Outcomes of Patients With Inflammatory Bowel Diseases Switched From Maintenance Therapy With a Biosimilar to Remicade.

BACKGROUND & AIMS: There is evidence that it is safe and effective for patients with inflammatory bowel diseases (IBD) to switch from maintenance therapy with an original infliximab drug to a biosimilar, but little is known about outcomes of reverse switches and/or multiple switches. We aimed to evaluate the effects of a reverse switch (from a biosimilar to Remicade) in a real-life cohort. METHODS: We performed a prospective observational study of 174 unselected and consecutive patients with IBD (136 with Crohn's disease [CD] and 38 with ulcerative colitis [UC]) who received maintenance therapy with the biosimilar in Hungary. In September 2017, patients were switched from the biosimilar (CT-P13) to Remicade, due to reimbursement policies. In our cohort, 8% (n = 14) patients had been previously exposed to the originator Remicade. We collected clinical and biochemical information from patients at baseline (time of the switch) and 16 and 24 weeks thereafter. Clinical remission was defined as a Crohn's disease activity index <150 points or no fistula drainage, or a partial Mayo score <3 points for patients with UC. Serum drug trough levels and anti-drug antibodies were measured at baseline and week 16. RESULTS: There was no significant difference in the proportion of patients in clinical remission at week 8 before the switch (82.5% with CD and 82.9% with UC), at baseline (80.6% with CD and 81.6% with UC), at week 16 (77.5% with CD and 83.7% with UC), or at week 24 (CD 76.3% with CD and 84.9% with UC) (P = .60 among groups for patients with CD and P = .98 among groups for patients with UC). For all patients, mean serum trough levels of infliximab were 5.33 ± 4.70 µg/mL at baseline and 5.69 ± 4.94 µg/mL at week 16 (P = .71); we did not find significant differences in prevalence of anti-drug antibody at baseline (16.2%) compared with week 16 (16.9%) (P = .87). Four infusion reactions occurred, until week 24 of follow up. There was no difference in outcomes or trough or antidrug antibody levels between patients with or without previous exposure to Remicade. CONCLUSIONS: We collected data from a real-life cohort of patients with CD or UC who were switched from maintenance therapy with a biosimilar to Remicade or were treated with only Remicade. No significant changes were observed in remission, trough levels, or antidrug antibodies in patients switched from the biosimilar to Remicade. No new safety signals were detected.

Therapeutic preferences and outcomes in newly diagnosed patients with Crohn's diseases in the biological era in Hungary: a nationwide study based on the National Health Insurance Fund database.

BACKGROUND: Accelerated treatment strategy, including tight disease control and early aggressive therapy with immunosuppressives (IS) and biological agents have become increasingly common in inflammatory bowel disease (IBD). The aim of the present study was to estimate the early treatment strategy and outcomes in newly diagnosed patients with Crohn's disease (CD) between 2004 and 2008 and 2009-2015 in the whole IBD population in Hungary based on the administrative database of the National Health Insurance Fund (OEP). METHODS: We used the administrative database of the OEP, the only nationwide state-owned health insurance provider in Hungary. Patients were identified through previously reported algorithms using the ICD-10 codes for CD in the out-, inpatient (medical, surgical) non-primary care records and drug prescription databases between 2004 and 2015. Patients were stratified according to the year of diagnosis and maximum treatment steps during the first 3 years after diagnosis. RESULTS: A total of 6173 (male/female: 46.12%/53.87%) newly diagnosed CD patients with physician-diagnosed IBD were found in the period of 2004-2015. The use of 5-ASA and steroids remained common in the biological era, while immunosuppressives and biologicals were started earlier and became more frequent among patients diagnosed after 2009. The probability of biological therapy was 2.9%/6.4% and 8.4%/13.7% after 1 and 3 years in patients diagnosed in 2004-2008/2009-2015. The probability of hospitalization in the first 3 years after diagnosis was different before and after 2009, according to the maximal treatment step (overall 55.7%vs. 47.4% (p = 0.001), anti-TNF: 73%vs. 66.7% (p = 0.103), IS: 64.6% vs. 56.1% (p = 0.001), steroid: 44.2%vs. 36.8% (p < 0.007), 5-ASA: 32.6% vs. 26.7% p = 0.157)). In contrast, surgery rates were not significantly different in patients diagnosed before and after 2009 according to the maximum treatment step (overall 16.0%vs.15.3%(p = 0.672) anti-TNF 26.7%vs.27.2% (p = 0.993), IS: 24.1%vs22.2% (p = 0.565), steroid 8.1%vs.7.9% (p = 0.896), 5-ASA 10%vs. 11% (p = 0.816)). CONCLUSIONS: IS and biological exposure became more frequent, while hospitalization decreased and surgery remained low but constant during the observation period. Use of steroids and 5-ASA remained high after 2009. The association between the maximal treatment step and hospitalization/surgery rates suggests that maximal treatment step can be regarded as proxy severity marker in patients with IBD.

Burden of Mental Health among Patients with Inflammatory Bowel Disease-A Cross-Sectional Study from a Tertiary IBD Center in Hungary.

Background: Inflammatory bowel diseases (IBDs) are chronic conditions that negatively affect the patient's quality of life. With the spread of the biopsychosocial model, the role of mental health in the activity and course of inflammatory bowel disease is becoming more and more recognized. Our study aimed to assess the prevalence of anxiety and depression in IBD patients in our tertiary referral center and determine the predictive factors of these mental conditions. Methods: A total of 117 patients were included consecutively between 1 December 2021 and 28 February 2022. We used a questionnaire to gather demographic information, disease course, and IBD-specific symptoms. We assessed anxiety symptoms using the GAD-7 and depressive complaints using the PHQ-9 questionnaire. We evaluated disease activity using CDAI and pMayo scores. Results: Of the 117 patients (male/female: 63/54), 88 suffered from Crohn's disease, and 29 were diagnosed with ulcerative colitis. Only 6 patients were taking medication for mood disorders, and 38 individuals sought mental support during their lifetime. A total of 15% of the population suffered from moderate-severe anxiety disorder, and 22% were affected by moderate-severe depression. The GAD-7 and PHQ9 values showed a significant correlation between the number of stools, bloody stools, abdominal pain, number of flare-ups, and CDAI scores. Conclusions: Our study confirmed that there is a high incidence of anxiety and depressive symptoms among IBD patients. Our results highlighted the symptoms that could be associated with mental disorders. It is important to assess the mental status of IBD patients to improve their quality of life.

Burden of perianal disease in Crohn's disease: Accelerating medical therapy and high rates of perianal surgery over the last four decades - Results from a population-based study over four decades.

BACKGROUND: Few population-based studies have investigated the prevalence and disease course of perianal manifestation in Crohn's disease. AIMS: To analyse the prevalence and outcomes of perianal Crohn's disease including medical therapies and need for perianal surgery, over different therapeutic eras based on the time of diagnosis; cohort A (1977-1995), cohort B (1996-2008), and cohort C (2009-2018) METHODS: Patient inclusion lasted between 1977 and 2018. We followed patients prospectively, and regularly reviewed both in-hospital and outpatient records. We defined a perianal surgical procedure as any perianal incision and excision, fistulotomy, or abscess drainage. RESULTS: We included 946 incident patients. Perianal disease at diagnosis was present in 17.4% (n = 165) of the total cohort, with a declining prevalence in cohorts A/B/C, respectively (24.7%/18.5%/13.2%; p = 0.001). By the end of follow-up, an additional 9.3% (n = 88) of the total cohort developed perianal disease. Cumulative immunosuppressive and biologic exposure increased over time; biologic use was higher in patients with perianal disease [pLog Rank < 0.001]. The overall rate of perianal surgery was 44.7% (113/253), with a probability of 28.3% (95% CI: 25.4-31.2) after 10 years, 41.0% (95% CI: 37.5-44.5) after 20 years, and 64.1% (95% CI: 59-69.2) after 30 years. There was no statistically significant difference in the probability of first perianal surgery among cohorts A/B/C [Log Rank = 0.594]. CONCLUSIONS: The burden of perianal disease and perianal surgery rates were high in this cohort. Therapeutic strategy was accelerated in patients with perianal Crohn's over time with higher exposure to immunosuppressives and biologics. Surgical management of perianal disease remained unchanged amongst the cohorts.

Efficacy, drug sustainability, and safety of ustekinumab treatment in Crohn's disease patients over three years.

Long-term data on ustekinumab in real-life Crohn's disease patients are still missing, though randomized controlled trials demonstrated it as a favorable therapeutic option. We aimed to evaluate ustekinumab's clinical efficacy, drug sustainability, and safety in a prospective, nationwide, multicenter Crohn's disease patient cohort with a three-year follow-up. Crohn's disease patients on ustekinumab treatment were consecutively enrolled from 9 Hungarian Inflammatory Bowel Disease centers between January 2019 and May 2020. Patient and disease characteristics, treatment history, clinical disease activity (Harvey Bradshaw Index (HBI)), biomarkers, and endoscopic activity (Simple Endoscopic Score for Crohn's Disease (SES-CD)) were collected for three-years' time. A total of 148 patients were included with an overall 48.9% of complex behavior of the Crohn's disease and 97.2% of previous anti-TNF exposure. The pre-induction remission rates were 12.2% (HBI), and 5.1% (SES-CD). Clinical remission rates (HBI) were 52.2%, 55.6%, and 50.9%, whereas criteria of an endoscopic remission were fulfilled in 14.3%, 27.5%, and 35.3% of the subjects at the end of the first, second, and third year, respectively. Dose intensification was high with 84.0% of the patients on an 8-weekly and 29.9% on a 4-weekly regimen at the end of year 3. Drug sustainability was 76.9% during the follow-up period with no serious adverse events observed. Ustekinumab in the long-term is an effective, sustainable, and safe therapeutic option for Crohn's disease patients with severe disease phenotype and high previous anti-TNF biological failure, requiring frequent dose intensifications.

[Esophageal candidiasis as an indicator condition]. / Candidaoesophagitis mint indikátorbetegség.

Esophageal candidiasis is the most common infectious disease of the esophagus. The diagnosis is based on gastroscopy, and in many cases, biopsy samples should be taken as well. If we do not know of any risk factors for an immunocompromised condition, it is a mutual responsibility to confirm or exclude any potential chronic disease in the background, thus not just the secondary complication but also the primary disease could be treated. Without this knowledge, in many cases, the correct diagnosis may be delayed for months or even years, which may risk the successful treatment. We present the case of a 58-year-old healthy woman without any chronic disease, who was referred to our clinic with dysphagia. Due to her complaints we performed a gastroscopy, upon which advanced esophageal candidiasis was diagnosed, hence she was started on oral systemic antifungal treatment. Although we could not explore any risk factors, further investigations behind the immunocompromised condition revealed a positive immunoserology test for HIV. The take-home message of our case is that in the case of esophageal candidiasis, the cause of immunosuppression must be searched for, of which HIV serology is crucial. Thanks to the prompt and correct diagnosis, we could start the suitable treatment of the underlying disease. Orv Hetil. 2023; 164(22): 878-880.

Objective Disease Monitoring Strategies from a Tertiary Inflammatory Bowel Disease Center in Hungary.

BACKGROUND: Emerging data suggest that a treat-to-target approach and early therapeutic intervention using regular objective disease assessment leads to improved outcomes. Our aim was to evaluate the value of objective disease monitoring during regular follow-up in a single tertiary inflammatory bowel disease center. METHODS: Consecutive inflammatory bowel disease patients (n = 161, Crohn's disease: 118/ulcerative colitis: 43; biological therapy: 70%) were included and followed up for 1 year between January and December 2018. Data on clinical disease activity, biomarkers, endoscopy, imaging, outpatient visits, treatment optimization, hospitalization, and surgery were collected. We compared the monitoring strategy according to the clinical activity (remission/flare/post-flare/continuous activity) every 3 months (assessment period). RESULTS: In total, n = 644 assessment periods were evaluated. Biomarkers were evaluated in 82.9%-83.9% of patients in each assess ment period regardless of clinical activity. Colonoscopy was more frequently performed in active disease (flare/continuous disease activ ity: 21.1%/18.9% vs. clinical remission: 10.1% per assessment period). Magnetic resonance imaging was performed in 7.7%-16.7%/ period in Crohn's disease patients, while the use of computed tomography was low (2.4%/period) and mainly performed in active dis ease. Treatment optimization was more frequent in patients with active disease (biological start/dose optimization: 31.1%/33.8%/ period, steroid start: 13.2%/period). Patients with continuous activity (2.62), flare (2.45), and post-flare (2.05) had higher mean patient visit counts compared to remission (1.68/period). CONCLUSIONS: Objective monitoring strategy was applied with routine assessment of clinical activity and biomarkers. Fast-track colo noscopic evaluations were adapted to the clinical stage of the disease while screening colonoscopies and magnetic resonance imaging were frequently used. Objective monitoring resulted in the early optimization of medical therapy and frequent specialist follow-up visits.

Declining Trends of Reoperations and Disease Behaviour Progression in Crohn's Disease over Different Therapeutic Eras-A Prospective, Population-Based Study from Western Hungary between 1977-2020, Data from the Veszprem Cohort.

BACKGROUND AND AIMS: Few population-based studies have investigated long-term surgery rates for Crohn's disease [CD]. Our aim was to analyse disease progression and surgery rates in a population-based cohort over different therapeutic eras, based on the time of diagnosis: cohort-A [1977-1995], cohort-B [1996-2008], and cohort-C [2009-2018]. METHODS: A total of 946 incident CD patients were analysed (male/female: 496/450; median age at diagnosis: 28 years [y]; interquartile range [IQR]: 22-40]). Patient inclusion lasted between 1977 and 2018. Immunomodulators have become widespread in Hungary since the mid-1990s and biologic therapies since 2008. Patients were followed prospectively, with both in-hospital and outpatient records reviewed regularly. RESULTS: The probability of disease behaviour progression from inflammatory [B1] to stenosing or penetrating phenotype [B2/B3] significantly decreased (27.1 ±â€…5.3%/21.5 ±â€…2.5%/11.3 ±â€…2.2% in cohorts A/B/C, respectively, after 5 years; 44.3 ±â€…5.9%/30.6 ±â€…2.8%/16.1 ±â€…2.9% after 10 years, respectively; [pLogRank <0.001]). The probability of first resective surgery between cohorts A/B/C were 33.3 ±â€…3.8%/26.5 ±â€…2.1%/28.1 ±â€…2.4%, respectively, after 5 years; 46.1 ±â€…4.1%/32.6 ±â€…2.2%/33.0 ±â€…2.7% after 10 years, respectively; and 59.1 ±â€…4.0%/41.4 ±â€…2.6% [cohorts A/B] after 20 years. There was a significant decrease in first resective surgery risk between cohorts A and B [plog rank = 0.002]; however, no further decrease between cohorts B and C [plog rank = 0.665]. The cumulative probability of re-resection in cohorts A/B/C was decreasing over time (17.3 ±â€…4.1%/12.6 ±â€…2.6%/4.7 ±â€…2.0%, respectively, after 5 years [plog rank = 0.001]). CONCLUSION: We report a continuous decline in reoperation rates and disease behaviour progression in CD over time, with the lowest values in the biologic era. In contrast, there was no further decrease in the probability of first major resective surgery after the immunosuppressive era.

Malignant solid tumor associated with hypereosinophilic syndrome / Malignus solid tumorhoz társuló hypereosinophil szindróma

Hypereosinophilic syndrome is characterized by chronic eosinophil overproduction, resulting in multiple organ damages due to eosinophil infiltration and mediator release. According to the etiology, we distinguish between myeloproliferative disorders, parasitic infections, solid tumors, T-cell lymphomas and idiopathic forms. In our case report, the 49-year-old man was hospitalized with weight loss, leg edema and tachycardia. In his laboratory tests increased biliary obstructive parameters as well as extreme leukocytosis and eosinophilia had been highlighted. We started our evaluation with a strong suspicion of hematologic malignancy. The CT scan of the thorax, abdomen and pelvis described hepatosplenomegaly, multiple intrahepatic lesions and an uncertain solitary cystic lesion in the tail of the pancreas with abnormal lymph nodes and pleural fluid. The described CT image and the other clinical parameters were primarily consistent with the manifestation of chronic myeloid leukemia. However, the diagnosis was not confirmed by peripheral blood smear, flow cytometry, bone marrow biopsy or genetic tests. After these results, we continued the assessment towards solid tumor associated leukemoid reaction, core biopsy was performed to verify the liver lesions. The biopsy confirmed the infiltration of a poorly differentiated epithelial tumor as a metastasis of pancreatobiliary carcinoma. To the best of our knowledge, this is the first case report on hypereosinophilic syndrome associated with gastrointestinal solid tumors in the Hungarian medical literature. It draws attention to the differential diagnosis of extreme leukocytosis and eosinophil ratios and by the absence of confirmed hematological disease the importance of early biopsy sampling of solid lesions.

Non-medical switch from the originator to biosimilar and between biosimilars of adalimumab in inflammatory bowel disease - a prospective, multicentre study.

INTRODUCTION: Clinical data on the efficacy and safety of non-medical switch between adalimumab(ADA) biosimilars are limited. AIMS: The aim of this study was to evaluate medium-term clinical efficacy, drug sustainability and safety comparing non-medical switches from the originator to biosimilar ADA, and between ADA biosimilars. METHODS: 276 consecutive patients on maintenance ADA therapy (n = 205 Crohn's disease, n = 71 ulcerative colitis) were included. Data on clinical efficacy, biomarkers and adverse events were collected at four time points: 8-12 weeks prior switch, at baseline/switch, 8-12 weeks and 20-24 weeks after switch. Drug survival was evaluated after a median 40(IQR:35-42) weeks follow-up. RESULTS: A total 174 patients underwent a non-medical switch from the originator to a biosimilar, and 102 patients had a biosimilar-to-biosimilar switch. No significant difference was found in clinical remission rates at any time point in patients switching from originator to biosimilar(87.3%/88.5%/86.5%/85.7%) or biosimilar to biosimilar(74.5%/78.4%/85.3%/79.8%). Mean C-reactive protein levels remained unchanged in both cohorts(p = 0.856 and p = 0.525). Drug survival was similar between the two cohorts with a probability of 91.6%(SE: 2.2) and 87.0%(SE:3.4) to stay on drug after 40 weeks(log-rank:0.96; p = 0.327). Five cases of injection related adverse events were reported. CONCLUSION: Clinical benefit was sustained following non-medical switch from originator to biosimilar, or between biosimilars in adalimumab treated IBD patients.

Ustekinumab is associated with superior treatment persistence but not with higher remission rates versus vedolizumab in patients with refractory Crohn's disease: results from a multicentre cohort study.

Background: Treatment with antitumor necrosis factor alpha (anti-TNF-α) is safe and effective as first-line therapy; however, its efficacy is limited due to primary nonresponse (PNR) and secondary loss of response (LOR), resulting in treatment discontinuation in approximately 40%-50% of cases. Vedolizumab (VDZ) and ustekinumab (UST) therapies could be good alternatives in patient with anti-TNF failure; however, no head-to-head randomized comparison of these drugs as second- or third-line treatments has been made. Objectives: This study aimed to assess the treatment persistence and comparative effectiveness of UST and VDZ in patients with refractory Crohn's disease (CD). Design: In this nationwide retrospective study, patients with CD on UST or VDZ maintenance therapy were enrolled. Clinical data at baseline, after induction, and at week 52 were obtained. Methods: Clinical and biochemical activities as well as corticosteroid-free remission (SFR) rates were assessed, while concomitant medications, comorbidities, hospitalizations, and surgeries were recorded during the follow-up to detect any predictors. Results: A total of 161 UST- and 65 VDZ-treated patients completed the follow-up. No significant difference in clinical or biochemical remission rates was observed after induction between the two treatment groups; however, clinical remission rate at week 52 was higher in UST group. UST showed superior drug persistence than VDZ (86.5%, 57.9%, p < 0.0001). The drug type was predictive of clinical SFR at week 52 [p = 0.011, odds ratio (OR) = 2.39 with UST]. Drug failure rates were higher for VDZ than those for UST (PNR rates: 21.54% and 4.97%, respectively, p < 0.001, OR = 8.267, p = 0.001). LOR and escalations were more common during UST treatment (61.5% versus 36.9%, p < 0.001; 64.2% versus 23.1%, p < 0.001). Hospital and surgical admission rates did not differ significantly. Only one adverse event occurred with VDZ at week 20, which led to drug cessation. Conclusions: VDZ and UST were safe and effective for treating patients with CD in whom anti-TNF therapy failed. UST showed superior drug persistence than VDZ, but dose escalation was more frequent. Biologicals used in lower treatment lines resulted in better drug persistence.

Clinical efficacy, drug sustainability and serum drug levels in Crohn's disease patients treated with ustekinumab - A prospective, multicenter cohort from Hungary.

INTRODUCTION: Although efficacy of ustekinumab (UST) has been demonstrated through randomized trials, data from real-life prospective cohorts are still limited. Our aim was to evaluate clinical efficacy, drug sustainability, dose intensification and results from therapeutic drug monitoring in UST treated patients with Crohn's disease (CD) using a prospective, nationwide, multicenter cohort. METHODS: Patients from 10 Inflammatory Bowel Disease centers were enrolled between 2019 January and 2020 May. Patient demographics, disease phenotype, treatment history, clinical disease activity (Crohn's Disease Activity Index(CDAI), Harvey Bradshaw Index(HBI)), biomarkers, and serum drug levels were obtained. Evaluations were performed at week8 (post-induction), w16-20, w32-36, and w52-56 follow-up visits. RESULTS: A total of 142 patients were included [57.4% female; complex disease behavior (B2/B3):48%, previous anti-TNF exposition:97%]. Clinical response and remission rates after induction(w8) were 78.1% and 57.7% using CDAI, and 82.5% and 51.8% based on HBI scores. The one-year clinical remission rate was 58%/57.3%(CDAI/HBI). Composite clinical and biomarker remission (CDAI<150 and C-reactive protein<10 mg/L) rates were 35.4%; 33.3%; 38.6% and 36.6% at w8/w16-20/w32-36 and w52-56. Drug sustainability was 81.9%(standard deviation(SD): 3.4) at 1 year(1y). Probability of dose intensification was high and introduced early, 42.2%(SD:4.2) at ~w32 and 51.9%(SD:4.4%) at 1y. CONCLUSION: Ustekinumab showed favorable drug sustainability and clinical efficacy in a patient population with severe disease phenotype and previous anti-tumor necrosis factor (anti-TNF) failure, however frequent dose intensification was required.

Incidence, Predictive Factors, Clinical Characteristics and Outcome of Non-variceal Upper Gastrointestinal Bleeding - A Prospective Population-based Study from Hungary.

BACKGROUND AND AIMS: Acute non-variceal upper gastrointestinal bleeding (UGIB) is associated with significant morbidity and mortality. Our aim was to evaluate the incidence, management, risk factors and outcomes of acute non-variceal UGIB in a population-based study from Hungary. METHODS: The present prospective one-year study involved six major community hospitals in Western Hungary covering a population of 1,263,365 persons between January 1 and December 31, 2016. Data collection included demographics, comorbidities endoscopic management, Glasgow-Blatchford score (GBS), Rockall score (RS) transfusion requirements, length of hospital stay and mortality. RESULTS: 688 cases of acute non-variceal UGIB were included with an incidence rate of 54.4 (95%CI: 50.5-58.6) per 100,000 per year. Endoscopy was performed within 12 hours in 71.8%. 5.3% of the patients required surgical treatment and the overall mortality was 13.5%. Weekend presentation was associated with increased transfusion requirements (p=0.047), surgery (p=0.016) and mortality (p=0.021). Presentation with hemodynamic instability or presence of comorbidities was associated with transfusion (p<0.001 both), second look endoscopy (p<0.001 both), re-bleeding (p<0.001 both), longer in-hospital stay (p<0.001 both) and mortality (p=0.017 and p<0.001). GBS was associated with transfusion requirement (AUC:0.82; cut-off: GBS >7points), while mortality was best predicted by the post-endoscopic RS (AUC:0.75; cut-off: RS >5points). CONCLUSIONS: Incidence rates of acute non-variceal UGIB in Western Hungary are in line with international trends. Longer pre-hospital time, comorbidities, hemodynamic instability, weekend presentation, treatment with anticoagulants or non-steroidal anti-inflammatory drugs was associated with worse outcomes.

Outcomes of variceal upper gastrointestinal bleeding: A prospective, multicenter, population-based study from West Hungary / A varixeredetu felso gastrointestinalis vérzések elemzése: yugat-magyarországi prospektív, multicentrikus, népességalapú vizsgálat

Összefoglaló. Bevezetés: Az akut varixeredetu gastrointestinalis vérzés napjainkban is jelentos morbiditással és mortalitással jár. Célkituzés: Célunk az akut varixeredetu felso gastrointestinalis vérzések incidenciájának, ellátási folyamatainak és kimeneteli tényezoinek átfogó felmérése volt. Módszer: Prospektív, multicentrikus vizsgálatunk keretében hat nyugat-magyarországi gasztroenterológiai centrum bevonásával elemeztük az ott diagnosztizált és kezelt, varixvérzo betegek adatait. Rögzítettük a demográfiai, az anamnesztikus, a diagnosztikus, valamint a terápiát és a betegség kimenetelét érinto adatokat. Minden beteg esetében kockázat- és predikcióbecslést végeztünk a Glasgow-Blatchford Score (GBS), a pre- és posztendoszkópos Rockall Score (RS) és az American Society of Anesthesiologists (ASA) Score alapján. Eredmények: A vizsgált egyéves periódusban (2016. 01. 01. és 2016. 12. 31. között) 108, akut varixeredetu gastrointestinalis vérzést találtunk (átlagéletkor: 59,6 év). Endoszkópos terápiára 57,4%-ban került sor, 39,8% sclerotherapiában, 18,5% ligatióban részesült. Transzfúziót a betegek 76,9%-a igényelt. A teljes halálozás 24,1% volt. A transzfúziós igény vonatkozásában a legmagasabb prediktív értéku a GBS volt (AUC: 0,793; cut-off: GBS >8 pont). Az ASA-pontszám szignifikáns összefüggést mutatott a transzfúzió-szükséglettel (OR 7,6 [CI 95% 2,7-21,6]; p<0,001), az endoszkópos intervencióval (OR 12,6 [CI 95% 3,4-46,5]; p = 0,033) és trendszeru kapcsolatot a mortalitással (OR 3,6 [0,8-16,7]; p = 0,095). Emellett a nemzetközi normalizált ráta (INR) értéke (p = 0,001) és a szérumkreatinin-szint (p = 0,002) állt kapcsolatban a mortalitással. Az endoszkópos intervenció aránya szignifikáns összefüggésben volt a varix Paquet-stádiumával (p<0,001) és az ASA-pontszámmal (OR = 12,6 [3,4-46,5]; p = 0,033). Következtetés: Nyugat-Magyarországon magas az akut varixeredetu vérzés elofordulási gyakorisága. Az ASA-pontszám és a GBS jó prediktív faktor a betegségkimenetel és a transzfúziós igény vonatkozásában. A megfigyelt magas mortalitás és az endoszkópos ligatio alacsony aránya indokolja a kezelési stratégiák optimalizálását akut varixeredetu gastrointestinalis vérzés esetén. Orv Hetil. 2021; 162(31): 1252-1259. INTRODUCTION: Acute variceal gastrointestinal bleeding is associated with significant morbidity and mortality. OBJECTIVE: Our aim was to evaluate the characteristics and prognostic factors in the management of acute upper gastrointestinal bleeding in a large multi-center study from Hungary. METHOD: This prospective one-year study (between January 1, 2016 and December 31, 2016) involved six community hospitals in Western Hungary. Data collection included demographic characteristics, vital signs at admission, comorbidities, medications, time to hospital admission and endoscopy, laboratory results, endoscopic management, risk assessment using Glasgow-Blatchford Score (GBS), Rockall Score (RS) and the American Society of Anesthesiologists (ASA) Physical Status Score, transfusion requirements, length of hospital stay and mortality. RESULTS: 108 cases (male: 69.4%) of acute variceal gastrointestinal bleeding were registered during the 1-year period. Endoscopic therapeutic intervention was performed in 57.4%. On initial endoscopy, 39.8% of the patients were treated with sclerotherapy and 18.5% had ligation. 76.9% of the patients required blood transfusion. The overall mortality (including in-hospital bleedings) was 24.1%. The GBS predicted transfusions (AUC: 0.793; cut-off: GBS >8 points). The ASA Score was associated with transfusion (OR 7.6 [CI 95% 2.7-21.6]; p<0.001), endoscopic intervention (OR 12.6 [CI 95% 3.4-46.5]; p = 0.033), and showed similar trend with mortality (OR 3.6 [0.8-16.7]; p = 0.095). The increased international normalized ratio (INR) and creatinine levels were associated with mortality (p = 0.001 and p = 0.002). CONCLUSION: Incidence rates of acute variceal gastrointestinal bleeding in Western Hungary are high. The ASA Score, GBS predicted outcomes and transfusion requirements. The observed high mortality rates, coupled with relatively low rates of endoscopic ligation, warrant optimization of management strategies in acute variceal gastrointestinal bleeding. Orv Hetil. 2021; 162(31): 1252-1259.

Anti-TNF dose escalation and drug sustainability in Crohn's disease: Data from the nationwide administrative database in Hungary.

BACKGROUND: A significant percentage of patients receiving anti-tumor necrosis factor alpha (anti-TNFα) agents lose clinical response over time. This study aims to provide representative real-world data on anti-TNFα drug sustainability, prevalence and predictors of anti-TNFα dose escalation. METHODS: In this nationwide, retrospective study, patients receiving infliximab or adalimumab therapy between 2013 and 2016 were included using the administrative claims database of the Hungarian National Health Insurance Fund. Demographic characteristics, drug sustainability, dose escalation, use of parallel medications were analyzed. RESULTS: 476 infliximab and 397 adalimumab patients were included. Dose escalation was observed in 7%, 9% and 22% of patients receiving originator/biosimilar infliximab and adalimumab during the complete follow-up, respectively. Dose escalation was associated with shorter disease duration (OR = 1.75, p = 0.026) and corticosteroid use. Drug retention rates were 62.7%, 72.3%, 75.4% after 1 year follow-up for Remicade®, Inflectra® and Humira®, which decreased to 38.3% and 52.1% for Remicade® and Humira® at 3 years. Drug sustainability was affected by steroid use prior biologic initiation in adalimumab treated patients (HR = 2.04, p < 0.001), while in infliximab treated patients dose escalation (HR = 0.51, p = 0.02) and gender (HR = 1.39, p = 0.033) were predictors of treatment discontinuation. CONCLUSION: Dose escalation rates were lower in this real-world administrative database study for both adalimumab and infliximab compared to published data. Drug retention rates were overall satisfactory, with no apparent difference between the legacy and biosimilar infliximab.

Biosimilars in IBD: Will it Benefit to Patients, Physicians or the Health Care System?

The introduction of biological drugs has revolutionized the management of inflammatory bowel diseases (IBD), however, the increasing financial burden of biologicals on the health care system is alarming. Biosimilars are considered to be equivalent to the reference medicinal product (RMP) in terms of pharmacokinetic properties, clinical effectiveness and safety. CT-P13 infliximab was the first biosimilar to be approved by the regulatory authorities EMA and US FDA, and others are becoming increasingly available as patents expire on the RMP. Emerging data suggests that one-way switching from the RMP to an approved biosimilar is safe and acceptable, however data on multiple-switching, reversed switching, or cross-switching between biosimilars is scarce. Accumulating data on biosimilars led to an increased acceptance amongst physicians and their use can be expected to offer increased availability for patients, and also better control of economic sustainability. This review discusses the available data on clinical efficacy and safety of approved biosimilar agents, and assesses the current impact and future perspectives of biosimilars on the health care system.

[The role of fecal calprotectin in the diagnosis and treatment of gastrointestinal diseases]. / A székletkalprotektin meghatározásának szerepe a bélbetegségek diagnosztikájában és kezelésében.

The diagnostics of gastrointestinal diseases have evolved significantly in the past few decades. Besides endoscopy and conventional imaging modalities, there is a growing interest for rapid point-of-care laboratory tests to help discriminate between diseases with similar clinical symptoms and/or help the follow-up of chronic conditions, predicting relapses. The fecal calprotectin testing is a routine diagnostic tool in many countries. It is also more and more accessible in Hungary as well. We aim to present a short review on the role and performance of fecal calprotectin test in the diagnosis and follow-up of gastrointestinal diseases, especially inflammatory bowel diseases, gastrointestinal infections, irritable bowel syndrome and pediatric conditions. By presenting the different cut-off values, sensitivity and specificity rates representative for each disease, we hope to further aid clinicians in decision-making regarding these conditions. Orv Hetil. 2019; 160(9): 322-328.

Biosimilars in ulcerative colitis: When and for who?

The introduction of biological agents has revolutionized the management of ulcerative colitis (UC). Biosimilars are considered to be equivalent to the reference biologic products in terms of pharmacokinetic properties, clinical effectiveness and safety and have now been approved in inflammatory bowel diseases (IBD). CT-P13 was the first biosimilar to infliximab that obtained regulatory approval by the EMA and US FDA. Accumulating data on biosimilars led to an increased acceptance amongst practicing gastroenterologists and their use can be associated with a potential reduction in healthcare costs. This review discusses the current state of knowledge on biosimilar use in UC. Authors review the existing data on clinical efficacy, safety and immunogenicity of biosimilar infliximab and adalimumab agents. Emerging data suggests that switching from originator to biosimilar is safe for CT-P13 infliximab, however data on other biosimilars, multiple-switching, reverse-switching, or cross-switching between biosimilars is lacking. The pathway for interchangeability of biosimilars is different in the US and Europe and many aspects have yet to be clarified by federal regulators. Since the approval of the first biosimilar, the biosimilar concept seems to be successful and has led to an increased use of biosimilar drugs in the treatment of UC worldwide with a better access for patients to biologic. Real-world data from prospective observational studies for 'follow-on' biosimilars is needed to ensure that safety, efficacy and immunogenicity is comparable to the originator in IBD, and that switching from the originator or among biosimilars is a safe option.