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
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 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
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
Our increase in knowledge of the pathophysiology of non-infectious uveitis(NIU)and other immune-mediated diseases has been mirrored over the last two decades by the expansion of therapeutic options in the realm of imm...Our increase in knowledge of the pathophysiology of non-infectious uveitis(NIU)and other immune-mediated diseases has been mirrored over the last two decades by the expansion of therapeutic options in the realm of immunosuppressive medications.Principal among these advances is the emergence of biologics,which offer the promise of targeted therapy and the hope of reduced toxicity when compared to corticosteroids and“standard”immunosuppression.Among the biologics,monoclonal antibodies blocking tumor necrosis factor alpha(TNF-α)have been shown to be a very effective therapeutic target for uveitis and many associated systemic inflammatory diseases.Multiple TNF blockers have shown benefit for uveitis,and in 2016,adalimumab became the first biologic and non-corticosteroid immunosuppressive to obtain Food and Drug Administration(FDA)approval in the treatment of NIU.Although effective,TNF blockers are not universally so,and safety concerns such as infection and demyelinating disease must be carefully considered and ruled out prior to their use,especially in patients with intermediate uveitis with which multiple sclerosis is a known association.Ongoing study has identified novel targets for regulation in the treatment of immune-mediated and inflammatory diseases.Interferons,interleukin and Janus kinase inhibitors in addition to antibodies targeting T cell and B cell activation highlight the expanding field of treatment modalities in NIU.Ongoing study will be required to better determine the safety and efficacy of biologics in the armamentarium of immunosuppressive treatments for NIU.展开更多
A 46-year-old female patient with terminal ileum Crohn’s disease and ankylosing spondylitis presented with recurrent angioedema and urticaria. Investigations ruled out hereditary angioedema, and environmental or food...A 46-year-old female patient with terminal ileum Crohn’s disease and ankylosing spondylitis presented with recurrent angioedema and urticaria. Investigations ruled out hereditary angioedema, and environmental or food allergen triggers. She was diagnosed with chronic idiopathic urticaria with angioedema, and was treated with a trial of intravenous immunoglobulin immunotherapy, danazol, prednisone and hydroxyzine. Due to ongoing bowel and arthritic complaints, she was started on infliximab infusions and within 2 treatments, she had complete resolution of the angioedema and urticaria, as well as of the bowel and arthritic symptoms. Unfortunately she developed allergic reactions to the infliximab and was switched to another anti-tumor necrosis factor （TNF）-a agent, adalimumab. Since then, she has had no further angioedema or urticaria, and her Crohn’s disease has been quiescent. This is the first known case report of chronic idiopathic urticaria with angioedema coexistent with Crohn’s disease that was successfully treated with anti-TNF-α agents.展开更多
Hepatitis B virus reactivation(HBVr)can occur in patients treated with immunosuppressive medications.Risk stratification for HBVr based on hepatitis B virus(HBV)serology and viral load is an important strategy to dete...Hepatitis B virus reactivation(HBVr)can occur in patients treated with immunosuppressive medications.Risk stratification for HBVr based on hepatitis B virus(HBV)serology and viral load is an important strategy to determine appropriate HBV monitoring and antiviral prophylaxis use.Recent advances in the understanding of pathophysiology of autoimmune diseases have led the development of cytokine-targeted therapies.Tumor necrosis factor(TNF)-αinhibitors have been widely used for patients with inflammatory bowel disease,psoriasis,and rheumatic diseases.Further,the clinical benefits of interleukin(IL)-12/23,IL-17,or Janus kinases inhibitors have been demonstrated in these patients.It is well known that TNF-αinhibitor use can lead to HBVr,however,the risk of HBVr in patients undergoing non-TNF-targeted biologics have not been fully understood.In this review,we discuss the risk of HBVr in patients treated with non-TNF-targeted biologics,and immunological mechanisms of these medications causing HBVr.展开更多
Corticosteroids and immunomodulators have been the mainstay therapies for Crohn’s disease. Corticosteroids are highly effective to control symptoms in the short- term, but they are not effective in maintaining remiss...Corticosteroids and immunomodulators have been the mainstay therapies for Crohn’s disease. Corticosteroids are highly effective to control symptoms in the short- term, but they are not effective in maintaining remission, they heal the mucosa in a reduced proportion of cases, and long-time exposure is associated with an increased risk of infections and mortality. Immunomodulators, azathioprine and methotrexate, heal the mucosa in a higher proportion of patients that corticosteroids but their onset of action is slow and they benefit less than half of patients with Crohn’s disease. In the last decade, medical therapy for Crohn’s disease has experienced a remarkable change due to the introduction of biologic therapy, and particularly the use of anti-tumour necrosis factor-alpha agents. Infliximab, adalimumab, and certolizumab pegol have demonstrated efficacy for induction and maintenance of remission in active Crohn’s disease. These agents have raised the bar for what is a suitable symptomatic response in Crohn’s disease and modification of the natural history of the disease has become a major goal in the treatment of Crohn’s disease. There are several data in the literature that suggest that early use of biologic therapy and achievement of mucosal healing contribute to disease course modification. However, many questions on early biological therapy for Crohn’s disease remain still unanswered.展开更多
Inflammatory bowel disease(IBD)is a group of chronic diseases that includes ulcerative colitis,Crohn’s disease,and indeterminate colitis.Patients with IBD require prolonged treatment and high utilization of healthcar...Inflammatory bowel disease(IBD)is a group of chronic diseases that includes ulcerative colitis,Crohn’s disease,and indeterminate colitis.Patients with IBD require prolonged treatment and high utilization of healthcare resources for proper management.The treatment of patients with IBD is focused on achieving therapeutic goals including clinical,biochemical,and endoscopic variables that result in improvement of the quality of life and prevention of disability.Advanced IBD treatment includes tumor necrosis factor inhibitors,integrin antagonist,antagonist of the p40 subunit of interleukin 12/23,and small molecule drugs.However,despite the multiple treatments available,about 40%of patients are refractory to therapy and present with persistent symptoms that have a great impact on their quality of life,with hospitalization and surgery being necessary in many cases.Dual therapy,a strategy sometimes applicable to refractory IBD patients,includes the combination of two biologics or a biologic in combination with a small molecule drug.There are two distinct scenarios in IBD patients in which this approach can be used:(1)Refractory active luminal disease without extraintestinal manifestations;and(2)patients with IBD in remission,but with active extraintestinal manifestations or immune-mediated inflammatory diseases.This review provides a summary of the results(clinical response and remission)of different combinations of advanced drugs in patients with IBD,both in adults and in the pediatric population.In addition,the safety profile of different combinations of dual therapy is analyzed.The use of newer combinations,including recently approved treatments,the application of new biomarkers and artificial intelligence,and clinical trials to establish effectiveness during long-term followup,are needed to establish new strategies for the use of advanced treatments in patients with refractory IBD.展开更多
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
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
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
Objective:Psoriasis is a chronic inflammatory systemic disease that severely impacts patients’ quality of life (QoL) and psychological health.While biologics have been shown to be effective in treating psoriatic lesi...Objective:Psoriasis is a chronic inflammatory systemic disease that severely impacts patients’ quality of life (QoL) and psychological health.While biologics have been shown to be effective in treating psoriatic lesions,thus improving QoL,real-life data regarding such effects remain scant.We administered a repeated cross-sectional survey to assess the effects of 8 weeks of biologics treatment on the QoL and mental health status of patients with moderate-to-severe plaque psoriasis.Methods:From March to May 2022,patients with moderate-to-severe plaque psoriasis were enrolled and treated with biologics in the outpatient clinic at the Dermatology Hospital of Southern Medical University.Assessments were performed before treatment and after 4 and 8 weeks of treatment with biologics.Psoriasis severity,QoL,and mental health status were evaluated using the Psoriasis Area and Severity Index (PASI),Dermatology Life Quality Index (DLQI),36-Item Short-form Health Survey (SF-36),and Hospital Anxiety and Depression Scale (HADS).A multivariate generalized estimating equations (GEE) analysis was used to account for repeated measures and to determine the effects of treatment duration and type of biological agent on relevant indicators.Results:Among the 78 enrolled patients,the ranges of pretreatment scores were 4.6 to 46.8 for the PASI,1 to 30 for the DLQI,31.5 to 100.0 for the physical component score (PCS) of the SF-36,16.6 to 100.0 for the mental component score (MCS) of the SF-36,0 to 15 for the HADS-A,and 0 to 17 for the HADS-D.After 8 weeks of biologics treatment,98.7% (77/78) of patients had obtained PASI 75.All assessed scores changed over time (GEE,P < 0.001).Moreover,there were group-by-time interaction effects for the DLQI score (GEE,P = 0.023) and PCS (GEE,P = 0.029).The HADS-A and HADS-D scores were both decreased at week 8 compared with pretreatment values.Correlation analyses revealed that higher DLQI scores were associated with lower levels of QoL and higher levels of anxiety or depression.Conclusion:Biologics are not only effective in the treatment of skin lesions but also exert beneficial effects upon the QoL and mental health of patients with psoriasis as determined in the short-term assessments conducted in this study.展开更多
BACKGROUND Real-world data on tofacitinib(TOF)covering a period of more than 1 year for a sufficient number of Asian patients with ulcerative colitis(UC)are scarce.AIM To investigate the long-term efficacy and safety ...BACKGROUND Real-world data on tofacitinib(TOF)covering a period of more than 1 year for a sufficient number of Asian patients with ulcerative colitis(UC)are scarce.AIM To investigate the long-term efficacy and safety of TOF treatment for UC,including clinical issues.METHODS We performed a retrospective single-center observational analysis of 111 UC patients administered TOF at Hyogo Medical University as a tertiary inflammatory bowel disease center.All consecutive UC patients who received TOF between May 2018 and February 2020 were enrolled.Patients were followed up until August 2020.The primary outcome was the clinical response rate at week 8.Secondary outcomes included clinical remission at week 8,cumulative persistence rate of TOF administration,colectomy-free survival,relapse after tapering of TOF and predictors of clinical response at week 8 and week 48.RESULTS The clinical response and remission rates were 66.3%and 50.5%at week 8,and 47.1%and 43.5%at week 48,respectively.The overall cumulative clinical remission rate was 61.7%at week 48 and history of anti-tumor necrosis factor-alpha(TNF-α)agents use had no influence(P=0.25).The cumulative TOF persistence rate at week 48 was significantly lower in patients without clinical remission than in those with remission at week 8(30.9%vs 88.1%;P<0.001).Baseline partial Mayo Score was significantly lower in responders vs non-responders at week 8(odds ratio:0.61,95%confidence interval:0.45-0.82,P=0.001).Relapse occurred in 45.7%of patients after TOF tapering,and 85.7%of patients responded within 4 wk after re-increase.All 6 patients with herpes zoster(HZ)developed the infection after achieving remission by TOF.CONCLUSION TOF was more effective in UC patients with mild activity at baseline and its efficacy was not affected by previous treatment with anti-TNF-αagents.Most relapsed patients responded again after re-increase of TOF and nearly half relapsed after tapering off TOF.Special attention is needed for tapering and HZ.展开更多
The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to...The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.展开更多
Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a com...Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.展开更多
BACKGROUND Remarkable progress over the last decade has equipped clinicians with many options in the treatment of inflammatory bowel disease.Clinicians now have the unique opportunity to provide individualized treatme...BACKGROUND Remarkable progress over the last decade has equipped clinicians with many options in the treatment of inflammatory bowel disease.Clinicians now have the unique opportunity to provide individualized treatment that can achieve and sustain remission in many patients.However,issues of primary non-response(PNR)and secondary loss of response(SLOR)to non-tumour necrosis factor inhibitor(TNFi)therapies remains a common problem.Specific issues include the choice of optimization of therapy,identifying when dose optimization will recapture response,establishing optimal dose for escalation and when to switch therapy.AIM To explores the issues of PNR and SLOR to non-TNFi therapies.METHODS This review explores the current evidence and literature to elucidate management options in cases of PNR/SLOR.It will also explore potential predictors for response following SLOR/PNR to therapies including the role of therapeutic drug monitoring(TDM).RESULTS In the setting of PNR and loss of response to alpha-beta7-integrin inhibitors and interleukin(IL)-12 and IL-23 inhibitors dose optimization is a reasonable option to capture response.For Janus kinase inhibitors dose optimization can be utilized to recapture response with loss of response.CONCLUSION The role of TDM in the setting of advanced non-TNFi therapies to identify patients who require dose optimization and as a predictor for clinical remission is not yet established and this remains an area that should be addressed in the future.展开更多
This article discusses the literature review article by Pacheco et al published in July 2024;the authors provided good reviews of perianal Crohn’s disease(CD),and challenges faced by clinicians in the management.CD,c...This article discusses the literature review article by Pacheco et al published in July 2024;the authors provided good reviews of perianal Crohn’s disease(CD),and challenges faced by clinicians in the management.CD,characterized by its chronic and relapsing nature,is an idiopathic condition that can involve any segment of the gastrointestinal tract.Perianal disease impacts up to 40%of patients with CD,with perianal fistulas constituting up to 80%of perianal lesions.Perianal CD can be highly incapacitating and profoundly diminish the overall well-being of patients.The management focuses on controlling the perianal sepsis and treating luminal CD.Biologics are crucial to the treatment approach,and results have been encouraging.The surgery focuses on controlling the sepsis,with more definitive treatments being fistula surgery,fecal diversion,and proctectomy as the last resort.This manuscript briefly describes the burden of CD,the challenges posed by perianal CD,and the role of different treatment modalities from colorectal surgeon’s perspective.展开更多
BACKGROUND Previous studies in the pre-biological era showed an association of wrist inflammation in juvenile idiopathic arthritis(JIA)with progressive disease course,polyarticular involvement and failure of methotrex...BACKGROUND Previous studies in the pre-biological era showed an association of wrist inflammation in juvenile idiopathic arthritis(JIA)with progressive disease course,polyarticular involvement and failure of methotrexate treatment.AIM To describe features of JIA,associated with wrist arthritis.METHODS Data from about 753 JIA patients were included in this retrospective cohort study.The clinical and laboratory features of patients with and without wrist involvement were analyzed.RESULTS Wrist involvement was found in oligoarthritis(5.8%),RF(−)/RF(+)polyarthritis(44.9%/15.0%),enthesitis-related arthritis(17.7%),and systemic(58.6%)JIA categories.Unilateral wrist involvement was typical for oligoarthritis patients,bilateral involvement was either equal to that of unilateral involvement or was more frequent in other categories.Wrist arthritis was found to be associated with female sex,a low incidence of uveitis,and more indications of systemic inflammation,including elevated levels of C-reactive protein,erythrocyte sedimentation rate,and platelets,as well as involvement of the cervical spine,temporomandibular,shoulder,elbow,metacarpophalangeal,proximal interphalangeal,distal interphalangeal,hip,ankle,and tarsus arthritis.The number of patients with hip osteoarthritis and hip replacement was also higher.Wrist arthritis was associated with a lower probability of achieving remission[hazard ratio(HR)=1.3(95%CI:1.0-1.7),P=0.055],and a higher probability of being treated with biologics[HR=1.7(95%CI:1.3-2.10,P=0.00009)].CONCLUSION Wrist arthritis in JIA patients is a marker of a severe disease course,characterized by more intensive inflammation,unfavorable outcomes,and.requiring more intensive treatment with early administration of biologics.Close monitoring of wrist inflammation with ultrasound and MR assessment with early biological treatment might improve the outcomes.展开更多
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 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Our increase in knowledge of the pathophysiology of non-infectious uveitis(NIU)and other immune-mediated diseases has been mirrored over the last two decades by the expansion of therapeutic options in the realm of immunosuppressive medications.Principal among these advances is the emergence of biologics,which offer the promise of targeted therapy and the hope of reduced toxicity when compared to corticosteroids and“standard”immunosuppression.Among the biologics,monoclonal antibodies blocking tumor necrosis factor alpha(TNF-α)have been shown to be a very effective therapeutic target for uveitis and many associated systemic inflammatory diseases.Multiple TNF blockers have shown benefit for uveitis,and in 2016,adalimumab became the first biologic and non-corticosteroid immunosuppressive to obtain Food and Drug Administration(FDA)approval in the treatment of NIU.Although effective,TNF blockers are not universally so,and safety concerns such as infection and demyelinating disease must be carefully considered and ruled out prior to their use,especially in patients with intermediate uveitis with which multiple sclerosis is a known association.Ongoing study has identified novel targets for regulation in the treatment of immune-mediated and inflammatory diseases.Interferons,interleukin and Janus kinase inhibitors in addition to antibodies targeting T cell and B cell activation highlight the expanding field of treatment modalities in NIU.Ongoing study will be required to better determine the safety and efficacy of biologics in the armamentarium of immunosuppressive treatments for NIU.
文摘A 46-year-old female patient with terminal ileum Crohn’s disease and ankylosing spondylitis presented with recurrent angioedema and urticaria. Investigations ruled out hereditary angioedema, and environmental or food allergen triggers. She was diagnosed with chronic idiopathic urticaria with angioedema, and was treated with a trial of intravenous immunoglobulin immunotherapy, danazol, prednisone and hydroxyzine. Due to ongoing bowel and arthritic complaints, she was started on infliximab infusions and within 2 treatments, she had complete resolution of the angioedema and urticaria, as well as of the bowel and arthritic symptoms. Unfortunately she developed allergic reactions to the infliximab and was switched to another anti-tumor necrosis factor （TNF）-a agent, adalimumab. Since then, she has had no further angioedema or urticaria, and her Crohn’s disease has been quiescent. This is the first known case report of chronic idiopathic urticaria with angioedema coexistent with Crohn’s disease that was successfully treated with anti-TNF-α agents.
文摘Hepatitis B virus reactivation(HBVr)can occur in patients treated with immunosuppressive medications.Risk stratification for HBVr based on hepatitis B virus(HBV)serology and viral load is an important strategy to determine appropriate HBV monitoring and antiviral prophylaxis use.Recent advances in the understanding of pathophysiology of autoimmune diseases have led the development of cytokine-targeted therapies.Tumor necrosis factor(TNF)-αinhibitors have been widely used for patients with inflammatory bowel disease,psoriasis,and rheumatic diseases.Further,the clinical benefits of interleukin(IL)-12/23,IL-17,or Janus kinases inhibitors have been demonstrated in these patients.It is well known that TNF-αinhibitor use can lead to HBVr,however,the risk of HBVr in patients undergoing non-TNF-targeted biologics have not been fully understood.In this review,we discuss the risk of HBVr in patients treated with non-TNF-targeted biologics,and immunological mechanisms of these medications causing HBVr.
文摘Corticosteroids and immunomodulators have been the mainstay therapies for Crohn’s disease. Corticosteroids are highly effective to control symptoms in the short- term, but they are not effective in maintaining remission, they heal the mucosa in a reduced proportion of cases, and long-time exposure is associated with an increased risk of infections and mortality. Immunomodulators, azathioprine and methotrexate, heal the mucosa in a higher proportion of patients that corticosteroids but their onset of action is slow and they benefit less than half of patients with Crohn’s disease. In the last decade, medical therapy for Crohn’s disease has experienced a remarkable change due to the introduction of biologic therapy, and particularly the use of anti-tumour necrosis factor-alpha agents. Infliximab, adalimumab, and certolizumab pegol have demonstrated efficacy for induction and maintenance of remission in active Crohn’s disease. These agents have raised the bar for what is a suitable symptomatic response in Crohn’s disease and modification of the natural history of the disease has become a major goal in the treatment of Crohn’s disease. There are several data in the literature that suggest that early use of biologic therapy and achievement of mucosal healing contribute to disease course modification. However, many questions on early biological therapy for Crohn’s disease remain still unanswered.
文摘Inflammatory bowel disease(IBD)is a group of chronic diseases that includes ulcerative colitis,Crohn’s disease,and indeterminate colitis.Patients with IBD require prolonged treatment and high utilization of healthcare resources for proper management.The treatment of patients with IBD is focused on achieving therapeutic goals including clinical,biochemical,and endoscopic variables that result in improvement of the quality of life and prevention of disability.Advanced IBD treatment includes tumor necrosis factor inhibitors,integrin antagonist,antagonist of the p40 subunit of interleukin 12/23,and small molecule drugs.However,despite the multiple treatments available,about 40%of patients are refractory to therapy and present with persistent symptoms that have a great impact on their quality of life,with hospitalization and surgery being necessary in many cases.Dual therapy,a strategy sometimes applicable to refractory IBD patients,includes the combination of two biologics or a biologic in combination with a small molecule drug.There are two distinct scenarios in IBD patients in which this approach can be used:(1)Refractory active luminal disease without extraintestinal manifestations;and(2)patients with IBD in remission,but with active extraintestinal manifestations or immune-mediated inflammatory diseases.This review provides a summary of the results(clinical response and remission)of different combinations of advanced drugs in patients with IBD,both in adults and in the pediatric population.In addition,the safety profile of different combinations of dual therapy is analyzed.The use of newer combinations,including recently approved treatments,the application of new biomarkers and artificial intelligence,and clinical trials to establish effectiveness during long-term followup,are needed to establish new strategies for the use of advanced treatments in patients with refractory IBD.
基金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.
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.
文摘Objective:Psoriasis is a chronic inflammatory systemic disease that severely impacts patients’ quality of life (QoL) and psychological health.While biologics have been shown to be effective in treating psoriatic lesions,thus improving QoL,real-life data regarding such effects remain scant.We administered a repeated cross-sectional survey to assess the effects of 8 weeks of biologics treatment on the QoL and mental health status of patients with moderate-to-severe plaque psoriasis.Methods:From March to May 2022,patients with moderate-to-severe plaque psoriasis were enrolled and treated with biologics in the outpatient clinic at the Dermatology Hospital of Southern Medical University.Assessments were performed before treatment and after 4 and 8 weeks of treatment with biologics.Psoriasis severity,QoL,and mental health status were evaluated using the Psoriasis Area and Severity Index (PASI),Dermatology Life Quality Index (DLQI),36-Item Short-form Health Survey (SF-36),and Hospital Anxiety and Depression Scale (HADS).A multivariate generalized estimating equations (GEE) analysis was used to account for repeated measures and to determine the effects of treatment duration and type of biological agent on relevant indicators.Results:Among the 78 enrolled patients,the ranges of pretreatment scores were 4.6 to 46.8 for the PASI,1 to 30 for the DLQI,31.5 to 100.0 for the physical component score (PCS) of the SF-36,16.6 to 100.0 for the mental component score (MCS) of the SF-36,0 to 15 for the HADS-A,and 0 to 17 for the HADS-D.After 8 weeks of biologics treatment,98.7% (77/78) of patients had obtained PASI 75.All assessed scores changed over time (GEE,P < 0.001).Moreover,there were group-by-time interaction effects for the DLQI score (GEE,P = 0.023) and PCS (GEE,P = 0.029).The HADS-A and HADS-D scores were both decreased at week 8 compared with pretreatment values.Correlation analyses revealed that higher DLQI scores were associated with lower levels of QoL and higher levels of anxiety or depression.Conclusion:Biologics are not only effective in the treatment of skin lesions but also exert beneficial effects upon the QoL and mental health of patients with psoriasis as determined in the short-term assessments conducted in this study.
文摘BACKGROUND Real-world data on tofacitinib(TOF)covering a period of more than 1 year for a sufficient number of Asian patients with ulcerative colitis(UC)are scarce.AIM To investigate the long-term efficacy and safety of TOF treatment for UC,including clinical issues.METHODS We performed a retrospective single-center observational analysis of 111 UC patients administered TOF at Hyogo Medical University as a tertiary inflammatory bowel disease center.All consecutive UC patients who received TOF between May 2018 and February 2020 were enrolled.Patients were followed up until August 2020.The primary outcome was the clinical response rate at week 8.Secondary outcomes included clinical remission at week 8,cumulative persistence rate of TOF administration,colectomy-free survival,relapse after tapering of TOF and predictors of clinical response at week 8 and week 48.RESULTS The clinical response and remission rates were 66.3%and 50.5%at week 8,and 47.1%and 43.5%at week 48,respectively.The overall cumulative clinical remission rate was 61.7%at week 48 and history of anti-tumor necrosis factor-alpha(TNF-α)agents use had no influence(P=0.25).The cumulative TOF persistence rate at week 48 was significantly lower in patients without clinical remission than in those with remission at week 8(30.9%vs 88.1%;P<0.001).Baseline partial Mayo Score was significantly lower in responders vs non-responders at week 8(odds ratio:0.61,95%confidence interval:0.45-0.82,P=0.001).Relapse occurred in 45.7%of patients after TOF tapering,and 85.7%of patients responded within 4 wk after re-increase.All 6 patients with herpes zoster(HZ)developed the infection after achieving remission by TOF.CONCLUSION TOF was more effective in UC patients with mild activity at baseline and its efficacy was not affected by previous treatment with anti-TNF-αagents.Most relapsed patients responded again after re-increase of TOF and nearly half relapsed after tapering off TOF.Special attention is needed for tapering and HZ.
文摘The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.
文摘Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.
文摘BACKGROUND Remarkable progress over the last decade has equipped clinicians with many options in the treatment of inflammatory bowel disease.Clinicians now have the unique opportunity to provide individualized treatment that can achieve and sustain remission in many patients.However,issues of primary non-response(PNR)and secondary loss of response(SLOR)to non-tumour necrosis factor inhibitor(TNFi)therapies remains a common problem.Specific issues include the choice of optimization of therapy,identifying when dose optimization will recapture response,establishing optimal dose for escalation and when to switch therapy.AIM To explores the issues of PNR and SLOR to non-TNFi therapies.METHODS This review explores the current evidence and literature to elucidate management options in cases of PNR/SLOR.It will also explore potential predictors for response following SLOR/PNR to therapies including the role of therapeutic drug monitoring(TDM).RESULTS In the setting of PNR and loss of response to alpha-beta7-integrin inhibitors and interleukin(IL)-12 and IL-23 inhibitors dose optimization is a reasonable option to capture response.For Janus kinase inhibitors dose optimization can be utilized to recapture response with loss of response.CONCLUSION The role of TDM in the setting of advanced non-TNFi therapies to identify patients who require dose optimization and as a predictor for clinical remission is not yet established and this remains an area that should be addressed in the future.
文摘This article discusses the literature review article by Pacheco et al published in July 2024;the authors provided good reviews of perianal Crohn’s disease(CD),and challenges faced by clinicians in the management.CD,characterized by its chronic and relapsing nature,is an idiopathic condition that can involve any segment of the gastrointestinal tract.Perianal disease impacts up to 40%of patients with CD,with perianal fistulas constituting up to 80%of perianal lesions.Perianal CD can be highly incapacitating and profoundly diminish the overall well-being of patients.The management focuses on controlling the perianal sepsis and treating luminal CD.Biologics are crucial to the treatment approach,and results have been encouraging.The surgery focuses on controlling the sepsis,with more definitive treatments being fistula surgery,fecal diversion,and proctectomy as the last resort.This manuscript briefly describes the burden of CD,the challenges posed by perianal CD,and the role of different treatment modalities from colorectal surgeon’s perspective.
基金Supported by Ministry of Science and Higher Education of the Russian Federation,No.075-15-2022-301.
文摘BACKGROUND Previous studies in the pre-biological era showed an association of wrist inflammation in juvenile idiopathic arthritis(JIA)with progressive disease course,polyarticular involvement and failure of methotrexate treatment.AIM To describe features of JIA,associated with wrist arthritis.METHODS Data from about 753 JIA patients were included in this retrospective cohort study.The clinical and laboratory features of patients with and without wrist involvement were analyzed.RESULTS Wrist involvement was found in oligoarthritis(5.8%),RF(−)/RF(+)polyarthritis(44.9%/15.0%),enthesitis-related arthritis(17.7%),and systemic(58.6%)JIA categories.Unilateral wrist involvement was typical for oligoarthritis patients,bilateral involvement was either equal to that of unilateral involvement or was more frequent in other categories.Wrist arthritis was found to be associated with female sex,a low incidence of uveitis,and more indications of systemic inflammation,including elevated levels of C-reactive protein,erythrocyte sedimentation rate,and platelets,as well as involvement of the cervical spine,temporomandibular,shoulder,elbow,metacarpophalangeal,proximal interphalangeal,distal interphalangeal,hip,ankle,and tarsus arthritis.The number of patients with hip osteoarthritis and hip replacement was also higher.Wrist arthritis was associated with a lower probability of achieving remission[hazard ratio(HR)=1.3(95%CI:1.0-1.7),P=0.055],and a higher probability of being treated with biologics[HR=1.7(95%CI:1.3-2.10,P=0.00009)].CONCLUSION Wrist arthritis in JIA patients is a marker of a severe disease course,characterized by more intensive inflammation,unfavorable outcomes,and.requiring more intensive treatment with early administration of biologics.Close monitoring of wrist inflammation with ultrasound and MR assessment with early biological treatment might improve the outcomes.
