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
BACKGROUND Oral 5-aminosalicylic acid(5-ASA)has been a cornerstone treatment for mild to moderate ulcerative colitis(UC),traditionally used to maintain remission.With the rise of advanced therapies(biologics and small...BACKGROUND Oral 5-aminosalicylic acid(5-ASA)has been a cornerstone treatment for mild to moderate ulcerative colitis(UC),traditionally used to maintain remission.With the rise of advanced therapies(biologics and small molecules),the role of 5-ASA has come under renewed scrutiny.While earlier systematic reviews affirmed its efficacy compared to placebo,these did not account for the advent of advanced therapies.AIM To assess the efficacy and safety of oral 5-ASA in maintaining remission in quiescent UC,compared to placebo,alternative 5-ASA formulations,and advanced therapies,in the era of biologics and small molecules.METHODS It was systematically searched MEDLINE,EMBASE,and the Cochrane Library,alongside conference proceedings(European Crohn’s and Colitis Organisation,British Society of Gastroenterology),for randomized controlled trials published between 2003 and 2024 in English.Eligible studies involved oral 5-ASA therapies for quiescent UC with a minimum treatment duration of six months.Outcomes included failure to maintain remission,adverse events,and serious adverse events(SAEs).Data were analyzed using Cochrane methods,with GRADE assessing evidence certainty.RESULTS From 44 studies(9967 participants),5-ASA was superior to placebo in maintaining remission,with 37%of 5-ASA users relapsing at 6-12 months compared to 55%of placebo users[risk ratios(RR):0.68;95%CI:0.61-0.76;high-certainty evidence].SAEs were rare and comparable between groups(RR:0.60;95%CI:0.19-1.84;low-certainty evidence).Comparative analyses suggested 5-ASA remains a viable option alongside advanced therapies,with notable differences in cost and safety profiles.CONCLUSION 5-ASA remains effective and safe for maintaining remission in quiescent UC,even in the advanced therapy era.However,tailored approaches are needed to balance efficacy,safety,and cost in clinical practice.This study provides critical insights to guide therapeutic strategies and underscores the enduring relevance of 5-ASA.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
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
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
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
Therapeutic drug monitoring(TDM)has emerged as a valuable tool for optimizing the use of biologics in inflammatory bowel disease(IBD).However,variations in focus,methodology,and recommendations among relevant guidelin...Therapeutic drug monitoring(TDM)has emerged as a valuable tool for optimizing the use of biologics in inflammatory bowel disease(IBD).However,variations in focus,methodology,and recommendations among relevant guidelines and consensuses have contributed to inconsistencies in their quality.This guideline synthesizes current evidence to standardize TDM of biologics in IBD,and improve patient outcomes.This multidisciplinary guideline was developed in collaboration with pharmacy,gastroenterology,and pharmacology associations in China.The guideline development group included 9 experts in clinical pharmacy,4 experts in TDM,8 gastroenterologists,and 2 methodologists.A comprehensive search was conducted across PubMed,Embase,Web of Science,the Cochrane Library databases,as well as key gastroenterology-relevant guideline websites.The Grading of Recommendations,Assessment,Development,and Evaluation(GRADE)approach was utilized,and this guideline was registered on the Guideline International Network website.Internal and external reviews were conducted.We proposed 5 clinical questions under two overarching themes.Based on the current evidence and the clinical opinions of the core working group members,the initial recommendations were made.Following comprehensive internal and external review processes,14 recommendations(1 strong and 13 weak)were finalized for the clinical questions.To our knowledge,this is the first evidence-based clinical practice guideline on TDM in patients with IBD developed using the GRADE approach.It addresses five key questions:whether TDM leads to better therapeutic outcomes than conventional treatment,what indicators should be monitored,when TDM should be initiated,what the therapeutic drug trough concentration thresholds are,and which TDM method(proactive or reactive)can better improve therapeutic outcomes.展开更多
Bone fractures represent a significant global healthcare burden.Although fractures typically heal on their own,some fail to regenerate properly,leading to nonunion,a condition that causes prolonged disability,morbidit...Bone fractures represent a significant global healthcare burden.Although fractures typically heal on their own,some fail to regenerate properly,leading to nonunion,a condition that causes prolonged disability,morbidity,and mortality.The challenge of treating nonunion fractures is further complicated in patients with underlying bone disorders where systemic and local factors impair bone healing.Traditional treatment approaches,including autografts,allografts,xenografts,and synthetic biomaterials,face limitations such as donor site pain,immune rejection,and insufficient mechanical strength,underscoring the need for alternative strategies.Biologic therapies have emerged as promising tools to enhance bone regeneration by leveraging the body’s natural healing processes.This review explores the critical role of conventional and emerging biologics in fracture healing.We categorize biologic therapies into protein-based treatments,gene and transcript therapies,small molecules,peptides,and cell-based therapies,highlighting their mechanisms of action,advantages,and clinical relevance.Finally,we examine the potential applications of biologics in treating fractures associated with bone disorders such as osteoporosis,osteogenesis imperfecta,rickets,osteomalacia,Paget’s disease,and bone tumors.By integrating biologic therapies with existing biomaterial-based strategies,these innovative approaches have the potential to transform clinical management and improve outcomes for patients with difficult-to-heal fractures.展开更多
In the pre-biologic era,immunomodulators such as azathioprine,6-mercaptopurine,and methotrexate(MTX)were widely used as first-line maintenance therapies in Crohn’s disease.However,in the current era shaped by biologi...In the pre-biologic era,immunomodulators such as azathioprine,6-mercaptopurine,and methotrexate(MTX)were widely used as first-line maintenance therapies in Crohn’s disease.However,in the current era shaped by biologics,their role has shifted toward adjunctive use,primarily in combination with anti-tumor necrosis factor agents to reduce immunogenicity.Amid growing concerns about thiopurine-associated risks,MTX is receiving renewed attention for its favorable safety profile;however,this agent remains inconsistently utilized in gastroenterology despite its frontline status in rheumatology.This discrepancy was highlighted in a recent nationwide survey by Bonnaud et al published in the World Journal of Gastroenterology,which offers timely insights into MTX prescribing behaviors among French gastroenterologists.Although 71%of respondents reported using MTX,primarily via subcutaneous injection,it is still perceived as a secondary choice after thiopurines.Importantly,this underuse appears to be driven more by clinical inertia and limited guidance rather than by lack of efficacy or safety concerns.Clinicians increasingly recognize the value of MTX,particularly in patients with joint involvement,Epstein-Barr virus negativity,or increased malignancy risk.Notably,even non-prescribers viewed the drug favorably,suggesting that usage barriers may be modifiable.In light of evolving treatment goals that prioritize safety,cost-effectiveness,and individualized care,this editorial argues that MTX should no longer be viewed as a fallback but as a strategic first-line option in well-defined high-risk populations.The survey underscores a persistent gap between guidelines and real-world practice,reinforcing the urgent need for clearer algorithms and education to support the repositioning of MTX in modern Crohn’s disease management.展开更多
The significance of patient-reported outcomes（PROs） is increasingly being acknowledged and quality of life（QOL） has become an integral element of the assessment of overall burden of disease.Psoriasis has been know...The significance of patient-reported outcomes（PROs） is increasingly being acknowledged and quality of life（QOL） has become an integral element of the assessment of overall burden of disease.Psoriasis has been known for its major impact on patients＇ QOL and various generic,dermatology-specific and psoriasis-specific self- administered psychometric instruments have been used over the years to assess the QOL of psoriasis patients.However,the Dermatology Life Quality Index（DLQI） is the most widely used QOL measure among these measures in psoriasis-related clinical trials. A number of topical and systemic treatments have been used in the management of psoriasis and lately biologics have emerged as a new and promising treatment modality for difficuIt-to-treat psoriasis.The evidence on the efficacy of these agents has been growing dramatically with QOL being used as one of the primary outcome measures in many clinical trials.The aim of this paper is to give an overview of the use of the DLQI as an outcome measure for assessing the QOL impact of biologies on psoriasis patients.Furthermore,the efficacy of five commonly used biologics has been compared in terms of their ability to improve the QOL assessed by the DLQI.This review has revealed that there is a variation in the efficacy of various biologies in terms of QOL improvement with the mean reduction in the DLQI scores being highest for ustekinumab 90 mg（mean DLQI score reduction=9.5）,followed by infliximab（8.5）,etanercept 50 mg,twice a week（7.7）,adalimumab（6.3）,and alefacept（4.0）.展开更多
Atopic dermatitis(AD)is a complex disease characterized by recurrent eczematous lesions and refractory pruritus that drastically impairs quality of life.Due to the chronic and relapsing course,patients are easily trap...Atopic dermatitis(AD)is a complex disease characterized by recurrent eczematous lesions and refractory pruritus that drastically impairs quality of life.Due to the chronic and relapsing course,patients are easily trapped in the debilitating condition.Classical therapies show limitations,especially for patients with moderate-to-severe phenotypes.Advanced new insights in targeted therapies exhibit great application prospects which were reinforced by the more profound understanding of the disease pathogenesis.However,the sustained efficiency,biosafety,and long-term benefits still remain in further exploration.This review summarizes recent clinical studies on oral small-molecule inhibitors and biological agents for pediatric AD patients,which provides the latest frontiers to clinicians.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BACKGROUND Oral 5-aminosalicylic acid(5-ASA)has been a cornerstone treatment for mild to moderate ulcerative colitis(UC),traditionally used to maintain remission.With the rise of advanced therapies(biologics and small molecules),the role of 5-ASA has come under renewed scrutiny.While earlier systematic reviews affirmed its efficacy compared to placebo,these did not account for the advent of advanced therapies.AIM To assess the efficacy and safety of oral 5-ASA in maintaining remission in quiescent UC,compared to placebo,alternative 5-ASA formulations,and advanced therapies,in the era of biologics and small molecules.METHODS It was systematically searched MEDLINE,EMBASE,and the Cochrane Library,alongside conference proceedings(European Crohn’s and Colitis Organisation,British Society of Gastroenterology),for randomized controlled trials published between 2003 and 2024 in English.Eligible studies involved oral 5-ASA therapies for quiescent UC with a minimum treatment duration of six months.Outcomes included failure to maintain remission,adverse events,and serious adverse events(SAEs).Data were analyzed using Cochrane methods,with GRADE assessing evidence certainty.RESULTS From 44 studies(9967 participants),5-ASA was superior to placebo in maintaining remission,with 37%of 5-ASA users relapsing at 6-12 months compared to 55%of placebo users[risk ratios(RR):0.68;95%CI:0.61-0.76;high-certainty evidence].SAEs were rare and comparable between groups(RR:0.60;95%CI:0.19-1.84;low-certainty evidence).Comparative analyses suggested 5-ASA remains a viable option alongside advanced therapies,with notable differences in cost and safety profiles.CONCLUSION 5-ASA remains effective and safe for maintaining remission in quiescent UC,even in the advanced therapy era.However,tailored approaches are needed to balance efficacy,safety,and cost in clinical practice.This study provides critical insights to guide therapeutic strategies and underscores the enduring relevance of 5-ASA.
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.
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.
基金National Key Research and Development Program of China(grant number 2023YFF1205000).
文摘Therapeutic drug monitoring(TDM)has emerged as a valuable tool for optimizing the use of biologics in inflammatory bowel disease(IBD).However,variations in focus,methodology,and recommendations among relevant guidelines and consensuses have contributed to inconsistencies in their quality.This guideline synthesizes current evidence to standardize TDM of biologics in IBD,and improve patient outcomes.This multidisciplinary guideline was developed in collaboration with pharmacy,gastroenterology,and pharmacology associations in China.The guideline development group included 9 experts in clinical pharmacy,4 experts in TDM,8 gastroenterologists,and 2 methodologists.A comprehensive search was conducted across PubMed,Embase,Web of Science,the Cochrane Library databases,as well as key gastroenterology-relevant guideline websites.The Grading of Recommendations,Assessment,Development,and Evaluation(GRADE)approach was utilized,and this guideline was registered on the Guideline International Network website.Internal and external reviews were conducted.We proposed 5 clinical questions under two overarching themes.Based on the current evidence and the clinical opinions of the core working group members,the initial recommendations were made.Following comprehensive internal and external review processes,14 recommendations(1 strong and 13 weak)were finalized for the clinical questions.To our knowledge,this is the first evidence-based clinical practice guideline on TDM in patients with IBD developed using the GRADE approach.It addresses five key questions:whether TDM leads to better therapeutic outcomes than conventional treatment,what indicators should be monitored,when TDM should be initiated,what the therapeutic drug trough concentration thresholds are,and which TDM method(proactive or reactive)can better improve therapeutic outcomes.
基金performed as part of the cmRNAbone project funded by the European Union’s Horizon 2020 research and innovation program under the Grant Agreement No 874790。
文摘Bone fractures represent a significant global healthcare burden.Although fractures typically heal on their own,some fail to regenerate properly,leading to nonunion,a condition that causes prolonged disability,morbidity,and mortality.The challenge of treating nonunion fractures is further complicated in patients with underlying bone disorders where systemic and local factors impair bone healing.Traditional treatment approaches,including autografts,allografts,xenografts,and synthetic biomaterials,face limitations such as donor site pain,immune rejection,and insufficient mechanical strength,underscoring the need for alternative strategies.Biologic therapies have emerged as promising tools to enhance bone regeneration by leveraging the body’s natural healing processes.This review explores the critical role of conventional and emerging biologics in fracture healing.We categorize biologic therapies into protein-based treatments,gene and transcript therapies,small molecules,peptides,and cell-based therapies,highlighting their mechanisms of action,advantages,and clinical relevance.Finally,we examine the potential applications of biologics in treating fractures associated with bone disorders such as osteoporosis,osteogenesis imperfecta,rickets,osteomalacia,Paget’s disease,and bone tumors.By integrating biologic therapies with existing biomaterial-based strategies,these innovative approaches have the potential to transform clinical management and improve outcomes for patients with difficult-to-heal fractures.
文摘In the pre-biologic era,immunomodulators such as azathioprine,6-mercaptopurine,and methotrexate(MTX)were widely used as first-line maintenance therapies in Crohn’s disease.However,in the current era shaped by biologics,their role has shifted toward adjunctive use,primarily in combination with anti-tumor necrosis factor agents to reduce immunogenicity.Amid growing concerns about thiopurine-associated risks,MTX is receiving renewed attention for its favorable safety profile;however,this agent remains inconsistently utilized in gastroenterology despite its frontline status in rheumatology.This discrepancy was highlighted in a recent nationwide survey by Bonnaud et al published in the World Journal of Gastroenterology,which offers timely insights into MTX prescribing behaviors among French gastroenterologists.Although 71%of respondents reported using MTX,primarily via subcutaneous injection,it is still perceived as a secondary choice after thiopurines.Importantly,this underuse appears to be driven more by clinical inertia and limited guidance rather than by lack of efficacy or safety concerns.Clinicians increasingly recognize the value of MTX,particularly in patients with joint involvement,Epstein-Barr virus negativity,or increased malignancy risk.Notably,even non-prescribers viewed the drug favorably,suggesting that usage barriers may be modifiable.In light of evolving treatment goals that prioritize safety,cost-effectiveness,and individualized care,this editorial argues that MTX should no longer be viewed as a fallback but as a strategic first-line option in well-defined high-risk populations.The survey underscores a persistent gap between guidelines and real-world practice,reinforcing the urgent need for clearer algorithms and education to support the repositioning of MTX in modern Crohn’s disease management.
文摘The significance of patient-reported outcomes（PROs） is increasingly being acknowledged and quality of life（QOL） has become an integral element of the assessment of overall burden of disease.Psoriasis has been known for its major impact on patients＇ QOL and various generic,dermatology-specific and psoriasis-specific self- administered psychometric instruments have been used over the years to assess the QOL of psoriasis patients.However,the Dermatology Life Quality Index（DLQI） is the most widely used QOL measure among these measures in psoriasis-related clinical trials. A number of topical and systemic treatments have been used in the management of psoriasis and lately biologics have emerged as a new and promising treatment modality for difficuIt-to-treat psoriasis.The evidence on the efficacy of these agents has been growing dramatically with QOL being used as one of the primary outcome measures in many clinical trials.The aim of this paper is to give an overview of the use of the DLQI as an outcome measure for assessing the QOL impact of biologies on psoriasis patients.Furthermore,the efficacy of five commonly used biologics has been compared in terms of their ability to improve the QOL assessed by the DLQI.This review has revealed that there is a variation in the efficacy of various biologies in terms of QOL improvement with the mean reduction in the DLQI scores being highest for ustekinumab 90 mg（mean DLQI score reduction=9.5）,followed by infliximab（8.5）,etanercept 50 mg,twice a week（7.7）,adalimumab（6.3）,and alefacept（4.0）.
文摘Atopic dermatitis(AD)is a complex disease characterized by recurrent eczematous lesions and refractory pruritus that drastically impairs quality of life.Due to the chronic and relapsing course,patients are easily trapped in the debilitating condition.Classical therapies show limitations,especially for patients with moderate-to-severe phenotypes.Advanced new insights in targeted therapies exhibit great application prospects which were reinforced by the more profound understanding of the disease pathogenesis.However,the sustained efficiency,biosafety,and long-term benefits still remain in further exploration.This review summarizes recent clinical studies on oral small-molecule inhibitors and biological agents for pediatric AD patients,which provides the latest frontiers to clinicians.
