Long-term effectiveness and safety of ustekinumab in bio-naïve and bio-experienced anti-tumor necrosis factor patients with Crohn's disease: a real-world multicenter Brazilian study.

BACKGROUND: The effectiveness of ustekinumab (UST) in the treatment of Crohn's disease (CD) has been demonstrated in the pivotal Phase 3 UNITI 1 and 2 and IM-UNITI studies in both anti-TNF-naïve and anti-TNF-exposed patients. Given the selective nature of pivotal trial designs, real-world effectiveness and safety studies are warranted. We report our experience with UST treatment in a large, real-world multicenter cohort of Brazilian patients with CD. METHODS: We performed a retrospective multicenter study including patients with CD, predominantly biologically refractory CD, who received UST. The primary endpoint was the proportion of patients in clinical remission at weeks 8, 24 and 56. Possible predictors of clinical and biological response/remission and safety outcomes were also assessed. RESULTS: Overall, 245 CD (mean age 39.9 [15-87]) patients were enrolled. Most patients (86.5%) had been previously exposed to biologics. According to nonresponder imputation analysis, the proportions of patients in clinical remission at weeks 8, 24 and 56 were 41.0% (n = 98/239), 64.0% (n = 153/239) and 39.3% (n = 94/239), respectively. A biological response was achieved in 55.4% of patients at week 8, and 59.3% were in steroid-free remission at the end of follow-up. No significant differences in either clinical or biological remission were noted between bio-naïve and bio-experienced patients. Forty-eight patients (19.6%) presented 60 adverse events during the follow-up, of which 8 (13.3%) were considered serious adverse events (3.2% of 245 patients). Overall, a proximal disease location, younger age, perianal involvement, and smoking were associated with lower rates of clinical remission over time. CONCLUSIONS: UST therapy was effective and safe in the long term in this large real-life cohort of Brazilian patients with refractory CD, regardless of previous exposure to other biological agents.

The Impact of Spirituality and Religiosity on Mental Health and Quality of Life of Patients with Active Crohn's Disease.

We aim to investigate the association among religious/spiritual coping (RSC), quality of life (QOL), and mental health in patients with active Crohn's disease (CD). This cross-sectional study included 102 patients with active CD. Religious and spiritual beliefs were common among patients, being positive RSC higher than negative RSC. Negative coping was associated with mood disorders (depressive or anxiety symptoms) through the Hospital Anxiety and Depression Scale (ß = 0.260, p < 0.01) but not with QOL (Inflammatory Bowel Disease Questionnaire) (ß = - 0.105, p = NS) after adjustments. Positive coping and other religious/spiritual beliefs and behaviors were not associated with either QOL or mental health. This study suggests that a negative RSC is associated with worse mental health outcomes. This may detrimentally impact adaptations to deal with CD in the active phase, although patients generally tend to use more common positive strategies. These findings may increase the awareness of health professionals while dealing with spiritual beliefs in patients with CD.

Impact of superimposed Clostridium difficile infection in Crohn's or ulcerative colitis flares in the outpatient setting.

PURPOSE: The prospective assessment of Clostridium difficile infection (CDI) impact in inflammatory bowel disease (IBD) flare in outpatient setting has been poorly investigated. We aimed to evaluate the prevalence and the associated factors with CDI in IBD outpatients presenting colitis flares as well as the outcomes following treatment. METHODS: In this prospective cohort study, conducted from October, 2014, to July, 2016, 120 IBD patients (55% presenting colitis flare) and 40 non-IBD controls were assessed for CDI. Multivariate regression analysis was performed to identify predictors of CDI. Outcome analysis was estimated for recurrent CDI, hospitalization, colectomy, and CDI-associated mortality. RESULTS: The number of patients with CDI was significantly higher in IBD patients experiencing flares than in both inactive IBD and non-IBD groups (28.8 vs. 5.6 vs. 0%, respectively; p = 0.001). Females (OR = 1.39, 95% CI, 1.13-17.18), younger age (OR = 0.77, 95% CI, 0.65-0.92), steroid treatment (OR = 7.42, 95% CI, 5.17-40.20), and infliximab therapy (OR = 2.97, 95% CI, 1.99-24.63) were found to be independently associated with CDI. There was a dose-related increase in the risks of CDI on patients which had taken prednisone. Those treated with vancomycin had a satisfactory response to therapy, but 21% presented recurrent CDI and 16% were hospitalized. Neither necessity of colectomy nor mortality was noticed in any patient during the investigation. CONCLUSIONS: In IBD outpatients presenting colitis flares, CDI is highly prevalent. Females, younger age, infliximab, and notably steroid therapy were independently associated with CDI. Most patients with CDI experienced mild-to-moderate disease, and prompt treatment with vancomycin was highly effective, which seems to reduce the serious complication risks.

A guide to prepare patients with inflammatory bowel diseases for anti-TNF-α therapy.

Current therapy of moderate-to-severe inflammatory bowel disease (IBD) often involves the use of anti-tumor necrosis factor alpha (TNF-α) agents. Although very effective, theses biologics place the patient at increased risk for developing infections and lymphomas, the latter especially when in combination with thiopurines. Appropriate patient selection, counseling, and education are all important features for the successful use of anti-TNF-α therapy. A thorough history to rule-out contraindications of this therapy and emphasis on monitoring guidelines are important steps preceding administration of anti-TNF-α agents. This therapy should only be considered if a recent evaluation has established that the patient has active IBD. In addition, it is important to exclude disease mimickers. Anti-TNF-α agents have been considered to present a globally favorable benefit/risk ratio. However, it is important that in routine practice, initiation of anti-TNF-α therapy be carefully discussed with the patient, extensively explaining the potential benefits and risks of such treatment. Prior to starting anti-TNF-α therapy, the patients need to be screened for latent tuberculosis, hepatitis B virus infection, and (usually) hepatitis C virus and HIV infection. Vaccination schedules of IBD patients should be evaluated and updated prior to the commencement of anti-TNF-α therapy. Ordinarily, immunization in adult patients with IBD should not deviate from recommended guidelines for the general population. With the exception of live vaccines, immunizations can be safely administered in patients with IBD, even those on immunosuppressants or biologics. The purpose of this review is providing an overview of appropriate steps to prepare patients with IBD for anti-TNF-α therapy.

Azathioprine is more effective than mesalazine at preventing recurrent bowel obstruction in patients with ileocecal Crohn's disease.

BACKGROUND: Patients with subocclusive Crohn's disease (CD) who received azathioprine (AZA) therapy had lower re-hospitalization rates due to all causes and for surgical management of CD compared to those treated with mesalazine during a 3-year period. We investigated whether AZA also was effective for prevention of recurrent bowel obstruction. MATERIAL/METHODS: Rates of recurrent bowel occlusion were compared between patients treated with AZA and those treated with mesalazine. We assessed the time interval-off intestinal obstruction as well as the occlusion-free survival for both groups. RESULTS: There was a significantly lower cumulative rate of patients with recurrent subocclusion in the AZA group (56%) compared with the mesalazine group (79%; OR 3.34, 95% CI 1.67-8.6; P=0.003), with the number needed to treat in order to prevent 1 subocclusion episode of 3.7 favoring AZA. The occlusion-free time interval was longer in the AZA group compared with the mesalazine group (28.8 vs. 18.3 months; P=0.000). The occlusion-free survival at 12, 24, and 36 months was significantly higher in the AZA group (91%, 81%, and 72%, respectively) than in the mesalazine group (64.7%, 35.3%, and 23.5%, respectively; P<0.05 for all comparisons). CONCLUSIONS: In an exploratory analysis of patients with subocclusive ileocecal CD, maintenance therapy with AZA is more effective than mesalazine for eliminating or postponing recurrent intestinal obstruction during 3 years of therapy.

Interaction between diet and genetics in patients with inflammatory bowel disease.

In this editorial, we comment on the article by Marangoni et al, published in the recent issue of the World Journal of Gastroenterology 2023; 29: 5618-5629, about "Diet as an epigenetic factor in inflammatory bowel disease". The authors emphasized the role of diet, especially the interaction with genetics, in promoting the inflammatory process in inflammatory bowel disease (IBD) patients, focusing on DNA methylation, histone modifications, and the influence of microRNAs. In this editorial, we explore the interaction between genetics, gut microbiota, and diet, in an only way. Furthermore, we provided dietary recommendations for patients with IBD. The Western diet, characterized by a low fiber content and deficiency the micronutrients, impacts short-chain fatty acids production and may be related to the pathogenesis of IBD. On the other hand, the consumption of the Mediterranean diet and dietary fibers are associated with reduced risk of IBD flares, particularly in Crohn's disease (CD) patients. According to the dietary guidance from the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD), the regular consumption of fruits and vegetables while reducing the consumption of saturated, trans, dairy fat, additives, processed foods rich in maltodextrins, and artificial sweeteners containing sucralose or saccharine is recommended to CD patients. For patients with ulcerative colitis, the IOIBD recommends the increased intake of natural sources of omega-3 fatty acids and follows the same restrictive recommendations aimed at CD patients, with the possible inclusion of red meats. In conclusion, IBD is a complex and heterogeneous disease, and future studies are needed to elucidate the influence of epigenetics on diet and microbiota in IBD patients.

Effectiveness and Safety of Ustekinumab for Ulcerative Colitis: A Brazilian Multicentric Observational Study.

Background: Real-world data on the effectiveness and safety of ustekinumab (UST) in ulcerative colitis (UC) are lacking in Latin America. In this study, we aimed to describe the effectiveness and safety of UST in a real-world multicenter cohort of Brazilian patients with UC. Methods: We conducted a multicenter retrospective observational cohort study, including patients with moderate-to-severe UC (total Mayo score 6-12, with an endoscopic subscore of 2 or 3) who received UST. The co-primary endpoints were clinical remission, defined as a total Mayo score ≤2 at 1 year, with a combined rectal bleeding and stool frequency subscore of ≤1, and endoscopic remission (endoscopic Mayo subscore of 0) within 1 year from baseline. Secondary endpoints included clinical response between weeks 12 and 16, endoscopic response within 1 year of starting UST, steroid-free clinical remission at week 52, and biochemical remission at week 52. We also evaluated UST treatment persistence and safety. Results: A total of 50 patients were included (female, n = 36, 72.0%), with a median disease duration of 9.2 years (1-27). Most patients had extensive colitis (n = 38, 76.0%), and 43 (86.0%) were steroid dependent at baseline. Forty patients (80.0%) were previously exposed to biologics (anti-TNF drugs, n = 31; vedolizumab [VDZ], n = 27). The co-primary endpoints of clinical remission at 1 year and endoscopic remission within 1 year were achieved by 50.0% and 36.0% of patients, respectively. Clinical response at weeks 12-16 was 56.0%, and endoscopic response, steroid-free clinical remission, and biochemical remission at week 52 were 68.0%, 46.5%, and 50.0%, respectively. The UST treatment persistence rate at 24 months was 73.7%. During the follow-up, 10 patients (20.0%) were hospitalized, mostly due to disease progression, and 3 patients required colectomy. Nine patients (18.0%) discontinued the drug mainly due to a lack of effectiveness. Twenty-seven adverse events (AEs) were reported, 16 of which were considered as serious AEs. Conclusions: In this real-world cohort of difficult-to-treat UC patients, UST was associated with improvements in clinical, biochemical, and endoscopic outcomes. The safety profile was favorable, consistent with the known profile of UST.

Effect of azathioprine or mesalazine therapy on incidence of re-hospitalization in sub-occlusive ileocecal Crohn's disease patients.

BACKGROUND: Although the cost of Crohn's disease (CD) treatment differs considerably, hospitalization and surgery costs account for most of the total treatment cost. Decreasing hospitalization and surgery rates are pivotal issues in reducing health-care costs. MATERIAL/METHODS We evaluated the effect of azathioprine (AZA) compared with mesalazine on incidence of re-hospitalizations due to all causes and for CD-related surgeries. In this controlled, randomized study, 72 subjects with sub-occlusive ileocecal CD were randomized for AZA (2-3 mg/kg per day) or mesalazine (3.2 g per day) therapy during a 3-year period. The primary end point was the re-hospitalization proportion due to all causes, as well as for surgical procedures during this period evaluated between the groups. RESULTS: On an intention-to-treat basis, the proportion of patients re-hospitalized within 36 months due to all causes was lower in patients treated with AZA compared to those on mesalazine (0.39 vs. 0.83, respectively; p=0.035). The AZA group had also significantly lower proportions of re-hospitalization for surgical intervention (0.25 vs. 0.56, respectively; p=0.011). The number of admissions (0.70 vs. 1.41, p=0.001) and the length of re-hospitalization (3.8 vs. 7.7 days; p=0.002) were both lower in AZA patients. CONCLUSIONS: Patients with sub-occlusive ileocecal CD treated with AZA had lower re-hospitalization rates due to all causes and for surgical management of CD compared to those treated with mesalazine during a 3-year period. The long-term use of AZA in ileocecal CD patients recovering from a sub-occlusion episode can save healthcare costs.

The Role of Pharmacogenetics in the Therapeutic Response to Thiopurines in the Treatment of Inflammatory Bowel Disease: A Systematic Review.

This study focuses on the use of thiopurines for treating inflammatory bowel diseases (IBD). These drugs undergo enzymatic changes within the body, resulting in active and inactive metabolites that influence their therapeutic effects. The research examines the role of genetic polymorphisms in the enzyme thiopurine S-methyltransferase (TPMT) in predicting the therapeutic response and adverse effects of thiopurine treatment. The TPMT genotype variations impact the individual responses to thiopurines. Patients with reduced TPMT activity are more susceptible to adverse reactions (AEs), such leukopenia, hepatotoxicity, pancreatitis, and nausea, which are common adverse effects of thiopurine therapy. The therapeutic monitoring of the metabolites 6-thioguanine nucleotides (6-TGN) and 6-methyl mercaptopurine (6-MMP) is proposed to optimize treatment and minimize AEs. Patients with higher 6-TGN levels tend to have better clinical responses, while elevated 6-MMP levels are linked to hepatotoxicity. Genotyping for TPMT before or during treatment initiation is suggested to tailor dosing strategies and enhance treatment efficacy while reducing the risk of myelosuppression. In conclusion, this study highlights the importance of considering genetic variations and metabolite levels in optimizing thiopurine therapy for IBD patients, focusing on balance therapeutic efficacy with the prevention of adverse effects and contributing to personalized treatment and better patient outcomes.

Combined clinical and radiological remission of rectovaginal fistulas using fractional CO2 vaginal laser: a case series and medium-term follow-up.

INTRODUCTION: Despite the advances in surgical and clinical approaches, there is no consensus regarding the best line of treatment from rectovaginal fistula (RVF). Faced with a challenging scenario in the approach of RVF, the fractional CO2 laser receives attention as a possible form of treatment. OBJECTIVES: A single-center, prospective, open-label study evaluating the effectiveness and safety of laser therapy for RVF treatment. SUBJECTS AND METHODS: The total of 15 patients was recruited at the Juiz de Fora University Hospital between August 2018 and July 2022. Inclusion criteria were presence of clinically suspects RVF of any etiology confirmed by pelvic magnetic resonance image (MRI) and gynecological examination. Five fractional CO2 laser sessions with monthly interval followed by complete evaluation through clinical examination and pelvic MRI were performed for all patients after the completion of treatment. Analysis of sexual function before and after the treatment was performed using Female Sexual Quotient (FSQ). RESULTS: The evaluation through physical examination showed no persistent inflammatory signs in the vagina for all patients. Additionally, 10 of out 15 (67.7%) patients achieved clinical remission of RVF symptoms, while 33.3% patients reported significant improvement. Of note, five patients who did not have previous sexual activity returned to regular sexual activity while seven patients who have baseline sexual activity had improvement in their sexual function as assessed by the FSQ. Three out of four ostomized patients had their ostomy reversed and remained without complains. All six patients with RVF secondary to Crohn's disease reported a marked improvement in symptoms and sexual function. In seven (47%) patients radiological remission was confirmed by pelvic MRI. CONCLUSION: CO2 fractional laser can be considered a promising and safe therapeutic alternative for the management of RVF.

Leukocytoclastic Vasculitis Secondary to Anti-Tumor Necrosis Factor Therapy in Inflammatory Bowel Diseases: A Multicenter Retrospective Cohort Study.

BACKGROUND: Vasculitis is an uncommon complication of biologics used to treat inflammatory bowel disease (IBD). This study describes a case series of vasculitis induced by anti-tumor necrosis factor (TNF) therapy in IBD patients. METHODS: Retrospective assessments were performed using the medical records of adult IBD patients who underwent outpatient clinical follow-ups between January 2010 and December 2019 in order to identify patients with vasculitis caused by anti-TNF therapy. RESULTS: There were 2442 patients altogether. Of these, 862 (35%) took anti-TNF medication. Five patients (0.6% of the overall patients; n = 3 (60%) Crohn's disease; n = 2 (40%), ulcerative colitis) were identified as having leukocytoclastic vasculitis (LCV) due to anti-TNF therapy; these patients were white, female, and non-smokers. The mean age of LCV diagnosis was 32.2 years, and the mean IBD duration was 7.2 years. The mean time between the start of biologic therapy and LCV onset was 30.8 months. Most of the patients were using adalimumab (80%; n = 4). All the patients were in remission at the time of the LCV diagnosis, and the vasculitis affected the skin in all cases. Anti-TNF therapy was discontinued in the five abovementioned patients, and the response of LCV to the oral steroids was significantly positive. Remarkably, all five patients experienced complete remission from LCV within 4-12 weeks after starting prednisone therapy, and none of them had LCV recurrence in the follow-up period (a mean duration of 28 months). CONCLUSIONS: LCV is an unusual complication of anti-TNF therapy in the IBD setting. In this context, clinicians should have a high degree of suspicion of LCV in patients who develop an unexplained cutaneous rash.

Efficacy of Early Optimization of Infliximab Guided by Therapeutic Drug Monitoring during Induction-A Prospective Trial.

Therapeutic drug monitoring (TDM) during induction therapy with anti-tumor necrosis factor drugs has emerged as a strategy to optimize response to these biologics and avoid undesired outcomes related to inadequate drug exposure. This study aimed to describe clinical, biological, and endoscopic remission rates at six months in Brazilian inflammatory bowel disease (IBD) patients following a proactive TDM algorithm guided by IFX trough levels (ITL) and antibodies to IFX (ATI) levels during induction, at week six. A total of 111 IBD patients were prospectively enrolled, excluding those previously exposed to the drug. ITL ≥ 10 µg/mL was considered optimal. Patients with suboptimal ITL (<10 µg/mL) were guided according to ATI levels. Those who presented ATI ≤ 200 ng/mL underwent dose intensification in the maintenance phase, and patients with ATI > 200 ng/mL discontinued IFX. In our study, proactive TDM was associated with persistence in the IFX rate at six months of 82.9%. At that time, rates of clinical, biological, and endoscopic remission in patients under IFX treatment were 80.2%, 73.9%, and 48.1%, respectively. Applying a simplified TDM-guided algorithm during induction seems feasible and can help improve patients' outcomes in clinical practice.

Vedolizumab in Mild-to-Moderate Crohn's Disease Patients Naïve to Biological Therapy: A Multicentric Observational Study.

Background: In real-world experience, the number of patients using vedolizumab as first-line biological therapy was low. We aimed to evaluate the effectiveness and safety of vedolizumab in mild-to-moderate Crohn's disease (CD) biologic-naïve patients. Methods: We performed a retrospective multicentric cohort study with patients who had clinical activity scores (Harvey-Bradshaw Index [HBI]) measured at baseline and weeks 12, 26, 52, as well as at the last follow-up. Clinical response was defined as a reduction ≥3 in HBI, whereas clinical remission as HBI ≤4. Mucosal healing was defined as the complete absence of ulcers in control colonoscopies. Kaplan-Meier survival analysis was used to assess the persistence with vedolizumab. Results: From a total of 66 patients, 53% (35/66) reached clinical remission at week 12. This percentage increased to 69.7% (46/66) at week 26, and 78.8% (52/66) at week 52. Mucosal healing was achieved in 62.3% (33/53) of patients. Vedolizumab was well tolerated, and most adverse events were minor. During vedolizumab treatment, 3/66 patients underwent surgery. Conclusions: This study demonstrates the effectiveness and safety of vedolizumab as a first-line biological agent in patients with mild-to-moderate CD.

SECOND BRAZILIAN CONSENSUS ON THE MANAGEMENT OF ULCERATIVE COLITIS IN ADULTS: A CONSENSUS OF THE BRAZILIAN ORGANIZATION FOR CROHN'S DISEASE AND COLITIS (GEDIIB).

BACKGROUND: Inflammatory bowel diseases are immune-mediated disorders that include Crohn's disease (CD) and ulcerative colitis (UC). UC is a progressive disease that affects the colorectal mucosa causing debilitating symptoms leading to high morbidity and work disability. As a consequence of chronic colonic inflammation, UC is also associated with an increased risk of colorectal cancer. OBJECTIVE: This consensus aims to provide guidance on the most effective medical management of adult patients with UC. METHODS: A consensus statement was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's Disease and Colitis [GEDIIB]). A systematic review including the most recent evidence was conducted to support the recommendations and statements. All recommendations/statements were endorsed using a modified Delphi Panel by the stakeholders/experts in inflammatory bowel disease with at least 80% or greater consensus. RESULTS AND CONCLUSION: The medical recommendations (pharmacological and non-pharmacological) were mapped according to the stage of treatment and severity of the disease onto three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus targeted general practitioners, gastroenterologists and surgeons who manage patients with UC, and supports decision-making processes by health insurance companies, regulatory agencies, health institutional leaders, and administrators.

SECOND BRAZILIAN CONSENSUS ON THE MANAGEMENT OF CROHN'S DISEASE IN ADULTS: A CONSENSUS OF THE BRAZILIAN ORGANIZATION FOR CROHN'S DISEASE AND COLITIS (GEDIIB).

BACKGROUND: Inflammatory bowel disease (IBD) is an immune-mediated disorder that includes Crohn's disease (CD) and ulcerative colitis. CD is characterized by a transmural intestinal involvement from the mouth to the anus with recurrent and remitting symptoms that can lead to progressive bowel damage and disability over time. OBJECTIVE: To guide the safest and effective medical treatments of adults with CD. METHODS: This consensus was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's disease and Colitis (GEDIIB)). A systematic review of the most recent evidence was conducted to support the recommendations/statements. All included recommendations and statements were endorsed in a modified Delphi panel by the stakeholders and experts in IBD with an agreement of at least 80% or greater consensus rate. RESULTS AND CONCLUSION: The medical recommendations (pharmacological and non-pharmacological interventions) were mapped according to the stage of treatment and severity of the disease in three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus is targeted towards general practitioners, gastroenterologists, and surgeons interested in treating and managing adults with CD and supports the decision-making of health insurance companies, regulatory agencies, and health institutional leaders or administrators.

Reply to "Six-minute walking test performance is associated with survival in cirrhotic patients" to the editor.

Use of the six-minute walk test has been proposed as a prognostic marker in liver cirrhosis. In the Letter to the Editor presented here, the authors highlight some important points, which were raised after the article was published in the November issue of the World Journal of Hepatology.

HIGH PREVALENCE OF NON-ADHERENCE TO ULCERATIVE COLITIS THERAPY IN REMISSION: KNOWING THE PROBLEM TO PREVENT LOSS.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disease whose manifestations can drastically affect the individual's quality of life, and therefore adherence to treatment is important in order to keep it in remission. OBJECTIVE: To verify the prevalence of non-adherence and the influence of sociodemographic, clinical and pharmacotherapeutic characteristics associated with non-adherence to treatment of UC in remission. METHODS: Cross-sectional study conducted with 90 individuals diagnosed with UC in remission. The information was collected through interviews during medical consultations at Medical Clinic of Gastroenterology of Hospital Universitário da Universidade Federal de Juiz de Fora. To verify the association of the variables under study with the outcome of interest and its measure of association, Student's t-test or Pearson's chi-square non-parametric test (P<0.05) was used and prevalence ratio and confidence interval were calculated. RESULTS: A high prevalence of non-adherence (77.8%) was found among patients with UC in remission. The individuals most likely to not adhere to the treatment were those aged less than 50 years, who were not engaged in paid work, with high scores for anxiety and who used more than one medication as part of the treatment of UC. CONCLUSION: These findings reinforce that acknowledging the factors that influence the non-adherence behavior is of paramount importance for the development of strategies by health care professionals, assuring that those will be really effective to prolong, as much as possible, one of the most successful ways to maintain the UC remission period: the use of medications.

Simultaneous Monitoring of Azathioprine Metabolites in Erythrocytes of Crohn's Disease Patients by HPLC-UV.

The conversion of azathioprine (AZA) to active 6-thioguanine nucleotides (6-TGN) is essential for its clinical efficacy; however, another metabolite formed, 6-methylmercaptopurine (6-MMP), is related to hepatotoxicity. Blood samples were collected from 37 patients under AZA's treatment, and a new HPLC-UV method was validated and applied for simultaneous quantification of 6-TGN and 6-MMP in erythrocytes of Crohn's disease (CD) patients. The concentration of 6-TGN and 6-MMP found ranged from 4.5 to 2,456 ρmol/8 × 108 red blood cells (RBCs) for 6-TGN and from 170 to 53,951 ρmol/8 × 108 RBCs for 6-MMP. Reduced levels of 6-MMP in patients into combo therapy with AZA and allopurinol (2,031 ρmol/8 × 108 RBCs) have been observed when compared to patients undergoing monotherapy with AZA (9,098 ρmol/8 × 108 RBCs). Additionally, there was a negative correlation (r = -83.7%, P < 0.05) between lymphocyte count and 6-TGN levels. The method developed is reliable, accurate and reproducible and can be used as an important tool in the monitoring routine of patients with CD under AZA treatment, allowing the individualization of the dose, monitoring adherence to the treatment and the evaluation of the clinical outcome of these patients.