Clinical remission and transmural healing of ustekinumab in patients with Crohn's disease / 北京大学学报(医学版)

Objective:To treat the Crohn's disease(CD)patients with ustekinumab(UST),to eva-luate their clinical and endoscopic remission,and to evaluate their transmural response(TR)and trans-mural healing(TH)condition using intestinal ultrasonography(IUS).Methods:Retrospective analysis was made on patients diagnosed with CD in Peking University People's Hospital from January 2020 to Au-gust 2022,who were treated with UST for remission induction and maintenance therapy.All the patients were evaluated on both week 8 and week 16/20 after treatment,including clinical,biochemical indica-tors,colonoscopy and IUS examination.Results:A total of 13 patients were enrolled in this study,inclu-ding 11 males and 2 females.The minimum age was 23 years,the maximum age was 73 years and the mean age was 36.92 years.All the patients were in the active stage of disease before treatment,and the average Best Crohn's disease activity index(Best CDAI)score was 270.12±105.55.In week 8,the Best CDAI score of the patients decreased from 270.12±105.55 to 133.16±48.66(t=4.977,P＜0.001).Eight patients achieved clinical remission while 5 patients remained in the active stage.Nine patients underwent colonoscopy evaluation.The average simple endoscopic score for Crohn's disease(SES-CD)score decreased from 10.71±7.14 before treatment to 6.00±7.81(t=2.483,P=0.048)in week 16/20.Four patients achieved endoscopic remission while 5 patients did not.In week 8,5 pa-tients achieved TR,2 patients achieved TH,the other 6 patients did not get TR or TH.In week 16/20,6 patients achieved TR,3 patients achieved TH while the other 4 patients did not get TR or TH.There was no significant statistical difference in the TR effect of UST between small intestine and colon lesions(Fisher test,P＞0.999).The rate of UST transmural response in the patients who had had previous bio-logical agent therapy was lower than those with no previous biological agent therapy,but there was no sig-nificant statistical difference(Fisher test,P=0.491).Conclusion:After treatment of UST,the clinical and endoscopic conditions of the CD patients had been improved,and some patients could achieve clini-cal remission and endoscopic remission.UST had good TR and TH effects on CD.TR might appear in week 8,and the TR effect increased in week 16/20.There was no significant statistical difference in the TR effect between small intestine and colon lesions.TR effect of UST was better in the patients who had no previous biological agent therapy than those who had had other biological agents,but the result had no significant statistical difference.

Short term clinical efficacy and influencing factors of ustekinumab monoclonal antibody in the treatment of Crohn's disease / 实用医学杂志

Objective To analyze the short-term clinical efficacy and influencing factors of ustekinumab monoclonal antibody(UST)in the treatment of Crohn′s disease(CD).Methods Retrospective cohort study was used to collect the clinical data of CD patients treated with UST in the 10th People′s Hospital affiliated to Tongji University from December 2020 to October 2022.The main analysis is the short-term clinical efficacy and influencing factors of UST treatment for CD at weeks 8 and 16,And analyze the endoscopic response rate of some patients.Results A total of 91 CD patients who first used UST were included.The 8-week clinical response rate of UST treat-ment for CD was 61.5%,and the clinical response rate was 45%;The clinical response rate at 16 weeks was 71.4%,and the clinical response rate was 54.9%.56 cases underwent endoscopic re-examination in our hospital,and the endoscopic response rate at 16 weeks was 41.1%.Univariate analysis showed that fistula(including anal fistula,personal history of anal fistula,and intestinal skin fistula)is associated with clinical remission in Crohn′s disease patients at 8/16 weeks.Further multivariate COX regression analysis showed that the presence of a history of anal fistula surgery was an independent protective factor affecting clinical remission in CD patients treated with UST at 8 weeks(HR = 0.04,95%CI:0.00～0.38;P = 0.005)and 16 weeks(HR = 0.04,95%CI:0.01～0.34;P = 0.003)compared to those without fistula;Narrow lesions are an independent risk factor for 16 week clinical remission in CD patients compared to non-narrow and non-penetrating lesions(HR = 1.75,95%CI:1.08～2.84;P = 0.023).No patients were found to have stopped medication due to serious adverse reactions.Conclusions UST can improve the clinical remission and response of CD patients at 8/16 weeks,and has good short-term clinical efficacy.CD patients with a personal history of anal fistula are recommended to use UST monoclonal antibodies,while patients with stenotic lesions should be cautious in using UST monoclonal antibodies.Whether the patient has undergone surgical treatment in the past,as well as whether UST has been used on the first or non-first line,has no significant impact on clinical remission.

Signal mining and evaluation of adverse events of four biological agents for the treatment of inflammatory bowel disease / 中国药房

OBJECTIVE To provide reference for safe drug use in the clinic by mining the adverse drug event （ADE） signals of 4 kinds of biological agents for the treatment of inflammatory bowel disease （IBD）. METHODS ADE data of infliximab， adalimumab， ustekinumab and vedolizumab were collected from the FDA adverse event reporting system between the first quarter in 2004 and the fourth quarter in 2022， and were mined by using reporting odds ratio （ROR） method and proportional reporting ratio （PRR） method. The system organ class （SOC） was used for the classification and statistics of drug ADE terminology. RESULTS & CONCLUSIONS A total of 65 173， 247 894， 37 596 and 6 134 ADE reports were retrieved for the above 4 biologic agents， involving 1 664， 1 731， 588， 303 ADE signals and 27， 27， 24， 26 SOC， respectively. The largest number of ADE reported of infliximab were various musculoskeletal and connective tissue diseases， and the signal intensity of disseminated tuberculosis was stronger. The largest number of ADE reported of adalimumab were systemic disease and various reactions at the administration site， and the signal intensity of papular at the injection site was stronger. The largest number of ADE reported of ustekinumab were various injuries， poisoning and operation complications， and the signal intensity of latent tuberculosis was slightly stronger. The largest number of ADE reported of vedolizumab were systemic diseases and various reactions at the administration site， and the signal intensity of shorter treatment response time was stronger. When clinically administering the four drugs， it is crucial to pay close attention to common ADEs and other ADE not mentioned in the drug label. For infliximab， clinicians should exercise caution due to the potential risk of synovitis and basal cell carcinoma； when prescribing adalimumab， caution should be exercised due to ADEs related to synovitis and hernia； for ustekinumab， the ADE associated with hepatobiliary diseases should be vigilant； for vedolizumab， clinicians should be vigilant for blood in the stool， increasing frequency of defecation. Except for ustekinumab， the other 3 biological agents also require attention for ADE associated with pregnancy.

Unmet need for and impact of adopting immunobiological drugs for moderate to severe plaque psoriasis in a pediatric population

ABSTRACT Objective Therefore, this study aimed to evaluate the impact of secukinumab and ustekinumab against moderate-to-severe plaque psoriasis in a Brazilian pediatric population with access to public healthcare. Methods A survey of immunobiological treatments registered for use against pediatric psoriasis at the National Health Surveillance Agency was conducted. These treatments were compared to the list available in the same treatment category in the public health system through the Clinical Protocol and Therapeutic Guidelines for psoriasis. A quantitative analysis of the data of patients treated with immunobiological drugs the previous year in accordance with the Clinical Protocol and Therapeutic Guidelines was performed using data available in the DATASUS portal. Results The public budget impact scenarios analyzed were comparable to the investment already planned for acquiring the only available drug option. Conclusion The incorporation of two therapeutic options in the Clinical Protocol and Therapeutic Guidelines list for moderate-to-severe pediatric psoriasis was feasible in a horizon of 5 years compared to the investment into the single option available to pediatric patients. These findings can facilitate the local analysis of budgetary impact and discussions on the feasibility of this therapeutic incorporation at the state level.

Tromboembolia pulmonar masiva en un paciente con enfermedad de Crohn y tuberculosis latente tratada con ustekinumab

La enfermedad inflamatoria intestinal (EII) es un espectro de enfermedades crónicas inmunomediadas que afectan tanto el tracto gastrointestinal, como otros sistemas extraintestinales, comportándose como una enfermedad sistémica. Los fenómenos tromboembólicos son una complicación frecuente en la EII, como consecuencia de los estados de hipercoagulabilidad que se asocian con la actividad de la enfermedad, y su aparición tiene un impacto negativo tanto en el pronóstico como en la sobrevida de los pacientes. Debido a ello, el control de la actividad inflamatoria de la EII es uno de los pilares en el control de los eventos tromboembólicos. Los medicamentos biológicos se asocian al control rápido del cuadro inflamatorio, sin embargo, siempre se discute el tema de seguridad para la reactivación de infecciones latentes, en particular tuberculosis. Presentamos el caso de un paciente de 37 años que debutó con trombosis venosa profunda en el miembro inferior izquierdo y posteriormente con tromboembolismo pulmonar masivo. Luego de investigar la etiología y ampliar la historia clínica se le diagnosticó Enfermedad de Crohn (EC). Al realizar los estudios previos al uso de biológicos, las pruebas de PPD y quantiferon resultaron positivas, luego de la discusión del caso se decidió iniciar tratamiento con ustekinumab.

Inflammatory bowel disease (IBD) is a spectrum of chronic immune-mediated diseases that affect the gastrointestinal tract and other extraintestinal systems, behaving as a systemic disease. Thromboembolic phenomena are a frequent complication in IBD, because of hypercoagulability states associated with disease activity, and their presence has a negative impact on prognosis and patient survival. Due to this, the control of the inflammatory activity of IBD is one of the pillars in the control of thromboembolic events. Biological drugs are associated with rapid control of the inflammatory process, however, the security profile for the reactivation of latent infections, particularly tuberculosis, is always discussed. We present the case of a 37-year-old patient who presented with deep vein thrombosis in the left lower limb and later with massive pulmonary thromboembolism. During his evaluation, he was diagnosed with Crohn's disease (CD). When carrying out the studies prior to the use of biologics, PPD and quantiferon tests were positive. After discussing the case, we decided to start treatment with ustekinumab.

Signal detection and analysis of the adverse events of ustekinumab based on OpenFDA database / 中国药房

OBJECTIVE To analyze the risk of adverse drug reaction of ustekinumab， so as to provide reference for rational drug use in clinic. METHODS The adverse events （AE） reports related to ustekinumab included in the FDA public data program （OpenFDA） database were analyzed after marketing （from September 25th 2009 to December 30th 2021）. The risk signals were mined for top 100 AE by the method of reporting odds ratio （ROR） and proportional reporting ratio （PRR）. RESULTS A total of 62 356 AE reports related to ustekinumab were retrieved， male patients （51.79%） were more than female patients （39.51%）. Results of ROR method and PRR method showed that 31 suspicious signals were mined， mainly infections and infectious diseases （9 kinds）， general disorders and administration site conditions （5 kinds）， skin and subcutaneous tissue disorders diseases （4 kinds）， musculoskeletal and connective tissue disorders （4 kinds）， etc. Fourteen suspicious signals were not included in the instructions， such as hepatic enzyme increase， basal cell carcinoma， pericarditis， pemphigus， hair loss， synovitis， glossodynia， etc. CONCLUSIONS During clinical dosing of ustekinumab， in addition to ADR mentioned in package inserts， great attention should be paid to the patient’s liver function， skin status， hair loss and cardiovascular-related risks，which is helpful to discover AE early and ensure the safety medication of patients.

Analysis of the short-term efficacy of ustekinumab as the first-line treatment for Crohn′s disease / 中华消化杂志

Objective:To evaluate the short-term efficacy of ustekinumab (UST) as the first-line treatment of Crohn′s disease (CD).Methods:From October 1, 2020 to March 1, 2023, at the First Affiliated Hospital of Soochow University, 64 CD patients treated with UST as first-line biologics were enrolled. The patients were classified using the Montreal classification. Clinical and endoscopic response and remission were assessed by Crohn′s disease activity index (CDAI) and simple endoscopic score for crohn′s disease (SES-CD), respectively. Clinical response was defined as a reduction in CDAI score ≥70, and clinical remission was defined as a CDAI score <150; Endoscopic response was defined as ≥50% reduction from baseline in SES-CD score, and endoscopic remission was defined as SES-CD score ≤2. The clinical response rate and clinical remission rate at week 24 and week 48, as well as the endoscopic response rate and endoscopic remission rate at week 48 were observed in CD patients (only 21 patients with endoscopic prognostic results). Mann-Whitney rank sum test was used for statistical analysis.Results:Among 64 CD patients, there were 47 males and 17 females, with an age of (33.5±13.7) years old. According to Montreal classification, there were 3 cases (4.7%) of type A1 (≤16 years old), 44 cases (68.8%) of type A2 (17 to 40 years old), and 17 cases (26.6%) of type A3 (>40 years old); 43 cases (67.2%) of type L1 (terminal ileum type), 10 cases (15.6%) of type L2 (colonic type), 8 cases (12.5%) of type L3 (ileocolonic type), 1 case (1.6%) of type L4 (upper gastrointestinal type), 2 cases (3.1%) of type L1+ L4; 23 cases (35.9%) of type B1 (non-stricturing, non-penetrating), 34 cases (53.1%) of type B2 (stricturing), 2 cases (3.1%) of type B3 (penetrating), 5 cases (7.8%) of type B2+ B3; 44 cases (68.8%) complicated with perianal lesions. Among 56 CD patients with UST maintenance therapy once every 8 weeks, the CDAI scores at week 24 and 48 after treatment were both lower than that at week 0 (64.46(30.61, 123.30), 34.24(15.77, 64.83) vs. 353.40(290.40, 391.30)), and the CDAI score at week 48 after treatment was lower than that at week 24 after treatment, and the differences were statistically significant ( Z=-9.01, -9.13, and -3.14; P<0.001, <0.001, and =0.002). The clinical response rate was 100.0% (56/56) and the clinical remission rate was 91.1% (51/56) at week 24; the clinical response rate was 100.0% (56/56) and the clinical remission rate was 98.2% (55/56) at week 48. Among 39 CD patients complicated with perianal lesions, the closure rate of anal lesions at week 24 was 87.2% (34/39) and at week 48 was 100.0% (39/39). Among 8 CD patients who received UST maintenance therapy once every 12 weeks, the CDAI scores at week 24 and 48 were both lower than that at week 0 (100.40(71.20, 171.30), 38.49(18.25, 143.50) vs. 268.00(242.60, 364.90)), and the differences were statistically significant ( Z=-3.26 and -3.36; both P<0.001). At week 24, 7 CD patients achieved clinical response and 5 CD patients achieved clinical remission. At week 48, 8 CD patients achieved clinical response and 6 CD patients achieved clinical remission. Among 5 CD patients complicated with perianal lesions, 3 CD patients achieved perianal closure at week 24 and all 5 CD patients achieved closure of perianal lesions at week 48. Among 21 CD patients who underwent endoscopic evaluation, 16 CD patients received UST maintenance therapy once every 8 weeks, the SES-CD score at week 48 was lower than that at week 0 (4.00(3.00, 7.75) vs. 9.50(7.25, 10.75)), and the difference was statistically significant ( Z=-3.43, P<0.001), among them, 9 CD patients achieved endoscopic response and 2 CD patients achieved endoscopic remission; 5 CD patients received UST maintenance therapy once every 12 weeks, there was no statistically significant difference in the SES-CD score at week 48 compared with that at week 0 (4.00(1.50, 6.50) vs. 7.00(3.50, 10.00)) ( P>0.05), among them, 3 CD patients achieved endoscopic response and 1 CD patients achieved endoscopic remission. Conclusion:UST as the first-line treatment for CD patients can achieve clinical efficacy (response or remission), and the maintenance therapy is beneficial for endoscopic remission and closure of perianal lesions.

Effects of vitamin D supplementation on the clinical efficacy of Crohn′s disease treated with ustekinumab: a retrospective analysis / 中华消化杂志

Objective:To retrospectively analyze the effects of vitamin D supplementation on the clinical efficacy of ustekinumab (UST) in treatment of patients with Crohn′s disease (CD).Methods:Seventy-one patients with moderate to severe active CD who received the first-line treatment UST from May 2021 to February 2023 were collected by searching the clinical database of the Second Affiliated Hospital of Wenzhou Medical University. The disease activity of CD was evaluated by Harvey-Bradshaw index (HBI) and intestinal inflammation was assessed by simplified endoscopic score for Crohn′s disease (SES-CD). The CD patients were divided into supplementary group ( n=41) and non-supplementary group ( n=30) based on whether vitamin D supplementation (400 U/d) was performed during UST treatment. According to the baseline serum 25 (OH) D level, the patients were divided into vitamin D deficiency group (<20 μg/L, n=42) and non-deficiency group (≥20 μg/L, n=29). The main end points were the differences in the clinical remission (HBI score ≤4) rate and mucosal healing (SES-CD score ≤2) rate between supplementary group and non-supplementary group at week 24 of UST treatment. The secondary end points were the differences in the clinical response (the reduction of HBI score ≥3 compared to week 0) rate and biochemical remission (C-reactive protein (CRP)≤5 mg/L) rate between supplementary group and non-supplementary group at week 8 of UST treatment. A multiple linear regression analysis was performed to investigate the relation between serum 25(OH) D levels and the clinicopathological characteristics of CD patients. Multivariate binary logistic regression models were used to analyze the factors affecting the clinical efficacy of UST at week 8 and 24. Independent sample t test, Mann-Whitney U test, Chi-square test and Fisher′s exact test were used for comparisons between the two groups. Paired t test was used to analyze the differences before and after UST treatment. Results:The results of multiple linear regression analysis for 71 CD patients showed that the baseline serum 25(OH)D level was independent influencing factor for the baseline CRP level ( β=-0.33, 95% confidence interval (95% CI) -0.41 to -0.08, P=0.041) and baseline HBI score ( β= -0.52, 95% CI -0.68 to -0.33, P=0.027). Compared with week 0, the serum 25(OH)D level of supplementary group increased at week 8 ((17.18±5.46) μg/L vs. (13.71±7.73) μg/L), and the difference was statistically significant ( t=-7.81, P<0.001), however, there was no significant difference of serum 25(OH)D in non-supplementary group ((14.85±3.92) μg/L vs. (15.69±5.48) μg/L, P>0.05). At week 8, the HBI score and median CRP level of supplementary group were both lower than those of non-supplementary group (5.71±1.88 vs. 8.34±2.27, 10.83 mg/L (3.95 mg/L, 21.07 mg/L) vs. 16.17 mg/L (6.91 mg/L, 35.48 mg/L)), and the diffierences were statistically significant ( t=0.48, Z=2.87; P<0.001 and =0.001). However, the clinical response rate and biochemical remission rate were both higher than those of non-supplementary group (68.3%, 28/41 vs. 40.00%, 12/30 and 43.9%, 18/41 vs. 13.3%, 4/30), and the differences were statistically significant ( χ2=5.64 and 6.21, P=0.018 and 0.013). Compared with week 0, the serum 25(OH)D level of supplementary group increased ((24.73±8.34) μg/L) at week 24, and the difference was statistically significant ( t=-6.83, P<0.001), however, there was no statistically significant difference in the serum 25(OH)D level of non-supplementary group ((15.59±7.24) μg/L vs. (15.69±5.48) μg/L, P>0.05). At week 24, the decrease of HBI score and SES-CD score of supplementary group were both greater than those of non-supplementary group (difference between week 24 and week 0 -8.96±1.45 vs. -5.33±0.59, -7.00(-10.00, -3.00) vs. -2.00(-2.50, -1.50), and the differences were statisticalcy significant ( t=-5.64 and Z=-3.27, P<0.001 and =0.039). Moreover, the clinical remission rate and mucosal healing rate were both higher than those of non-supplementary group (65.9%, 27/41 vs. 26.7%, 8/30, and 61.0%, 25/41 vs. 30.0%, 9/30), and the differences were statistically significant ( χ2=10.64 and 6.66, P=0.001 and 0.010). At week 24, the analysis of non-supplementary group indicated that the clinical remission rate and mucosal healing rate of patients received vitamin D supplementary therapy were both higher than those of patients without vitamin D supplementary therapy (69.0%, 20/29 vs. 3/13, and 58.6%, 17/29 vs. 2/13), and the differences were statistically significant ( χ2=4.43 and 5.14, P=0.035 and 0.023). Vitamin D supplementing therapy was an independent influencing factor of clinical response rate and biochemical remission rate at week 8, clinical remission rate and mucosal healing rate at week 24 for UST treatment of CD ( OR(95% CI) were 5.83(1.15 to 7.59), 4.91(3.67 to 6.98), 5.13(2.88 to 9.44), 7.01(1.16 to 20.97), respectively; P<0.001, <0.001, <0.001, =0.036). Conclusion:Vitamin D supplementation may help to improve the clinical efficacy of UST treatment in CD patients, especially in patients with vitamin D deficiency.

Efficacy and safety of ustekinumab in the treatment of moderate to severe plaque psoriasis in Singapore

INTRODUCTION@#Ustekinumab is a human monoclonal antibody that binds to the p40 subunit of both interleukin (IL)-12 and IL-23, and it is approved for the treatment of moderate to severe plaque psoriasis. In this study, we assessed the efficacy and safety of patients receiving ustekinumab for psoriasis.@*METHODS@#This retrospective study included all adults with chronic plaque psoriasis who were prescribed ustekinumab in a tertiary dermatologic centre between December 2009 and December 2015. Efficacy end points included a proportion of patients achieving at least 50% and 75% improvement from baseline psoriasis area and severity index (PASI) and body surface area (BSA) at Weeks 4 and 16.@*RESULTS@#A total of 99 patients were prescribed ustekinumab; 69% of these were Chinese, followed by 15% Indians and 9% Malays. 31 patients had documented PASI scores and 55 patients had documented BSA improvements. In patients with recorded PASI scores, 29 (93.5%) of 31 patients achieved PASI 50, and 21 (67.7%) of 31 achieved PASI 75 at week 16. In patients with recorded BSA, 43 (78.2%) of 55 had at least 50% BSA improvement, and 31 (56.4%) of 55 achieved 75% BSA improvement at 16 weeks. Regarding safety, no patient experienced tuberculosis reactivation. A total of 11 (11%) of 99 patients had latent tuberculosis infection and were treated with prophylactic isoniazid. No patient experienced serious adverse events. No cardiovascular events, cutaneous malignancies or deaths were reported over six years.@*CONCLUSION@#Ustekinumab is safe and efficacious in the treatment of patients with moderate to severe plaque psoriasis in a multiethnic Asian population.

Ustequinumabe no manejo da doença de Crohn: um estudo observacional brasileiro / Ustekinumab in crohn's disease management: a brazilian observational study

ABSTRACT Background: Real-world data on the use of Ustekinumab (UST) in Brazilian and Latin American patients with Crohn's disease (CD) are scarce. Objective: The primary endpoint was assessment of clinical remission at weeks 8 and 52, and secondary endpoints were: assessment of clinical response at weeks 8 and 52, endoscopic remission, adverse events, and rates of CD-related abdominal surgery during follow-up. Methods: observational and retrospective study, including patients with CD treated at two centers, who received UST at any time during their treatment. Remission and clinical response were defined as a Harvey-Bradshaw index ≤4 and ≥3 points reduction, respectively. Results: Seventy-four patients were included, 85.1% previously exposed to anti-TNFs. Clinical remission was observed in 45.8% and 59.4% of patients at weeks 8 and 52, respectively. The clinical response rates were 54.2% and 67.6% at weeks 8 and 52. Endoscopic remission was observed in 21.8% of patients. Seventeen patients had adverse events, mostly mild infections, with 22.9% of patients undergoing abdominal surgery (ileocolectomy being the most common procedure). Conclusion UST therapy resulted in significant rates of remission and clinical response, as described in other real-world studies. Few patients had adverse events during treatment, showing its adequate safety profile.

RESUMO Contexto: Dados de vida real sobre o uso de Ustequinumabe (UST) em pacientes brasileiros e latino-americanos com doença de Crohn (DC) são escassos. Objetivo: O desfecho primário foi a avaliação da remissão clínica nas semanas 8 e 52, e os desfechos secundários foram: avaliação da resposta clínica nas semanas 8 e 52, remissão endoscópica, eventos adversos e taxas de cirurgia abdominal relacionada à DC durante o seguimento. Métodos: Estudo observacional e retrospectivo, incluindo pacientes com DC tratados em dois centros, que receberam UST em qualquer momento do tratamento. A remissão e a resposta clínica foram definidas como índice de Harvey-Bradshaw ≤4 e ≥3 pontos de redução, respectivamente. Resultados: Foram incluídos 74 pacientes, 85,1% previamente expostos a anti-TNFs. A remissão clínica foi observada em 45,8% e 59,4% dos pacientes nas semanas 8 e 52, respectivamente. As taxas de resposta clínica foram de 54,2% e 67,6% nas semanas 8 e 52. A remissão endoscópica foi observada em 21,8% dos pacientes. Dezessete pacientes apresentaram eventos adversos, principalmente infecções leves, sendo 22,9% dos pacientes submetidos à cirurgia abdominal (sendo a ileocolectomia o procedimento mais comum). Conclusão: A terapia com UST resultou em taxas significativas de remissão e resposta clínica, conforme descrito em outros estudos do mundo real. Poucos pacientes apresentaram eventos adversos durante o tratamento, mostrando seu adequado perfil de segurança.

Tratamiento exitoso con risankizumab en paciente con psoriasis y HIV / Successful treatment with risankizumab in a patient with psoriasis and HIV

Resumen El tratamiento de la psoriasis en pacientes HIV positivos resulta un desafío, ya que pueden requerir tratamientos sistémicos de carácter inmunosupresor tales como con agentes biológicos, lo que conlleva a un mayor riesgo de infecciones. Se presenta el caso de un paciente HIV positivo con psoriasis grave sin compromiso artropático, refractaria a otros tratamientos. Existen datos limitados sobre el uso de terapias biológicas en pacientes HIV positivos, pero algunos informes de caso sugieren que su uso es eficaz y seguro. Específicamente, la aparición de anticuerpos monoclonales selectivos para la interleucina 23 tales como risankizumab, pueden ofrecer una terapéutica segura y eficaz para pacientes HIV positivos con psoriasis refractaria a otros tratamientos. De todas maneras, se requieren estudios controlados para definir por completo su seguridad y eficacia.

Abstract The treatment of psoriasis in HIV-positive patients is challenging, as they may require systemic immunosuppressive treatment such as biological agents, leading to an increased risk of infections. A case report of an HIV positive patient with severe psoriasis without arthropathic compromise, refractory to other treatments, is presented. There are limited data on the use of biological therapies in HIV-positive patients, but isolated case reports suggest that their use is effective and safe. Specifically, the emergence of monoclonal antibodies selective for interleukin 23 such as risankizumab may offer a safe and effective therapy for HIV-positive patients with psoriasis refractory to other treatments. In any case, controlled studies are required to fully define its safety and efficacy.

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.

Analysis of Clinical Efficacy and Safety of Ustekinumab in Treatment of Inflammatory Bowel Disease / 胃肠病学

Background: The efficacy of ustekinumab (UST) in the treatment of patients with inflammatory bowel disease (IBD) has been affirmed abroad, but its efficacy and safety have not been reported in China due to its short term of use. Aims: To analyze the clinical efficacy and safety of UST in the treatment of IBD. Methods: The clinical data of IBD patients treated with UST from November 2020 to June 2022 in the First Affiliated Hospital of Air Force Medical University were analyzed retrospectively. Results: A total of 46 patients with IBD treated with UST were enrolled, including 41 patients with Crohn’s disease (CD) and 5 patients with ulcerative colitis (UC). At the 8

Progress of Research on Therapeutic Drug Monitoring in Treatment of Novel Biological Agents for Inflammatory Bowel Disease / 胃肠病学

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disease, and its treatment includes traditional medicines and biological agents. Therapeutic drug monitoring is an important tool to optimize the treatment of biological agents. Therapeutic drug monitoring of tumor necrosis factor inhibitors has been used to guide the clinical decision ⁃ making. However, the value of therapeutic drug monitoring of novel biological agents (vedolizumab and ustekinumab) in IBD remains unclear. This article summarized the pharmacokinetics, drug concentration and treatment outcome, optimization of the novel biological agents in the treatment of IBD.

Psoriasis paradójica palmoplantar secundaria al tratamiento de la colitis ulcerosa con adalimumab / Paradoxical psoriasis of the palms and soles due to treatment of ulcerative colitis with adalimumab

Los anticuerpos anti-TNF-a (tumor necrosis factor alpha) se utilizan para tratar tanto la psoriasis como la enfermedad inflamatoria intestinal (EII). Sin embargo, estos fármacos han sido implicados en la ocurrencia de la psoriasis paradójica en los pacientes sin antecedentes de psoriasis que reciben tratamiento por una colitis ulcerosa (CU) y otras enfermedades autoinmunes. Se presenta el caso de un paciente de 29 años, sin antecedentes de dermatosis, que desarrolló una psoriasis palmoplantar paradójica por el uso del adalimumab que recibía por un diagnóstico de CU. El cuadro remitió al suspender el medicamento y recurrió al reiniciarlo, motivo por el cual se rotó al ustekinumab. La CU respondió satisfactoriamente, sin nuevas lesiones dermatológicas.

Anti TNF-a (tumor necrosis factor alpha) antibodies are used to treat both psoriasis and inflammatory bowel disease (IBD). However, these drugs have been implicated in the occurrence of the so-called paradoxical psoriasis in patients with no previous history of psoriasis, who receive treatment for ulcerative colitis and other autoimmune diseases. We present a 29-year-old male patient, with no previous history of dermatosis, who developed paradoxical palmar-plantar psoriasis due to the use of adalimumab that he was receiving for a diagnosis of ulcerative colitis. The condition remitted when the drug was suspended and recurred when it was restarted, and for that reason, treatment was rotated to ustekinumab. Ulcerative colitis responded satisfactorily, with no new dermatological lesions.

Recalcitrant Pityriasis Rubra Pilaris Treated with Ustekinumab / 대한피부과학회지

No abstract available.

Treatment Outcomes and Response Pattern of Ustekinumab in Korean Patients with Psoriasis: A Retrospective Single-center Study / 대한피부과학회지

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disease affecting 2~3% of the worldwide population. Ustekinumab, an IL-12/23p40 inhibitor, is a biologic reported to be effective and safe in treating psoriasis. However, there are limited data on the treatment outcomes of ustekinumab in patients with psoriasis in Korea. OBJECTIVE: To evaluate the treatment outcomes and response pattern of ustekinumab in patients with psoriasis in Korea. METHODS: This was a retrospective single-center study. Eighty-four patients with psoriasis treated with ustekinumab were analyzed. Each patient's medical records, psoriasis area and severity index (PASI) score, and body surface area were reviewed at baseline and up to week 52. RESULTS: A total of 84 patients were included (male:female=1.8:1). The mean age was 44.5 years. At week 16, 86.7% achieved PASI75, 59.0% achieved PASI90, and 20.5% achieved PASI100. By week 16, 84.8% of subjects had attained PASI75 for the head region, whereas 79.0% had attained it for the lower extremities, indicating a relatively slower treatment response of psoriatic lesions on the lower extremities. Four patients discontinued treatment due to lack of effect. No severe adverse events occurred during the follow-up period. CONCLUSION: Ustekinumab demonstrated highly effective and safe treatment profiles in Korean psoriatic patients, consistent with the previous reports from mainly Western countries. Psoriasis severity and treatment responsiveness may vary with body region.

Ustekinumab is effective in biological refractory Crohn's disease patients–regardless of approval study selection criteria

BACKGROUND/AIMS: Ustekinumab is effective in active Crohn's disease. In a retrospective study, we assessed the clinical outcome in nonresponders to anti-tumor necrosis factor therapy, and/or conventional therapy and/or the α4β7-integrin inhibitor vedolizumab. As approval study populations do not always reflect the average “real world” patient cohort, we assessed weather patients who would not have qualified for approval studies show similar outcomes. METHODS: Forty-one patients with mild to severe active Crohn's disease were treated with ustekinumab (intravenous 6 mg per kg/body weight) followed by subcutaneous ustekinumab (90 mg) at week 8. Depending on the clinical response maintenance therapy was chosen every 8 or 12 weeks. Clinical response was defined by Crohn's Disease Activity Index (CDAI) decline, decline of stool frequency or clinical improvement. Inclusion criteria for approval studies were assessed. RESULTS: The 58.5% (24/41) showed clinical response to ustekinumab. The 58.3% of this group (14/24) achieved clinical remission. Clinical response correlated significantly with drop of stool frequency and improvement of CDAI score. The 39 out of 41 patients had no side effects and we observed no serious infections. About a third of our patients would not have met ustekinumab approval study criteria. However, patients who did not meet study criteria showed clinical improvement numerically in the same range compared to patients who would have qualified for approval studies. CONCLUSIONS: Ustekinumab is effective, safe and well tolerated in a highly therapy refractory patient cohort. Even though a reasonable number of patients did not meet ustekinumab approval study criteria, approval study results seem to be representative to the overall patient cohort.

Analise de custo por resposta de adalimumabe, etanercepte, guselcumabe, infliximabe, ixequizumabe, secuquinumabe e ustequinumabe para tratamento de psoríase em placas moderada a grave sob a perspectiva do Sistema de Saúde Suplementar brasileiro / Cost per response analysis of adalimumab, etanercept, guselkumab, infliximab, ixekizumab, secukinumab and ustekinumab for the treatment of moderate to severe plaque psoriasis from the Brazilian private health care system perspective

O OBJETIVO: deste estudo é avaliar o custo por resposta das terapias biológicas disponíveis no Brasil para o tratamento da psoríase em placas moderada a grave na perspectiva do Sistema de Saúde Suplementar. MÉTODOS: A resposta PASI 90 foi o desfecho avaliado neste estudo. Dados clíni-cos foram calculados com base na razão de risco de uma metanálise em rede, comparando adalimu-mabe, etanercepte, infliximabe, ixequizumabe, secuquinumabe e ustequinumabe a guselcumabe, cujo dado foi obtido no estudo clínico. Foram considerados apenas os custos de medicamentos. O caso-base avaliou o custo por resposta do ano de indução do tratamento. Além disso, conduziu-se uma análise de orçamento fixo. Em um cenário alternativo, analisou-se o custo por resposta do ano de manutenção. Uma análise de sensibilidade avaliou incertezas dos dados clínicos. RESULTADOS: O menor custo por resposta foi de guselcumabe (R$ 98.643), seguido de ixequizumabe (R$ 112.549), ustequinumabe (R$ 124.078), secuquinumabe (R$ 160.930), infliximabe (R$ 208.039), adalimumabe (R$ 208.686) e etanercepte (R$ 639.124). Resultados similares foram observados no cenário alterna-tivo, considerando os custos no ano de manutenção. Guselcumabe demonstrou ser a terapia que tratou mais pacientes com sucesso, considerando um cenário de orçamento fixo. Conclusão: O presente estudo demonstrou que, na perspectiva do Sistema de Saúde Suplementar brasileiro, gu-selcumabe possui o menor custo por resposta entre as terapias biológicas para psoríase em placas moderada a grave, além de tratar com sucesso mais pacientes em um cenário de orçamento fixo.

Objective: This study aims to evaluate the cost per response of the biologic therapies available for moderate to severe plaque psoriasis treatment in Brazil from a private payer perspective Methods: Treatment response evaluated in this study was the achievement of PASI 90. Clinical data was calculated based on the risk ratio of a network meta-analysis comparing adalimumab, etanercept, infliximab, ixekizumab, secukinumab and ustekinumab to guselkumab, which data was extracted from clinical trials. Only drug acquisition cost were considered. Base case analysis evaluated the first year of treatment cost per response Besides that, a fixed budget analysis was conducted. An alternative scenario analysis considered the maintenance year cost per response. A sensitivity analysis evaluated the clinical data uncertainties. Results: The lowest cost per response was obtained with guselkumab (R$98.643), followed by ixekizumab (R$ 112.549), ustekinumab (R$ 124.078), secukinumab (R$ 160.930), infliximab (R$ 208.039), adalimumab (R$ 208.686), and etanercept (R$ 639.124). Similar results were found in the alternative scenario, with maintenance year costs. Guselkumab demonstrated to be the therapy which successfully treats more patients with a fixed budget. Conclusion: In conclusion, this study demonstrated that, from the Brazilian private payer perspective, guselkumab presents the lowest cost per response among the avail-able biologic therapies for moderate to severe plaque psoriasis, and is able to successfully treat more patients in a limited budget scenario.

Emerging Therapies: What Are Promising in the Near Future? / 대한소화기학회지

The treatment of inflammatory bowel disease has evolved with the development of anti-TNF agents. In spite of long-term effectiveness, many patients do not respond or no longer responds to these drugs. Therefore, the development of new drugs that act on different inflammatory pathways has become necessary. Vedolizumab, a gut-specific biological agent, inhibits interaction α4β7 integrin with mucosal addressin cell adhesion molecule-1 without inhibiting systemic immune responses. Long-term vedolizumab therapy in patients with Crohn's disease and ulcerative colitis was safe and effective. Additionally, vedolizumab can be used in patients already failed an anti-TNF therapy. Ustekinumab is a fully human immunoglobulin G1 kappa monoclonal antibody that blocks the p40 subunit of IL-12 and IL-23. Ustekinumab will be a clinically effective agent to use in medically-refractory Crohn's disease especially as a second line drug. Tofacitinib is an oral, small molecule that inhibits JAK1, JAK3 and in a lesser extent, JAK2. Perhaps the most attractive things of these JAK inhibitors is that they are given orally instead of parenterally. Early results showed that patients with moderately to severely active ulcerative colitis receiving tofacitinib were more likely to achieve remission at 8 weeks than those receiving placebo. However, these results have not been as robust in Crohn's disease. Much of the positioning will depend on the safety profile such as opportunistic infection and atherogenic risk. The challenges for the future are to determine the therapeutic drug monitoring-guided dose optimization, optimal timing and drug combinations to produce the most effective, and safest outcomes for IBD patients.