Administration Of Infliximab Research Articles

Сравнительная эффективность генно-инженерных биологических препаратов в реальной клинической практике по данным МЕРА

Background: the list expansion of genetically engineered biological drugs (GEBD) used for the treatment of ankylosing spondylitis (AS) determines the relevance of studies aimed at comparing them and determining their place in this disease treatment. Real clinical practice studies are the preferred source of this data type. Aim: to evaluate the efficacy of various GEBD in patients with AS according to the Moscow Unified Arthritis Registry (MUAR). Material and methods: the analysis of the MUAR data was carried out. These included clinical cases with GEBD, for which there were data of a completed visit after 6 months or more after the treatment initiation. Parameters values achieved during treatment with various drugs were analyzed. The comparison was conducted during a multivariate analysis with adjustments for the identified confounders. Non-clinical parameters that were reliably and independently associated with the achieved BASDAI index (CRP) values were considered as confounders. Results: the study included 363 treatment episodes with GEBP in 361 patients. As mutually independent significant predictors of the achieved ASDAS (confounders) values, GEBD treatment duration were established until the evaluation of indicators (p<0.001) and the age of the patient (p=0.006). Significant association between the established values of the studied parameters and the used GEBD were found for the achieved ASDAS (p=0.033) and ESR (p=0.007) values. In a pairwise drug comparison using the conservative Šidák correction, the achieved values of ASDAS and ESR during infliximab and adalimumab administration were significantly less than during certolizumab pegol administration. Conclusion: infliximab, adalimumab, etanercept, certolizumab pegol, golimumab, secukinumab in real clinical practice demonstrate generally similar clinical efficacy in the treatment of AS. The effect of golimumab and secukinumab, recently introduced into clinical practice, does not significantly differ from the effect produced by long-term TNF-α inhibitors. Certain disease activity preservation in a significant part of patients gives grounds to continue the search for new treatment methods. KEYWORDS: ankylosing spondylitis, genetically engineered biological drugs, tumor necrosis factor inhibitors, C-reactive protein, confounders, registry. FOR CITATION: Rosochkina E.A., Lukina G.V., Koltsova E.N. et al. Comparative efficacy of genetically engineered biological drugs in real clinical practice according to the Moscow Unified Arthritis Registry (MUAR) data. Russian Medical Inquiry. 2021;5(2):58–63. DOI: 10.32364/2587-6821-2021-5-2-58-63.

P011 Physical Activity Levels in Daily Life of Patients with Moderate-to-Severe Crohn's Disease Before and After Infliximab-Induced Remission.

BACKGROUND: Although the role of physical activity (PA) in inflammatory bowel disease (IBD) patients is not well defined, several studies about its effect on disease’s etiology and activity have addressed this issue. In addition, Crohn’s disease (CD) patients seem to have a lower level of PA and this behavior is associated with disease activity. This study evaluated a cohort of patients with moderately-to-severely active CD submitted to anti-TNF therapy in order to compare the exercise capacity and physical activity in daily life before and after anti-TNF-therapy induced remission. It is hypothesized that CD patients who achieved anti-TNF-therapy-induced remission present significant improvement in the previous levels of exercise capacity and PA in daily life. METHODS: In this prospective longitudinal study conducted between March 2015 and June 2018, 44 adult outpatients with active CD were evaluated at two different moments: before infliximab (IFX) administration and 24 weeks after infliximab therapy. We included patients with CD, aged ≥ 18 years and under 65 years, with a 3-month history of active disease, defined as a Harvey-Bradshaw index (HBI) score of 8 or higher and a serum level of C-reactive protein of more than 5.0 mg per liter, with indication for anti-tumor necrosis factor alpha therapy, i.e. refractory disease unresponsive to conventional therapies or steroid-dependent and those presenting with aggressive disease or features of poor prognosis prediction, such as extensive bowel disease, complex fistulizing disease, or severe endoscopic lesion as defined by the presence of deep and extensive ulcers. Eligible patients received induction therapy consisting of intravenous injections of 5 mg/Kg of IFX at weeks 0, 2, and 6 followed by maintenance infusion (5 mg/Kg) at weeks 14 and 22. Participants were followed until week 24. Patients were evaluated for PA in daily life using accelerometer, exercise capacity, peripheral muscle strength, anthropometry, and body composition. The primary endpoint was an increase in the total number of steps/day in daily life at week 24 in CD patients achieving IFX-induced remission. Secondary endpoints included improvement in the shuttle walking test (SWT), the handgrip strength (HS), active time, and inactive time. RESULTS: Thirty-eight (86.4%) patients achieved infliximab-induced remission at the end of 24 weeks and presented a significant increment from baseline in number of steps taken of 1092 (7440 ± 2980 vs. 6348 ± 3177, respectively; P = 0.006). The inactive time was significantly reduced when compared to baseline period (454.2 ± 106.3 vs. 427.9 ± 97.8, respectively; P = 0.033). There was no difference in the distance walked before and after IFX therapy. CONCLUSION: Infliximab-induced remission followed by maintenance therapy has shown to be effective for increasing PA levels in daily life as shows by increase in the number of steps taken per day as well as by reduced inactive time on patients with moderately-to-severely active CD. Given the important role of PA for patients with CD, anti-TNF therapy may be useful therapeutic strategy along with targeted PA recommendations for increasing PA levels. Furthermore, strategies of treatment associated with an exercise program must be considered for this population.

Infliximab-induced remission improves physical activity in patients with active Crohn's disease.

To compare the level of physical activity (PA), exercise capacity, and body composition before and after infliximab-induced clinical remission in patients with Crohn's disease (CD). This prospective longitudinal study evaluated 44 adult outpatients with active CD before infliximab administration and 24 weeks after infliximab therapy. The patients were evaluated for PA in daily life, exercise capacity, muscle strength, and body composition. 38 (86.4%) patients achieved infliximab-induced remission at 24 weeks and presented an increment in the number of steps taken of 1092 (7440±2980 vs. 6348±3177, respectively; p=0.006). The inactive time was reduced when compared to the baseline value (454.2±106.3 vs. 427.9±97.8, respectively; p=0.033). There was no difference in the distance walked before and after infliximab therapy, while there was an increase in the fat mass index in responders to infliximab compared to the baseline (19.1±7.6 vs. 14.9±5.8; p=0.001). Infliximab-induced remission was shown to be effective for increasing physical activity by improving the number of steps and reducing inactive time. The maintenance of clinical remission associated with incentives to regular PA may contribute to making these patients reach an ideal level of PA.

PGI6 DISEASE BURDEN OF MODERATE TO SEVERE CROHN'S DISEASE UNDER CURRENT TREATMENT PATTERN IN CHINA

To estimate the disease burden of moderate to severe Crohn's disease (MS-CD) under current treatment pattern in China. A decision-analytic model was constructed to simulate the Chinese patients with MS-CD and the age and gender-matched Chinese general population over lifetime time horizon for the differences in overall survival, quality-adjusted life years (QALYs), and lifetime direct medical costs. Literature search was conducted to identify appropriate evidence to estimate the model variables. Base case analysis and sensitivity analysis were conducted for the point estimations and uncertainty of the disease burden of MS-CD. The Chinese MS-CD patients were associated with reduced average overall survival by 2.221 years (42.794 years vs. 45.014 years), reduced average QALY by 7.666 QALY (34.063 QALY vs. 41.768 QALY), and increased average life-time direct medical costs by ¥681,910 (¥893,807 vs. ¥211,897). The reduced QALY associated with MS-CD was highly sensitive to quality of life of disease remission (change: 12.079 QALYs) and active disease (change: 1.009 QALYs),mortality of active disease (change:-1.280 QALYs), and treatment effect of infliximab for induction therapy (change: 0.939) and immunosuppressants for maintenance therapy (change: -0.905). The lifetime direct medical costs associated with MS-CD was highly sensitive to administration of infliximab for maintenance therapy (change: ¥426,022), compliance of infliximab (change: ¥-347,445), drug acquisition costs of infliximab (change: ¥244,187), and hospital costs associated with active disease (change: ¥211,009). The probabilistic sensitivity analysis with 5,000 Monte Carlo simulations estimated the median and 95% credible interval of reduced QALY ( -7.076 QALY, -15.136 to -3.186 QALY) and increased lifetime direct medical costs (¥694,054, ¥363,376 to ¥1,215,003). The disease burden of MS-CD in Chinese patients was mainly characterized with reduced QALY and increased medical costs that were highly sensitive to quality of life, infliximab treatment, and activity disease .

The effect of early trough level of infliximab on subsequent disease course in patients with Crohn disease

Decreased trough level of infliximab (TLI) is associated with diminished efficacy in patients with Crohn disease (CD). We examined whether TLI at 14 weeks subsequent to the start of infliximab (IFX) treatment would impact long-term clinical course.Serum IFX levels and antibodies to IFX (ATI) at 14 and 54 weeks after IFX administration were measured in 12 patients with mild to moderate CD. We examined patient background, clinical severity, blood test values, and the relationship between ATI and TLI up to 108 weeks.We compared the group with TLI < 3 μg/mL at 14 weeks (TLI(14) < 3 group) the group with TLI > 3 μg/mL (TLI(14) ≥ 3 group). Patients in the TLI(14) ≥ 3 group were significantly more likely to use immunomodulators before IFX treatment induction (P = .01). At 54 weeks, 2 cases of ATI production were observed in the TLI(14) < 3 group, but no ATI production was observed in the TLI(14) ≥ 3 group. TLI in the TLI(14) ≥ 3 group at 54 weeks was significantly higher than in the TLI(14) < 3 group (6.5 μg/mL vs 1.0 μg/mL; P < .01). Although CD activity index and serum albumin values in the TLI(14) ≥ 3 group at 14, 54, and 108 weeks significantly improved compared to baseline, these improvements were not observed in the TLI(14) < 3 group. The remission maintenance rate at 108 weeks evaluated with the Kaplan–Meier method was significantly higher in the TLI(14) ≥ 3 group than the TLI(14) < 3 group (100% vs 33.3%; P = .02).The TLI 14 weeks after IFX treatment in patients with CD affects long-term outcome.

Baseline Clearance of Infliximab Is Associated With Requirement for Colectomy in Patients With Acute Severe Ulcerative Colitis

Hospitalized patients with acute severe ulcerative colitis (ASUC) often require surgery. Although the tumor necrosis factor antagonist infliximab is an effective salvage therapy to prevent colectomy in patients with ASUC, optimal dosing is unclear. Calculated infliximab clearance has been associated with important outcomes in patients with ulcerative colitis, but its utility in patients with ASUC has not been established. We assessed the relationship between calculated the baseline infliximab clearance before infliximab salvage therapy and the requirement for colectomy in patients hospitalized for ASUC. We obtained data from hospitalized patients with ASUC who initiated infliximab therapy. We then calculated the baseline infliximab drug clearance in these patients based on an existing formula. The primary aim was to compare clearance between patients who required colectomy 6 months later and patients who did not require colectomy. Receiver operating characteristic curve analyses evaluated clearance thresholds for colectomy. Multivariable logistic regression analysis evaluated factors associated with colectomy. In 39 patients with ASUC, the median baseline calculated clearance was higher in patients requiring colectomy at 6 months than in patients without colectomy (0.733 vs 0.569 L/d; P= .005). An infliximab clearance threshold of 0.627 L/d identified patients who required colectomy with 80.0% sensitivity and 82.8% specificity (area under the curve, 0.80). A higher proportion of patients with infliximab clearance of 0.627 L/d or more underwent colectomy within 6 months (61.5%) than patients with lower infliximab clearance values (7.7%) (P= .001). Multivariable analysis identified baseline infliximab clearance as the only factor associated with colectomy. The infliximab dose in the hospital was higher in patients who required colectomy. Results were similar at 30 days and 1 year. In patients hospitalized with ASUC, higher values of calculated infliximab clearance before infliximab administration is associated with higher rates of colectomy. Although patients who required colectomies received higher doses, data on infliximab concentrations are lacking. Infliximab pharmacokinetic models are needed for patients with ASUC to allow comparative trials on clearance-based vs standard dosing.

A patient with colitis-associated cancer who developed clinically manifest Crohn\u2019s disease only after surgery

BackgroundPatients with prolonged inflammatory bowel disease have a greater risk of colorectal cancer, known as colitis-associated cancer. Here we describe an unusual case of colitis-associated cancer.Case presentationThe subject is a 41-year-old male who has not presented digestive symptoms and has an appreciable medical history. He consulted a nearby doctor with left flank pain. A colonoscopy revealed a lateral spreading tumor (granular-type) in his descending colon. With a clinical diagnosis of cancer, D3 left hemicolectomy was performed and a small intestine stoma was constructed. The pathological diagnosis of the tumor was mucinous adenocarcinoma, pT4a(SE), pN2a, which was associated with dysplasia in the surface area. Post-operative ileus was prolonged and the endoscopic examination revealed longitudinal ulcers in the ileum. These ulcers responded quite well to the administration of infliximab, confirming the final diagnosis of Crohn’s disease. Pathological re-examination revealed that the tumor was dysplasia-associated type, and another dysplasia was confirmed near the tumor. Furthermore, mural scars and sporadic lymphoid aggregates were noted in the colon tissues, which suggested pre-existing Crohn’s disease. The patient died of peritoneal dissemination of cancer on day 207 after surgery.ConclusionThe present case was diagnosed as colitis-associated cancer with clinically latent Crohn’s disease, who developed clinically manifest Crohn’s disease only after surgery. Our review of literature revealed no cases comparable to ours.

The Interplay between Mucosal Microbiota Composition and Host Gene-Expression is Linked with Infliximab Response in Inflammatory Bowel Diseases.

Even though anti-TNF therapy significantly improves the rates of remission in inflammatory bowel disease (IBD) patients, there is a noticeable subgroup of patients who do not respond to treatment. Dysbiosis emerges as a key factor in IBD pathogenesis. The aim of the present study is to profile changes in the gut microbiome and transcriptome before and after administration of the anti-TNF agent Infliximab (IFX) and investigate their potential to predict patient response to IFX at baseline. Mucosal biopsy samples from 20 IBD patients and nine healthy controls (HC) were examined for differences in microbiota composition (16S rRNA gene sequencing) and mucosal gene expression (RT-qPCR) at baseline and upon completion of IFX treatment, accordingly, via an in silico pipeline. Significant differences in microbiota composition were found between the IBD and HC groups. Several bacterial genera, which were found only in IBD patients and not HC, had their populations dramatically reduced after anti-TNF treatment regardless of response. Alpha and beta diversity metrics showed significant differences between our study groups. Correlation analysis revealed six microbial genera associated with differential expression of inflammation-associated genes in IFX treatment responders at baseline. This study shows that IFX treatment has a notable impact on both the gut microbial composition and the inflamed tissue transcriptome in IBD patients. Importantly, our results identify enterotypes that correlate with transcriptome changes and help differentiate IFX responders versus non-responders at baseline, suggesting that, in combination, these signatures can be an effective tool to predict anti-TNF response.

Hypoalbuminemia and Bandemia Predict Failure of Infliximab Rescue Therapy in Acute Severe Ulcerative Colitis.

Infliximab rescue therapy is effective in patients with corticosteroid refractory acute severe ulcerative colitis, but predictors of response remain poorly understood. We aimed to identify predictors of colectomy in this high-risk patient population. Patients hospitalized with acute severe ulcerative colitis who received infliximab after failing intravenous corticosteroid therapy between July 2012 and June 2017 were retrospectively identified. Stepwise regression with backward elimination was used to identify predictors of colectomy at 90days and 1year. Ninety-day and 1-year colectomy rates were compared between the patients who received 5mg/kg and 10mg/kg IFX rescue dose. Sixty-three patients met the eligibility criteria. Twenty-nine patients received 5mg/kg, and 34 received 10mg/kg infliximab dose. Serum albumin on admission (OR 0.10; p = 0.04) and band neutrophil percentage at the time of infliximab administration (OR 1.21; p = 0.02) were independent predictors of 90-day colectomy. A combination of serum albumin ≤ 2.5g/dl and band neutrophil count ≥ 13% had a 100% positive predictive value for 90-day colectomy. Unadjusted 90-day and 1-year colectomy rates were similar in the 5mg/kg and 10mg/kg infliximab groups. After adjusting for confounding factors, 10mg/kg infliximab dose was potentially protective for 90-day (OR 0.07; p = 0.06) but not for 1-year colectomy (OR 0.19; p = 0.16). Bandemia and low serum albumin are independent predictors of failure of infliximab rescue therapy in acute severe ulcerative colitis. Serum albumin ≤ 2.5g/dl and band neutrophil count ≥ 13% had a 100% positive predictive value for 90-day colectomy.

Impact of infliximab administration before plasma exchange therapy on patients with Kawasaki disease.

Plasma exchange is a therapeutic option in refractory Kawasaki disease (KD). However, the effects of other immunosuppressive treatments on plasma exchange therapy have not been studied. We investigated the effect of infliximab on plasma exchange in KD as well as on the outcome in patients with KD. We studied 16 patients with intravenous immunoglobulin-resistant KD who finally underwent plasma exchange. The patients were divided into two groups: patients who received infliximab before plasma exchange (infliximab group) and patients who did not (non-infliximab group). The infliximab group showed a lesser median number of required total plasma exchange sessions (P = .002) and higher change and reduction rates in C-reactive protein before and after the first plasma exchange (both P = .027) than that of the non-infliximab group. Infliximab administered before plasma exchange reduced the number of total plasma exchange sessions and improved the plasma exchange efficacy.

Safety and Efficacy of Twice-Weekly Versus Once-Weekly Infliximab for Refractory Acute Graft-Versus-Host Disease in Pediatric Patients

Background Acute graft-versus-host disease (aGVHD) is a leading cause of morbidity and mortality in patients receiving allogenic hematopoietic stem cell transplants (HCST). Because of the role of tumor necrosis factor in development of GVHD, infliximab was identified as a treatment option in refractory disease. Current literature reports use of infliximab given once-weekly (OW), in 2016 our institutional protocol was changed to twice-weekly (TW) administration of infliximab. The objective of this study was to describe safety and efficacy TW infliximab versus OW in pediatric patients with steroid-refractory gastrointestinal (GI) aGVHD. Methods A retrospective chart review of HSCT patients receiving infliximab for treatment of steroid refractory GI aGVHD from January 2013 to July 2018 was conducted. Efficacy was categorized as complete response (CR), partial response (PR), or non-response (NR) as defined by the Keystone Criteria. Patient demographics, indication for transplant, conditioning regimen, GVHD prophylaxis, severity of aGVHD, days to response, adverse events or reasons for discontinuation of infliximab, and patient outcome were collected. Results Thirteen patients met inclusion criteria, 7 patients in the OW group and 6 patients in TW group. All patients received four doses of infliximab at 10 mg/kg/dose. The overall response to infliximab was 93%, with CR of 71% and 50% and a PR 29% and 33% respectively in OW and TW group. Seventeen percent of the patients in the TW did not respond to therapy. Response to therapy was an average of 10.6 days in the TW group versus 15.8 days in the OW group. Overall all-cause mortality was 15%, with 29% in the OW group and 0% in the TW group. Relapse rate of aGVHD was a 100% in the OW group and 0% in TW group. Development of chronic GVHD was 43% in OW group and 33% in TW group. Incidence of infection was similar between the groups. No patients discontinued infliximab due to adverse events. Conclusion Our results suggest that twice-weekly infliximab is safe and effective for treatment of steroid-refractory aGVHD. The TW regimen may provide a more rapid response, less GVHD relapse, and lower risk of chronic GHVD development. The impact of a twice-weekly dosing regimen should be investigated further. 1 | Page

P010 Measurement of colonic mucosal content of biologics with the use of magnetic resonance imaging (MRI): A pilot study in patients with ulcerative colitis

Abstract Background Anti-tumour necrosis factor antagonists (infliximab) as well as other molecules with different modes of action, including anti-integrin agents (vedolizumab), are currently used in patients with ulcerative colitis (UC Numerous studies have demonstrated a positive correlation between serum biologic drug concentrations and favourable therapeutic outcomes, whereas low or undetectable drug concentrations can lead to treatment failure. However, despite immunological issues, lack of and or loss of response may also be attributed to drug pharmacokinetics, of which penetration to the target tissue (colon wall) may play a crucial role Methods We used MRI to perform biochemical analyses of infliximab, adalimumab and vedolizumab concentrations testing the hypothesis that MRI relaxation time can be used to track antibodies in both mucosal biopsy samples and serum. All MR scans were performed with an Optima MR360 from General Electric Healthcare. To determine spin–lattice (T1) and spin–spin (T2) relaxation times, the Fast Spin Echo (FSE) sequence was used. Results The measured values of T1 relaxation times for infliximab, adalimumab, and vedolizumab were 2227 ± 35 ms, 2000 ± 22 ms and 1288 ± 15 ms, respectively. The obtained T2 relaxation times were 130 ± 11 ms, 90 ± 5, and 75 ± 10 ms, respectively. A decrease of both T1 and T2 values of 15 ± 3% are observed in serum from patients with ulcerative colitis. The values of infliximab and adalimumab were similar; the values of vedolizumab measurements in serum were about 50% lower. We find primary evidence that in T1 and T2 decreased in serum samples with ulcerative colitis and increase with the administration of infliximab, adalimumab and vedolizumab drugs. Samples of healthy tissue have T1 and T2 in the range of 2700 ± 5 ms and 150 ms ± 5 ms, respectively. A 30% decrease in T1 and T2 are observed for samples with ulcerative colitis. In this pilot study, we observed that values of T1 and T2 for tissues and serum that contain infliximab and adalimumab are similar, but vedolizumab shows a difference of about 30% when compared with infliximab and adalimumab. Conclusion MRI is an excellent method for quantitative and qualitative measurements of drug content in tissues and biological fluids. This is an innovative use of magnetic resonance imaging to develop a methodology for imaging of drugs that act as contrast agents via interaction with water in serum and tissue.

P604 Can we reduce intravenous monoclonal antibody observation times without compromising patient safety? A single centre retrospective observational study

Abstract Background Monoclonal antibodies (MAbs) are integral to inflammatory bowel disease (IBD) management. The administration of intravenous (IV) MAbs, infliximab and vedolizumab, for Brighton and Sussex University Hospital patients is via an outpatient clinic. Licensing specifies lengthy observation times; infliximab for induction (infusion 1 to 3) and maintenance (infusion 4 onwards) requires 1 to 2 h observation. Vedolizumab for induction (infusion 1 to 2) requires 2 h observation and maintenance (infusion 3 onwards) 1-h observation. This can affect waiting times; 33% UK patients waited longer than two weeks for infliximab. A reduction in observation times could improve capacity but needs to be done without compromising patient safety. Methods A single centre observational study was conducted. Retrospective data were collected on all current patients receiving infliximab or vedolizumab at BSUH. Data were collected over 12 weeks (April to July 2019); patients seen twice in this period were included once. The presence of reaction from current and previous infusions was determined by patient questioning and patient records review. Reaction occurrence, nature and management were recorded. There is not a grading system for IBD infusion-related reactions. To standardise we used the cancer Common Terminology Criteria for Adverse Events; grade 3 and above is designated severe (grade 5 being death). Results For infliximab 130 patients were reviewed with 2607 infusions administered in total. For vedolizumab 69 patients were reviewed with 557 infusions administered in total. Due to the small sample size significance could not be reached. The survival plot indicates high levels of ‘no reactions’ observed in the first 4 infusions of infliximab 97.7% (+1.6%, -4.7%), and first 3 infusions of vedolizumab 96.9% (+2.3%, −8.8%). Considering capacity over 12 weeks, for infliximab a minimum of 121 could be recouped and 64 h for vedolizumab. Extrapolated this could equate to 740 h per year. Conclusion All reactions occurred within three infusions, were non-severe and managed within the infusion clinic. By removing the observation period from infusion 4 onwards, infusion clinic capacity could be increased but further data from multiple centres are required to prove significance.

Safety of infliximab in real clinical practice

A wide range of highly effective genetically engineered biological preparations introduced into clinical rheumatology in recent years causes a special interest in their safety.Purpose of the study. Evaluation of the safety of infliximab therapy in patients with rheumatoid arthritis.Materials and methods. The authors' own data, which analyzed the undesirable effects of infliximab in 135 patients with rheumatoid arthritis in actual clinical practice, are presented. A case report of the adverse reaction of combination therapy with leflunomide and infliximab is presented.Results and its discussion. The overall tolerability of infliximab was satisfactory. Adverse events were observed in 28.1 % of cases, including 19.1 % of patients (14.1 %) had serious side effects that required discontinuation of the drug.Findings. In most cases, infliximab is safe for use in actual clinical practice. Patients should be informed about the risks of undesirable effects and the need for a rheumatologist's examination before each infliximab administration before prescribing therapy.

Short note: Infliximab recovery in a simulated intestinal fluid of the upper intestine tract

The oral administration of Infliximab (IFX) antibody would ensure a direct action on inflamed intestinal tissues without side effects. Thus, investigations about its resilience within the intestinal environment are required. Quantify the IFX recovery in a simulated upper intestinal environment. IFX was incubated for different times until 120min in simulated intestinal fluid (SIF) which differed (i) for pH (7.2 vs 6.8, Exp 1), (ii) for addition or not with pancreatin (Exp 2) and (iii) for addition or not with bovine serum albumin in presence of pancreatin (BSA, Exp 3). In Exp 1 the IFX incubated without pancreatin was degraded by about 15% by SIF pH change from 7.2 to 6.8 and after 120min it was reduced by about 20%. In Exp 2 the presence of pancreatin determined an intense and rapid IFX degradation (recovery < 33%, within 30min), but when BSA was added to simulate the presence of food protein (Exp 3) the IFX half-life ranged between 59 and 70min. A discrete in vitro stability of IFX in the upper intestine environment was demonstrated, if food protein is available and competes with pancreatin proteases.

Assessment of the State of Cell Membranes against the Background of Prolonged Use of Anticytokine Therapy in Patients with Ulcerative Colitis

Biological therapy in the treatment of immune-mediated conditions has changed their course, the quality of life of patients and the prognosis of diseases. The accumulated by mankind 20 years of experience with the use of genetically engineered drugs has led to a number of questions regarding, among other issues, safety in the long-term administration of biological therapy. Patients suffering from ulcerative colitis revealed changes in cell membranes, reflecting their structural and energy characteristics. Long-term administration of Infliximab leads to the stabilization of energy processes in the erythrocyte membrane and improves homeostatic function of the kidneys.The aim of the studywas to evaluate the effect of long-term use of TNF-α blockers (Infliximab) on the structural and functional characteristics of cell membranes and the functional state of the kidneys in patients with moderate to severe ulcerative colitis.Materials and methods. We examined 103 patients with moderate to severe ulcerative colitis during the period of acute attack and remission, of which 28 patients received basic therapy using the drug Infliximab (IFX) for 10 years, 75 patients received standard basic treatment. The patients of the biological therapy group took the original drug Infliximab – Remicade. The comparison group consisted of 30 healthy volunteers, comparable by sex and age. The analysis of the state of erythrocyte membranes was carried out using a set of physicochemical methods: UV spectroscopy (SF-46m spectrophotometer), high-performance thin-layer reaction paper chromatography, membrane ultrafiltration, erythrocyte NMR spectroscopy on phosphoric (31P) and proton (1H) nuclei. The functional state of the kidneys was evaluated using a dynamic scintigraphic study (with the technemage –Tc-99m).Results.Prolonged use of anticytokine therapy with Infliximab for 10 years in patients with ulcerative colitis, upon reaching deep remission, improves endogenous intoxication, restores the structural and functional characteristics of cell membranes, normalizes cell energy metabolism and does not negatively affect the functional state of the kidneys.

Intratympanic infliximab is a safe and effective rescue therapy for refractory immune-mediated hearing loss.

To determine the efficacy and safety of the intratympanic infiltration of infliximab at the hearing threshold of patients in follow-up for refractory immune-mediated hearing loss. 17 patients were collected with relapses, despite maintenance treatment with oral azathioprine associated or not with oral prednisone at low doses (between 5 and 7.5ml/day) or refractory relapses to previous intratympanic corticoid treatment being 19 affected ears infiltrated. We measured the hearing threshold by Pure-Tone Average (PTA) 500-3000Hz, 125-8000Hz and 250-8000Hz in pre-infiltration (baseline) and follow-up 3weeks post-infiltration with auditory threshold at frequencies 125-8000Hz. The average age was 50.68years (±15.23years). After the administration of intratympanic infliximab, an improvement of the hearing threshold was showed in the Pure-Tone Average (PTA) calculated at 500-3000Hz (p = 0.004), 125-8000Hz (p = 0.001) and 250-8000Hz (p = 0.006). An immediate improvement in low frequencies also was observed: 125, 250 and 500Hz (p = 0.009, p = 0.002 and p < 0.001 respectively) also at 1000Hz (p = 0.004) and a persistence of the effect at 3months in the low frequencies: 125Hz (p = 0.020), 250Hz (p = 0.006) and 500Hz (p = 0.002). Infliximab intratympanic infiltration improves the hearing threshold in patients with immune-mediated hearing loss. The effect of improving the hearing threshold is higher in low frequencies and persists within 3months of the infiltration. The administration of intratympanic infliximab is an effective and safe technique.

PBI20 SECUKINUMAB VS. ADALIMUMAB AND INFLIXIMAB FOR THE TREATMENT OF ANKYLOSING SPONDYLITIS: A COST PER RESPONDER ANALYSIS AT 52 WEEKS FROM A GREEK PERSPECTIVE

This analysis estimated and compared long-term Cost Per Responder (CPR) based on the ASAS outcomes following 52 weeks treatment for ankylosing spondylitis (AS) with Secukinumab (SEC), compared to Adalimumab (ADA) and Infliximab (INF) for Greek NHS Analysis is based on a matching-adjusted indirect comparison (MAIC). CPR calculated using long-term response rates from MAIC based on MEASURE 2, ATLAS & ADEPT RCTs. The CPR was estimated by dividing drug acquisition cost for the course of treatment with its response rate. Drug costs were based on December 2017 price bulletin and the number of doses required for 52 weeks. (infliximab administration cost also estimated). MAIC showed that ASAS response rates were significantly higher for SEC compared to ADA at 52 weeks. ASAS20 response rates were 81% vs 65%, ASAS40 response rates were 62% vs. 47% and ASAS5/6 response rates were 72% vs. 55% for SEC and ADA, respectively. The CPR for ASAS20 responders were €7,073 vs. €10,139, for ASAS40 responders were €9,195 vs. €14,096 & for ASAS5/6 responders were €7,918 vs. €12,061 for SEC and ADA, respectively. The CPR for ASAS20/40/5/6 responders were 34%/38%/38% lower, respectively, for SEC compared to ADA. ACR20 response rates were 91% vs. 69% & ASAS5/6 response rates were 33% vs. 23% for SEC and INF, respectively. CPR for ACR20 responders were €6,298 vs. €16,046 & for ASAS5/6 responders were €17,281 vs €47,746 for SEC and INF, respectively. Sensitivity analyses confirmed results robustness. The CPR for all ASAS outcomes at 52 weeks were consistently lower for SEC vs. ADA and INF, leading to important savings for Greek Social Security Fund . These findings indicate that may be more efficient treat AS biologic naive patients in Greece with SEC vs. ADA or INF. A potential weakness is that the comparison between drugs is indirect and based on a statistical model.

Evaluation of efficacy and comparative frequency of adverse events in patients with ulcerative colitis receiving the original infliximab and its biosimilar. One year of observation

To investigate efficacy of original Infliximab (IFX) and its biosimilar in treating patients with ulcerative colitis (UC) and determine the frequency of adverse events during 1 year follow - up period. Our cohort consisted of 98 ulcerative colitis patients, treated with original IFX and its biosimilar since December 2017 till December 2018 years. Original Infliximab was prescribed in 56 UC patients (57.1%) during 5 years and longer; 16 patients (16.3%) were switched to IFX biosimilar; 13 UC bio - naïve patients (13.3%) received original IFX, 29 (29.6%) patients - biosimilar IFX. In 14 patients (14.3%) original infliximab was rotated with biosimilar. We picked out 42 patients to assess efficacy of original IFX and biosimilar. Twelve patients, received original IFX and 28 patients, treated with its biosimilar, showed significant clinical improvement by decreasing Mayo index from 9.7±0.4 and 10.2±0.2 points to 1.9±0.09 and 2.1±0.1 points, accordingly. Also we noticed positive change in laboratory markers - CRP decrease from 89.6±8.7 mg/l and 77.5±8.0 mg/l to 6.5±0.8 mg/l and 6.9±0.8 mg/l (p>0.05), albumin increase from 30.1±4.7 g/l and 29.6±3.6 g/l to 34.1±6.3 g/l and 32.8±5.9 g/l (p>0.05), increase of serum iron levels from 6.4±0.5 mcg/l and 7.1±0.65 mcg/l to 14.6±4.4 mcg/l and 15.9±5.1 mcg/l (p>0.05), hemoglobin increase from 104.7±9.8 g/l and 102.2±8.8 g/l till 124±11.3 g/l and 121±10.9 g/l (p>0.05), and fecal calprotectin decrease from 1680±134 mcg/g and 1720±126 mcg/g till 245.5±33.4 mcg/g and 230.5±29.8 mcg/g (p>0.05). During 1 year follow - up 12 UC patients, treated with original IFX and its biosimilar, developed adverse events. The majority of adverse events (n=8) were registered in patients, rotating administration of original IFX and its biosimilar. IFX biosimilar is effective as well as original IFX. Frequency of adverse events, occurred in patients, treated with original IFX, was comparable with adverse events frequency in patients, received biosimilar IFX. Frequency of adverse events was significantly higher in UC patients, rotating original IFX and its biosimilar.

Prediction of clinical effects of infliximab administered for inflammatory bowel disease based on pharmacokinetic and pharmacodynamic modeling.

Infliximab (IFX) is used as a therapeutic agent for ulcerative colitis (UC) and Crohn's disease (CD). Although the dosage regimen has been established through clinical trial experience, it has yet to be assessed with a pharmacokinetic and pharmacodynamic model. The present study analysed sequential changes of clinical response in patients with ulcerative colitis and Crohn's disease following repeated administrations of infliximab using the pharmacokinetic/pharmacodynamic model. In addition, the dosage regimen presently used for patients with ulcerative colitis was evaluated, as well as the potential efficacy gained by increasing the dose and/or reducing the interval of administration for patients with Crohn's disease. Furthermore, the possibility of evaluating the difference between both diseases with regard to the efficacy of infliximab was investigated. Sequential changes in the clinical response values obtained with our model were in good agreement with the observed values following administration of infliximab in patients with ulcerative colitis and Crohn's disease. The results showed the importance of a loading dose for patients with ulcerative colitis, as well as the efficacy of increasing the dose and reducing the interval for patients with Crohn's disease. Also, the efficacy of infliximab for both diseases is suggested to be similar. In conclusion, our results show a possible modeling scenario that can accommodate the clinical response to infliximab administered for ulcerative colitis and Crohn's disease. Furthermore, it provides confirmation for the present dosage regimens given for these diseases.