Therapeutic drug monitoring in inflammatory bowel disease patients on vedolizumab.

OBJECTIVE: We aimed to investigate whether vedolizumab (VDZ) levels were associated with inflammatory markers or clinical or endoscopic scoring in inflammatory bowel disease (IBD). METHODS: Besides demographic data, clinical scoring, endoscopic data, and laboratory markers of IBD patients treated with VDZ from 2015 to 2020 who had trough levels drawn on maintenance therapy were collected at baseline and at follow-up (after at least 8 weeks on VDZ therapy or after change in dose frequency). Low drug levels were defined as VDZ trough <20 µg/mL. RESULTS: We identified 89 patients with a mean age of 42.9 years. Of the 90 total trough levels drawn, 61.1% were low. Among patients on every 8 week (Q8 week) VDZ dosing, 81.5% had low troughs. After increasing dosing frequency to Q4 weeks, all patients showed improvement in VDZ levels, but 30.6% remained <20 µg/mL. Higher VDZ levels on Q8 week dosing were associated with higher albumin levels (P = 0.01). While higher VDZ levels on Q4 week dosing were associated with higher albumin (P = 0.02), lower erythrocyte sedimentation rate (P = 0.04) and higher likelihood of having mild disease or endoscopic remission (P = 0.01). No significant association was found between VDZ levels and clinical scoring, body mass index, hemoglobin, vitamin D or platelet levels on either Q8 or Q4 week dosing. CONCLUSIONS: Higher VDZ troughs were associated with higher albumin, mild endoscopic disease or endoscopic remission. Patients who continue to have low VDZ troughs despite Q4 week dosing may require a change in therapy.

Choosing Therapy for Moderate to Severe Crohn's Disease.

The availability of approved therapies for Crohn's disease has significantly increased over the past decade. To choose the appropriate therapy for the patient, ideally head to head studies, and data on positioning could help the provider individualize the decision. Due to the paucity of head-to-head trial data, we turn to network meta-analysis and real-world studies to help guide our treatment choices. Ultimately, the best approach is to consider each patient on an individual basis, taking into consideration the characteristics of their disease, individual risk factors, extra-intestinal manifestations, co-morbid conditions, patient age, cost, and personal preferences. In this review, we summarize the evidence comparing biologic as well as small molecule therapies for the treatment of moderate-to-severe Crohn's disease. We have summarized the evidence in relation to factors such as efficacy, fistulizing disease, pregnancy, infection risk, and co-existing conditions.

Clinical Evaluation of Upadacitinib in the Treatment of Adults with Moderately to Severely Active Ulcerative Colitis (UC): Patient Selection and Reported Outcomes.

This review addresses appropriate patient selection for upadacitinib, a Janus kinase inhibitor approved by the FDA and EMA for treatment of moderately to severely active ulcerative colitis (UC). Janus kinase molecules can contribute to the inflammatory pathway, so inhibiting certain of them may prove efficacious in treating UC and may reduce safety concerns. Upadacitinib is the newest Janus kinase inhibitor to be approved for UC, so it is timely and relevant to review patient selection and when to consider this medication. We will discuss efficacy and safety data from the pivotal clinical trials on upadacitinib. These data can be shared with patients and can inform the use of these agents in clinical practice.

Impact of pre-operative transjugular intrahepatic portosystemic shunt on post-operative outcomes following non-transplant surgeries in patients with decompensated cirrhosis.

Background: Patients with cirrhosis have a high risk for morbidity and mortality in relation to abdominal surgery. Despite improvements in surgical techniques and intensive care, major abdominal surgery still remains a challenge. Major factors determining short- and long-term survival and perioperative complications in this patient population include severity of liver dysfunction, degree of portal hypertension (PHTN), and the presence of related complications such as ascites. Elective transjugular intrahepatic portosystemic shunt (TIPS) placement prior to surgery has been reported to improve perioperative outcomes, but available data is limited to case reports and small case series. We aimed to determine the impact of elective TIPS placement on perioperative outcomes after abdominal-pelvic surgeries in patients with cirrhosis. Methods: We performed a retrospective chart review of patients who underwent elective TIPS and compared these patients with a cohort of cirrhotic patients who underwent any abdominal surgeries without TIPS placement. The primary outcomes were mortality at 30 days and 1 year following surgery. Other post-operative outcomes compared between the two groups, included: blood loss, worsening ascites, wound leak, infections, encephalopathy, liver decompensation, and length of hospitalization. Results: Among 38 patients with cirrhosis who underwent abdominal surgery, 20 patients underwent pre-operative elective TIPS placement. Demographic characteristics of the two groups were comparable including age, gender, and body mass index (BMI). The median age was 62 years with a male predominance (62.5%). Both groups had similar etiologies of cirrhosis with hepatitis C virus (HCV) (34.2%) being most common. The most frequent indications for surgery were strangulated hernia (50%) in the TIPS group and acute cholecystitis (55.6%) in the non-TIPS group. Mean pre-TIPS hepato-venous portal gradient (HVPG) was 16.5 mmHg and mean post-TIPS HVPG was 7.0 mmHg. Mortality at 1 month was not statistically different between the groups (20% vs. 5.6%, respectively, P=0.19). The 1-year mortality was also not statistically different between the two groups (20% vs. 11.1%, P=0.36). Conclusions: We found no statistically significant difference in mortality or rate of post-operative complications between patients who received pre-operative TIPS and those who did not in our age-matched cohort.

P013 Resolution of Infliximab Associated Infusion Hypersensitivity After Switching to Biosimilar Infliximab-dyyb.

CASE: Background: Administration of infliximab for the treatment of inflammatory bowel disease has a well-recognized risk of infusion-related (IR) adverse events. The recent introduction of the biosimilar infliximab-dyyb (Inflectra®) has been shown to have similar efficacy with comparable safety profile when compared to infliximab; however, although the active ingredients are similar, the inactive ingredients are different. We present a case of a 26-year-old female with ulcerative colitis who had resolution of her IR hypersensitivity when switched from infliximab to infliximab-dyyb. CASE DESCRIPTION: A 26-year-old female with a past medical history of ulcerative pancolitis presented to our clinic with the chief complaint of rash associated with her infliximab infusions. She described pruritic raised lesions which would occur on her upper and lower extremities during her infusions. She denied any shortness of breath or wheezing, and her symptoms were well controlled with methylprednisolone 40mg IV prior to her infusions. Previously, she had been treated for her UC with oral mesalamine, azathioprine and intermittent prednisone and did not have any adverse reactions to these medications. She has no known allergies to other medications and her peripheral eosinophil count was 1.6%. She was initially started on infliximab 5mg/kg every 8 weeks since 2013 and had achieved clinical as well as endoscopic remission with her most recent colonoscopy graded as Mayo 0. On account of her infusion reaction, drug antibodies were checked but were not detected. Infliximab level was 8.8 µg/ml. Due to insurance she was required to switch to infliximab-dyyb. After switching to the biosimilar, she has not had any infusion related reactions and no longer requires premedication with methylprednisolone with her infusions. DISCUSSION: Immediate IR reactions have been reported in 5-23% of IBD patients receiving infliximab and those who develop antibodies towards infliximab have a 2-fold risk of acute IR events. Side effects have been reported to be the primary reason for discontinuation of infliximab, and studies have shown that discontinuation can lead to an increased risk of relapse of inflammatory bowel disease. Although infliximab and infliximab-dyyb have analogous active ingredients, the inactive ingredients differ. Specifically, infliximab-dyyb lacks monobasic sodium phosphate and dibasic sodium phosphate, which acts as an emulsifier which we believe contributed to her IR with originator biologic infliximab. It is important to recognize these differences as IR hypersensitivities may be attributed to inactive ingredients; especially when antibodies are negative. Our case report suggests that a switch to biosimilar infliximab in patients may provide added benefit especially in those that have reactions occurring from inactive ingredients in the originator biologic.

Autosplenectomy in a Patient with Paroxysmal Nocturnal Hemoglobinuria (PNH).

Autosplenectomy (AS) is a known complication of diseases such as sickle cell anemia, celiac disease, and inflammatory bowel disease. We report the first known case of AS due to paroxysmal nocturnal hemoglobinuria (PNH). A 24-year-old Caucasian male had evidence of hemolytic anemia at the age of 14 and was diagnosed with PNH at the age of 16. He had recurrent episodes of sepsis due to dialysis line infections from poor hygiene, and blood cultures had been positive for multiple organisms including Staphylococcus aureus, Enterococcus faecalis, and Streptococcus pneumoniae. The patient's peripheral blood smears since the age of 14 years demonstrated Howell-Jolly bodies in conjunction with thrombocytopenia and hemolytic anemia, but abdominal ultrasonography reported a normal appearing spleen. The patient presented with septicemia two years after starting eculizumab, and his peripheral blood smear showed extensive Howell-Jolly bodies, Pappenheimer bodies, acanthocytes, and target cells. Splenic ultrasonography demonstrated an atrophic spleen with multifocal scarring, and absent splenic uptake of liver-spleen scintigraphy, consistent with AS. Clinicians should remain vigilant of the potential sequelae of PNH and consider the possibility of the development of AS.

A Rare Case of Infective Endocarditis Caused by Gemella haemolysans.

Gemella haemolysans is a gram-positive coccoid, facultative anaerobe of the mucous membranes. In rare cases, it has been identified as an opportunistic pathogen in the development of endocarditis. Here, we describe a case of infective endocarditis in a patient with a bicuspid aortic valve. A 38-year-old man presented with the complaint of exertional dyspnea of one month duration. He was found to have leucocytosis and his blood cultures grew Gemella haemolysans. Trans-esophageal echocardiography showed a bicuspid aortic valve with 1.5 x 1.5 cm vegetative mass, severe aortic regurgitation, and an aortic root abscess. The patient was started on intravenous ampicillin and gentamycin. He then underwent mechanical aortic valve replacement and bovine reconstruction of the left ventricular outflow tract. Our case highlights the importance of considering atypical pathogens as causative agents of infective endocarditis.

Definition, Pathogenesis, and Management of That Cursed Dyspepsia.

Dyspepsia is an umbrella term used to encompass a number of symptoms thought to originate from the upper gastrointestinal tract. These symptoms are relatively nonspecific; not surprisingly, therefore, a myriad of conditions may present with any one or a combination of these symptoms. Therein lays the clinician's first challenge: detecting the minority who may have a potentially life-threatening disorder, such as gastric cancer, from a population whose symptoms are, for the most part, considered functional in origin. The second challenge lies in the definition and management of those individuals with functional dyspepsia (FD); the major focus of this review. The Rome process has addressed the issue of FD definition and a look back at the evolution of Rome criteria for this disorder illustrates the complexities that have so frustrated us. There has been no shortage of hypotheses to explain symptom pathogenesis in FD; initially focused on gastric sensorimotor dysfunction, these have now strayed well into the duodenum and have come to entertain such factors as immune responses and the microbiome. FD has proven to be an equally challenging area for therapeutics; while the staple approaches of acid suppression and eradication of Helicobacter pylori have some limited efficacy in select populations, strategies to ameliorate symptoms in the majority of sufferers based on presumed pathophysiology have largely foundered. Lacking a validated biomarker(s) FD continues to be an elusive target and is likely to remain so until we can better define the various phenotypes that it must surely contain.