New onset inflammatory bowel disease after initiation of anti-IL-17a treatment: a case series.

Immune mediated inflammatory diseases (IMIDs) are a heterogenous group of inflammatory disorders of joint, skin, and gut characterized by both shared and distinct pathological pathways. This complexity has therapeutic implications, as not all IMIDs exhibit responsiveness to available biologicals. Moreover, cases have been documented where patients undergoing biologic therapy experience paradoxical occurrences of either a new IMID or a flare-up of a previously asymptomatic one. Treatment with anti- IL-17a has been approved for ankylosing spondylitis, psoriasis, and psoriatic arthritis, but was not found effective for the treatment of inflammatory bowel disease (IBD). This case series describes four patients with new onset IBD under treatment with an IL-17a inhibitor for a rheumatological or dermatological indication.

Plaque psoriasis with renal dysfunction successfully treated with ixekizumab.

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.

Biologic anti-IL17 drugs in erythrodermic psoriasis.

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.

Efficacy of Ixekizumab in Chinese Patients with Moderate-to-Severe Psoriasis and Special Body Area Involvement: Sub-analysis of a Randomized, Double-Blind, Multicenter Phase 3 Study.

INTRODUCTION: Special body area involvement is common in psoriasis and can be challenging to treat. We investigated the efficacy of ixekizumab (IXE) in Chinese patients with moderate-to-severe psoriasis and fingernail, scalp, or palmoplantar involvement. METHODS: A post-hoc sub-analysis of a phase 3 trial, in which patients were randomized to receive placebo, IXE 80 mg every 2 (IXE Q2W) or 4 (IXE Q4W) weeks. At Week 12, patients classified as IXE responders [static Physician's Global Assessment (sPGA) score of 0 or 1 [0,1)] were re-randomized (2:1) to IXE Q4W or placebo until Week 60. Efficacy was assessed by body-region specific parameters including Nail Psoriasis Severity Index (NAPSI), Psoriasis Scalp Severity Index (PSSI), and Palmoplantar Psoriasis Area Severity Index (PPASI). RESULTS: Of 438 patients, 99.1% (434) had ≥ 1 special area involvement [fingernail (76.5%, 335), scalp (97.3%, 426), palmoplantar (27.9%, 122)]. Significantly greater improvements from baseline in NAPSI score were observed with IXE Q4W and Q2W at Week 12 versus placebo (p < 0.001 for both). These improvements were further increased and sustained over 60 weeks in IXE Q4W and Q2W responders who were re-randomized to IXE Q4W, who achieved a 77.9% and 89.7% improvement from baseline, respectively, at Week 60. Significantly higher proportions of patients receiving IXE Q4W and Q2W achieved NAPSI 50 at Week 12 versus placebo (44.4%, 36.6% vs. 14.1%; p < 0.001 and < 0.01, respectively). Similarly, significantly higher proportions of patients receiving IXE Q4W and Q2W achieved PSSI 100 and PPASI 100 at Week 12 versus placebo (60.6% and 65.1% vs. 1.2%, and 67.4%, 84.3% vs. 21.4%, respectively; p < 0.001 for all comparisons). Improvements across all outcomes were sustained in patients re-randomized to IXE Q4W until Week 60. CONCLUSION: IXE led to a rapid onset of action and sustained efficacy over 60 weeks in Chinese patients with moderate-to-severe psoriasis and special body area involvement. CLINICALTRIALS: gov identifier, NCT03364309.

Treatment-emergent Candida infections in patients with psoriasis, psoriatic arthritis, and axial spondyloarthritis treated with ixekizumab: an integrated safety analysis of 25 clinical studies.

BACKGROUND: This safety analysis investigates treatment-emergent mucosal/cutaneous Candida infections in patients treated with ixekizumab (IXE), an anti-interleukin-17A monoclonal antibody, across the approved indications: psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA). RESEARCH DESIGN AND METHODS: Safety data were pooled from 25 clinical studies. Incidence rates (IRs) are expressed as per 100 patient-years (PY), using the entire duration of exposure. RESULTS: Candida infections had an IR of 1.9 per 100 PY in patients with PsO (N = 6892; total PY = 18025.7), 2.0 per 100 PY in patients with PsA (N = 1401; total PY = 2247.7), and 1.2 per 100 PY in patients with axSpA (N = 932; total PY = 2097.7). The majority of treatment-emergent Candida infections were: (i) experienced only once by patients (IR = 1.3;IR = 1.6;IR = 1.0), (ii) mild/moderate in severity (IR = 0.8/0.9;IR = 1.5/0.4;IR = 0.8/0.5) as opposed to severe (IR = 0.0; IR = 0.0; IR = 0.0), (iii) oral Candida or genital Candida (IR = 0.9/0.6;IR = 1.0/0.7;IR = 0.4/0.6), (iv) marked as recovered/resolved during the studies (89.3%;93.8%;90.3%), (v) not leading to IXE discontinuation (0.0%;0.0%;0.1% discontinued), (vi) managed with topical (34.7%;22.2%;11.5%) or no anti-fungal medications (63.5%;77.8%;80.8%) as opposed to systemic therapies (1.5%;0.0%;7.7%), (vii) typically resolved before next visit. CONCLUSIONS: This integrated safety analysis shows that the risk of developing Candida infections is low with IXE, and the severity is mild-to-moderate in most instances across the approved IXE indications. TRIAL REGISTRATION: A comprehensive list of the clinical trials and their registration numbers is reported in Table S1 of the supplemental material.

Ixekizumab (IXE) is a drug approved for the treatment of psoriasis, psoriatic arthritis, and axial spondyloarthritis. IXE belongs to the class of molecules that blocks a protein called interleukin-17A. Since interleukin-17A is involved in the defense against fungi, the clinical use of this class of drug has the potential to increase the risk of developing fungal infections, such as Candida infections.Therefore, researchers collected safety data from 25 clinical studies comprising 9225 adult patients treated with IXE: 6892 with psoriasis, 1401 with psoriatic arthritis, and 932 with axial spondyloarthritis. Researchers looked at the rate of new cases of Candida infections, the so-called incidence rate, and found that 1.9 per 100 patient-years experienced at least 1 Candida infection in the psoriasis group, 2.0 per 100 patient-years in the psoriatic arthritis group, and 1.2 per 100 patient-years in the axial spondyloarthritis group.Across indications, the majority of Candida infections (i) were experienced only once by patients, (ii) were mild or moderate in severity, (iii) involved infections caused by superficial skin fungus in the mouth or genitals, (iv) were considered recovered/resolved during the studies, (v) did not lead to IXE discontinuation, (vi) were managed with topical anti-fungal medications or no medications, and (vii) were typically resolved before next visit.In conclusion, this safety analysis shows that the risk of developing Candida infections is low with IXE, and the severity is mild-to-moderate in most instances across the approved IXE indications.

Analysis of the shorter drug survival times for Janus kinase inhibitors and interleukin-17 inhibitors compared with tumor necrosis factor inhibitors in a real-world cohort of axial spondyloarthritis patients - a retrospective analysis from the RHADAR network.

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.

Ixekizumab Treatment Patterns and Health Care Resource Utilization Among Patients with Axial Spondyloarthritis: A Retrospective United States Claims Database Study.

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.

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.

Rare Case Report of Primary Active Pulmonary Tuberculosis During Ixekizumab Treatment for Plaque Psoriasis.

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.

Ixekizumab Improved Refractory Erythrodermic Psoriasis with Comorbid Diffuse Alopecia: A Case Report with 52-Week Follow-Up.

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).

A narrative review of the literature: The role of biologics and JAK inhibitors in vitiligo.

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.

Evaluation of serial QuantiFERON-TB Gold in tube test results and tuberculosis infection status in patients with psoriasis receiving anti-IL-17 treatment (secukinumab and ixekizumab): Real-world data from a tuberculosis-endemic country.

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.

Effectiveness and Drug Survival of Ixekizumab and Secukinumab in Patients with Moderate to Severe Plaque Psoriasis: Real-World Data from Bucharest, Romania.

Purpose: 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.

Severely complicated ear infection in a patient treated with ixekizumab: a case report.

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.

Retention Rate of Ixekizumab in Psoriatic Arthritis: A Real-World Study.

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.

Rapid clearance of extensive juvenile pityriasis rubra pilaris with ixekizumab.

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.

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

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