Persistence, effectiveness and safety of ustekinumab and vedolizumab therapy for complex perianal fistula in Crohn's disease: The HEAL study from GETECCU.

BACKGROUND: The efficacy of ustekinumab and vedolizumab for treating complex perianal fistula in Crohn's disease has been barely studied. We aimed to assess treatment persistence, clinical remission, and safety of these drugs in this context. METHODS: Crohn's disease patients who had received ustekinumab or vedolizumab for the indication of active complex perianal fistula, were included. Clinical remission was defined according to Fistula Drainage Assessment Index (no drainage through the fistula upon gentle pressure) based on physicians' assessment. RESULTS: Of 155 patients, 136 received ustekinumab, and 35 vedolizumab (16 received both). Median follow-up for ustekinumab was 27 months. Among those on ustekinumab, 54 % achieved remission, and within this group, 27 % relapsed during follow-up. The incidence rate of relapse was 11 % per patient-year. Multivariate analysis found no variables associated with treatment discontinuation or relapse. Median follow-up time for patients receiving vedolizumab was 19 months. Remission was achieved in 46 % of the patients receiving vedolizumab, and among them, 20 % relapsed during follow-up. The incidence rate of relapse was 7 % per patient-year. Adverse events were mild in 6 % on ustekinumab and 8 % on vedolizumab. CONCLUSION: Ustekinumab and vedolizumab appear effective, achieving remission in around half of complex perianal fistula patients, with favorable safety profiles.

Efficacy and safety of biological treatment for inflammatory bowel disease in elderly patients: Results from a GETECCU cohort.

INTRODUCTION: Biological therapies used for the treatment of inflammatory bowel disease (IBD) have shown to be effective and safe, although these results were obtained from studies involving mostly a young population, who are generally included in clinical trials. The aim of our study was to determine the efficacy and safety of the different biological treatments in the elderly population. METHODS: Multicenter study was carried out in the GETECCU group. Patients diagnosed with IBD and aged over 65 years at the time of initiating biological therapy (infliximab, adalimumab, golimumab, ustekinumab or vedolizumab) were retrospectively included. Among the patients included, clinical response was assessed after drug induction (12 weeks of treatment) and at 52 weeks. Patients' colonoscopy data in week 52 were assessment, where available. Regarding complications, development of oncological events during follow-up and infectious processes occurring during biological treatment were collected (excluding bowel infection by cytomegalovirus). RESULTS: A total of 1090 patients were included. After induction, at approximately 12-14 weeks of treatment, 419 patients (39.6%) were in clinical remission, 502 patients (47.4%) had responded without remission and 137 patients (12.9%) had no response. At 52 weeks of treatment 442 patients (57.1%) had achieved clinical remission, 249 patients had responded without remission (32.2%) and 53 patients had no response to the treatment (6.8%). Before 52 weeks, 129 patients (14.8%) had discontinued treatment due to inefficacy, this being significantly higher (p<0.0001) for Golimumab - 9 patients (37.5%) - compared to the other biological treatments analyzed. With respect to tumor development, an oncological event was observed in 74 patients (6.9%): 30 patients (8%) on infliximab, 23 (7.14%) on adalimumab, 3 (11.1%) on golimumab, 10 (6.4%) on ustekinumab, and 8 (3.8%) on vedolizumab. The incidence was significantly lower (p=0.04) for the vedolizumab group compared to other treatments. As regards infections, these occurred in 160 patients during treatment (14.9%), with no differences between the different biologicals used (p=0.61): 61 patients (19.4%) on infliximab, 39 (12.5%) on adalimumab, 5 (17.8%) on golimumab, 22 (14.1%) on ustekinumab, and 34 (16.5%) on vedolizumab. CONCLUSIONS: Biological drug therapies have response rates in elderly patients similar to those described in the general population, Golimumab was the drug that was discontinued most frequently due to inefficacy. In our experience, tumor development was more frequent in patients who used anti-TNF therapies compared to other targets, although its incidence was generally low and that this is in line with younger patients based on previous literature.

Efficacy and safety of proactive drug monitoring in inflammatory bowel disease treated with anti-TNF agents: A systematic review and meta-analysis.

BACKGROUND AND AIMS: A systematic review and a meta-analysis of the literature was conducted to assess efficacy and safety of proactive therapeutic drug monitoring (TDM) versus conventional management during maintenance treatment with anti-tumour necrosis factor (anti-TNFα) in patients with inflammatory bowel disease (IBD). METHODS: A search was conducted up to January 2022 (MEDLINE, EMBASE, and the Cochrane Library). The primary outcome was the ability to maintain clinical remission at 12 months. The certainty of evidence was determined using the GRADE approach. RESULTS: Nine studies were identified: one systematic review, six randomised clinical trials, and two cohort studies. No superior efficacy of proactive TDM [relative risk 1.16; 95% confidence interval (CI): 0.98-1.37, n=528; I2=55%] was shown. Proactive TDM could improve the durability of anti-TNFα treatment [odds ratio (OR) 0.12; 95%CI: 0.05-0.27; n=390; I2=45%), prevent acute infusion reactions (OR 0.21; 95%CI: 0.05-0.82; n=390; I2=0%), decrease adverse events (OR 0.38; 95%CI: 0.15-0.98; n=390; I2=14%), and reduce the probability of surgery, at lower economical expenditure. CONCLUSIONS: The analysed evidence did not confirm the superiority of proactive TDM of anti-TNFα treatment over conventional management in patients with IBD, so proactive TDM should not currently be recommended.

Seroprevalencia del SARS-CoV-2 en los pacientes con enfermedades inmunomediadas en tratamiento con terapias biológicas y sintéticos dirigidos / Seroprevalence of SARS-CoV-2 antibodies in patients with immune-mediated inflammatory diseases treated with biological and synthetic targeted therapies

INTRODUCCIÓN: La seroprevalencia del SARS-CoV-2 en las enfermedades inflamatorias inmunomediadas (IMID) sigue siendo fuente de controversia. OBJETIVO: Comparar la seroprevalencia de anticuerpos (Ac) anti SARS-CoV-2 en pacientes con IMID en tratamientos con fármacos antirreumáticos modificadores de la enfermedad biológicos (FAMEb) o sintéticos dirigidos (FAMEsd) frente a un grupo de personas sin IMID. MÉTODOS: Estudio de pacientes con IMID y tratamientos con FAMEb y FAMEsd y de individuos sin IMID. Mediante la técnica de inmunoensayo por quimioluminiscencia indirecta, se determinaron las serologías IgG frente al SARS-CoV-2 entre octubre/2020 y mayo/2021. RESULTADOS: Se estudiaron 1.100 sujetos, 550 pacientes con IMID y 550 personas sin IMID. Se observó una seroprevalencia de 16% (88/550) en los pacientes frente a 19,3% (106/550) en el grupo de personas sin IMID, sin significación estadística (OR 0,790 [IC 95% 0,558-1,118]). Comparando los tratamientos con FAMEb o FAMEsd, se observó una tendencia a una menor seroprevalencia con rituximab, en relación con los individuos sin IMID (OR 0,296 [IC 95% 0,0871,007]). Asimismo, se encontró menor seroprevalencia en los pacientes que además de su FAMEb recibían tratamiento con metotrexato, en comparación con el grupo de personas sin IMID (OR 0,432 [IC 95% 0,223-0,835]). CONCLUSIONES: Las IMID en tratamiento con FAMEb o FAMEsd no influyen en la seroprevalencia frente al SARS-CoV-2 de los pacientes. El tratamiento concomitante con metotrexato disminuye de forma significativa la seroprevalencia en estos pacientes.

BACKGROUND: The seroprevalence of SARS-CoV-2 in immunemediated inflammatory diseases (IMID) remains controversial. AIM: To compare the seroprevalence of antibodies (Ab) to SARS-CoV-2 in patients with IMID receiving treatment with biological diseasemodifying antirheumatic drugs (bDMARD) or targeted synthetic (tsDMARD) versus a group of people without IMID. METHODS: Study of patients with IMID and treatments with bDMARD and tsDMARD and individuals without IMID. IgG serology against SARS-CoV-2 was measured using the two-step sandwich immunoassay technique by indirect chemiluminescence between October 2020 and May 2021. RESULTS: A total of 1100 subjects were studied, 550 patients with IMID and 550 persons without IMID. A seroprevalence of 16% (88/550) was observed in patients versus 19.3% (106/550) in the group of people without IMID, without statistical significance (OR 0.790 [95% CI 0.558-1.118]). Comparing the treatments with bD- MARD or tsDMARD, there was a tendency to lower seroprevalence with rituximab, in relation to individuals without IMID (OR 0.296 [95% CI 0.087-1.007]). In addition, lower seroprevalence was found in patients who received methotrexate treatment in addition to their bDMARD, compared to the group of individuals without IMID (OR 0.432 [95% CI 0.223-0.835]). CONCLUSIONS: IMIDs in treatment with bDMARDs or tsDMARDs do not influence the seroprevalence against SARS-CoV-2 in patients. Concomitant treatment with methotrexate significantly decreased seroprevalence in these patients.

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.

The association between de novo inflammatory bowel disease and celiac disease.

INTRODUCTION: controversial data have been reported on the potential association between celiac disease (CeD) and inflammatory bowel disease (IBD). OBJECTIVE: to study the prevalence of CeD in patients newly diagnosed cases with IBD. METHODS: an observational, retrospective study was performed in patients with newly diagnosed IBD who were screened for CeD by anti-tissue transglutaminase antibodies (anti-tTG) measurements and an endoscopic duodenal biopsy. No patients had received corticosteroids, immunosuppressants or biologic drugs within the three months prior to gastroscopy. In the presence of Marsh 1, other causes were ruled out. CeD was diagnosed in patients positive for anti-tTG, compatible duodenal biopsy findings and a good response to a gluten-free diet. RESULTS: a total of 163 patients were screened for CeD. Of these, six (3.7%) were positive for anti-tTG and four were diagnosed with CeD (three had ulcerative colitis, one had Crohn's disease). All patients with both CeD and IBD had normal IgA levels, positive anti-tTG and CeD genetic markers. CONCLUSIONS: the prevalence of CeD in our patients with IBD was higher than that reported in the literature for other series of patients with IBD. A combination of anti-tTG testing and CeD genetics may screen patients for CeD in this population of patients with IBD.

Radiofrequency ablation for hepatocellular carcinoma and liver metastases: experience in Hospital La Paz.

INTRODUCTION: Radiofrequency ablation for patients presenting with non-resectable primary or metastatic liver tumours seems to be a valid therapeutic alternative. In the present study, we show a descriptive list of indications, results and complications of Radiofrequency Ablation Technique for treating non-resectable solid hepatic tumours. MATERIALS AND METHODS: Twenty two patients were included in this study; eleven of them (50%) sustained liver metastases from colorectal adenocarcinoma, ten patients (45.5%) had hepatocellular carcinoma and 1 patient had insulinoma. RESULTS: Local recurrence rate of hepatocellular carcinoma was 22.7% and 27.3% for colorectal carcinoma, after a respective median follow-up of 21 and 14 months. Complications rate was 6.9% and technique-associated mortality rate was 0%. CONCLUSIONS: Radiofrequency ablation is an easy to make, safe and useful technique for the treatment of primary and metastatic liver tumours.

[Secondary prophylaxis with elastic band ligation in esophageal-gastric varices]. / Profilaxis secundaria mediante ligadura con bandas elásticas en varices esofagogástricas.

The aim of the present study was to determine the usefulness of elastic band ligation in the prevention of hemorrhage recurrence due to esophageal-gastric varices. Sixty-five patients who survived an episode of variceal hemorrhage were included in the study. Twenty-nine patients (45%) were Child-Pugh class A, 25 (38%) were class B, and 11 (17%) were class C. The cause of cirrhosis was hepatitis C virus and alcohol in 45% and 31% of the patients, respectively. The first ligation session was performed between the third and fifth day after the hemorrhagic episode and subsequent sessions were carried out at intervals of 3-4 weeks. The ligation sessions were performed with antibiotic prophylaxis. A mean of 2.7 bands were placed per session (range 1-5), and the mean number of sessions required per patient to achieve variceal eradication was 2.5 (range 1-6). The rate of bleeding recurrence was 24.6% (16 episodes). In conclusion, endoscopic elastic band ligation is a useful technique for the eradication of esophageal varices and for the prevention of bleeding recurrence.