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Introduction: Limited real-world data are available comparing multiple biologics on their adherence, persistence, and the use of concomitant biologics in the treatment of moderate-to-severe psoriasis in clinical practice. The objective was to compare persistence of and adherence to ixekizumab (IXE) treatment, as monotherapy or with concomitant medication, versus patients receiving other commonly prescribed biologics. Methods: Patients who newly initiated IXE, adalimumab (ADA), etanercept (ETN), secukinumab (SEC), or ustekinumab (UST) in IBM MarketScan® databases with diagnosis of psoriasis were identified. Treatment comparisons on medication persistence, adherence, and monotherapy were based on balanced samples after inverse probability of treatment weighting (IPTW). Results: A higher proportion of patients receiving IXE had had previous biologic therapies (50.3%) versus other biologics (ADA: 9.1%, ETN: 10.9%, SEC: 33.9%, UST: 19.7%). Patients treated with IXE showed statistically (p < 0.001) greater persistence than patients treated with SEC, ADA, UST, or ETN at both 1-year follow-up and up to 3 years of follow-up. Adherence for patients treated with IXE was significantly (p < 0.001) higher compared to ADA, ETN, and UST at both 1-year follow-up and up to 3 years of follow-up. There was no significantly higher adherence in patients treated with IXE compared to those treated with SEC at 1-year follow-up, but IXE had higher adherence than SEC (p < 0.05) at 1–3 year follow-up. IXE showed longer time on monotherapy than ADA (p < 0.001), ETN (p < 0.001), SEC (p < 0.05), and UST (p < 0.001) for both 1-year and 1–3 year follow-up. Sensitivity analyses on persistence, adherence, and monotherapy with further model adjustments after IPTW confirmed the findings. Conclusions: Patients treated with IXE were more persistent on and adherent to treatment and remained on monotherapy longer compared to those on all other commonly prescribed biologics combined or with individual biologics. [ABSTRACT FROM AUTHOR]

Abstract Background Psoriasis is a chronic immune-mediated inflammatory skin disease which can also involve joints. It is often associated with burdensome comorbidities which negatively impact prognosis and quality of life (QoL). Biologic agents have been shown to be effective in controlling disease progression, but their use is associated with higher costs compared with traditional systemic treatments. The economic analysis of the CANOVA (EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: an obserVAtional longitudinal study of real-life clinical practice) study aims to assess the costs and cost-effectiveness of biologics in a real-world context in Italy. Methods The annualised overall direct costs of moderate-to-severe plaque psoriasis management, the annualised cost of biologic drugs and the cost per responder in the Italian National Health System perspective were assessed. More specifically, the cost per response and cost per sustained response of the most prescribed biologic therapies for the treatment of moderate-to-severe plaque psoriasis within the CANOVA study were assessed using the Psoriasis Area Severity Index (PASI) at several score levels (75, 90 and 100%). Results The most frequently used biologic therapies for plaque psoriasis were secukinumab, ustekinumab, adalimumab originator, and ixekizumab. Cost of biologics was the driver of expenditure, accounting for about 98% of total costs. Adalimumab originator was the biologic with the lowest cost per responder ratio (range: €7848 - €31,378), followed by secukinumab (range: €9015 - €33,419). Ustekinumab (range: €11,689 – €39,280) and ixekizumab (range: €11,092 – €34,289) ranked respectively third and fourth, in terms of cost-effectiveness ratio. As concerns the cost per sustained response analysis, secukinumab showed the lowest value observed (€21,375) over the other options, because of its high response rate (86% vs. 60–80%), which was achieved early in time. Conclusion Biologic therapy is a valuable asset for the treatment of moderate-to-severe plaque psoriasis. Concomitant assessment of treatment costs against the expected therapeutic response over time can provide physicians and payers additional insights which can complement the traditional risk-benefit profile assessment and drive treatment decisions.

Abstract Background Patients with non-radiographic axial spondyloarthritis experience negative impacts on sleep, work productivity, and activity impairment. Ixekizumab, a monoclonal antibody selectively targeting interleukin-17A, has shown efficacy in treating the signs and symptoms of non-radiographic axial spondyloarthritis. This analysis evaluated the effect of ixekizumab treatment on sleep, work productivity, and activity impairment in patients with non-radiographic axial spondyloarthritis. Methods COAST-X ( NCT02757352 ) was a 52-week, phase 3, multicenter, randomised placebo-controlled trial evaluating 80-mg ixekizumab every 2 weeks and every 4 weeks in patients with active non-radiographic axial spondyloarthritis. Sleep disturbance was measured with the Jenkins Sleep Evaluation Questionnaire (JSEQ) and analysed using mixed-effects models for repeated measures. Work productivity and activity impairment were measured using the Work Productivity and Activity Impairment Questionnaire for Spondyloarthritis and analysed using analysis of covariance. Absenteeism, presenteeism, and overall work impairment were assessed for patients reporting paid work; activity impairment was assessed regardless of work status. Results Overall, patients treated with both dosing regimens of ixekizumab reported numerically greater improvements in sleep than placebo through Week 52. At Weeks 16 and 52, patients treated with ixekizumab every 4 weeks had significantly greater improvements in presenteeism (p = 0.007 and p = 0.003, respectively) and overall work impairment (p = 0.014 and p = 0.005, respectively) and numeric improvements in absenteeism than placebo. Patients treated with ixekizumab every 2 weeks had numerically greater improvements in absenteeism, presenteeism, and overall work impairment than placebo. Both dosing regimens of ixekizumab were associated with significantly greater improvements in activity impairment than placebo (ixekizumab every 4 weeks: p = 0.003 at Week 16 and p = 0.004 at Week 52; ixekizumab every 2 weeks: p = 0.007 at Week 16 and p = 0.006 at Week 52). Conclusions Treatment with ixekizumab improved sleep, work productivity, and activity impairment in patients with nr-axSpA. Improvements in presenteeism and overall work impairment were sustained and consistent in the patients treated with ixekizumab every 4 weeks from Week 16 to Week 52. Improvements in activity impairment were sustained and consistent in both ixekizumab-treated groups from Week 16 to Week 52. Trial registration NCT02757352 , May 2, 2016.

Biologics, as IL17 inhibitors, are frequently prescribed for moderate to severe plaque psoriasis. Although mucocutaneous candida infections are a well-known side effect of IL-17 inhibitors, there is no data about dermatophyte infection under this therapy. Generalized tinea corporis can mimic the clinical picture of psoriasis, especially if concomitant treatment with topical corticosteroids is used. Therefore, physician should be aware of this differential diagnosis if they suspect a loss of efficacy of IL-17-inhibitors with a flare-up of psoriasis.

INTRODUCTION:Palmoplantar psoriasis (PP) and palmoplantar pustulosis (PPP) are diseases affecting the hands and/or feet that can cause marked physical discomfort and functional disability. The tumor necrosis factor-alpha antagonists adalimumab, etanercept, and infliximab, the interleukin (IL)-17A inhibitors ixekizumab and secukinumab, and the IL-23 or IL-12/IL-23 inhibitors guselkumab and ustekinumab have been well studied for the treatment of moderate to severe plaque psoriasis. Less is known about the efficacy and safety of these agents for the treatment of PP (hyperkeratotic and pustular forms) and PPP. The aim of this review was to investigate the efficacy of biologic therapy for the treatment of hyperkeratotic PP, pustular PP, and PPP. METHODS:A systematic search of the medical electronic databases (Medline, Embase, and Cochrane Library) was conducted to identify studies or case reports which both used biologic therapy for the treatment of hyperkeratotic PP, pustular PP, and PPP and reported treatment outcomes. RESULTS:The systematic search identified 579 published articles, of which 44 were included in the analysis. Seven of the articles involved randomized placebo-controlled trials, two were open label trials, and the remaining were cohort studies, case series, or case reports. In the randomized controlled trials on the treatment of hyperkeratotic PP, adalimumab, guselkumab, infliximab, ixekizumab, and secukinumab each demonstrated superiority to placebo at 16, 16, 14, 12, and 12 or 16 weeks, respectively (p  0.05), although an open label study demonstrated that four of five patients on a therapeutic regimen of ustekinumab 90 mg achieved clinical clearance at 16 weeks. For the treatment of PPP, etanercept and ustekinumab 45 mg were not superior to placebo at 12 and 16 weeks, respectively (p > 0.05). A combined analysis of studies for hyperkeratotic PP demonstrated that 94.7%, 90.0%, 82.5%, 89.1%, and 86.7% of patients experienced an improvement of at least 50% upon treatment with adalimumab, guselkumab, ixekizumab, secukinumab, and ustekinumab, respectively. In a combined analysis of case reports examining PPP, infliximab showed the greatest efficacy at 100.0% clinical improvement of patients from case reports, followed by ustekinumab at 58.8% clinical improvement. Few serious adverse events were reported, but several were reported in patients treated with infliximab or secukinumab. CONCLUSION:Biologic therapy is effective and well-tolerated for the treatment of hyperkeratotic PP, but less data are available on the treatment of pustular PP or PPP. Adalimumab, guselkumab, ixekizumab, secukinumab, and ustekinumab all showed > 80% efficacy for the treatment of hyperkeratotic PP, while infliximab and ustekinumab showed moderate efficacy for the treatment of pustular PP, and infliximab was the most efficacious treatment for PPP.

Die generalisierte pustuläre Psoriasis (GPP) ist eine schwere und potenziell lebensbedrohliche Art der Psoriasis. Wir stellen den Fall eines Patienten mit schwerer GPP vor, die zunächst erfolglos mit Cyclosporin behandelt wurde. Wir haben uns für die Behandlung des Patienten mit Ixekizumab entschieden, einem Anti-IL-17-Antikörper, der für seine schnelle Wirkung bei Psoriasis vulgaris bekannt ist und auch bei GPP als wirksam beschrieben wurde. Der Zustand des Patienten verbesserte sich schnell, mit Auflösung der aktiven Läsionen nach der ersten Verabreichung. Die Behandlung wird seit 2 Jahren ohne unerwünschte Ereignisse und mit anhaltender Krankheitsüberwachung fortgesetzt. Ixekizumab könnte als sichere und effektive Option bei Patienten mit GPP angesehen werden. [ABSTRACT FROM AUTHOR]

BackgroundRecent studies into the pathogenesis of psoriasis have identified the importance of interleukin 17 (IL-17) in disease activity and have thus provided a new target for biologic therapy. Ixekizumab, the most recent US Food and Drug Administration (FDA)-approved anti-IL-17 biologic agent, appears to be a promising medication for patients suffering from moderate-to-severe plaque psoriasis.MethodsWe reviewed the results of phase III trials for ixekizumab in order to assess the efficacy, safety, and impact on quality of life of this agent in the treatment of plaque psoriasis. Additionally, we compared these results to phase II and phase III trials for other biologic psoriasis medications including the anti-IL-23 agents tildrakizumab and guselkumab, the combined anti-IL-12 and anti-IL-23 agent ustekinumab, and the anti-IL-17 agents brodalumab and secukinumab.ResultsPooled results from individual studies demonstrate that among the most efficacious dosing regimens of these anti-interleukin therapies, ixekizumab achieves higher Psoriasis Area and Severity Index 75 rates and similar or higher static Physician Global Assessment 0-1 rates than the other anti-IL-17 and anti-IL-23 agents. The safety profile of ixekizumab is similar to these agents, with nasopharyngitis, upper respiratory infection, headache, arthralgia, and injection-site erythema as the most commonly reported adverse events.ConclusionIxekizumab is a highly efficacious, newly FDA-approved treatment for moderate-to-severe plaque psoriasis that demonstrates a robust clinical response, significant improvement in patient quality of life, and a favorable safety profile.

BackgroundTreatment for pediatric psoriasis is challenging because of the lack of real-world evidence, especially for biological therapies.ObjectivesThis study evaluated the efficacy and safety of biologics in children with psoriasis based on real-world evidence.MethodsPediatric psoriasis patients aged

The article describes the peculiarities of drug provision for patients with psoriatic arthritis (PsA) in the Republic of Karelia. We present a clinical case of effective treatment with interleukin 17 inhibitor ixekizumab (IXE) in a randomized clinical trial and real clinical practice in a patient with PsA. The distinctive feature of this case is the severity of PsA course that was not controlled by standard methods of therapy. IXE treatment was characterized by a rapid clinical improvement of both articular and skin symptoms and subsequent achievement of remission, which lasted for 3 years (on the therapy). The forced interruption of the treatment led to the relapse of the disease in a short amount of time. In 2 years IXE therapy was resumed; after 6 months of continuing treatment a stable remission of PsA was achieved. The patient is still in clinical remission (on therapy).

Data in the scientific literature on the use of biologic therapy in localized forms of psoriasis elucidate mostly the problems of treatment of palmoplantar, scalp psoriasis and nail psoriasis. At the same time, the number of scientific data on the effect of biological therapy on genital psoriasis is extremely limited. Important that the quality of life on patients with genital psoriasis has very low level, which indicates a significant influence on the psychological and social well-being. At the same time, the limited number of therapeutic approaches makes this problem even more urgent. Unfortunately, special clinical trials for such patients are rather an exception. Ixekizumab has been reported an effectiveness for patients with anogenital psoriasis. New data on the comparative efficacy of ixekizumab and secukinumab give hope us for new opportunity for the treatment of genital psoriasis.

In recent years, highly effective target drugs – inhibitors of interleukin 17A (iIL17A) – monoclonal antibodies, – have been widely used to treat patients with psoriatic arthritis (PsA). The efficacy of iIL-17A in psoriasis, PsA, and axial spondyloarthritis has been proven in large multicenter randomized clinical and observational studies. The accumulated evidence and first direct comparative studies with inhibitors of tumor necrosis factor α (iTNFα) suggest that this class of drugs is becoming one of the key drugs in PsA, and the choice of this therapy is more justified, which is reflected in international recommendations. The 2019 revised EULAR guidelines consider iIL 17 first-line biologics along with iTNF-α, whereas iIL-17A is a drug of choice in patients with significant concomitant skin psoriasis.

Ixekizumab (Taltz®) is a humanized anti-IL-17A monoclonal antibody approved for the treatment of various inflammatory diseases including psoriasis and psoriatic arthritis. Despite the favorable efficacy and safety, ixekizumab is also known for its high incidence of injection site reactions (ISRs), ranging from 6% to 55% in different studies according to different definitions and studied population. However, specific risk factors for ixekizumab-induced injection site reactions in patients with psoriatic diseases had not been well studied. In this retrospective study, we found that overweight or obesity might be a protective predictor for the occurrence of ixekizumab-induced ISRs in patients with psoriatic disease. Meanwhile, having a positive family history of psoriasis might be a potential risk factor. Last but not least, patients with diarrhea following ixekizumab injection were associated with a higher risk of developing ISRs. Future high-quality studies with larger samples are warranted to verify the relationship.

Introduction: Differences in psoriatic arthritis (PsA) treatment response between sexes for ixekizumab, an interleukin-17A antagonist, are largely unexplored. This analysis used data from randomized clinical trials (RCTs) evaluating ixekizumab to study differences in treatment response between male and female patients with PsA. Methods: We used pooled data from patients enrolled in SPIRIT-P1 and SPIRIT-P2 (NCT01695239 and NCT02349295, respectively), phase 3 RCTs evaluating ixekizumab every 4 and 2 weeks in patients with active PsA. Subgroups of patients were defined by sex (male, female). Efficacy was measured by the proportion of male and female patients achieving American College of Rheumatology 20%/50%/70% improvement criteria (ACR20/50/70), minimal disease activity or very low disease activity (MDA/VLDA), and Disease Activity Index for Psoriatic Arthritis (DAPSA) scores representing low disease activity (LDA) or remission through week 156. Changes from baseline in components of the above measures were also assessed through week 156. Results: Compared to male patients at baseline, female patients were older, had higher body mass index and lower C-reactive protein levels, and had worse tender joint count, Health Assessment Questionnaire Disability Index, and Leeds Enthesitis Index scores. Through week 156, female patients in all treatment arms had lower response rates than male patients in all analyzed composite measures (ACR20/50/70; MDA/VLDA; DAPSA LDA/remission), with significant differences observed at multiple timepoints in both ixekizumab treatment arms. Female patients also had smaller numeric changes from baseline in the composite measures' individual components. Conclusion: Compared to female patients, male patients had greater response rates in ACR20/50/70, MDA/VLDA, and DAPSA LDA/remission and numerically larger improvements in these measures' individual components, although clinical significance is unclear. Continued efforts to understand sex differences in treatment response may provide insights that can help optimize clinical decision making. Trial registration: ClinicalTrials.gov identifiers, NCT01695239 and NCT02349295. [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]

Introduction: We report a comprehensive summary of the safety outcomes in adult patients with moderate-to-severe psoriasis with up to 5 years of exposure to ixekizumab. Methods: Long-term safety of the IL-17A antagonist ixekizumab was assessed from 17 randomized trials. Treatment-emergent adverse events (TEAEs)-adjusted incidence rates (IRs) per 100 patient-years (PY) within 1-year time periods through 19 March 2021 were calculated for all patients treated with at least one dose of ixekizumab. Reported cases of major adverse cerebro-cardiovascular events (MACE) and inflammatory bowel disease (IBD) were adjudicated. Results: A total of 6892 adult patients with a cumulative exposure of 18,025.7 PY were included. The IRs per 100 PY for any TEAE and serious adverse events (AEs) were 32.5 and 5.4. IR of discontinuation because of AE was 2.9. A total of 36 deaths were reported. IR of serious infections was low (1.3). There were no confirmed cases of reactivation of tuberculosis (TB). IR of Candida infections (IR 1.9) was low; most cases of Candida were localized, and no systemic cases were reported. IRs of injection site reactions and allergic/hypersensitivity were 5.9 and 5.6, respectively. No confirmed cases of anaphylaxis were observed. IRs were low for malignancies, depression, cytopenia, and MACE (all ≤ 1.2). IBD events were uncommon, although a total of 31 patients (IR 0.2) had confirmed IBD (ulcerative colitis, n = 18; Crohn disease, n = 13). Across safety topics, IRs decreased or remained constant over time. Conclusions: The long-term safety profile for ixekizumab is consistent with that previously reported in patients with psoriasis. No new or unexpected safety events were detected. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: Assess baseline characteristics and treatment response to ixekizumab (IXE) categorised by sex in patients with radiographic axial spondyloarthritis (r-axSpA) and non-radiographic axSpA (nr-axSpA) up to 52 weeks. Methods: Data were analysed from three randomised controlled trials of IXE through 52 weeks. Patients fulfilled ASAS classification criteria for r-axSpA or nr-axSpA and were randomised to receive 80 mg subcutaneous administration of IXE every 2 weeks (Q2W) or 4 weeks (Q4W), or placebo (16 weeks COAST-V/W; 52 weeks COAST-X). Baseline characteristics and treatment outcomes were assessed. Patients were categorised by sex; methods included non-responder imputation for categorical variables, and modified baseline observation carried forward for continuous efficacy variables. Results: At presentation, female patients had higher disease burden as reflected by significantly higher spinal pain at night, fatigue scores and pain/swelling in joints other than the neck, back or hip. ASAS40 response rate with the approved label dose, IXEQ4W, was achieved in 39% of male patients with r-axSpA by week 16, and 44% by week 52. For female patients, 16.7% and 33.3% achieved ASAS40 at week 16 and 52, respectively. In nr-axSpA, 46% of male patients achieved ASAS40 at week 16 and 30% at week 52. In total, 23.9% of female patients achieved ASAS40 at week 16, and 30.4% at week 52. Conclusions: This analysis demonstrates that for the axSpA disease spectrum, female patients present with higher disease burden. Following treatment with IXE, there is a higher proportion of male responders up to 16 weeks, while female patients show less robust responses for the first 16 weeks but larger responses from weeks 16 through 52. Trial Registration Numbers: NCT02696785, NCT02696798 and NCT02757352. [ABSTRACT FROM AUTHOR]

Introduction: Subcutaneous (SC) injection is a common route of drug administration; however, injection site pain (ISP) might create a negative patient experience. We evaluated ISP, bioequivalence, and overall safety of the citrate-free (CF) formulation of ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A. Methods: Two phase 1, single-blind studies were conducted in healthy participants. The crossover study A (NCT03848403) evaluated pain intensity on injection as measured by visual analog scale of pain (VAS) scores. Subjects (N = 70) were randomized 1:1:1 at the beginning to three possible treatment sequences and received a 1 mL SC injection of the three formulations sequentially in the abdomen on days 1, 8, and 15, respectively. A mixed-effects repeated measures analysis model was used to analyze VAS score by time post-injection. Study B (NCT04259346) evaluated the bioequivalence of a single 80 mg dose of CF formulation compared to the original commercial formulation. Subjects (N = 245) were randomized 1:1 to either commercial or CF formulation and received a single SC injection into the abdomen, arm, or thigh. Results: Primary endpoint was achieved in both studies. In study A, least-squares mean (LSM) difference of VAS scores immediately post injection between commercial (n = 61) and CF formulation (n = 63) was − 21.7 (p < 0.0001), indicating a lower degree of pain associated with CF formulation. In study B, bioequivalence of the CF formulation was established as 90% CIs for the ratio of geometric LSM AUC0–tlast, AUC0–∞, and Cmax between treatments were contained within the prespecified limits of 0.8 and 1.25. Except for less ISP in the CF formulation, overall safety profile was comparable. Conclusion: Ixekizumab CF formulation proved to be bioequivalent, was associated with less ISP, and had no other notable differences in the safety profile compared to the original commercial formulation. Trail Registration: ClinicalTrials.gov identifier NCT03848403, NCT04259346. [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]

The pharmacologic effect(s) of biotherapeutics directed against soluble targets are driven by the magnitude and duration of free target suppression at the tissue site(s) of action. Interleukin (IL)-17A is an inflammatory cytokine that plays a key role in the pathogenesis of psoriasis. In this work, clinical trial data from two monoclonal antibodies (mAbs) targeting IL-17A for treatment of psoriasis (secukinumab and ixekizumab) were analyzed simultaneously to quantitatively predict their target engagement (TE) profiles in psoriatic skin. First, a model-based meta-analysis (MBMA) for clinical responses was conducted separately for each drug based on dose. Next, a minimal physiologically-based pharmacokinetic (mPBPK) model was built to assess skin site IL-17A target engagement for ixekizumab and secukinumab simultaneously. The mPBPK model captured the observed drug PK, serum total IL-17A, and skin drug concentration-time profiles reasonably well across the different dosage regimens investigated. The developed mPBPK model was then used to predict the average TE (i.e., free IL-17A suppression) in skin achieved over a 12-weeks treatment period for each drug following their respective regimens and subsequently assess the TE-efficacy response relationship. It was predicted that secukinumab achieved 98.6% average TE in the skin at 300 mg q4w SC while ixekizumab achieved 99.9% average TE under 160 mg (loading) followed by 80 mg q2w SC. While direct quantification of free IL-17A levels at the site of action is technically challenging, integrated mPBPK-MBMA approaches offer quantitative predictions of free IL-17A levels at the site of action to facilitate future drug development via IL-17A suppression in psoriasis. [ABSTRACT FROM AUTHOR]

Introduction: The lifetime incidence of nail psoriasis in patients with psoriasis is 80–90%, with 23–27% of patients having nail psoriasis at any given time. Nail psoriasis is even more prevalent in patients with comorbid psoriatic arthritis. Complete psoriasis clearance, an achievable therapeutic goal, should ideally include the resolution of nail psoriasis. Here, we assessed simultaneous skin and nail clearance in patients with psoriasis across five head-to-head trials comparing ixekizumab with other biologics. Methods: Data were assessed in patients with moderate-to-severe psoriasis (with or without psoriatic arthritis) with nail psoriasis at baseline from the IXORA-R, IXORA-S, UNCOVER-2, UNCOVER-3, and SPIRIT-H2H trials. Ixekizumab patients received IXEQ2W to week 12 and IXEQ4W beyond week 12. PASI 100 depicted complete skin clearance, and PGA-F 0 (IXORA-R) or NAPSI 0 (all other trials) depicted complete nail clearance. Treatment comparisons were evaluated using the Cochran-Mantel-Haenszel test. Non-responder imputation was used for missing data. Results: Ixekizumab achieved significantly greater simultaneous skin and nail complete clearance than etanercept (UNCOVER-2: p < 0.001 and UNCOVER-3: p < 0.001) at week 12, demonstrating an efficacious and rapid response. Across all five head-to-head trials, ixekizumab achieved a high rate of simultaneous skin and nail clearance (range: 28.6–45.9% of patients) by week 24 that was maintained up to week 52 (range: 40.5–51.4% of patients). Ixekizumab achieved numerically greater simultaneous complete clearance than guselkumab at week 24 (p = 0.079), but statistically significant greater simultaneous clearance compared to ustekinumab (p < 0.001) and adalimumab (p = 0.006) at week 24 and week 52 (p < 0.001 and p = 0.007, respectively). Conclusion: In five head-to-head trials, ixekizumab-treated patients had higher rates of simultaneous complete skin and nail clearance compared to etanercept, guselkumab, ustekinumab, and adalimumab, thereby reinforcing ixekizumab's ability to achieve high levels of efficacy in multiple domains of psoriatic disease. Trial registration: NCT01474512, NCT01597245, NCT01646177, NCT03573323, NCT02561806, and NCT03151551. [ABSTRACT FROM AUTHOR]

Axial spondyloarthritis is a chronic inflammatory rheumatic disease that affects the axial skeleton and causes severe pain and disability. It may be also associated with extra-articular manifestations. Early diagnosis and appropriate treatment can reduce the severity of the disease and the risk of progression. The biological disease-modifying antirheumatic drugs (bDMARDs) tumor necrosis factor alpha (TNFα) inhibitors (TNFi) and the anti-interleukin (IL)-17A antibodies secukinumab and ixekizumab are effective agents to reduce disease activity and minimize the inflammation that damages the joints. New alternatives such as Janus kinase (JAK) inhibitors are also available. Unfortunately, response rates to bDMARDs are far from optimal, and many patients experience so-called treatment failure. The definition of treatment failure definition is often vague and may depend on the rigorousness of the therapeutic goal, the inclusion or not of peripheral symptoms/extra-articular manifestations, or patients' overall health. After an exhaustive bibliographic review, we propose a definition based on loss of the following status: low disease activity assessed by Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP, absence of extra-articular manifestations, and low disease impact on the patients' general health. Apart from discontinuing the therapy because of safety or intolerance reasons, two types of treatment failure can be differentiated depending on when it occurs: primary failure (no response within 6 months after treatment initiation, or lack of efficacy) and secondary failure (response within 6 months but lost thereafter, or loss of efficacy over time). Physicians should carefully consider the moment and the reason for the treatment failure to decide the next therapeutic step. In the case of primary failure on a first TNFi, it seems reasonable to switch to another class of drugs, i.e., an anti-IL-17 agent, as phase III trials showed that the response to IL-17 blockade was higher than to placebo in patients previously exposed to TNFi. When secondary failure occurs, and loss of efficacy is suspected to be caused by antidrug antibodies (ADAs), it is advisable to analyze serum TNFi and ADAs concentrations, if possible; in the presence of ADAs and low TNFi levels, changing the TNFi is rational as it may restore the TNFα blocking capacity. If ADAs are absent/low with adequate drug therapeutic levels, switching to another target might be the best strategy. [ABSTRACT FROM AUTHOR]

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Abstract Background Psoriasis is a common chronic inflammatory skin disease associated with overproduction of interleukin-17A (IL-17A). IL-17A monoclonal antibodies (mAbs) have shown clinical efficacy in psoriasis patients. Although a series of different overlapping mechanisms have been found to establish a link between psoriasis and cardiovascular diseases, the underlying mechanisms of the two types of diseases and the potential efficacy of IL-17A mAbs in amelioration of cardiovascular comorbidities remain unclear. Methods Serum samples from two study cohorts including 117 individuals were analyzed using a high-throughput UHPLC-MS platform. Non-targeted metabolic profiling analysis was first conducted with samples from 28 healthy individuals and from 28 psoriasis patients before and after 12-weeks of ixekizumab treatment in study cohort 1. Study cohort 2 was additionally recruited to validate the correlations of the identified metabolites with cardiovascular diseases. Results A total of 43 differential metabolites, including lysophospholipids, free fatty acids, acylcarnitines and dicarboxylic acids, were accurately identified in study cohort 1, and the analysis showed that lipid metabolism was impaired in psoriasis patients. Compared with healthy individuals, psoriasis patients had higher levels of lysophosphatidylcholines, lysophosphatidylinositols, lysophosphatidic acids and free fatty acids, but lower levels of acylcarnitines and dicarboxylic acids. The identified dicarboxylic acid levels were inversely correlated with psoriasis area and severity index (PASI) scores (P

Objective: to conduct a cost-effectiveness study of major biologic disease-modifying antirheumatic drugs (bDMARDs) used for the treatment of ankylosing spondylitis (AS) in Russian health care system with the focus on the new effective drug netakimab (NTK).Patients and methods. Based on the available meta-analysis, a Markov model for therapy was constructed using reference drugs. Then, based on the simulation results, a Cost-Effectiveness Analysis (CEA) and a Budget Impact Analysis (BIA) were carried out. The robustness of the result has been confirmed by several sensitivity analyzes.Results and discussion. NTK showed an advantage in CEA, including the cases when the direct costs of therapy were lower for the reference drug (which shows the greater efficacy of NTK). According to the BIA, the extension of NTK administration in naive patients was consistently associated with a decrease in the budgetary burden. Sensitivity analyzes confirmed the robustness of the result.Conclusion. NTK has clinical and economic advantage in the treatment of AS, it is attractive in terms of both patient's and health care benefit in general. More extensive use of NTK can save more than 5 billion RUB.

Objective: to evaluate the economic impact of the use of various biologic disease-modifying antirheumatic drugs (bDMARDs) from the group of inhibitors of interleukins (iIL) 12/23 and iIL17 in adult patients with psoriatic arthritis (PsA) with insufficient response to therapy with TNFα inhibitors (TNFα inhibitors).Patients and methods. A Microsoft Excel model has been developed, it allows to calculate the average cost of treatment of 1 patient with PsA who needs a second-line bDMARD from the iIL12/23 or iIL17 group. Only direct medical costs (drug costs) were considered. Cost minimization analysis and budget impact analysis were carried out.Results and discussion. The results of a network meta-analysis demonstrate no statistically significant differences in efficacy and safety between ixekizumab (IXE) and secukinumab (SEC) and superiority SEC over ustekinumab when used in adult patients with active PsA with insufficient response to or intolerance of previous therapy with synthetic disease-modifying antirheumatic drugs or TNFα inhibitors. The analysis of cost minimization showed that the total cost of 1 patient managing for 1 year using IXE is 26% lower than treatment with SEC: on a 2 year horizon, the difference is 27%. Analysis of the impact on the budget revealed that on the horizon of 1 year the simulated distribution will lead to budget savings of 16,796,131 rubles, which will allow additional treatment of 17 patients with IXE, after 2 years the budget savings will amount to 39,289,373 rubles, which will allow to treat additionally 52 patients. The sensitivity analysis confirmed the robustness of the study results.Conclusion. Thus, in adult patients with PsA requiring second-line bDMARDs, the use of IXE is more effective than the use of SEC and provides reduction in direct medical costs. The use of IXE will not have a significant impact on costs under the State Guarantee Program, but it can increase the availability of bDMARDs in patients with active PsA who have not responded to the previous therapy, without increasing the budget.

Abstract Background The efficacy and safety of ixekizumab (IXE) with and without continuous concomitant methotrexate (MTX), for up to 52 weeks of treatment, were evaluated in patients with active psoriatic arthritis (PsA). Methods Patients with active PsA who were biologic-naive (SPIRIT-P1) or had prior inadequate response to tumor necrosis factor inhibitors (SPIRIT-P2) were randomized to 80 mg IXE every 4 (IXE Q4W) or 2 weeks (IXE Q2W), after a 160-mg initial dose. In this post hoc analysis, efficacy and safety were assessed up to week 52 in the subgroups of patients who received (i) IXE as monotherapy and (ii) IXE along with a stable dose of MTX (no dose tapering or increase). Efficacy outcomes included, but were not limited to, the percentage of patients achieving the American College of Rheumatology (ACR) responses. Results Out of 455 patients initially randomized to IXE, 177 (38.9%) received monotherapy, 230 (50.5%) had concomitant MTX use, and 48 (10.5%) had other concomitant medication. Overall, 183 (40.2%) received IXE with a stable dose of concomitant MTX for 1 year. At week 52, the percentage of patients achieving ACR20/50/70 responses in IXE Q4W monotherapy versus concomitant MTX groups were 66.3% versus 55.3%, 48.4% versus 38.8%, and 35.8% versus 27.1%, respectively; these responses were generally similar with IXE Q2W. The safety profiles were similar between patients receiving IXE with or without concomitant MTX. Conclusions In this post hoc analysis, treatment with IXE demonstrated sustained efficacy in patients with PsA up to 1 year of treatment, with or without concomitant MTX therapy. Trial registration ClinicalTrials.gov NCT01695239 and NCT02349295 .

Introduction: The randomised, open-label, assessor-blinded, parallel-group SPIRIT-H2H trial (NCT03151551) demonstrated superiority of ixekizumab over adalimumab in simultaneously achieving improvement in joint symptoms (American College of Rheumatology [ACR]50) and clearance of skin lesions (Psoriasis Area and Severity Index [PASI]100) in biologic-naïve patients with active psoriatic arthritis (PsA) and plaque psoriasis (PsO) at Week 24. Additionally, this higher efficacy of ixekizumab versus adalimumab was maintained through Week 52. Objectives: This analysis aimed to investigate the efficacy and safety of ixekizumab and adalimumab in the subgroup of patients with PsA and moderate-to-severe PsO through W52. Methods: Efficacy and safety outcomes were analysed in patients with PsA and moderate-to-severe PsO (PASI ≥12, Body Surface Area ≥10%, static Physician Global Assessment ≥3) through W52. Categorical and continuous outcomes were analysed using logistic regression models and mixed model for repeated measures, respectively. Results: More ixekizumab- versus adalimumab-treated patients simultaneously achieved PASI100 and ACR50 at W24 (40.8% versus 17.6%, p=0.015) and W52 (38.8% versus 17.6%, p=0.026). Likewise, more ixekizumab- versus adalimumab-treated patients achieved PASI100 (59.2% versus 25.5%, p=0.001) and PASI90 (81.6% versus 60.8%, p=0.028) through W52, and nail PsO clearance at W24. Joint symptom improvements were comparable between treatment groups. No new safety findings were reported. Conclusions: Ixekizumab had higher efficacy than adalimumab in simultaneous achievement of ACR50 and PASI100 at W24 and W52 in patients with PsA and moderate-to-severe PsO. Ixekizumab-treated patients also showed higher response rates for nail PsO clearance and for reporting minimal or no impact on quality of life at Week 24.

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]

BackgroundAn increasing number of injectable biologics are now available for the treatment of psoriasis. However, for individuals who have never received this therapy, the process of performing a self-injection can be daunting. There is lack of patient educational material on how to perform and optimize this treatment.ObjectiveThe objective of this study is to present a freely available online guide and video on biologic injections that is informative to patients and increases the success and compliance of patients starting this therapy.MethodsThe self-injection technique taught at the University of California-San Francisco Psoriasis and Skin Treatment Center as well as available information from the literature were reviewed to design a practical guide for patients receiving biologic injections.ResultsWe created a printable guide and video resource that describes how to improve the injection process, pain management, travel planning, and common concerns with biologic injectables.ConclusionThis guide is beneficial for patients who wish to improve their experience with biologic self-injections, for healthcare providers who prescribe these treatments, and for trainees learning about this modality.

IntroductionInterleukin-17 inhibitors are the newest class of monoclonal antibodies approved by the US Food and Drug Administration for the treatment of psoriasis. Preclinical and Phase II studies of ixekizumab, a high-affinity anti-IL-17A monoclonal antibody, have proved promising.MethodsWe conducted an extensive literature search using the PubMed database to assess the efficacy and safety profile of ixekizumab. The search included the following key words: "psoriasis" and "IL-17" or "ixekizumab." We also reviewed citations within articles to identify relevant sources.ResultsBy week 12, the percentage of patients achieving a 75% improvement from baseline Psoriasis Area and Severity Index (PASI 75) was comparable among the three Phase III trials (UNCOVER-1, 89%; UNCOVER-2, 90%; UNCOVER-3, 87%). Ixekizumab continued to be efficacious through 60 weeks of treatment. The safety profile of ixekizumab was favorable; the most frequently reported adverse events consisted of nasopharyngitis, upper respiratory tract infection, injection-site reaction, and headache.ConclusionOverall, ixekizumab demonstrated rapid clinical improvement and favorable short-term safety profile in Phase III trials. The results support ixekizumab as an effective therapeutic option for patients with moderate-to-severe plaque-type psoriasis.

Aims: Ixekizumab is a high‐affinity monoclonal antibody that selectively targets interleukin‐17A used in the treatment of adult and paediatric patients with moderate‐to‐severe psoriasis. This analysis evaluated the pharmacokinetics (PK) of ixekizumab and the exposure–efficacy relationship in paediatric patients aged 6 to <18 years with psoriasis. Methods: Population PK and exposure–efficacy models were developed. The models used data from paediatric patients with psoriasis participating in the Phase 3 IXORA‐PEDS trial in which patients were dosed according to weight categories. The exposure–efficacy model is a Psoriasis Area and Severity Index (PASI) time course model using data up to Week 12, a co‐primary efficacy endpoint. Results: A 2‐compartment population PK model describes the PK of ixekizumab in paediatric patients with the effect of body weight incorporated on clearance and volume terms using an allometric relationship. The weight category‐based dosing ensured that ixekizumab mean trough serum concentrations in paediatric patients with psoriasis (3.20–3.33 μg/mL) were within the range of concentrations observed in adult patients with psoriasis (mean [standard deviation]: 3.48 [2.16] μg/mL) administered an efficacious dosing regimen. The observed PASI response rates at Week 12 in paediatric patients (91.9/81.8/52.5% for PASI75/90/100) are well predicted by the final exposure–efficacy model and response rates are similar or higher than those achieved in adults (86.2/66.6/35.0% for PASI75/90/100). Conclusion: This analysis is the first to describe the PK and exposure–efficacy relationship of ixekizumab in paediatric patients with psoriasis. The analyses support the selection of the weight category‐based ixekizumab dosing regimens approved for use in paediatric patients with psoriasis. [ABSTRACT FROM AUTHOR]

Introduction: Both early clinical improvement and long-term maintenance of clinical efficacy of treatments matter to patients with psoriasis. We compared cumulative clinical benefits of treatment with biologics over 1 year based on the area under the curve (AUC) for Psoriasis Area and Severity Index (PASI) 100 and PASI 90 responses in patients with moderate-to-severe psoriasis using a network meta-analysis (NMA). Methods: Published phase 3 randomized, placebo- or active-controlled clinical trial data for biologics approved for the treatment of moderate-to-severe psoriasis were obtained from a systematic literature review up to 30 September 2020. Eighteen clinical trials that included data from baseline to 48 or 52 weeks where AUC could be calculated were included. Data were compared using a fixed-effect model with a separate random-effect baseline model to account for effects of the placebo arm. Cumulative clinical benefit was estimated using the AUC for PASI 100 and PASI 90 responses (complete and almost-complete skin clearance, respectively). Normalized AUC was compared using Bayesian NMA. Cumulative days of response were calculated using normalized AUC and study duration. Results: Interleukin (IL)-17 and IL-23 inhibitors demonstrated greater cumulative clinical benefits for both PASI 100 and PASI 90 versus IL-12/23 and tumor necrosis factor inhibitors. Over 52 weeks, cumulative days with PASI 100 were greatest with ixekizumab [158.7 (95% credible interval, 147.4, 170.0) days] followed by risankizumab [154.0 (144.9, 163.4) days]; PASI 90 days were greatest with risankizumab [249.3 (239.5, 259.2) days] followed by ixekizumab [238.8 (227.1, 250.8) days]. Both ixekizumab and risankizumab showed greater cumulative days with PASI 100 or PASI 90 responses versus secukinumab [117.9 (110.7, 125.2) and 215.5 (208.2, 223.1) days, respectively] and greater cumulative days with PASI 100 versus guselkumab [130.7 (120.5, 140.9) days]. Conclusion: For complete and almost-complete skin clearance, ixekizumab and risankizumab provided the greatest cumulative clinical benefits over 1 year. [ABSTRACT FROM AUTHOR]

Introduction: Biologics have expanded the treatment options in the management of patients with moderate-to-severe psoriasis. The objective of this study was to describe patient characteristics and previous treatments in psoriasis patients newly treated with guselkumab, secukinumab, or ixekizumab. Methods: This retrospective study included patients ≥ 18 years old with psoriasis in the USA who were newly treated with guselkumab, secukinumab, or ixekizumab between 1 July 2017 and 31 March 2019 in the Modernizing Medicine Data Services database (MMDS). Patients were indexed on their first prescription or injection record of guselkumab, secukinumab, or ixekizumab, and three mutually exclusive cohorts were created. Patients were required to have evidence of moderate-to-severe psoriasis, defined as Physician Global Assessment (PGA) score of 3 or 4, or body surface area (BSA) ≥ 10% on index date or within 12 months before index. Baseline characteristics, including treatment history, were reported for each cohort. Results: The study population included 461 guselkumab, 619 secukinumab, and 375 ixekizumab patients. The median age across cohorts was 51–52 years. Median baseline BSA ranged from 15% to 20%; 16.1–29.3% of patients had a PGA of 4 and over half of patients were obese prior to index. Approximately 40% of patients had comorbid cardiovascular disease and 20.8–24.2% of patients had a psychiatric disorder. About half of patients in each cohort had prior biologic use, of which adalimumab was most common (28.2–34.9%) across the cohorts. Conclusion: This real-world study describes the characteristics of patients with moderate-to-severe psoriasis receiving biologic treatments. [ABSTRACT FROM AUTHOR]

Introduction: Persistence and adherence to psoriasis treatments reflect overall drug effectiveness, tolerability, and convenience. Limited data are available on the treatment patterns of ixekizumab, an interleukin (IL)-17A antagonist, vs. guselkumab, an IL-23 inhibitor. Our objective was to evaluate real-life psoriasis drug treatment patterns with ixekizumab vs. guselkumab. Methods: This retrospective observational study used United States insurance claims data from IBM Watson MarketScan Databases to analyze treatment patterns (including adherence, persistence, time on monotherapy, switching, and use of concomitant medications) for patients with 1 year, ≥ 6 months, and up to 30 months of follow-up. Outcomes were compared between ixekizumab and guselkumab on the balanced sample after applying inverse probability of treatment weighting (IPTW). Results: Data for 1414 eligible patients (ixekizumab, N = 674 and guselkumab, N = 740) were assessed. Over the 1-year follow-up, adherence was greater for ixekizumab vs. guselkumab when evaluated by proportion of days covered ≥ 80% [odds ratio (OR) 1.77 (95% confidence interval, 1.41, 2.21), p < 0.001] and by medication possession ratio ≥ 80% [OR = 1.92 (1.54, 2.38), p < 0.001]. Persistence was longer for ixekizumab vs. guselkumab with a 60-day allowable gap [non-persistence hazard ratio (HR) (95% confidence interval): 0.80 (0.69, 0.93), p = 0.005], but there were no differences with a 90-day allowable gap [HR = 0.98 (0.83, 1.17), p = 0.850]. Results assessed in patients with ≥ 6 months follow-up confirmed these findings. This retrospective analysis of a United States claims database used prescription refill data to estimate persistence/adherence. Conclusions: Based on real-world evidence using claims data, patients with psoriasis treated with ixekizumab had a greater adherence to and an equal or greater persistence with therapy vs. patients treated with guselkumab. Plain Language Summary: In real-world settings, how consistently patients take a drug (adherence) and how long they continue taking it (persistence) are thought to reflect patients' satisfaction with the combination of efficacy and tolerability of the treatment. In this study of patients with psoriasis, we compared these measures—regularity of prescription refills and continued time on drug—between patients receiving ixekizumab or guselkumab for their psoriasis. This information was taken from a large insurance claims database, and so reflects results among commercially insured patients in the United States. We found that patients taking ixekizumab more consistently obtained prescription refills during the study period. Patients taking ixekizumab or guselkumab continued treatment for similar lengths of time when we allowed a longer gap of 90 days between prescription refills, but when a shorter gap of 60 days was allowed, those on ixekizumab spent a longer time on treatment. The findings were consistent regardless of prior treatment with other similar drugs (biologics). Overall, these findings indicate that for ixekizumab, which is dosed once every 4 weeks, and guselkumab, which is dosed once every 8 weeks, patients took ixekizumab more regularly and continued on the drug for about the same or a longer amount of time compared to patients taking guselkumab. These results may help dermatology practitioners in selecting biologic drugs for their patients with psoriasis. [ABSTRACT FROM AUTHOR]

Background: Real-world data on long-term treatment patterns associated with interleukin-17A inhibitors in plaque psoriasis are lacking.Objective: To compare ixekizumab or secukinumab treatment patterns over a 24-month period among plaque psoriasis patients.Methods: Adult patients with psoriasis who had 1 or more claims for ixekizumab or secukinumab between March 1, 2016, and October 31, 2019, and with 24 months of follow-up after starting treatment were identified from IBM MarketScan claims databases. Inverse probability of treatment weighting and multivariable models were employed to balance cohorts and estimate the risks of nonpersistence, discontinuation, and switching and odds of highly adherent treatment (proportion of days covered ≥ 80%).Results: A total of 471 ixekizumab and 990 secukinumab users were included. Compared to secukinumab, ixekizumab use was associated with a 20% lower risk of nonpersistence (hazard ratio, 0.80; 95% CI, 0.70-0.92), a 17% lower risk of discontinuation (hazard ratio, 0.83; 95% CI, 0.72-0.96), and a 42% higher odds of being highly adherent to treatment (odds ratio, 1.42; 95% CI, 1.12-1.80). No difference in risk of switching was observed (hazard ratio, 0.83; 95% CI, 0.68-1.01).Limitations: Disease severity and clinical outcomes were unavailable.Conclusion: Over 24 months, ixekizumab users exhibited better persistence and adherence, and a lower risk of discontinuation than secukinumab users in real-world settings. [ABSTRACT FROM AUTHOR]

Introduction: Ixekizumab, a selective interleukin-17A antagonist, was compared with adalimumab in the SPIRIT-H2H study (NCT03151551) in patients with psoriatic arthritis (PsA) and concomitant psoriasis. This post hoc analysis reports outcomes to week 52 in patients from SPIRIT-H2H, stratified by baseline psoriasis severity. Methods: SPIRIT-H2H was a 52-week, multicenter, randomized, open-label, rater-blinded, parallel-group study of biologic disease-modifying antirheumatic drug (DMARD)-naïve patients (N = 566) with PsA and active psoriasis (≥ 3% body surface area involvement). Patients were randomized to ixekizumab or adalimumab (1:1) with stratification by baseline concomitant use of conventional synthetic DMARDs and psoriasis severity (with/without moderate-to-severe psoriasis). Patients received on-label dosing according to psoriasis severity. The primary endpoint was the proportion of patients simultaneously achieving ≥ 50% improvement in American College of Rheumatology criteria (ACR50) and 100% improvement in Psoriasis Area Severity Index (PASI100) at week 24. Secondary endpoints included musculoskeletal, disease activity (defined by composite indices), skin and nail, quality of life and safety outcomes. In this post hoc analysis, primary and secondary endpoints of SPIRIT-H2H were analyzed by baseline psoriasis severity. Results: A greater proportion of patients achieved the combined endpoint of ACR50 + PASI100 and PASI100 with ixekizumab compared with adalimumab at weeks 24 and 52, regardless of baseline psoriasis severity. ACR response rates were similar for ixekizumab and adalimumab across both patient subgroups. For musculoskeletal outcomes, similar efficacy was seen for ixekizumab and adalimumab, but ixekizumab showed greater responses for skin outcomes regardless of psoriasis severity. The safety profiles of ixekizumab and adalimumab were consistent between subgroups. Conclusions: Regardless of baseline psoriasis severity, ixekizumab demonstrated greater efficacy than adalimumab with respect to simultaneous achievement of ACR50 + PASI100, and showed consistent and sustained efficacy across PsA-related domains. It also demonstrated higher response rates for skin outcomes. These subgroup analyses highlight the efficacy of ixekizumab in patients with PsA irrespective of the severity of concomitant psoriasis. [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]

Psoriasis vulgaris is a chronic immune-mediated inflammatory disease of the skin. Biologic therapy has been available for more than 10 years and has become one of the standard treatments for patients with moderate to severe psoriasis. Initially, only biologics against tumour necrosis factor alpha (TNF-α) were used, and only later did drugs against different interleukins (ILs), including IL-17 or IL-23, became available. The side effects of biologic therapy include paradoxical adverse events (PAEs), such as palmoplantar pustular reaction, especially with anti-TNF-α drugs. We present the case of a 49-year-old female patient with diabetes and psoriasis and psoriatic arthritis treated with an adalimumab biosimilar who developed a severe PAE of the palmoplantar pustular type. Treatment with adalimumab was stopped and the patient switched to ixekizumab which was successful. When a paradoxical reaction develops during biologic therapy, especially when it is severe as in our patient, switching to another class of biologics is advised. [ABSTRACT FROM AUTHOR]