RESUMEN
BACKGROUND: Numerous studies have compared the efficacy of ustekinumab (UST) and anti-TNF agents [infliximab (IFX) or adalimumab(ADA)] in moderate to severe Crohn's disease (CD) patients. This study aims to compare the efficacy of UST, IFX, and ADA while differentiating between bio-naïve and bio-experienced patients, which is an underexplored aspect, particularly in Asia. METHODS: We conducted a retrospective multi-center study from 2012 to 2023, categorizing patients into bio-naïve and bio-experienced groups. We evaluated clinical remission rates after induction therapy and clinical outcomes, including CD-related hospitalization, intestinal resection, and drug discontinuation during maintenance therapy. RESULTS: Among the 214 bio-naïve CD patients, 60 received UST, 108 received IFX, and 46 received ADA. After 1:1 propensity score matching between UST and anti-TNF agents groups, 59 patients were analyzed in each group (45 in the IFX group and 14 in the ADA group). We found no significant differences in clinical remission rates (P = 0.071), CD-related hospitalization (P = 0.800), intestinal resection (P = 0.390), or drug discontinuation (P = 0.052) between the UST, IFX, and ADA groups in bio-naïve CD patients. In bio-experienced CD patients, with 35 in the UST group and 13 in the anti-TNF agents group, the UST group showed a lower risk of drug discontinuation (P = 0.004) than the anti-TNF agents group. CONCLUSIONS: This study suggests that UST, IFX, and ADA are equally effective in bio-naïve CD patients, while in bio-experienced patients, mostly with previous exposure to anti-TNF agents, UST may offer superior drug durability.
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Adalimumab , Enfermedad de Crohn , Infliximab , Inducción de Remisión , Ustekinumab , Humanos , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/cirugía , Adalimumab/uso terapéutico , Infliximab/uso terapéutico , Estudios Retrospectivos , Femenino , Masculino , Adulto , Ustekinumab/uso terapéutico , Resultado del Tratamiento , Fármacos Gastrointestinales/uso terapéutico , Persona de Mediana Edad , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Hospitalización/estadística & datos numéricos , Adulto JovenAsunto(s)
Psoriasis , Índice de Severidad de la Enfermedad , Ustekinumab , Uveítis , Humanos , Psoriasis/tratamiento farmacológico , Ustekinumab/uso terapéutico , Ustekinumab/efectos adversos , Femenino , Masculino , Persona de Mediana Edad , Uveítis/tratamiento farmacológico , Adulto , Factores de Riesgo , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab/uso terapéutico , Adalimumab/efectos adversos , Resultado del Tratamiento , Etanercept/uso terapéutico , Etanercept/efectos adversos , Medición de Riesgo , Fármacos Dermatológicos/uso terapéutico , Fármacos Dermatológicos/efectos adversos , Infliximab/uso terapéutico , Infliximab/efectos adversosRESUMEN
The mechanism underlying intestinal fibrosis, the main complication of inflammatory bowel disease (IBD), is not yet fully understood, and there is no therapy to prevent or reverse fibrosis. We evaluated, in in vitro cellular models, the ability of different classes of drugs currently used in IBD to counteract two pivotal processes of intestinal fibrosis, the differentiation of intestinal fibroblasts to activated myofibroblasts using CCD-18Co cells, and the epithelial-to-mesenchymal transition (EMT) of intestinal epithelial cells using Caco-2 cells (IEC), both being processes induced by transforming growth factor-ß1 (TGF-ß1). The drugs tested included mesalamine, azathioprine, methotrexate, prednisone, methylprednisolone, budesonide, infliximab, and adalimumab. The expression of fibrosis and EMT markers (collagen-I, α-SMA, pSmad2/3, occludin) was assessed by Western blot analysis and by immunofluorescence. Of the drugs used, only prednisone, methylprednisolone, budesonide, and adalimumab were able to antagonize the pro-fibrotic effects induced by TGF-ß1 on CCD-18Co cells, reducing the fibrosis marker expression. Methylprednisolone, budesonide, and adalimumab were also able to significantly counteract the TGF-ß1-induced EMT process on Caco-2 IEC by increasing occludin and decreasing α-SMA expression. This is the first study that evaluates, using in vitro cellular models, the direct antifibrotic effects of drugs currently used in IBD, highlighting which drugs have potential antifibrotic effects.
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Budesonida , Transición Epitelial-Mesenquimal , Fibrosis , Enfermedades Inflamatorias del Intestino , Factor de Crecimiento Transformador beta1 , Humanos , Células CACO-2 , Transición Epitelial-Mesenquimal/efectos de los fármacos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/patología , Enfermedades Inflamatorias del Intestino/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Budesonida/farmacología , Adalimumab/farmacología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Metilprednisolona/farmacología , Mesalamina/farmacología , Prednisona/farmacología , Miofibroblastos/efectos de los fármacos , Miofibroblastos/metabolismo , Antiinflamatorios/farmacología , Infliximab/farmacología , Infliximab/uso terapéutico , Azatioprina/farmacología , Metotrexato/farmacología , Intestinos/efectos de los fármacos , Intestinos/patología , Diferenciación Celular/efectos de los fármacosRESUMEN
Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, is a chronic condition characterized by relapsing and remitting inflammation of the gastrointestinal tract. The pathogenesis involves a complex interplay of genetic, environmental, and immune factors. Treatment paradigms have evolved significantly over the past few decades, with the introduction of biologics, particularly anti-TNF (tumor necrosis factor) agents, marking a significant advancement. Anti-TNF therapies, including infliximab, adalimumab, golimumab, and certolizumab pegol, have efficacy in inducing and maintaining remission, promoting mucosal healing, and improving the quality of life in moderate to severe IBD patients. The early and appropriate use of these agents can mitigate disease progression and reduce the dependency on corticosteroids, enhancing long-term patient outcomes. Nevertheless, these therapies are expensive and are associated with potential adverse effects, including increased risk of infections and malignancies. This review discusses the mechanisms, clinical efficacy, safety profiles, and therapeutic positioning of anti-TNF agents in IBD management, integrating current Korean treatment guidelines.
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Anticuerpos Monoclonales Humanizados , Productos Biológicos , Enfermedades Inflamatorias del Intestino , Factor de Necrosis Tumoral alfa , Humanos , Adalimumab/uso terapéutico , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Certolizumab Pegol/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/patología , Infliximab/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: The optimal infliximab dose intensification strategy to address loss of response associated with subtherapeutic infliximab trough levels remains uncertain, as does whether post-intensification trough and treatment targets should influence this decision. OBJECTIVES: This pharmacokinetic simulation study aimed to identify infliximab dose intensification strategies capable of achieving post-intensification infliximab trough thresholds associated with clinical and objective treatment targets in Crohn's disease and ulcerative colitis. METHODS: A validated pharmacokinetic infliximab model, applied to 200 simulated patients, identified those with subtherapeutic (< 3.00 mg/L) trough levels after 30 weeks of standard (5 mg/kg 8-weekly) dosing, and subsequently applied 10 dose intensification strategies over a further 32 weeks. The proportion of simulations achieving 32-week post-intensification infliximab trough levels associated with endoscopic remission (ulcerative colitis > 7.50 mg/L, Crohn's disease > 9.70 mg/L) was the primary outcome, with perianal fistula healing (Crohn's disease > 10.10 mg/L) and clinical improvement (ulcerative colitis > 3.70 mg/L, Crohn's disease > 7.00mg/L) evaluated as secondary outcomes. All outcomes were stratified by intensity of dose intensification, with standard (≤ 10 mg/kg 8-weekly or 5 mg/kg 4-weekly; n = 5) and intensive (> 10 mg/kg 8-weekly or 5 mg/kg 4-weekly; n = 5) dosing strategies defined, respectively. RESULTS: The median pre-intensification infliximab trough level was 0.91 mg/L (interquartile range 1.37). Intensive dosing strategies were more likely to achieve infliximab trough concentrations associated with endoscopic remission (ulcerative colitis 36.48% vs. 10.80%, Crohn's disease 25.98 vs. 4.68%), perianal fistula healing (24.52% vs. 4.36%) and clinical improvement (ulcerative colitis 61.90% vs. 34.86%, Crohn's disease 40.32 vs. 12.08%) than standard intensification strategies (all p < 0.01). When controlling for cumulative (mg/kg) infliximab dose over 32 weeks, strategies that concurrently dose increased and interval shortened achieved the highest infliximab trough levels (all p < 0.01). CONCLUSION: This simulation-based analysis highlights the potential of using post-intensification infliximab trough thresholds associated with aspirational treatment targets in Crohn's disease and ulcerative colitis to guide choice of infliximab dose intensification strategy. Intensive dose intensification strategies, particularly those that concurrently dose increase and interval shorten, appear to achieve higher infliximab levels than standard dose intensification strategies. This may be particularly important in the pursuit of stringent endpoints, such as endoscopic remission and fistula healing, which have been consistently associated with higher infliximab trough levels. These findings require validation across real-world cohorts.
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Colitis Ulcerosa , Enfermedad de Crohn , Infliximab , Infliximab/farmacocinética , Infliximab/administración & dosificación , Infliximab/uso terapéutico , Humanos , Enfermedad de Crohn/tratamiento farmacológico , Colitis Ulcerosa/tratamiento farmacológico , Fármacos Gastrointestinales/farmacocinética , Fármacos Gastrointestinales/administración & dosificación , Fármacos Gastrointestinales/uso terapéutico , Relación Dosis-Respuesta a Droga , Simulación por Computador , Adulto , Masculino , Resultado del Tratamiento , Femenino , Enfermedades Inflamatorias del Intestino/tratamiento farmacológicoRESUMEN
BACKGROUND: Pemphigus vulgaris (PV) is a potentially life-threatening mucocutaneous autoimmune disease that affects desmoglein-1 and desmoglein-3, leading to intraepithelial vesiculobullous lesions. In the oral mucosa, PV lesions can mimic other diseases such as mucous membrane pemphigoid, other forms of pemphigus, recurrent aphthous stomatitis, erythema multiforme, Stevens-Johnson syndrome, and virus-induced ulcers like herpes simplex virus (HSV), making diagnosis challenging. The co-occurrence of PV with Crohn's disease is rare and predominantly seen in younger patients. The therapeutic mainstay for both PV and Crohn's disease usually involves systemic corticosteroids combined with immunosuppressants and immunobiological drugs. Literature indicates that the use of these drugs, particularly TNF-alpha inhibitors, for managing autoimmune diseases like Crohn's can potentially induce other autoimmune diseases known as autoimmune-like syndromes, which include episodes of lupus-like syndrome and inflammatory neuropathies. There are few cases in the literature reporting the development of PV in individuals with CD undergoing infliximab therapy. CASE REPORT: A young female with severe Crohn's disease, treated with the TNF-alpha inhibitor infliximab, developed friable pseudomembranous oral ulcerations. Histopathological and immunofluorescence analyses confirmed these as PV. The treatment included clobetasol propionate and low-level photobiomodulation, which resulted in partial improvement. The patient later experienced severe intestinal bleeding, requiring intravenous hydrocortisone therapy, which improved both her systemic condition and oral lesions. Weeks later, new ulcerations caused by herpes virus and candidiasis were identified, leading to treatment with oral acyclovir, a 21-day regimen of oral nystatin rinse, and photodynamic therapy, ultimately healing the oral infections. To manage her condition, the gastroenterologists included methotrexate (25 mg) in her regimen to reduce the immunogenicity of infliximab and minimize corticosteroid use, as the patient was in remission for Crohn's disease, and the oral PV lesions were under control. CONCLUSION: Young patients with Crohn's disease should be referred to an oral medicine specialist for comorbidity investigation, as oral PV and opportunistic infections can arise during immunosuppressive therapy. The use of TNF-alpha inhibitors in patients treated for inflammatory bowel disease, such as Crohn's, should be carefully evaluated for potential side effects, including oral PV.
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Enfermedad de Crohn , Herpes Simple , Factores Inmunológicos , Infliximab , Pénfigo , Humanos , Pénfigo/tratamiento farmacológico , Pénfigo/complicaciones , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/tratamiento farmacológico , Femenino , Herpes Simple/complicaciones , Herpes Simple/tratamiento farmacológico , Factores Inmunológicos/efectos adversos , Factores Inmunológicos/uso terapéutico , Infliximab/uso terapéutico , Infliximab/efectos adversos , Adulto , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Enfermedades de la Boca/tratamiento farmacológico , Enfermedades de la Boca/complicacionesRESUMEN
BACKGROUND: Ulcerative colitis (UC) is a chronic immune-mediated inflammation of the colorectum, for which infliximab (IFX) is currently the mainstay of treatment. However, one-third of patients with UC still fail to benefit from the IFX therapy, and early exposure to IFX impairs the efficacy of other subsequent biologics. Therefore, personalized therapeutic system is urgently needed to assist in clinical decision-making and precision treatment. METHODS: Four microarray datasets of colonic biopsies from UC patients treated with IFX were obtained from the GEO database to form the Training Cohort and Validation Cohort. Differentially expressed genes (DEGs) in Training Cohort were identified and enriched for GO, KEGG and immune cell infiltration analysis. A prediction model for IFX efficacy was developed based on the LASSO and Logistic regression. The predictive accuracy of the model was verified by the Validation Cohort, and the model-genes/proteins were validated by immunohistochemistry. Gene-drug, gene-ncRNA interaction analysis were performed to identify drugs or non-coding RNAs (ncRNAs) that potentially interacted with the model-genes. Homology Modeling and Molecular Docking were conducted to filter the optimal candidate as the subsequent adjuvant or alternative for IFX in predicted non-responders. At last, the down-regulation of the key model-gene/protein CYP24A1 by the drug candidate Deferasirox was verified by Western Blot and qRT-PCR Assay based on cellular experiments. RESULTS: A total of 113 DEGs were identified in the Training Cohort, mainly enriched in inflammatory cell chemotaxis, migration, and response to molecules derived from intestinal microbiota. Activated pro-inflammatory innate immune cells, including neutrophils, M1 macrophages, activated dendritic cells and mast cells, were significantly enriched in colons of non-responders. The prediction model based on three model-genes (IFI44L, CYP24A1, and RGS1) exhibited strong predictive efficacy, with AUC values of 0.901 and 0.80 in the Training and Validation Cohorts, respectively. Higher expression of the three model-genes/proteins in colons of non-responders to IFX was confirmed by clinical colonic mucosal biopsies. 4 Drugs (Calcitriol, Lunacalcipol, Deferasirox, Telaprevir), 15 miRNAs and 66 corresponding lnRNAs interacting with model-genes were identified. The protein 3D structure of the key model-gene/protein (human-derived CYP24A1) was developed. Through the Molecular Docking and cellular experimental validation, Deferasirox, which significantly down-regulated both the RNA and protein expression of CYP24A1, was identified as the optimal adjuvant or alternative for IFX in predicted non-responders with UC. CONCLUSION: This study developed a novel prediction model for pre-assessing the efficacy of IFX in patients with UC, as the first step towards personalized therapy. Meanwhile, drugs and non-coding RNAs were provided as potential candidates to develop the next-step precise treatment for the predicted non-responders. In particular, Defeasirox appears to hold promise as an adjuvant or alternative to IFX for the optimization of UC therapy.
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Colitis Ulcerosa , Infliximab , Humanos , Infliximab/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/genética , Colitis Ulcerosa/inmunología , Fármacos Gastrointestinales/uso terapéutico , Simulación del Acoplamiento Molecular , Perfilación de la Expresión GénicaRESUMEN
RATIONALE: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by continuous inflammation of the colonic mucosa. Autoimmune hepatitis (AIH) is a chronic liver disease characterized by hypergammaglobulinemia, circulating autoantibodies, interface hepatitis, and favorable response to immunosuppression. An association between IBD and AIH is uncommon, and experts have suggested that in patients with overlapping IBD and AIH, the anti-tumor necrosis factor agents can be used. Therefore, this study reports a rare case of a patient with liver cirrhosis due to AIH and UC refractory to conventional treatment and discusses the risks and benefits of using anti-tumor necrosis factor in both conditions. PATIENT CONCERNS: A 28-year-old female presented with symptoms of diarrhea, abdominal pain, asthenia, and inappetence, accompanied by abdominal collateral circulation, anemia, alteration of liver enzymes, and elevation of C-reactive protein levels. DIAGNOSES: The patient underwent a liver biopsy, which was consistent with liver cirrhosis due to AIH. Colonoscopy showed an inflammatory process throughout the colon, compatible with moderately active UC. INTERVENTIONS: The patient received mesalazine, azathioprine, and corticotherapy, with no control of the inflammatory process. Faced with refractoriness to drug treatment and side effects of corticosteroids with an increased risk of severe infection due to cirrhosis, we opted to use infliximab for the treatment of UC. The patient presented with a clinical response and infliximab therapy was maintained. OUTCOMES: Eight months after starting infliximab therapy, the patient developed pneumonia with complications from disseminated intravascular coagulation and died. LESSONS SUBSECTIONS: AIH is a rare cause of elevated transaminase levels in patients with UC. The best treatment to control the 2 conditions should be evaluated with vigilance for the side effects of medications, mainly infections, especially in patients with cirrhosis.
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Colitis Ulcerosa , Hepatitis Autoinmune , Cirrosis Hepática , Humanos , Femenino , Adulto , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/complicaciones , Hepatitis Autoinmune/tratamiento farmacológico , Hepatitis Autoinmune/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/complicaciones , Medición de Riesgo , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Infliximab/uso terapéutico , Infliximab/efectos adversosAsunto(s)
Enfermedad de Crohn , Glomerulonefritis por IGA , Infliximab , Humanos , Enfermedad de Crohn/tratamiento farmacológico , Infliximab/efectos adversos , Infliximab/uso terapéutico , Infliximab/administración & dosificación , Glomerulonefritis por IGA/tratamiento farmacológico , Masculino , Adulto , Femenino , Factores de Tiempo , Fármacos Gastrointestinales/efectos adversos , Fármacos Gastrointestinales/uso terapéutico , Fármacos Gastrointestinales/administración & dosificación , Persona de Mediana EdadRESUMEN
To characterize the microbiome and metabolic profile in Crohn's disease (CD) patients with different outcome after infliximab (IFX) treatment. The clinical data of a cohort of 35 patients with moderate-to-severe CD admitted at Jinling hospital between Oct 2022 and Dec 2023 were collected. Stool samples at baseline were collected to perform 16SrRNA and ITS2 sequencing and LC-MS untargeted metabolomics. Of these, seven discontinued IFX and underwent surgery during the induction period, and 28 received IFX at weeks 0, 2, and 6, each administered intravenously. Clinical remission was assessed based on the clinical symptoms and HBI at baseline and week 14. Baseline microbial richness and evenness was not significantly different between remission and non-remission group. The taxonomic community analysis identified decrease of Ruminococcus, Lachnoclostridium, Akkermansia in bacterial community and decrease of Asterotremella and Wallemia in fungal community in the non-remission group. LC-MS analysis showed that histamine, creatinine and L-proline significantly increased in remission group, while androsterone, berberine and episterol significantly decreased. The combined prediction model of histamine, androsterone, and episterol demonstrated a high predictive value of remission in patients after IFX treatment (AUC=0.898, p<0.001). Together, these data might facilitate a priori determination of optimal therapeutics for CD patients.
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Enfermedad de Crohn , Heces , Microbioma Gastrointestinal , Infliximab , Metabolómica , Inducción de Remisión , Humanos , Infliximab/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/microbiología , Enfermedad de Crohn/metabolismo , Masculino , Femenino , Adulto , Metabolómica/métodos , Microbioma Gastrointestinal/efectos de los fármacos , Heces/microbiología , Heces/química , Inducción de Remisión/métodos , Fármacos Gastrointestinales/uso terapéutico , Adulto Joven , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Introduction: Immune-related epidermal necrolysis (irEN), including Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN), represents a potentially lethal reaction to immune checkpoint inhibitors. An optimal treatment strategy remains undefined. This study evaluates the effectiveness and safety of combination therapy with corticosteroids and tumor necrosis factor inhibitors (TNFi) in treating irEN patients. Methods: In this single-center, prospective, observational study, patients with irEN received either corticosteroid monotherapy or a combination therapy of corticosteroids and TNFi (etanercept for SJS, infliximab for TEN). The primary endpoint was re-epithelization time, with secondary endpoints including corticosteroid exposure, major adverse event incidence, acute mortality rates, and biomarkers indicating disease activity and prognosis. The study was registered at the Chinese Clinical Trial Registry (ChiCTR2100051052). Results: Thirty-two patients were enrolled (21 SJS, 11 TEN); 14 received combination therapy and 18 received corticosteroid monotherapy. IrEN typically occurred after 1 cycle of ICI administration, with a median latency of 16 days. Despite higher SCORTEN scores in the combination group (3 vs. 2, p = 0.008), these patients experienced faster re-epithelization (14 vs. 21 days; p < 0.001), shorter corticosteroid treatment duration (22 vs. 32 days; p = 0.005), and lower prednisone cumulative dose (1177 mg vs. 1594 mg; p = 0.073). Major adverse event rates were similar between groups. Three deaths occurred due to lung infection or disseminated intravascular coagulation, with mortality rates for both groups lower than predicted. Potential risk factors for increased mortality included continuous reduction in lymphocyte subset counts (CD4+ T cells, CD8+ T cells, natural killer cells) and consistent rises in inflammatory markers (serum ferritin, interleukin-6, TNF-α). Re-epithelization time negatively correlated with body mass index and positively correlated with epidermal detachment area and serum levels of interleukin-6 and TNF-α. Conclusions: Corticosteroids combined with TNFi markedly promote re-epithelization, reduce corticosteroid use, and decrease acute mortality in irEN patients without increasing major adverse events, offering a superior alternative to corticosteroid monotherapy. Inflammatory markers and lymphocyte subsets are valuable for assessing disease activity and prognosis.
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Corticoesteroides , Quimioterapia Combinada , Inhibidores de Puntos de Control Inmunológico , Síndrome de Stevens-Johnson , Inhibidores del Factor de Necrosis Tumoral , Humanos , Síndrome de Stevens-Johnson/etiología , Síndrome de Stevens-Johnson/mortalidad , Síndrome de Stevens-Johnson/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Corticoesteroides/uso terapéutico , Adulto , Anciano , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Etanercept/efectos adversos , Etanercept/uso terapéutico , Resultado del Tratamiento , Infliximab/uso terapéutico , Infliximab/efectos adversosRESUMEN
Treatment of pyoderma gangrenosum (PG) is challenging due to the absence of standardized guidelines and the lack of evidence-based, effective treatment options. Here, we performed a systematic review to summarize the use of biologics and their efficacy in the treatment of PG. We searched PubMed/MEDLINE, EMBASE, and Cochrane electronic databases from their inception to September 22nd, 2022, and included 82 peer-reviewed studies with a total of 108 patients. Infliximab, adalimumab, and etanercept were the most utilized biologic therapies in the treatment of PG in 64.8% (70/108), 16.7% (18/108), and 11.1% (12/108) of the cases, respectively. With respect to treatment response, 88.9% (96/108) of the patients achieved complete resolution of PG with biologic therapies. The average number of days to improvement and resolution of PG treated after starting biologic therapies was 30 and 161, respectively. PG recurred in 15.5% (11/71) of those reported the outcome. Our study suggests that biologic therapies may be an attractive therapeutic option for PG with an excellent efficacy.
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Piodermia Gangrenosa , Humanos , Piodermia Gangrenosa/tratamiento farmacológico , Resultado del Tratamiento , Productos Biológicos/uso terapéutico , Terapia Biológica/métodos , Infliximab/uso terapéutico , Etanercept/uso terapéutico , Adalimumab/uso terapéutico , Recurrencia , Fármacos Dermatológicos/uso terapéuticoAsunto(s)
Enfermedades Inflamatorias del Intestino , Factor de Necrosis Tumoral alfa , Humanos , Niño , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Infliximab/uso terapéutico , Infliximab/efectos adversos , Adolescente , Fármacos Gastrointestinales/uso terapéutico , Fármacos Gastrointestinales/efectos adversos , Resultado del Tratamiento , Colitis Ulcerosa/tratamiento farmacológicoRESUMEN
A randomized, double-blind, placebo-controlled clinical trial was conducted to investigate the efficacy of infliximab, abatacept, and cenicriviroc in treating patients hospitalized with COVID-19. The patient's clinical status was assessed daily on an 8-point ordinal scale. We evaluated the totality of evidence on the efficacy of the 3 immunomodulators by considering all possible changes in the clinical status of each patient over time. We demonstrated that infliximab accelerated improvement and reduced deterioration of clinical status when added to standard of care. There was also evidence for the benefit of abatacept. There was no evidence for the benefit of cenicriviroc.
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Abatacept , Tratamiento Farmacológico de COVID-19 , COVID-19 , Infliximab , SARS-CoV-2 , Humanos , Abatacept/uso terapéutico , Infliximab/uso terapéutico , Método Doble Ciego , Masculino , Persona de Mediana Edad , Femenino , Resultado del Tratamiento , Anciano , Hospitalización , Adulto , Agentes Inmunomoduladores/uso terapéuticoRESUMEN
INTRODUCTION: There are scarce data on the occurrence of dermal lesions in patients with inflammatory bowel disease (IBD) treated with anti-tumor necrosis factor α (anti-TNFα) antibodies. Characteristics of the skin lesions, their clinical course, and impact on treatment are of high importance. OBJECTIVES: The aim of this study was to assess the prevalence, risk factors, and clinical sequelae of dermal lesions in IBD patients treated with anti-TNFα antibodies. PATIENTS AND METHODS: This retrospective, singlecenter study evaluated 541 IBD patients treated with anti-TNFα drugs and 688 IBD individuals with no history of anti-TNFα treatment. RESULTS: Higher prevalence of dermal lesions was noted in the patients on anti-TNFα therapy than in the individuals not receiving such treatment (30.9% vs 16.4%; P <0.001). Risk factors for dermal lesions included higher body mass index (BMI), Crohn disease located in the small intestine, and longer duration of therapy. Some types of dermal lesions were associated with anti-TNFα therapy; these included infusion reactions and injection site reactions, cutaneous infection, psorasiform reactions, and lupuslike symptoms. Overall, 5.9% of the patients on anti-TNFα therapy required treatment change or discontinuation due to dermal lesions (alopecia, lupuslike symptoms, melanoma, and psoriasis). CONCLUSIONS: We observed a higher prevalence of dermal lesions in patients with IBD undergoing anti-TNFα therapy than in the treatment-naive group, although development of such lesions rarely necessitated a change in or discontinuation of treatment. Patients with IBD should regularly undergo follow-up dermatologic evaluation, which may improve detection of dermal lesions. Moreover, biologic therapy in IBD patients requires close collaboration with an experienced dermatologist.
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Enfermedades Inflamatorias del Intestino , Factor de Necrosis Tumoral alfa , Humanos , Masculino , Femenino , Adulto , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Estudios Retrospectivos , Polonia , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Persona de Mediana Edad , Factores de Riesgo , Enfermedades de la Piel/inducido químicamente , Enfermedades de la Piel/etiología , Prevalencia , Adulto Joven , Infliximab/uso terapéutico , Infliximab/efectos adversos , AncianoRESUMEN
INTRODUCTION: Stricture is a common complication in Crohn's disease (CD). Accurate identification of strictures that poorly respond to biologic therapy is essential for making optimal therapeutic decisions. The aim of this study was to determine the association between ultrasound characteristics of strictures and their therapeutic outcomes. METHODS: Consecutive CD patients with symptomatic strictures scheduled for biologic therapy were retrospectively recruited at a tertiary hospital. Baseline intestinal ultrasound was conducted to assess stricture characteristics, including bowel wall thickness, length, stratification, vascularity, and creeping fat wrapping angle. Patients were followed up for a minimum of 1 year, during which long-term outcomes including surgery, steroid-free clinical remission, and mucosal healing were recorded. Statistical analyses were performed. RESULTS: A total of 43 patients were enrolled. Strictures were located in the ileocecal region (39.5%), colon (37.2%), anastomosis (20.9%), and small intestine (2.3%). The median follow-up time was 17 months (interquartile range 7-25), with 27 patients (62.8%) undergoing surgery. On multivariant analysis, creeping fat wrapping angle > 180° (odds ratio: 6.2, 95% confidence interval [CI]: 1.1-41.1) and a high Limberg score (odds ratio: 2.3, 95% CI: 1.4-6.0) were independent predictors of surgery, with an area under the curve of 0.771 (95% CI: 0.602-0.940), accuracy of 83.7%, sensitivity of 96.3%, and specificity of 62.5%. On Cox survival analysis, creeping fat >180° was significantly associated with surgery (hazard ratio, 5.2; 95% CI: 1.2-21.8; P = 0.03). In addition, creeping fat was significantly associated with steroid-free clinical remission ( P = 0.015) and mucosal healing ( P = 0.06). DISCUSSION: Intestinal ultrasound characteristics can predict outcomes in patients with stricturing CD who undertook biologic therapy.
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Productos Biológicos , Enfermedad de Crohn , Ultrasonografía , Humanos , Enfermedad de Crohn/diagnóstico por imagen , Enfermedad de Crohn/tratamiento farmacológico , Masculino , Femenino , Adulto , Estudios Retrospectivos , Constricción Patológica/diagnóstico por imagen , Constricción Patológica/etiología , Productos Biológicos/uso terapéutico , Resultado del Tratamiento , Persona de Mediana Edad , Adulto Joven , Infliximab/uso terapéutico , Estudios de Seguimiento , Mucosa Intestinal/diagnóstico por imagen , Mucosa Intestinal/patologíaRESUMEN
INTRODUCTION: Expeditious initiation of biologic therapy is important in patients with inflammatory bowel disease (IBD). However, initiation of biologics in the outpatient setting may be delayed by various clinical, social, and financial variables. AIM: To evaluate the delay in initiation of an advanced therapy in IBD and to identify factors that contributed to this delay. METHODS: This was a multi-center retrospective study. Outpatients who were initiated on a biologic therapy from 3/1/2019 to 9/30/20 were eligible for the study. Univariate and multivariate linear regression analyses were performed to identify variables associated with a delay in biologic treatment initiation. Delay was defined as the days from decision date (prescription placement) to first infusion or delivery of medication. RESULTS: In total 411 patients (Crohn's disease, n = 276; ulcerative colitis, n = 129) were included in the analysis. The median [interquartile range-(IQR)] delay for all drugs was 20 [12-37] days (infliximab, 19 [13-33] days; adalimumab, 10 [5-26] days; vedolizumab, 21 [14-42] days; and ustekinumab, 21 [14-42] days). Multivariate linear regression analysis identified that the most important variables associated with delays in biologic treatment initiation was self-identification as Black, longer distance from treatment site, and lack of initial insurance coverage approval. CONCLUSION: There may be a significant delay in biologic treatment initiation in patients with IBD. The most important variables associated with this delay included self-identification as Black, longer distance from site, and lack of initial insurance coverage approval.
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Tiempo de Tratamiento , Humanos , Femenino , Masculino , Estudios Retrospectivos , Adulto , Persona de Mediana Edad , Tiempo de Tratamiento/estadística & datos numéricos , Enfermedad de Crohn/tratamiento farmacológico , Colitis Ulcerosa/tratamiento farmacológico , Ustekinumab/uso terapéutico , Adalimumab/uso terapéutico , Productos Biológicos/uso terapéutico , Fármacos Gastrointestinales/uso terapéutico , Terapia Biológica/métodos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Factores de Tiempo , Infliximab/uso terapéutico , Infliximab/administración & dosificación , Enfermedades Inflamatorias del Intestino/tratamiento farmacológicoRESUMEN
The intestine constantly encounters and adapts to the external environment shaped by diverse dietary nutrients. However, whether and how gut adaptability to dietary challenges is compromised in ulcerative colitis is incompletely understood. Here, we show that a transient high-fat diet exacerbates colitis owing to inflammation-compromised bile acid tolerance. Mechanistically, excessive tumor necrosis factor (TNF) produced at the onset of colitis interferes with bile-acid detoxification through the receptor-interacting serine/threonine-protein kinase 1/extracellular signal-regulated kinase pathway in intestinal epithelial cells, leading to bile acid overload in the endoplasmic reticulum and consequent apoptosis. In line with the synergy of bile acids and TNF in promoting gut epithelial damage, high intestinal bile acids correlate with poor infliximab response, and bile acid clearance improves infliximab efficacy in experimental colitis. This study identifies bile acids as an "opportunistic pathogenic factor" in the gut that would represent a promising target and stratification criterion for ulcerative colitis prevention/therapy.
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Ácidos y Sales Biliares , Infliximab , Factor de Necrosis Tumoral alfa , Animales , Humanos , Masculino , Ratones , Apoptosis/efectos de los fármacos , Ácidos y Sales Biliares/metabolismo , Colitis/metabolismo , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/patología , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/patología , Dieta Alta en Grasa/efectos adversos , Progresión de la Enfermedad , Infliximab/uso terapéutico , Infliximab/farmacología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Ratones Endogámicos C57BL , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: Cases of psoriasis associated with Tocilizumab (TCZ) are scarce. OBJECTIVE: To describe a new case of TCZ-associated psoriasis and to perform a case-based review of similar cases. METHODS: We searched Medline/Pubmed, Embase, Scopus, Web of Science, and Directory of Open Access Journals databases using the terms « Tocilizumab ¼ and « Psoriasis ¼ in the French and English literature. RESULTS: We report a 70-year-old woman with a history of Rheumatoid Arthritis who developed Infliximab-induced plaque psoriatic eruption of the soles and palms, that resolved after Infliximab interruption, then relapsed after TCZ relay, and eventually resolved after TCZ interruption. Including our case, we identified 16 cases of TCZ-induced psoriatic eruption. Three (21%) out of 14 patients had a history of cutaneous psoriasis - data were not available for 2 patients. Eight (50%) patients had previously received TNFα antagonists. TCZ was stopped for 10 patients and continued for 4 patients. For the 2 remaining patients, the interval between two injections of TCZ was shortened. All the patients with available follow-up data had an improvement of the eruption within 4 weeks. CONCLUSION: To conclude, in case of TCZ-induced psoriatic eruption and in light of the published cases, we suggest using topical steroids and reassessing the patient 4 weeks later. If no healing is obtained, we suggest stopping TCZ, and treating the underlying disease with another drug. When no other drug is available, while waiting for more data regarding the value of IL-6 levels, it can be discussed to increase TCZ regimen, as it has been successful for 2 authors. Efficacy assessment of the chosen attitude should not take place before 4 weeks.
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Anticuerpos Monoclonales Humanizados , Artritis Reumatoide , Psoriasis , Humanos , Femenino , Anticuerpos Monoclonales Humanizados/efectos adversos , Anciano , Psoriasis/inducido químicamente , Psoriasis/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Infliximab/efectos adversos , Infliximab/uso terapéutico , Erupciones por Medicamentos/etiología , Erupciones por Medicamentos/tratamiento farmacológico , Antirreumáticos/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Although biologic agents are very effective, long-term comparative studies demonstrating their safety relative to one another are still lacking. METHODS: A total of 124 patients with psoriasis were followed up for 30 months; 74 received anti-TNF-alpha inhibitors (adalimumab, etanercept, infliximab), 33 were on ustekinumab, and 17 were treated with secukinumab. The rates of adverse events in these groups were recorded and statistically analyzed. RESULTS: Infliximab-treated patients showed a high occurrence of asymptomatic, but increased liver enzymes, fatigue, and respiratory as well as dermatologic infections. Adalimumab-treated patients were more often affected by musculoskeletal disorders and infections of all types. Patients treated with secukinumab presented with higher rates of cardiovascular disorders as well as respiratory and dermatologic infections. The group receiving etanercept was more often diagnosed with musculoskeletal and reproductive disorders, specifically menstrual disorders. The rates of therapy discontinuation and serious adverse events did not reach statistically significant values. CONCLUSION: A higher incidence of adverse events was observed among adalimumab-, and infliximab-treated patients, with ustekinumab found to have the safest profile. Our results demonstrate that a personalized approach, including evaluation of a patient's risk profile, is necessary before commencing a biologic. Further research is warranted to confirm the findings of our study.