Efficacy and safety of Ixekizumab vs. low-dose IL-2 vs. Colchicine vs. standard of care in the treatment of patients hospitalized with moderate-to-critical COVID-19: A pilot randomized clinical trial (STRUCK: Survival Trial Using Cytokine Inhibitors)

ABSTRACT Background: Cases of coronavirus disease 2019 (COVID-19) requiring hospitalization continue to appear in vulnerable populations, highlighting the importance of novel treatments. The hyperinflammatory response underlies the severity of the disease, and targeting this pathway may be useful. Herein, we tested whether immunomodulation focusing on interleukin (IL)-6, IL-17, and IL-2, could improve the clinical outcomes of patients admitted with COVID-19. Methods: This multicenter, open-label, prospective, randomized controlled trial was conducted in Brazil. Sixty hospitalized patients with moderate-to-critical COVID-19 received in addition to standard of care (SOC): IL-17 inhibitor (ixekizumab 80 mg SC/week) 1 dose every 4 weeks; low-dose IL-2 (1.5 million IU per day) for 7 days or until discharge; or indirect IL-6 inhibitor (colchicine) orally (0.5 mg) every 8 hours for 3 days, followed by 4 weeks at 0.5 mg 2x/day; or SOC alone. The primary outcome was accessed in the "per protocol" population as the proportion of patients with clinical improvement, defined as a decrease greater or equal to two points on the World Health Organization's (WHO) seven-category ordinal scale by day 28. Results: All treatments were safe, and the efficacy outcomes did not differ significantly from those of SOC. Interestingly, in the colchicine group, all participants had an improvement of greater or equal to two points on the WHO seven-category ordinal scale and no deaths or patient deterioration were observed. Conclusions: Ixekizumab, colchicine, and IL-2 were demonstrated to be safe but ineffective for COVID-19 treatment. These results must be interpreted cautiously because of the limited sample size.

Short-term effectiveness of ixekizumab in the treatment of psoriasis: a single-center retrospective study / 中华皮肤科杂志

Objective:To evaluate the real-world short-term effectiveness of ixekizumab in the treatment of psoriasis, and to investigate factors influencing the effectiveness.Methods:Baseline data and short-term effectiveness evaluation results were retrospectively collected from patients with psoriasis, who received ixekizumab treatment in Department of Dermatology, Xiangya Hospital from November 2019 to September 2021. A descriptive analysis was performed on the baseline characteristics of patients, continuous data were described as median (lower quartile, upper quartile), and categorical data were described as percentages. Comparisons of disease severity scores before and after the treatment with ixekizumab were performed using Wilcoxon signed-rank test or paired McNemar test. Multivariable logistic regression analysis was conducted to explore factors influencing the effectiveness of 4-week ixekizumab treatment.Results:A total of 118 patients with psoriasis were included, including 94 males and 24 females, and their age [ M ( Q1, Q3) ] was 43.4 (32.5, 53.0) years; plaque psoriasis (99 cases, 83.9%) and severe psoriasis (72 cases, 68.6%) predominated among the 118 patients, and skin lesions were mainly located on the scalp (59/116, 50.9%). Among the 49 patients who had received 2-week ixekizumab treatment, 27 (55.1%) achieved a 50% improvement in the psoriasis area and severity index (PASI) score (PASI50) ; after 4-week treatment, 44 (89.8%), 30 (61.2%), 13 (26.5%) and 10 (20.4%) patients achieved PASI50/75/90/100 respectively, and their PASI scores (2.1 [1.1, 7.1]), involved body surface area (3.9% [0.5%, 14.5%]), dermatology life quality index scores (1.0 [0.0, 2.0]) and physician global assessment (PGA) scores (1.0 [1.0, 3.0]) were significantly lower than the corresponding scores at baseline (12.4 [8.8, 23.2], 22.0% [11.3%, 43.4%], 6.0 [3.0, 11.0], 4.0 [3.0, 5.0], respectively; all P < 0.001]. Multivariable logistic regression analysis showed that the baseline body mass index was significantly associated with the PASI75 response rate ( OR = 0.814, 95% CI: 0.659 - 0.958, P = 0.029) and the proportion of patients with PGA0/1 ( OR = 0.743, 95% CI: 0.562 - 0.917, P = 0.017) after 4-week ixekizumab treatment, and the baseline BSA score was significantly associated with the proportion of patients with PGA0/1 after 4-week ixekizumab treatment ( OR = 0.924, 95% CI: 0.870 - 0.968, P = 0.003) . Conclusion:The 4-week ixekizumab treatment significantly decreased the severity of psoriasis, and may be more effective in patients with lower disease severity and lower body mass index at baseline.

Atualização do custo-efetividade por resposta de adalimumabe, etanercepte, guselcumabe, infliximabe, ixequizumabe, secuquinumabe e ustequinumabe no tratamento de psoríase em placas moderada a grave sob a perspectiva do Sistema de Saúde Suplementar brasileiro / An update of a cost-effectiveness per response of adalimumab, etanercept, guselcumab, infliximab, ixekizumab, secukinumab and ustekinumab for treatment of moderate to severe plaque psoriasis from the perspective of the Brazilian Supplementary Health System

Objetivo: Os agentes biológicos representam um grande avanço no tratamento da psoríase em placas moderada a grave. No entanto, variações de eficácia, segurança e custos dos tratamentos podem dificultar a escolha do agente terapêutico. Este estudo teve como objetivo atualizar o custo por resposta dos agentes biológicos disponíveis para psoríase no ROL de Procedimentos e Eventos em Saúde (ROL) da Agência Nacional de Saúde Suplementar (ANS). Métodos: Uma análise de custo por resposta foi utilizada para avaliar a razão de custo pelo desfecho Índice de Gravidade e Área da Psoríase (PASI) 90. Os resultados foram apresentados para o primeiro ano (ano I), que compreende a fase de indução e a fase manutenção até completar 52 semanas e foi realizada uma análise da efetividade do tratamento num cenário de orçamento fixo. Os custos dos tratamentos foram calculados com base nos preços de fábrica (PF18%) da Tabela da Câmara de Regulação do Mercado de Medicamentos de junho de 2021. Resultados: Para o ano I, o guselcumabe apresentou melhor resultado para custo por resposta (R$ 130.467) PASI 90, seguido por ixequizumabe, ustequinumabe, secuquinumabe, adalimumabe, infliximabe e etanercepte. No cenário com orçamento fixo, o guselcumabe demonstrou ser o agente capaz de tratar com sucesso (PASI 90) o maior número de pacientes. Atualização do custo-efetividade por resposta para psoríase em placas moderada a grave. Conclusão: Sob a perspectiva do Sistema de Saúde Suplementar do Brasil, o guselcumabe apresentou o melhor custo por resposta PASI 90, sendo, assim, a terapia com melhor custo-efetividade no tratamento da psoríase em placas moderada a grave disponível no ROL.

Objective: Biological agents represent a major advance in the treatment of moderate-to-severe plaque psoriasis. However, variations of efficiency, safety and costs of treatments make it difficult to select the drug. This study aims to update the cost per response of biological agents available in the Health Procedures and Events Roll (ROL) of the National Supplementary Health Agency (ANS). Methods: A cost-per-response analysis was used to assess the cost per outcome of Psoriasis Area and Severity Index (PASI) 90. Results were presented for the first year (I), which comprises induction and maintenance for 52 weeks and a fixed budget scenario analysis. Treatment costs were calculated based on the prices of the 2021 Medicines Market Regulation Chamber Table. Results: Analysis of year I, guselkumab showed the best result for cost per cost (R$ 130,467) PASI 90, followed by ixekizumab, ustekinumab, secukinumab, adalimumab, infliximab, and etanercept. In the fixedbudget analysis, guselkumab is the therapy capable of successfully treating (PASI 90) the largest number of patients. Conclusion: From the perspective of the Supplementary Health System in Brazil, guselkumab showed the best cost per response PASI 90, thus being the most cost-effective therapy in the treatment of moderate to severe plaque psoriasis available in the Brazilian ROL.

Pharmacoeconomic Evaluation of Ixekizumab in the Treatment of Moderate-to-severe Plaque Psoriasis / 中国药房

OBJECTIVE：To evaluate the drug economy of ixekizumab in the treatment of moderate-to-severe plaque psoriasis. METHODS： Literatures were retrieved from PubMed ， Embase， The Cochrane Library ， CNKI and Wanfang database ， supplemented by manual search ，search time from the database establishment to Oct. 31st，2019，using Chinese and English search terms included “Ixekizumab”“Taltz”“Psoriasis”“Pharmacoeconomics”“Cost-benifit analysis ”“Cost-effectiveness analysis ” “Cost-utility analysis ”，etc. The literatures were screened according to inclusion and exclusion criteria. Relevant pharmacoeconomic studies about ixekizumab in the treatment of moderate-to-severe plaque psoriasis were collected ，and the study methods and pharmacoeconomic evaluation results were summarized. RESULTS ：A total of 8 literatures were included ，involving 9 studies. The overall quality of the studies was high. All the studies were distributed in foreign countries such as Canada ，the United States and the United Kingdom. All the studies adopted Markov model. The health outcomes showed that ixekizumab could bring more quality-adjusted life years. Compared with methotrexate combined with phototherapy ，infliximab，ustekinumab and secukinumab ， the incremental cost-utility ratio （ICUR）of ixekizumab was different in different studies. CONCLUSIONS ：Ixekizumab has certain economic advantages for the treatment of moderate-to-severe plaque psoriasis ，but there is still a lack of relevant research in China and it is urgent to carry out relevant research suitable for Chinese.