Ulcerative colitis(UC)is a major form of inflammatory bowel disease(IBD)worldwide.Better understanding of the pathogenesis of UC has led to the development of novel therapeutic agents that target specific mediators of...Ulcerative colitis(UC)is a major form of inflammatory bowel disease(IBD)worldwide.Better understanding of the pathogenesis of UC has led to the development of novel therapeutic agents that target specific mediators of the inflammatory cascade.A number of biological agents have been approved by the U.S.Food and Drug Administration(FDA)for the treatment of UC and several more are currently in various phases of drug development.The commonly used agents include TNFa antagonists(e.g.infliximab,adalimumab,and golimumab)and anti-integrin agents(vedolizumab).These biological agents have profoundly influenced the management of UC patients,especially those with refractory disease.This paper reviews the currently available knowledge and evidence for the use of various biological agents in the treatment of UC.展开更多
Biological therapy revolutionized the treatment of inflammatory bowel disease(IBD)during the last decade.These monoclonal antibodies,which target tumor necrosis factor(TNF),integrins or IL12/23,have been approved—or ...Biological therapy revolutionized the treatment of inflammatory bowel disease(IBD)during the last decade.These monoclonal antibodies,which target tumor necrosis factor(TNF),integrins or IL12/23,have been approved—or are in development for—both Crohn’s disease(CD)and ulcerative colitis(UC).Early use of these agents taught clinicians that induction and maintenance therapy,coupled with immunomodulator agents,reduced the immunogenicity of these agents,and led to sustained remission in many patients.More recent data has demonstrated that,through dose adjustments,optimizing serum drug levels may also provide more durable maintenance of remission,and improved mucosal healing.This review examines clinical practices that may enhance clinical outcomes from biological therapy in IBD.展开更多
Biologic agents have now been used in the management of inflammatory bowel disease(IBD)for many years where experience,expertise and confidence in their use has developed over time.In the United Kingdom,there are well...Biologic agents have now been used in the management of inflammatory bowel disease(IBD)for many years where experience,expertise and confidence in their use has developed over time.In the United Kingdom,there are well established guidelines and recommendations for both single agent biologic treatments,and with combination therapy of a biologic agent with a small molecule agent in maintenance therapy.In recent times,there has been increasing interest and experience using dual biologic therapy(DBT)in IBD,primarily in difficult to treat and refractory cases with high disease burden.However,published data on use,experience and safety profiles is limited and large-scale studies remain low in number in this developing area.We therefore aim to present a summary and review of the available published data in this area to help us better understand the emerging role of DBT in IBD.展开更多
AIM To analyze access(availability, affordability and acceptability) to biologicals for Crohn's disease(CD) in ten European countries and to explore the associations between these dimensions, the uptake of biologi...AIM To analyze access(availability, affordability and acceptability) to biologicals for Crohn's disease(CD) in ten European countries and to explore the associations between these dimensions, the uptake of biologicals and economic development.METHODS A questionnaire-based survey combined with desk research was carried out in May 2016. Gastroenterologists from the Czech Republic, France, Germany, Hungary, Latvia, Poland, Romania, Slovakia, Spain and Sweden were invited to participate and provide data on the availability of biologicals/biosimilars, reimbursement criteria, clinical practice and prices, and use of biologicals. An availability score was developed to evaluate the restrictiveness of eligibility and administrative criteria applied in the countries. Affordability was defined as the annual cost of treatment as a share of gross domestic product(GDP) per capita. Correlations with the uptake of biologicals, dimensions of access and GDP per capita were calculated.RESULTS At the time of the survey, infliximab and adalimumab were reimbursed in all ten countries, and vedolizumab was reimbursed in five countries(France, Germany, Latvia, Slovakia, Sweden). Reimbursement criteria were the least strict in Sweden and Germany, and the strictest in Hungary, Poland and Slovakia. Between countries, the annual cost of different biological treatments differed 1.6-3.3-fold. Treatments were the most affordable in Sweden(13%-37% of the GDP per capita) and the least affordable in the Central and Eastern European countries, especially in Hungary(87%-124%) and Romania(141%-277%). Biosimilars made treatments more affordable by driving down the annual costs. The number of patients with CD on biologicals per 100000 population was strongly correlated with GDP per capita(0.91), although substantial differences were found in the uptake among countries with similar economic development. Correlation between the number of patients with CD on biologicals per 100000 population and the availability and affordability was also strong(-0.75,-0.69 respectively). CONCLUSION Substantial inequalities in access to biologicals were largely associated with GDP. To explain differences in access among countries with similar development needs further research on acceptance.展开更多
BACKGROUND Solitary fibrous tumor(SFT)of the central nervous system is rare.It is predominantly benign and rarely malignant.There is no established standardized treatment regimen for malignant intracranial SFTs.CASE S...BACKGROUND Solitary fibrous tumor(SFT)of the central nervous system is rare.It is predominantly benign and rarely malignant.There is no established standardized treatment regimen for malignant intracranial SFTs.CASE SUMMARY We present a rare case of SFT in a 9-year-old girl with a space-occupying effect in the frontal-parietal lobes.She underwent craniotomy,and the mass was resected.Immunohistochemistry examination of the specimen showed that Ki-67 proliferation index staining was highly positive in 80%of tumor cells.Whole exome sequencing of the surgical tissue showed 38 somatic gene mutations and 1 gene amplification such as fibroblast growth factor receptor 4 or TP53.At 1.5 mo after surgery,head magnetic resonance imaging revealed that the tumor had recurred.The patient received 60 Gy and 30 fractions of intensity modulated radiotherapy.The patient then received anlotinib 8 mg po qd for 1-14 d of a 21 d cycle.Following this regimen,the patient achieved stable disease for>17 mo.Magnetic resonance imaging at 1.5 year after surgery showed that the tumor had not progressed.CONCLUSION This is the first reported case of SFT of the central nervous system treated with surgery,radiotherapy and anlotinib.This regimen may be an effective treatment option for malignant intracranial SFT patients.展开更多
BACKGROUND Little is known about the safety and efficacy of using two or more biologics for the treatment of immune-mediated diseases,including Crohn’s disease(CD).CASE SUMMARY This case report and narrative review d...BACKGROUND Little is known about the safety and efficacy of using two or more biologics for the treatment of immune-mediated diseases,including Crohn’s disease(CD).CASE SUMMARY This case report and narrative review demonstrate the potential safety of dual biologic therapy(DBT)in a 45-year-old female with two separate immunemediated diseases.She had a history of multiple sclerosis for which she was receiving treatment with ocrelizumab,and she had been recently diagnosed with CD after presenting with diarrhoea.The CD diagnosis was confirmed radiologically,endoscopically,histologically,and biochemically.The patient received treatment with vedolizumab,a gut-specific inhibitor of theα4β7 integrin on leukocytes.No adverse reactions were observed for the duration of treatment.The safety of ocrelizumab and vedolizumab for the treatment of different immune-mediated diseases was demonstrated.CONCLUSION DBT may be a safe and effective option for the treatment of refractory disease or multiple immunemediated diseases.Newer biologics,which have improved safety profiles and gut specificity,may provide promising avenues for treatment.However,caution must be exercised in the appropriate selection of biologics given their inherent immunosuppressive properties,side effects,and efficacy profiles.Current evidence suggests that biologic therapy is not associated with a worse prognosis in patients with coronavirus disease 2019,but treatment decisions should be made in a multidisciplinary setting.Further research from controlled trials is needed to better understand the safety profile of DBT in CD.The immunopathological mechanisms underlying DBT also remain to be clarified.展开更多
BACKGROUND Despite the overload of publications on Crohn’s disease(CD),no comprehensive analysis of biologic therapy for CD has been reported.AIM To determine knowledge gaps and identify areas of interest of biologic...BACKGROUND Despite the overload of publications on Crohn’s disease(CD),no comprehensive analysis of biologic therapy for CD has been reported.AIM To determine knowledge gaps and identify areas of interest of biologic therapy for CD.METHODS The top 100 highest-cited original articles were identified from January 1991 to December 2020 in the Clarivate Analytics Web of Science Core Collection database.We conducted a bibliometric analysis of biologic therapy for CD based on total citations,summarized the bibliographic information of the articles related to CD biologic therapy,and explored the research hotspots.RESULTS The top 100 highest-cited original articles were identified with total citations ranging from 307 to 2978.The 2000s(Period II,n=66)yielded the most influential original articles and saw the most dramatic growth.Among the top 10 countries,including 8 European countries and 2 North American countries,the United States(n=37)and Belgium(n=20)contributed the most publications.Among the top 10 institutions,the University Hospital Gasthuisberg in Belgium(n=23),the University of Chicago in the United States(n=20),and the Mayo Clinic in the United States(n=17)published the most papers.Regarding authors,Rutgeerts P in Belgium(n=32),Sandborn WJ in the United States(n=23),and Feagan BG in Canada(n=18)published the highest number of studies.The cooperation relationships between the United States and Europe were most frequent.Gastroenterology(impact factor=22.682)published the most articles on biologic therapy for CD(n=32)with 17654 total citations.Anti-tumor necrosis factor biologics and monoclonal antibodies were the most studied topics.CONCLUSION The bibliometric analysis emphasized the key contributions to the development of the specialized field.These data would provide useful research insights into biologic therapy for CD for clinicians and researchers.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
Managing inflammatory bowel disease(IBD)during the coronavirus disease 2019(COVID-19)pandemic has been a challenge faced by clinicians and their patients,especially concerning whether to proceed with biologics and imm...Managing inflammatory bowel disease(IBD)during the coronavirus disease 2019(COVID-19)pandemic has been a challenge faced by clinicians and their patients,especially concerning whether to proceed with biologics and immunosuppressive agents in the background of a global outbreak of a highly contagious new coronavirus(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2).The knowledge about the impact of this virus on patients with IBD,although it is still scarce,is rapidly evolving.In particular,concerns surrounding medications’impact for IBD on the risk of acquiring SARS-CoV-2 infection or developing COVID-19,and potentially exacerbate viral replication and the COVID-19 course,are a current thinking of both practicing clinicians and providers caring for patients with IBD.Managing patients with IBD infected with SARS-CoV-2 depends on both the clinical activity of the IBD and the occasional development and severity of COVID-19.In this review,we summarize the current data regarding gastrointestinal involvement by SARS-CoV-2 and pharmacologic and surgical management for IBD concerning this infection,and the COVID-19 impact on both the patient's psychological functioning and endoscopy services,and we concisely summarize the telemedicine roles during the COVID-19 pandemic.展开更多
Ovarian cancer is one of the most common malignant tumors in female reproductive organs.Due to the lack of effective screening and early diagnosis methods,the vast majority of patients with ovarian cancer are in advan...Ovarian cancer is one of the most common malignant tumors in female reproductive organs.Due to the lack of effective screening and early diagnosis methods,the vast majority of patients with ovarian cancer are in advanced stages once diagnosed.Precision therapy mainly includes immunotherapy,targeted therapy,biological therapy,and gene therapy.At present,precision therapy is increasingly used in the clinical treatment of ovarian cancer due to its advantages,such as fewer side effects and a high degree of killing.This article summarizes the recent advances in the precise treatment of ovarian cancer.展开更多
Co-stimulatory molecules are key mediators in the regulation of immune responses and knowledge of its different families,structure,and functions has improved in recent decades.Understanding the role of co-stimulatory ...Co-stimulatory molecules are key mediators in the regulation of immune responses and knowledge of its different families,structure,and functions has improved in recent decades.Understanding the role of co-stimulatory molecules in pathological processes has allowed the development of strategies to modulate cellular functions.Currently,modulation of co-stimulatory and co-inhibitory molecules has been applied in clinical applications as therapeutic targets in diseases and promising results have been achieved.展开更多
BACKGROUND Hematopoietic stem cell(HSC)transplantation(HSCT)is being accepted as a standard of care in various inflammatory diseases.The treatment of rheumatoid arthritis(RA)has been closely evolving with the understa...BACKGROUND Hematopoietic stem cell(HSC)transplantation(HSCT)is being accepted as a standard of care in various inflammatory diseases.The treatment of rheumatoid arthritis(RA)has been closely evolving with the understanding of disease pathogenesis.With the rising resistance to the traditional disease-modifying antirheumatic drugs and targeted biological therapy,researchers are in pursuit of other methods for disease management.Since the ultimate goal of the ideal treatment of RA is to restore immune tolerance,HSCT attracts much attention considering its reparative,paracrine,and anti-inflammatory effects.However,a systematic review of studies on HSCT in RA is lacking.AIM To investigate the role of HSCT in the management of RA.METHODS A detailed search of PubMed,Scopus,EMBASE,Cochrane,and the Web of Science databases was made to identify the relevant articles till September 2020 following Cochrane and PRISMA guidelines.We extracted data including the number of patients,source of hematopoietic stem cells,their mobilization and conditioning regimens,results,and complications from the eligible studies.Results were dichotomized into success(ACR 50/70)and failure(ACR 20)based on the improvement from baseline characteristics.The methodological quality of the included studies was also assessed.Analysis was performed using OpenMeta[Analysis]software.RESULTS We included 17 studies(1 randomized controlled trial,11 prospective,and 5 retrospective studies)with 233 patients for analysis.HSCT provided a significantly beneficial overall improvement in the clinical grades of ACR criteria(Z=11.309,P<0.001).However,the remission was noted only till 24 mo and later on the significance of the result was lost(Z=1.737,P=0.082).A less than 1%treatmentrelated mortality was noted from the included studies.No major drug-related toxicities were noted in any of the included studies.All patients who underwent allogeneic HSCT received immunosuppression in the conditioning regimen to counteract the graft-vs-host reaction which made them vulnerable to infections.It is noted that the source of hematopoietic stem cells did not play a role in altering the functional outcome and both autologous(Z=9.972,P<0.001)and allogenic(Z=6.978,P<0.001)sources produced significant improvement in the outcome compared to the pre-operative state despite having a significant heterogeneity among the studies reporting them(I2=99.4,P<0.001).CONCLUSION Although the available literature is encouraging towards the use of HSCT in refractory cases with significant improvement from baseline till 2 years,the inclusion of HSCT into the standard of care of RA needs further exploration.展开更多
<strong>Background:</strong> Psoriasis, a chronic, systemic, inflammatory disease with prominent skin involvement, affects approximately 2% - 4% of the world population. Common variants of psoriasis are pl...<strong>Background:</strong> Psoriasis, a chronic, systemic, inflammatory disease with prominent skin involvement, affects approximately 2% - 4% of the world population. Common variants of psoriasis are plaque psoriasis, inverse psoriasis, guttate psoriasis, erythrodermic psoriasis, pustular form either palmoplantar pustular psoriasis or generalized pustular psoriasis, nail psoriasis, and psoriatic arthritis. Progressive Symmetrical Erythrokeratoderma (PSEK) is a rare genetic disorder, characterized by fixed, well-defined erythematous and hyperkeratotic plaques distributed predominantly on the elbows, knees, trunk, and dorsal surfaces of hands and feet. Clinically has the same presentation to psoriasis especially at early onset and could be confused with psoriasis but histopathological findings and progression of the psoriatic disease can differentiate between both conditions. <strong>Aim:</strong> To document a new variant of a severe, recalcitrant type of psoriasis with a history of recurrent attacks of exacerbations and partial remissions especially in lesions involving lower extremities that are clinically PSEK-like in presentation, but histopathologically consistent with psoriasis. <strong>Case report:</strong> A 12-year-old childhood male, known case of Down’s syndrome, presented to our clinic with a history of severely pruritic skin rashes involving the perioral area, corners of the mouth, bilateral elbows, dorsal hands, scrotum, and both lower extremities for 6 years duration. The rashes gradually progressed with time to form fixed lesions in the last 2 years. He was received multiple treatment modalities, including topical steroids, topical vitamin D derivatives, and narrowband UVB phototherapy without significant improvement and the lesions became more worsened over time. <strong>Conclusion:</strong> psoriasis can be presenting with a new variant of a severe, recalcitrant, and difficult to treat type in Down syndrome cases with a history of recurrent attacks of exacerbations and partial remissions especially in lesions involving lower extremities which are clinically PSEK-like in presentation, but histopathologically consistent with psoriasis. However, early diagnosis and strict management are important in controlling the severity of the condition.展开更多
The proportion of hepatitis B virus(HBV) previously exposed patients who receive immunosuppressive treatment is usually very small. However, if these individuals are exposed to potent immunosuppressive compounds, the ...The proportion of hepatitis B virus(HBV) previously exposed patients who receive immunosuppressive treatment is usually very small. However, if these individuals are exposed to potent immunosuppressive compounds, the risk of HBV reactivation(HBVr) increases with the presence of hepatitis B surface antigen(HBsAg) in the serum. Chronic HBsAg carriers have a higher risk than those who have a total IgG anticore as the only marker of resolved/occult HBV disease. The loss of immune control in these patients may results in the reactivation of HBV replication within hepatocytes. Upon reconstitution of the immune system, infected hepatocytes are once again targeted and damaged by immune surveillance in an effort to clear the virus. There are different virological scenarios, and a wide spectrum of associated drugs with specific and stratified risk for the development of HBVr. Some of this agents can trigger a severe degree of hepatocellular damage, including hepatitis, acute liver failure, and even death despite employment of effective antiviral therapies. Currently, HBVr incidence seems to be increasing around the world; a fact mainly related to the incessant appearance of more powerful immunosuppressive drugs launched to the market. Moreover, there is no consensus on the length of prophylactic treatment before the patients are treated with immunosuppressive therapy, and for how long this therapy should be extended once treatment is completed. Therefore, this review article will focus on when to treat, when to monitor, what patients should receive HBV therapy, and what drugs should be selected for each scenario. Lastly, we will update the definition, risk factors, screening, and treatment recommendations based on both current and different HBV management guidelines.展开更多
Inflammatory bowel disease(IBD)is a chronic condition that significantly affects the quality of life of its patients.Biologic drugs have been the mainstay treatment in the management of IBD patients but despite their ...Inflammatory bowel disease(IBD)is a chronic condition that significantly affects the quality of life of its patients.Biologic drugs have been the mainstay treatment in the management of IBD patients but despite their significant contribution,there remains a proportion of patients that do not respond or lose response to treatment.Therapeutic drug monitoring(TDM)involves measuring levels of serum drug concentrations and anti-drug antibodies.TDM of biologic drugs initially emerged to understand treatment failure in other immune mediated inflammatory diseases.This was then introduced in IBD to rationalize primary non-response or secondary loss of response,given that low serum drug concentrations or the formation of anti-drug antibodies are variably associated with treatment failure.The aim of this narrative review is to provide an overview regarding the current use of TDM in clinical practice and to present the evidence available regarding its use in both proactive and reactive clinical settings in preventing and managing treatment failure.This review also presents the existing evidence regarding the association of various clinical outcomes with specific thresholds of drug concentrations,in everyday practice.A narrative review of published articles and conference abstracts regarding the use of TDM in IBD management,through an electronic search using PubMed and ScienceDirect.TDM has proven to be superior and more cost effective in guiding management of patients with treatment failure compared to empiric dose escalation or change in treatment.Despite a trend towards an association between clinical outcomes and drug concentrations,proactive TDM based strategies have not been shown to achieve clear benefit in long-term outcomes.In the clinical setting,TDM has proven to be useful in managing IBD patients,and its use in the reactive setting,as an additional tool to help manage patients with treatment failure,is being promoted as newer guidelines and consensus groups implement TDM as part of the management plan.展开更多
BACKGROUND Gastroenteropancreatic neuroendocrine tumours(GEP-NETs)are slow-growing cancers that arise from diffuse endocrine cells in the gastrointestinal tract(GINETs)or the pancreas(P-NETs).They are relatively uncom...BACKGROUND Gastroenteropancreatic neuroendocrine tumours(GEP-NETs)are slow-growing cancers that arise from diffuse endocrine cells in the gastrointestinal tract(GINETs)or the pancreas(P-NETs).They are relatively uncommon,accounting for 2%of all gastrointestinal malignancies.The usual treatment options in advanced GEP-NET patients with metastatic disease include chemotherapy,biological therapies,and peptide receptor radionuclide therapy.Understanding the impact of treatment on GEP-NET patients is paramount given the nature of the disease.Health-related quality of life(HRQoL)is increasingly important as a concept reflecting the patients’perspective in conjunction with the disease presentation,severity and treatment.AIM To conduct a systematic literature review to identify literature reporting HRQoL data in patients with GEP-NETs between January 1985 and November 2019.METHODS The PRISMA guiding principles were applied.MEDLINE,Embase and the Cochrane library were searched.Data extracted from the publications included type of study,patient population data(mid-gut/hind-gut/GI-NET/P-NET),sample size,intervention/comparators,HRQoL instruments,average and data spread of overall and sub-scores,and follow-up time for data collection.RESULTS Forty-three publications met the inclusion criteria.The heterogeneous nature of the different study populations was evident;the percentage of female participants ranged between 30%-60%,whilst average age ranged from 53.8 to 67.0 years.Eight studies investigated GI-NET patients only,six studies focused exclusively on P-NET patients and the remaining studies involved both patient populations or did not report the location of the primary tumour.The most commonly used instrument was the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30(n=28)with consistent results across studies;the GI-NET-specific module Quality of Life Questionnaire-GINET21 was used in six of these studies.A number of randomised trials demonstrated no HRQoL changes between active treatment and placebo arms.The Phase III NETTER-1 study provides the best data available for advanced GEP-NET patients;it shows that peptide receptor radionuclide therapy can significantly improve GEP-NET patients’HRQoL.CONCLUSION HRQoL instruments offer a means to monitor patients’general disease condition,disease progression and their physical and mental well-being.Instruments including the commonly used European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and GINET21 lack,however,validation and a defined minimal clinical important difference specifically for GINET and P-NET patients.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
Recently,biological drugs have played a leading role in the treatment of inflammatory bowel disease,and therapeutic drug monitoring(TDM)may be useful in maximizing their effectiveness.TDM involves the measurement of s...Recently,biological drugs have played a leading role in the treatment of inflammatory bowel disease,and therapeutic drug monitoring(TDM)may be useful in maximizing their effectiveness.TDM involves the measurement of serum drug and anti-drug antibodies concentrations as the basis for dosage adjustments or drug conversions to achieve a higher response rate.We believe that concentration thresholds should be individualized based on patients’disease severity,extent and phenotype,and therapeutic purposes should also be considered,with higher cut-offs mainly needed for endoscopic and fistula healing than for symptomatic remission.Proactive and reactive TDM can help optimize treatment,especially in patients receiving anti-tumour necrosis factor,and guide dose adjustment or drug conversion with lower cost.TDM is a promising approach to achieve precision medicine and targeted medicine in the future.展开更多
Background:Concerns exist regarding the potential development of tuberculosis in patients with rheumatoid arthritis(RA)treated with biological and targeted drugs.We assessed systematically whether biological therapy i...Background:Concerns exist regarding the potential development of tuberculosis in patients with rheumatoid arthritis(RA)treated with biological and targeted drugs.We assessed systematically whether biological therapy increased the risk of tuberculosis in patients with RA by meta-analysis of randomized controlled trials(RCTs).Methods:A systematic literature search was conducted in PubMed,Embase,the Cochrane Library,and China Biology Medicine disc for RCTs evaluating biological therapy in patients with RA from inception through August 2021.Traditional meta-analysis and network meta-analysis were performed to compare the risk of tuberculosis for each biologics class in patients with RA.Peto odds ratio(Peto OR)and its 95%confidence interval(CI)were calculated as the primary effect measure.Results:In total,39 studies with 20,354 patients were included in this meta-analysis,and 82 patients developed tuberculosis.The risk of tuberculosis was increased in patients treated with biologics compared with non-biologics(Peto OR:3.86,95%CI:2.36-6.32,P<0.001).Also,tumor necrosis factor-α(TNF-α)inhibitors had a higher probability of developing tuberculosis than placebo(Peto OR:3.98,95%CI:2.30-6.88,P<0.001).However,network meta-analysis demonstrated that there was no significant difference in the risk of tuberculosis for each biologics class in patients with RA.Noticeably,tuberculosis was significantly more common in patients treated with a high dose compared with patients receiving a low dose of tofacitinib(Peto OR:7.39,95%CI:2.00-27.31,P=0.003).Conclusion:This meta-analysis demonstrates the evidence of an elevated risk of tuberculosis in patients with RA treated with TNF-αinhibitors,and a dose-dependent elevated risk of tuberculosis in patients treated with tofacitinib.展开更多
Background: Concerns exist regarding the risk of infections in patients with spondyloarthritis (SpA) treated with biologics. We assessed the risk of infections of biological and targeted drugs in patients with SpA by ...Background: Concerns exist regarding the risk of infections in patients with spondyloarthritis (SpA) treated with biologics. We assessed the risk of infections of biological and targeted drugs in patients with SpA by performing a meta-analysis based on randomized controlled trials (RCTs).Methods: A systematic literature search was conducted in PubMed, Embase, Web of Science, the Cochrane Library, and China Biology Medicine Disc for RCTs evaluating the risk of infections of biological therapy in patients with SpA from inception through August 9, 2021. We calculated a pooled Peto odds ratio (OR) for infections in biologics-treated patientsvs. placebo patients. The risk of bias on the included RCTs was assessed by using the Cochrane Risk of Bias Tool.Results: In total, 62 studies were included in this meta-analysis. Overall, the risk of infection (Peto OR: 1.16, 95% confidence interval [CI]: 1.07-1.26,P < 0.001), serious infection (Peto OR: 1.65, 95% CI: 1.26-2.17,P < 0.001), upper respiratory tract infection (URTI) (Peto OR: 1.17, 95% CI: 1.04-1.32,P = 0.008), nasopharyngitis (Peto OR: 1.25, 95% CI: 1.10-1.42,P < 0.001), andCandida infection (Peto OR: 2.64, 95% CI: 1.48-4.71,P = 0.001) were increased in SpA patients treated with biologics compared with placebo. Sensitivity analysis based on biologics classes was conducted, and results demonstrated that compared with placebo, there was a higher risk of infection for tumor necrosis factor (TNF)-α inhibitors (Peto OR: 1.38, 95% CI: 1.13-1.68,P = 0.001) and interleukin (IL)-17 inhibitors (Peto OR: 1.55, 95% CI: 1.08-2.22,P = 0.018) in axial SpA, and for Janus kinase inhibitors in peripheral SpA (Peto OR: 1.39, 95% CI: 1.14-1.69,P = 0.001);higher risk of serious infection for IL-17 inhibitors in peripheral SpA (Peto OR: 3.46, 95% CI: 1.26-9.55,P = 0.016) and axial SpA (Peto OR: 2.01, 95% CI: 1.38-2.91,P < 0.001);higher risk of URTI for TNF-α inhibitors in axial SpA (Peto OR: 1.37, 95% CI: 1.05-1.78,P= 0.019), and for apremilast in peripheral SpA (Peto OR: 1.60, 95% CI: 1.08-2.36,P = 0.018);higher risk of nasopharyngitis for TNF-α inhibitors in axial SpA (Peto OR: 1.41, 95% CI: 1.05-1.90,P = 0.022) and peripheral SpA (Peto OR: 1.49, 95% CI: 1.09-2.05,P = 0.013), and for IL-17 inhibitors in axial SpA (Peto OR: 1.35, 95% CI: 1.01-1.82,P = 0.044);higher risk of herpes zoster for Janus kinase inhibitors in peripheral SpA (Peto OR: 2.18, 95% CI: 1.03-4.62,P = 0.043);higher risk ofCandida infection for IL-17 inhibitors in peripheral SpA (Peto OR: 2.52, 95% CI: 1.31-4.84,P= 0.006).Conclusions: This meta-analysis shows that biological therapy in patients with SpA may increase the risk of infections, including serious infections, URTI, nasopharyngitis, andCandida infection, which should be paid attention to in our clinical practice.展开更多
文摘Ulcerative colitis(UC)is a major form of inflammatory bowel disease(IBD)worldwide.Better understanding of the pathogenesis of UC has led to the development of novel therapeutic agents that target specific mediators of the inflammatory cascade.A number of biological agents have been approved by the U.S.Food and Drug Administration(FDA)for the treatment of UC and several more are currently in various phases of drug development.The commonly used agents include TNFa antagonists(e.g.infliximab,adalimumab,and golimumab)and anti-integrin agents(vedolizumab).These biological agents have profoundly influenced the management of UC patients,especially those with refractory disease.This paper reviews the currently available knowledge and evidence for the use of various biological agents in the treatment of UC.
文摘Biological therapy revolutionized the treatment of inflammatory bowel disease(IBD)during the last decade.These monoclonal antibodies,which target tumor necrosis factor(TNF),integrins or IL12/23,have been approved—or are in development for—both Crohn’s disease(CD)and ulcerative colitis(UC).Early use of these agents taught clinicians that induction and maintenance therapy,coupled with immunomodulator agents,reduced the immunogenicity of these agents,and led to sustained remission in many patients.More recent data has demonstrated that,through dose adjustments,optimizing serum drug levels may also provide more durable maintenance of remission,and improved mucosal healing.This review examines clinical practices that may enhance clinical outcomes from biological therapy in IBD.
文摘Biologic agents have now been used in the management of inflammatory bowel disease(IBD)for many years where experience,expertise and confidence in their use has developed over time.In the United Kingdom,there are well established guidelines and recommendations for both single agent biologic treatments,and with combination therapy of a biologic agent with a small molecule agent in maintenance therapy.In recent times,there has been increasing interest and experience using dual biologic therapy(DBT)in IBD,primarily in difficult to treat and refractory cases with high disease burden.However,published data on use,experience and safety profiles is limited and large-scale studies remain low in number in this developing area.We therefore aim to present a summary and review of the available published data in this area to help us better understand the emerging role of DBT in IBD.
基金Supported byúNKP-16-4/BCE-0025 New National Excellence Program of the Ministry of Human Capacities(Hungary)
文摘AIM To analyze access(availability, affordability and acceptability) to biologicals for Crohn's disease(CD) in ten European countries and to explore the associations between these dimensions, the uptake of biologicals and economic development.METHODS A questionnaire-based survey combined with desk research was carried out in May 2016. Gastroenterologists from the Czech Republic, France, Germany, Hungary, Latvia, Poland, Romania, Slovakia, Spain and Sweden were invited to participate and provide data on the availability of biologicals/biosimilars, reimbursement criteria, clinical practice and prices, and use of biologicals. An availability score was developed to evaluate the restrictiveness of eligibility and administrative criteria applied in the countries. Affordability was defined as the annual cost of treatment as a share of gross domestic product(GDP) per capita. Correlations with the uptake of biologicals, dimensions of access and GDP per capita were calculated.RESULTS At the time of the survey, infliximab and adalimumab were reimbursed in all ten countries, and vedolizumab was reimbursed in five countries(France, Germany, Latvia, Slovakia, Sweden). Reimbursement criteria were the least strict in Sweden and Germany, and the strictest in Hungary, Poland and Slovakia. Between countries, the annual cost of different biological treatments differed 1.6-3.3-fold. Treatments were the most affordable in Sweden(13%-37% of the GDP per capita) and the least affordable in the Central and Eastern European countries, especially in Hungary(87%-124%) and Romania(141%-277%). Biosimilars made treatments more affordable by driving down the annual costs. The number of patients with CD on biologicals per 100000 population was strongly correlated with GDP per capita(0.91), although substantial differences were found in the uptake among countries with similar economic development. Correlation between the number of patients with CD on biologicals per 100000 population and the availability and affordability was also strong(-0.75,-0.69 respectively). CONCLUSION Substantial inequalities in access to biologicals were largely associated with GDP. To explain differences in access among countries with similar development needs further research on acceptance.
文摘BACKGROUND Solitary fibrous tumor(SFT)of the central nervous system is rare.It is predominantly benign and rarely malignant.There is no established standardized treatment regimen for malignant intracranial SFTs.CASE SUMMARY We present a rare case of SFT in a 9-year-old girl with a space-occupying effect in the frontal-parietal lobes.She underwent craniotomy,and the mass was resected.Immunohistochemistry examination of the specimen showed that Ki-67 proliferation index staining was highly positive in 80%of tumor cells.Whole exome sequencing of the surgical tissue showed 38 somatic gene mutations and 1 gene amplification such as fibroblast growth factor receptor 4 or TP53.At 1.5 mo after surgery,head magnetic resonance imaging revealed that the tumor had recurred.The patient received 60 Gy and 30 fractions of intensity modulated radiotherapy.The patient then received anlotinib 8 mg po qd for 1-14 d of a 21 d cycle.Following this regimen,the patient achieved stable disease for>17 mo.Magnetic resonance imaging at 1.5 year after surgery showed that the tumor had not progressed.CONCLUSION This is the first reported case of SFT of the central nervous system treated with surgery,radiotherapy and anlotinib.This regimen may be an effective treatment option for malignant intracranial SFT patients.
文摘BACKGROUND Little is known about the safety and efficacy of using two or more biologics for the treatment of immune-mediated diseases,including Crohn’s disease(CD).CASE SUMMARY This case report and narrative review demonstrate the potential safety of dual biologic therapy(DBT)in a 45-year-old female with two separate immunemediated diseases.She had a history of multiple sclerosis for which she was receiving treatment with ocrelizumab,and she had been recently diagnosed with CD after presenting with diarrhoea.The CD diagnosis was confirmed radiologically,endoscopically,histologically,and biochemically.The patient received treatment with vedolizumab,a gut-specific inhibitor of theα4β7 integrin on leukocytes.No adverse reactions were observed for the duration of treatment.The safety of ocrelizumab and vedolizumab for the treatment of different immune-mediated diseases was demonstrated.CONCLUSION DBT may be a safe and effective option for the treatment of refractory disease or multiple immunemediated diseases.Newer biologics,which have improved safety profiles and gut specificity,may provide promising avenues for treatment.However,caution must be exercised in the appropriate selection of biologics given their inherent immunosuppressive properties,side effects,and efficacy profiles.Current evidence suggests that biologic therapy is not associated with a worse prognosis in patients with coronavirus disease 2019,but treatment decisions should be made in a multidisciplinary setting.Further research from controlled trials is needed to better understand the safety profile of DBT in CD.The immunopathological mechanisms underlying DBT also remain to be clarified.
基金Supported by the National Natural Science Foundation of China,No.81800540Key Research and Development Project of Zhejiang Province,No.2018C03083.
文摘BACKGROUND Despite the overload of publications on Crohn’s disease(CD),no comprehensive analysis of biologic therapy for CD has been reported.AIM To determine knowledge gaps and identify areas of interest of biologic therapy for CD.METHODS The top 100 highest-cited original articles were identified from January 1991 to December 2020 in the Clarivate Analytics Web of Science Core Collection database.We conducted a bibliometric analysis of biologic therapy for CD based on total citations,summarized the bibliographic information of the articles related to CD biologic therapy,and explored the research hotspots.RESULTS The top 100 highest-cited original articles were identified with total citations ranging from 307 to 2978.The 2000s(Period II,n=66)yielded the most influential original articles and saw the most dramatic growth.Among the top 10 countries,including 8 European countries and 2 North American countries,the United States(n=37)and Belgium(n=20)contributed the most publications.Among the top 10 institutions,the University Hospital Gasthuisberg in Belgium(n=23),the University of Chicago in the United States(n=20),and the Mayo Clinic in the United States(n=17)published the most papers.Regarding authors,Rutgeerts P in Belgium(n=32),Sandborn WJ in the United States(n=23),and Feagan BG in Canada(n=18)published the highest number of studies.The cooperation relationships between the United States and Europe were most frequent.Gastroenterology(impact factor=22.682)published the most articles on biologic therapy for CD(n=32)with 17654 total citations.Anti-tumor necrosis factor biologics and monoclonal antibodies were the most studied topics.CONCLUSION The bibliometric analysis emphasized the key contributions to the development of the specialized field.These data would provide useful research insights into biologic therapy for CD for clinicians and researchers.
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Managing inflammatory bowel disease(IBD)during the coronavirus disease 2019(COVID-19)pandemic has been a challenge faced by clinicians and their patients,especially concerning whether to proceed with biologics and immunosuppressive agents in the background of a global outbreak of a highly contagious new coronavirus(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2).The knowledge about the impact of this virus on patients with IBD,although it is still scarce,is rapidly evolving.In particular,concerns surrounding medications’impact for IBD on the risk of acquiring SARS-CoV-2 infection or developing COVID-19,and potentially exacerbate viral replication and the COVID-19 course,are a current thinking of both practicing clinicians and providers caring for patients with IBD.Managing patients with IBD infected with SARS-CoV-2 depends on both the clinical activity of the IBD and the occasional development and severity of COVID-19.In this review,we summarize the current data regarding gastrointestinal involvement by SARS-CoV-2 and pharmacologic and surgical management for IBD concerning this infection,and the COVID-19 impact on both the patient's psychological functioning and endoscopy services,and we concisely summarize the telemedicine roles during the COVID-19 pandemic.
文摘Ovarian cancer is one of the most common malignant tumors in female reproductive organs.Due to the lack of effective screening and early diagnosis methods,the vast majority of patients with ovarian cancer are in advanced stages once diagnosed.Precision therapy mainly includes immunotherapy,targeted therapy,biological therapy,and gene therapy.At present,precision therapy is increasingly used in the clinical treatment of ovarian cancer due to its advantages,such as fewer side effects and a high degree of killing.This article summarizes the recent advances in the precise treatment of ovarian cancer.
基金Supported by Institute of Ophthalmology“Fundacion Conde de Valenciana”Velazquez-Soto H received fellowship 294674 from CONACYT during his doctoral studies in Programa de Doctorado en Ciencias Medicas,Odontologicas y de la Salud(Farmacologia Clinica),Universidad Nacional Autonoma de Mexico(UNAM)Real F with CVU 917729,recieved fellowship from CONACYT during his master studies in Programa de Maestria en Ciencias Medicas,Odontologicas y de la Salud(Farmacologia Clinica),Universidad Nacional Autonoma de Mexico(UNAM).
文摘Co-stimulatory molecules are key mediators in the regulation of immune responses and knowledge of its different families,structure,and functions has improved in recent decades.Understanding the role of co-stimulatory molecules in pathological processes has allowed the development of strategies to modulate cellular functions.Currently,modulation of co-stimulatory and co-inhibitory molecules has been applied in clinical applications as therapeutic targets in diseases and promising results have been achieved.
文摘BACKGROUND Hematopoietic stem cell(HSC)transplantation(HSCT)is being accepted as a standard of care in various inflammatory diseases.The treatment of rheumatoid arthritis(RA)has been closely evolving with the understanding of disease pathogenesis.With the rising resistance to the traditional disease-modifying antirheumatic drugs and targeted biological therapy,researchers are in pursuit of other methods for disease management.Since the ultimate goal of the ideal treatment of RA is to restore immune tolerance,HSCT attracts much attention considering its reparative,paracrine,and anti-inflammatory effects.However,a systematic review of studies on HSCT in RA is lacking.AIM To investigate the role of HSCT in the management of RA.METHODS A detailed search of PubMed,Scopus,EMBASE,Cochrane,and the Web of Science databases was made to identify the relevant articles till September 2020 following Cochrane and PRISMA guidelines.We extracted data including the number of patients,source of hematopoietic stem cells,their mobilization and conditioning regimens,results,and complications from the eligible studies.Results were dichotomized into success(ACR 50/70)and failure(ACR 20)based on the improvement from baseline characteristics.The methodological quality of the included studies was also assessed.Analysis was performed using OpenMeta[Analysis]software.RESULTS We included 17 studies(1 randomized controlled trial,11 prospective,and 5 retrospective studies)with 233 patients for analysis.HSCT provided a significantly beneficial overall improvement in the clinical grades of ACR criteria(Z=11.309,P<0.001).However,the remission was noted only till 24 mo and later on the significance of the result was lost(Z=1.737,P=0.082).A less than 1%treatmentrelated mortality was noted from the included studies.No major drug-related toxicities were noted in any of the included studies.All patients who underwent allogeneic HSCT received immunosuppression in the conditioning regimen to counteract the graft-vs-host reaction which made them vulnerable to infections.It is noted that the source of hematopoietic stem cells did not play a role in altering the functional outcome and both autologous(Z=9.972,P<0.001)and allogenic(Z=6.978,P<0.001)sources produced significant improvement in the outcome compared to the pre-operative state despite having a significant heterogeneity among the studies reporting them(I2=99.4,P<0.001).CONCLUSION Although the available literature is encouraging towards the use of HSCT in refractory cases with significant improvement from baseline till 2 years,the inclusion of HSCT into the standard of care of RA needs further exploration.
文摘<strong>Background:</strong> Psoriasis, a chronic, systemic, inflammatory disease with prominent skin involvement, affects approximately 2% - 4% of the world population. Common variants of psoriasis are plaque psoriasis, inverse psoriasis, guttate psoriasis, erythrodermic psoriasis, pustular form either palmoplantar pustular psoriasis or generalized pustular psoriasis, nail psoriasis, and psoriatic arthritis. Progressive Symmetrical Erythrokeratoderma (PSEK) is a rare genetic disorder, characterized by fixed, well-defined erythematous and hyperkeratotic plaques distributed predominantly on the elbows, knees, trunk, and dorsal surfaces of hands and feet. Clinically has the same presentation to psoriasis especially at early onset and could be confused with psoriasis but histopathological findings and progression of the psoriatic disease can differentiate between both conditions. <strong>Aim:</strong> To document a new variant of a severe, recalcitrant type of psoriasis with a history of recurrent attacks of exacerbations and partial remissions especially in lesions involving lower extremities that are clinically PSEK-like in presentation, but histopathologically consistent with psoriasis. <strong>Case report:</strong> A 12-year-old childhood male, known case of Down’s syndrome, presented to our clinic with a history of severely pruritic skin rashes involving the perioral area, corners of the mouth, bilateral elbows, dorsal hands, scrotum, and both lower extremities for 6 years duration. The rashes gradually progressed with time to form fixed lesions in the last 2 years. He was received multiple treatment modalities, including topical steroids, topical vitamin D derivatives, and narrowband UVB phototherapy without significant improvement and the lesions became more worsened over time. <strong>Conclusion:</strong> psoriasis can be presenting with a new variant of a severe, recalcitrant, and difficult to treat type in Down syndrome cases with a history of recurrent attacks of exacerbations and partial remissions especially in lesions involving lower extremities which are clinically PSEK-like in presentation, but histopathologically consistent with psoriasis. However, early diagnosis and strict management are important in controlling the severity of the condition.
文摘The proportion of hepatitis B virus(HBV) previously exposed patients who receive immunosuppressive treatment is usually very small. However, if these individuals are exposed to potent immunosuppressive compounds, the risk of HBV reactivation(HBVr) increases with the presence of hepatitis B surface antigen(HBsAg) in the serum. Chronic HBsAg carriers have a higher risk than those who have a total IgG anticore as the only marker of resolved/occult HBV disease. The loss of immune control in these patients may results in the reactivation of HBV replication within hepatocytes. Upon reconstitution of the immune system, infected hepatocytes are once again targeted and damaged by immune surveillance in an effort to clear the virus. There are different virological scenarios, and a wide spectrum of associated drugs with specific and stratified risk for the development of HBVr. Some of this agents can trigger a severe degree of hepatocellular damage, including hepatitis, acute liver failure, and even death despite employment of effective antiviral therapies. Currently, HBVr incidence seems to be increasing around the world; a fact mainly related to the incessant appearance of more powerful immunosuppressive drugs launched to the market. Moreover, there is no consensus on the length of prophylactic treatment before the patients are treated with immunosuppressive therapy, and for how long this therapy should be extended once treatment is completed. Therefore, this review article will focus on when to treat, when to monitor, what patients should receive HBV therapy, and what drugs should be selected for each scenario. Lastly, we will update the definition, risk factors, screening, and treatment recommendations based on both current and different HBV management guidelines.
文摘Inflammatory bowel disease(IBD)is a chronic condition that significantly affects the quality of life of its patients.Biologic drugs have been the mainstay treatment in the management of IBD patients but despite their significant contribution,there remains a proportion of patients that do not respond or lose response to treatment.Therapeutic drug monitoring(TDM)involves measuring levels of serum drug concentrations and anti-drug antibodies.TDM of biologic drugs initially emerged to understand treatment failure in other immune mediated inflammatory diseases.This was then introduced in IBD to rationalize primary non-response or secondary loss of response,given that low serum drug concentrations or the formation of anti-drug antibodies are variably associated with treatment failure.The aim of this narrative review is to provide an overview regarding the current use of TDM in clinical practice and to present the evidence available regarding its use in both proactive and reactive clinical settings in preventing and managing treatment failure.This review also presents the existing evidence regarding the association of various clinical outcomes with specific thresholds of drug concentrations,in everyday practice.A narrative review of published articles and conference abstracts regarding the use of TDM in IBD management,through an electronic search using PubMed and ScienceDirect.TDM has proven to be superior and more cost effective in guiding management of patients with treatment failure compared to empiric dose escalation or change in treatment.Despite a trend towards an association between clinical outcomes and drug concentrations,proactive TDM based strategies have not been shown to achieve clear benefit in long-term outcomes.In the clinical setting,TDM has proven to be useful in managing IBD patients,and its use in the reactive setting,as an additional tool to help manage patients with treatment failure,is being promoted as newer guidelines and consensus groups implement TDM as part of the management plan.
文摘BACKGROUND Gastroenteropancreatic neuroendocrine tumours(GEP-NETs)are slow-growing cancers that arise from diffuse endocrine cells in the gastrointestinal tract(GINETs)or the pancreas(P-NETs).They are relatively uncommon,accounting for 2%of all gastrointestinal malignancies.The usual treatment options in advanced GEP-NET patients with metastatic disease include chemotherapy,biological therapies,and peptide receptor radionuclide therapy.Understanding the impact of treatment on GEP-NET patients is paramount given the nature of the disease.Health-related quality of life(HRQoL)is increasingly important as a concept reflecting the patients’perspective in conjunction with the disease presentation,severity and treatment.AIM To conduct a systematic literature review to identify literature reporting HRQoL data in patients with GEP-NETs between January 1985 and November 2019.METHODS The PRISMA guiding principles were applied.MEDLINE,Embase and the Cochrane library were searched.Data extracted from the publications included type of study,patient population data(mid-gut/hind-gut/GI-NET/P-NET),sample size,intervention/comparators,HRQoL instruments,average and data spread of overall and sub-scores,and follow-up time for data collection.RESULTS Forty-three publications met the inclusion criteria.The heterogeneous nature of the different study populations was evident;the percentage of female participants ranged between 30%-60%,whilst average age ranged from 53.8 to 67.0 years.Eight studies investigated GI-NET patients only,six studies focused exclusively on P-NET patients and the remaining studies involved both patient populations or did not report the location of the primary tumour.The most commonly used instrument was the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30(n=28)with consistent results across studies;the GI-NET-specific module Quality of Life Questionnaire-GINET21 was used in six of these studies.A number of randomised trials demonstrated no HRQoL changes between active treatment and placebo arms.The Phase III NETTER-1 study provides the best data available for advanced GEP-NET patients;it shows that peptide receptor radionuclide therapy can significantly improve GEP-NET patients’HRQoL.CONCLUSION HRQoL instruments offer a means to monitor patients’general disease condition,disease progression and their physical and mental well-being.Instruments including the commonly used European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and GINET21 lack,however,validation and a defined minimal clinical important difference specifically for GINET and P-NET patients.
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.
文摘Recently,biological drugs have played a leading role in the treatment of inflammatory bowel disease,and therapeutic drug monitoring(TDM)may be useful in maximizing their effectiveness.TDM involves the measurement of serum drug and anti-drug antibodies concentrations as the basis for dosage adjustments or drug conversions to achieve a higher response rate.We believe that concentration thresholds should be individualized based on patients’disease severity,extent and phenotype,and therapeutic purposes should also be considered,with higher cut-offs mainly needed for endoscopic and fistula healing than for symptomatic remission.Proactive and reactive TDM can help optimize treatment,especially in patients receiving anti-tumour necrosis factor,and guide dose adjustment or drug conversion with lower cost.TDM is a promising approach to achieve precision medicine and targeted medicine in the future.
文摘Background:Concerns exist regarding the potential development of tuberculosis in patients with rheumatoid arthritis(RA)treated with biological and targeted drugs.We assessed systematically whether biological therapy increased the risk of tuberculosis in patients with RA by meta-analysis of randomized controlled trials(RCTs).Methods:A systematic literature search was conducted in PubMed,Embase,the Cochrane Library,and China Biology Medicine disc for RCTs evaluating biological therapy in patients with RA from inception through August 2021.Traditional meta-analysis and network meta-analysis were performed to compare the risk of tuberculosis for each biologics class in patients with RA.Peto odds ratio(Peto OR)and its 95%confidence interval(CI)were calculated as the primary effect measure.Results:In total,39 studies with 20,354 patients were included in this meta-analysis,and 82 patients developed tuberculosis.The risk of tuberculosis was increased in patients treated with biologics compared with non-biologics(Peto OR:3.86,95%CI:2.36-6.32,P<0.001).Also,tumor necrosis factor-α(TNF-α)inhibitors had a higher probability of developing tuberculosis than placebo(Peto OR:3.98,95%CI:2.30-6.88,P<0.001).However,network meta-analysis demonstrated that there was no significant difference in the risk of tuberculosis for each biologics class in patients with RA.Noticeably,tuberculosis was significantly more common in patients treated with a high dose compared with patients receiving a low dose of tofacitinib(Peto OR:7.39,95%CI:2.00-27.31,P=0.003).Conclusion:This meta-analysis demonstrates the evidence of an elevated risk of tuberculosis in patients with RA treated with TNF-αinhibitors,and a dose-dependent elevated risk of tuberculosis in patients treated with tofacitinib.
文摘Background: Concerns exist regarding the risk of infections in patients with spondyloarthritis (SpA) treated with biologics. We assessed the risk of infections of biological and targeted drugs in patients with SpA by performing a meta-analysis based on randomized controlled trials (RCTs).Methods: A systematic literature search was conducted in PubMed, Embase, Web of Science, the Cochrane Library, and China Biology Medicine Disc for RCTs evaluating the risk of infections of biological therapy in patients with SpA from inception through August 9, 2021. We calculated a pooled Peto odds ratio (OR) for infections in biologics-treated patientsvs. placebo patients. The risk of bias on the included RCTs was assessed by using the Cochrane Risk of Bias Tool.Results: In total, 62 studies were included in this meta-analysis. Overall, the risk of infection (Peto OR: 1.16, 95% confidence interval [CI]: 1.07-1.26,P < 0.001), serious infection (Peto OR: 1.65, 95% CI: 1.26-2.17,P < 0.001), upper respiratory tract infection (URTI) (Peto OR: 1.17, 95% CI: 1.04-1.32,P = 0.008), nasopharyngitis (Peto OR: 1.25, 95% CI: 1.10-1.42,P < 0.001), andCandida infection (Peto OR: 2.64, 95% CI: 1.48-4.71,P = 0.001) were increased in SpA patients treated with biologics compared with placebo. Sensitivity analysis based on biologics classes was conducted, and results demonstrated that compared with placebo, there was a higher risk of infection for tumor necrosis factor (TNF)-α inhibitors (Peto OR: 1.38, 95% CI: 1.13-1.68,P = 0.001) and interleukin (IL)-17 inhibitors (Peto OR: 1.55, 95% CI: 1.08-2.22,P = 0.018) in axial SpA, and for Janus kinase inhibitors in peripheral SpA (Peto OR: 1.39, 95% CI: 1.14-1.69,P = 0.001);higher risk of serious infection for IL-17 inhibitors in peripheral SpA (Peto OR: 3.46, 95% CI: 1.26-9.55,P = 0.016) and axial SpA (Peto OR: 2.01, 95% CI: 1.38-2.91,P < 0.001);higher risk of URTI for TNF-α inhibitors in axial SpA (Peto OR: 1.37, 95% CI: 1.05-1.78,P= 0.019), and for apremilast in peripheral SpA (Peto OR: 1.60, 95% CI: 1.08-2.36,P = 0.018);higher risk of nasopharyngitis for TNF-α inhibitors in axial SpA (Peto OR: 1.41, 95% CI: 1.05-1.90,P = 0.022) and peripheral SpA (Peto OR: 1.49, 95% CI: 1.09-2.05,P = 0.013), and for IL-17 inhibitors in axial SpA (Peto OR: 1.35, 95% CI: 1.01-1.82,P = 0.044);higher risk of herpes zoster for Janus kinase inhibitors in peripheral SpA (Peto OR: 2.18, 95% CI: 1.03-4.62,P = 0.043);higher risk ofCandida infection for IL-17 inhibitors in peripheral SpA (Peto OR: 2.52, 95% CI: 1.31-4.84,P= 0.006).Conclusions: This meta-analysis shows that biological therapy in patients with SpA may increase the risk of infections, including serious infections, URTI, nasopharyngitis, andCandida infection, which should be paid attention to in our clinical practice.
