Upadacitinib for refractory ulcerative colitis with primary nonresponse to infliximab and vedolizumab:A case report

BACKGROUND Many patients with ulcerative colitis(UC)do not respond well to,or tolerate conventional and biological therapies.There is currently no consensus on the treatment of refractory UC.Studies have demonstrated that the selective Janus kinase 1 inhibitor upadacitinib,a small-molecule drug,is effective and safe for treating UC.However,no studies have revealed that upadacitinib is effective in treating refractory UC with primary nonresponse to infliximab and vedolizumab.CASE SUMMARY We report the case of a 44-year-old male patient with a chief complaint of bloody diarrhoea with mucus and pus,in addition to dizziness.The patient had recurrent disease after receiving mesalazine,prednisone,azathioprine,infliximab and vedolizumab over four years.Based on the endoscopic findings and pathological biopsy,the patient was diagnosed with refractory UC.In particular,the patient showed primary nonresponse to infliximab and vedolizumab.Based on the patient’s history and recurrent disease,we decided to administer upadacitinib.During hospitalisation,the patient was received upadacitinib under our guidance.Eight weeks after the initiation of upadacitinib treatment,the patient’s symptoms and endoscopic findings improved significantly.No notable adverse reactions have been reported to date.CONCLUSION Our case report suggests that upadacitinib may represent a valuable strategy for treating refractory UC with primary nonresponse.

Nursing Care of Infliximab for Injection in Crohn’s Disease

Objective: To summarize the nursing experience of infliximab injection in the treatment of Crohns disease. Methods: 25 patients with Crohns disease admitted to our hospital from November 2017 to February 2024 were treated with infliximab. The therapeutic effect and adverse drug reactions were observed, nursing intervention was given, and follow-up was performed at 2 weeks, 6 weeks after the first treatment and every 2 months after the treatment cycle. According to Crohns disease activity index (CDAI) score, 23 cases with 4 were classified as remission stage and 2 cases with 6 were classified as mild activity stage. Infliximab-treated Crohns patients had a good prognosis and minor adverse reactions. A correct grasp of the basic knowledge of the drug, standardized operation, attention to the psychological state of the patient, close observation of the change of the patients condition, and predictability of the treatment of adverse drug reactions are the guarantee of smooth treatment.

Infliximab vs adalimumab:Points to consider when selecting antitumor necrosis factor agents in pediatric patients with Crohn’s disease

Biologic agents with various mechanisms against Crohn’s disease(CD)have been released and are widely used in clinical practice.However,two anti-tumor necrosis factor(TNF)agents,infliximab(IFX)and adalimumab(ADL),are the only biologic agents approved by the Food and Drug Administration for pediatric CD currently.Therefore,in pediatric CD,the choice of biologic agents should be made more carefully to achieve the therapeutic goal.There are currently no headto-head trials of biologic agents in pediatric or adult CD.There is a lack of accumulated data for pediatric CD,which requires the extrapolation of adult data for the positioning of biologics in pediatric CD.From a pharmacokinetic point of view,IFX is more advantageous than ADL when the inflammatory burden is high,and ADL is expected to be advantageous over IFX in sustaining remission in the maintenance phase.Additionally,we reviewed the safety profile,immunogenicity,preference,and compliance between IFX and ADL and provide practical insights into the choice of anti-TNF therapy in pediatric CD.Careful evaluation of clinical indications and disease behavior is essential when prescribing anti-TNF agents.In addition,factors such as the efficacy of induction and maintenance of remission,safety profile,immunogenicity,patient preference,and compliance play an important role in evaluating and selecting treatment options.

玻璃体内注射Infliximab对实验性自身免疫性葡萄膜炎的治疗作用

目的观察玻璃体内注射Infliximab对实验性自身免疫性葡萄膜炎(experimental autoimmune uveitis,EAU)的治疗作用。方法雌性新西兰大白兔32只,随机分为3组,其中模型对照组和正常对照组各8只,治疗组16只。模型对照组和治疗组用牛血清蛋白作为异体抗原,玻璃体内、耳缘静脉两次注射法诱导EAU模型(双眼均造模)。造模成功后次日,各组分别行玻璃体内注射1次,正常对照组和模型对照组注射生理盐水0.1mL,治疗组注射10g·L-1Infliximab0.1mL。于造模前及造模后5d、10d、15d4个时间点行兔活体眼部检查,并抽取房水行ELISA法检测房水中肿瘤坏死因子-α(tumor necrosis factor,TNF-α)和白细胞介素-2(interleukin-2,IL-2)的含量;各时间点摘除双侧眼球行组织病理学观察。结果造模前,各组房水中TNF-α和IL-2含量比较差异均无统计学意义。造模后5d,模型对照组和治疗组房水中TNF-α和IL-2含量差异均无统计学意义(均为P>0.05),但均较正常对照组高(均为P<0.05)。造模后10d、15d,模型对照组房水中TNF-α分别为(652.29±102.76)ng·L-1、(372.63±47.59)ng·L-1,治疗组分别为(395.88±48.97)ng·L-1、(140.44±41.69)ng·L-1,两组相比差异均有统计学意义(均为P=0.00);模型对照组房水中IL-2分别为(85.55±7.74)ng·L-1、(64.10±7.78)ng·L-1,治疗组分别为(40.89±8.81)ng·L-1、(26.48±7.71)ng·L-1,两组相比差异亦均有统计学意义(均为P=0.00)。造模后10d,治疗组的组织病理学显示炎症较模型对照组有明显减轻。正常对照组始终无阳性体征和病理改变。结论 Infliximab能显著抑制牛血清蛋白诱导的EAU模型房水中TNF-α、IL-2的产生,减轻EAU眼部炎症反应和病理损害,对EAU有治疗作用。

单克隆抗体Infliximab治疗克罗恩病研究进展

Infliximab是一种嵌合型单克隆抗体,可靶向克罗恩病(Crohn disease,CD)发病机制中起重要作用的促炎细胞因子-人肿瘤坏死因子-α（TNF-α）。Infliximab通过与巨噬细胞和T细胞表面的TNF-α结合而拮抗TNF-α的生物活性。临床试验显示,infliximab治疗复发的中至重度CD病人有效,可促进肠黏膜愈合和瘘闭合。Infliximab比大多数传统CD治疗药物起效迅速,且药物不良反应较小。推荐剂量为5mg·kg-1,2h内静脉输注。可间隔8周重复给药以预防复发。Infliximab可有效治疗CD,并提高病人的生活质量。

Infliximab在克罗恩病治疗中的现状及展望

Infliximab是一直接针对肿瘤坏死因子 α(TNF α)的嵌合性单克隆抗体。 1998年 5月美国FDA正式批准infliximab用于对常规保守治疗无效以及活动性瘘道形成的中 重度克罗恩病 (CD)患者。本文对infliximab在克罗恩病治疗中的现状及展望作一综述。

Infliximab在溃疡性结肠炎中的研究进展

肿瘤坏死因子α(TNF-α)是炎症性肠病黏膜炎症中的一种关键介质,其嵌合型单克隆抗体Infliximab可拮抗其生物活性,起全面抗炎作用。Infliximab已用于克罗恩病的诱导和维持缓解,但在溃疡性结肠炎中研究较少。本文就Infliximab在溃疡性结肠炎中的治疗做一综述。

Infliximab治疗难治性克罗恩病并发腹腔脓肿1例

患者1例:反复腹痛、腹泻12年余,加重20d伴发热入院,据临床表现、影像学及肠镜检查确诊为难治性克罗恩病,于0,2,6wk时,静脉滴注Infliximab(5mg/kg)进行诱导治疗,隔8wk后再予静脉滴注1次,进行维持缓解治疗.患者于首次滴注后21wk发生腹腔脓肿.提示接受Infliximab治疗的患者可能增加感染的潜在危险,值得引起重视.

单克隆抗体Infliximab治疗炎症性肠病的研究进展

Infliximab是一种嵌合型单克隆抗体,可靶向炎症性肠病(IBD)发病机制中起重要作用的促炎细胞因子-人肿瘤坏死因子-α(TNF-α)。Infliximab通过与巨噬细胞和T细胞表面的TNF-α结合而拮抗TNF-α的生物活性。Infliximab比大多数治疗IBD传统药物起效迅速,且药物不良反应较小。Infliximab可以有效治疗IBD,提高患者的生活质量。

Infliximab联合免疫球蛋白治疗噬血细胞综合征疗效观察

目的:观察抗肿瘤坏死因子单克隆抗体(infliximab)联合免疫球蛋白治疗噬血细胞综合征疗效。方法:大剂量免疫球蛋白(10 g/d×4 d)联合2次Infliximab(100mg/d)。结果:1例有多个脏器功能损害的患者诊断为柯萨奇病毒感染合并噬血细胞综合征,治疗后病情完全缓解。结论:噬血细胞综合征本身只是一种过度免疫反应,infliximab可能成为阻断细胞因子的重要治疗手段。

抗炎症介质治疗窗使用Infliximab对大鼠ANP并MODS模型的实验疗效

目的探讨抗炎症介质治疗窗使用Infliximab(TNF-α单抗)对急性坏死性胰腺炎(ANP)并多脏器功能衰竭(MODS)模型的实验疗效。方法经胰胆管逆行注射4.5%牛磺胆酸钠制备大鼠ANP并MODS模型。24只SD大鼠随机分为假手术组、模型组和Infliximab治疗组(Infliximab 8 mg/kg于建模后6 h尾静脉注射)。建模后24h处死大鼠,分别检测血清TNF-α、淀粉酶、总胆红素、肌酐、PaO2/FiO2以及胰腺组织病理等指标。结果 Infliximab治疗组的血清TNF-α、淀粉酶、总胆红素、肌酐值和胰腺组织病理评分均较模型组显著降低,PaO2/FiO2显著升高(均P<0.05);肝、肾、呼吸功能障碍以及MODS发生率较模型组显著降低(P<0.05)。结论抗炎症介质治疗窗使用Infliximab对ANP并MODS具有良好疗效,有助于抑制胰腺炎症和降低MODS发生率。

肿瘤坏死因子-α基因-238位点单核苷酸多态性与Infliximab治疗类风湿性关节炎疗效的相关性

目的探讨肿瘤坏死因子-α(TNF-α)基因-238位点基因单核苷酸多态性(SNP)与Infliximab(英夫利昔单抗)治疗类风湿性关节炎(RA)疗效的相关性。方法对102例中国RA患者使用Infliximab进行治疗,以28处关节疾病活动度评分(DAS28)、健康评估问卷(HAQ)评分及美国风湿病学会(ACR)与欧洲抗风湿病联盟(EULAR)共同制定的RA临床缓解新标准为工具,评估Infliximab对RA的疗效。采用TaqMan MGB探针法检测TNF-α基因-238位点的SNP。统计分析TNF-α基因-238位点的SNP与Infliximab治疗RA疗效的相关性。结果具有GG基因型的RA患者在治疗后DAS28评分和HAQ评分均显著降低(P<0.05),而具有AA基因型及AG基因型的RA患者在治疗后DAS28评分和HAQ评分均无显著变化(P>0.05)。具有GG基因型的RA患者在治疗后达到临床缓解新标准的比例为91.8%,显著高于非GG基因型的RA患者。除有2例RA患者因对Inflix-imab过敏而退出试验外,未见结核、肿瘤发生等严重不良反应。结论 TNF-α基因-238位点的SNP与Inflix-imab治疗RA疗效可能相关,具有GG基因型的RA患者对Infliximab的疗效反应较好,而具有AA基因型及AG基因型的RA患者疗效反应则相对较差。

Infliximab induces remission in cryptogenic multifocal ulcerous stenosing enteritis:First case

We present the case of a 29-year-old patient with a history of abdominal pain and vomiting.Based on wireless video capsule findings he was previously diagnosed with ileal Crohn's disease at a different institution,although the clinical and radiological picture was not typical and the response to corticosteroids was poor.We performed a single-balloon enteroscopy showing a short,ulcerous stenosis 50 cm proximal from Bauhin's valve.The endoscopic and clinical histopathological findings were compatible with cryptogenic multifocal ulcerous stenosing enteritis(CMUSE).High dose corticosteroids were again started,without effect.The monoclonal tumor necrosis factor-α(TNF-α) antibody infliximab was added to the medical therapy.After induction therapy,both clinical and endoscopic amelioration was obtained.Larger case studies are needed to confirm the efficacy of TNF-α inhibition in steroid refractory CMUSE.

Efficacy of early treatment with infliximab in pediatric Crohn’s disease

AIM: To investigate the effectiveness of early infliximab use for induction and maintenance therapy in pediatric Crohn’s disease. METHODS: We performed a retrospective chart review of 36 patients with Crohn’s disease. Ten patients (group A) were treated with mesalamine after induction therapy with oral prednisolone, and 13 patients (group B) were treated with azathioprine after induction therapy with oral prednisolone. Thirteen patients (group C) received infliximab and azathioprine for induction and maintenance therapy for the first year, and were treated with azathioprine after 1 year. All patients were followed for at least 24 mo. Efficacy was determined by the relapse rate using the pediatric Crohn’s disease activity index score in each group at 12 and 24 mo. RESULTS: At the 1 year follow-up, the relapse ratee, Mi Jin Kim, Hae Jeong Lee, Yon Ho Choe (23.1%, 3 of 13 patients) in group C was lower than that (61.5%, 8 of 13 patients) in group B (P = 0.047). At the 2 years follow-up, the relapse rate (38.5%, 5 of 13 patients) in group C was lower than that (76.9%, 10 of 13 patients) in group B (P = 0.047). Adverse events in group C were fewer than in groups A and B. CONCLUSION: Early induction with infliximab at diagnosis, known as "top-down" therapy, was effective for reducing the relapse rate compared to conventional therapies for at least 2 years.

Long-term outcome of infliximab combined with surgery for perianal fistulizing Crohn's disease

AIM:To evaluate the efficacy and long-term outcome of infliximab combined with surgery to treat perianal fistulizing Crohn’s disease(CD).METHODS:The work was performed as a prospective study.All patients received infliximab combined withsurgery to treat perianal fistulizing CD,which was followed by an immunosuppressive agent as maintenance therapy.RESULTS:A total of 28 patients with perianal fistulizing CD were included.At week 30,89.3%(25/28)of the patients were clinically cured with an average healing time of 31.4 d.The CD activity index decreased to70.07±77.54 from 205.47±111.13(P<0.01)after infliximab treatment.The perianal CD activity index was decreased to 0.93±2.08 from 8.54±4.89(P<0.01).C-reactive protein,erythrocyte sedimentation rate,platelets,and neutrophils all decreased significantly compared with the pretreatment levels(P<0.01).Magnetic resonance imaging results for 16 patients after therapy showed that one patient had a persistent presacral-rectal fistula and another still had a cavity without clinical symptoms at follow-up.After a median follow-up of 26.4 mo(range:14-41 mo),96.4%(27/28)of the patients had a clinical cure.CONCLUSION:Infliximab combined with surgery is effective and safe in the treatment of perianal fistulizing CD,and this treatment was associated with better longterm outcomes.

Weber-Christian disease with ileocolonic involvement successfully treated with infliximab

Weber-Christian disease(WCD) is an inflammatory disease whose main histological feature is lobular panniculitis of adipose tissue. The location of panniculitis determines the clinical presentation,being the subcutaneous adipose tissue the most frequent one,followed by liver,spleen,bone marrow and mesenteric adipose tissue.Systemic corticosteroids are first line treatment,but other options should be considered if systemic symptoms are observed or in case of refractory clinical situation.We report herein a case with WCD showing orbital,mesenteric and ileocolonic involvement,which required surgical treatment and also developed postoperative recurrence.Symptoms were resolved by administration of thalidomide and,afterwards,infliximab.To our knowledge,this is the first report of Weber-Christian disease with luminal ileocolonic involvement,treated with infliximab.

Noninfectious interstitial lung disease during infliximab therapy:Case report and literature review

Pulmonary abnormalities are not frequently encountered in patients with inflammatory bowel diseases.However,lung toxicity can be induced by conventional medications used to maintain remission,and similar evidence is also emerging for biologics.We present the case of a young woman affected by colonic Crohn’s disease who was treated with oral mesalamine and became steroid-dependent and refractory to azathioprine and adalimumab.She was referred to our clinic with a severe relapse and was treated with infliximab,an antitumor necrosis factor α(TNF-α)antibody,to induce remission.After an initial benefit,with decreases in bowel movements,rectal bleeding and C-reactive protein levels,she experienced shortness of breath after the 5thinfusion.Noninfectious interstitial lung disease was diagnosed.Both mesalamine and infliximab were discontinued,and steroids were introduced with slow but progressive improvement of symptoms,radiology and functional tests.This represents a rare case of interstitial lung disease associated with infliximab therapy and the effect of drug withdrawal on these lung alterations.Given the increasing use of anti-TNF-α therapies and the increasing reports of pulmonary abnormalities in patients with inflammatory bowel diseases,this case underlines the importance of a careful evaluation of respiratory symptoms in patients undergoing infliximab therapy.

Infliximab in pediatric inflammatory bowel disease rapidly decreases fecal calprotectin levels

AIM: To study the response to infliximab in pediatric inflammatory bowel disease (IBD), as reflected in fecal calprotectin levels. METHODS: Thirty-six pediatric patients with IBD [23 Crohn's disease (CD), 13 ulcerative colitis (UC); median age 14 years] were treated with infliximab. Fecal calprotectin was measured at baseline, and 2 and 6 wk after therapy, and compared to blood inflammatory markers. Maintenance medication was unaltered until the third infusion but glucocorticoids were tapered off if the patient was doing well. RESULTS: At introduction of infliximab, median fecal calprotectin level was 1150 μg/g (range 54-6032 μg/g). By week 2, the fecal calprotectin level had declined to amedian 261 μg/g (P < 0.001). In 37% of the patients, fecal calprotectin was normal (< 100 μg/g) at 2 wk. By week 6, there was no additional improvement in the fecal calprotectin level (median 345 μg/g). In 22% of the patients, fecal calprotectin levels increased by week 6 to pretreatment levels or above, suggesting no response (or a loss of early response). Thus, in CD, the proportion of non-responsive patients by week 6 seemed lower, because only 9% showed no improvement in their fecal calprotectin level when compared to the respective figure of 46% of the UC patients (P < 0.05). CONCLUSION: When treated with infliximab, fecal calprotectin levels reflecting intestinal inflammation normalized rapidly in one third of pediatric patients suggesting complete mucosal healing.