IMMU-40. IMMUNE PROFILING OF MATCHED PRIMARY AND RECURRENT GLIOBLASTOMA TUMORS IDENTIFIED CD64 AS A NEGATIVE PREDICTOR FOR SURVIVAL

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi101-vi101
Author(s):  
Tala Shekarian ◽  
Marie-Françoise Ritz ◽  
Tomàs Martins ◽  
Philip Schmassmann ◽  
Gregor Hutter
Keyword(s):  
Therapeutic Option ◽  
Specific Cell ◽  
Tumor Resistance ◽  
Expression Ratio ◽  
Recurrent Tumors ◽  
Treatment Naïve ◽  
Time To Relapse ◽  
Negative Predictor ◽  
Recurrent Gbm ◽  
Matched Treatment

Abstract BACKGROUND To target tumor-induced immune evasion mechanisms of glioblastoma for clinical research, we aimed at characterizing the immunological changes in patient-matched treatment-naïve and recurrent GBM samples. MATERIAL AND METHODS Proteins and total RNA were extracted from 15 patient-matched treatment-naïve (primary) and recurrent GBM fresh frozen tumor samples. The expression of genes involved in brain immune responses were compared using Nanostring panels encompassing Cancer and Neuroinflammation genes. Correlation analysis using log2-transformed patient-matched recurrent/primary expression ratio (log2(P/R)) and clinical outcome data (time to relapse and overall survival (OS)) was conducted. Proteomic was conducted to compare total protein expressions. Moreover, immunostaining was performed on a tissue microarray of matched tumor samples to visualize CD64+ cells, CD47+ tumor cells and microglia in order to assess quantitative transcriptome of these specific cell types using GeoMX technology. Functional assays are designed for deciphering phagocytosis induction by factors produced by primary and recurrent tumors. RESULTS Genes significantly differentially expressed between primary and recurrent tumors revealed “Antigen presentation” and “Microglia Pathogen Phagocytosis” as the most significant pathways enriched in recurrent tumors. Considering individual genes, a strong negative correlation (R2>0.4) between log2(R/P) and time to relapse and OS was found for 2 genes, FCGR1A (CD64) and CD47. We observed that only CD64 expression levels in recurrent samples also negatively correlated with OS. CD64 and CD47 proteins were quantified by proteomic analysis and log2 (R/P) of their levels also negatively correlated with time to relapse. Immunostaining revealed numerous CD64-positive cells in tumor biopsies resembling bushy or amoeboid microglia. CONCLUSION Upregulation of CD64 and CD47 expressions in recurrent GBM was identified as a negative predictor for time to relapse and OS. This suggests an important role of CD64 and CD47 and related inflammation dysregulation in tumor resistance and regrowth. Interfering with CD64-induced functions may represent a novel therapeutic option for GBM.

scholarly journals Machine-Learning-Based Radiomics MRI Model for Survival Prediction of Recurrent Glioblastomas Treated with Bevacizumab

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1263
Author(s):  
Samy Ammari ◽  
Raoul Sallé de Chou ◽  
Tarek Assi ◽  
Mehdi Touat ◽  
Emilie Chouzenoux ◽  
...  
Keyword(s):  
Machine Learning ◽  
Therapeutic Option ◽  
Binary Classification ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Machine Learning Algorithms ◽  
Survival Prediction ◽  
Classification Models ◽  
Angiogenic Therapy ◽  
Recurrent Gbm

Anti-angiogenic therapy with bevacizumab is a widely used therapeutic option for recurrent glioblastoma (GBM). Nevertheless, the therapeutic response remains highly heterogeneous among GBM patients with discordant outcomes. Recent data have shown that radiomics, an advanced recent imaging analysis method, can help to predict both prognosis and therapy in a multitude of solid tumours. The objective of this study was to identify novel biomarkers, extracted from MRI and clinical data, which could predict overall survival (OS) and progression-free survival (PFS) in GBM patients treated with bevacizumab using machine-learning algorithms. In a cohort of 194 recurrent GBM patients (age range 18–80), radiomics data from pre-treatment T2 FLAIR and gadolinium-injected MRI images along with clinical features were analysed. Binary classification models for OS at 9, 12, and 15 months were evaluated. Our classification models successfully stratified the OS. The AUCs were equal to 0.78, 0.85, and 0.76 on the test sets (0.79, 0.82, and 0.87 on the training sets) for the 9-, 12-, and 15-month endpoints, respectively. Regressions yielded a C-index of 0.64 (0.74) for OS and 0.57 (0.69) for PFS. These results suggest that radiomics could assist in the elaboration of a predictive model for treatment selection in recurrent GBM patients.

TMOD-08. DEVELOPING DERIVATIVE GBM PDX, IN VIVO, FROM TREATMENT NAÏVE SOURCES

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi217-vi217
Author(s):  
David James ◽  
Craig Horbinski ◽  
Roger Stupp ◽  
Atique Ahmed
Keyword(s):  
Mutagenic Effect ◽  
Recurrent Glioblastoma ◽  
Response To Treatment ◽  
Mismatch Repair Gene ◽  
Repair Gene ◽  
Msh6 Mutation ◽  
Treatment Naïve ◽  
Post Therapy ◽  
Recurrent Gbm

Abstract PURPOSE Post-therapy recurrent glioblastoma (GBM) patient-derived xenografts (PDX), developed from corresponding treatment-naïve PDX, could serve as useful resources for identifying therapeutics with activity against recurrent GBM. The goal of this study was to determine whether treatment-naïve intracranial GBM PDX, in mice receiving radiotherapy (RT) and/or temozolomide (TMZ), acquire the same mutations that occur in post-RT+TMZ GBMs from patients. METHODS Luciferase-modified, treatment-naïve GBM PDX were engrafted in the brains of athymic nude mice, followed by treatment with RT only (2 Gy/day x 5), TMZ only (10 mg/kg/day x 5), or RT+TMZ. Bioluminescence imaging was used to monitor intracranial tumor growth, response to treatment, and recurrence from treatment. Some mice with recurrent tumors received additional TMZ treatment. When mice became symptomatic, intracranial tumors were resected and engrafted subcutaneously in a new mouse host, then sequentially propagated subcutaneously into additional host mice. After the third passage, whole-exome sequencing (WES) was done, comparing post-therapy with treatment-naïve PDX sequence variants. RESULTS Analysis of PDX WES showed the following: 1) TMZ consistently caused more genes to incur coding sequence mutations than RT, as much as 13x more; 2) TMZ-treated tumor mutations were mostly G-C to A-T transitions (71-92%), consistent with the known mutagenic effect of TMZ; and 3) post-therapy PDX acquire similar mutations as do recurrent GBMs in patients, for example involving DNA mismatch repair gene MSH6. One of the derivative PDX with MSH6 mutation has been retested for response to RT and TMZ, with results showing its having become TMZ, but not RT resistant. CONCLUSIONS The mutation profiles of RT+TMZ-treated PDX are similar to those reported for GBMs that recur after RT+TMZ in patients. The new PDX resources described here may prove useful for identifying effective treatments against recurrent GBM.

scholarly journals Antiangiogenic therapies for pheochromocytoma and paraganglioma

2020 ◽  
Vol 27 (7) ◽  
pp. R239-R254 ◽  
Author(s):  
Camilo Jimenez ◽  
Sasan Fazeli ◽  
Alejandro Román-Gonzalez
Keyword(s):  
Clinical Trials ◽  
Specific Activity ◽  
Therapeutic Option ◽  
High Specific Activity ◽  
Vascular Tumors ◽  
Tumor Resistance ◽  
Skeletal Tissue ◽  
Antiangiogenic Therapies ◽  
Emergence Of Resistance ◽  
Unites States

Metastatic pheochromocytomas and paragangliomas are rare, highly vascular tumors that spread primarily to the lymph nodes, skeletal tissue, lungs, and liver. Tumor morbidity is related to their size, location, hormonal activity, vascular nature, and rate of progression. Systemic therapies for this indication are limited. Only high-specific-activity iodine-131 metaiodobenzylguanidine is approved in the Unites States for treatment of these patients, and not all patients are candidates for this radiopharmaceutical. Antiangiogenic medications are currently being evaluated in prospective clinical trials for patients with metastatic pheochromocytomas and paragangliomas, and preliminary results have been encouraging. Antiangiogenic medications frequently offer antineoplastic effects with sometimes durable responses. However, cardiovascular toxicity and the development of tumor resistance may limit their efficacy. Experience derived from clinical trials is being used to identify mechanisms to effectively improve drug toxicity and possibly prevent the emergence of resistance. Therefore, antiangiogenic medications represent a therapeutic option for patients with metastatic pheochromocytomas and paragangliomas. Furthermore, in the world of oncology, there is strong scientific interest in the development of clinical trials that combine antiangiogenic medications with other modalities such as immunotherapy, radiopharmaceuticals, and hypoxia inhibitors since these combinations may substantially enhance clinical outcomes, including survivorship. In this review, we examine the progress made to date on antiangiogenic treatments for patients with metastatic pheochromocytomas and paragangliomas.

scholarly journals GENE-02. ESTABLISHING PERSONALIZED TREATMENT OPTIONS FOR RECURRENT HIGH-GRADE GLIOMAS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi97-vi98
Author(s):  
Ann-Christin Hau ◽  
Linsey Houben ◽  
Eliane Klein ◽  
Anais Oudin ◽  
Daniel Stieber ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Drug Response ◽  
Treatment Strategies ◽  
Differential Sensitivity ◽  
Personalized Treatment ◽  
High Grade ◽  
Evolutionary Trajectory ◽  
Recurrent Tumors ◽  
Treatment Naïve ◽  
Tumor Organoids

Abstract BACKGROUND High grade glioma (HGG) patients develop resistance to standard treatment leading to disease progression and limited life expectancy. Recent advances in the molecular characterisation of treatment-naïve HGGs based on next generation sequencing and DNA methylation analyses have led to a better delineation of HGG-subtypes and identification of distinct genomic abnormalities opening opportunities for personalized treatment strategies. METHODS We collected 300 fresh glioma specimen with approximately 100 longitudinal samples of initial and recurrent tumors from 43 matched patients. We succeeded in generating a live-biobank of HGG patient-derived orthotopic xenografts (PDOX) and 3D tumor organoids that neatly recapitulates the mutational spectrum including structural DNA variations and methylation-based subtypes of gliomas. A highlight is the generation of 19 PDOXs of paired initial and relapse HGGs from 9 glioma patients, enabling high-throughput drug screens. We performed comprehensive molecular profiling using arrayCGH, DNA-methylation and targeted DNA sequencing on patient specimen and their derivatives, 3D tumor organoids and PDOXs. RESULTS Detailed analysis of the paired longitudinal samples indicated that PDOXs closely recapitulate the evolutionary trajectory of the parental tumors. Furthermore, targeted genomic sequencing of paired HGGs suggests that relapse tumors also accumulate somatic mutations in epigenetic effectors. Based on patient-derived material we carried out drug response screening on 3D tumor organoids using a compound library matching the majority of genes that were assessed with targeted sequencing. Differential drug responses between initial and recurrent tumors were observed and the prevailing primary drug response profiles were essentially recapitulad in the relapse setting. CONCLUSIONS Response assessment of treatment-naïve gliomas and their recurrences provides crucial information on the differential sensitivity between initial and relapsed HGGs and offers novel personalized therapeutic options for the relapse setting. Furthermore, in depth correlation of the profiled somatic molecular landscape with drug response will enable pharmacogenomic predictions of potential inhibitors in the clinical setting.

scholarly journals Chaperoning STAT3/5 by Heat Shock Proteins: Interest of Their Targeting in Cancer Therapy

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 21 ◽  
Author(s):  
Gaëtan Jego ◽  
François Hermetet ◽  
François Girodon ◽  
Carmen Garrido
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Cell Fate ◽  
Protein Quality ◽  
Immune Cell ◽  
Therapeutic Option ◽  
Specific Cell ◽  
Shock Proteins ◽  
Multicellular Organisms ◽  
Stat5 Transcription Factor

While cells from multicellular organisms are dependent upon exogenous signals for their survival, growth, and proliferation, commitment to a specific cell fate requires the correct folding and maturation of proteins, as well as the degradation of misfolded or aggregated proteins within the cell. This general control of protein quality involves the expression and the activity of molecular chaperones such as heat shock proteins (HSPs). HSPs, through their interaction with the STAT3/STAT5 transcription factor pathway, can be crucial both for the tumorigenic properties of cancer cells (cell proliferation, survival) and for the microenvironmental immune cell compartment (differentiation, activation, cytokine secretion) that contributes to immunosuppression, which, in turn, potentially promotes tumor progression. Understanding the contribution of chaperones such as HSP27, HSP70, HSP90, and HSP110 to the STAT3/5 signaling pathway has raised the possibility of targeting such HSPs to specifically restrain STAT3/5 oncogenic functions. In this review, we present how HSPs control STAT3 and STAT5 activation, and vice versa, how the STAT signaling pathways modulate HSP expression. We also discuss whether targeting HSPs is a valid therapeutic option and which HSP would be the best candidate for such a strategy.

ShRNA Targeting p190BCR-ABL Successfully Eliminates Ph-ALL Cells with or without ABL Kinase Domain Mutation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1838-1838
Author(s):  
Muneyoshi Futami ◽  
Toshiyuki Hatano ◽  
Yasushi Soda ◽  
Seiichiro Kobayashi ◽  
Makoto Miyagishi ◽  
...  
Keyword(s):  
Lentiviral Vector ◽  
High Titer ◽  
Therapeutic Option ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Kinase Domain ◽  
Leukemia Cells ◽  
Specific Cell ◽  
Dependent Manner ◽  
Abl Kinase

Abstract In the majority of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (Ph-ALL) cases, the resulting BCR-ABL gene generates 190 kD active tyrosine kinase (p190) which is responsible for leukemogenesis and can be a molecular target for therapy. Although a series of ABL kinase inhibitors including imatinib, nilotinib and dasatinib reveal potent activities against Ph-ALL, acquired resistance caused by point mutations in the kinase domain such as T315I still remains to be overcome. That is why a novel strategy is desired in the treatment of Ph-ALL. We previously reported that lentiviral delivery of maxizyme targeting p190 specifically induced apoptosis of Ph-ALL cells (Blood 104:356, 2004). Since RNA interference proved to be a more powerful tool in selective gene silencing, we applied this technology to test whether specific and efficient killing of Ph-ALL cells could be achieved by down-regulation of p190. We designed a series of 21-mer and 27-mer small hairpin RNA (shRNA) targeting p190 mRNA and constructed plasmid vectors expressing these shRNA, which were screened by transfection of 293T/p190 cells to determine optimal target sites. As a result, three candidate sequences were identified; junctional 27-mer, junctional 21-mer and ABL 21-mer. Then, we inserted each of the shRNA expression cassettes into the lentiviral vector (HIV-U6/shRNA) and prepared high titer virus stock for infection of leukemia cells. shBCR-ABL/21, but not shBCR-ABL/27, induced significant and specific cell death of p190+ Ph-ALL cells in a time-dependent manner. shABL was more potent than shBCR-ABL/21 and also active against p210+ CML cells as well as 293 cells, but did not substantially affect Ph-negative leukemia cells. Both shABL and shBCR-ABL/21 completely inhibited growth of Ba/F3 cells harboring either wild-type or mutant p190 which renders those resistant to imatinib. Furthermore, both shRNA at low multiplicity of infection additively cooperated with imatinib in growth inhibition of Ba/F3-p190 cells. These data suggest that shRNA targeting p190 may become a therapeutic option in Ph-ALL by improvement of its delivery system like liposome. Growth of BA/F3-p190BCR-ABL Cells transduced with shRNA Targeting p190BCR-ABL Growth of BA/F3-p190BCR-ABL Cells transduced with shRNA Targeting p190BCR-ABL

scholarly journals Subclonal evolution and expansion of THY1-positive cells is associated with recurrence in glioblastoma

2021 ◽  
Author(s):  
Wajd N. Al-Holou ◽  
Hanxiao Wang ◽  
Visweswaran Ravikumar ◽  
Morgan Oneka ◽  
Roel GW Verhaak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Treatment Resistance ◽  
Cell Phenotype ◽  
Perivascular Niche ◽  
Clinical Databases ◽  
Recurrent Tumors ◽  
Treatment Naïve

AbstractGlioblastoma(GBM) is a lethal disease characterized by treatment resistance and recurrence. To investigate the mechanisms that drive treatment resistance in GBM, we developed a longitudinal in vivo recurrence model utilizing patient-derived GBM explants to produce paired specimens pre- and post-recurrence following temozolomide(TMZ) and radiation(IR) therapy. These studies revealed in replicate cohorts, a common gene expression profile upon recurrence, characterized by an upregulation of transcripts associated with a mesenchymal and stem cell phenotype, including TGFβ1, TGFβ2, SOX2, ZEB2, GLI2 and THY1(CD90), with greater than one-hundred-fold increase in THY1 levels. Analyses of clinical databases revealed the association of this transcriptional profile with worse overall survival and elevation in recurrent tumors. We then isolated THY1-positive cells from treatment-naïve patient samples which demonstrated inherent resistance to chemoradiation when implanted intracranially. Additionally, using image-guided biopsies from treatment-naïve human GBM we conducted spatial whole transcriptomic analyses. This revealed rare THY1+ regions characterized by elevation of the mesenchymal and stem-like gene expression profile, previously identified in our in vivo recurrent samples, which co-localized with a macrophage gene signature within the perivascular niche. Since TGFβ signaling contributes to a mesenchymal/stem-like phenotype and therapeutic resistance, and to investigate its effect on THY1, we inhibited TGFβRI kinase activity in vivo which resulted in decreased expression of genes characteristic of a mesenchymal/stem-like phenotype, including THY1. Notably, TGFβRI inhibition restored sensitivity to TMZ/IR in recurrent tumors in vivo. These studies reveal that post-TMZ/IR recurrence may result from tumor repopulation by pre-existing, therapy-resistant, THY1-positive mesenchymal/stem-like cells within the perivascular niche.One Sentence SummaryTHY1 positive tumor cells drive resistance in glioblastoma

Interim results from the OPTIMAL trial: A phase II clinical trial of combination nivolumab, ipilimumab, and taxane in patients with untreated metastatic non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21683-e21683
Author(s):  
Jeffrey Melson Clarke ◽  
Xiaofei F. Wang ◽  
Lin Gu ◽  
Marvaretta Miesha Stevenson ◽  
Tom Stinchcombe ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Therapeutic Option ◽  
Objective Response ◽  
Phase Ii Clinical Trial ◽  
Response To Treatment ◽  
Smoking History ◽  
Weekly Paclitaxel ◽  
Clinical Activity ◽  
Treatment Naïve

e21683 Background: Combination chemo-immunotherapy is a well-established frontline therapeutic option for treatment naïve NSCLC. Dual immune checkpoint blockade (ICB) with nivolumab (nivo) and ipilimumab (ipi) has demonstrated improved clinical outcomes compared with chemotherapy alone in this setting. Combination dual ICB with low-dose chemotherapy may have advantages of preventing early disease progression and potentiating immunogenic response to treatment. Methods: We are conducting a single arm phase II clinical trial of nivo 360 mg IV Q3 weeks, ipi 1 mg/kg IV Q6 weeks, and weekly paclitaxel 80 mg/m2 IV on d1 and d8 of a 21 day cycle in ECOG 0-1 patients (pts) with treatment naïve NSCLC. Paclitaxel is stopped after a total of 4-6 cycles. The primary endpoint of the trial is progression free survival (PFS) with secondary endpoints of safety and objective response rate (ORR) by independent radiologic review. Interim results are presented from the first 23 evaluable pts, of a planned sample size of 49. Results: 23 pts were enrolled and evaluable with a mean age 63.8 years, 56.5% ECOG 0, 87% current/previous smoking history, and 70% adenocarcinoma. PDL1 score for < 1%, 1-49%, ³ 50% was seen in 9 (39.1%), 4 (17.4%), and 10 (43.5%) pts, respectively. Median time of follow up was 6.5 months (range 1.4–15.0). Partial response was observed in 14 pts, stable disease was seen in 8 pts, and 1 pt progressed during cycle 1, resulting in an ORR of 61%. Grade 3 or higher toxicity at least possibly attributed to study treatment was seen in 47.8% of 23 AE evaluable patients, of which included 4 cases of secondary adrenal insufficiency. Other toxicity rates were as expected for the respective agents. Conclusions: This is the first trial to evaluate weekly paclitaxel with nivo plus ipi in pts with untreated NSCLC. This regimen has demonstrated highly encouraging clinical activity with a manageable toxicity profile. The study is ongoing and updated results will be presented at the annual meeting. Clinical trial information: NCT03573947.

scholarly journals Comparative Transcriptomic Analysis of Temozolomide Resistant Primary GBM Stem-Like Cells and Recurrent GBM Identifies Up-Regulation of the Carbonic Anhydrase CA2 Gene as Resistance Factor

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 921 ◽  
Author(s):  
Ricarda Hannen ◽  
Martin Selmansberger ◽  
Maria Hauswald ◽  
Axel Pagenstecher ◽  
Andrea Nist ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Patient Survival ◽  
Clinical Samples ◽  
P Value ◽  
Sequencing Analysis ◽  
First Line ◽  
Recurrent Tumors ◽  
Comparative Transcriptomic Analysis ◽  
Recurrent Gbm

About 95% of patients with Glioblastoma (GBM) show tumor relapse, leaving them with limited therapeutic options as recurrent tumors are most often resistant to the first line chemotherapy standard Temozolomide (TMZ). To identify molecular pathways involved in TMZ resistance, primary GBM Stem-like Cells (GSCs) were isolated, characterized, and selected for TMZ resistance in vitro. Subsequently, RNA sequencing analysis was performed and revealed a total of 49 differentially expressed genes (|log2-fold change| > 0.5 and adjusted p-value < 0.1) in TMZ resistant stem-like cells compared to their matched DMSO control cells. Among up-regulated genes, we identified carbonic anhydrase 2 (CA2) as a candidate gene correlated with glioma malignancy and patient survival. Notably, we describe consistent up-regulation of CA2 not only in TMZ resistant GSCs on mRNA and protein level, but also in patient-matched clinical samples of first manifest and recurrent tumors. Co-treatment with the carbonic anhydrase inhibitor Acetazolamid (ACZ) sensitized cells to TMZ induced cell death. Cumulatively, our findings illustrate the potential of CA2 as a chemosensitizing target in recurrent GBM and provide a rationale for a therapy associated inhibition of CA2 to overcome TMZ induced chemoresistance.

scholarly journals Long-Term Clinical Remission in Biologically Naïve Crohn’s Disease Patients with Adalimumab Therapy, Including Analyses of Switch from Adalimumab to Infliximab

2016 ◽  
Vol 10 (2) ◽  
pp. 283-291 ◽  
Author(s):  
Tsutomu Mizoshita ◽  
Satoshi Tanida ◽  
Keiji Ozeki ◽  
Takahito Katano ◽  
Takaya Shimura ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Dose Escalation ◽  
Clinical Remission ◽  
Therapeutic Option ◽  
Serious Adverse Events ◽  
Adalimumab Therapy ◽  
Treatment Naïve ◽  
Trough Levels

There is little evidence regarding the maintenance of long-term clinical remission by adalimumab (ADA) therapy in Crohn’s disease (CD) patients naïve to anti-tumor necrosis factor treatment (naïve CD patients), since most CD patients are treated with ADA after infliximab (IFX) therapy. The long-term clinical response to ADA was retrospectively analyzed in 17 naïve CD patients for at least 24 months, and the serum trough IFX levels were evaluated in patients switching from ADA to IFX. Of the 17 naïve CD patients, 14 (82.4%) maintained long-term clinical remission with ADA therapy for at least 24 months, without serious adverse events. The clinical condition of 7 patients was observed for more than 36 months, and 3, 1, 1, and 2 cases maintained remission at months 42, 48, 54, and 60 after ADA therapy, respectively. Three patients (17.6%) switched from ADA to IFX less than 24 months after the start of ADA therapy, and they had remission, retaining trough levels of IFX higher than 1 μg/ml, occasionally by dose escalation. In conclusion, maintenance ADA therapy achieves long-term clinical remission in naïve CD patients. Switching from ADA to IFX is an important therapeutic option in CD patients showing loss of response to ADA, occasionally with dose escalation, based on the analysis of serum IFX trough levels.

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