Infliximab Biosimilar (Remsima™) in Therapy of Inflammatory Bowel Diseases Patients: Experience from One Tertiary Inflammatory Bowel Diseases Centre

2017 ◽  
Vol 35 (1-2) ◽  
pp. 91-100 ◽  
Author(s):  
M. Kolar ◽  
D. Duricova ◽  
M. Bortlik ◽  
V. Hruba ◽  
N. Machkova ◽  
...  

Background: The evidence on the efficacy and safety of biosimilar infliximab (IFX) in patients with inflammatory bowel diseases (IBD) is sparse. Methods: Consecutive IBD patients visiting our centre were included. One cohort composed of prospectively followed patients who were switched from original to biosimilar IFX between January and March 2015. The second cohort included retrospectively assessed anti-tumor necrosis factor α-naïve patients who started therapy between January 2015 and January 2016. Disease activity was assessed using standard clinical indices, endoscopic evaluation, and laboratory parameters (blood count, C-reactive protein (CRP) and fecal calprotectin (FC)). Trough levels and anti-drug antibodies (ATIs) were also measured. Patients were evaluated 56 weeks (W56) after switch and at week 14 (W14) and week 46 (W46) in the naïve cohort. Results: Seventy-four IBD patients were switched to biosimilar IFX and 119 naïve patients newly initiated therapy with the preparation. Disease activity remained stable in a majority of switched patients (remission at week 0 (W0) vs. W56: 72.2 vs. 77.8%; median difference of both Harvey-Bradshaw index and Simple Clinical Colitis Activity Index between W0 and W56 was 0). When W0 and W56 were compared, no significant difference in CRP (4.3 ± 8.0 vs. 3.3 ± 3.8 mg/l; p = 0.89) and FC (135 ± 153 vs. 199 ± 225 µg/g; p = 0.17) was observed. In total, 92% of Crohn's disease (CD) and 83% of ulcerative colitis (UC) patients responded to induction therapy (W14) with biosimilar IFX. At W46, the response rate was 86% in CD and 64% in UC. Moreover, half of UC patients experienced mucosal healing at W14 and improvement of perianal disease occurred in 95% of CD at W46. In this cohort, clear steroid-sparing effect was observed. No increase in immunogenicity was found in switched patients (ATI positivity: 9.5 vs. 6.0%, p = 0.54) and the type and frequency of adverse events were comparable to the original preparation in both cohorts. Conclusion: Switching of IBD patients from original to biosimilar IFX is effective and safe.

2020 ◽  
Vol 77 ◽  
pp. 105-110
Author(s):  
Amihai Rottenstreich ◽  
Tali Mishael ◽  
Sorina Grisaru Granovsky ◽  
Benjamin Koslowsky ◽  
Hagai Schweistein ◽  
...  

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 772-772
Author(s):  
P. Kulakova ◽  
G. Lukina ◽  
E. Alexandrova ◽  
A. Novikov ◽  
A. Klimets ◽  
...  

Background:Аnkylosing spondylitis (AS) and inflammatory bowel diseases (IBD) have many common features. Approximately one in two patients with axial spondyloarthritis have subclinical (histologically confirmed) inflammation of the intestine, and 5-10% of subclinical inflammation turns into Crohn’s disease (CD) or Ulcerative colitis (UC) [1]. Colonoscopy is usually used to diagnose IBD, but this procedure is invasive. Laboratory biomarkers, as fecal calprotectin (FC) and serum calprotectin (SC) can used to diagnosis of IBD. But there is no consensus regarding SC clinical utility. SC is exposed to proteolytic enzymes, but its level also increases with inflammation in the intestine and is associated with a higher disease activity [2]. SC levels positively correlate with CRP, ESR, disease activity in AS, but not as obvious as with FC [3,4].Objectives:The aim of this study was to evaluate the possibility of using SC in the diagnosis of IBD in patients with AS.Methods:In the analysis were included 50 patients with AS, fulfilling the modified New York criteria, among them man -36 (72%), woman -14 (28%), mean age of patients was 42.5 ±9.9, mean disease duration – 13.4±8.7 years. All patients were examined with ESR, CRP, FC (range: 100-1800 µg /g), esophagogastroduodenoscopy, colonoscopy and quantitative analysis of the SC level using ELISA (BUHLMANN MRP8/14 ELISA, range: 0.4-3.9 µg /ml).Results:All patients had a high disease activity, mean BASDAI was 5.3 ± 1.8, mean ASDAS CRP 3.7 ± 1.01, mean ASDAS ESR 3.6 ± 1.01. 80 % patients had high FC level (more than 100 µg / g), while only 18% patients had an increase of SC level. IBD were diagnosed in 11 cases: 6 patients (12 %) with CD and 5 patients (10 %) - UC, in the remaining cases (78%) was no intestinal pathology. Only 2 patients with IBD had a high SC level. SC level was more correlated with ESR (r=0.5) and CRP (r=0.5) (p <0.05) levels, than with FC level (r=0.4) (p <0.05).Conclusion:The results showed that there is currently insufficient data to assess the possibility of using SC in the diagnosis of IBD in patients with AS. There is a significant association between the SC, CRP and ESR, but not fecal calprotectin. Potentially SC may be more representative of systemic inflammation than an intestinal inflammation.References:[1]Klingberg, E., Strid, H., Stahl, A.et al. A longitudinal study of fecal calprotectin and the development of inflammatory bowel disease in ankylosing spondylitis. A longitudinal study of fecal calprotectin and the development of inflammatory bowel disease in ankylosing spondylitis. Arthritis Res Ther 2017. 19(1):21[2]Kalla R, Kennedy NA, Ventham NT, Boyapati RK, Adams AT, Nimmo ER, Visconti MR, Drummond H, Ho GT, Pattenden RJ, Wilson DC, Satsangi J. Serum Calprotectin: A Novel Diagnostic and Prognostic Marker in Inflammatory Bowel Diseases. Am J Gastroenterol. 2016 Dec;111(12):1796-1805[3]Hu H, Du F, Zhang S, Zhang W. Serum calprotectin correlates with risk and disease severity of ankylosing spondylitis and its change during first month might predict favorable response to treatment. Mod Rheumatol. 2019 Sep;29(5):836-842.[4]Azramezani Kopi T, Shahrokh S, Mirzaei S, Asadzadeh Aghdaei H, Amini Kadijani A. The role of serum calprotectin as a novel biomarker in inflammatory bowel diseases: a review study. Gastroenterol Hepatol Bed Bench. 2019;12(3):183-189.Disclosure of Interests:None declared.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S215-S216
Author(s):  
R Amihai ◽  
T Mishael ◽  
S Grisaru-Granovski ◽  
B Koslowsky ◽  
G Abitbol ◽  
...  

Abstract Background Inflammatory bowel diseases (IBDs) are commonly diagnosed in reproductive-aged women and can substantially affect pregnancy outcomes. Non-invasive monitoring of IBD during the prenatal course is particularly challenging as traditional laboratory biomarkers are often affected by pregnancy-related physiologic changes. We aimed to evaluate the role of fecal calprotectin (FC) in monitoring disease activity and predicting relapse among IBD women throughout gestation. Methods Women with IBD attending a multidisciplinary clinic for the preconception, antenatal and postnatal treatment were prospectively recruited during 2014–2018. FC levels were determined with an enzyme-linked immunoassay. Results A total of 265 FC (preconception, n = 41; first trimester, n = 48; second trimester, n = 84; third trimester, n = 76; postpartum, n = 16) measurements were obtained in 157 pregnancies. Higher FC concentrations were found in all time points in those with active disease than those in remission as assessed by either physician global assessment or disease clinical scores. FC levels were significantly correlated with physician global assessment and disease activity indices in all 5 periods of investigation. Excluding those with disease flare at the time of conception, disease relapse was encountered during the prenatal course in 40 (31.5%) of the remaining 127 pregnancies. FC levels were significantly higher in those who experienced a disease flare later in the course of gestation as compared with those who maintained clinical remission (median 341 vs. 224 μg/g, p = 0.04). Conclusion FC appears to be a reliable marker of ongoing disease activity throughout the prenatal course as well as a predictor of imminent disease flare among IBD pregnant patients.


2017 ◽  
Vol 26 (3) ◽  
pp. 239-244 ◽  
Author(s):  
Antonio Tursi ◽  
Leonardo Allegretta ◽  
Nello Buccianti ◽  
Nicola Della Valle ◽  
Walter Elisei ◽  
...  

Background & Aims: Golimumab (GOL) has been recently approved in Italy for the treatment of ulcerative colitis (UC) unresponsive to standard treatments. Our aims were to assess the real-life efficacy and safety of GOL in managing UC outpatients in Italian primary Inflammatory Bowel Diseases (IBD) centres.Methods: Consecutive UC outpatients with at least 3-months follow-up were enrolled. Primary end-point was the induction and maintenance of remission in UC, defined as Mayo score ≤2, at 6-month follow-up.Results: Ninety-three patients were enrolled. At 6-month follow-up, remission was obtained in 34 (36.5%) patients. Shorter duration of disease was the only significant predictive factor of remission. Clinical response was achieved in 60 (64.5%) patients, while mucosal healing (MH) was obtained in 18 (19.3%) patients. Sixteen (47.0%) patients under remission were still under therapy with steroids. C-reactive protein and fecal calprotectin significantly dropped during the follow-up (p<0.001 for both proteins). Adverse events occurred in 4 (4.3%) patients and 3 of them stopped treatment. Colectomy was performed in only one patient (1.1%).Conclusions: Golimumab seems to be safe and effective in inducing and maintaining remission in real life UC outpatients.Abbreviations: ADA: Adalimumab; CRP: C-reactive Protein; GOL: Golimumab; FC: Fecal calprotectin; IBD: Inflammatory Bowel Diseases; IFX: Infliximab; IQR: Interquartile range; MH: Mucosal Healing; SC: Subcutaneously; TBC: Tuberculosis; TNFα: Tumor necrosis factor α; UC: Ulcerative Colitis.    


2021 ◽  
Vol 10 (17) ◽  
pp. 3905
Author(s):  
Edyta Szymanska ◽  
Aldona Wierzbicka ◽  
Maciej Dadalski ◽  
Jaroslaw Kierkus

Background: Recent data indicate that increased intestinal permeability plays a key role in the pathogenesis of inflammatory bowel diseases (IBD) and correlates with disease flare. Since zonulin related proteins (ZRP) are the proteins that increase permeability in the epithelial layer of the small intestine by reversibly modulating the intercellular tight junctions, they may serve as a new, noninvasive biomarker of disease activity. The aim of this study was to investigate fecal ZRP in pediatric IBD patients as well as its correlation with disease activity and fecal calprotectin (FCP). Methods: Ninety-four individuals: 47 Crohn’s disease (CD) patients, 41 ulcerative colitis (UC) patients, and 6 healthy controls were examined for fecal ZRP. Values were correlated to IBD type, disease activity for IBD patients, and FCP for all children included in the study. A stool specimen was collected the day before the visit to the hospital, then fecal ZRP and FCP were tested using the ELISA test. Non-parametric statistical tests were used for data analysis. Results: The level of fecal ZRP was higher among IBD patients compared to the control group (CG): medians for CD—113.3 (53.6–593.6) ng/mL; UC—103.6 (50.7–418.3) ng/mL; and CG—46.9 (31.8–123.0) ng/mL (p < 0.05). No difference in fecal ZRP concentration was observed between children with CD and those with UC (p = 0.55). A slight correlation between disease activity (PCDAI for CD and PUCAI for UC) and the fecal ZRP level was found for CD (p = 0.03/R = 0.33), but not UC (p = 0.62/R = 0.08), patients. A correlation between fecal ZRP and FCP was observed (R = 0.73, p = 0.00). Conclusions: Fecal ZRP levels are increased among those with IBD, are associated with CD activity, and strongly correlate with FCP. Further research into the role of intestinal permeability in IBD and the clinical usefulness of ZRP in IBD is warranted.


Author(s):  
Armando Tripodi ◽  
Luisa Spina ◽  
Laura Francesca Pisani ◽  
Lidia Padovan ◽  
Flaminia Cavallaro ◽  
...  

Abstract Background Inflammatory bowel diseases (IBD) are characterized by an increased thrombosis risk of uncertain etiology. Coagulation derangement arising from inflammation may be a triggering factor. We hypothesized that strong inflammation inhibitors (eg, anti-tumor necrosis factor-α drugs) may affect coagulation. Methods Forty patients with IBD were compared with 57 control patients for coagulation factors and endogenous thrombin potential (ETP), the latter being the most sensitive marker of in vivo pro- and anticoagulation balance. We measured ETP in the presence and absence of thrombomodulin (the physiologic protein C [PC] activator). Coagulation at different timepoints was also assessed for 28 of these patients during infliximab treatment. Results The median ETP (nM thrombin × minutes) and range (minimum-maximum) were each higher in patients at baseline than in control patients in both the absence (2120 [1611-3041] vs 1865 [1270-2337]) and the presence (1453 [464-2522] vs 831 [104-1741]) of thrombomodulin. The ETP ratio (with/without thrombomodulin) was high at baseline (0.73 [0.21-0.90] vs 0.45 [0.07-0.85]). The ETP and ETP ratio declined during treatment and were significantly lower at the end than at baseline. Factor (F) VIII and fibrinogen, which were high at baseline, decreased during treatment and at the end were significantly lower than at baseline. The FVIII/PC ratio, which was high in patients at baseline, declined during treatment and at the end was lower than at baseline. C-reactive protein recorded at the end of treatment was lower than at baseline. Conclusions Patients with IBD have a procoagulant imbalance as shown by increased ETP at baseline. The ETP decreases during treatment with infliximab, which is related to decreased FVIII and FVIII/PC ratio. This effect is also related to the improvement of inflammation as shown by decreased fibrinogen and C-reactive protein.


2015 ◽  
Vol 52 (1) ◽  
pp. 50-54 ◽  
Author(s):  
Lorete Maria da Silva KOTZE ◽  
Renato Mitsunori NISIHARA ◽  
Sandra Beatriz MARION ◽  
Murilo Franco CAVASSANI ◽  
Paulo Gustavo KOTZE

Background Determination of fecal calprotectin can provide an important guidance for the physician, also in primary care, in the differential diagnosis of gastrointestinal disorders, meanly between inflammatory bowel diseases and irritable bowel syndrome. Objectives The aims of the present study were to prospectively investigate, in Brazilian adults with gastrointestinal complaints, the value of fecal calprotectin as a biomarker for the differential diagnosis between functional and organic disorders and to correlate the concentrations with the activity of inflammatory bowel diseases. Methods The study included consecutive patients who had gastrointestinal complaints in which the measurement levels of fecal calprotectin were recommended. Fecal calprotectin was measured using a Bühlmann (Basel, Switzerland) ELISA kit Results A total of 279 patients were included in the study, with median age of 39 years (range, 18 to 78 years). After clinical and laboratorial evaluation and considering the final diagnosis, patients were allocated into the following groups: a) Irritable Bowel Syndrome: 154 patients (102 female and 52 male subjects). b) Inflammatory Bowel Diseases group: 112 patients; 73 with Crohn’s disease; 38 female and 35 male patients; 52.1% (38/73) presented active disease, and 47.9% (35/73) had disease in remission and 39 patients with ulcerative colitis;19 female and 20 male patients; 48.7% (19/39) classified with active disease and 49.3% (20/39) with disease in remission. A significant difference (P<0.001) was observed between the median value of fecal calprotectin in Irritable Bowel Syndrome group that was 50.5 µg/g (IQR=16 - 294 µg/g); 405 µg/g (IQR=29 - 1980 µg/g) in Crohn’s disease patients and 457 µg/g (IQR=25 - 1430 µg/g) in ulcerative colitis patients. No difference was observed between the values found in the patients with Crohn’s disease and ulcerative colitis. Levels of fecal calprotectin were significantly lower in patients with inflammatory bowel diseases in remission when compared with active disease (P<0.001). Conclusions The present study showed that the determination of fecal calprotectin assists to differentiate between active and inactive inflammatory bowel diseases and between inflammatory bowel diseases and irritable bowel syndrome.


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