Use Of Infliximab Research Articles

Systematic Review and Meta-analysis: Loss of Response and Need for Dose Escalation of Infliximab and Adalimumab in Ulcerative Colitis.

Loss of response to infliximab or adalimumab in ulcerative colitis occurs frequently, and dose escalation may aid in regaining clinical benefit. This study aimed to systematically assess the annual loss of response and dose escalation rates for infliximab and adalimumab in ulcerative colitis. A systematic search was conducted from August 1999 to July 2021 for studies reporting loss of response and dose escalation during infliximab and/or adalimumab use in ulcerative colitis patients with primary response. Annual loss of response, dose escalation rates, and clinical benefit after dose escalation were calculated. Subgroup analyses were performed for studies with 1-year follow-up or less. We included 50 unique studies assessing loss of response (infliximab, n = 24; adalimumab, n = 21) or dose escalation (infliximab, n = 21; adalimumab, n = 16). The pooled annual loss of response for infliximab was 10.1% (95% confidence interval [CI], 7.1-14.3) and 13.6% (95% CI, 9.3-19.9) for studies with 1-year follow-up. The pooled annual loss of response for adalimumab was 13.4% (95% CI, 8.2-21.8) and 23.3% (95% CI, 15.4-35.1) for studies with 1-year follow-up. Annual pooled dose escalation rates were 13.8% (95% CI, 8.7-21.7) for infliximab and 21.3% (95% CI, 14.4-31.3) for adalimumab, regaining clinical benefit in 72.4% and 52.3%, respectively. Annual loss of response was 10% for infliximab and 13% for adalimumab, with higher rates during the first year. Annual dose escalation rates were 14% (infliximab) and 21% (adalimumab), with clinical benefit in 72% and 52%, respectively. Uniform definitions are needed to facilitate more robust evaluations.

USE OF INFLIXIMAB AS THERAPEUTIC OPTION FOR STEROID-RESISTANT PARADOXICAL REACTION IN TB

SESSION TITLE: TB and TB-Involved Case PostersSESSION TYPE: Case Report PostersPRESENTED ON: 10/17/2022 12:15 pm - 01:15 pmINTRODUCTION: Paradoxical reaction (PR) is an immune-mediated disease exacerbation precipitated by initiation of antitubercular therapy (ATT). Unlike IRIS (immune reconstitution inflammatory syndrome), a hyperinflammatory response to HIV/AIDS treatment, PR is independent of antiretroviral therapy (ART). Standard guideline therapy for PR is limited, with glucocorticoids as a standard of care. We describe a case of steroid-resistant tuberculin PR that improved with experimental Infliximab therapy.CASE PRESENTATION: 42-year-old HIV negative female with a history of rheumatoid arthritis on methotrexate and ovarian cancer on chemotherapy, presented with dyspnea and left-sided weakness. Chest imaging demonstrated a diffuse miliary pattern (image 1). QuantiFERON testing was positive. Cerebrospinal fluid studies, bronchoalveolar lavage and sputum cultures detected Mycobacterium tuberculosis (TB). Cultures demonstrated no antimicrobial resistance. Magnetic Resonance Imaging demonstrated lesions favoring CNS tuberculomas (image 2).There was transient clinical improvement with expanded ATT (Rifampin, Isoniazid, Pyrazinamide, Levofloxacin, Linezolid, Dexamethasone) but the disease continued to worsen despite increasing dosage of the glucocorticoid. Emergent salvage therapy with Infliximab significantly improved the intracranial and respiratory disease burden (image 3) with near resolution of clinical findings.DISCUSSION: An overexaggerated cell-mediated immune response against killed or damaged mycobacterium results in PR [1]. Moreover, granulomatous host response to TB may sequester the organism from administered antitubercular treatment [2]. Manipulation of immunomodulation by targeting tumor necrosis factor alpha (TNF alpha) is a proposed potential therapeutic option for PR [2] as it can decrease inflammation and disrupt granulomatous formations.CONCLUSIONS: There are only handful case reports exploring alternatives for steroid resistant PR. TNF-a inhibition is a potential valid treatment option in such cases [2].Reference #1: Blackmore, T. K., Manning, L., Taylor, W. J., & Wallis, R. S. (2008). Therapeutic Use of Infliximab in Tuberculosis to Control Severe Paradoxical Reaction of the Brain and Lymph Nodes. Clinical Infectious Diseases, 47(10), e83–e85. https://doi.org/10.1086/592695Reference #2: Briner, M., Oberholzer, M., Chan, A., & Wagner, F. (2021). Potential disease trigger as a therapeutic option: infliximab for paradoxical reaction in tuberculosis of the central nervous system. BMJ Case Reports, 14(8), e235511. https://doi.org/10.1136/bcr-2020-235511DISCLOSURES: No relevant relationships by Nicholas KlimbergNo relevant relationships by Pallabi ShresthaNo relevant relationships by Sarah UpsonNo relevant relationships by Kenji Yoshino SESSION TITLE: TB and TB-Involved Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Paradoxical reaction (PR) is an immune-mediated disease exacerbation precipitated by initiation of antitubercular therapy (ATT). Unlike IRIS (immune reconstitution inflammatory syndrome), a hyperinflammatory response to HIV/AIDS treatment, PR is independent of antiretroviral therapy (ART). Standard guideline therapy for PR is limited, with glucocorticoids as a standard of care. We describe a case of steroid-resistant tuberculin PR that improved with experimental Infliximab therapy. CASE PRESENTATION: 42-year-old HIV negative female with a history of rheumatoid arthritis on methotrexate and ovarian cancer on chemotherapy, presented with dyspnea and left-sided weakness. Chest imaging demonstrated a diffuse miliary pattern (image 1). QuantiFERON testing was positive. Cerebrospinal fluid studies, bronchoalveolar lavage and sputum cultures detected Mycobacterium tuberculosis (TB). Cultures demonstrated no antimicrobial resistance. Magnetic Resonance Imaging demonstrated lesions favoring CNS tuberculomas (image 2). There was transient clinical improvement with expanded ATT (Rifampin, Isoniazid, Pyrazinamide, Levofloxacin, Linezolid, Dexamethasone) but the disease continued to worsen despite increasing dosage of the glucocorticoid. Emergent salvage therapy with Infliximab significantly improved the intracranial and respiratory disease burden (image 3) with near resolution of clinical findings. DISCUSSION: An overexaggerated cell-mediated immune response against killed or damaged mycobacterium results in PR [1]. Moreover, granulomatous host response to TB may sequester the organism from administered antitubercular treatment [2]. Manipulation of immunomodulation by targeting tumor necrosis factor alpha (TNF alpha) is a proposed potential therapeutic option for PR [2] as it can decrease inflammation and disrupt granulomatous formations. CONCLUSIONS: There are only handful case reports exploring alternatives for steroid resistant PR. TNF-a inhibition is a potential valid treatment option in such cases [2]. Reference #1: Blackmore, T. K., Manning, L., Taylor, W. J., & Wallis, R. S. (2008). Therapeutic Use of Infliximab in Tuberculosis to Control Severe Paradoxical Reaction of the Brain and Lymph Nodes. Clinical Infectious Diseases, 47(10), e83–e85. https://doi.org/10.1086/592695 Reference #2: Briner, M., Oberholzer, M., Chan, A., & Wagner, F. (2021). Potential disease trigger as a therapeutic option: infliximab for paradoxical reaction in tuberculosis of the central nervous system. BMJ Case Reports, 14(8), e235511. https://doi.org/10.1136/bcr-2020-235511 DISCLOSURES: No relevant relationships by Nicholas Klimberg No relevant relationships by Pallabi Shrestha No relevant relationships by Sarah Upson No relevant relationships by Kenji Yoshino

S2729 Failed Tofacitinib Rescue Therapy in Acute Severe Ulcerative Colitis Refractory to Steroids and Anti-TNF Therapy

Introduction: Acute severe ulcerative colitis (ASUC) is a life-threatening condition that may lead to complications such as toxic megacolon, infection, perforation, or hemorrhage. Current medical therapy has a high failure rate with approximately a third of patients requiring colectomy. Case Description/Methods: A 60-year-old Indian man with a three-year history of ulcerative proctitis on mesalamine therapy was admitted to the hospital for diarrhea, abdominal pain, and hematochezia after failing outpatient oral prednisone and rectal budesonide foam. His vital signs on admission were normal. Labs showed WBC of 12.5, Hgb of 10.6, platelet count of 530, albumin of 2.7, CRP of 143.2, ESR of 75, and fecal calprotectin of 1860. C. difficile testing was negative. CT scan showed mild colonic wall thickening. The patient was started on IV methylprednisolone 60 mg/daily. Colonoscopy which showed severe (Mayo Score 3) pancolitis with negative CMV on biopsies. Surgery was consulted after his symptoms did not improve after five days of steroid therapy and he required several blood transfusions. Due to the unavailability of inpatient Infliximab use in our hospital at the time, he was started on Adalimumab and received 160 mg dose, followed by another 160 mg injection in 9 days due to the lack of significant improvement after first dose. The patient refused to undergo colectomy until all medical therapies failed. Given some data on the treatment of ASUC with Tofacitinib, he was started on a 10 mg dose three times daily. CRP declined initially but quickly worsened. Patient decided to transfer care to another tertiary center for colectomy. While awaiting transfer, he developed brisk lower GI bleeding and became hypotensive. He was moved to the ICU and required emergent exploratory laparotomy with colectomy and an end ileostomy, three weeks after his admission to the hospital. Discussion: Despite recent data demonstrating some efficacy of tofacitinib as a rescue therapy with concomitant IV steroids, our case failed to respond to this treatment. Further delay in surgical intervention likely resulted in the need for emergent surgery. Data to support rescue tofacitinib is based on observational and retrospective case-control data with several limitations. Clinicians should be cautious delaying a definitive surgical intervention until more robust data supports tofacitinib rescue therapy for this sick population. Fortunately, this patient had an uncomplicated post-op course and was discharged to rehab in ten days.

S1734 Etanercept: A Rare Cause of Drug-Induced Pancreatitis

Introduction: Despite causing as low as 0.1% of cases of acute pancreatitis (AP), drug-induced pancreatitis(DIP) is a growing and notable cause of AP. Prior data comes from case reports and series, with definitive studies and trials lacking. To definitively diagnose DIP, a latency period with reintroduction of the medication associated with a return of symptoms is required. This is often not feasible due to risk of disastrous complications. DIP presents an uncommon cause of AP, with no established diagnostic algorithm. Amongst these cases, etanercept-induced pancreatitis presents a rare subset rarely reported in the literature. Case Description/Methods: Our patient is a 65-year-old female with a history of rheumatoid arthritis (RA) who presented endorsing 3 days of epigastric abdominal pain. Labs indicated a normal liver function tests, calcium of 10.1mg/dl, lipase of 1012U/L, and triglycerides of 187 mg/dl. Abdominal imaging indicated hepatic steatosis, with no findings of AP nor notable biliary/gallbladder pathology. Patient was started on fluids with clinical improvement noted. Antinuclear antibody(ANA) and immunoglobulin G4(IgG4) would be negative. The patient was advised to stop etanercept therapy and follow up with gastroenterology and rheumatology outpatient. She has since been discharged and is doing well off etanercept outpatient. Discussion: Since being first reported in the 1950s, DIP has been associated with over 500 medications per the World Health Organization. It is a diagnosis of exclusion, with common etiologies of alcohol abuse, gallstone disease, and other metabolic derangements having to be ruled out first. TNF-a inhibitors are involved in the treatment of a variety of autoimmune conditions. AP is not a commonly reported effect of these medications. Limited prior case reports attribute pancreatitis to infliximab and adalimumab use. To our knowledge, there are only 2 prior case reports of AP in the setting of recent etanercept initiation. After excluding more common causes of AP via imaging and labs, medication review was only notable for etanercept, which was started recently. A variety of mechanisms for DIP have been proposed. These include pancreatic/biliary duct constriction, direct cytotoxic effects, metabolic effects, and accumulation of potentially toxic metabolites. We hope to bring greater awareness to etanercept as a cause of drug-induced pancreatitis. Further studies are needed to elucidate its association with pancreatitis.

Rapid infusion of infliximab biosimilars and the incidence and severity of infusion-related reactions in patients with inflammatory bowel disease.

Infliximab is an anti-tumour necrosis factor agent used in the treatment of inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis. While the use of infliximab is well established in the treatment of IBD, there are now four recently FDA-approved infliximab biosimilars that are increasingly used due to their cost-benefit for patients, institutions and payors. In addition, shortening the length of infliximab infusions from 120 min (standard infusion) to 60 min or less (rapid infusion) has been shown to safely provide further cost-benefit while also improving patient convenience. The safety of rapid infusions has been well-established for the infliximab reference product, however, there are limited data available regarding the safety of rapid infusions for infliximab biosimilars. The purpose of this study was to compare the incidence and severity of infusion reactions among patients with IBD receiving rapid infusion of infliximab reference product compared with infliximab biosimilar. This was a retrospective analysis of electronic health record data of patients with a diagnosis of IBD receiving an infliximab reference product or infliximab biosimilar infusion between December 2020 and December 2021. Patient-level variables included demographics, immunomodulator use, IBD-related hospitalization and infliximab trough concentration and antibody levels. Infusion-related variables of interest included total number of infusions, drug, dose, dosing interval, infusion time and use of pre-medications. Infusion-related reactions were defined as safety concerns documented by the administering nurse (anaphylaxis, shortness of breath, hypotension, swelling, rash, pruritus, hives, flushing, chest pain, muscle pain, joint pain, fevers, chills, headache or hypertension) or administration of emergency medications. Fisher's exact test was used to compare reaction rates. A total of 188 patients met inclusion criteria for analysis, and a total of 1124 infusions were administered during the study period. There were no statistically significant differences among any of the pre-specified outcomes. There were no differences in the incidence of infusion reactions among rapid infusion (60 min) infliximab and infliximab biosimilars (p=0.863). Additionally, there were no differences in the incidence of infusion reactions among standard infusion (120 min) infliximab and infliximab biosimilars (p=0.993). Finally, there were no differences among the rate of infusion reactions between rapid infusion of infliximab biosimilars and standard infusion of infliximab biosimilars (p=0.536). Eight patients experienced safety issues, with three patients requiring emergency medications (1.6% of 188 patients). Rapid infusions of infliximab biosimilars were not associated with an increase in the incidence of infusion reactions compared with: rapid infusion of infliximab reference product, standard infusion of infliximab biosimilars, or standard infusion of infliximab reference product. This should reassure clinicians that rapid infusions of infliximab biosimilars are safe in clinical practice.

Infliximab in hidradenitis suppurativa: A systematic review and meta-analysis.

Hidradenitis suppurativa (HS) is a chronic inflammatory often recalcitrant to treatment. There is a lack of an updated systematic data review for infliximab use in HS. We conducted a systematic review and meta‐analysis of literature on infliximab in HS. This study was performed following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines and was pre‐registered on PROSPERO (CRD42021283596). In 9/2021, MEDLINE and EMBASE were systematically searched for articles on infliximab in HS. Non‐English, duplicate, and studies with <5 HS patients were excluded. Study quality was assessed utilizing Cochrane Risk of Bias for prospective trials and Newcastle‐Ottawa Scale for cohort studies. Random effects meta‐analytical model, Cochran's Q statistic, and I squared index were performed. Nineteen articles (314 patients) met inclusion criteria (six prospective, 13 retrospective studies). All patients with HS severity data available (n = 299) had moderate‐to‐severe disease. Outcome measures used for meta‐analysis of the pooled response rate were largely based on clinician reported outcomes (16 studies). One utilized both clinician and patient assessment. Two utilized patient‐reported response alone. The pooled response rate of HS patients to infliximab was 83% (95% CI, 0.71–0.91). The most common adverse events (AEs) included non‐serious infections (13.2%) and infusion reaction (2.9%). The rate of serious AEs was 2.9%. Study limitations include the small number of prospective studies and heterogeneity between studies. Overall, infliximab is an effective treatment for moderate‐to‐severe HS. Efficacy of infliximab in HS should be compared to other biologics in larger, randomized controlled trials.

Biological therapy in psoriatic arthritis patients with and without previous biologic experience

Objective: this study evaluated the biological therapy effects on disease activity, functionality, quality of life, drug survival, and safety of patients with psoriatic arthritis naïve and experienced in biological therapy. Methods: a oneyear prospective observational study was performed. The outcomes assessed were drug survival, disease activity, functionality, quality of life, and safety. Multiple linear regression was used to assess predictive factors for clinical response.Results: a total of 205 patients were included, 155 of whom were biologic naïve and 50 biologic experienced. Drug survival rate was greater for naïve patients than experienced patients at 6 months, but not at 12 months. Drug survival rates were 71.5% for naïve patients and 70.0% for experienced patients at 12 months. All clinical parameters improved for both biologic naïve and experienced patients. At 12 months, 63% of naïve patients and 52% of experienced patients had an improvement in their quality of life. Besides, 48% of naïve patients and 42% of experienced patients had an improvement in functionality. The axial disease improved in 67% of naïve individuals and 56% of experienced patients. Good control of peripheral disease was achieved by 49% of naïve patients and 44% of experiencedpatients. Female sex, use of etanercept or infliximab, and lower functionality or quality of life at baseline were the main predictors of poor clinical response. Conclusion: Patients’ health improved after starting biological therapy. In general, biologic experienced patients had more adverse reactions and lesser effectiveness.

Combined anti-mediator therapy for severe destructive forms of acute necrotizing pancreatitis in rats

Introduction: Inflammatory mediators play a major role in pathogenesis of acute pancreatitis with TNF (tumor necro­sis factor) as the most important one. Development of effective combined therapy could help to decrease tissue damage, improve results and, finally, diminish the mortality rate in this severe pathology.&#x0D; Materials and methods: All the studies were performed on 120 female white Wistar rats, weighing 250±25g. Acute pancreatitis reproduced by an intracanalicular injection of bile salts compound.&#x0D; Results and discussion: The data obtained in the course of the study on the pronounced pancreatoprotective effect of infliximab are explained by its key role in the onset of the systemic inflammatory response, and, therefore, with the blockade of tumor necrosis factor alpha in the early stages, there is no pronounced secondary damage to the pancreas, which is reflected in a significant decrease in edema from 4.87±0.03 in the model up to 2.75±0.04, and as a conse­quence, an improvement in the blood supply of the acinar tissue from 182.38±15.92 PU up to 287.92±14.64 PU, which is expressed in a decrease in the zones of necrosis and in a decrease in mortality and, finally, efficiency coefficient from 13480.000 to 4283.348. A selective blocker of cysteinyl leukotrienes has a less pronounced protective reaction against damage to pancreatocytes, but to a much greater extent than octreotide. That is expressed by changes in the efficiency coefficient to the level of 8621.18 in montelukast group and 12767.30 in octreotide group, respectively. On the other hand, the effect of the use of infliximab does not surpass that of montelukast, and their combined use has a pronounced additive effect, which is proved by the efficiency coefficient at the level of 2390.33. This reaction is explained by the fact that TNF alpha-mediated pathway of activation of leukotriene biosynthesis is the main, but not the only one.&#x0D; Conclusion: The combined anti-mediator therapy provides a great opportunity to improve the standard therapy of acute pancreatitis.

Increased Hospitalization for IBD Patients Seen in the ER During the COVID-19 Pandemic.

BackgroundDuring the COVID-19 pandemic, the focus of many health care systems shifted in order to prioritize and allocate resources toward treating those affected by COVID-19. What this has meant for other patient populations remains unclear. We aimed to determine if there have been changes to acute care access for patients with inflammatory bowel disease (IBD) during the COVID-19 pandemic.MethodsA retrospective cohort study was performed in IBD patients seen during (March 1, 2020 to August 31, 2020) and before (March 1, 2019 to August 31, 2019) the COVID-19 pandemic. IBD-related emergency room (ER) access, hospitalization, inpatient care and follow-up and post-discharge ER access were assessed.ResultsA total of 1229 participants were included. A higher proportion of patients accessed ER during the pandemic (44.6% versus 37.2%, P = 0.0097). A higher proportion of hospitalizations resulted from IBD-related ER visits during the pandemic period (41.6% versus 32.4%, OR = 1.48, 95% CI = 1.14 to 1.94, P = 0.0047), though length of stay was shorter (7.13 ± 8.95 days versus 10.11 ± 17.19 days, P = 0.015) and use of rescue infliximab was less. No change was seen in inpatient surgical intervention. Despite similar proportions of follow-up appointments post-hospital discharge (pre-pandemic, 77.9% versus pandemic, 78.3%), more ER visits occurred in the first 30 days following hospitalization for patients in the pandemic cohort (24.4% versus 11.1%, P = 0.0015).ConclusionThese data highlight the need for ER services and hospitalization amongst IBD patients during the COVID-19 pandemic. This suggests that a return to pre-pandemic IBD care infrastructure is needed to mitigate the need for acute care access.

Atomic Force Microscopy Application for the Measurement of Infliximab Concentration in Healthy Donors and Pediatric Patients with Inflammatory Bowel Disease.

The use of infliximab has completely changed the therapeutic landscape in inflammatory bowel disease. However, despite its proven efficacy to induce and maintain clinical remission, increasing evidence suggests that treatment failure may be associated with inadequate drug blood concentrations. The introduction of biosensors based on different nanostructured materials for the rapid quantification of drugs has been proposed for therapeutic drug monitoring. This study aimed to apply atomic force microscopy (AFM)-based nanoassay for the measurement of infliximab concentration in serum samples of healthy donors and pediatric IBD patients. This assay measured the height signal variation of a nanostructured gold surface covered with a self-assembled monolayer of alkanethiols. Inside this monolayer, we embedded the DNA conjugated with a tumor necrosis factor able to recognize the drug. The system was initially fine-tuned by testing known infliximab concentrations (0, 20, 30, 40, and 50 nM) in buffer and then spiking the same concentrations of infliximab into the sera of healthy donors, followed by testing pediatric IBD patients. A good correlation between height variation and drug concentration was found in the buffer in both healthy donors and pediatric IBD patients (p-value < 0.05), demonstrating the promising use of AFM nanoassay in TDM.

Clinical results following colonic resection for ulcerative colitis in elderly individuals (elderly-onset vs. nonelderly onset)

BackgroundThe incidence of ulcerative colitis (UC) is increasing, but there are few reports comparing elderly UC patients undergoing colectomy for elderly-onset UC (EO) and nonelderly-onset UC (NEO). The aim of this study was to analyze the differences between EO and NEO patients who underwent UC-related surgery.MethodsWe identified 1973 patients with UC who underwent colectomy at Hyogo College of Medicine between January 1, 1984, and December 31, 2018. Only patients aged 65 years old and older who underwent colectomy were enrolled in this study (n = 221, 11.2%), and their clinical records were retrospectively reviewed. Patients were divided into two groups according to their age at disease onset: those with onset at younger than 60 years old (NEO) and at 60 years old or older (EO).ResultsIn the 221 UC patients who underwent colectomy at 65 years old or older, there were 155 cases of EO and 66 cases of NEO. The main surgical indication in NEO patients was colitis-associated cancer/dysplasia (32/66, 47%). In contrast, refractory to medical treatment was the leading cause of surgery in EO patients (80/155, 52%). The distributions of surgical indications were different between the two groups (p < 0.01). The preoperative daily dose of steroids was significantly higher in the EO group than in the NEOgroup (0 mg vs. 10 mg, p < 0.01). The rates of immunosuppressant, infliximab (IFX) and adalimumab use did not differ significantly between the groups. Significantly more patients underwent emergency surgery in the EO group than in the NEO group (14% vs. 35%, p < 0.01). The proportions of patients with postoperative morbidity (Clavien-Dindo grade III or higher) were 17.4% (27/155) in the EO group and 13.6% (9/66) in the NEO group. There was no significant difference between the two groups (p = 0.48). The prognosis of the EO patients who underwent UC-related emergency surgery was worse than that of the NEO patients (p < 0.01). In the EO group, 8 (14.8%) of 54 patients died within 30 postoperative days, while there were no deaths in the NEO group.ConclusionAmong elderly UC patients undergoing UC-related surgery, EO patients undergoing emergency surgery had very poor outcomes, and the mortality rate was 14.8%. In such cases, it is important for physicians and surgeons to begin communication at an early stage so that the optimal surgical timeframe is not missed.

Efficacy and Safety of Infliximab Retreatment in Crohn's Disease: A Multicentre, Prospective, Observational Cohort (REGAIN) Study from the GETAID.

The objective of this study was to describe the efficacy and safety of infliximab (IFX) reintroduction in Crohn's disease (CD) after stopping for loss of response or intolerance. We conducted a prospective multicenter observational cohort study including adult patients with clinically (CD Activity Index &gt;150) and objectively active luminal CD in whom IFX was reintroduced after at least 6 months of discontinuation. The reasons for the initial discontinuation could be a secondary loss of response or IFX intolerance. The reintroduction schedule included 3 IFX infusions at weeks 0, 4, and 8, after a systematic premedication. The primary end point was the efficacy of IFX retreatment at week 26 defined by a CD Activity Index of &lt;150 in the absence of IFX discontinuation or use of corticosteroids, surgery, or other biologic. At week 26, 24 patients (35%) among the 69 analyzed reached the primary end point. No significant difference was observed between rates of clinical remission at week 26 in patients with prior LOR (n = 48) and those with IFX intolerance (n = 21) (35% and 33%, P = 0.87, respectively). Thirty-two acute infusion reactions were recorded in 27 patients, leading to withdrawal of IFX in 20 patients. No pharmacokinetic characteristic at baseline but detection of positive anti-drug antibodies at week 4 was predictive of IFX failure or infusion reaction at week 26. In this first prospective cohort study, IFX retreatment was safe and effective in one-third of the patients with CD, regardless the reason of prior discontinuation. Early detection of anti-drug antibodies can predict subsequent IFX reintroduction failure and infusion reactions.

Anti-TNF therapy for ulcerative colitis in Brazil: a comparative real-world national retrospective multicentric study from the Brazilian study group of IBD (GEDIIB)

BackgroundAnti-TNF therapy represented a landmark in medical treatment of ulcerative colitis (UC). There is lack of data on the efficacy and safety of these agents in Brazilian patients. The present study aimed to analyze rates of clinical and endoscopic remission comparatively, between adalimumab (ADA) and infliximab (IFX), in Brazilian patients with UC, and evaluate factors associated with clinical and endoscopic remission after 1 year of treatment. MethodsA national retrospective multicenter study (24 centers) was performed including patients with UC treated with anti-TNF therapy. Outcomes as clinical response and remission, endoscopic remission and secondary loss of response were measured in different time points of the follow-up. Baseline predictive factors of clinical and endoscopic remission at week 52 were evaluated using logistic regression model. Indirect comparisons among groups (ADA and IFX) were performed using Student's t, Pearson χ2 or Fisher's exact test when appropriated, and Kaplan Meier analysis.ResultsOverall, 393 patients were included (ADA, n = 111; IFX, n = 282). The mean age was 41.86 ± 13.60 years, 61.58% were female, most patients had extensive colitis (62.40%) and 19.39% had previous exposure to a biological agent. Overall, clinical remission rate was 66.78%, 71.62% and 82.82% at weeks 8, 26 and 52, respectively. Remission rates were higher in the IFX group at weeks 26 (75.12% vs. 62.65%, p < 0.0001) and 52 (65.24% vs. 51.35%, p < 0.0001) when compared to ADA. According to Kaplan–Meier survival curve loss of response was less frequent in the Infliximab compared to Adalimumab group (p = 0.001). Overall, endoscopic remission was observed in 50% of patients at week 26 and in 65.98% at week 52, with no difference between the groups (p = 0.114). Colectomy was performed in 23 patients (5.99%). Age, non-prior exposure to biological therapy, use of IFX and endoscopic remission at week 26 were associated with clinical remission after 52 weeks. Variables associated with endoscopic remission were non-prior exposure to biological therapy, and clinical and endoscopic remission at week 26. ConclusionsIFX was associated with higher rates of clinical remission after 1 year in comparison to ADA. Non-prior exposure to biological therapy and early response to anti-TNF treatment were associated with higher rates of clinical and endoscopic remission.

Infusion reaction incidence after switching all patients to an infliximab biosimilar in an Australian hospital

AbstractTo date, two infliximab biosimilar brands have been approved for use in Australia. In 2020, Queensland Health encouraged biosimilar use by removing the infliximab originator from their state formulary and left only one infliximab biosimilar (Renflexis®; Samsung Bioepis, Sydney, NSW, Australia). The aim was to conduct a quality assurance study examining the incidence of infusion reactions after switching all patients to the one approved biosimilar brand of infliximab. This was a retrospective study of medical charts of all patients who received an infliximab dose at a tertiary hospital between 10 June to 30 September 2020. The number of infusion reactions to the first dose of Renflexis® (Samsung Bioepis) was compared to the two doses immediately prior to the switch with an alternative brand. The study received ethics exemption (2020100904CM). A total of 370 doses of infliximab were dispensed to 139 patients, of which 320 doses (86.5%) were Renflexis® (Samsung Bioepis). There were three patients excluded from the study. A total of 119 patients (88%) were switched to the Renflexis® (Samsung Bioepis) brand and two of these patients (1.7%) experienced a true infusion reaction. When compared to doses prior to the switch, three of 116 patients (2.6%) with data available experienced an infusion reaction for the dose immediately prior, and one of 113 patients (0.9%) for two doses prior. No treatment‐naïve patients (n = 17) initiated on Renflexis® (Samsung Bioepis) experienced an infusion reaction. The use of a biosimilar infliximab, in both treatment‐naïve patients and those and switching from alternative brands, does not appear to have an increased incidence of infusion reactions.

Historical aspects and current understanding of autoimmune hepatitis. When is liver transplantation indicated? (Review)

Autoimmune hepatitis (AIH) can occur at any age and is more common in women. The disease is a manifestation of autoimmune predisposition caused in genetically susceptible people exposed to certain environmental factors. The pathogenetic mechanism of AIH is not yet fully understood, but it involves an aggressive cellular immune response. The pathogenesis and severity of AIH also depend on various cytokines. This disease is characterized by elevated levels of transaminases – aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Liver histology plays a crucial role in confirming or supporting the clinical diagnosis of AIH. Diagnosis of AIH remains a challenge in clinical practice. AIH is one of the few liver diseases for which pharmacologic treatment has been shown to improve survival. Standard treatment is based on high-dose prednisone alone or prednisolone plus azathioprine. It leads to disease remission in 80%-90% of patients. Approximately 20% of patients do not respond to the standard steroid treatment and are treated with second-line immunosuppressive drugs: mycophenolate mofetil, budesonide, cyclosporine, tacrolimus, everolimus, and sirolimus. There have been reports on the use of infliximab and rituximab. In the natural course of AIH and resistance to therapy, there is a tendency for cirrhosis to develop and for the disease to progress to an end stage. These patients, as well as those diagnosed with fulminant liver failure, require liver transplantation.

Infliximab Is Not Associated With a General Long-Term Weight Gain in Patients With Inflammatory Bowel Disease: A Nationwide Study.

Patients with Crohn's disease (CD) and ulcerative colitis (UC) may lose weight during periods of active disease and may gain weight when inflammation heals. Studies have hypothesized an association between antitumor necrosis factor-alpha (anti-TNF-α) and unintended weight gain during maintenance therapy, and this association has not been previously clarified. In a nationwide observational study based on Danish national health registries, we included patients who initiated therapy with infliximab and followed changes in weight during induction therapy (0-90 days) and maintenance therapy (91-270 days). The association between the use of infliximab and weight gain was analyzed by a multilevel mixed-effects linear regression model. Among 851 patients with CD and UC who initiated infliximab therapy, long-term weight gain was not observed during maintenance therapy in most of the patients. Women with CD who were underweight at the initiation of therapy had an average weight gain of 7.5 kg. Men and women with CD and UC with normal or increased body mass index had an average weight gain of <2 kg during maintenance therapy. Underweight men with CD and UC gained 2.9 kg (95% confidence interval 2.1-3.6) and 2.9 kg (95% confidence interval 1.9-3.9), respectively, in the first 90 days, although neither group had statistically significant weight gain in the maintenance period. Less than 3% of the patients had weight gain greater than 10% of their baseline body weight during the study period. Weight gain among patients treated with anti-TNF-α therapies is unlikely to be due to an effect from anti-TNF-α therapy.

Infliximab therapy in refractory sarcoidosis: a multicenter real-world analysis

BackgroundInfliximab is a monoclonal antibody that binds and neutralizes circulating tumor necrosis factor-alpha, a key inflammatory cytokine in the pathophysiology of sarcoidosis. Despite the paucity of randomized clinical trials, infliximab is often considered a therapeutic option for refractory disease. Our study aimed to investigate the effectiveness of infliximab in patients with refractory sarcoidosis.MethodsSarcoidosis patients from three tertiary centres were retrospectively identified by pharmacy records based on treatment with infliximab. Treatment with Infliximab was initiated in patients who failed first and second line immunomodulators as determined by a multidisciplinary team of Respirologists, Dermatologists, ENT specialists, Rheumatologists, and Neurologists. Participants were characterized by the primary organ for which infliximab was initiated and the total number of organs involved. Clinical outcomes were categorized as treatment success versus failure. We defined treatment success as (A) improvement of cutaneous, upper airway, lymph node, gastrointestinal, eye, or joint manifestations; or (B) improvement or no change in central nervous system (CNS) or pulmonary manifestations.Results33 patients with refractory sarcoidosis were identified. The proportion of treatment success was 100% (95% CI 54.1–100) in CNS, 91.7% (95% CI 61.5–99.8) in cutaneous, 78.6% (95% CI 49.2–95.3) in pulmonary and 71.5% (95% CI 29.0–96.3) in upper airway disease. The use of infliximab was associated with a reduction prednisone dose by 50%.ConclusionInfliximab is possibly an effective therapy for refractory sarcoidosis, with the greatest value in neurologic and cutaneous manifestations. Across all disease presentations, infliximab facilitated a clinically relevant reduction in corticosteroid dose. Relapse is common after discontinuation of infliximab.

Adalimumab for the Treatment of Pediatric Populations With Non-Infectious Uveitis

&#x0D; Two systematic reviews, 1 economic evaluation, and 2 evidence-based guidelines were identified regarding the clinical effectiveness (including safety), cost-effectiveness, and use of adalimumab in pediatric populations with non-infectious uveitis.&#x0D; Pooled data of the SYCAMORE and ADJUVITE randomized controlled trials comparing adalimumab to placebo demonstrated that adalimumab significantly increased the likelihood of reducing or interrupting corticosteroid use (which is beneficial as long-term corticosteroid use can result in cataracts and glaucoma). Adalimumab significantly increased the event of a satisfactory response rate, but there was no difference in safety assessed as systemic adverse events and local adverse effects.&#x0D; Specific to the ADJUVITE trial, visual acuity slightly worsened before and after treatment with adalimumab and it was unclear if adalimumab increased control of intraocular inflammation.&#x0D; Specific to the SYCAMORE trial, adalimumab significantly lowered the risk of treatment failure and the rate and number of adverse events and serious adverse events were higher in the adalimumab group compared to the placebo group. For the adalimumab group, the most common adverse event type was infections and infestations and the most common serious adverse events were glaucoma, cataracts, injection site reactions, arthritis, and arthralgia.&#x0D; In the perspective of the health care system in the UK, adalimumab plus methotrexate was not found to be cost-effective compared to methotrexate alone (modelled by placebo data) in uveitis associated with juvenile idiopathic arthritis.&#x0D; Cost-effectiveness analyses of adalimumab at a discounted price lowered the incremental cost-effectiveness ratio, which supports the potential use of biosimilars in the future due to cost savings.&#x0D; Both guidelines recommended the use of treatment that blocks proteins that cause inflammation (tumour necrosis factor-alpha inhibitors) such as adalimumab in combination with an immunosuppressive agent such as methotrexate (i.e., adalimumab plus methotrexate) in patients with uveitis associated with juvenile idiopathic arthritis who are not responsive to initial treatment (e.g., topical corticosteroids) and are at risk for severe uveitis or vision threatening complications.&#x0D; The American College of Rheumatology/ Arthritis Foundation recommended the use of adalimumab and infliximab over etanercept with no preference between adalimumab and infliximab. Conversely, the guideline from multiple interdisciplinary German groups recommended that adalimumab and infliximab are the first- and second-choice tumour necrosis factor-alpha inhibiting drugs, respectively. They recommended a treatment switch to infliximab then golimumab when adalimumab is not effective or there is treatment failure with adalimumab.&#x0D;

Infliximab Treatment Persistence among Japanese Patients with Chronic Inflammatory Diseases: A Retrospective Japanese Claims Data Study.

Infliximab (IFX) has contributed to the treatment of several chronic inflammatory diseases, including Crohn's disease (CD), ulcerative colitis (UC), psoriasis (Pso), and rheumatoid arthritis (RA). However, the loss of response in some patients with long-term IFX therapy has been a major problem. Randomized controlled trials (RCTs) are limited in their short duration and lack of generalizability to the real-world population. We aimed to describe the persistence rates of IFX therapy to estimate its long-term effectiveness in clinical practice. Claims data from the Japan Medical Data Center database from January 2005 to June 2017 were used. The study population was identified based on the International Classification of Diseases, 10th Revision and the Anatomical Therapeutic Chemical Classification System. The 5-year persistence rates of IFX therapy were estimated using the Kaplan-Meier method. Overall, 281, 235, 41, and 222 patients with CD, UC, Pso, and RA, respectively, were selected. The 5-year persistence rates for IFX claims were 62.9, 38.9, 22.1, and 28.1% in patients with CD, UC, Pso, and RA, respectively. Patients with CD and UC administered IFX beyond the median dose had higher persistence rates. In patients with RA, female sex and no prior use of other biologics were associated with longer persistence. In conclusion, IFX persistence rates differed across chronic inflammatory diseases, which did not correspond to the results of the major RCTs. Factors associated with longer IFX persistence were identified in each disease group. Our findings may provide useful information to facilitate the proper use of IFX.

Infliximab Superior to IVIG for Rescue in IVIG-Refractory Kawasaki Disease

Infliximab Superior to IVIG for Rescue in IVIG-Refractory Kawasaki Disease