The role of 18F-FDG PET/CT in Neurolymphomatosis: A Comprehensive Imaging Approach.

Neurolymphomatosis (NL) is an uncommon and rare neurologic disorder characterised by extranodal lymphoma, where the tumour cells invade the cranial nerves, nerve plexus, nerve root, spinal nerve roots, trunk nerves or peripheral nerves. MRI is the modality of choice, but is often challenging in detection of early recurrence, assessing residual disease and response evaluation. 18FFDG PET/CT has superior diagnostic performance compared with body CT in the evaluation of NL. 18F-FDG PET-CT is helpful in evaluation of disease extent and potential to guide biopsy. 18F-FDG PETCT is a highly sensitive technique for early localisation of NL than MRI or CT alone. Besides diagnostic and prognostic value in NL, it might be very helpful in response assessment.

Anti-programmed-death-receptor-1 (PD-1) antibody (Pembrolizumab) induced pancreatitis diagnosed on 18F-FDG PET/CT.

Immunotherapy related adverse events are commonly seen with immune check point inhibitors therapy. We report the case of a 40-year-old female diagnosed with stage IVB endometroid grade III endometrial cancer, on pembrolizumab immunotherapy, an anti-programmed-death-receptor-1 (PD-1) antibody. Patient was referred for 18F-FDG PET/CT for restaging. 18F-FDG PET/CT demonstrated diffuse increased FDG uptake throughout the body of the pancreas associated with fat stranding in the peripancreatic region, suggestive of pembrolizumab-induced pancreatitis. The diagnosis was confirmed by elevated amylase and lipase levels. immune-related adverse events (irAE) are frequently identified on 18F-FDG PET-CT, which may lead to early diagnosis, close clinical follow-up, and appropriate clinical management of immune-related adverse events.

The Great Imitator: Pulmonary Paraganglioma Mimicking Pulmonary Metastasis of Breast Cancer on 18 F-FDG PET/CT.

ABSTRACT: Primary pulmonary paragangliomas are rare neuroendocrine tumors and are often discovered incidentally as nonfunctioning masses. We report a case of 58-year-old woman recently diagnosed with multifocal right breast cancer and suspicious right axillary lymph nodes. 18 F-FDG PET/CT showed a well-defined marginated lesion in the lower lobe of the right lung with intense FDG uptake. Findings were suspicious for pulmonary metastases. CT-guided biopsy results were consistent with a paraganglioma. Paragangliomas can mimic metastases, especially if they are large or have a high degree of FDG uptake, and careful evaluation of imaging features and clinical findings can help differentiate these entities. Most of the time biopsy is necessary to confirm the diagnosis.

Efficacy and Safety of Approximately 3 Years of Continuous Ozanimod in Moderately to Severely Active Ulcerative Colitis: Interim Analysis of the True North Open-label Extension.

BACKGROUNDS AND AIMS: This interim analysis from the True North open-label extension [OLE] study examines efficacy and safety of approximately 3 years of continuous ozanimod treatment in patients with moderately to severely active ulcerative colitis. METHODS: Clinical responders after 52 weeks of ozanimod during the phase 3 True North study, who continued treatment in the OLE, were evaluated. Efficacy, including endoscopic and histological endpoints, was assessed during the OLE for approximately 2 additional years through OLE Week 94, using observed case [OC] and nonresponder imputation [NRI] analyses. Adverse events were monitored from True North baseline through OLE data cutoff and expressed as exposure-adjusted incidence rates. RESULTS: This analysis included 131 patients; 54% had achieved corticosteroid-free remission at True North Week 52. In OC analyses, clinical response, clinical remission, and corticosteroid-free remission were achieved by 91.4%, 69.1%, and 67.9% of patients, respectively, at OLE Week 94 [146 weeks of total treatment]. Similarly, endoscopic improvement, histological remission, and mucosal healing were achieved by 73.3%, 67.3%, and 56.3% of patients, respectively, at OLE Week 94. Efficacy rates were lower using NRI analyses, but maintenance of efficacy was demonstrated through OLE Week 94. No new safety signals emerged from this analysis. Serious infections, malignancy, cardiovascular events, and hepatic events occurred infrequently. CONCLUSIONS: Among patients who achieved clinical response after 1 year of ozanimod treatment during True North, a high percentage sustained clinical and mucosal efficacy over 2 additional years in the OLE. No new safety signals were observed with long-term ozanimod use.

Calcaneus metastasis: a rare presentation of poorly differentiated thyroid cancer.

Summary: A 60-year-old woman presented to our clinic with an acute onset 3 months history of right ankle pain. The patient had a history of poorly differentiated thyroid cancer, which was treated with total thyroidectomy, left lateral neck dissection levels II-V and central neck dissection levels VI-VII followed by postoperative I-131 radioactive iodine (131I) ablation therapy 3.7 GBq 6 months ago. The post-131I WBS showed residual iodine-avid thyroid tissue with no other iodine-avid disease or metastasis. SPECT/CT of the neck and chest showed nonavid bilateral pulmonary nodules, discrete nodal masses in mediastinum and nonavid bone lesions. FDG-PET CT scan showed FDG-avid mediastinal lymph nodes (LN), innumerable non-FDG-avid subcentimetric pulmonary nodules and few FDG-avid lytic lesions in the skeleton. X-ray and MRI of the right ankle showed a well-marginated lytic lesion in the posterior body of calcaneus and 5 × 6 cm soft tissue mass lesion, respectively. The histopathology of the calcaneus mass confirmed a positive immunostaining for thyroid origin which includes thyroglobulin and TTF-1 with PAX-8. Endobronchial mediastinal and bronchial LN biopsy confirmed thyroid cancer metastasis. Gene mutation showed HRAS and GNA13 with a high tumor mutational burden. We describe a rare case of poorly differentiated thyroid cancer in a patient who presented with right ankle pain; we confirmed the cause to be a calcaneus metastasis from the thyroid cancer, with calcaneus being an extremely rare site for bone metastases. Gene mutations points toward treatment with immune checkpoint inhibitors. Learning points: Poorly differentiated thyroid carcinoma (PDTC) usually metastasizes to lung and bone but can rarely occur in the calcaneus. Patients with distant metastases have significantly worse long-term prognosis. Radiotherapy is effective in reducing the metastatic pains as well as reducing the size of the metastasis. PAX-8 staining can be used to differentiate thyroid carcinomas from lung adenocarcinomas. The importance of searching for gene mutations to decide the treatment of PDTC.

18 F-FDG PET/CT Imaging of Pulmonary Hamartomas : Metabolic and Functional Characterization.

ABSTRACT: Pulmonary hamartoma is the most common benign tumor of the lung and often discovered incidentally on imaging. We report the case of a 49-year-old woman recently diagnosed with left breast cancer with suspicious left axillary lymph nodes. 18 F-FDG PET/CT showed well-circumscribed, lobulated, low-attenuation soft tissue mass in the right lower lobe lung with mild to no significant metabolic activity. CT-guided biopsy showed the lesion composed of fat, cartilage, and smooth muscle, admixed with fibroconnective tissue. The findings are consistent with pulmonary hamartoma. The presence of fat in a well-circumscribed solitary pulmonary nodule along with low metabolic activity helps in the characterization of the lesion, which can alter patient management.

The Role Of 18F-FDG PET/CT In Evaluation Of Primary CNS Lymphoma: The Path Less Travelled.

Primary central nervous system lymphoma (PCNSL) is a rare but highly aggressive lymphoma with increasing incidence in immunocompromised patients. MRI is the modality of choice in evaluating brain lesions. However, MRI is often challenging in the detection of early recurrence, assessing residual disease and response evaluation in PCNSL. 18F-FDG PET/CT has superior diagnostic performance compared with body CT in the evaluation of lymphoma. 18F-FDG PET-CT is helpful in evaluating evaluation of disease extent and differentiating primary CNS lymphoma from systemic lymphoma. Besides diagnostic and prognostic value in primary CNS lymphoma, it might also be helpful in response assessment. The role of FDG-PET in PCNSL is not fully defined. In this article we have reviewed the potential role of 18F-FDG PET/CT in initial diagnosis, baseline staging, restaging, evaluation of treatment response, prognostication, and survival analysis of PCNSL.

Variations of azygos vein: a cadaveric study with clinical relevance.

The azygos vein can be formed as a single root, two roots, and three roots, namely lateral, intermediate and the medial roots respectively. The hemiazygos vein and the accessory hemiazygos vein are the tributaries of azygos vein rather than its left side equivalents. Its variations, especially in young persons without any relevant risk factors, may result in thromboembolic illness. This study aimed to describe the morphological and morphometric variations of azygos system of veins. The present study was conducted on thirty formalin fixed adult human cadavers by dissecting azygos vein from formation to termination and variations were noted. The azygos vein was formed by a single root in 56.7%, by two roots: the lateral root and intermediate root in 36.7% cases and by the lateral root and medial root in 6.6%. The vertebral level of termination of azygos vein was seen at the level of T4 vertebrae in 70% cases, at the level of T3 vertebrae in 20% of cases and at the level of T5 vertebrae in 10% cases. The course of azygos vein was varying in 13.3%. These morphological variations can be useful while performing mediastinal surgery, mediastinoscopy, surgery of the deformations of the vertebral column, neurovascular surgeries of the retroperitoneal organs, disc herniation and fracture of thoracic vertebrae.

68Ga-DOTA-peptide PET/CT for radiotherapy planning and evaluating treatment response in the management of meningiomas.

Meningiomas overexpress somatostatin receptors (SSTR). PET imaging with SSTR ligands such as 68Ga-DOTA-peptide has recently shown high diagnostic accuracy in identification of meningiomas due to lack of normal bone and brain activity. PET-derived parameters, especially gross tumour volume (GTV) delineation improves inter-observer variability and appears to be particularly promising for RT planning. The potential strength of 68Ga-DOTA in the ongoing assessment of treatment response and disease progression in meningioma, particularly in the post-surgical and post-radiation settings is encouraging. More prospective randomized studies with large cohorts of patients are required to define the effective role of this modality.

Tumour sink effect on 68Ga-PMSA PET/CT: A case of diffuse metastatic disease of prostate cancer.

68Ga-PMSA imaging has revolutionized both diagnosis and radioligand therapy selection in patients with metastatic prostate cancer. We report a case of a 59-year-old recently diagnosed prostate cancer with high PSA level pf >2000ng/ml referred for 68Ga-PSMA PET/CT. 68Ga-PSMA PET/CT showed diffuse intense tracer uptake throughout the axial and appendicular skeleton with significantly lower uptake of 68Ga-PSMA in normal organs in a configuration of "tumour sink effect". Findings are in keeping with diffuse skeletal infiltration and suspected marrow infiltration. Given the extensive nature of bone disease and pattern, 177Lu-PSMA-targetted radioligand therapy was thought to be more appropriate in a given situation with a favourable toxicity profile.

Accumulation of 131Iodine in the nasolacrimal sac/duct after radioiodine therapy for papillary thyroid cancer.

SPECT/CT is a powerful tool for assessing unexpected concentrations of radioiodine resulting from benign uptake in organs with sodium-iodide symporter (NIS) expression. We report a case of accumulation of 131Iodine in the nasolacrimal sac/duct after radioiodine therapy for papillary thyroid cancer. A whole-body scan was taken 3 days after the administration of 5.5 GBq of 131Iodine. SPECT/CT images localized the focal tracer uptake in the nasolacrimal sac/duct likely due to nasolacrimal duct obstruction secondary to prior radioiodine or iodine therapies. Hybrid SPECT/CT allows precise anatomical localization and help differentiate benign mimics of disease, which can alter patient management.

Non-invasive Serological Monitoring for Crohn's Disease Postoperative Recurrence.

INTRODUCTION: Crohn's disease recurs after intestinal resection. This study evaluated accuracy of a new blood test, the Endoscopic Healing Index [EHI], in monitoring for disease recurrence. METHODS: Patients enrolled in the prospective POCER study [NCT00989560] underwent a postoperative colonoscopic assessment at 6 [2/3 of patients] and 18 months [all patients] following bowel resection, using the Rutgeerts score [recurrence ≥i2]. Serum was assessed at multiple time points for markers of endoscopic healing using the EHI, and paired with the Rutgeerts endoscopic score as the reference standard. RESULTS: A total of 131 patients provided 437 serum samples, which were paired with endoscopic assessments available in 94 patients [30 with recurrence] at 6 months and 107 patients [44 with recurrence] at 18 months. The median EHI at 6 months was significantly lower in patients in remission [Rutgeerts 

Reverse Liver Spleen Uptake on [ 68 Ga]Ga-PSMA-11 PET/CT.

ABSTRACT: An 80-year-old man underwent [ 68 Ga]Ga-PSMA-11 PET/CT for staging of high-risk prostate cancer. Homogeneously increased liver uptake, more than 3-fold the splenic uptake, was seen. There was no hepatic lesion evident on CT. A higher liver to splenic uptake is more typical of some 18 F-labeled PSMA PET/CT but unusual in 68 Ga-labeled PSMA PET/CT scan. Further evaluation revealed a history of impaired renal function, bilateral renal atrophy, relatively decreased renal uptake of [ 68 Ga]Ga-PSMA-11, and prominent bowel activity. We concluded that impaired renal function and subsequent poor excretion resulted in increased hepatic excretion, hence the unusual increased homogeneous hepatic uptake.

Evaluation of Diagnostic Value of SPECT/CT Imaging in Post-radioiodine Therapy in Thyroid Cancer.

Objectives: This study aimed to investigate the value of single photon emission computed tomography/computed tomography (SPECT/CT) imaging in well-differentiated thyroid cancer (DTC) after radioiodine (I-131) ablation/therapy for clinical staging and risk stratification. It also aimed to determine whether SPECT/CT would change the management plan or predict the clinical outcomes of DTC patients. Methods: A total of 78 DTC patients underwent first post radioiodine therapy "Whole body iodine-131 scintigraphy (WBS) along with SPECT/CT" at the Department of Radiology and Molecular imaging, Sultan Qaboos University Hospital, Muscat, Oman, between January 2014 and August 2017. Differences between WBS and SPECT/CT, change in clinical staging, risk stratification and management were recorded. The clinical outcome at 6-12 months was recorded. A generalised McNemar test was used to assess disagreement between WBS and SPECT/CT. Results: According to the American Thyroid Association (ATA) risk stratification, the sample showed low (35.8%), intermediate (53.8%) and high-risk groups (10.2%) on WBS, which changed to 44.8%, 38.4% and 16.6%, respectively, on SPECT/CT imaging. Overall change in risk stratification was noted in 16.7% and TNM stage in 11.5% of patients after SPECT/CT imaging. SPECT/CT changed the therapeutic plan and clinical outcome in 19.2% of patients. Conclusion: SPECT/CT allows better detection and characterisation of metastatic lymph nodes and distant metastasis in DTC patients compared to WBS imaging alone. It alters TNM staging, ATA risk classification and management in a significant number of patients. It is recommended that SPECT/CT should be done routinely along with WBS in well-differentiated thyroid carcinoma.

Patients With Low Drug Levels or Antibodies to a Prior Anti-Tumor Necrosis Factor Are More Likely to Develop Antibodies to a Subsequent Anti-Tumor Necrosis Factor.

Therapeutic drug monitoring (TDM) with measurement of serum drug and antidrug antibodies (ADAb) is used widely to confirm therapeutic exposure, rule out immunogenicity, and optimize treatment of biologics in patients with inflammatory bowel diseases.1 A recent genome-wide association study found the variant HLA-DQA1∗05 to increase the risk of development of antibodies against infliximab (IFX) and adalimumab (ADM) 2-fold, regardless of concomitant immunomodulator use.2,3 However, there is currently limited evidence showing whether patients who develop antibodies to 1 anti-tumor necrosis factor (TNF) are prone to develop antibodies to the subsequent anti-TNF. Our aim was to investigate the risk of subsequent antibody development in cases (with ADAb to prior anti-TNF) versus control subjects (without ADAb to prior anti-TNF) using a large cohort of patients with inflammatory bowel diseases who underwent TDM with a drug-tolerant assay.

Preoperative Serum Vedolizumab Levels Do Not Impact Postoperative Outcomes in Inflammatory Bowel Disease.

BACKGROUND: Vedolizumab has been proposed to lead to fewer postoperative complications because of its gut specificity. Studies, however, suggest an increased risk of surgical site infections, yet the data are conflicting. OBJECTIVE: This study aimed to assess the effect of vedolizumab drug levels on postoperative outcomes in patients undergoing major abdominal surgery for IBD. DESIGN: This was a retrospective study of a prospectively maintained database. SETTING: Patients were operated on by a single surgeon at an academic medical center. PATIENTS: A total of 72 patients with IBD undergoing major abdominal surgery were included. INTERVENTIONS: Patients were exposed preoperatively to vedolizumab. MAIN OUTCOME MEASURES: The primary outcome measured was the postoperative morbidity in patients who had IBD with detectable vs undetectable vedolizumab levels. RESULTS: A total of 72 patients were included in the study. Thirty-eight patients had detectable vedolizumab levels (>1.6 µg/mL), and 34 had undetectable vedolizumab levels. The overall rate of complications was 39%, and ileus was the most common complication. There were no significant differences in clinical variables between the detectable and undetectable vedolizumab level patient groups except for the time between the last dose and surgery (p < 0.01). There were 42 patients in the ulcerative colitis cohort; 48% had an undetectable vedolizumab level and 52% had a detectable vedolizumab level. There were no differences in any postoperative morbidity between ulcerative colitis groups. The Crohn's cohort had 27 patients; 48% had an undetectable vedolizumab levels and 52% had a detectable vedolizumab level. There was a significantly lower incidence of postoperative ileus in patients who had Crohn's disease with detectable vedolizumab levels compared with patients with an undetectable vedolizumab level (p < 0.04). LIMITATIONS: Limitations include a low overall patient population and a high rate of stoma formation. CONCLUSIONS: Serum vedolizumab levels do not influence postoperative morbidity in IBD. Vedolizumab may reduce the incidence of postoperative ileus in patients with Crohn's disease. See Video Abstract at http://links.lww.com/DCR/B574. LOS NIVELES DE VEDOLIZUMAB EN SUERO PREOPERATORIO, NO AFECTAN LOS RESULTADOS POSTOPERATORIOS EN LA ENFERMEDAD INFLAMATORIA INTESTINAL: ANTECEDENTES:Se ha propuesto que el vedolizumab presenta menos complicaciones postoperatorias debido a su especificidad intestinal. Sin embargo, estudios sugieren un mayor riesgo de infecciones en el sitio quirúrgico, aunque los datos son contradictorios.OBJETIVO:Evaluar el efecto en los niveles del fármaco vedolizumab, en resultados postoperatorios de pacientes sometidos a cirugía mayor abdominal, por enfermedad inflamatoria intestinal.DISEÑO:Estudio retrospectivo de una base de datos mantenida prospectivamente.ENTORNO CLÍNICO:Pacientes intervenidos por un solo cirujano en un centro médico académico.PACIENTES:Un total de 72 pacientes con enfermedad inflamatoria intestinal sometidos a cirugía mayor abdominal.INTERVENCIONES:Exposición preoperatoria a vedolizumab.PRINCIPALES MEDIDAS DE VALORACIÓN:Morbilidad postoperatoria en pacientes con enfermedad inflamatoria intestinal, con niveles detectables versus no detectables de vedolizumab.RESULTADOS:Se incluyó en el estudio a un total de 72 pacientes. Treinta y ocho pacientes tuvieron niveles detectables de vedolizumab (> 1,6 mcg / ml) y 34 con niveles no detectables de vedolizumab. La tasa global de complicaciones fue del 39% y el íleo fue la complicación más común. No hubo diferencias significativas en las variables clínicas entre los grupos de pacientes con niveles detectables y no detectables de vedolizumab, excepto por el intervalo de tiempo entre la última dosis y la cirugía (p <.01). La cohorte de colitis ulcerosa tuvo 42 pacientes, el 48% con un nivel no detectable de vedolizumab y el 52% un nivel detectable de vedolizumab. No hubo diferencias en ninguna morbilidad postoperatoria entre los grupos de colitis ulcerosa. La cohorte de Crohn tuvo 27 pacientes, 48% con niveles no detectables de vedolizumab y el 52% con niveles detectables de vedolizumab. Hubo una incidencia significativamente menor de íleo postoperatorio en pacientes de Crohn con niveles detectables de vedolizumab, comparados con los pacientes con un nivel no detectable de vedolizumab (p <0,04).LIMITACIONES:Las limitaciones incluyen una baja población general de pacientes y una alta tasa de formación de estomas.CONCLUSIONES:Los niveles séricos de vedolizumab no influyen en la morbilidad postoperatoria de la enfermedad inflamatoria intestinal. Vedolizumab puede reducir la incidencia de íleo postoperatorio en pacientes de Crohn. Consulte Video Resumen en http://links.lww.com/DCR/B574.

Noninvasive Targeted Crohn Disease Management by Combining Endoscopic Healing Index and Therapeutic Drug Monitoring.

Background and Aims: Therapeutic drug monitoring (TDM) with measurement of serum drug and antidrug antibody concentrations is used to optimize tumor necrosis factor antagonists (anti-TNF). The endoscopic healing index (EHI) is a validated serum-based assay to measure mucosal inflammation in adults with Crohn disease (CD). Our objectives were to evaluate the relationship between EHI and TDM results and to determine the anti-TNF concentration range associated with EHI <20 (consistent with endoscopic remission). Methods: Adult and pediatric patients with CD (N = 1731) were selected retrospectively from a clinical laboratory cohort. Patients were selected if they had an ICD-10 code for CD and if results for EHI and TDM were available within 30 days of each other. The relationship between EHI and TDM results was examined and the anti-TNF concentration range associated with EHI <20 vs >50 was evaluated. Results: Median anti-TNF concentration was higher in patients with EHI <20 vs >50 for infliximab (N = 796): 11.1 vs 3.4 µg/mL and for adalimumab (N = 935): 9.2 vs 5.0 µg/mL (P < 0.0001 both drugs). Patients with antibodies to infliximab (12.8%) or adalimumab (14.9%) had lower anti-TNF concentrations (P < 0.001 both drugs) and higher EHI (P < 0.01 both drugs). The concentration range for infliximab: 5-15 µg/mL (5-9 µg/mL in pediatric patients) and for adalimumab: 5-10 µg/mL (8 µg/mL in pediatric patients) best discriminated EHI <20 vs >50. Conclusions: We report the anti-TNF concentration range associated with EHI <20. Combined testing of EHI and TDM is proposed as a noninvasive approach for treat-to-target management which could improve the ability to monitor disease and optimize anti-TNF therapy.

Association Between Vedolizumab Levels, Anti-vedolizumab Antibodies, and Endoscopic Healing Index in a Large Population of Patients with Inflammatory Bowel Diseases.

BACKGROUND: The aim of this study was to assess the relationship between serum vedolizumab (VDZ) concentrations and antibodies to VDZ (ATV) in a large cohort of patients with inflammatory bowel diseases. Furthermore, we evaluated the association between serum VDZ concentrations and a novel serum-based biomarker panel designated as the endoscopic healing index (EHI), developed and validated for identifying mucosal inflammation in patients with Crohn's disease (CD). METHODS: Retrospective study where results from patient samples submitted to a commercial clinical laboratory were included. Serum VDZ and ATV levels were analyzed using a drug-tolerant assay. In CD patients for whom both VDZ and EHI were available, VDZ concentrations were correlated with EHI. serum VDZ threshold analysis was performed using ROC curves, and the serum VDZ concentrations that best differentiated EHI < 20 (previously associated with endoscopic remission) were chosen. RESULTS: A total of 9356 patients were included in the VDZ/ATV analysis. Detectable ATV was observed in 2.9% patients with significantly lower serum VDZ concentrations when compared to those with undetectable ATV [3.9 µg/mL (0-9.0) vs. 11.3 µg/mL (5.9-20.6), p < 0.0001]. Of the patients with serum VDZ result, 287 patients had a concomitant EHI test. An inverse correlation was observed between VDZ concentration and EHI (rho = - 0.20, p < 0.001). A serum VDZ concentration ≥ 15.7 µg/ml was best correlated wi th an EHI < 20 [AUROC: 0.67 (95% CI 0.57-0.77)]. CONCLUSIONS: Incidence of ATVs was low, but significantly associated with lower VDZ levels. A serum VDZ concentration threshold of ≥ 15.7 µg/ml was associated with endoscopic remission as defined by an EHI < 20.

Immunogenicity of Tumor Necrosis Factor Antagonists and Effect of Dose Escalation on Anti-Drug Antibodies and Serum Drug Concentrations in Inflammatory Bowel Disease.

BACKGROUND: Infliximab and adalimumab concentrations are associated with important outcomes in inflammatory bowel disease (IBD). Antibodies to infliximab (ATI) and adalimumab (ATA) are associated with reduced drug concentrations and worse outcomes. Because the efficacy of dose escalation to overcome antibodies is unclear, we assessed the impact of this strategy to overcome immunogenicity in IBD. METHODS: Infliximab and adalimumab dosing, drug, and antibody concentrations were extracted from a database of patients with IBD having specimens collected for therapeutic drug monitoring. The primary outcome compared proportions with either infliximab ≥5 µg/mL or adalimumab ≥7.5 µg/mL and undetectable antibodies between dose-escalated and non-escalated patients. Area under the receiver operating characteristic curve analyses determined antibody concentrations below which dose escalation was associated with the primary outcome. RESULTS: The study included 63,176 patients treated with infliximab and 46,429 patients treated with adalimumab. We detected ATI and ATA in 23.6% (n = 14,900) of patients treated with infliximab and 19.6% (n = 9101) of patients treated with adalimumab. In patients with ATI, infliximab dose escalation (n = 453) yielded higher proportions achieving the primary outcome (47.5% vs 30.9%; P < 0.001), greater drug concentration increases (5.9 µg/mL vs 0.2 µg/mL; P < 0.001), and ATI reductions (4.3 U/mL vs 1.9 U/mL; P = 0.002) compared to no escalation (n = 204). An ATI threshold of 8.55 U/mL was associated with achieving the primary outcome with dose escalation (area under the curve = 0.66). For patients with ATI ≤8.55 U/mL (n = 274), higher proportions (59.1% vs 29.6%; P < 0.001) achieved the primary outcome compared with those with ATI >8.55 U/mL (n = 179). No patients treated with adalimumab achieved the primary outcome (0/390), regardless of dose escalation (n = 87). CONCLUSION: Dose escalation increased drug concentrations and eliminated antibodies with infliximab but not adalimumab. Initial ATI ≤8.55 U/mL was associated with increased efficacy of dose escalation using this assay.