17 inhibitors for other indications including psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, and asthma yielded similar results. Conclusion: IL-17 inhibitors do not appear to increase risk of HZ. However, IL-17 inhibitors are relatively new medications, and further long-term data may be necessary to confirm this finding. Nevertheless, HZ vaccination should be considered on a case-bycase basis prior to initiating IL-17 therapy. [ABSTRACT FROM AUTHOR]

Background: Ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets interleukin-17A, has shown superiority to ustekinumab (UST) and etanercept in skin clearance from randomized clinical trials in patients with moderate-to-severe psoriasis. Objective: To compare cumulative benefits of IXE versus UST over 52 weeks of treatment. Methods: Cumulative clinical benefit of IXE and UST was assessed by evaluating the area under the curve (AUC) for responders of Psoriasis Area and Severity Index (PASI), itch numeric rating scale (Itch NRS), and Dermatology Life Quality Index (DLQI) outcomes over 52 weeks using data from IXORA-S trial comparing IXE (N = 136) and UST (N = 166). Normalized cumulative benefit was calculated to obtain the percentage of the maximum AUC for each outcome measure. Missing values were imputed using non-responder imputation. Results: Significantly greater cumulative benefits were obtained for IXE compared with UST. Normalized cumulative benefit with IXE versus UST for PASI 75/90/100, Itch NRS (0), and DLQI (0,1) were 83.1% and 67.6%; 68.9% and 46.5%; 41.1% and 23.4%; 40.4% and 30.9%; and 62.2% and 46.6%, respectively. Cumulative clinical benefit ratios for IXE:UST were 1.23 for PASI 75, 1.48 for PASI 90, and 1.76 for PASI 100, indicating an increase in the cumulative clinical benefit for IXE versus UST as the clearance levels increased. Conclusions: IXE showed greater cumulative clinical benefit than UST. [ABSTRACT FROM AUTHOR]

Introduction: Psoriasis is a chronic, immune-mediated disease with significant associated comorbidities. Its pathogenesis is likely multifactorial, however, the interleukin-23/T helper 17 pathway has been identified as a critical axis in its pathogenesis. Interleukin-17A is the primary effector of this pathway and overexpression of IL-17A results in epidermal hyperplasia and an overly robust inflammatory response, resulting in the skin plaques and systemic inflammation seen in psoriasis. Targeted anti IL-17 therapies have demonstrated efficacy in the treatment of moderate-to-severe plaque psoriasis. Areas covered: A PubMed search was conducted for relevant literature. Secukinumab, ixekizumab, and brodalumab are anti IL-17 inhibitors currently approved for the treatment of moderate-to-severe plaque psoriasis. The efficacy and safety data from key phase III clinical trials are reviewed here. Expert opinion: By targeting a key mediator of the interleukin-23/T helper 17 pathway, IL-17 antagonists are an effective treatment for plaque psoriasis. It has demonstrated efficacy and a favorable safety profile in key phase III clinical trials. In addition to efficacy, IL-17 antagonists have also shown long-term maintenance of treatment response and a quick onset of action. The efficacy of IL-17 inhibitors in the treatment of moderate-to-severe psoriasis underscores the importance of the IL-23/Th17 pathway in the pathogenesis of psoriasis. [ABSTRACT FROM AUTHOR]

Background: Regarding treatment of psoriasis, dermatologists now use new, highly effective targeted therapies. Among such, biologic therapies have become a mainstay in patients with moderate to severe psoriasis; yet, a substantial proportion of patients show insufficient or no treatment response. Current literature has insufficient evidence for successful treatment when switching biologics after multiple failures, in particular when the biologics share a common mechanism of action. Objectives: To compile a case series of patients with moderate to severe psoriasis who had primary or secondary loss of response to multiple previous systemic treatments. We specifically focused on patients recently treated with the anti-IL-17A antibody secukinumab, who further received the anti-IL-17A antibody ixekizumab as subsequent therapy. Patients and methods: We performed a retrospective cohort analysis. Inclusion criteria were patients with moderate to severe psoriasis vulgaris (as defined by European consensus and the German guidelines), who have previously been treated with systemic therapies including three or more biological therapies. All patients treated with anti-IL-17A antibody secukinumab experienced a primary and/or secondary treatment failure and subsequently received the anti-IL-17A antibody ixekizumab. The primary outcome was treatment response to ixekizumab using PASI score; the secondary outcome was incidence of adverse events. Results: Twelve patients were included. At week 6 of ixekizumab treatment, PASI 75 was achieved in 91.7%, PASI 90 in 66.7%, PASI 100 in 8.3% of patients. At week 12, PASI 75 was achieved in 100%, PASI 90 in 100%, PASI 100 in 58.3% of the cohort. Throughout the observation period, no severe adverse events were observed. Conclusions: Ixekizumab proved to be an effective and safe therapeutic option for patients with prior systemic therapies, including biological treatments with the same mechanism of action. Thus, failure of secukinumab does not preclude future therapy success with a second IL-17A-directed therapy. [ABSTRACT FROM AUTHOR]

Three main biologics target the IL-17 pathway; these include secukinumab, ixekizumab, brodalumab, all of which are approved for treatment of moderate-to-severe plaque psoriasis. We performed a systematic review of the literature to determine if IL-17 inhibitors are prone to develop anti-drug antibodies (ADA) and how efficacy of treatment is influenced. A total of 14 papers were reviewed. Only one secukinumab trial detected treatment-emergent ADA in 4 out of 996 (0.41%) patients during the 52-week treatment period. Two of these patients (1 on 150-mg retreatment as needed and 1 on 150-mg fixed interval) were found to have neutralizing antibodies; however, they were not associated with decreased efficacy. One paper reported ADAs against ixekizumab. One out of 1150 (9%) developed titers to ixekizumab after receiving 160-mg-loading dose followed by 80 mg every 2 weeks. Nineteen out of 1150 (1.7%) developed high titer (>1:1280) which impacted clinical outcomes. Three studies did detect ADA against brodalumab; however, none were neutralizing. It is difficult to draw a conclusion from our findings given the variability in ADA development. Most trials did not develop ADA, and if they did, the majority of the time they were not neutralizing. Only ixekizumab showed decreased efficacy, but no increased adverse events in cases with neutralizing ADA. [ABSTRACT FROM AUTHOR]

Acrodermatitis continua of hallopeau (ACH) is a rare chronic inflammatory variant of pustular psoriasis often restricted to the distal portions the digits in the hands and feet. ACH is of a chronic relapsing nature and is invariably recalcitrant to many available topical and systemic anti-psoriatic therapies. On account of its low prevalence and high resistance to treatments, no clinical guideline of ACH exists. We present a patient with ACH resistant to multiple therapies, including the biologic adalimumab, who was successfully treated with an IL-17 inhibitor (ixekizumab). We believe our unique treatment with an excellent outcome may assist other dermatologists if faced with this condition. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate short- and long-term efficacy and safety of ixekizumab in patients according to psoriasis severity. Materials and methods: Data were integrated from clinical trials (UNCOVER-2, UNCOVER-3). Patients received placebo, 80-mg ixekizumab every 2 weeks (IXEQ2W), every 4 weeks (IXEQ4W), or 50 mg etanercept (ETN) biweekly for 12 weeks, then open-label IXEQ4W (UNCOVER-3). Psoriasis severity was categorized by baseline Psoriasis Area and Severity Index (PASI <20 and ≥20). Efficacy was evaluated by percentage reaching PASI 75, 90, 100, and absolute PASI ≤5, ≤2, and ≤1. Results: Significantly more patients with PASI ≥20 (vs. PASI <20) were male and had higher body weight. After 12 weeks, both severity groups had significantly more IXEQ2W- than ETN-treated patients reach PASI 75, 90, 100, and absolute PASI ≤5, ≤2, ≤1. Fewer PASI ≥20 vs. PASI <20 patients across treatments reached PASI ≤5, ≤2, and ≤1 at week 12. Efficacy was maintained during 156 weeks of ixekizumab treatment with no differences between groups. The IXEQ2W safety profile was similar between groups except for injection-site reactions (significantly higher in PASI <20). Conclusions: Ixekizumab demonstrated a high level of efficacy and had a consistent safety profile in patients with different baseline psoriasis severity levels. [ABSTRACT FROM AUTHOR]

Introduction: Secukinumab, an interleukin-17A (IL-17A) antagonist, is the first non-TNF alpha inhibitor agent licensed for ankylosing spondylitis (AS), which opens up a new era of alternative cytokine targets beyond TNF. Areas covered: This review explores the pathophysiology and scientific evidence behind the use of this new mode of action and discusses the basis for its efficacy and clinical utility in the management of AS. In particular, how the emergent data points towards the efficacy of secukinumab and ixekizumab, a second emergent IL-17A blocker, in AS has helped focus research into the IL-23/17 axis in entheseal driven disease in man and how IL-17A inhibition may be linked to the presence of innate and adaptive immune cell populations capable of IL-17A elaboration in these target tissues. Expert commentary: Collectively these emergent data point towards an efficacious role of IL-17A inhibition strategies targeting AS pathogenesis in a fundamental way whilst carrying a good safety profile. [ABSTRACT FROM AUTHOR]

Introduction: Psoriasis is a chronic immune-mediated skin disease with a multifactorial etiology. Studies have shown that the inflammatory cytokine interleukin-17A (IL-17A) is a key mediator in the pathogenesis. Targeted biologics have changed the outcome for patients in a variety of diseases including psoriasis. Ixekizumab is a humanized monoclonal antibody directed against IL-17A and it has been approved for the treatment of moderate-to-severe plaque psoriasis, and recently also psoriatic arthritis. Areas covered: In this review, we summarize the latest clinical study results on ixekizumab. Long-term Phase III study data on efficacy and safety are now available for both plaque psoriasis and psoriatic arthritis. Additionally, new indications for ixekizumab are under investigation. Expert commentary: Overall, the efficacy and safety of ixekizumab are promising. In plaque psoriasis, the efficacy of ixekizumab was superior to etanercept and ustekinumab, while the efficacy was comparable to adalimumab in psoriatic arthritis. The safety profile has also been found very tolerable and similar to other biologics; however, vigilance regarding non-invasive Candida infections is necessary. Also, caution is advised when treating patients with concomitant inflammatory bowel disease, since ixekizumab could cause exacerbations. Long-term studies in real-life treatment settings are needed to decide the actual potential and safety of ixekizumab. [ABSTRACT FROM AUTHOR]

Introduction: Psoriatic arthritis (PsA) is a heterogeneous inflammatory disorder with articular, peri-articular, and extra-articular features along with selected co-morbidities as a sequela to chronic inflammation. There is accumulating evidence that the Th-17 signaling pathway is of critical importance in PsA pathogenesis. Areas covered: Ixekizumab (IXE) is a humanized immunoglobulin G subclass 4 (IgG4) monoclonal antibody directed against IL-17A. Two phase III randomized clinical trials, SPIRIT-P1 and SPIRIT-P2, unequivocally demonstrated superiority of IXE (80 mg every two or 4 weeks) dosing over placebo in moderate-to-severe PsA patients that failed either NSAIDs, conventional disease-modifying anti-rheumatic drugs (csDMARDs), or tumor necrosis factor-α inhibitors (TNFi) for numerous articular and cutaneous parameters. IXE also delayed structural progression of PsA. No new safety signals were identified as compared with chronic plaque psoriasis studies which included many more patients. Expert opinion: IXE is a highly effective treatment for moderate to severe PsA patients, including those that have been previously exposed to csDMARD and TNFi. Most domains of PsA significantly improved with IXE treatment and disease modification was achieved. [ABSTRACT FROM AUTHOR]

Background: The development of biologic agents directed against distinct cytokines and receptors has advanced the therapeutic options available for psoriasis patients. Evidence from preclinical studies suggests that IL-17 may contribute to the pathogenesis of psoriasis. Objective: The objective was to review the safety and efficacy profile for each IL-17 inhibitor by evaluating phase III clinical trial data. Methods: We reviewed the results of phase III clinical trials for the IL-17 inhibitors secukinumab, ixekizumab, and brodalumab. Results: At week 12, the proportion of patients reaching Psoriasis Area and Severity Index (PASI 75) was above 60% for the most efficacious dose of each agent with favorable and comparable safety profiles. The most commonly reported adverse events were nasopharyngitis, headache, and upper respiratory tract infection. Conclusions: The clinical improvement among psoriasis patients on IL-17 inhibitors is similar or superior to the improvement seen with commercially produced biologic agents available accompanied by a favorable short-term safety profile. The results of the phase III trials indicate that IL-17 inhibitors are effective therapeutic options for psoriasis patients. [ABSTRACT FROM AUTHOR]

Background: Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin-17 A. Objective: Examine the efficacy of ixekizumab in clearing psoriasis within different body regions. Methods: Data from 3 placebo- (PBO) or PBO- and etanercept (ETN)-controlled trials were integrated. Patients with moderate-to-severe psoriasis were randomized to 12 weeks of PBO (UNCOVER-1, -2, -3, N = 792; UNCOVER-2, -3, N = 361), 50 mg ETN twice weekly (N = 740), or 80 mg ixekizumab every 2 (IXE Q2W; N = 1169; N = 736) or 4 weeks (IXE Q4W; N = 1165; N = 733) after a 160-mg starting dose. Results: Mean percent improvements in regional Psoriasis Area and Severity Index (PASI) were noted at Week 1 and increased through Week 12 in the IXE Q2W (approved dosing regimen) group for each body region. Week 12 improvements were 91.4% (head/neck); 92.8% (trunk); 89.9% (arms); and 88.7% (legs) (all regions p < .001 vs. PBO). Mean regional PASI improvements at Week 12 were ≥84.2% for ixekizumab versus ≤70.9% for ETN in all regions (p < .001). Scaling and thickness reduced faster than erythema. Conclusions: Within 12 weeks of ixekizumab treatment, all signs of psoriasis across all body regions reached clinically meaningful improvements, with the head/neck and trunk responding quicker than psoriasis of the arms and legs, especially with reduced scaling and thickness. [ABSTRACT FROM AUTHOR]

Introduction:Interleukin 17 (IL-17) antagonism provides a highly effective approach for treating psoriasis. Exacerbations of inflammatory bowel disease have been reported in anti-IL-17 psoriasis trials. Aim:To characterize the relationship between IL-17 inhibition and inflammatory bowel disease. Methods:A review of English-language articles was performed. Search terms included IL-17, psoriasis, inflammatory bowel disease, secukinumab, ixekizumab and brodalumab. Results:IL-17 A inhibition, IL-17RA inhibition and IL-17 knockout led to induction or exacerbation of colitis in mouse models. The placebo groups fared better than the treatment group in controlled trials of anti-IL-17 antibody and anti-IL-17 receptor for Crohn’s disease (CD). A brodalumab study (N = 1576) revealed one reported CD case. An ixekizumab study (N = 3736) evaluating moderate-to-severe psoriasis, four patients reported CD and seven reported UC while ixekizumab every 2 weeks led to a moderate exacerbation of UC in one patient and new-onset CD in one patient. A secukinumab study (N = 3430) revealed exposure adjusted incidence rates of 0.11 and 0.15 per 100 patient-years for CD and UC, respectively. Discussion:Anti-IL-17 medications are associated with IBD exacerbation. Caution should be used in prescribing these medications in patients with diagnosed IBD or personal history suggestive of IBD. [ABSTRACT FROM PUBLISHER]

Background:Scalp is a frequently affected and difficult-to-treat area in psoriasis patients. Objective:We assessed the efficacy of ixekizumab in the treatment of patients with scalp psoriasis over 60 weeks using the Psoriasis Scalp Severity Index (PSSI). Methods:In three Phase 3, multicenter, double-blind, placebo-controlled trials, patients with moderate-to-severe psoriasis in UNCOVER-1 (N = 1296), UNCOVER-2 (N = 1224) and UNCOVER-3 (N = 1346) were randomized to subcutaneous 80 mg ixekizumab every two weeks (Q2W) or every four weeks (Q4W) after a 160 mg starting dose, or placebo through Week 12. Additional UNCOVER-2 and UNCOVER-3 cohorts were randomized to 50 mg bi-weekly etanercept through Week 12. Patients entering the open-label long-term extension (LTE) (UNCOVER-3) received ixekizumab Q4W; UNCOVER-1 and UNCOVER-2 included a blinded maintenance period in which static physician global assessment (sPGA) 0/1 responders were re-randomized to placebo, ixekizumab Q4W, or 80 mg ixekizumab every 12 weeks (Q12W) through Week 60. Results:In patients with moderate-to-severe psoriasis with baseline scalp involvement, PSSI 90 and 100 were achieved at Week 12 in higher percentages of patients treated with ixekizumab Q2W (81.7% and 74.6%) or ixekizumab Q4W (75.6% and 68.9%) compared with patients treated with placebo (7.6% and 6.7%;p < .001 each ixekizumab arm versus placebo) or etanercept (55.5% and 48.1%;p < .001 each ixekizumab arm versus etanercept). These outcomes were maintained through Week 60 of the maintenance (UNCOVER-1 and UNCOVER-2) and LTE (UNCOVER-3) period in patients who continued on ixekizumab Q4W. Conclusion:Ixekizumab was efficacious in treating scalp psoriasis in patients with moderate-to-severe psoriasis, with most patients achieving complete or near-complete resolution of scalp psoriasis and maintaining this response over 60 weeks. [ABSTRACT FROM PUBLISHER]

Psoriasis is a chronic, immune-mediated, inflammatory dermatosis, affecting 2–3% of the US population. While first-generation cytokine antagonists targeting tumor necrosis factor alpha (TNF-α)-dependent pathways have produced favorable responses in the treatment of psoriasis, higher levels of efficacy in a greater proportion of patients have been shown in trials with antibodies targeting interleukin (IL)-17A and the IL-17 receptor subunit. This examines the role of IL-17 inhibitors in the treatment of plaque psoriasis. The efficacy and safety results from the phase-3 trials with monoclonal antibodies targeting IL-17RA (brodalumab) and IL-17A (ixekizumab and secukinumab) validate IL-17 as a highly effective therapeutic target for the treatment of plaque psoriasis. [ABSTRACT FROM PUBLISHER]

Interleukin (IL) 17-A appears to be integral to the pathogenesis of chronic plaque psoriasis. Recent clinical trials have shown that blockade of this cytokine with the biologic therapies—secukinumab, ixekizumab and brodalumab—have led to unprecedented treatment efficacy for psoriasis. In addition, their dual efficacy towards psoriatic arthritis increases their potential clinical utility and they promise to be an important treatment option for patients who have tumour necrosis factor inhibitor resistant disease. Here, we present the evidence for the high treatment efficacy of the IL-17A inhibitors but also discuss some potential questions and areas of research needed, including the lack of evidence behind the drug survival, immunogenicity and safety profile. [ABSTRACT FROM PUBLISHER]

Background: Studies investigating the molecular basis of psoriasis have established the central roles of TNFα, interleukin (IL)-12, IL-22 and IL-23 and there is increasing evidence that IL-17 plays a critical role in the complex pathophysiology. Preclinical studies suggest that IL-17 is a desirable therapeutic target for psoriasis treatment. Methods: We reviewed the results of the phase II clinical trials for the anti-IL-17 agents secukinumab, ixekizumab and brodalumab in order to assess the efficacy and safety profile of each agent. Results: By week 12, the proportion of patients reaching Psoriasis Area and Severity Index (PASI 75) was comparable among the most efficacious dosage between the different agents (secukinumab 82%, ixekizumab 83% and brodalumab 82%; p < 0.001 compared to placebo for all agents). The safety profiles of the agents were similar with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections and injection site reaction. A small percentage of patients experienced low-grade neutropenia that was predominantly transient and asymptomatic. Conclusion: The anti-IL-17 agents demonstrated a rapid and robust clinical improvement accompanied by a favorable short-term safety profile. The results of the phase II trials support the theory that the IL-17 pathway is an essential target in psoriasis treatment. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a chronic skin condition traditionally believed to involve the Th1 pathway. Recently, the IL-23/Th17/IL-17 pathway has been highlighted in the pathogenesis of psoriasis and other autoimmune inflammatory conditions. From a clinician's perspective, we sought to review the basic science data relevant to IL-17's role in psoriasis pathogenesis. Methods: We performed a Pubmed and Web of Knowledge search for English articles starting from 1990 that discussed the Th17 pathway. Search terms such as 'IL-17' and 'psoriasis' were utilized. Results: The IL-17 pathway is regulated by IL-23, a cytokine that is vital for the expansion and maintenance of the Th17 cell population. Th17 derived cytokines (IL-17A, IL-17F, IL-17A/F and IL-22) were elevated in both psoriasis-like murine models and human psoriatic lesional biopsies. Ixekizumab (anti-IL-17A) treatment of psoriasis was found to normalize levels of IL-17 downstream gene products. Conclusion: Both preclinical and clinical studies support the central role of IL-17 in the pathogenesis of psoriasis. [ABSTRACT FROM AUTHOR]

Ixekizumab is an injectable monoclonal antibody against IL-17A approved by the US Food and Drug Administration for the treatment of plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. We present what we believe is the first case of herpes zoster (shingles) in a patient 12 weeks after starting ixekizumab for presumed erythrodermic psoriasis. It is important to be aware of potential side effects of immunomodulatory medications, particularly those that are new to the market. [ABSTRACT FROM AUTHOR]