Ustekinumab safety and effectiveness in patients with ulcerative colitis: results from a large real-life study.

BACKGROUND: Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist recently approved for treating ulcerative colitis (UC) but with limited real-world data. Therefore, we evaluated the effectiveness and safety of UST in patients with UC in a real-world setting. RESEARCH DESIGN AND METHODS: This is a multicenter, retrospective, observational cohort study. The primary endpoints were the clinical remission rate (partial Mayo score, PMS, ≤1) and the safety of UST. Other endpoints were corticosteroid-free remission (CSFR) rate, clinical response rate (PMS reduction of at least 2 points), and fecal calprotectin (FC) reduction at week 24. RESULTS: We included 256 consecutive patients with UC (M/F 139/117, median age 52). The clinical remission and clinical response rates at eight weeks were 18.7% (44/235) and 53.2% (125/235), respectively, and 27.6% (42/152) and 61.8% (94/152) at 24 weeks, respectively. At 24 weeks, CSFR was 20.3% (31/152), and FC significantly dropped at week 12 (p = 0.0004) and 24 (p = 0.038). At eight weeks, patients naïve or with one previous biologic treatment showed higher remission (p = 0.002) and clinical >response rates (p = 0.018) than patients previously treated with ≥ 2. Adverse events occurred in six patients (2.3%), whereas four patients (1.6%) underwent colectomy. CONCLUSION: This real-world study shows that UST effectively and safely treats patients with UC.

Use of tofacitinib as first or second-line therapy is associated with better outcomes in patients with ulcerative colitis: data from a real-world study.

BACKGROUND: Data regarding the real-world (RW) use of tofacitinib (TOF) in patients with ulcerative colitis (UC) are limited. We aimed to investigate TOF's RW efficacy and safety in Italian UC patients. RESEARCH DESIGN AND METHODS: A retrospective assessment of clinical and endoscopic activity was performed according to the Mayo score. The primary endpoints were to evaluate the effectiveness and safety of TOF. RESULTS: We enrolled 166 patients with a median follow-up of 24 (IQR 8-36) weeks. Clinical remission was achieved in 61/166 (36.7%) and 75/166 (45.2%) patients at 8-week and 24-week follow-ups, respectively. The optimization was requested in 27 (16.3%) patients. Clinical remission was achieved more frequently when TOF was used as a first/second line rather than a third/fourth line treatment (p = 0.007). Mucosal healing was reported in 46% of patients at the median follow-up time. Colectomy occurred in 8 (4.8%) patients. Adverse events occurred in 12 (5.4%) patients and severe in 3 (1.8%). One case of simple Herpes Zoster and one of renal vein thrombosis were recorded. CONCLUSIONS: Our RW data confirm that TOF is effective and safe in UC patients. It performs remarkably better when used as the first/second line of treatment.

Real-world efficacy and safety of vedolizumab in managing ulcerative colitis versus Crohn's disease: results from an Italian multicenter study.

BACKGROUND: Vedolizumab (VDZ) can be used to treat refractory ulcerative colitis (UC) and Crohn's disease (CD). We assessed whether there are differences in treating UC vs CD with VDZ. RESEARCH DESIGN AND METHODS: Mayo score in UC and the Harvey-Bradshaw Index (HBI) in CD scored the clinical activity. Achievement and maintenance of clinical remission during the follow-up, and safety were the primary endpoints. RESULTS: 729 patients (475 with UC and 254 with CD), median follow-up of 18 (IQR 6-36) months, were enrolled. Clinical remission at the 6th month of treatment was achieved in 488 (66.9%) patients (74.4% in CD vs 62.9% in UC, p<0.002) while, during the follow-up, no difference was found (81.5% in the UC group and 81.5% pts in the CD group; p=0.537). The clinical remission at the 6th month of treatment (p=0.001) and being naïve to biologics (p<0.0001) were significantly associated with prolonged clinical remission. The clinical response was significantly higher in UC (90.1%) vs CD (84.3%) (p=0.023), and surgery occurred more frequently in CD (1.9% in UC vs 5.1% in CD, p=0.016). CONCLUSION: We found differences when using VDZ in UC vs CD in real life. These parameters can help the physician predict this drug's longterm efficacy.

Comparison of Performances of Adalimumab Biosimilars SB5, ABP501, GP2017, and MSB11022 in Treating Patients with Inflammatory Bowel Diseases: A Real-Life, Multicenter, Observational Study.

BACKGROUND: Adalimumab (ADA) biosimilars have entered the therapeutic armamentarium of inflammatory bowel disease (IBD), allowing for the treatment of a greater number of patients for their reduced cost than the originator. However, comparative data on the efficacy and safety of the various ADA biosimilars remains scarce.We compare the efficacy and safety of ADA biosimilars SB5, ABP501, GP2017, and MSB11022 in treating IBD outpatients in a real-life Italian setting. METHODS: A retrospective analysis was performed on consecutive IBD outpatients with complete clinical, laboratory, and endoscopic data. Clinical activity was measured using the Mayo score in ulcerative colitis (UC) and the Harvey-Bradshaw Index in Crohn's disease (CD). The primary endpoints were the following: (1) induction of remission in patients new to biologics and patients new to ADA but previously exposed to other anti-tumor necrosis factor agents or other biologics; (2) maintenance of remission in patients switched from the ADA originator to an ADA biosimilar; and (3) safety of various biosimilars. RESULTS: A total of 533 patients were enrolled according to the inclusion criteria: 162 patients with UC and 371 patients with CD. Clinical remission was obtained in 79.6% of patients new to biologics and 59.2% of patients new to ADA but not to other biologics; clinical remission was maintained in 81.0% of patients switched from the originator, and adverse events were recorded in 6.7% of patients. There was no significant difference between the 4 ADA biosimilars for each predetermined endpoint. CONCLUSIONS: Adalimumab biosimilars are effective and safe in IBD treatment, both in new patients and in patients switched from the ADA originator. No difference in efficacy and safety was found between ADA biosimilars.

We treated 533 IBD patients with adalimumab (ADA) biosimilars SB5, APB501, GP2017, and MSB11022. No differences between these 4 ADA biosimilars were found for reaching remission in naive patients, maintaining remission for nonmedical switching, clinical response, steroid-free remission, surgery rate, mucosal healing, or safety.

Replacement of Adalimumab Originator to Adalimumab Biosimilar for a Non-Medical Reason in Patients with Inflammatory Bowel Disease: A Real-life Comparison of Adalimumab Biosimilars Currently Available in Italy.

BACKGROUND AND AIMS: Adalimumab (ADA) biosimilars have been included into the therapeutic armamentarium of inflammatory bowel disease (IBD); however, comparative data on the efficacy and safety of the different ADA biosimilars after replacing the ADA originator for a non-medical reason remains scarce. We aimed to compare in a real-life setting the efficacy and safety of four ADA biosimilars SB5, APB501, GP2017, and MSB11022 in IBD patients after replacing the originator for a non-medical reason. METHODS: A multicenter retrospective study was performed on consecutive IBD patients, analyzing clinical, laboratory, and endoscopic data. The primary endpoints of the study were maintenance of clinical remission and safety of the different biosimilars. RESULTS: 153 patients were enrolled, 26 with UC and 127 with CD. Clinical remission was maintained in 124 out of 153 (81%) patients after a median (IQR) follow-up of 12 (6-24) months, without any significant difference between the four ADA biosimilars. ADA biosimilars dosage was optimized in five patients (3.3%). Loss of remission was significantly higher in UC patients (10/26 patients, 38.5%) than in CD patients (19/127 patients, 14.9%, p<0.025). Adverse events occurred in 12 (7.9%) patients; the large majority were mild. CONCLUSIONS: No difference in efficacy and safety was found between ADA biosimilars when used to replace the ADA originator for a non-medical reason. However, in UC patients the replacement of ADA originator for this reason should be carefully assessed.

Comparison of performances of infliximab biosimilars CT-P13 versus SB2 in the treatment of inflammatory bowel diseases: a real-life multicenter, observational study in Italy.

BACKGROUND: To compare the performances of Infliximab (IFX) biosimilar CT-P13 and SB2 in the treatment of Inflammatory Bowel Diseases (IBD) outpatients in Italy. RESEARCH DESIGN AND METHODS: Three hundred and eighty IBD outpatients were retrospectively evaluated. The primary endpoint was to compare the two IFX biosimilars in terms of reaching and maintenance of remission at any timepoint. RESULTS: 197 patients with Ulcerative Colitis (UC) and 183 patients with Crohn's Disease (CD) treated with CT-P13 or SB2 and having a median (IQR) follow-up of 12 (6-36) months were compared: 230 (60.5%) were naïve to anti-TNFα, 20 (5.26%) were switched from IFX originator or from IFX CT-P13 to IFX SB2. Clinical remission was achieved in 133 (67.5%) UC patients and in 164 (89.6%) CD patients (p < 0.000), with no differences between CT-P13 and SB2 in the rate of remission in UC (p = 0.667) and CD (p = 0.286). Clinical response, steroid-free remission, rate of surgery, mucosal healing (MH) in UC, switching from IFX originator or from other biosimilar, and safety were similar. Higher MH rate was obtained in CD patients treated with CT-P13 (p = 0.004). CONCLUSION: This first comparative study found that both IFX biosimilars CT-P13 and SB2 are effective and safe in managing IBD outpatients.

Application of the Biopsy-Sparing ESPGHAN Guidelines for Celiac Disease Diagnosis in Adults: A Real-Life Study.

BACKGROUND: Current adult celiac disease diagnosis requires histological confirmation. However, pediatric guidelines have proposed biopsy-sparing algorithms. AIMS: To explore the applicability of the ESPGHAN criteria and assess the accuracy of serology in predicting disease in adults. METHODS: We evaluated 234 consecutive adults showing elevated anti-tTG titers, EMA-positivity, and genetic susceptibility. Patients underwent upper endoscopy with duodenal biopsy. We determined optimal anti-tTG cutoff levels using ROC curves. RESULTS: Mean anti-tTG levels were 71.1 ± 66.5 U/ml; mean normalized levels were 14.8 ± 14.1 × ULN (mean ± SD). Partial/total villous atrophy was present in 36%/55% of cases, respectively. Anti-tTG levels correlated with histology (r s = 0.397, p < 0.001). AUC was similar before and after normalization (0.803 vs 0.807). Applying the ESPGHAN criterion (≥10 × ULN), we calculated a 97.66% PPV. ROC curve analysis showed an optimal cutoff of ≥16 × ULN, with a PPV of 98.86%. Eleven different assays were used for anti-tTG titer determination: Two were prevalent, labeled A (n = 141) and B (n = 59). They performed differently regarding disease prediction (AUC = 0.689 vs 0.925, p < 0.01), showing distinct optimal cutoff values (14.3 × ULN vs 3.7 × ULN), even after standardization (-0.14 vs -1.2). CONCLUSION: In adult symptomatic patients showing EMA-positivity and genetic susceptibility, anti-tTG titers correlated with histology. ESPGHAN criteria performed similarly to previous studies. However, a calculated 16 × ULN cutoff showed an improved PPV. Among prevalent assays, PPV peaked differently both after normalization and standardization, indicating intrinsic differences in performance, thus preventing uniform prediction of disease in a real-life setting. Assay-specific optimal cutoffs seem possible, but would complicate diagnostic criteria. However, biopsy-sparing strategies in adults could prove useful in challenging patients.

Iron deficiency anemia despite effective gluten-free diet in celiac disease: Diagnostic role of small bowel capsule endoscopy.

BACKGROUND & AIM: Iron deficiency anemia (IDA) is associated with celiac disease (CD). Although gluten-free diet (GFD) is an efficient treatment for CD, IDA remains an occasional finding during follow-up and correlates to inadequate gluten exclusion. Little is known regarding persistent IDA despite effective GFD. We aimed to evaluate the role of small bowel capsule endoscopy (SBCE) in this setting. METHODS: We prospectively included consecutive patients undergoing GFD for ≥24 months with persistent concomitant IDA. Patients were assessed serologically and, if negative, underwent endoscopic evaluation. RESULTS: Twenty-six patients underwent esophago-gastro-duodenoscopy (EGD), colonoscopy and SBCE. Altogether, 11 patients resulted positive. EGD showed mucosal lesions in 7: erosive gastritis (n=3), erosive duodenitis (n=1), active CD (n=3). Colonoscopy showed hemorrhoids in 2. SBCE was positive in 6 cases: erosive jejunitis (n=3, 1 eventually diagnosed as refractory CD, 2 as Crohn's disease), angiodysplasias (n=2), lymphangectasia (n=1). Some overlap was observed between procedures, since in 4 subjects EGD and SBCE produced significant findings. However, in 3 cases SBCE documented severe disease, not found at EGD. Hypoalbuminemia was significantly associated with a positive SBCE outcome (p<0.01). CONCLUSION: SBCE yielded significant findings in 23% of celiacs with persistent IDA despite adequate GFD. These were associated to hypoalbuminemia, indicating their occurrence at more severe stages of the disease.

Helicobacter pylori isolates from proximal and distal stomach of patients never treated and already treated show genetic variability and discordant antibiotic resistance.

INTRODUCTION: The treatment failure of Helicobacter pylori (H. pylori) infection may be mainly because of antibiotic resistance and the presence of a mixed infection in the same patient. AIM: To investigate the incidence of mixed infection and discordant antibiotic resistance in patients never treated and already treated. MATERIALS AND METHODS: Susceptibility test to amoxicillin, rifabutin, tinidazole, clarithromycin, levofloxacin, and moxifloxacin was conducted on H. pylori strains culture from 76 patients never treated and 72 patients already treated unsuccessfully. DNA fingerprinting was determined on H. pylori strains harboring in the same patient with a discordant resistance to the same antibiotic. RESULTS: Forty percent of patients never treated and 53% of patients already treated showed a pangastric infection. The overall resistance to amoxicillin, clarithromycin, and tinidazole was significantly higher in patients with pangastric infection in comparison with those with the infection in the antrum (P<0.05). Discordant resistance was present in 33% of patients never treated, and 21% of patients already treated. DNA fingerprinting showed substantial differences among DNA patterns suggesting a mixed infection. CONCLUSION: Culture and susceptibility test should be performed when necessary not only in the antrum but also in the fundus of patients with H. pylori infection.