Therapeutic drug monitoring in inflammatory bowel diseases. Position statement of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis. / Monitorización terapéutica de los fármacos biológicos en la enfermedad inflamatoria intestinal. Documento de Posicionamiento del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU).

The treatment of inflammatory bowel disease has undergone a significant transformation following the introduction of biologic drugs. Thanks to these drugs, treatment goals have evolved from clinical response and remission to more ambitious objectives, such as endoscopic or radiologic remission. However, even though biologics are highly effective, a significant percentage of patients will not achieve an initial response or may lose it over time. We know that there is a direct relationship between the trough concentrations of the biologic and its therapeutic efficacy, with more demanding therapeutic goals requiring higher drug levels, and inadequate exposure being common. Therapeutic drug monitoring of biologic medications, along with pharmacokinetic models, provides us with the possibility of offering a personalized approach to treatment for patients with IBD. Over the past few years, relevant information has accumulated regarding its utility during or after induction, as well as in the maintenance of biologic treatment, in reactive or proactive strategies, and prior to withdrawal or treatment de-escalation. The aim of this document is to establish recommendations regarding the utility of therapeutic drug monitoring of biologics in patients with inflammatory bowel disease, in different clinical practice scenarios, and to identify areas where its utility is evident, promising, or controversial.

Severe outbreak of ulcerative colitis and cerebral neoplasia. Difficult management in COVID time.

A 61-year-old male diabetic patient, diagnosed with ulcerative colitis (UC) 30 years ago, currently under treatment with mesalazine is presented. He was admitted to the emergency department due to a severe outbreak of UC, with 15 depositions daily, rectal bleeding and poor general condition. A brain CT-scan was carried out in the emergency department due to a sudden self-limited aphasia. A left frontal lesion of 45x38 mms with a prominent perilesional edema and with a displacement of the midline was reported. This was believed to be a meningioma (figure 1A). Urgent neurosurgery was not performed, prioritizing the severe flare-up UC. Based on this, full-dose metilprednisolone was administered.

Perianal Paget's disease.

The incidence of extramammary Paget's disease (EMPD) is very low. It is very important to distinguish between primary Paget's disease and secondary to another process. An 85-year-old man consulted for the presence of an erythematous plaque located in the anal and gluteal area, confirming Paget cells in the biopsy.

GIST. Duodenopancreatectomía. Tumor neuroendocrino no funcionante.

Zollinger Ellison syndrome is an unusual entity. This termn is used to describe the clinical manifestations of a gastrin-synthesizing neoplasm. Gastrinomas occur mainly in the duodenum and pancreas. Primary gastrinomas are rarely found in other intra-abdominal sites, such as the ovary, bile ducts, spleen or kidney, or even more unusual in extra-abdominal locations. Several studies provide strong evidence that gastrinomas can also occur in the lymph nodes. However, the existence of primary lymph node gastrinomas is controversial.

Ustekinumab in Crohn's disease: real-world outcomes and predictors of response.

BACKGROUND: ustekinumab is a monoclonal antibody that inhibits interleukins IL-12 and IL-23, and is approved for the treatment of Crohn's disease (CD) and, more recently, also ulcerative colitis (UC). The aim of this study was to evaluate the effectiveness and safety of ustekinumab, as well as to identify possible predictive factors of response in a real-life setting. METHODS: an observational, retrospective, multicenter study was carried out in 4 hospitals in Andalusia. Adult patients with a confirmed diagnosis of CD treated with ustekinumab from 2017 to 2019 were included. Clinical response was analyzed at 3, 6 and 12 months of treatment. Clinical disease activity was assessed with the Harvey-Bradshaw index (HBI) and the Crohn's Disease Activity Index (CDAI); biochemical response was assessed with lab parameters such as CRP and ESR. One-year ustekinumab drug-survival was analyzed. RESULTS: a total of 98 patients were analyzed (mean age, 43 years; 52 % were male); 56 % had failed with ≥ 2 previous biologicals therapies. At 3 months, 69 % of the patients were in response and 40.8 % in remission. At 6 months, 56 % were in clinical remission. At 12 months, 73.7 % were in clinical response and 60.5 % in remission. Corticosteroid-free remission was 32.4 %, 44 %, and 47.4 % at 3, 6, and 12 months, respectively. Cumulative survival after one year of treatment with ustekinumab was 85.3 %. Biochemical parameters such as CRP and ESR showed a statistically significant decrease between baseline and control levels at 3, 6, and 12 months. A lower HBI at baseline and female sex were predictors of corticosteroid-free clinical remission in a univariate analysis. In the multivariate analysis no variables were found as predictors of corticosteroid-free clinical remission. CONCLUSION: ustekinumab therapy is safe and useful, inducing clinical response in more than 50 % of patients, including patients who failed with other biological therapies.

Double strangeness: a young male with intestinal obstruction secondary to gastrointestinal follicular lymphoma.

Primary follicular lymphomas (FL) of the gastrointestinal (GI) tract are very rare and constitute < 4 % of all non-Hodgkin's lymphomas at this location. We report our experience with primary FL of the GI tract.

Cut-off ranges of infliximab serum levels in Crohn's disease in the clinical practice.

INTRODUCTION: between 30 % and 40 % of patients treated with infliximab lose response during maintenance. Therapeutic drug monitoring could be used to optimize management in these situations. However, infliximab serum levels are not well defined. The aim of this study was to determine the cut-off range of infliximab serum levels in Crohn's disease patients in remission in the clinical practice. METHODS: an observational retrospective study was performed from 2016 to 2017. Patients were included with established Crohn's disease, who had been on a maintenance dose schedule of infliximab. Infliximab levels and antibodies to infliximab were measured at least twice in all patients, after induction and after six months of treatment. Clinical remission was defined as ≤ 4 using the Harvey-Bradshaw index. Cluster analysis was used to analyze the results. RESULTS: one hundred and five Crohn's disease patients were included in the study; 57.1 % were male with a mean age of 39 years (SD ± 12.9). The median (range) time of the disease was eleven years (7-15) and the median (range) time of follow-up was 32 months (22-38). Patients who achieved remission had infliximab serum levels between 4.26-8.26 ug/ml versus 0.06-1.43 ug/ml in patients who did not achieve remission after induction. Infliximab serum levels were 2.84-7.75 ug/ml and 0.05-2.69 ug/ml in patients who achieved remission versus those who did not achieve remission after six months of treatment. Overall, 4.26-8.26 ug/ml was found to be the best cut-off range for remission. CONCLUSIONS: in our clinical practice, serum levels of infliximab in Crohn's disease patients should be higher than 4 ug/ml to achieve clinical remission.

Switching from reference infliximab to CT-P13 in patients with inflammatory bowel disease: results of a multicenter study after 12 months.

BACKGROUND AND AIMS: infliximab has changed the natural history of inflammatory bowel disease (IBD). The advent of biosimilar treatments such as CT-P13 will hopefully improve the availability of biological therapies. Data with regard to drug switching are currently limited. The objective of the study was to assess the effectiveness and safety of switching from the reference product (RP), infliximab, to CT-P13 in patients with IBD. METHODS: this was a multicenter prospective observational study in patients with Crohn's disease (CD) and ulcerative colitis (UC). All patients had switched from infliximab RP (Remicade®) to CT-P13 treatment and were followed up for 12 months. The efficacy endpoint was the change in clinical remission assessed at 0 and 12 months, according to the Harvey-Bradshaw score and partial Mayo score for patients with CD and UC, respectively. Adverse events were monitored and recorded throughout the study. RESULTS: a total of 167 patients (116 CD/51 UC) were included; 88.8% (103/116) of patients with CD were in remission at the time of the drug switch and 69.7% were in remission at 12 months. The Harvey-Bradshaw (HB) score significantly changed at 12 months (p = 0.001); 84.3% (43/51) of patients with UC were in remission at the time of the drug switch and 76.7% were in remission at 12 months. No significant changes in the median partial Mayo score (p = 0.87) were observed at 12 months. Serious adverse events related to medication were reported in 12/167 (7.2%) cases. CONCLUSION: switching from infliximab RP to CT-P13 is safe and effective at 12 months. The loss of efficacy at 12 months was 15.7%.