Biological treatment interruption in inflammatory bowel disease: Motivation and predictive factors.

BACKGROUND: Loss-of-response and adverse events (AE) to biologics have been linked to HLA-DQA1*05 allele. However, the clinical factors or biologic used may influence treatment duration. Our objective was to evaluate the influence of clinical and therapeutic factors, along with HLA, in biological treatment discontinuation. METHODS: A retrospective study of consecutive IBD patients treated with biologics between 2007 and 2011 was performed. Main outcome was treatment discontinuation due to primary non-response (PNR), secondary loss of response (SLR) or AE. HLA-DQA1 genotyping was done in all patients. Regression analyses were used to assess risk factors of treatment discontinuation. RESULTS: One hundred fifty patients (61% male) with 312 biologic treatments were included. 147 (47%) were discontinued with a cumulative probability of 30%, 41% and 56% at 1, 2 and 5 years. The use of infliximab (p=0.006) and articular manifestations (p<0.05) were associated with treatment discontinuation. Considering cause of withdrawal, Ulcerative Colitis (UC) had a higher proportion of PNR (HR=4.99; 95% CI=1.71-14.63; p=0.003), SLR was higher if biologics had been indicated due to disease flare (HR=2.32; 95% CI=1.05-5.09; p=0.037) while AE were greater with infliximab (HR=2.46; 95% CI=1.48-4.08; p<0.001) or spondylitis (HR=2.46; 95% CI=1.78-6.89; p<0.001). According to the biological drug, HLA-DQA1*05 with adalimumab showed more SLR in cases with Crohn's disease (HR=3.49; 95% CI=1.39-8,78; p=0.008) or without concomitant immunomodulator (HR=2.8; 95% CI=1.1-6.93; p=0.026). CONCLUSIONS: HLA-DQ A1*05 was relevant in SLR of IBD patients treated with adalimumab without immunosupression. In patients treated with other biologics, clinical factors were more important for treatment interruption, mainly extensive UC or extraintestinal manifestations and having indicated the biologic for flare.

Autoimmune hepatitis triggered by COVID-19.

We present the case of a 60-year-old female with no drug allergies or toxic habits, with hypothyroidism, and receiving treatment with levothyroxine. She was admitted in February 2021 and presented with choluria of 72 hours duration; there were no abdominal or respiratory clinical symptoms, and no related fever. Medical examination findings included mucocutaneous jaundice and a recorded oxygen saturation of 97 % in ambient air. There was a notable pattern of cytolysis compatible with acute hepatitis, and no history hepatotoxic drugs. Screening was performed for acute hepatitis in addition to serology testing, determination of autoantibodies and immunoglobulins, a PCR test for COVID, and a radiologic study.

LONG-TERM EVOLUTION OF CONTINENCE AND QUALITY OF LIFE AFTER SPHINCTEROPLASTY FOR OBSTETRIC FECAL INCONTINENCE.

PURPOSE: Evaluate the long-term evolution of continence and patient's quality of life after surgical treatment for obstetric fecal incontinence. METHODS: A prospective longitudinal study was conducted including consecutive patients who underwent sphincteroplasty for severe obstetric fecal incontinence. The first phase analyzed changes in continence and impact on quality of life. The second phase studied the long-term evolution reevaluating the same group of patients six years later. Degree of fecal incontinence was calculated using the Cleveland Clinic Score. Quality of life assessment was carried out with the Fecal Incontinence Quality of Life Scale. RESULTS: 35 patients with median age of 55 (range, 28-73) completed the study. Phase One Results: After a postoperative follow-up of 30 months (4-132), Cleveland Clinic Score had improved significantly from a preoperative of 15.7 ± 3.1 to 6.1 ± 5 (p <0.001). Phase Two Results: median follow-up in phase two was 110 months (76- 204). The Cleveland Clinic Score lowered to 8.4 ± 4.9 (p = 0.04). There were no significant differences between phases one and two in terms of quality of life: lifestyle (3.47 ± 0.75 vs. 3.16 ± 1.04), coping/behavior (3.13 ± 0.83 vs 2.80 ± 1.09), depression/self-perception (3.65 ± 0.80 vs 3.32 ± 0.98) and embarrassment (3.32 ± 0.9 vs 3.12 ± 1). CONCLUSION: Sphincteroplasty offers good short-medium term outcomes in continence and quality of life for obstetric fecal incontinence treatment. Functional clinical results deteriorate over time but did not impact on patients' quality of life.

Thiopurine adherence: a high prevalence with low impact on UC outcomes.

INTRODUCTION: thiopurines are used as maintenance therapy in patients with ulcerative colitis (UC). There are contradictory results regarding the relationship between adherence to treatment and risk of relapse. OBJECTIVES: to quantify and evaluate the trends in thiopurine prescription rates, and to determine the impact and risk factors of non-adherence. METHODS: analytical, observational, retrospective study of UC patients taking thiopurines included in the ENEIDA single-center registry from October 2017 to October 2019. Adult patients in clinical remission at the beginning of the study on thiopurines maintenance treatment for at least 6 months before recruitment were included. Adherence was evaluated with an electronic pharmaceutical prescription system. Adherence was considered when 80 % or more of the prescribed medication was dispensed at the pharmacy. Kaplan-Meier curves and a regression model were used to examine year-to-year treatment dispensation, and to identify factors associated with non-adherence. RESULTS: a total of 41 patients were included, of whom 71 % were males with a mean age of 44 (14), and 26.8 % were concomitantly managed with biological therapy. Overall, 22 % were non-adherent to thiopurines. No predictive factors of non-adherence were identified. Adherence rate did not correlate with disease activity during two years of follow-up (OR 1.6; 95 % CI = 0.3-9.1). Left-sided colitis and concomitant biological treatment were related with disease relapse (p ≤ 0.01). CONCLUSION: adherence to thiopurines in UC patients is high (78 %). Non-adherence is not related to clinical or pharmacological factors. Adherence rate was not associated with disease activity.

Crohn's disease. / Enfermedad de Crohn.

Crohn's disease is a chronic inflammatory bowel disease of unknown etiology associated with an impaired immune response, with periods of activity and remission. It is characterised by patchy and transmural lesions which can affect the entire gastrointestinal tract, from the mouth to the anus. The most frequent symptoms are abdominal pain and diarrhoea, which can seriously affect patients' quality of life. The increasing incidence and prevalence of the disease in our area has had a large impact on clinical practice, with the rapid development of diagnostic and therapeutic techniques. To reduce the risk of complications, primary care physicians and gastroenterologists should be familiar with the management of the disease.

Amyloidosis in Inflammatory Bowel Disease: A Systematic Review of Epidemiology, Clinical Features, and Treatment.

BACKGROUND AND AIMS: Amyloidosis is a rare complication of inflammatory bowel disease [IBD]; its low prevalence has hindered both descriptive and therapeutic studies. The aim of this study was to estimate the prevalence of amyloidosis in IBD and the risk factors associated with this complication. METHODS: This paper presents an observational study, followed by a systematic review of the epidemiological and clinical characteristics of the disease and a review of the diagnostic and therapeutic options. RESULTS: The prevalence of amyloidosis among IBD patients is 0.53% (95% confidence interval [CI]: 0.32-0.75), although epidemiological data suggest that it may be under-diagnosed. The phenotype most frequently associated with amyloidosis is males with aggressive and extensive Crohn's disease, fistulising behaviour, perianal disease, and extra-intestinal complications, with the development of proteinuria and renal failure. CONCLUSIONS: Identifying risk factors of amyloidosis in IBD patients and screening for proteinuric renal dysfunction are useful to improve diagnostic accuracy. Referral of biopsies to a tertiary centre should also be considered, to improve diagnostic accuracy. Although there is no reliable evidence on the effectiveness of treatment, it seems reasonable to treat the underlying disease with potent immunosuppression to minimise inflammatory activity, thereby switching off amyloidogenesis.

A pharmacokinetic approach to model-guided design of infliximab schedules in ulcerative colitis patients.

BACKGROUND: Infliximab, an anti-tumour necrosis factor approved for treatment of Crohn´s disease and ulcerative colitis, is administered at predefined interdose intervals. On insufficient response or loss of response, treatment can be intensified. The lack or loss of response is likely related to complex pharmacokinetics of infliximab. AIMS: To explore optimal dosing strategies of infliximab in treatment-naïve patients with ulcerative colitis through predictive Monte Carlo simulations based on a validated population PK model. METHODS: A population of 2,000 treatment-naïve patients was generated by Montecarlo simulation. Six dosing strategies for maintenance therapy were simulated on this population. Strategies 1 and 2 consisted on 5 mg/kg and 6 mg/kg doses, respectively, and 8 weeks inter-dose interval. Strategies 3 and 4 used Individualized doses, adjusted to albumin level, sex and body weight, and a fix interdose interval of 8 weeks to achieve a target trough concentration of 5 mg/L or 6 mg/L, respectively. Strategies 5 and 6 used a fix dose of 5 mg/kg and individualized inter-dose intervals, adjusted to the same covariates, to achieve a target concentration, of 5 mg/L or 6 mg/L, respectively. RESULTS: Strategies 2-6 reached trough levels statistically higher than strategy 1 (p < 0.05). Strategy 5 proved to be the best dosing strategy. It was associated with a higher proportion of responder patients than strategy 1 (62 % vs. 40 %) without reaching higher peak concentrations. CONCLUSIONS: Optimization of maintenance treatment of colitis with infliximab by a pharmacokinetic approach could benefit infliximab-naive patients with ulcerative colitis.

[Analysis of experience in the use of dynamic pelvic magnetic resonance imaging in the assessment of obstructive defaecation syndrome]. / Análisis de nuestra experiencia mediante el uso de resonancia magnética dinámica pelviana en la evaluación del síndrome de defecación obstructiva.

INTRODUCTION: The aetiological diagnosis of obstructive defaecation syndrome (ODS) requires, among others, imaging tests. The purpose of this study is to descriptively analyse and compare the findings of dynamic pelvic magnetic resonance imaging (DPMRI) with the clinical examinations in patients with ODS. MATERIAL AND METHODS: A prospective comparative study was made between the physical examination and the DPMRI, with a descriptive analysis of the results. A total of 30 patients were included (2 males and 28 females), with a median age of 60 (range 23-76) years, with symptoms of ODS. An anamnesis and detailed physical examination and a DPMRI were performed on all of them. Functional (anismus) and morphological changes (rectocele, enterocele, intussusception, etc.), were analysed. RESULTS: The physical examination did not detect anomalies in 6 (20%) patients. A rectocele was diagnosed in 21 (70%) of the cases, and 2 (6.7%) a rectal mucosal prolapse. The DPMRI showed evidence of pelvic floor laxity in 22 (73.3%) cases, an enterocele in 4 (13.3%), a sigmoidocele in 2 (6.7%), intussusception in 8 (26.7%), rectal mucosal prolapse in 4 (13.3%), anismus in 3 (10%), and a cystocele in 4 (13.3%). The rectocele was the most frequent diagnosis, being given in 26 (86.6%) patients. CONCLUSIONS: Magnetic resonance imaging provides an overall pelvic assessment with good definition of the tissues, and does not use ionising radiation, is well tolerated, and provides us with complementary information to arrive at the diagnosis, and establish the best treatment for ODS. Larger studies comparing videodefaecography (VD), currently considered the Gold Standard technique, are needed to be able to demonstrate whether it is superior or not to DPMRI.

[Impact of endorectal advancement flaps in fecal incontinence]. / Impacto de los colgajos transanales de avance en la continencia fecal.

OBJECTIVE: The aim of this study was the prospective evaluation of the functional results of a series endorectal advancement flaps in the treatment of complex anal fistulas. MATERIAL AND METHODS: A total of 90 patients were operated on for a complex anal fistula by means of fistulectomy and endorectal advancement flap. The functional results were evaluated using the Wexner continence scale and an anorectal manometry study before and after surgery. RESULTS: There were seven patients with fistula recurrence (7.7%) and the same surgical procedure was performed on five of them, resulting in healing in all cases. Significant reductions in maximum resting pressure (83.85+/-30.96 vs 46.51+/-18.67; p<0.001) and maximum squeeze pressure (220.97+/-100.21 vs 183.06+/-75.36; p<0.001) were seen 3 months after surgery. On the continence scale, 80% of patients had a normal continence with a value of 0 on the postoperative Wexner scale, while 20% recorded changes in continence values, most of them lower than 3 points. CONCLUSIONS: Endorectal advancement flap is an effective surgical procedure in complex anal fistulas treatment, with a low recurrence rate. Only 20% of the patients showed changes in the continence value.