Colorectal cancer (CRC) screening programs have been implemented to reduce the burden of the disease. When an advanced colonic lesion is detected, clinical practice guidelines recommend endoscopic surveillance with different intervals between explorations. Endoscopic surveillance is producing a considerable increase in the number of colonoscopies, with a limited effect on the CRC incidence. Instead, participation in CRC screening programs based on the fecal immunochemical test (FIT) could be a non-inferior alternative to endoscopic surveillance to reduce 10-year CRC incidence. Based on this hypothesis, we have designed a multicenter and randomized clinical trial within the Spanish population CRC screening programs to compare FIT surveillance with endoscopic surveillance. We will include individuals aged from 50 to 65 years with complete colonoscopy and advanced lesions resected within the CRC screening programs. Patients will be randomly allocated to perform an annual FIT and colonoscopy if fecal hemoglobin concentration is ≥10 µg/g, or to perform endoscopic surveillance. On the basis of the non-superior CRC incidence, we will recruit 1894 patients in each arm. The main endpoint is 10-year CRC incidence and the secondary endpoints are diagnostic yield, participation, adverse effects, mortality and cost-effectiveness. Our results may modify the clinical practice after advanced colonic resection in CRC screening programs.

Background: Organised colorectal cancer (CRC) screening programmes have been widely implemented across Europe; however, robust population-level evaluations of their real-world effectiveness, particularly for programmes based exclusively on faecal immunochemical testing (FIT), remain limited. The Galician CRC screening programme was progressively implemented between 2013 and 2019. Methods: We conducted a population-based ecological time-series study using data from the Galician Tumour Registry (ICD-10 C18–C21) for 2015–2023. Age-standardised mortality (ASMR) and incidence (ASIR) rates were analysed. They were calculated using the direct standardisation method, applying age-specific rates to the 2013 European Standard Population (ESP2013). Structural changes associated with programme implementation were evaluated using interrupted time-series (ITS) models, estimating annual percent change (APC) before and after implementation and the net change in slope (ΔAPC). Absolute and relative changes in ASMR and ASIR were calculated by comparing 2015–2017 and 2019–2023. Analyses were performed for the overall population and for individuals aged 50–69 years. Results: Between 2015 and 2023, overall CRC mortality declined significantly (APC −3.00%; 95% CI −3.37 to −2.63). ITS analysis demonstrated a marked modification of mortality trajectories following programme implementation. Mortality shifted from an increasing pre-implementation slope (APC +13.70%; 95% CI 10.12, 17.39) to a significant annual decline post-implementation (APC −3.62%; 95% CI −4.47, −2.76), yielding a ΔAPC of −17.32. In individuals aged 50–69 years, the structural change was more pronounced (ΔAPC −19.88), with post-implementation mortality decreasing by −8.08% annually (95% CI −10.43, −5.66). Incidence showed a comparable structural modification. Overall APC changed from +15.26% (95% CI 5.48, 25.95) before implementation to −2.48% (95% CI −5.29, 0.41) afterwards (ΔAPC −17.74). In the screening-eligible population, APC shifted from +21.32% (95% CI 4.60, 40.71) to −3.74% (95% CI −7.62, 0.30), corresponding to a ΔAPC of −25.06. Descriptively, ASMR declined from 41.92 to 35.91 per 100,000 (−14.33%), and ASIR from 98.37 to 85.16 per 100,000 (−13.42%) between 2015 and 2017 and between 2019 and 2023. Relative reductions were larger in individuals aged 50–69 years and were more pronounced for colon cancer than for rectal cancer. Conclusions: Implementation of an organised FIT-based screening programme was associated with a structural change in CRC mortality and incidence trends, particularly among individuals aged 50–69 years.

Background: Most colorectal cancer patients diagnosed are candidates for surgical resection with curative intent, although colorectal surgery is associated with some complications that could be life-threatening. Antibiotic prophylaxis is commonly used for the prevention of infectious postoperative complications. However, this intervention can change the composition of intestinal microbiota and promote adverse inflammatory outcomes in colorectal cancer patients. The combination of different fungal extracts could be beneficial because of their role in gut microbiota modulation and their anti-inflammatory activity. Objective: Based on this hypothesis, we have designed a double-bind, randomized clinical trial to evaluate the effect of the nutraceutical fungal extract Micodigest 2.0 on complications of surgery for colorectal cancer resection. Methods: Colorectal cancer candidates for surgery will be considered for inclusion in the study. After evaluation by the multidisciplinary tumor board, patients who meet selection criteria will be screened, stratified according to tumor location, and randomly allocated to be treated with Micodigest 2.0 or placebo. Treatment will be continued until admission for surgery (4-6 weeks). Participants will undergo a medical and clinical evaluation including baseline and preadmission quality of life, microbiome composition, inflammatory and nutritional status, adverse events, and adherence assessments. The main end point of the study is the surgery complication rate. We will evaluate complications using the Clavien-Dindo classification. It will be necessary to recruit 144 patients to find a relevant clinical difference. We will also evaluate the effect of the nutraceutical on microbiome composition, inflammatory response, nutritional status, and quality of life, as well as the effect of these variables on surgical complications. Results: This study was funded in 2020 by the Center for Industrial Technology Development. Recruitment began in September 2021 and is expected to be completed in September 2022. Data will be analyzed and the results will be disseminated in 2023. Conclusions: The results of this protocol study could help to reduce surgery complications in patients with colorectal cancer using the new treatment Micodigest. This study could also identify new features associated with colorectal surgery complications. In summary, this study trial could improve the management of colorectal cancer patients. Trial Registration: Clinical Trials.gov NCT04821258; https://clinicaltrials.gov/ct2/show/NCT04821258 International Registered Report Identifier (IRRID): DERR1-10.2196/34292

Biosimilars represent a significant opportunity in the treatment of inflammatory bowel disease (IBD). Our aim is to assess the effectiveness and safety of the five approved adalimumab (ADA) biosimilars in IBD patients naive to biologics. IBD patients naive to biologics from eight Spanish hospitals were enrolled. We included patients who started ADA biosimilars between November 2018 and January 2022. The study endpoints included (1) induction of remission at week 8; (2) drug persistence at the conclusion of the follow-up period; and (3) safety of the five ADA biosimilars. In total, 383 patients were included. After induction, 63.8% of patients were in clinical remission. In total, 114 (29.8%) patients discontinued treatment during follow-up. Clinical remission was maintained in 78.4% of patients after a median follow-up of 18 (12-24) months. Dose intensification was performed in 35 (9.1%) patients during follow-up. There was no significant difference in effectiveness for the 5-ADA biosimilars. Additionally, drug persistence was significantly higher in Crohn's disease (CD) patients (P = .012), in the group of patients co-treated with immunomodulators (IMM) (P = .001) and in patients with post-induction (at week 8) ADA levels ≥ 7 μg/mL (P = .002). Adverse events were reported in 30 (7.8%) patients with no significant difference between ADA biosimilars. ADA biosimilars are safe and effective in inducing and maintaining remission in a real-life population of bio-naive IBD patients. Furthermore, there is no significant difference between the 5-ADA biosimilars. Drug persistence was significantly higher in patients with CD treated with IMM and with post-induction ADA levels ≥7 μg/mL.

Background It has become increasingly clear that appropriate initial management of rheumatoid arthritis (RA) increases the chances of success and improves long-term prognosis. Therefore, rheumatologists need prognostic biomarkers to select patients requiring aggressive management. It is possible that anti-carbamylated protein antibodies (anti-CarPA) may serve as such biomarkers because they are associated with erosions and their progression, and with mortality in some studies. Recently, the possibility that they are also associated with disease activity in early arthritis (EA) has been examined by several studies with discordant results. Objectives We aimed to explore the relationship between variation in disease activity and anti-CarPA in EA patients. Methods EA patients from two prospective clinics, Hospital Universitario La Paz (n=492) and Hospital Universitario La Princesa (n=501), were included. DAS28 was available at baseline and at months 6 (M6), 12 (M12) and 24 (M24) of follow-up. Anti-CarPA were determined in baseline serum samples by ELISA using in vitro carbamylated fetal calf serum. Student t test and main effects general linear regression were used for analysis. Results The 27.4% of EA patients that were positive for anti-CarPA showed higher DAS28 at baseline than the negative patients (4.93 vs 4.31, p=1.6x10–⁸). The difference persisted at all visits during follow-up (3.60 vs 3.19 at M6; 3.47 vs 3.09 at M12; and 3.31 vs 2.79 at M24; all with p≤0.001). These differences were independent of patient sex and age, smoking, time since symptoms onset, the specific EA clinic and the year of onset. In addition, they persisted after accounting for the presence of RF or ACPA at baseline (p=1.3x10–⁵, and p=5.7x10–⁵, respectively) and at later visits (p<0.05 for all analyses). Analysis of the relation between anti-CarPA and ΔDAS28 showed association only with ΔDAS28 from baseline to M6 (p=0.005). In this period, the positive patients showed less decrease of DAS28 than the negative patients. This was independent of all the variables mentioned above and of the initial DAS28. As a result of this association, 20.5% of the anti-CarPA positive patients reached remission at M6, in comparison with 34.6% of the negative patients. In contrast, ΔDAS28 from M6 to M12 and from M12 to M24 were small and not associated with anti-CarPA. Conclusions Anti-CarPA were associated with high disease activity at presentation and with less improvement in the first 6 months of follow-up in EA patients. These results reinforce the possibility that anti-CarPA could be useful in the clinic as prognostic biomarkers. Acknowledgements Supported by grants PI14/01651 and RD16/0012/0014,/0011,/0012 of the Instituto de Salud Carlos III (Spain) that are partially financed by the ERDF Disclosure of Interest None declared