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Coloboma, congenital heart disease, ichthyosiform dermatosis, intellectual disability, conductive hearing loss, and epilepsy (CHIME) syndrome is a rare autosomal recessive neuroectodermal disorder caused by PIGL gene mutations. There is emerging literature to support the use of interleukin‐17 (IL‐17) antagonists in the treatment of certain ichthyosiform dermatoses. Here, we report a case of severe ichthyosiform dermatosis in a child with CHIME syndrome who was recalcitrant to multiple topical medications and dupilumab. This is the first reported case of successful treatment of congenital ichthyosiform dermatosis in a CHIME syndrome patient with ixekizumab, an IL‐17A antagonist. [ABSTRACT FROM AUTHOR]

Background: Psoriasis (PSO) involves about 1–3% of the population, and around 75% of women develop PSO before the age of 40. Official guidelines on the treatment of woman with anti-IL17 and anti-IL23 during this potential childbearing time are not currently available. Objective: To investigate the effectiveness and safety of biologic treatments in women of childbearing age. Methods: At the Dermatology Clinic of the University of Turin, Italy, 172 women aged 20–55 years underwent IL-17 and IL-23 inhibitor therapy for moderate-severe PSO and were followed up to 52 weeks in a real-life, retrospective, single-center study. Results: Overall, 40% of patients achieved PASI 100 at week 16, and 72% at week 52. A similar trend was observed for PASI 90 and PASI < 3 with almost 80% and 90% of patients achieving the target at 52 weeks. As for PASI 100, a statistically significant difference (p = 0.004) was found at 16 weeks, with 23.84% of patients achieving PASI 100, with IL-17 and 15.70% with the IL-23 inhibitor. No statistically significant differences were found at 28 and 52 weeks. No statistically significant differences in PASIs at any time points were recorded across the different biologic agents. Forty-six patients discontinued treatment. The most reported side effects were headache, nausea, asthenia, injection site pain, and rhinitis. Conclusions: This study showed that biologic drugs are effective and safe in women of childbearing age, with negligible side effects. [ABSTRACT FROM AUTHOR]

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

Background: In comparison with TNF‐α inhibitors, anti‐IL‐17A agents are considered to have a lower risk of active tuberculosis (TB) or latent TB infection (LTBI) reactivation. Methods: In this study, we aimed to evaluate the TB infection status and serial QuantiFERON‐TB‐Gold in tube test (QFT) results of psoriasis patients using IL‐17 inhibitors (secukinumab [SEC] and ixekizumab [IXE]) in a real‐world setting from a tuberculosis‐endemic country. Patients who used an anti‐IL‐17 agent for at least 3 months in our follow‐up were included in the study. Patients' clinical and demographic features, baseline QFT results and latest QFT results (if any), and TB infection status were noted from the past medical records. Results: A total of 717 patients, of whom 333 (46.4%) were female, were included in the study. The cumulative exposure time to an anti‐IL‐17 agent was 14,147 patient‐months, 9743 patient‐months for SEC and 4404 patient‐months for IXE. Also, 459 (SEC = 305/IXE = 154) patients used an anti‐IL‐17 agent for ≥ 12 months. Of these, 125 had positive baseline QFT results. In all, 334 had negative baseline QFT results. The latest QFT result of 309 was also negative (persistent seronegative group). During follow‐up, the QFT results of 10 patients changed from negative to positive (positive seroconversion group). Seven of them were using SEC and three were using IXE, respectively. No case of active TB infection was detected. Conclusion: In our study, the positive seroconversion rate of 10/334 seems high, but this did not translate to active disease. However, closer monitoring may be required, especially in patients with advanced age, the presence of PsA, long disease duration and long anti‐IL‐17 treatment duration. [ABSTRACT FROM AUTHOR]

Objectives To assess the frequency of simultaneous distal interphalangeal (DIP) joint disease and adjacent nail psoriasis (finger unit) among patients with psoriatic arthritis (PsA) and compare the efficacy of the IL-17A antagonist ixekizumab (IXE) and the TNF-α inhibitor adalimumab (ADA). Methods This post hoc analysis evaluated the simultaneous occurrence of DIP joint involvement (tenderness and/or swelling) and adjacent nail psoriasis among patients with PsA from the SPIRIT-H2H (NCT03151551) trial comparing IXE to ADA. Among patients with simultaneous DIP joint involvement and adjacent nail psoriasis in ≥1 digit at baseline, treatment effects were assessed through week 52 for each affected finger unit; 'finger unit' defines the connected DIP joint and adjacent nail of an individual digit. Results A total of 354 patients had simultaneous DIP joint involvement and adjacent nail psoriasis in ≥1 finger unit at baseline. Among them, 1309 (IXE: 639; ADA: 670) finger units had baseline DIP joint tenderness and/or swelling and adjacent nail psoriasis. Proportions of affected finger units achieving complete resolution were significantly higher with IXE vs ADA as early as week 12 (38.8% vs 28.4%, P  < 0.0001) and at all post-baseline assessments through week 52 (64.9% vs 57.5%, P  = 0.0055). Conclusion In this study cohort, patients with DIP joint involvement almost always had adjacent nail psoriasis. Greater resolution of DIP joint tenderness, swelling and adjacent nail psoriasis was achieved at all time points over 52 weeks through targeting IL-17A with IXE than TNF-α with ADA, which is noteworthy given prior comparable musculoskeletal outcomes for both drug classes. [ABSTRACT FROM AUTHOR]

Background: Generalized pustular psoriasis (GPP) is a rare, potentially life‐threatening skin disease often requiring long‐term therapy. We aimed to evaluate the use of Interleukin (IL)‐17A inhibitors (secukinumab and ixekizumab) in GPP patients over 96 weeks. Methods: We retrospectively analyzed a case series of 18 patients with GPP who received secukinumab (n = 13) and ixekizumab (n = 5) therapy with a 96‐week follow‐up period. The primary effectiveness analysis included determining the percentage of patients who achieved ≥90% or 100% improvement in the Generalized Pustular Psoriasis Area and Severity Index (GPPASI) score. Adherence was captured using the medication possession ratio (MPR). Results: Using the as‐observed (AO) method, 87% and 67% of patients treated with secukinumab or ixekizumab achieved GPPASI 90 and 100 responses, respectively. At Week 96, the mean GPPASI improvements from baseline GPPASI were 96.3% (95% CI: 0.91–1.01) using the AO method. After Week 48, 14 patients tapered (n = 8) or terminated (n = 6) the treatment. High‐adherence therapy (MPR ≥ 80%) was significantly superior to the low‐adherence group in the rate of patients achieving a GPPASI 100 response (AO, 100% vs. 38%, P < 0.05). By Week 96, 5 (27.8%) patients had new GPP flares, and 4 (80%) were in the low‐adherence group. No new safety signals occurred. Conclusion: IL‐17A inhibitors led to effective and sustained improvement in GPP patients, and high‐adherence therapy had long‐term positive effects on skin clearance. Given its relapsing nature, improving compliance is beneficial for long‐term clinical management. [ABSTRACT FROM AUTHOR]

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

Psoriasis is an immune‐mediated chronic inflammatory skin disease and chronic kidney disease is one of the common comorbidities of psoriasis. Ixekizumab, a humanized IgG4 monoclonal antibody, has been approved for the treatment of moderate‐to‐severe plaque psoriasis in recent years. However, ixekizumab has not been studied in a population of patients with renal insufficiency. We report two cases of plaque psoriasis patients with renal dysfunction successfully treated with ixekizumab without dose reduction，which experience no side effects and does not cause further kidney injury. [ABSTRACT FROM AUTHOR]

Introduction: Real-world data on ixekizumab utilization in axial spondyloarthritis (axSpA) are limited. We evaluated ixekizumab treatment patterns and health care resource utilization (HCRU) in patients with axSpA using United States Merative L.P. MarketScan® Claims Databases. Methods: This retrospective cohort study included adults with axSpA who initiated ixekizumab during the index period (September 2019–December 2021). Index date was the date of the first ixekizumab claim. All patients had continuous medical and pharmacy enrollment during the 12-month pre-index and follow-up periods. Descriptive statistics were used to assess patient demographics (index date); clinical characteristics (pre-index period); treatment patterns (12-month follow-up period); and HCRU (pre-index and 12-month follow-up periods). Results: The study included 177 patients (mean age 45.8 years; females 54.8%) with axSpA who initiated ixekizumab. Overall, 79.1% of patients reported prior biologic use; of these, 70.7% received tumor necrosis factor-alpha inhibitors (TNFi) and 49% received secukinumab. The mean (standard deviation [SD]) Charlson Comorbidity Index score was 1.1 (1.3) and ~ 27% of patients reported ≥2 comorbidities. The median (inter-quartile range [IQR]) number of ixekizumab prescription refills was 7 (4–11). The mean (SD) Proportion of Days Covered (PDC) for ixekizumab was 0.6 (0.3) and adherence (PDC ≥80%) was 34.5% (N = 61). Overall, 26.6% (N = 47) of patients switched to a non-index medication and 54.2% (N = 96) of patients discontinued ixekizumab. Among the patients who discontinued ixekizumab (N = 96), 19.8% (N = 19) restarted ixekizumab and 49.0% (N = 47) switched to a non-index medication. The median (IQR) ixekizumab persistence was 268 (120–366) days. Mean axSpA-related outpatient, inpatient, and emergency room visits were similar between the pre-index and follow-up periods. Treatment patterns were largely similar between biologic-experienced patients (N = 140; 79.1%) and the overall population. Conclusions: Despite high comorbidity burden and majority of the patients being biologic-experienced, patients initiating ixekizumab for axSpA showed favorable persistence profiles during the 12-month follow-up period. Plain Language Summary: Axial spondyloarthritis (axSpA) affects the patients' ability to perform daily activities and can have a major impact on their quality of life. Ixekizumab is approved in the United States for the treatment of axSpA. However, real-world data on utilization of ixekizumab are limited. We used administrative claims databases to evaluate real-world treatment patterns and health care resource utilization in adult patients with axSpA who were receiving ixekizumab in the United States. The study showed that more than a quarter of the patients receiving ixekizumab had at least two comorbidities. A majority of the patients (79%) reported that they had received at least one biologic before initiating ixekizumab. Even with the high comorbidity burden and the previous exposure to biologics, patients showed favorable persistence to ixekizumab. Of the patients who discontinued ixekizumab, subsequently, 20% re-initiated ixekizumab and approximately half of the patients switched to an alternative medication. There was no increase in axSpA-related health care resource utilization following ixekizumab treatment. The study findings suggest that ixekizumab is an effective treatment option for patients with axSpA. [ABSTRACT FROM AUTHOR]

We report a case of a severe ear infection in a 35-year-old man treated with ixekizumab for psoriasis. Ixekizumab is a humanized monoclonal antibody that selectively prevents the interaction between interleukin 17 A and its receptor. Biologicals like ixekizumab are used to achieve symptom relief in autoimmune diseases including psoriasis. Unlike the mild upper respiratory tract infections usually described as side-effects of this treatment, we report a case of a patient who presented with a severe otitis media, complicated with a facial paresis and nasopharyngeal abscess. To the best of our knowledge, this is the first case presenting a severe, complicated ear infection as a possible side effect of ixekizumab. We conclude that when using ixekizumab, vigilance for upper airway infections is needed and if necessary, interruption of therapy should be considered. However, further research is needed to confirm this hypothesis. [ABSTRACT FROM AUTHOR]

In recent years Janus kinase inhibitors (JAKi) have joined tumor necrosis factor inhibitors (TNFi) and interleukin (IL)-17 inhibitors (IL-17i) as approved disease modifying anti-rheumatic drugs (DMARD) for moderate to severe forms of axial spondyloarthritis (axSpA). Drug survival in axSpA patients has not been well studied in a real-world outpatient scenario since the approval of JAKi. We aimed to analyze the three drug classes based on modes of actions (MoA) for their persistence rates among German axSpA outpatients. A retrospective analysis of the RHADAR database for axSpA patients with a new initiation of TNFi, IL-17i, or JAKi treatment between January 2015 and October 2023 was conducted. Analyses included Kaplan-Meier curves and adjusted Cox regressions for drug discontinuation. 1222 new biological DMARD (TNFi [n = 954], IL-17i [n = 190]) or JAKi (n = 78) treatments were reported. The median drug survival was 31 months for TNFi, 25 for IL-17i, and 18 for JAKi. The corresponding 2-year drug survival rate was 79.6%, 72.6%, and 62.8% for TNFi, IL-17i, and JAKi, respectively. The probability for discontinuation for JAKi was significantly higher compared with TNFi (HR 1.91 [95% CI 1.22–2.99]) as well as for IL-17i compared with TNFi (HR 1.43 [95% CI 1.02–2.01]), possibly related to more frequent use of TNFis as first-line therapy. IL-17i and JAKi discontinuation probabilities were similar. Primary non-response was the reason for drug discontinuation in most cases across all MoA. TNFi treatment might persist longer than JAKi and IL-17i in German axSpA outpatients, possibly related to more severe or refractory disease in patients with JAKi-treated or IL-17i-treated axSpA. [ABSTRACT FROM AUTHOR]

Background: Erythrodermic psoriasis (EP) is a potentially life-threatening disease, and there is currently no consensus regarding its optimal treatment. Biological drugs approved for Psoriasis Vulgaris treatment have been used as alternatives to traditional medications. Objective: To evaluate the clinical response and tolerability of anti- interleukin 17 (IL17) biologic drugs during a 2-year-follow-up. Methods: This was a retrospective prospective study. EP cases, defined as >75% body surface area involvement, in patients ≥18 years old treated with anti-IL17 for at least 6 consecutive months were enrolled and then followed until 104 weeks. Patient characteristics, overall clinical responses, Psoriasis Area Severity Index score changes, and adverse events were analyzed. Results: Sixteen patients met the criteria, of which 50% had achieved the Psoriasis Area Severity Index 100 response at week 12 and in 93.7% at week 24. In the prospective observation of the cohort, 87.5% were still in remission at week 52 and 81.25% at 104 weeks, without adverse events. The 3 patients in whom the treatment was interrupted lost efficacy and were switched to other therapies. Limitations: Only descriptive analysis was conducted due to the limited number of patients. Conclusions: A satisfactory long-term clinical response without adverse effects was observed in this case series, suggesting the interest of anti-IL17 in EP treatment.

Abstract Introduction Real-world data on ixekizumab utilization in axial spondyloarthritis (axSpA) are limited. We evaluated ixekizumab treatment patterns and health care resource utilization (HCRU) in patients with axSpA using United States Merative L.P. MarketScan® Claims Databases. Methods This retrospective cohort study included adults with axSpA who initiated ixekizumab during the index period (September 2019–December 2021). Index date was the date of the first ixekizumab claim. All patients had continuous medical and pharmacy enrollment during the 12-month pre-index and follow-up periods. Descriptive statistics were used to assess patient demographics (index date); clinical characteristics (pre-index period); treatment patterns (12-month follow-up period); and HCRU (pre-index and 12-month follow-up periods). Results The study included 177 patients (mean age 45.8 years; females 54.8%) with axSpA who initiated ixekizumab. Overall, 79.1% of patients reported prior biologic use; of these, 70.7% received tumor necrosis factor-alpha inhibitors (TNFi) and 49% received secukinumab. The mean (standard deviation [SD]) Charlson Comorbidity Index score was 1.1 (1.3) and ~ 27% of patients reported ≥2 comorbidities. The median (inter-quartile range [IQR]) number of ixekizumab prescription refills was 7 (4–11). The mean (SD) Proportion of Days Covered (PDC) for ixekizumab was 0.6 (0.3) and adherence (PDC ≥80%) was 34.5% (N = 61). Overall, 26.6% (N = 47) of patients switched to a non-index medication and 54.2% (N = 96) of patients discontinued ixekizumab. Among the patients who discontinued ixekizumab (N = 96), 19.8% (N = 19) restarted ixekizumab and 49.0% (N = 47) switched to a non-index medication. The median (IQR) ixekizumab persistence was 268 (120–366) days. Mean axSpA-related outpatient, inpatient, and emergency room visits were similar between the pre-index and follow-up periods. Treatment patterns were largely similar between biologic-experienced patients (N = 140; 79.1%) and the overall population. Conclusions Despite high comorbidity burden and majority of the patients being biologic-experienced, patients initiating ixekizumab for axSpA showed favorable persistence profiles during the 12-month follow-up period.

Biao Song,1– 3,&ast; Xiaohan Liu,1– 3,&ast; Hongzhong Jin1– 3 1Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 3National Clinical Research Center for Dermatologic and Immunologic Diseases, Peking Union Medical College Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongzhong Jin, Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China, Email jinhongzhong@263.netAbstract: Erythrodermic psoriasis (EP) is a severe and rare variant of psoriasis, accounting for less than 3% of cases. It is characterized by widespread scaling and erythema that affects more than 90% of the body surface area. Alopecia can manifest as a symptom associated with the disease, further exacerbating the impact on the patient’s quality of life. We present the case of a patient with severe EP and diffuse alopecia who did not respond to conventional therapies. The patient was subsequently treated with ixekizumab as per labeled usage, resulting in complete resolution of both psoriatic skin lesions (Psoriasis area and severity index/PASI 100) and alopecia (The Severity of Alopecia Tool/SALT 0).Keywords: erythrodermic psoriasis, alopecia, ixekizumab

Yuan Li, Jiejie Lu, Jingqiu Fu Department of Cosmetic Dermatology, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of ChinaCorrespondence: Jingqiu Fu, Department of Cosmetic Dermatology, The Fifth People’s Hospital of Hainan Province, No. 8 Longhua Road, Longhua District, Haikou, 570100, Hainan, People’s Republic of China, Email 619734489@qq.comAbstract: Biologic agents have become a mainstay in the treatment of psoriasis, particularly in moderate to severe, refractory, and special types of the disease. Among these, ixekizumab is a humanized IgG4 monoclonal antibody targeting interleukin-17A, approved for the treatment of moderate to severe plaque psoriasis. Its adverse effects include infections such as nasopharyngitis, upper respiratory tract infections, and injection site reactions. While the incidence of tuberculosis (TB) associated with IL-17A antagonists is extremely low, this paper reports a case of active pulmonary tuberculosis occurring after ten doses of ixekizumab treatment for chronic plaque psoriasis. This highlights the importance for clinicians to remain vigilant regarding tuberculosis infection in patients undergoing therapy with this class of medications, emphasizing the need for enhanced screening and monitoring for tuberculosis during treatment.Keywords: interleukin-17A antagonists, ixekizumab, psoriasis, primary active pulmonary tuberculosis

Introduction: Ixekizumab, an interleukin 17A (IL-17A) inhibitor, has demonstrated rapid and sustained improvement in the signs and symptoms in patients with active radiographic axial spondyloarthritis (r-axSpA) in global and Chinese populations. We studied the effect of ixekizumab on patient-reported outcomes (PROs) (including patient global, spinal pain, stiffness, and fatigue) and overall health-related quality of life (HRQoL) of ixekizumab in the phase 3 study in China. Methods: In this Chinese phase 3, randomized, double-blind, placebo-controlled study, patients with r-axSpA were randomized (1:1) to receive ixekizumab 80 mg every 4 weeks (IXEQ4W; starting dose 160 mg) or placebo for 16 weeks. At week 16, patients receiving placebo were switched to IXEQ4W, and those receiving IXEQ4W continued, until week 52. Data for patient global, spinal pain, spinal pain at night, stiffness, and fatigue were collected through week 52. Minimally clinical important differences (MCIDs) were determined for spinal pain and spinal pain at night. The subgroup analyses by baseline disease duration since diagnosis and baseline C-reactive protein (CRP) level were conducted post hoc. Results: Compared with placebo, patients treated with IXEQ4W reported significantly greater improvement with a rapid onset in changes from baseline of PROs (patient global, spinal pain, spinal pain at night, stiffness, and fatigue) through week 16. Improvements were maintained through week 52. A similar trend of improvement was also observed in MCID response in spinal pain and spinal pain at night. The improvement in overall HRQoL was supported by EQ-5D-5L assessment. Subgroup analyses demonstrated that IXEQ4W provided significantly greater efficacy at week 16 compared with placebo, irrespective of baseline disease duration or baseline CRP level. Conclusion: IXEQ4W provided rapid and sustained improvement in clinically relevant PROs and overall HRQoL through 1-year treatment in Chinese patients with r-axSpA. Regardless of the baseline disease duration or baseline CRP level, consistent efficacy was observed. Trial Registration: ClinicalTrials.gov identifier NCT04285229. [ABSTRACT FROM AUTHOR]

Introduction: A previous network meta-analysis established 16-week relative efficacy with bimekizumab, an inhibitor of interleukin (IL)-17F in addition to IL-17A, versus other treatments for patients with radiographic axial spondyloarthritis (r-axSpA; i.e., ankylosing spondylitis), including the IL-17A inhibitors secukinumab and ixekizumab. This matching-adjusted indirect comparison (MAIC) assessed 52-week relative efficacy of bimekizumab versus secukinumab and ixekizumab. Methods: Individual patient data from BE MOBILE 2 (bimekizumab 160 mg; N = 220) were matched to pooled summary data from MEASURE 1/2/3/4 (secukinumab 150 mg), MEASURE 3 (secukinumab 300 mg; escalated dose for inadequate responders), COAST-V (ixekizumab) and COAST-V/-W (ixekizumab). BE MOBILE 2 patients were reweighted using propensity score weights based on age, sex, ethnicity, tumor necrosis factor inhibitor (TNFi) exposure, weight, baseline ASDAS and BASFI (secukinumab) and baseline BASDAI (ixekizumab), and 52-week efficacy outcomes from the trial recalculated. Odds ratios (OR) or mean difference for unanchored comparisons are reported with 95% confidence intervals (CI). Results: At week 52, MAIC demonstrated that patients may have higher likelihood of improvement in key efficacy outcomes with bimekizumab versus secukinumab 150 mg (e.g., ASAS40: [OR (95% CI): 1.48 (1.05, 2.10); p = 0.026]; effective sample size [ESS] = 177). Differences in 52-week efficacy outcomes between bimekizumab and secukinumab 300 mg dose escalation were non-significant (ESS = 120). Bimekizumab versus ixekizumab 80 mg comparisons (COAST-V only; ESS = 84) also suggested that differences were non-significant for most key efficacy outcomes. Other ixekizumab comparisons (COAST-V/-W; ESS = 45) suggested bimekizumab may have higher comparative efficacy for many of the same efficacy outcomes, however ixekizumab analyses were limited by poor population overlap, likely due to the greater proportion of patients with previous TNFi exposure. Conclusions: Patients treated with bimekizumab may have a higher likelihood of achieving improved longer-term efficacy versus secukinumab 150 mg, suggesting bimekizumab may be a favorable therapeutic option for r-axSpA. Differences in efficacy outcomes with bimekizumab versus ixekizumab 80 mg were mostly non-significant, depending on the populations considered. [ABSTRACT FROM AUTHOR]

Objectives: Ixekizumab, an interleukin (IL)-17A inhibitor, exerts its therapeutic effects in psoriasis by inhibiting the interleukin (IL)-17 signaling pathway. Common adverse reactions to ixekizumab include injection site reactions and upper respiratory tract infections (URIs), while occurrences of inflammatory bowel disease (IBD) and multiple mucosal ulcers are infrequent. We present a case of a 51-year-old man who developed multiple mucosal ulcers after ixekizumab treatment. Methods: A 51-year-old man presented to our hospital with a 1-month history of pharyngalgia. The flexible laryngoscope displayed mild hyperemia in the pharyngeal mucosa and tonsils, redness and swelling of the epiglottis, as well as multiple ulcers in the oral cavity, uvula, and epiglottis. These ulcers did not improve with conventional treatment. Results: Upon evaluation, the ulcers were an immune-related adverse event induced by ixekizumab. Consequently, a decision was made to discontinue the drug and initiate a therapeutic regimen including corticosteroids and thalidomide. Eventually, the patient's symptoms abated. Conclusions: Biologics are now becoming increasingly popular in psoriasis. It is vital for clinicians to be aware of this potential adverse event and to identify and intervene early to alleviate patients' suffering. [ABSTRACT FROM AUTHOR]

We aimed to examine the drug retention rate (DRR) of the interleukin-17 inhibitor ixekizumab in a real-world monocentric cohort of psoriatic arthritis (PsA) patients and to assess the predictors of drug discontinuation. Consecutive PsA patients who underwent treatment with ixekizumab from October 2019 to February 2023 were enrolled in this observational, retrospective, monocentric study. Clinical records were assessed at baseline and throughout the follow-up period. We collected sociodemographic data, smoking habits, body mass index, the presence of Human Leukocyte Antigen B27, comorbidities, disease involvement and duration, previous therapy, discontinuation of ixekizumab, reasons for discontinuation, and adverse events (AEs). DRR was evaluated as time to drug discontinuation and assessed through Kaplan–Meier curves. Baseline factors predicting drug discontinuation were investigated through logistic regression models. Eighty PsA patients were included in this study. Ixekizumab was administered at a dose of 160 mg by subcutaneous injection at baseline, followed by 80 mg every four weeks thereafter. Ixekizumab had a 38-month-cumulative DRR of 43.8%, accounting for both inefficacy and AEs. When considering only inefficacy, the DRR was 62.6%. Comorbidities (p = 0.665), obesity (p = 0.665), smoking (p = 0.884), disease duration ≤ 2 years (p = 0.071), axial (p = 0.131) and skin involvement (p = 0.460), and previous therapies, including conventional synthetic (p = 0.504) and biological (p = 0.474) Disease-Modifying Antirheumatic Drugs (bDMARDs), as well as the number of previous bDMARDs or targeted synthetic Disease-Modifying Antirheumatic Drugs (tsDMARDs), did not significantly affect the DRR (p = 0.349). Multivariate analysis found no independent predictors of drug discontinuation. The most frequent AEs leading to discontinuation were skin reactions; no severe infections were observed. In our real-world study, comorbidities, disease duration, and previous therapies did not affect the DRR of ixekizumab. Ixekizumab had a favorable safety profile, with no severe AEs observed. [ABSTRACT FROM AUTHOR]

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.

The letter published in the Journal of Cutaneous Immunology & Allergy discusses the successful treatment of psoriasis vulgaris in a patient with concurrent Sjögren's syndrome and incomplete systemic lupus erythematosus using ixekizumab, an anti-IL-17A antibody. The case study highlights the improvement in skin manifestations of psoriasis and dry eye symptoms associated with Sjögren's syndrome. The authors suggest that IL-17A inhibitors like ixekizumab may have therapeutic potential for autoimmune diseases like Sjögren's syndrome and systemic lupus erythematosus, although further research is needed to establish a direct causal relationship. [Extracted from the article]

ABSTRACT Linear psoriasis is a rare clinical presentation of psoriasis characterized by erythematous scaly plaques distributed along Blaschko's lines. We describe an 8‐year‐old male with a linear Blaschkoid plaque in which biopsy findings and clinical history were consistent with linear psoriasis. The lesion showed only mild improvement with topical steroid therapy but exhibited significant clearance with the biologic agent ixekizumab, an IL‐17A inhibitor. With limited supporting literature regarding management, this case report illustrates the clinical manifestation, diagnosis, and an effective management strategy for linear psoriasis in a pediatric patient. [ABSTRACT FROM AUTHOR]

Juvenile pityriasis rubra pilaris is a rare inflammatory skin disorder currently without any FDA‐approved treatments, and lesions can be refractory to conventional treatment with topical corticosteroids, methotrexate, and oral retinoids. We herein present a case of a 6‐year‐old boy who attained clearance of extensive juvenile pityriasis rubra pilaris within 2 weeks of starting ixekizumab therapy. Therapeutic effect has been durable at 6 months, and patient continues on therapy without adverse effects. Our case highlights a new, rapidly effective treatment option for pediatric patients with this rare condition. [ABSTRACT FROM AUTHOR]

Abstract Introduction Ixekizumab, an interleukin 17A (IL-17A) inhibitor, has demonstrated rapid and sustained improvement in the signs and symptoms in patients with active radiographic axial spondyloarthritis (r-axSpA) in global and Chinese populations. We studied the effect of ixekizumab on patient-reported outcomes (PROs) (including patient global, spinal pain, stiffness, and fatigue) and overall health-related quality of life (HRQoL) of ixekizumab in the phase 3 study in China. Methods In this Chinese phase 3, randomized, double-blind, placebo-controlled study, patients with r-axSpA were randomized (1:1) to receive ixekizumab 80 mg every 4 weeks (IXEQ4W; starting dose 160 mg) or placebo for 16 weeks. At week 16, patients receiving placebo were switched to IXEQ4W, and those receiving IXEQ4W continued, until week 52. Data for patient global, spinal pain, spinal pain at night, stiffness, and fatigue were collected through week 52. Minimally clinical important differences (MCIDs) were determined for spinal pain and spinal pain at night. The subgroup analyses by baseline disease duration since diagnosis and baseline C-reactive protein (CRP) level were conducted post hoc. Results Compared with placebo, patients treated with IXEQ4W reported significantly greater improvement with a rapid onset in changes from baseline of PROs (patient global, spinal pain, spinal pain at night, stiffness, and fatigue) through week 16. Improvements were maintained through week 52. A similar trend of improvement was also observed in MCID response in spinal pain and spinal pain at night. The improvement in overall HRQoL was supported by EQ-5D-5L assessment. Subgroup analyses demonstrated that IXEQ4W provided significantly greater efficacy at week 16 compared with placebo, irrespective of baseline disease duration or baseline CRP level. Conclusion IXEQ4W provided rapid and sustained improvement in clinically relevant PROs and overall HRQoL through 1-year treatment in Chinese patients with r-axSpA. Regardless of the baseline disease duration or baseline CRP level, consistent efficacy was observed. Trial Registration ClinicalTrials.gov identifier NCT04285229.

Stefana Bucur,1,2 Elena-Daniela Serban,1 Bogdan Vasile Ileanu,3 Raluca Simona Costache,4,5 Alin Codrut Nicolescu,6 Traian Constantin,7,8 Daniel Octavian Costache,1,9 Maria-Magdalena Constantin1,2 1 2nd Department of Dermatology, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania; 2 2nd Department of Dermatology, Colentina Clinical Hospital, Bucharest, Romania; 3Center for Health Outcomes and Evaluation, Bucharest, Romania; 4Department of Internal Medicine and Gastroenterology, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania; 5Department of Gastroenterology, Central Military Emergency University Hospital “Dr. Carol Davila”, Bucharest, Romania; 6Department of Dermatology, “Agrippa Ionescu” Emergency Clinical Hospital, Bucharest, 011773, Romania; 7Department of Urology, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania; 8Department of Urology, “Prof. Dr. Theodor Burghele” Hospital, Bucharest, 050659, Romania; 9Department of Dermatology, Central Military Emergency University Hospital “Dr. Carol Davila”, Bucharest, RomaniaCorrespondence: Elena-Daniela Serban, 37 Dionisie Lupu Street, Bucharest, 020021, Romania, Email elena-daniela.serban@drd.umfcd.roPurpose: Multiple biological therapies have been developed for the treatment of inflammatory diseases, including moderate to severe plaque psoriasis. Choosing the optimal treatment for psoriasis can depend on several factors and is strongly influenced by a drug’s efficacy and safety profile. Continuous treatment with biological therapies is recommended to achieve effective disease management in patients with psoriasis. However, in real-world, patients often discontinue biologic therapy within the first year of treatment. Therefore, in this study, we aimed to investigate the effectiveness and drug survival of two anti-interleukin 17 agents (ixekizumab and secukinumab) in a group of adult patients with moderate to severe psoriasis from Bucharest, Romania.Patients and Methods: We designed an observational, non-interventional, retrospective study of 255 adult patients with moderate to severe psoriasis receiving ixekizumab and secukinumab. We performed descriptive statistics and inferential methods, such as z-test, median test and Kaplan Meier curve comparison, to characterize the groups with two biological treatments.Results: Patients treated with ixekizumab had a longer drug survival compared to those treated with secukinumab with lower risks of non-persistence, discontinuation and switching therapy. Patients age-groups and psoriasis durations found to be significant factors in drug survival.Conclusion: This study contributes to the understanding of the drug survival profile and the factors that may influence it in ixekizumab and secukinumab treatment in a real-world setting.Keywords: anti-IL-17 effectiveness, anti-IL-17 drug survival, ixekizumab, secukinumab

Abstract Introduction Skin involvement in patients with psoriatic arthritis (PsA) worsens the severity and burden of disease. Ixekizumab (IXE), a selective interleukin (IL)-17A antagonist, was compared to placebo (PBO) in the SPIRIT-P1 (NCT01695239) and SPIRIT-P2 (NCT02349295) studies in patients with PsA and evidence of plaque psoriasis. This post hoc analysis reports musculoskeletal, skin, and nail outcomes through week 24 in patients from SPIRIT-P1 and SPIRIT-P2, stratified by mild, moderate, or severe psoriasis at baseline. Methods This post hoc analysis pooled patients from SPIRIT-P1 and SPIRIT-P2 who were randomly assigned to PBO or IXE 80 mg every 4 weeks (Q4W) or every 2 weeks (Q2W). Efficacy outcomes were analyzed through week 24 by baseline psoriasis severity, defined by percent body surface area (BSA) affected; mild = BSA 10%. The primary outcomes assessed were the proportion of patients achieving American College of Rheumatology (ACR)20, ACR50, and ACR70 responses. Secondary outcomes included musculoskeletal, disease activity, skin and nail, and health-related quality-of-life measures. Results Similar proportions of patients achieved ACR20/ACR50/ACR70 over time across all severity subgroups and treatment arms. More than one-third of IXE-treated patients achieved ACR20 at week 4, or ACR50 at week 24, with no significant differences according to psoriasis severity at baseline. Disease activity outcomes were similar through week 24 with both IXEQ4W and IXEQ2W, regardless of psoriasis severity at baseline. There were no significant differences over 24 weeks in the proportions of IXE-treated patients with mild, moderate, or severe baseline psoriasis who achieved Minimal Disease Activity (MDA). Across all severity subgroups, IXE demonstrated Psoriasis Area Severity Index 100 response as early as week 4, and approximately one-third of IXE-treated patients achieved total skin clearance at week 24. Conclusion IXE demonstrated rapid and consistent efficacy in joint, skin, and nail for patients with PsA, regardless of baseline psoriasis severity. Trial Registration SPIRIT-P1 (NCT01695239), SPIRIT-P2 (NCT02349295).

Abstract Introduction The introduction of biological therapies has revolutionized the treatment of moderate-to-severe plaque psoriasis. In particular, ixekizumab, an inhibitor of interleukin-17A, has shown great results in terms of efficacy and safety in both clinical trials and real-world experiences. However, there is a lack of long-term real-world data available for ixekizumab. Methods We conducted a multicenter real-life study to evaluate the effectiveness and safety of ixekizumab in patients with moderate-to-severe plaque psoriasis. Psoriasis Area and Severity Index score (PASI) was collected at baseline and after 1, 2, 3, 4, and 5 years. The occurrence of any adverse events was recorded at each time point. Results We enrolled 1096 patients treated with ixekizumab for at least 1 year. At week 52, the percentages of PASI 90 and PASI 100 were 85.04% and 69.07%, respectively. After 5 years of treatment with ixekizumab, out of 145 patients, a PASI 90 response was achieved by 86.90% of patients, while complete skin clearance was reached by 68.28% of patients. We did not observe any new significant safety findings throughout the study period. Conclusion This study supports the long-term effectiveness and safety of ixekizumab in a real-world setting.

Modern pathogenetic therapy of inflammatory rheumatic diseases (IRD) is aimed not only at reducing disease activity (although achieving remission and low disease activity remains the main goal of treatment), but also at eliminating as quickly and completely as possible the main symptoms that cause a decrease in the quality of life of patients. Particular importance is attached to effective control of chronic pain – the main and most distressing manifestation of IRD. To solve this problem, the pathogenesis of chronic pain in IRD continues to be actively studied, aimed at finding new ”targets” of pharmacotherapy. Thus, the role of central sensitization (CS) and comorbid fibromyalgia in the formation of clinical manifestations of IRD is now clearly proven. Signs of CS, depending on the instrument of its detection, are determined in 20–40% of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA).Interleukin (IL) 17 plays a fundamental role in the development of chronic pain in IIRD. This cytokine takes a leading position in the development of the ”cytokine cascade”, inducing the synthesis of various cytokines and chemokines, as well as chemotaxis and activation of neutrophils and T cells. Induction of synthesis of inflammatory mediators (including prostaglandin E2) determines the role of IL-17 in activation of nociceptors and their sensitization. IL-17 also takes an active part in neuroimmune interactions by activating glia cells and affecting receptors present on the membrane of neurons of the posterior horns of the spinal cord. This defines the role of IL-17 as one of the inductors of CS development. Pharmacologic blockade of IL-17 is a known pathway to suppress the activity of IIRPs such as PsA and AxSpA. However, this mechanism also allows for significant effects on chronic pain. In particular, the IL-17 inhibitor ixekizumab has shown high analgesic potential in a series of studies in PsA and AxSpA (SPIRIT-P1 and SPIRIT-P2, COAST V and COAST W). It is important to note that this drug demonstrated a very rapid analgesic effect: pain intensity was significantly reduced already 7 days after the first injection. These data suggest a specific effect of ixekizumab on the nociceptive system, independent of the anti-inflammatory effect. This fact allows us to consider ixekizumab as a drug of choice for the treatment of patients with PsA and AxSpA who experience severe pain and have signs of CS and fibromyalgia.

Abstract Introduction Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for the treatment of moderate-to-severe plaque psoriasis. Since scalp psoriasis can be burdensome and challenging to treat with non-systemic therapies, this post hoc analysis focused on scalp psoriasis in patients with moderate-to-severe plaque psoriasis and baseline scalp involvement. The analysis considered a holistic concept of clearance through 5 years of ixekizumab treatment. Methods Ixekizumab-treated patients with baseline scalp involvement were pooled from three multicenter, randomized, double-blind, placebo-controlled, phase 3 trials (integrated UNCOVER-1/2 and UNCOVER-3). Analyses were performed on a subpopulation of patients who achieved complete resolution of scalp psoriasis at Week 60 (i.e., Week 60 Psoriasis Scalp Severity Index [PSSI-0] responders) and on the overall patient population (i.e., Week 60 PSSI-0 responders and non-responders), which was used as a reference. Clinical outcomes (PSSI), patient-reported outcomes (Itch Numeric Rating Scale [NRS] score, Skin Pain Visual Analogue Scale [VAS]), quality of life (Dermatology Life Quality Index [DLQI]), and concurrent outcomes were assessed from baseline through 5 years. Descriptive statistics of observed data were reported. Results After 60 weeks of ixekizumab treatment, 88.4% (UNCOVER-1/2) and 75.9% (UNCOVER-3) of patients with baseline scalp involvement achieved complete clearance (PSSI-0) of scalp psoriasis. Substantial improvements in the clinical outcomes (PSSI), patient-reported outcomes (Itch NRS, Skin Pain VAS), and quality of life (DLQI) were achieved by Week 60 and sustained through Week 264 in the Week 60 PSSI-0 responders and in the overall patient population. Additionally, a significant proportion of Week 60 PSSI-0 responders achieved concurrent complete scalp and skin clearance and quality of life improvement through 5 years. Conclusions Continued treatment with ixekizumab provided long-term sustained scalp clearance over 5 years to patients with moderate-to-severe plaque psoriasis and baseline scalp involvement, and holistic improvements occurred across clinical outcomes, patient-reported outcomes, and quality of life. Clinical Trial Numbers NCT01474512 (UNCOVER-1), NCT01597245 (UNCOVER-2), and NCT01646177 (UNCOVER-3).