Current Prescribing Practices in Psoriatic Arthritis - Comparison between the Uk and Europe

Background/Aims Psoriatic arthritis (PsA) is a multi-system disease with a range of management options. Treatment may vary by geographic location. We compared disease characteristics and prescribing practices in the UK and Europe in the post-Covid era. Methods The ASSIST study was a cross-sectional observational study of PsA patients aged 18 years and older selected from 24 centres across 5 countries (UK, France, Germany, Italy and Spain) between July 2021 and March 2022 (IRAS: 287039). Patients attending a face-to-face appointment with a diagnosis of PsA made by a rheumatologist were selected by systematic sampling at each centre and treated in routine clinical practice. Patient and disease characteristics, current treatment and treatment decisions (medications unchanged, switched, added or reduced) were recorded. The analysis was descriptive, with no imputation of missing data. Results 503 patients were included, with arthritis subtype, patient age, disease activity and duration shown (Table 1). Physician- and patient-reported disease severity was highest in the UK, where median patient age was lowest. Conventional synthetic (cs) DMARDS constituted a higher percentage of current PsA treatment in UK than continental Europe (66.4% vs 44.9%), whereas biologic use was more frequent in Europe (68.1% vs 36.4%). Adalimumab was the most commonly used biologic in the UK and Spain. Adalimumab and secukinumab were equally used in Germany, and ixekizumab and adalimumab were joint-first in Italy. Implementing change to the current PsA treatment was most common in the UK, predominantly being a treatment increase. This may reflect the higher level of disease activity or younger patient age in the UK than other countries, as treatment escalation is more likely earlier in the disease course. In the UK, treatment escalation was more commonly achieved by medication addition (26.2%) than medication switch (14%) or dose increase (7.5%). In Europe, medication addition and switch were of more similar frequency (10.9% vs 9.85%). Conclusion Disease characteristics and treatment strategies varied between countries, but particularly between UK and the rest of Europe. In contrast to mainland Europe, csDMARDs predominated in the UK, perhaps reflecting current NICE guidelines. Treatment escalation was most common in the UK, in keeping with higher disease activity. (Table Presented).

Anti-IL17A, Ixekizumab, for treatment-resistant chronic venous leg ulcers: A phase II randomized, double-blind, placebo-controlled pilot trial

Chronic venous leg ulcers cause significant morbidity in patients and the majority reoccur after resolution. The current standard of care, double layer compression, is not effective in all patients. Interleukin 17A (IL17) antagonist therapy has been shown to promote healing in murine models of chronic wounds. This has not previously been explored in humans. Therefore, we aim to undertake a phase II randomized, double-blinded, placebo-controlled pilot trial to assess whether Ixekizumab, an anti-IL17A therapy, is effective at reducing chronic venous ulcer size. In addition, to determine the feasibility and safety of undertaking a randomized control trial. Patients with a venous leg ulcer not responsive to 4 weeks of compression therapy were recruited. Participant were randomized to receive either Ixekizumab (80mg) or placebo injected subcutaneously every fortnight for 12 weeks while continuing standard of care. From 30 eligible, 4 patients consented, were enrolled and randomized. Initially, COVID-19 risk, medical history and distance from recruiting site were the main causes of exclusion or refusal to participate. All participants completed the 12-week treatment period. At completion, two participants in the Ixekizumab group reduced by >40% and one completely resolved their ulcer. Ulcers in the Ixekizumab group reduced by an average size of 955mm2 to 529mm2at baseline to final review respectively (p-value 0.12). The placebo group reduced in size by <5%.There were no adverse events related to the intervention. This pilot clinical trial investigated a novel treatment for chronic venous ulcers and showed IL17 inhibition does not impede and may improve chronic wound healing. It also showed a lack of major safety issues in using anti-IL17A therapy in this population. Moreover, the findings reinforce the feasibility of a larger trial to more accurately evaluate anti-inflammatory strategies in chronic wounds.Copyright © 2023

Ixekizumab treatment in patients with moderate-to-severe plaque psoriasis in a real-world clinical setting.

BACKGROUND: The efficacy and safety reports of ixekizumab for moderate-to-severe plaque psoriasis may vary between clinical trials and real-world studies. AIM: To analyze the real-world data of ixekizumab therapy to evaluate its efficacy and safety and highlight the factors influencing the treatment response in the real-world scenario. PATIENTS/METHODS: Data of 82 adult patients with moderate-to-severe chronic plaque psoriasis are included in this study. Psoriasis area severity index (PASI) 75/90/100 responses at 4, 16, 24, and 48 weeks were analyzed retrospectively from patient charts by examining demographic and clinical characteristics of the patients, especially their previous biologic experience, obesity, and involvement of hard-to-treat areas. RESULTS: PASI75, PASI90, and PASI100 responses were achieved in 92.4%, 86.1%, and 26.6% patients at week 16 and maintained till week 48 in 92.3%, 86.5%, and 17.3% patients. PASI90 responses in obese patients were significantly lower than non-obese patients at week 4 (33.3% vs. 69.6%, p = 0.042), but this difference was minimized by week 16 (82.4% vs. 90%, p = 0.405). PASI90 responses in biologic-naive patients were significantly higher than biologic-experienced patients at week 16 (p = 0.015). Involvement of hard-to-treat areas was negatively associated with PASI90 responses at week 16 (OR: 1591805.842; 95% CI: 1.223-2071404486740.201; p = 0.047). CONCLUSION: Ixekizumab provides an effective and safe biologic treatment option to patients with moderate-to-severe plaque psoriasis. Obesity, though it affects the early treatment response (till week 4), does not upset the overall treatment response beyond week 16. Previous biologic exposure and involvement of hard-to-treat areas are important prognostic factors for achieving high PASI responses in psoriatic patients.

Adalimumab, Ustekinumab, and Secukinumab in the Management of Hidradenitis Suppurativa: A Review of the Real-Life Experience.

To date, adalimumab (ADA) is the only biotechnology drug approved for the management of hidradenitis suppurativa (HS), an inflammatory skin condition. However, it quickly became apparent that the efficacy of adalimumab in daily practice was highly variable. In our review, we highlighted the current evidence from literature on the use of biologics in HS in a real-life setting, particularly adalimumab, secukinumab and ustekinumab. Data on the effectiveness and safety of biologic drugs in HS management have been analyzed. Even if the results are promising, more studies are needed. In our opinion, the armamentarium of drugs for HS management is increasing, and treatment will be based on a tailored-tail approach, minimizing the risk of adverse events. In this context, we want to point out the reported effectiveness and safety data concerning adalimumab, ustekinumab and secukinumab as well as ixekizumab.

Efficacy and Safety of Ixekizumab in Chinese Patients with Moderate-to-Severe Plaque Psoriasis: 60-Week Results from a Phase 3 Study

Objective: Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin-17A and is approved for treating moderate-to-severe psoriasis. This phase 3, multicenter, randomized, double-blind, placebo-controlled trial (NCT03364309;registered December 6, 2017) evaluated the safety and efficacy of ixekizumab in Chinese patients with moderate-to-severe psoriasis. Method(s): 438 patients were randomized 2:2:1 to 80 mg ixekizumab every 2 weeks (IXE Q2W, n = 176), 80 mg ixekizumab every 4 weeks (IXE Q4W, n = 174), or placebo (n = 88). Efficacy was assessed by evaluating the static Physician's Global Assessment score of 0 or 1 (sPGA [0,1]) and Psoriasis Area and Severity Index (PASI) 75/90/100 responses, and nonresponder imputation was used for handling missing data. The safety profile was evaluated by assessing treatment emergent adverse events (AEs) and serious AEs. Result(s): At week 12, the sPGA (0,1) response rates were 3.4%, 79.9%, and 86.4% in the placebo, IXE Q4W, and IXE Q2W groups, respectively. The PASI 75/90/100 response rates were 8.0%/2.3%/0.0%, 87.4%/75.9%/29.3%, and 93.8%/82.4%/33.0% in the placebo, IXE Q4W, and IXE Q2W groups, respectively. Ixekizumab led to rapid PASI 50 responses, as early as week 1, whereas PASI 75 and sPGA (0,1) responses were observed from week 2. sPGA (0,1) and sPGA (0) responses were maintained through week 60 in a higher proportion of patients receiving IXE Q4W vs. placebo. The safety profile was consistent with previous studies of ixekizumab in psoriasis. Conclusion(s): Ixekizumab showed a rapid onset of action and high efficacy that was maintained through 60 weeks and was well tolerated with no unexpected AEs, in Chinese patients with moderate-to-severe plaque psoriasis. Copyright © 2022 International Journal of Dermatology and Venereology. All right reserved.

Drug safety evaluation of ixekizumab for psoriasis: a review of the current knowledge.

INTRODUCTION: Since Anti-IL-17s availability, concerns about their safety have been raised due to the inhibition of physiological activities that IL-17A plays in the immune response against infections. Ixekizumab is a humanized monoclonal antibody specifically targeting IL-17A approved for the treatment of moderate-to-severe psoriasis. AREAS COVERED: The aim of this review is to evaluate the safety profile of ixekizumab in moderate-to-severe psoriasis patients. A compressive literature review has included articles since March 2022. EXPERT OPINION: In our analysis, most of the reported AEs were mild or moderate and rarely required treatment discontinuation. Among the class-specific AEs to consider during ixekizumab treatment, there are the risk of Candida infections and the risk of IBD, both of which were reported more frequently than placebo or other biologics (etanercept, ustekinumab, and guselkumab). However, the reported candidiasis resulted in mild-to-moderate and easily managed. The risk of IBD (both exacerbation and de novo diagnosis) represents a class effect of IL-17 inhibitors, which should be well evaluated before considering starting ixekizumab treatment. The most common AEs were represented by nasopharyngitis, upper respiratory tract infection, and injection-site reactions. The analyzed studies confirmed the favorable safety profile of ixekizumab even in more recently published studies.

COVID19 VACCINATION in PATIENTS with AXIAL and PERIPHERAL SPONDYLOARTHRITIS and PSORIATIC ARTHRITIS: ADVERSE EVENTS and IMPACT on DISEASE ACTIVITY

Background: There is scarce evidence on the rate of adverse events and the consequences on disease activity after vaccination against covid19 Objectives: To evaluate adverse events to vaccination and disease fares after vaccination in patients with axial spondyloarthritis (axSpA), peripheral spondy-loarthritis (pSpA) and psoriatic arthritis (PsA) and to evaluate factors associated with adverse event. Methods: Cross-sectional, observational, descriptive study. Consecutive patients with diagnosis of ankylosing spondylitis (AS) and non-radiographic axial spondy-loarthritis (nr-axSpA) according to ASAS 2009 criteria;pSpA according to ASAS 2011 criteria and PsA according to CASPAR criteria were included. Demographic data, disease clinimetry, treatments, vaccination received and post-vaccination adverse events were recorded. We evaluated, according to medical criteria, whether the patient presented a fare disease after vaccination and whether it was mild, moderate or severe. We also evaluated the factors associated with the presence of at least one mild adverse event. Statistical analysis: descriptive statistics were performed, qualitative variables were expressed as frequency and percentage (%), numerical variables as mean and standard deviation (SD) or median and percentile25-75. Binary logistic regression was performed using the presence of at least one mild adverse event to vaccination as the dependent variable. Results: 210 patients were included with a mean age of 45 (SD 15) years. The diagnoses were: AS 50 (23.8%), nr-axSpA 10 (4.8), pSpA 9 (4.3%), PsA 141 (67%) and time of disease evolution in months 109 (SD 96). Regarding comorbidities, the following frequencies were reported: arterial hypertension 60 (30%), diabetes mellitus 25 (12%), heart failure 4 (2%), asthma/EPOC 15 (7%), infammatory bowel disease 2 (1%), acute anterior uveitis 20 (9.5%), psoriasis 128 (61%). Sixteen percent (n=33) of the patients had SARS-CoV-2 infection prior to vaccination. Regarding treatments, those used were: antiTNF 88 (42%), Tofacitinib 6 (2.9%), Ustekinumab 2 (1%), Secukinumab 35 (17%), Ixekizumab 2 (1%), methotrexate 98 (47%), lefunomide 7 (3. 3), sulfasalazine 7 (3.3), apremilast 1 (0.5%), continuous NSAIDs 26 (12.4%) and NSAIDs on demand 103 (49%). Vaccines received were: Sputnik V 109 (51.9%), Oxford Vaccine, AstraZeneca 63 (30%), Janssen 1 (0.5%), BioNTech Vaccine, Pfzer 1 (0.5%), Sinopharm 33 (15.7%), Moderna 0%, Novavax 0% and others;3 (1.4%). Thirty-eight percent (n=80) of patients reported having mild post-vaccination symptoms, of which 3.75% did not resolve, 41% resolved with medication and 39% resolved ad integrum without medication. The presence of mild adverse event to the vaccine was associated with lower use of methotrexate (31% vs 56 %, p<0.001), and lower age (54 (SD 14) vs 47 (SD 12), p<0.001), and lower BMI (25 (24-30.5) vs 28 (25-31), p<0.001);while no association was found with sex, diagnosis, comorbidities, treatments, desease activity or vaccines. In the logistic regression analysis all the variables remained independently associated with a lower probability of presenting a mild adverse event: methotrexate: OR: 0.30, 95%CI 0.15-0.58, p<0.001, age: OR: 0.97, 95%CI 0.95-0.99, p: 0.03, BMI: OR: 0.92, 95%CI 0.95-0.99, p: 0.02. Sixty-one percent (n=129) of patients received the 2nd dose of vaccination, which 27% (n=35) presented mild adverse event and only 1 (0.8%) patient suffered post vaccination disease fare. Conclusion: Vaccination against COVID19 appears to be safe in this population, with only mild adverse events and low frequency of fare disease. Mild adverse events were associated with less use of methotrexate, younger age and lower BMI.

Healthcare resource utilization and costs among patients with psoriasis treated with ixekizumab or adalimumab over 2 years of follow-up in real-world settings.

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

Treatment of Two Patients with Erythrodermic Psoriasis with Ixekizumab During COVID-19 Pandemic

Erythrodermic psoriasis (EP) is the most severe form of psoriasis. Here, we report two cases of EP who achieved Psoriasis Area and Severity Index (PASI) 100 with the treatment of ixekizumab during Coronavirus disease-19 (COVID-19) pandemic. A female and a male patient with EP applied to dermatology outpatient clinic of our hospital. Treatment with standard dose ixekizumab (160 mg sc at week 0 and then 80 mg sc every 2 weeks for 12 weeks) led to PASI 100 response in our first case after only 5 weeks and in our second case after 6 weeks. To date, there have been six patients with EP who reached PASI 100 with ixekizumab treatment, one of them could achieve to this level earliest at week 6, one of them earliest at week 8 and four of them earliest at week 12, whereas our first case reached PASI 100 at week 5 and our second case reached at week 6. Our cases were deemed worthy of presentation because our female patient was the case with the fastest response to PASI 100 with ixekizumab, and our two cases were the first reported patients who reached PASI 100 during COVID-19 pandemic. Our patients continue ixekizumab treatment without any side effects and remain self-isolated at home.

Ixekizumab May Improve Renal Function in Psoriasis.

BACKGROUND: Psoriasis is a chronic dermatological condition characterized by lesions on extensor surfaces, hands, feet, and genital areas. Chronic renal failure is often associated with metabolic syndrome and inflammatory conditions, such as psoriasis. CASE REPORT: In this paper, we report a patient with stage-three chronic renal failure that improved his renal condition after treatment with ixekizumab, an anti-IL17A drug used in the treatment of various cutaneous and rheumatological conditions. CONCLUSIONS: IL17A blockage may help to treat various autoimmune and inflammatory conditions, such as psoriasis, that may lead to renal impairment. Further investigation is necessary in order to prove the effectiveness of this drug in renal conditions.

Safety and Efficacy of Ixekizumab and Antiviral Treatment for Patients with COVID-19: A structured summary of a study protocol for a Pilot Randomized Controlled Trial.

OBJECTIVES: A severe epidemic of COVID-19 has broken out in China and has become a major global public health event. We focus on the Acute Respiratory Distress Syndrome (ARDS)-like changes and overactivation of Th17 cells (these produce cytokines) in patients with COVID-19. We aim to explore the safety and efficacy of ixekizumab (an injectable drug for the treatment of autoimmune diseases) to prevent organ injury caused by the immune response to COVID-19. Ixekizumab is a human monoclonal antibody that binds to interleukin-17A and inhibits the release of pro-inflammatory cytokines and chemokines. TRIAL DESIGN: The experiment is divided into two stages. In the first stage, the open trial, 3 patients with COVID-19 are treated with ixekizumab, and the safety and efficacy are observed for 7 days. In the second stage, 40 patients with COVID-19 are randomly divided into two groups at 1:1 for 14 days. This is a two-center, open-label, randomized controlled pilot trial with 2-arm parallel group design (1:1 ratio). PARTICIPANTS: Patients with COVID-19 aged 18-75 with increased Interleukin (IL)-6 levels will be enrolled, but patients with severe infections requiring intensive care will be excluded. The trial will be undertaken in two centers. The first stage is carried out in Xiangya Hospital of Central South University, and the second stage is carried out simultaneously in the Third Xiangya Hospital of Central South University. INTERVENTION AND COMPARATOR: In the first stage, three subjects are given ixekizumab ("Taltz") (80 mg/ml, 160 mg as a single hypodermic injection) and antiviral therapy (α-interferon (administer 5 million U by aerosol inhalation twice daily), lopinavir/ritonavir (administer 100mg by mouth twice daily, for the course of therapy no more than 10 days), chloroquine (administer 500mg by mouth twice daily, for the course of therapy no more than 10 days), ribavirin (administer 500mg by intravenous injection two to three times a day, for the course of therapy no more than 10 days), or arbidol (administer 200mg by mouth three times a day, for the course of therapy no more than 10 days), but not more than 3 types). The treatment course of the first stage is 7 days. In the second stage, 40 randomized patients will receive the following treatments--Group 1: ixekizumab (80 mg/ml, 160 mg as a single hypodermic injection) with antiviral therapy (the same scheme as in the first stage); Group 2: antiviral therapy alone (the same scheme as in the first stage). The length of the second treatment course is 14 days. MAIN OUTCOMES: The primary outcome is a change in pulmonary CT severity score (an imaging tool for assessing COVID-19, which scores on the basis of all abnormal areas involved). Pulmonary CT severity score is assessed on the 7th day, 14th day, or at discharge. RANDOMISATION: In the second stage, 40 patients with COVID-19 are randomly divided into two groups at 1:1 for 14 days. The eLite random system of Nanjing Medical University is used for randomization. BLINDING (MASKING): The main efficacy indicator, the CT results, will be evaluated by the third-party blinded and independent research team. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): In the second stage, 40 patients with COVID-19 are randomly divided into two groups at 1:1 for 14 days. TRIAL STATUS: Trial registration number is ChiCTR2000030703 (version 1.7 as of March 19, 2020). The recruitment is ongoing, and the date recruitment was initiated in June 2020. The anticipated date of the end of data collection is June 2021. TRIAL REGISTRATION: The name of the trial register is the Chinese Clinical Trial Registry. The trial registration number is ChiCTR2000030703 ( http://www.chictr.org.cn/ ). The date of trial registration is 10 March 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).