Real-World Evidence of Tofacinitib in Ulcerative Colitis: Short-Term and Long-Term Effectiveness and Safety.

INTRODUCTION: The objective of this study was to assess the durability, short-term and long-term effectiveness, and safety of tofacitinib in ulcerative colitis (UC) in clinical practice. METHODS: This is a retrospective multicenter study including patients with UC who had received the first tofacitinib dose at least 8 weeks before the inclusion. Clinical effectiveness was based on partial Mayo score. RESULTS: A total of 408 patients were included. Of them, 184 (45%) withdrew tofacitinib during follow-up (mean = 18 months). The probability of maintaining tofacitinib was 67% at 6 m, 58% at 12 m, and 49% at 24 m. The main reason for tofacitinib withdrawal was primary nonresponse (44%). Older age at the start of tofacitinib and a higher severity of clinical activity were associated with tofacitinib withdrawal. The proportion of patients in remission was 38% at week 4, 45% at week 8, and 47% at week 16. Having moderate-to-severe vs mild disease activity at baseline and older age at tofacitinib start were associated with a lower and higher likelihood of remission at week 8, respectively. Of 171 patients in remission at week 8, 83 (49%) relapsed. The probability of maintaining response was 66% at 6 m and 54% at 12 m. There were 93 adverse events related to tofacitinib treatment (including 2 pulmonary thromboembolisms [in patients with risk factors] and 2 peripheral vascular thrombosis), and 29 led to tofacitinib discontinuation. DISCUSSION: Tofacitinib is effective in both short-term and long-term in patients with UC. The safety profile is similar to that previously reported.

Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn's Disease Patients on Ustekinumab.

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index ≤ 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission.

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn's Disease Patients: The SUSTAIN Study.

BACKGROUND: Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn's disease (CD) patients in real-world clinical practice. METHODS: A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. RESULTS: A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). CONCLUSIONS: Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice.

This large retrospective study demonstrated the short- and long-term effectiveness and safety of ustekinumab in patients with Crohn's disease in real-world clinical practice, including those with refractory disease.

Incidence of inflammatory bowel disease and phenotype at diagnosis in 2011: results of the Epi-IBD 2011 study in the Vigo area.

OBJECTIVE: to validate the incidence of inflammatory bowel disease (IBD) reported in Vigo in 2010 within the Epi-IBD study, which was the highest incidence reported so far in Spain. METHODS: an epidemiological, prospective, population-based inception cohort study. All incident cases of IBD living in the Vigo area at diagnosis from January 1 to December 31, 2011 were included. RESULTS: one hundred patients were diagnosed (62 % men; median age, 43.27 years): 49 with ulcerative colitis (UC), 34 with Crohn's disease (CD), and 17 with IBD unclassified (IBDU). The incidence (per 100,000 inhabitants/year) was 17.56 (CD: 5.97; UC: 8.60; IBDU: 2.98), similar to that reported in 2010. The incidence in the non-pediatric population was 19.66 (CD: 6.89, UC: 9.52; IBDU: 3.04). CD and UC phenotype was similar in 2010 and 2011. CONCLUSION: this study supports the increased incidence of EII in the Vigo area reported in 2010.

Tofacitinib in Ulcerative Colitis: Real-world Evidence From the ENEIDA Registry.

AIM: To evaluate the effectiveness and safety of tofacitinib in ulcerative colitis [UC] in real life. METHODS: Patients from the prospectively maintained ENEIDA registry and treated with tofacitinib due to active UC were included. Clinical activity and effectiveness were defined based on Partial Mayo Score [PMS]. Short-term response/remission was assessed at Weeks 4, 8, and 16. RESULTS: A total of 113 patients were included. They were exposed to tofacitinib for a median time of 44 weeks. Response and remission at Week 8 were 60% and 31%, respectively. In multivariate analysis, higher PMS at Week 4 (odds ratio [OR] = 0].2; 95% confidence interval [CI] = 0].1-0.4) was the only variable associated with lower likelihood of achieving remission at Week 8. Higher PMS at Week 4 [OR = 0.5; 95% CI = 0.3-0.7] and higher PMS at Week 8 [OR = 0.2; 95% CI = 0.1-0.5] were associated with lower probability of achieving remission at Week 16. A total of 45 patients [40%] discontinued tofacitinib over time. Higher PMS at Week 8 was the only factor associated with higher tofacitinib discontinuation [hazard ratio = 1.5; 95% CI = 1.3-1.6]. A total of 34 patients had remission at Week 8; of these, 65% had relapsed 52 weeks after achieving remission; the dose was increased to 10 mg/12 h in nine patients, and five of them reached remission again. Seventeen patients had adverse events. CONCLUSIONS: Tofacitinib is effective and safe in UC patients in real practice, even in a highly refractory cohort. A relevant proportion of patients discontinue the drug over time, mainly due to primary failure.

Increased risk of thiopurine-related adverse events in elderly patients with IBD.

BACKGROUND: Thiopurines are the most widely used immunosuppressants in IBD although drug-related adverse events (AE) occur in 20%-30% of cases. AIM: To evaluate the safety of thiopurines in elderly IBD patients METHODS: Cohort study including all adult patients in the ENEIDA registry who received thiopurines. Patients were grouped in terms of age at the beginning of thiopurine treatment, specifically in those who started thiopurines over 60 years or between 18 and 50 years of age. Thiopurine-related AEs registered in the ENEIDA database were compared. RESULTS: Out of 48 752 patients, 1888 started thiopurines when over 60 years of age and 15 477 under 50 years of age. Median treatment duration was significantly shorter for those who started thiopurines >60 years (13 [IQR 2-55] vs 32 [IQR 5-82] months; P < .001). Patients starting >60 years had higher rates of all types of myelotoxicity, digestive intolerance and hepatotoxicity. Thiopurines were discontinued due to AEs (excluding malignancies and infections) in more patients starting >60 years (67.2% vs 63.1%; P < .001). Elderly age and female sex were independent risk factors for most AEs. CONCLUSION: In elderly IBD patients, thiopurines are associated with an increased risk of non-infectious, non-neoplastic, AEs.

Vitamin D deficiency in a European inflammatory bowel disease inception cohort: an Epi-IBD study.

BACKGROUND: Serum vitamin D level is commonly low in patients with inflammatory bowel disease (IBD). Although there is a growing body of evidence that links low vitamin D level to certain aspects of IBD such as disease activity and quality of life, data on its prevalence and how it varies across disease phenotype, smoking status and treatment groups are still missing. MATERIALS AND METHODS: Patients diagnosed with IBD between 2010 and 2011 were recruited. Demographic data and serum vitamin D levels were collected. Variance of vitamin D level was then assessed across different treatment groups, disease phenotype, disease activity and quality of life scores. RESULTS: A total of 238 (55.9% male) patients were included. Overall, 79% of the patients had either insufficient or deficient levels of vitamin D at diagnosis. Patients needing corticosteroid treatment at 1 year had significantly lower vitamin D levels at diagnosis (median 36.0 nmol/l) (P=0.035). Harvey-Bradshaw Index (P=0.0001) and Simple Clinical Colitis Activity Index scores (P=0.0001) were significantly lower in patients with higher vitamin D level. Serum vitamin D level correlated significantly with SIBQ score (P=0.0001) and with multiple components of SF12. Smokers at diagnosis had the lowest vitamin D levels (vitamin D: 34 nmol/l; P=0.053). CONCLUSION: This study demonstrates the high prevalence of low vitamin D levels in treatment-naive European IBD populations. Furthermore, it demonstrates the presence of low vitamin D levels in patients with IBD who smoke.

Assessing medication adherence in inflammatory bowel diseases. A comparison between a self-administered scale and a pharmacy refill index.

BACKGROUND: Medication non-adherence in inflammatory bowel disease (IBD) has a negative impact on disease outcome. Different tools have been proposed to assess non-adherence. We aimed to compare a self-administered scale and a pharmacy refill index as a reliable measure of medication adherence and to determine what factors are related to adherence. METHODS: Consecutive non-active IBD outpatients were asked to fill in the self-reported Morisky Medication Adherence Scale (MMAS-8) and the Beliefs about Medication Questionnaire (BMQ). Pharmacy refill data were reviewed from the previous three or six months and the medication possession ratio (MPR) was calculated. Non-adherence was defined as MMAS-8 scores < 6 or MPR < 0.8. RESULTS: Two-hundred and three patients were enrolled (60% ulcerative colitis, 40% Crohn's disease); 51% were men, and the mean age was 46.3 (14) years. Seventy-four per cent of patients were on monotherapy and 26% on combination therapy; altogether, 65% received mesalazine, 46% thiopurines and 16% anti-tumor necrosis factor alfa. Non-adherence rate assessed by MPR was 37% and 22.4% by MMAS-8. Receiver operator curve analysis using a MMAS-8 cut-off of six gave an area under the curve of 0.6 (95% CI 0.5-0.7), p = 0.001. This score had an 85% sensitivity and 34% specificity to predict medication non-adherence, with negative and positive predictive values of 57% and 70% respectively. High scores in the BMQ potential for harm of medication were significantly associated with MPR non-adherence (p = 0.01). CONCLUSION: The accuracy of MMAS-8 to identify medication non-adherence in inactive IBD outpatients in our setting is poor due to a low specificity and a negative predictive value. Psychosocial factors such as beliefs about medication seem to be related to IBD non-adherence.

Incidence and phenotype at diagnosis of inflammatory bowel disease. Results in Spain of the EpiCom study.

INTRODUCTION: Incidence of inflammatory bowel disease (IBD) is increasing progressively. Few recent epidemiological prospective studies are available in Spain. The Epicom study, a population-based inception cohort of unselected IBD patients developed within the European Crohn's and Colitis Organization, was started in 2010. Vigo is the only Spanish area participating. OBJECTIVE: To describe the incidence of IBD in the Vigo area and the phenotypical characteristics at diagnosis and to compare them with previous data available in Spain. MATERIAL AND METHODS: Epidemiological, descriptive, prospective, and population-based study. All incident cases of IBD during 2010 and living in the Vigo area at diagnosis were included. The Copenhagen Diagnostic criteria were used to define cases. Background population at the start of the study was 579,632 inhabitants. Data were prospectively entered in the EpiCom database. RESULTS: A total of 106 patients were included (57.5% men, median age 39.5 years). Of them 53 were diagnosed of as Crohn's disease (CD), 47 ulcerative colitis (UC) and six IBD unclassified (IBDU). The incidence rate per 100,000 per year for patients aged 15 years or older was 21.4 (10.8 for CD, 9.4 for UC, 1.2 IBDU). Including pediatric population incidence rates were 18.3 (10.3 CD, 8.7 UC, 1.2 IBDU). Median time since onset of symptoms until diagnosis was 2 months. CONCLUSIONS: The incidence rate of IBD in Vigo is the highest compared to former Spanish cohorts, especially in CD patients. Median time since onset of symptoms until diagnosis is relatively short.

[Intermediate-risk gastrointestinal stromal tumor: diagnosis through hydrogastric ultrasonography]. / Tumor estromal gástrico de riesgo intermedio: diagnóstico mediante ecografía hidrogástrica.

Evaluation of submucosal lesions of the digestive tract with conventional endoscopy is unsatisfactory since this technique does not allow direct observation or correct evaluation of the size and layer of origin of the tumor; therefore, in most patients an etiological diagnosis cannot be established with this procedure. However, in most patients, endoscopic ultrasonography can resolve these problems: to a fair degree of certainty, this technique can differentiate malignant from benign lesions, measure their size, and establish their layer of origin. Endoscopic ultrasonography is the technique of choice to establish the presence and characteristics of submucosal tumors and their suitability for treatment. Moreover, this procedure can identify tumors that can be removed endoscopically without excessive risk. Hydrogastric ultrasonography can be an effective substitute for echoendoscopy when evaluating submucosal lesions and for staging tumors of the gastric antrum when echoendoscopy is not available or in patients in whom it cannot be performed. Hydrogastric ultrasonography is safe, inexpensive and very well tolerated by patients. We present the case of a female patient with a gastric GIST that was evaluated using hydrogastric ultrasonography. The size, layer of origin, and malignancy of the tumor were accurately established.