Pediatric inflammatory bowel disease(PIBD)is a chronic inflammatory disorder of the gastrointestinal tract,with rising global incidence and prevalence.Over the past two decades,biologics have added to the therapeutic ...Pediatric inflammatory bowel disease(PIBD)is a chronic inflammatory disorder of the gastrointestinal tract,with rising global incidence and prevalence.Over the past two decades,biologics have added to the therapeutic armamentarium and revolutionized the approach to treatment of inflammatory bowel disease.The available biologics include monoclonal antibodies which target inflammatory cytokines(anti-tumor necrosis factor alpha,anti-interleukin 12/23)or recruitment of leucocytes to the gastrointestinal tract(anti-alpha4beta7 integrin)and small molecules(Janus kinase inhibitors,sphingosine 1-phosphate-inhibitors)which modify the proinflammatory signaling.Considering their potential disease-modifying ability,recent pediatric guidelines from the West have advocated upfront use of biologics in appropriate clinical scenarios as a top-down approach rather than the conventional step-up approach.Although real-world studies are available regarding the clinical efficacy of biologics in PIBD,there is paucity of long-term outcome and safety data in children.Also,little information is available about the best approach in the newly industrialized-developing countries where PIBD is rising but at the same time,infections are prevalent and resources are limited.In this review,we summarize the efficacy and safety profile of biologics and small molecule drugs and discuss the challenges in the management of PIBD,especially in the developing world,and future directions.展开更多
BACKGROUND Endoscopic healing(EH)is a key therapeutic target in Crohn’s disease(CD).Proximal small bowel(SB)lesions in patients with CD are associated with a significant risk of strictures and bowel resection.Assessi...BACKGROUND Endoscopic healing(EH)is a key therapeutic target in Crohn’s disease(CD).Proximal small bowel(SB)lesions in patients with CD are associated with a significant risk of strictures and bowel resection.Assessing SB in patients with CD is necessary because of its significant therapeutic implications.The advent of biologic therapies,including infliximab,ustekinumab,and vedolizumab,has significantly altered CD treatment.However,data on the efficacy of biologics in achieving EH,specifically in the proximal SB of patients with CD,remain limited.AIM To assess the effectiveness of biologics for EH in patients with jejunal and/or proximal ileal CD.METHODS Between 2017 and 2023,we retrospectively included 110 consecutive patients with isolated proximal SB CD,identified through baseline balloon-assisted enteroscopy.These patients completed 1-year of treatment with infliximab,ustekinumab,or vedolizumab,and underwent a second balloon-assisted enteroscopy at 1 year.Complete EH was defined as a modified Simple Endoscopic Score for CD(SES-CD)of<3,while EH of the jejunum and proximal ileum was defined as a segmental modified SES-CD of 0.RESULTS In total,64 patients were treated with infliximab,28 with ustekinumab,and 18 with vedolizumab.The complete EH rate at 1 year was 20.9%(23/110),with 29.6%(19/64)for infliximab,10.7%(3/28)for ustekinumab,and 5.5%(1/18)for vedolizumab.The median modified SES-CD significantly decreased compared to baseline[5(2-8)vs 8(6-9),P<0.001].The jejunal and proximal ileal EH rates at 1 year were 30.8%(12/39)and 15.5%(16/103),respectively.Multiple logistic regression analysis showed that stricturing or penetrating disease[odds ratio(OR)=0.261,95%CI:0.087-0.778,P=0.016],prior exposure to biologics(OR=0.080,95%CI:0.010-0.674,P=0.020),and moderate-tosevere endoscopic disease(OR=0.277,95%CI:0.093-0.829,P=0.022)were associated with a lower likelihood of achieving EH at 1 year.CONCLUSION Only 20.9%of patients with isolated proximal SB CD achieved complete EH after 1 year of biologic therapy.展开更多
Many placebo controlled trials and meta-analyses evaluated the efficacy of different drugs for the treatment of inflammatory bowel disease (IBD), including immunosuppressants and biologics. Their use is indicated in m...Many placebo controlled trials and meta-analyses evaluated the efficacy of different drugs for the treatment of inflammatory bowel disease (IBD), including immunosuppressants and biologics. Their use is indicated in moderate to severe disease in non responders to corticosteroids and in steroid-dependent patients, as induction and maintainance treatment. Infliximab, as well as cyclosporine, is considered a second line therapy in the case of severe ulcerative colitis, or non-responders to intravenous corticosteroids. An adequate dosage and duration of therapy with thiopurines should be reached before evaluating their efficacy. Methotrexate is a valid option in patients with Crohn’s disease but its use is confined to patients who are intolerant or non-responders to thiopurines. Evidence for the use of methotrexate in ulcerative colitis is insufficient. The use of thalidomide and mycophenolate mofetil is not recommended in patients with inflammatory bowel disease, these treatments could be considered in case of failure of all other therapeutic options. In patients with moderately active ulcerative colitis, refractory to thiopurines, the use of tacrolimus is considered an alternative to biologics. An increase of the dose or a decrease in the interval of administration of biological treatment could be useful in the presence of an incomplete clinical response. In the case of primary failure of an anti-tumor necrosis factor alpha a switch to another one should be considered. Data on the efficacy of combination therapy are up to now insufficient to consider this strategy in all IBD patients. The final outcome of the treatment should be considered the clinical remission, with mucosa healing, and not the clinical response. The evaluation of serum concentration of thiopurine methyl transferase activity, thiopurine metabolites, biologic serum levels and antibiologic antibodies could be useful for the management of the treatment but it has not been routinely applied in clinical practice. The evidence of high risk development of lymphoma and cutaneous malignancies should be considered in patients treated with immunosuppressants and biologics for a long period.展开更多
The advent of biologics and small molecules in inflammatory bowel disease(IBD)has marked a significant turning point in the prognosis of IBD,decreasing the rates of corticosteroid dependence,hospitalizations and impro...The advent of biologics and small molecules in inflammatory bowel disease(IBD)has marked a significant turning point in the prognosis of IBD,decreasing the rates of corticosteroid dependence,hospitalizations and improving overall quality of life.The introduction of biosimilars has also increased affordability and enhanced access to these otherwise costly targeted therapies.Biologics do not yet represent a complete panacea:A subset of patients do not respond to first-line anti-tumor necrosis factor(TNF)-alpha agents or may subsequently demonstrate a secondary loss of response.Patients who fail to respond to anti-TNF agents typically have a poorer response rate to second-line biologics.It is uncertain which patient would benefit from a different sequencing of biologics or even a combination of biologic agents.The introduction of newer classes of biologics and small molecules may provide alternative therapeutic targets for patients with refractory disease.This review examines the therapeutic ceiling in current treatment strategies of IBD and the potential paradigm shifts in the future.展开更多
BACKGROUND Biologic therapy resulted in a significant positive impact on the management of inflammatory bowel disease(IBD) however data on the efficacy and side effects of these therapies in the elderly is scant.AIM T...BACKGROUND Biologic therapy resulted in a significant positive impact on the management of inflammatory bowel disease(IBD) however data on the efficacy and side effects of these therapies in the elderly is scant.AIM To evaluate retrospectively the drug sustainability, effectiveness, and safety of the biologic therapies in the elderly IBD population.METHODS Consecutive elderly(≥ 60 years old) IBD patients, treated with biologics [infliximab(IFX), adalimumab(ADAL), vedolizumab(VDZ), ustekinumab(UST)] followed at the McGill University Inflammatory Bowel Diseases Center were included between January 2000 and 2020.Efficacy was measured by clinical scores at 3, 6-9 and 12-18 mo after initiation of the biologic therapy. Patients completing induction therapy were included. Adverse events(AEs) or serious AE were collected during and within three months of stopping of the biologic therapy.RESULTS We identified a total of 147 elderly patients with IBD treated with biologicals during the study period, including 109 with Crohn’s disease and 38 with ulcerative colitis. Patients received the following biologicals: IFX(28.5%), ADAL(38.7%), VDZ(15.6%), UST(17%). The mean duration of biologic treatment was 157.5(SD = 148) wk. Parallel steroid therapy was given in 34% at baseline,19% at 3 mo, 16.3% at 6-9 mo and 6.5% at 12-18 mo. The remission rates at 3, 6-9 and 12-18 mo were not significantly different among biological therapies. Kaplan-Meyer analysis did not show statistical difference for drug sustainability(P = 0.195), time to adverse event(P = 0.158) or infection rates(P = 0.973) between the four biologics studied. The most common AEs that led to drug discontinuation were loss of response, infusion/injection reaction and infection.CONCLUSION Current biologics were not different regarding drug sustainability, effectiveness, and safety in the elderly IBD population. Therefore, we are not able to suggest a preferred sequencing order among biologicals.展开更多
The management of rheumatoid arthritis(RA) in the past three decades has undergone a paradigm shift from symptomatic relief to a "treat-to-target" approach. This has been possible through use of various conv...The management of rheumatoid arthritis(RA) in the past three decades has undergone a paradigm shift from symptomatic relief to a "treat-to-target" approach. This has been possible through use of various conventional and biologic disease modifying anti-rheumatic drugs(DMARDs) which target disease pathogenesis at a molecular level. Cost and infection risk preclude regular use of biologics in resource-constrained settings. In therecent years, evidence has emerged that combination therapy with conventional DMARDs is not inferior to biologics in the management of RA and is a feasible cost-effective option.展开更多
Our increase in knowledge of the pathophysiology of non-infectious uveitis(NIU)and other immune-mediated diseases has been mirrored over the last two decades by the expansion of therapeutic options in the realm of imm...Our increase in knowledge of the pathophysiology of non-infectious uveitis(NIU)and other immune-mediated diseases has been mirrored over the last two decades by the expansion of therapeutic options in the realm of immunosuppressive medications.Principal among these advances is the emergence of biologics,which offer the promise of targeted therapy and the hope of reduced toxicity when compared to corticosteroids and“standard”immunosuppression.Among the biologics,monoclonal antibodies blocking tumor necrosis factor alpha(TNF-α)have been shown to be a very effective therapeutic target for uveitis and many associated systemic inflammatory diseases.Multiple TNF blockers have shown benefit for uveitis,and in 2016,adalimumab became the first biologic and non-corticosteroid immunosuppressive to obtain Food and Drug Administration(FDA)approval in the treatment of NIU.Although effective,TNF blockers are not universally so,and safety concerns such as infection and demyelinating disease must be carefully considered and ruled out prior to their use,especially in patients with intermediate uveitis with which multiple sclerosis is a known association.Ongoing study has identified novel targets for regulation in the treatment of immune-mediated and inflammatory diseases.Interferons,interleukin and Janus kinase inhibitors in addition to antibodies targeting T cell and B cell activation highlight the expanding field of treatment modalities in NIU.Ongoing study will be required to better determine the safety and efficacy of biologics in the armamentarium of immunosuppressive treatments for NIU.展开更多
A 46-year-old female patient with terminal ileum Crohn’s disease and ankylosing spondylitis presented with recurrent angioedema and urticaria. Investigations ruled out hereditary angioedema, and environmental or food...A 46-year-old female patient with terminal ileum Crohn’s disease and ankylosing spondylitis presented with recurrent angioedema and urticaria. Investigations ruled out hereditary angioedema, and environmental or food allergen triggers. She was diagnosed with chronic idiopathic urticaria with angioedema, and was treated with a trial of intravenous immunoglobulin immunotherapy, danazol, prednisone and hydroxyzine. Due to ongoing bowel and arthritic complaints, she was started on infliximab infusions and within 2 treatments, she had complete resolution of the angioedema and urticaria, as well as of the bowel and arthritic symptoms. Unfortunately she developed allergic reactions to the infliximab and was switched to another anti-tumor necrosis factor （TNF）-a agent, adalimumab. Since then, she has had no further angioedema or urticaria, and her Crohn’s disease has been quiescent. This is the first known case report of chronic idiopathic urticaria with angioedema coexistent with Crohn’s disease that was successfully treated with anti-TNF-α agents.展开更多
Hepatitis B virus reactivation(HBVr)can occur in patients treated with immunosuppressive medications.Risk stratification for HBVr based on hepatitis B virus(HBV)serology and viral load is an important strategy to dete...Hepatitis B virus reactivation(HBVr)can occur in patients treated with immunosuppressive medications.Risk stratification for HBVr based on hepatitis B virus(HBV)serology and viral load is an important strategy to determine appropriate HBV monitoring and antiviral prophylaxis use.Recent advances in the understanding of pathophysiology of autoimmune diseases have led the development of cytokine-targeted therapies.Tumor necrosis factor(TNF)-αinhibitors have been widely used for patients with inflammatory bowel disease,psoriasis,and rheumatic diseases.Further,the clinical benefits of interleukin(IL)-12/23,IL-17,or Janus kinases inhibitors have been demonstrated in these patients.It is well known that TNF-αinhibitor use can lead to HBVr,however,the risk of HBVr in patients undergoing non-TNF-targeted biologics have not been fully understood.In this review,we discuss the risk of HBVr in patients treated with non-TNF-targeted biologics,and immunological mechanisms of these medications causing HBVr.展开更多
Corticosteroids and immunomodulators have been the mainstay therapies for Crohn’s disease. Corticosteroids are highly effective to control symptoms in the short- term, but they are not effective in maintaining remiss...Corticosteroids and immunomodulators have been the mainstay therapies for Crohn’s disease. Corticosteroids are highly effective to control symptoms in the short- term, but they are not effective in maintaining remission, they heal the mucosa in a reduced proportion of cases, and long-time exposure is associated with an increased risk of infections and mortality. Immunomodulators, azathioprine and methotrexate, heal the mucosa in a higher proportion of patients that corticosteroids but their onset of action is slow and they benefit less than half of patients with Crohn’s disease. In the last decade, medical therapy for Crohn’s disease has experienced a remarkable change due to the introduction of biologic therapy, and particularly the use of anti-tumour necrosis factor-alpha agents. Infliximab, adalimumab, and certolizumab pegol have demonstrated efficacy for induction and maintenance of remission in active Crohn’s disease. These agents have raised the bar for what is a suitable symptomatic response in Crohn’s disease and modification of the natural history of the disease has become a major goal in the treatment of Crohn’s disease. There are several data in the literature that suggest that early use of biologic therapy and achievement of mucosal healing contribute to disease course modification. However, many questions on early biological therapy for Crohn’s disease remain still unanswered.展开更多
Inflammatory bowel disease(IBD)is a group of chronic diseases that includes ulcerative colitis,Crohn’s disease,and indeterminate colitis.Patients with IBD require prolonged treatment and high utilization of healthcar...Inflammatory bowel disease(IBD)is a group of chronic diseases that includes ulcerative colitis,Crohn’s disease,and indeterminate colitis.Patients with IBD require prolonged treatment and high utilization of healthcare resources for proper management.The treatment of patients with IBD is focused on achieving therapeutic goals including clinical,biochemical,and endoscopic variables that result in improvement of the quality of life and prevention of disability.Advanced IBD treatment includes tumor necrosis factor inhibitors,integrin antagonist,antagonist of the p40 subunit of interleukin 12/23,and small molecule drugs.However,despite the multiple treatments available,about 40%of patients are refractory to therapy and present with persistent symptoms that have a great impact on their quality of life,with hospitalization and surgery being necessary in many cases.Dual therapy,a strategy sometimes applicable to refractory IBD patients,includes the combination of two biologics or a biologic in combination with a small molecule drug.There are two distinct scenarios in IBD patients in which this approach can be used:(1)Refractory active luminal disease without extraintestinal manifestations;and(2)patients with IBD in remission,but with active extraintestinal manifestations or immune-mediated inflammatory diseases.This review provides a summary of the results(clinical response and remission)of different combinations of advanced drugs in patients with IBD,both in adults and in the pediatric population.In addition,the safety profile of different combinations of dual therapy is analyzed.The use of newer combinations,including recently approved treatments,the application of new biomarkers and artificial intelligence,and clinical trials to establish effectiveness during long-term followup,are needed to establish new strategies for the use of advanced treatments in patients with refractory IBD.展开更多
Treatment strategies for inflammatory bowel disease(IBD)are rapidly evolving with the development of biologics and small molecule drugs(SMDs).However,these drugs are not guaranteed to be effective in all patients,and ...Treatment strategies for inflammatory bowel disease(IBD)are rapidly evolving with the development of biologics and small molecule drugs(SMDs).However,these drugs are not guaranteed to be effective in all patients,and a“ceiling effect”of biologic monotherapy may occur.This issue highlights an unmet need for optimizing the use of biologics and predicting therapeutic responses.Thus,the development of new drugs with novel mechanisms of action is urgently needed for patients with primary nonresponse and secondary loss of response to conventional biologics and SMDs.In addition,combining different biologics or SMDs has been proposed as a novel strategy to enhance treatment efficacy in IBD,which theoretically has multidimensional anti-inflammatory potential.Based on the current evidence available for IBD,dual targeted therapy may be a promising strategy for refractory IBD patients who have failed in multiple biologic treatments or who have extraintestinal manifestation.Additionally,identifying the subgroup of IBD patients who are responding to biological combination therapies is also equally important in stable disease remission.In this review,we summarize the newly developed biologics and SMDs and the current status of biologics/SMDs to highlight the development of individualized treatment in IBD.展开更多
BACKGROUND Although blood concentration of biologics is an important composition of disease management in inflammatory bowel disease(IBD)patients,complexity and uncertainty of biological management encourage many disp...BACKGROUND Although blood concentration of biologics is an important composition of disease management in inflammatory bowel disease(IBD)patients,complexity and uncertainty of biological management encourage many disputes in predicting the outcome of IBD patients through blood concentration of biologics.AIM To verify the predictive value of blood concentration of biologics on endoscopic inactivity in IBD patients under different situations.METHODS We searched PubMed/MEDLINE,Embase,and Web of Science up to May 2020 and identified IBD patients as the research cohort as well as the correlations between blood concentration of biologics and endoscopic inactivity in IBD patients as the research direction.RESULTS A total of 23 articles with 30 clinical studies and 1939 IBD patients were included.The predictive cut-off value of blood concentration of infliximab on mucosal healing should be 2.7-10.6μg/mL in IBD.Blood concentration of infliximab reaching 5.0-12.7μg/mL or more increased the probability of fistula healing/closure in perianal fistulizing Crohn's disease.Blood concentration of adalimumab reaching 7.2-16.2μg/mL or more could predict mucosal healing in IBD.The predictive cut-off value of blood concentration of adalimumab on fistula healing/closure should be 5.9-9.8μg/mL in perianal fistulizing Crohn's disease.Blood concentration of vedolizumab surpassing 25.0μg/mL indicated mucosal healing in ulcerative colitis patients under maintenance therapy and the predictive cut-off value of blood concentration on mucosal healing or endoscopic remission under induction therapy in IBD could be 8.0-28.9μg/mL.CONCLUSION Blood concentration of biologics should not be utilized to predict endoscopic inactivity of IBD independently due to discrepancies in clinical studies,whereas conducting therapeutic drug monitoring intensively contributes to precise therapy.展开更多
The optimal duration of biological treatment, particularly anti-TNF, in inflammatory bowel disease （IBD） is a very important question both for patients and physicians. There is no published evidence to clearly and d...The optimal duration of biological treatment, particularly anti-TNF, in inflammatory bowel disease （IBD） is a very important question both for patients and physicians. There is no published evidence to clearly and definitely answer this question. However data on natural history of IBD, long term safety of biologics, immunosuppressors （IS） cessation and some preliminary studies on biologics cessation may help us to discuss this topic. The decision to stop a biological treatment is currently based on a compromise between the benefits and risks associated with the prolongation of this treatment. IBD, more particularly CD, are characterized by the development of complications and the need for recurrent hospitalizations and surgeries in approximately 2/3 of cases. In these patients potentially in need of biological treatments, it is probable that, as it has been demonstrated for IS, the longer a stable remission has be achieved under treatment, the lower the risk of relapse is alter treatment cessation. Further prospective studies should now aim at disclosing patient characteristics associated with a low risk of relapse to imple- ment this strategy.展开更多
为了明确长期使用微生物杀虫剂和化学农药对水稻田土壤微生物种群数量和代谢功能多样性的影响,本文采用分离培养技术和Biolog微平板法相结合对长期施用微生物农药苏云·稻纵颗(CnmeGV·Bt)和化学杀虫剂的稻田土壤微生物数量、...为了明确长期使用微生物杀虫剂和化学农药对水稻田土壤微生物种群数量和代谢功能多样性的影响,本文采用分离培养技术和Biolog微平板法相结合对长期施用微生物农药苏云·稻纵颗(CnmeGV·Bt)和化学杀虫剂的稻田土壤微生物数量、代谢功能活性及碳源利用类型多样性等进行研究。结果表明:与常规化学杀虫剂相比较,施用CnmeGV·Bt后土壤中细菌、真菌、放线菌数量均显著增加,分别为化学杀虫剂处理的1.86倍、1.75倍和1.34倍。进一步筛选发现真菌中木霉菌数量高于化学杀虫剂处理,差异显著。细菌中芽孢杆菌、溶磷功能菌、解钾功能菌数量与化学杀虫剂处理无显著差异。不同处理后土壤微生物群落平均颜色变化率(AWCD值)随时间变化趋势基本一致,开始的48 h AWCD变化很小,48~144 h快速升高。CnmeGV·Bt处理后AWCD值在48~192 h均显著高于化学杀虫剂处理。CnmeGV·Bt处理后土壤微生物群落Shannon多样性指数之间无显著变化,Simpson指数和Invsimpson指数显著提高。CnmeGV·Bt处理后土壤微生物对多种类型碳源的利用发生变化。对7种糖类、2种氨基酸类、6种己糖酸类、7种羧酸、酯和脂肪酸类的利用强度显著高于化学杀虫剂处理。对4种糖类、3种羧酸、酯和脂肪酸类的利用强度显著低于化学杀虫剂处理。主成分分析表明,与CnmeGV·Bt处理相关的碳源主要是葡糖醛酰胺、粘液酸、果胶、L-鼠李糖、?-甲酰-D-葡糖苷等,与化学杀虫剂处理相关的碳源主要是龙胆二糖、L-岩藻糖、D-苹果酸等。研究结果说明稻田应用微生物杀虫剂替代化学杀虫剂能够促进土壤微生物数量及其代谢功能,对于Bt类生物农药应用的环境行为及生态效应评价具有重要意义。展开更多
Over the past decade,the therapeutic armamentarium for inflammatory bowel disease(IBD)has substantially expanded with the incorporation of multiple classes of advanced therapies.Currently,in addition to tumor necrosis...Over the past decade,the therapeutic armamentarium for inflammatory bowel disease(IBD)has substantially expanded with the incorporation of multiple classes of advanced therapies.Currently,in addition to tumor necrosis factor-α inhibitors,the therapeutic arsenal for IBD includes anti-integrin agents,interleukin(IL)-12/23p40 and IL-23p19 antibodies,Janus kinase inhibitors,and sphingosine 1-phosphate receptor modulators.Although advances in IBD pharmacotherapy have enabled disease remission and improved control of intestinal inflammation in many individuals previously considered clinically'intractable',they have also increased the complexity of decision-making related to the initial positioning and sequencing of therapies in the heterogeneous clinical presentations of IBD.Until molecular and genetic markers capable of predicting therapeutic responses become available in practice,the choice of initial and subsequent therapy in individuals with IBD is based on factors including disease severity,phenotype,risk of complications,comorbidities,extraintestinal manifestations,and the balance between efficacy,safety,convenience,and access.This review explores the factors that influence treatment decisions regarding initial therapy selection and sequencing across IBD scenarios,offering practical tips for personalizing therapy based on the safety and efficacy of advanced treatments and the individual's risk of disease-or therapy-related adverse outcomes.展开更多
BACKGROUND Uveitis associated with juvenile idiopathic arthritis(U-JIA)is a vision-threatening condition.Estimates of prevalence of uveitis in patients with known juvenile idiopathic arthritis range from 11.6%to 30.0%...BACKGROUND Uveitis associated with juvenile idiopathic arthritis(U-JIA)is a vision-threatening condition.Estimates of prevalence of uveitis in patients with known juvenile idiopathic arthritis range from 11.6%to 30.0%.First-line treatment includes topical glucocorticoids;methotrexate(MTX)is used if topical corticosteroids are ineffective.In severe cases biological therapy like adalimumab may be prescribed.Complications,including vision loss,may be related to the disease and the ongoing treatment(topical corticosteroids).In severe cases surgical intervention is often necessary and is typically associated with poor vision outcomes.AIM To highlight the characteristics of operated U-JIA and to identify predictors of treatment failure.METHODS A retrospective cohort study analyzed data from 68 pediatric patients(under 18 years old)with U-JIA between 2007 and 2023.The study focused on demographic,clinical,treatment,and outcome variables.Survival analysis using Kaplan-Meier curves and the Cox proportional hazards model was performed to estimate the impact of surgical intervention on the course of uveitis and to identify predictors of treatment failure.RESULTS Eye surgery was performed on 17(25%)patients with U-JIA.It was associated with an earlier onset of uveitis(P=0.017),lower uveitis remission rate[odds ratio=5.29,95%confidence interval(CI):1.23-24.90,P=0.015],longer time to remission(P=0.036),reduced probability of achieving remission on MTX(P=0.033),and the necessity of the following treatment with biological diseasemodifying antirheumatic drugs(odds ratio=5.60;95%CI:1.11-55.19,P=0.021)with similar efficacy with biological treatments in operated and non-operated cases.Kaplan-Meier curves showed a borderline difference in time to surgical intervention based on the MTX initiation cutoff(P=0.065)although earlier MTX initiation might be associated with a higher likelihood of deferred surgery.CONCLUSION Operated patients exhibited an aggressive early-onset uveitis profile that needed early and more intensive treatment.Delayed and failed MTX treatment as well as delayed switching to biologics often required subsequent eye surgery.展开更多
BACKGROUND Chronic idiopathic uveitis(CIU)and juvenile idiopathic arthritis-associated uveitis(U-JIA)are both vision-threatening conditions that share similar autoimmune mechanisms,but treatment approaches differ sign...BACKGROUND Chronic idiopathic uveitis(CIU)and juvenile idiopathic arthritis-associated uveitis(U-JIA)are both vision-threatening conditions that share similar autoimmune mechanisms,but treatment approaches differ significantly.In managing U-JIA,various treatment options are employed,including biological and non-biological disease-modifying anti-rheumatic drugs.These drugs are effective in clinical trials.Given the lack of established diagnostic and treatment guidelines as well as the limited number of therapeutic options available,patients with CIU frequently do not receive optimal and timely immunosuppression.This study highlighted the necessity for additional research to develop novel diag-nostic techniques,targeted therapies,and enhanced treatment outcomes for young individuals with CIU.AIM To compare the characteristics and outcomes of U-JIA and CIU.METHODS A retrospective cohort study analyzed data from 110 pediatric patients(under 18 years old)with U-JIA and 40 pediatric patients with CIU.Data was collected between 2012 and 2023.The study focused on demographic,clinical,treatment,and outcome variables.RESULTS The median onset age of arthritis was 6.4 years(2.7 years;9.3 years).In 28.2%of cases uveitis preceded the onset of arthritis.In 17.3%of cases it occurred simultan-eously.In 53.6%of cases it followed arthritis.Both groups had similar onset ages,antinuclear antibodies/human leukocyte antigen positivity rates,and ESR levels,with a slight predominance of females(60.9%vs 42.5%,P=0.062),and higher C-reactive protein levels in the U-JIA group.Anterior uveitis was more prevalent in patients with U-JIA(P=0.023),although the frequency of symptomatic,unilateral,and complicated forms did not differ significantly.The use of methotrexate(83.8%vs 96.4%)and biologics(64.7%vs 82.1%)was comparable,as was the rate of remission on methotrexate treatment(70.9%vs 56.5%)and biological therapy(77.8%vs 95%),but a immunosuppressive treatment delay in CIU observed.Patients with CIU were less likely to receive methotrexate[hazard ratio(HR)=0.48,P=0.005]or biological treatment(HR=0.42,P=0.004),but they were more likely to achieve remission with methotrexate(HR=3.70,P=0.001).CONCLUSION Treatment of uveitis is often limited to topical measures,which can delay systemic therapy and affect the outcome.Methotrexate and biological agents effectively manage eye inflammation.It is essential to develop standardized protocols for the diagnosis and management of uveitis,and collaboration between rheumatologists and ophthal-mologists is needed to achieve optimal outcomes in the treatment of CIU.展开更多
Chronic obstructive pulmonary disease(COPD)is a persistent airflow obstructive disease caused by airway and/or alveolar abnormalities and has become the third leading cause of death worldwide.Dupilumab,the first fully...Chronic obstructive pulmonary disease(COPD)is a persistent airflow obstructive disease caused by airway and/or alveolar abnormalities and has become the third leading cause of death worldwide.Dupilumab,the first fully humanized monoclonal antibody targeting the IL-4 receptor subunit alpha(IL-4Rα),is mainly used to treat COPD patients with elevated blood eosinophils that cannot be effectively controlled by traditional drugs.Studies have shown that dupilumab effectively improves pulmonary function,reduces airway inflammation and exacerbation rate,and significantly improves quality of life in COPD patients by blocking interleukin-4(IL-4)and interleukin-13(IL-13)signaling.Several clinical trials and real-world studies have shown that dupilumab significantly reduces the rate of exacerbations,particularly in patients with high baseline eosinophil or FeNO levels.In addition,dupilumab showed positive efficacy in improving lung function,reducing airway inflammation and improving the quality of life of patients.Although the preliminary efficacy of dupilumab in the treatment of COPD is promising,its safety and efficacy need to be further validated,particularly in long-term use and in different patient subgroups.Future studies should focus on the precise classification of COPD,the exploration of relevant biomarkers,and the use of dupilumab at different stages of treatment in order to achieve personalized treatment.展开更多
文摘Pediatric inflammatory bowel disease(PIBD)is a chronic inflammatory disorder of the gastrointestinal tract,with rising global incidence and prevalence.Over the past two decades,biologics have added to the therapeutic armamentarium and revolutionized the approach to treatment of inflammatory bowel disease.The available biologics include monoclonal antibodies which target inflammatory cytokines(anti-tumor necrosis factor alpha,anti-interleukin 12/23)or recruitment of leucocytes to the gastrointestinal tract(anti-alpha4beta7 integrin)and small molecules(Janus kinase inhibitors,sphingosine 1-phosphate-inhibitors)which modify the proinflammatory signaling.Considering their potential disease-modifying ability,recent pediatric guidelines from the West have advocated upfront use of biologics in appropriate clinical scenarios as a top-down approach rather than the conventional step-up approach.Although real-world studies are available regarding the clinical efficacy of biologics in PIBD,there is paucity of long-term outcome and safety data in children.Also,little information is available about the best approach in the newly industrialized-developing countries where PIBD is rising but at the same time,infections are prevalent and resources are limited.In this review,we summarize the efficacy and safety profile of biologics and small molecule drugs and discuss the challenges in the management of PIBD,especially in the developing world,and future directions.
基金Supported by the Program of Guangdong Provincial Clinical Research Center for Digestive Diseases,No.2020B1111170004.
文摘BACKGROUND Endoscopic healing(EH)is a key therapeutic target in Crohn’s disease(CD).Proximal small bowel(SB)lesions in patients with CD are associated with a significant risk of strictures and bowel resection.Assessing SB in patients with CD is necessary because of its significant therapeutic implications.The advent of biologic therapies,including infliximab,ustekinumab,and vedolizumab,has significantly altered CD treatment.However,data on the efficacy of biologics in achieving EH,specifically in the proximal SB of patients with CD,remain limited.AIM To assess the effectiveness of biologics for EH in patients with jejunal and/or proximal ileal CD.METHODS Between 2017 and 2023,we retrospectively included 110 consecutive patients with isolated proximal SB CD,identified through baseline balloon-assisted enteroscopy.These patients completed 1-year of treatment with infliximab,ustekinumab,or vedolizumab,and underwent a second balloon-assisted enteroscopy at 1 year.Complete EH was defined as a modified Simple Endoscopic Score for CD(SES-CD)of<3,while EH of the jejunum and proximal ileum was defined as a segmental modified SES-CD of 0.RESULTS In total,64 patients were treated with infliximab,28 with ustekinumab,and 18 with vedolizumab.The complete EH rate at 1 year was 20.9%(23/110),with 29.6%(19/64)for infliximab,10.7%(3/28)for ustekinumab,and 5.5%(1/18)for vedolizumab.The median modified SES-CD significantly decreased compared to baseline[5(2-8)vs 8(6-9),P<0.001].The jejunal and proximal ileal EH rates at 1 year were 30.8%(12/39)and 15.5%(16/103),respectively.Multiple logistic regression analysis showed that stricturing or penetrating disease[odds ratio(OR)=0.261,95%CI:0.087-0.778,P=0.016],prior exposure to biologics(OR=0.080,95%CI:0.010-0.674,P=0.020),and moderate-tosevere endoscopic disease(OR=0.277,95%CI:0.093-0.829,P=0.022)were associated with a lower likelihood of achieving EH at 1 year.CONCLUSION Only 20.9%of patients with isolated proximal SB CD achieved complete EH after 1 year of biologic therapy.
文摘Many placebo controlled trials and meta-analyses evaluated the efficacy of different drugs for the treatment of inflammatory bowel disease (IBD), including immunosuppressants and biologics. Their use is indicated in moderate to severe disease in non responders to corticosteroids and in steroid-dependent patients, as induction and maintainance treatment. Infliximab, as well as cyclosporine, is considered a second line therapy in the case of severe ulcerative colitis, or non-responders to intravenous corticosteroids. An adequate dosage and duration of therapy with thiopurines should be reached before evaluating their efficacy. Methotrexate is a valid option in patients with Crohn’s disease but its use is confined to patients who are intolerant or non-responders to thiopurines. Evidence for the use of methotrexate in ulcerative colitis is insufficient. The use of thalidomide and mycophenolate mofetil is not recommended in patients with inflammatory bowel disease, these treatments could be considered in case of failure of all other therapeutic options. In patients with moderately active ulcerative colitis, refractory to thiopurines, the use of tacrolimus is considered an alternative to biologics. An increase of the dose or a decrease in the interval of administration of biological treatment could be useful in the presence of an incomplete clinical response. In the case of primary failure of an anti-tumor necrosis factor alpha a switch to another one should be considered. Data on the efficacy of combination therapy are up to now insufficient to consider this strategy in all IBD patients. The final outcome of the treatment should be considered the clinical remission, with mucosa healing, and not the clinical response. The evaluation of serum concentration of thiopurine methyl transferase activity, thiopurine metabolites, biologic serum levels and antibiologic antibodies could be useful for the management of the treatment but it has not been routinely applied in clinical practice. The evidence of high risk development of lymphoma and cutaneous malignancies should be considered in patients treated with immunosuppressants and biologics for a long period.
文摘The advent of biologics and small molecules in inflammatory bowel disease(IBD)has marked a significant turning point in the prognosis of IBD,decreasing the rates of corticosteroid dependence,hospitalizations and improving overall quality of life.The introduction of biosimilars has also increased affordability and enhanced access to these otherwise costly targeted therapies.Biologics do not yet represent a complete panacea:A subset of patients do not respond to first-line anti-tumor necrosis factor(TNF)-alpha agents or may subsequently demonstrate a secondary loss of response.Patients who fail to respond to anti-TNF agents typically have a poorer response rate to second-line biologics.It is uncertain which patient would benefit from a different sequencing of biologics or even a combination of biologic agents.The introduction of newer classes of biologics and small molecules may provide alternative therapeutic targets for patients with refractory disease.This review examines the therapeutic ceiling in current treatment strategies of IBD and the potential paradigm shifts in the future.
文摘BACKGROUND Biologic therapy resulted in a significant positive impact on the management of inflammatory bowel disease(IBD) however data on the efficacy and side effects of these therapies in the elderly is scant.AIM To evaluate retrospectively the drug sustainability, effectiveness, and safety of the biologic therapies in the elderly IBD population.METHODS Consecutive elderly(≥ 60 years old) IBD patients, treated with biologics [infliximab(IFX), adalimumab(ADAL), vedolizumab(VDZ), ustekinumab(UST)] followed at the McGill University Inflammatory Bowel Diseases Center were included between January 2000 and 2020.Efficacy was measured by clinical scores at 3, 6-9 and 12-18 mo after initiation of the biologic therapy. Patients completing induction therapy were included. Adverse events(AEs) or serious AE were collected during and within three months of stopping of the biologic therapy.RESULTS We identified a total of 147 elderly patients with IBD treated with biologicals during the study period, including 109 with Crohn’s disease and 38 with ulcerative colitis. Patients received the following biologicals: IFX(28.5%), ADAL(38.7%), VDZ(15.6%), UST(17%). The mean duration of biologic treatment was 157.5(SD = 148) wk. Parallel steroid therapy was given in 34% at baseline,19% at 3 mo, 16.3% at 6-9 mo and 6.5% at 12-18 mo. The remission rates at 3, 6-9 and 12-18 mo were not significantly different among biological therapies. Kaplan-Meyer analysis did not show statistical difference for drug sustainability(P = 0.195), time to adverse event(P = 0.158) or infection rates(P = 0.973) between the four biologics studied. The most common AEs that led to drug discontinuation were loss of response, infusion/injection reaction and infection.CONCLUSION Current biologics were not different regarding drug sustainability, effectiveness, and safety in the elderly IBD population. Therefore, we are not able to suggest a preferred sequencing order among biologicals.
文摘The management of rheumatoid arthritis(RA) in the past three decades has undergone a paradigm shift from symptomatic relief to a "treat-to-target" approach. This has been possible through use of various conventional and biologic disease modifying anti-rheumatic drugs(DMARDs) which target disease pathogenesis at a molecular level. Cost and infection risk preclude regular use of biologics in resource-constrained settings. In therecent years, evidence has emerged that combination therapy with conventional DMARDs is not inferior to biologics in the management of RA and is a feasible cost-effective option.
文摘Our increase in knowledge of the pathophysiology of non-infectious uveitis(NIU)and other immune-mediated diseases has been mirrored over the last two decades by the expansion of therapeutic options in the realm of immunosuppressive medications.Principal among these advances is the emergence of biologics,which offer the promise of targeted therapy and the hope of reduced toxicity when compared to corticosteroids and“standard”immunosuppression.Among the biologics,monoclonal antibodies blocking tumor necrosis factor alpha(TNF-α)have been shown to be a very effective therapeutic target for uveitis and many associated systemic inflammatory diseases.Multiple TNF blockers have shown benefit for uveitis,and in 2016,adalimumab became the first biologic and non-corticosteroid immunosuppressive to obtain Food and Drug Administration(FDA)approval in the treatment of NIU.Although effective,TNF blockers are not universally so,and safety concerns such as infection and demyelinating disease must be carefully considered and ruled out prior to their use,especially in patients with intermediate uveitis with which multiple sclerosis is a known association.Ongoing study has identified novel targets for regulation in the treatment of immune-mediated and inflammatory diseases.Interferons,interleukin and Janus kinase inhibitors in addition to antibodies targeting T cell and B cell activation highlight the expanding field of treatment modalities in NIU.Ongoing study will be required to better determine the safety and efficacy of biologics in the armamentarium of immunosuppressive treatments for NIU.
文摘A 46-year-old female patient with terminal ileum Crohn’s disease and ankylosing spondylitis presented with recurrent angioedema and urticaria. Investigations ruled out hereditary angioedema, and environmental or food allergen triggers. She was diagnosed with chronic idiopathic urticaria with angioedema, and was treated with a trial of intravenous immunoglobulin immunotherapy, danazol, prednisone and hydroxyzine. Due to ongoing bowel and arthritic complaints, she was started on infliximab infusions and within 2 treatments, she had complete resolution of the angioedema and urticaria, as well as of the bowel and arthritic symptoms. Unfortunately she developed allergic reactions to the infliximab and was switched to another anti-tumor necrosis factor （TNF）-a agent, adalimumab. Since then, she has had no further angioedema or urticaria, and her Crohn’s disease has been quiescent. This is the first known case report of chronic idiopathic urticaria with angioedema coexistent with Crohn’s disease that was successfully treated with anti-TNF-α agents.
文摘Hepatitis B virus reactivation(HBVr)can occur in patients treated with immunosuppressive medications.Risk stratification for HBVr based on hepatitis B virus(HBV)serology and viral load is an important strategy to determine appropriate HBV monitoring and antiviral prophylaxis use.Recent advances in the understanding of pathophysiology of autoimmune diseases have led the development of cytokine-targeted therapies.Tumor necrosis factor(TNF)-αinhibitors have been widely used for patients with inflammatory bowel disease,psoriasis,and rheumatic diseases.Further,the clinical benefits of interleukin(IL)-12/23,IL-17,or Janus kinases inhibitors have been demonstrated in these patients.It is well known that TNF-αinhibitor use can lead to HBVr,however,the risk of HBVr in patients undergoing non-TNF-targeted biologics have not been fully understood.In this review,we discuss the risk of HBVr in patients treated with non-TNF-targeted biologics,and immunological mechanisms of these medications causing HBVr.
文摘Corticosteroids and immunomodulators have been the mainstay therapies for Crohn’s disease. Corticosteroids are highly effective to control symptoms in the short- term, but they are not effective in maintaining remission, they heal the mucosa in a reduced proportion of cases, and long-time exposure is associated with an increased risk of infections and mortality. Immunomodulators, azathioprine and methotrexate, heal the mucosa in a higher proportion of patients that corticosteroids but their onset of action is slow and they benefit less than half of patients with Crohn’s disease. In the last decade, medical therapy for Crohn’s disease has experienced a remarkable change due to the introduction of biologic therapy, and particularly the use of anti-tumour necrosis factor-alpha agents. Infliximab, adalimumab, and certolizumab pegol have demonstrated efficacy for induction and maintenance of remission in active Crohn’s disease. These agents have raised the bar for what is a suitable symptomatic response in Crohn’s disease and modification of the natural history of the disease has become a major goal in the treatment of Crohn’s disease. There are several data in the literature that suggest that early use of biologic therapy and achievement of mucosal healing contribute to disease course modification. However, many questions on early biological therapy for Crohn’s disease remain still unanswered.
文摘Inflammatory bowel disease(IBD)is a group of chronic diseases that includes ulcerative colitis,Crohn’s disease,and indeterminate colitis.Patients with IBD require prolonged treatment and high utilization of healthcare resources for proper management.The treatment of patients with IBD is focused on achieving therapeutic goals including clinical,biochemical,and endoscopic variables that result in improvement of the quality of life and prevention of disability.Advanced IBD treatment includes tumor necrosis factor inhibitors,integrin antagonist,antagonist of the p40 subunit of interleukin 12/23,and small molecule drugs.However,despite the multiple treatments available,about 40%of patients are refractory to therapy and present with persistent symptoms that have a great impact on their quality of life,with hospitalization and surgery being necessary in many cases.Dual therapy,a strategy sometimes applicable to refractory IBD patients,includes the combination of two biologics or a biologic in combination with a small molecule drug.There are two distinct scenarios in IBD patients in which this approach can be used:(1)Refractory active luminal disease without extraintestinal manifestations;and(2)patients with IBD in remission,but with active extraintestinal manifestations or immune-mediated inflammatory diseases.This review provides a summary of the results(clinical response and remission)of different combinations of advanced drugs in patients with IBD,both in adults and in the pediatric population.In addition,the safety profile of different combinations of dual therapy is analyzed.The use of newer combinations,including recently approved treatments,the application of new biomarkers and artificial intelligence,and clinical trials to establish effectiveness during long-term followup,are needed to establish new strategies for the use of advanced treatments in patients with refractory IBD.
基金Jiangsu Provincial Health Commission,No.M2021013the Science Foundation of Jinling Hospital,No.YYMS2021035.
文摘Treatment strategies for inflammatory bowel disease(IBD)are rapidly evolving with the development of biologics and small molecule drugs(SMDs).However,these drugs are not guaranteed to be effective in all patients,and a“ceiling effect”of biologic monotherapy may occur.This issue highlights an unmet need for optimizing the use of biologics and predicting therapeutic responses.Thus,the development of new drugs with novel mechanisms of action is urgently needed for patients with primary nonresponse and secondary loss of response to conventional biologics and SMDs.In addition,combining different biologics or SMDs has been proposed as a novel strategy to enhance treatment efficacy in IBD,which theoretically has multidimensional anti-inflammatory potential.Based on the current evidence available for IBD,dual targeted therapy may be a promising strategy for refractory IBD patients who have failed in multiple biologic treatments or who have extraintestinal manifestation.Additionally,identifying the subgroup of IBD patients who are responding to biological combination therapies is also equally important in stable disease remission.In this review,we summarize the newly developed biologics and SMDs and the current status of biologics/SMDs to highlight the development of individualized treatment in IBD.
基金Supported by The National Natural Science Foundation of China,No.81473506Zhejiang TCM Science and Technology Project,No.2019ZA056,No.2016ZA092,and No.2021ZA057.
文摘BACKGROUND Although blood concentration of biologics is an important composition of disease management in inflammatory bowel disease(IBD)patients,complexity and uncertainty of biological management encourage many disputes in predicting the outcome of IBD patients through blood concentration of biologics.AIM To verify the predictive value of blood concentration of biologics on endoscopic inactivity in IBD patients under different situations.METHODS We searched PubMed/MEDLINE,Embase,and Web of Science up to May 2020 and identified IBD patients as the research cohort as well as the correlations between blood concentration of biologics and endoscopic inactivity in IBD patients as the research direction.RESULTS A total of 23 articles with 30 clinical studies and 1939 IBD patients were included.The predictive cut-off value of blood concentration of infliximab on mucosal healing should be 2.7-10.6μg/mL in IBD.Blood concentration of infliximab reaching 5.0-12.7μg/mL or more increased the probability of fistula healing/closure in perianal fistulizing Crohn's disease.Blood concentration of adalimumab reaching 7.2-16.2μg/mL or more could predict mucosal healing in IBD.The predictive cut-off value of blood concentration of adalimumab on fistula healing/closure should be 5.9-9.8μg/mL in perianal fistulizing Crohn's disease.Blood concentration of vedolizumab surpassing 25.0μg/mL indicated mucosal healing in ulcerative colitis patients under maintenance therapy and the predictive cut-off value of blood concentration on mucosal healing or endoscopic remission under induction therapy in IBD could be 8.0-28.9μg/mL.CONCLUSION Blood concentration of biologics should not be utilized to predict endoscopic inactivity of IBD independently due to discrepancies in clinical studies,whereas conducting therapeutic drug monitoring intensively contributes to precise therapy.
文摘The optimal duration of biological treatment, particularly anti-TNF, in inflammatory bowel disease （IBD） is a very important question both for patients and physicians. There is no published evidence to clearly and definitely answer this question. However data on natural history of IBD, long term safety of biologics, immunosuppressors （IS） cessation and some preliminary studies on biologics cessation may help us to discuss this topic. The decision to stop a biological treatment is currently based on a compromise between the benefits and risks associated with the prolongation of this treatment. IBD, more particularly CD, are characterized by the development of complications and the need for recurrent hospitalizations and surgeries in approximately 2/3 of cases. In these patients potentially in need of biological treatments, it is probable that, as it has been demonstrated for IS, the longer a stable remission has be achieved under treatment, the lower the risk of relapse is alter treatment cessation. Further prospective studies should now aim at disclosing patient characteristics associated with a low risk of relapse to imple- ment this strategy.
文摘为了明确长期使用微生物杀虫剂和化学农药对水稻田土壤微生物种群数量和代谢功能多样性的影响,本文采用分离培养技术和Biolog微平板法相结合对长期施用微生物农药苏云·稻纵颗(CnmeGV·Bt)和化学杀虫剂的稻田土壤微生物数量、代谢功能活性及碳源利用类型多样性等进行研究。结果表明:与常规化学杀虫剂相比较,施用CnmeGV·Bt后土壤中细菌、真菌、放线菌数量均显著增加,分别为化学杀虫剂处理的1.86倍、1.75倍和1.34倍。进一步筛选发现真菌中木霉菌数量高于化学杀虫剂处理,差异显著。细菌中芽孢杆菌、溶磷功能菌、解钾功能菌数量与化学杀虫剂处理无显著差异。不同处理后土壤微生物群落平均颜色变化率(AWCD值)随时间变化趋势基本一致,开始的48 h AWCD变化很小,48~144 h快速升高。CnmeGV·Bt处理后AWCD值在48~192 h均显著高于化学杀虫剂处理。CnmeGV·Bt处理后土壤微生物群落Shannon多样性指数之间无显著变化,Simpson指数和Invsimpson指数显著提高。CnmeGV·Bt处理后土壤微生物对多种类型碳源的利用发生变化。对7种糖类、2种氨基酸类、6种己糖酸类、7种羧酸、酯和脂肪酸类的利用强度显著高于化学杀虫剂处理。对4种糖类、3种羧酸、酯和脂肪酸类的利用强度显著低于化学杀虫剂处理。主成分分析表明,与CnmeGV·Bt处理相关的碳源主要是葡糖醛酰胺、粘液酸、果胶、L-鼠李糖、?-甲酰-D-葡糖苷等,与化学杀虫剂处理相关的碳源主要是龙胆二糖、L-岩藻糖、D-苹果酸等。研究结果说明稻田应用微生物杀虫剂替代化学杀虫剂能够促进土壤微生物数量及其代谢功能,对于Bt类生物农药应用的环境行为及生态效应评价具有重要意义。
文摘Over the past decade,the therapeutic armamentarium for inflammatory bowel disease(IBD)has substantially expanded with the incorporation of multiple classes of advanced therapies.Currently,in addition to tumor necrosis factor-α inhibitors,the therapeutic arsenal for IBD includes anti-integrin agents,interleukin(IL)-12/23p40 and IL-23p19 antibodies,Janus kinase inhibitors,and sphingosine 1-phosphate receptor modulators.Although advances in IBD pharmacotherapy have enabled disease remission and improved control of intestinal inflammation in many individuals previously considered clinically'intractable',they have also increased the complexity of decision-making related to the initial positioning and sequencing of therapies in the heterogeneous clinical presentations of IBD.Until molecular and genetic markers capable of predicting therapeutic responses become available in practice,the choice of initial and subsequent therapy in individuals with IBD is based on factors including disease severity,phenotype,risk of complications,comorbidities,extraintestinal manifestations,and the balance between efficacy,safety,convenience,and access.This review explores the factors that influence treatment decisions regarding initial therapy selection and sequencing across IBD scenarios,offering practical tips for personalizing therapy based on the safety and efficacy of advanced treatments and the individual's risk of disease-or therapy-related adverse outcomes.
文摘BACKGROUND Uveitis associated with juvenile idiopathic arthritis(U-JIA)is a vision-threatening condition.Estimates of prevalence of uveitis in patients with known juvenile idiopathic arthritis range from 11.6%to 30.0%.First-line treatment includes topical glucocorticoids;methotrexate(MTX)is used if topical corticosteroids are ineffective.In severe cases biological therapy like adalimumab may be prescribed.Complications,including vision loss,may be related to the disease and the ongoing treatment(topical corticosteroids).In severe cases surgical intervention is often necessary and is typically associated with poor vision outcomes.AIM To highlight the characteristics of operated U-JIA and to identify predictors of treatment failure.METHODS A retrospective cohort study analyzed data from 68 pediatric patients(under 18 years old)with U-JIA between 2007 and 2023.The study focused on demographic,clinical,treatment,and outcome variables.Survival analysis using Kaplan-Meier curves and the Cox proportional hazards model was performed to estimate the impact of surgical intervention on the course of uveitis and to identify predictors of treatment failure.RESULTS Eye surgery was performed on 17(25%)patients with U-JIA.It was associated with an earlier onset of uveitis(P=0.017),lower uveitis remission rate[odds ratio=5.29,95%confidence interval(CI):1.23-24.90,P=0.015],longer time to remission(P=0.036),reduced probability of achieving remission on MTX(P=0.033),and the necessity of the following treatment with biological diseasemodifying antirheumatic drugs(odds ratio=5.60;95%CI:1.11-55.19,P=0.021)with similar efficacy with biological treatments in operated and non-operated cases.Kaplan-Meier curves showed a borderline difference in time to surgical intervention based on the MTX initiation cutoff(P=0.065)although earlier MTX initiation might be associated with a higher likelihood of deferred surgery.CONCLUSION Operated patients exhibited an aggressive early-onset uveitis profile that needed early and more intensive treatment.Delayed and failed MTX treatment as well as delayed switching to biologics often required subsequent eye surgery.
文摘BACKGROUND Chronic idiopathic uveitis(CIU)and juvenile idiopathic arthritis-associated uveitis(U-JIA)are both vision-threatening conditions that share similar autoimmune mechanisms,but treatment approaches differ significantly.In managing U-JIA,various treatment options are employed,including biological and non-biological disease-modifying anti-rheumatic drugs.These drugs are effective in clinical trials.Given the lack of established diagnostic and treatment guidelines as well as the limited number of therapeutic options available,patients with CIU frequently do not receive optimal and timely immunosuppression.This study highlighted the necessity for additional research to develop novel diag-nostic techniques,targeted therapies,and enhanced treatment outcomes for young individuals with CIU.AIM To compare the characteristics and outcomes of U-JIA and CIU.METHODS A retrospective cohort study analyzed data from 110 pediatric patients(under 18 years old)with U-JIA and 40 pediatric patients with CIU.Data was collected between 2012 and 2023.The study focused on demographic,clinical,treatment,and outcome variables.RESULTS The median onset age of arthritis was 6.4 years(2.7 years;9.3 years).In 28.2%of cases uveitis preceded the onset of arthritis.In 17.3%of cases it occurred simultan-eously.In 53.6%of cases it followed arthritis.Both groups had similar onset ages,antinuclear antibodies/human leukocyte antigen positivity rates,and ESR levels,with a slight predominance of females(60.9%vs 42.5%,P=0.062),and higher C-reactive protein levels in the U-JIA group.Anterior uveitis was more prevalent in patients with U-JIA(P=0.023),although the frequency of symptomatic,unilateral,and complicated forms did not differ significantly.The use of methotrexate(83.8%vs 96.4%)and biologics(64.7%vs 82.1%)was comparable,as was the rate of remission on methotrexate treatment(70.9%vs 56.5%)and biological therapy(77.8%vs 95%),but a immunosuppressive treatment delay in CIU observed.Patients with CIU were less likely to receive methotrexate[hazard ratio(HR)=0.48,P=0.005]or biological treatment(HR=0.42,P=0.004),but they were more likely to achieve remission with methotrexate(HR=3.70,P=0.001).CONCLUSION Treatment of uveitis is often limited to topical measures,which can delay systemic therapy and affect the outcome.Methotrexate and biological agents effectively manage eye inflammation.It is essential to develop standardized protocols for the diagnosis and management of uveitis,and collaboration between rheumatologists and ophthal-mologists is needed to achieve optimal outcomes in the treatment of CIU.
文摘Chronic obstructive pulmonary disease(COPD)is a persistent airflow obstructive disease caused by airway and/or alveolar abnormalities and has become the third leading cause of death worldwide.Dupilumab,the first fully humanized monoclonal antibody targeting the IL-4 receptor subunit alpha(IL-4Rα),is mainly used to treat COPD patients with elevated blood eosinophils that cannot be effectively controlled by traditional drugs.Studies have shown that dupilumab effectively improves pulmonary function,reduces airway inflammation and exacerbation rate,and significantly improves quality of life in COPD patients by blocking interleukin-4(IL-4)and interleukin-13(IL-13)signaling.Several clinical trials and real-world studies have shown that dupilumab significantly reduces the rate of exacerbations,particularly in patients with high baseline eosinophil or FeNO levels.In addition,dupilumab showed positive efficacy in improving lung function,reducing airway inflammation and improving the quality of life of patients.Although the preliminary efficacy of dupilumab in the treatment of COPD is promising,its safety and efficacy need to be further validated,particularly in long-term use and in different patient subgroups.Future studies should focus on the precise classification of COPD,the exploration of relevant biomarkers,and the use of dupilumab at different stages of treatment in order to achieve personalized treatment.
