Administration Of Infliximab Research Articles

Retrospective analysis of infliximab in the treatment of Kawasaki disease

Objective: To investigate the efficacy and safety of infliximab (IFX) therapy for children with Kawasaki disease. Methods: Sixty-eight children with Kawasaki disease who received IFX therapy in Children's Hospital of Fudan University from January 2014 to April 2021 were enrolled. The indications for IFX administration, changes in laboratory parameters before and after IFX administration, response rate, drug adverse events and complications and outcomes of coronary artery aneurysms (CAA) were retrospectively analyzed. Comparisons between groups were performed with unpaired Student t test or Mann-Whitney U test or chi-square test. Results: Among 68 children with Kawasaki disease, 52 (76%) were males and 16 (24%) were females. The age of onset was 2.1 (0.5, 3.8) years. IFX was administered to: (1) 35 children (51%) with persistent fever who did not respond to intravenous immunoglobulin (IVIG) or steroids, 28 of the 35 children (80%) developed CAA before IFX therapy; (2) 32 children (47%) with continuous progression of CAA; (3) 1 child with persistent arthritis. In all cases, IFX was administered as an additional treatment (the time from the onset of illness to IFX therapy was 21 (15, 30) days) which consisted of second line therapy in 20 (29%), third line therapy in 20 (29%), and fourth (or more) line therapy in 28 (41%). C-reactive protein (8 (4, 15) vs. 16 (8, 43) mg/L, Z=-3.38, P=0.001), serum amyloid protein A (17 (10, 42) vs. 88 (11, 327) mg/L, Z=-2.36, P=0.018) and the percentage of neutrophils (0.39±0.20 vs. 0.49±0.21, t=2.63, P=0.010) decreased significantly after IFX administration. Fourteen children (21%) did not respond to IFX and received additional therapies mainly including steroids and cyclophosphamide. There was no significant difference in gender, age at IFX administration, time from the onset of illness to IFX administration, the maximum coronary Z value before IFX administration, and the incidence of systemic aneurysms between IFX-sensitive group and IFX-resistant group (all P>0.05). Infections occurred in 11 cases (16%) after IFX administration, including respiratory tract, digestive tract, urinary tract, skin and oral infections. One case had Calmette-Guérin bacillus-related adverse reactions 2 months after IFX administration. All of these adverse events were cured successfully. One child died of CAA rupture, 6 children were lost to follow up, the remaining 61 children were followed up for 6 (4, 15) months. No CAA occurred in 7 children before and after IFX treatment, while CAA occurred in 54 children before IFX treatment. CAA regressed in 23 (43%) children at the last follow-up, and the diameter of coronary artery recovered to normal in 10 children. Conclusion: IFX is an effective and safe therapeutic choice for children with Kawasaki disease who are refractory to IVIG or steroids therapy or with continuous progression of CAA.

Analysis of the disease activity of ulcerative colitis with and without concomitant primary sclerosing cholangitis: An investigation using a nationwide database in Japan.

AimsPrimary sclerosing cholangitis (PSC) is a relatively common complication of ulcerative colitis (UC). Only a few studies have investigated the impact of PSC on the clinical course of UC, and their conclusions are contradictory. Therefore, we aimed to compare the disease activity of UC with and without PSC.Methods and ResultsWe collected UC patient data using the Diagnosis Procedure Combination database system in Japan and classified eligible admissions into two groups based on their diagnosis of either UC alone or UC associated with PSC. We then compared therapeutic details (medical treatment and surgery) between the two groups. Multivariable logistic regression analysis and propensity score matching was also performed. The rates of systemic steroid injection and infliximab administration in patients with PSC were lower than those in patients without PSC (21% vs. 28%, P = 0.012, 9.6% vs. 16%, P = 0.01, respectively). The rates of surgery, colorectal cancer, duration of hospital stay, and in‐hospital mortality did not differ between the two groups. Multivariable analysis revealed that concomitant PSC was a clinical factor that reduced the odds of systemic steroid injection (odds ratio [OR] = 0.66, 95% confidence interval [CI]: 0.49–0.90, P = 0.008) and infliximab (OR = 0.48, 95% CI: 0.32–0.74, P = 0.0008) administration.ConclusionUC patients with PSC might have less UC disease activity than those with UC alone.

P013 Resolution of Infliximab Associated Infusion Hypersensitivity After Switching to Biosimilar Infliximab-dyyb.

Background: Administration of infliximab for the treatment of inflammatory bowel disease has a well-recognized risk of infusion-related (IR) adverse events. The recent introduction of the biosimilar infliximab-dyyb (Inflectra®) has been shown to have similar efficacy with comparable safety profile when compared to infliximab; however, although the active ingredients are similar, the inactive ingredients are different. We present a case of a 26-year-old female with ulcerative colitis who had resolution of her IR hypersensitivity when switched from infliximab to infliximab-dyyb. A 26-year-old female with a past medical history of ulcerative pancolitis presented to our clinic with the chief complaint of rash associated with her infliximab infusions. She described pruritic raised lesions which would occur on her upper and lower extremities during her infusions. She denied any shortness of breath or wheezing, and her symptoms were well controlled with methylprednisolone 40mg IV prior to her infusions. Previously, she had been treated for her UC with oral mesalamine, azathioprine and intermittent prednisone and did not have any adverse reactions to these medications. She has no known allergies to other medications and her peripheral eosinophil count was 1.6%. She was initially started on infliximab 5mg/kg every 8 weeks since 2013 and had achieved clinical as well as endoscopic remission with her most recent colonoscopy graded as Mayo 0. On account of her infusion reaction, drug antibodies were checked but were not detected. Infliximab level was 8.8 μg/ml. Due to insurance she was required to switch to infliximab-dyyb. After switching to the biosimilar, she has not had any infusion related reactions and no longer requires premedication with methylprednisolone with her infusions. Immediate IR reactions have been reported in 5-23% of IBD patients receiving infliximab and those who develop antibodies towards infliximab have a 2-fold risk of acute IR events. Side effects have been reported to be the primary reason for discontinuation of infliximab, and studies have shown that discontinuation can lead to an increased risk of relapse of inflammatory bowel disease. Although infliximab and infliximab-dyyb have analogous active ingredients, the inactive ingredients differ. Specifically, infliximab-dyyb lacks monobasic sodium phosphate and dibasic sodium phosphate, which acts as an emulsifier which we believe contributed to her IR with originator biologic infliximab. It is important to recognize these differences as IR hypersensitivities may be attributed to inactive ingredients; especially when antibodies are negative. Our case report suggests that a switch to biosimilar infliximab in patients may provide added benefit especially in those that have reactions occurring from inactive ingredients in the originator biologic.

Secondary Mania induced by TNF-α inhibitors: A systematic review.

A growing number of studies support a bidirectional relationship between inflammation and bipolar disorders. Tumor necrosis factor‐α (TNF‐α) inhibitors have recently attracted interest as potential therapeutic compounds for treating depressive symptoms, but the risk for triggering mood switches in patients with or without bipolar disorders remains controversial. Thus, we conducted a systematic review to study the anti‐TNF‐α medication‐induced manic or hypomanic episodes. PubMed, Scopus, Medline, and Embase databases were screened for a comprehensive literature search from inception until November 2020, using The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. Out of the initial 75 references, the screening resulted in the inclusion of four case reports (each describing one patient) and a cohort study (in which 40 patients out of 7600–0.53% – experienced elated mood episodes after infliximab administration). Of these 44 patients, 97.7% experienced a manic episode and 2.3% hypomania. 93.2% of patients had no history of psychiatric disorder or psychotropic treatment. Only 6.8% had a history of psychiatric disorders with the affective spectrum (4.6% dysthymia and 2.3% bipolar disorder). The time of onset of manic or hypomanic symptoms varied across TNF‐α inhibitors with an early onset for Infliximab and a later onset for Adalimumab and Etanercept. These findings suggest that medications targeting the TNF‐α pathway may trigger a manic episode in patients with or without affective disorders. However, prospective studies are needed to evaluate the relative risk of such side effects and identify the population susceptible to secondary mania.

Perianal disease onset age is associated with distinct disease features and need for intestinal resection in perianal Crohn\u2019s disease: a ten-year hospital-based observational study in China

Background and aimsThe significance of different ages of perianal disease (PD) onset in patients with perianal Crohn’s disease (PCD) remains unknown. We aimed to investigate the impact of paediatric-onset PD (POP) and adult-onset PD (AOP) on the Crohn’s disease (CD) course in a Chinese cohort.MethodsThe medical records of diagnosed PCD patients from 2008 to 2018 were reviewed retrospectively. The cumulative incidence and predictors of intestinal resection were calculated using the Kaplan–Meier and logistic regression analysis.ResultsComplex perianal fistulas (71.7% vs 50.0%, p = 0.011) and infliximab (IFX) treatment (33.3% vs 22.0%, p = 0.044) were more common among the POP patients (age < 18 years old, n = 84). A younger PD onset age (15.1 ± 2.9 vs 30.2 ± 10.5 years, p < 0.001) and shorter PCD diagnostic delay (12 vs 24 months, p = 0.033) was found in the POP cohort. AOP patients (age ≥ 18 years old, n = 209) had a higher rate of current smoking (12.9% vs 4.8%, p = 0.040), stricturing behaviour (42.1% vs 27.4%, p = 0.024) and intestinal resection (21.1% vs 4.8%, p = 0.001). The cumulative probability of intestinal resection in AOP patients was higher than that in POP patients (p = 0.007). In multivariable analysis, AOP (OR: 4.939, 95% CI 1.538–15.855, p = 0.007), stricturing behaviour (OR: 1.810, 95% CI 1.008–3.251, p = 0.047) and rectal inflammation (OR: 3.166, 95% CI 1.119–8.959, p = 0.030) were predictive factors for CD-related intestinal resection in all PCD patients. AOP patients with complex perianal fistula (OR: 2.257, 95% CI 1.041–4.891, p = 0.039) and POP patients with rectal inflammation (OR: 3.166, 95% CI 1.119–8.959, p = 0.030) were more likely to suffer intestinal resection. The IFX administration significantly decreased the rate of intestinal resection in AOP patients (r = − 0.900, p = 0.037).ConclusionsThe AOP patients have more complicated luminal disease and higher rate of intestinal resection than COP patients. The perianal diseases onset-age can provide clinical treatment guidance for individual management of CD patients.

S3346 TNF-alpha Inhibitor Adherence Review: Healthcare Practitioner Administration Compared to Self-Administration

Introduction: Adherence is the extent to which a person’s behavior coincides with health related advice. Poor medication adherence leads to poorer clinical outcomes. TNF-alpha inhibitors (TNF inhibitors) have a significant relationship between clinical outcome and rate of medication adherence. TNF inhibitors are either self-administered (SA) or administered by a healthcare practitioner (HC P-administered), such as a Registered Nurse (RN). To better understand medication adherence in SA and HCP-administered TNF inhibitor populations, an analysis was conducted to measure medication adherence to the HCP-administered product, infliximab, through an alternate site infusion pharmacy. These results were then compared to SA medication adherence rates according to previously published analyses. The comparative results show that administration of infliximab by an RN results in higher medication adherence rates than those reported for SA TNF inhibitor patients. Methods: The analysis was conducted using data extracted from a CPR+ dispensing system, targeting infliximab dispenses with a start of service date (SVC START DT) between 1/1/20 and 8/31/20. Unique patients with at least two SVC START DT values were included. The eligibility of each patient was considered to end as of their final SVC START DT. Adherence was calculated using the industry-standard metric “Proportion of Days Covered” (PDC) methodology. Medication coverage of each treatment was calculated as: Medication Coverage = SVC START DT + Days Supply -1 Adherence was reported as a percentage of analyzed patients with a PDC value of 80% and as the average PDC value of the analyzed population. Results: A 92% average PDC was observed in the overall infliximab RN administered population, with 89% of patients at or above the 80% PDC threshold required to be considered “adherent”. No statistically significant difference in average PDC across age band, sex, or disease state was observed. Conclusion: In this study, patients receiving infliximab administered by an RN (HCP-administered) have a very high adherence rate, as measured by PDC. As it has been reported that patients utilizing SA TNF inhibitors have an average adherence rate of only 37%, these data represent a substantial improvement over SA treatment as it relates to adherence. Additional patient factors not related to the method of administration that could affect adherence including treatment outcomes were not evaluated.Table 1.: Overall Patient Adherence.

Assessment of the Nephroprotective Properties of the Erythropoietin Mimetic Peptide and Infliximab in Kidney Ischemia-Reperfusion Injury in Rats.

Chronic kidney disease (CKD) or acute kidney injury (AKI) causes impaired kidney function, leading to cognitive impairment, neuropathy, and cerebrovascular disease. Due to kidney damage, toxinsstay in thebloodrather thanleavingthebodythrough the urine, and brain function is affected by kidney-brain interaction. The present study aimed to investigate the protective effects of erythropoietin mimetic peptide (pHBSP) and infliximab on ischemic renal reperfusion injury. The experiment was performed on 70 white male Wistar laboratory rats which received recombinant erythropoietin, pHBSP, and infliximab. Under anesthesia, traumatic vascular clamps were applied to the left renal pedicle for 40 min, and nephrectomy was performed on the right. Functional tests and laboratory tests were performed 5 min and 24 h after the reperfusion. Thereafter, 24 h after the surgery, the plasma creatinine and urea levels in the sham-operated animals were obtained at 45.9±0.8 mmol/L and 6.7±0.2 mmol/L, respectively. Plasma creatinine and urea levels in the control group animals were 102.63±3.6 mmol/L and 21.80±1.29 mmol/L, respectively. The administration of pHBSP and infliximab to the animals with ischemia-reperfusion kidney injury has a pronounced nephroprotective effect, as compared to erythropoietin. There was a significant decrease in blood levels of creatinine and urea, improvement of microcirculation in the kidney, normalization of glomerular filtration rate, and fractional sodium excretion. The results of the study demonstrated pointed to the prospects of pHBSP and infliximab administration in ischemia-reperfusion kidney injury and justified the feasibility of further research in this field.

Infliximab (an antitumor necrosis factor) induced lupus in a patient with inflammatory bowel disease

Infliximab is a monoclonal antibody that works by inhibiting the proinflammatory cytokine and tumor necrosis factor-alpha. Systemic lupus erythematosus is an autoimmune disease that affects multiple organs, and its pathogenesis involves abnormal immune complexes, environment factors, and genetics. Several reports have documented a controversy regarding infliximab-induced lupus disease. This paper reports on infliximab-induced lupus in an 18-year-old Saudi female having short stature, hypogonadism, and Crohn's disease with ileocolonic fistula. The patient developed reactive arthritis, and serology showed positive anti-double strand DNA and antihistone antibodies after infliximab administration, suggesting drug-induced lupus. More cohort studies are recommended to monitor the presentation and reversibility of infliximab-induced lupus disease.

Improvement in recurring nivolumab-induced pneumonitis with repetitive administration of infliximab in a patient with head and neck cancer: A case report

Severe pneumonitis induced by nivolumab, an anti-programmed cell death-1 monoclonal antibody, is a rare but potentially fatal immune-related adverse event. In cases of steroid-refractory pneumonitis, an appropriate therapeutic strategy using anti-tumor necrosis factor-α (TNF-α) antibody has not been established. A 59-year-old female was diagnosed with hypopharyngeal squamous cell carcinoma. Previous therapies including chemoradiotherapy and throat laryngectomy were performed, but metastatic recurrence appeared in the intrapulmonary and mediastinal lymph nodes. The patient was administered nivolumab. On the 14th day of nivolumab administration, the patient experienced dyspnea and computed tomography of the chest showed multiple consolidations in the right lung. She was diagnosed with nivolumab-induced pneumonitis. Because the pneumonitis was refractory to steroid therapy, she was administered infliximab, and the pneumonitis improved. On the 72nd and 101st days of nivolumab administration, nivolumab-induced pneumonitis re-appeared with an elevated serum TNF-α concentration. In each occurrence of pneumonitis, repetitive administration of infliximab improved the pneumonitis. Repetitive administration of infliximab may be effective for treating recurrent nivolumab-induced pneumonitis that is associated with an increased serum TNF-α concentration.

Budget Impact Analysis of the Introduction of Subcutaneous Infliximab (CT-P13 SC) for the Treatment of Rheumatoid Arthritis in the United Kingdom.

CT-P13 subcutaneous (SC)-the first and only SC version of infliximab-is approved by the European Medicines Agency for the treatment of rheumatoid arthritis (RA). This new mode of infliximab administration will allow patients to self-inject at home, significantly reducing the number of outpatient visits and costs of intravenous (IV) administration. This paper describes the economic impact of introducing CT-P13 SC to the market from the UK societal perspective. The budget impact analysis was conducted to assess the financial impact of the adoption of CT-P13 SC over a 5-year period. A prevalence-based budget impact model was developed incorporating epidemiological data, administration cost data, and market share data. The analysis compared a "world with" CT-P13 SC scenario to a "world without" CT-P13 SC. A sensitivity analysis included dose escalation up to 4.1 mg/kg to reflect the real-world care delivery setting. Compared to the "world without" scenario, the introduction of CT-P13 SC resulted in cost savings of ₤69.3 million in the UK over a 5-year period. In the scenario analysis, the saving increased to ₤173.5 million over 5 years. Use of CT-P13 SC may lead to substantial cost savings for the UK society.

P453 The use of immunosuppresants is associated with high treatment persistence rates for infliximab and adalimumab as first or second line anti-TNF therapy in patients with inflammatory bowel disease

Abstract Background The aim of this study was to investigate the factors associated with treatment persistence for infliximab and adalimumab, as 1st or 2nd line anti-TNF therapy, in patients with inflammatory bowel disease (IBD). Methods A retrospective study of patients with IBD from the registry of our department who received infliximab (IFX) or adalimumab (ADA), during the period of 2002–2019 was performed. The persistence rate of IFX and ADA at 1 and 3 years from treatment initiation as 1st and 2nd line anti-TNF therapy respectively was calculated. In addition, possible related factors were analyzed. Results We included 185 patients with IBD, naive to biologics, who initiated with anti-TNF treatment [105 men (57%), mean age (± SD) 44.5 ± 14.7 years, Crohn’s disease 144 (78%), median disease duration (IQR) 13 (7–20) years, 120 (65%) under IFX, 100 (55%) in combination with immunosuppressive therapy for at least 6 months]. In 59 patients [Crohn’s disease 47 (80%)] IFX or ADA was used as 2nd line anti-TNF therapy. The duration of administration and persistence rate of IFX and ADA as 1st and 2nd line treatment are shown in Table 1. In univariate analysis statistically significant associations between the persistence rates of anti-TNF therapy as first-line therapy, with the use of immunosuppressants (P = 0.04) and treatment intensification (P = 0.01) in both 1st and 3rd year (P = 0.01 and 0.04 respectively) were found. No other significant association between demographic, disease type and clinical parameters and treatment persistence was found. Regarding the 2nd line anti-TNF treatment, persistence of therapy in the 1st year was associated with treatment intensification (P = 0.02) and in the 3rd year of administration with the combination with immunosuppressants (P = 0.05). In multivariate analysis only the use of immunosuppresants remained statistically significant associated both in 1st and 3rd year of treatment in 1st line therapy (P=0.05 and P=0.003 respectively). This was also the case in 2nd line therapy but only in the 3rd year of treatment (P=0.05). Conclusion The persistence rates of IFX and ADA used both as a 1st and 2nd line therapy in IBD patients are significantly associated with the combined use of immunosuppressants.

Infliximab prevents systemic bone loss and suppresses tendon inflammation in a collagen-induced arthritis rat model.

Reduced Bone Mineral Density (BMD) and tendon abnormalities, such as tenosynovitis and enthesitis, are prevalent comorbidities in patients with rheumatoid arthritis (RA). The aim of the present study was to investigate the effect of chronic treatment with infliximab on BMD and tendon inflammation in an animal model of inflammatory arthritis. Collagen-Induced Arthritis (CIA) was induced in rats, followed by long-term intraperitoneal administration of infliximab. Two additional groups of animals received methotrexate either as a monotherapy or as a co-treatment to infliximab. BMD was evaluated by Micro-Computed Tomography (Micro-CT) and bone histological examination. Tendon inflammation was assessed histologically and by quantitative ELISA analysis of pro-inflammatory cytokines in tendon tissues. Both methotrexate and infliximab treatment alleviated joint inflammation and reduced paw edema. Infliximab-treated animals exhibited an improved trabecular microarchitecture on micro-CT and histological analysis compared to both non-treated and methotrexate-treated animals. Infliximab almost reversed the pathological changes in tendons induced by CIA. Finally, we observed statistically significant declines in tendon TNF-a and IL-23 levels after infliximab treatment. Our study provides evidence that infliximab prevents arthritis-related osteoporosis and suppresses tendon inflammation in an animal model of inflammatory arthritis, in addition to controlling disease activity. These findings offer perspectives for the management of osteoporosis and enthesitis in RA.

Infliximab formulation strategy for a stable ileo-colonic targeted oral dosage form intended for the topical treatment of inflammatory bowel disease

Research shows that topically active infliximab therapy may be efficacious in the treatment of inflammatory bowel disease (IBD) with expected fewer side effects related to systemic exposure. Oral administration of infliximab with site-specific delivery could enable such therapy. In the present study, infliximab was incorporated in a sugar glass matrix (IFX-I) for additional stability and compounding flexibility after which IFX-I was compounded to ileo-colonic-targeted tablets containing 5 mg infliximab (ColoPulse-IFX). Potential critical steps in the production process that may decrease the formulation stability were identified and investigated. Furthermore, the long-term stability of IFX-I (6 months) and ColoPulse-IFX (12 months) stored either at room temperature (25 °C ± 2 °C/60% RH ± 5% RH) or refrigerated (5 °C ± 3 °C) was investigated according to ICH guidelines. Size-exclusion chromatography, fluorescence spectroscopy, and ELISA analyses were used to investigate the infliximab stability, content, tertiary protein structure, and potency at t0, t3, t6, t9, and t12 months. The coating performance of ColoPulse-IFX was investigated in a gastrointestinal simulation system at t0 and t12 months. All the analyses showed that IFX-I and ColoPulse-IFX were stable, potent, and that the coating performance was maintained during the entire storage period at both storage conditions. Thus, IFX-I is a stable dry-powder formulation and ColoPulse-IFX is a promising oral dosage form for the topical treatment of ileo-colonic IBD. This formulation strategy may serve as a new platform for the development of oral peptide or protein formulations that are targeted to the ileo-colonic region in IBD.

Effects of Long-Term Methotrexate, Infliximab, and Tocilizumab Administration on Bone Microarchitecture and Tendon Morphology in Healthy Wistar Rats.

ObjectiveRheumatic diseases are associated with bone loss, both systemic and periarticular, and tendon abnormalities. The aim of this study is to examine the effect of three antiarthritic drugs, methotrexate, an anti-folate metabolite; infliximab, a Tumor Necrosis Factor-alpha (TNF-α) inhibitor; and tocilizumab, an antibody against Interleukin-6 (IL-6) receptor, on bone microarchitecture and tendon morphology in the absence of an inflammatory state.Materials and methodsThirty-five, 8- to 9-week-old, male, Wistar rats were randomly allocated into five groups: negative control (CTRL), vehicle (VEH), methotrexate (MTX), infliximab (INFX), and tocilizumab (TCZ). After 8 weeks of antiarthritic drug intraperitoneal administration, animals were euthanized and rat tibiae and patellar tendons were histologically examined.ResultsAll sections exhibited normal bone microarchitecture. Histological scores in all groups corresponded to normal bone mineral density. No no apparent differences in tenocyte morphology and architecture of collagen fibers were observed.ConclusionsThe results of this study indicate that long-term administration of methotrexate, infliximab, and tocilizumab had no effect on bone microarchitecture and tendon morphology in rats in the absence of an inflammatory condition.

Posterior reversible encephalopathy syndrom u dítěte s ulcerózní kolitidou

Posterior Reversible Encephalopathy Syndrome (PRES) is a clinical-neuroradiological entity with acute onset, defined as a vasogenic brain edema associated with neurotoxic impairment. We report the case of an eight-year-old boy with severe ulcerative colitis and celiac disease, who was treated with infliximab and azathioprine. On the 10th day after infliximab administration, a 45-minute unconsciousness developed with generalized convulsions and pupil miosis, accompanied by arterial hypertension. The boy was treated with anticonvulsants and antihypertensives. The state of consciousness improved ad integrum. Magnetic resonance imaging (MRI) of the brain revealed symmetric areas of high-intensity signal involving occipital and fronto-parietal lobes. Lumbar puncture was negative. Repeat MRI, seven days from the onset, showed resolution of the previous changes. The condition was assessed as PRES that developed as a complication of treatment (infliximab, azathioprine) in a patient with active ulcerative colitis. The case indicates a possible risk of developing PRES in patients with uncompensated inflammatory bowel disease, receiving immunosuppressive and/or bio­logical treatment and/or developing arterial hypertension

A case of refractory pouchitis complicated by cytomegalovirus infection requiring administration of ganciclovir and infliximab

Pouchitis is a frequent complication of surgical treatment of ulcerative colitis (UC), and is typically treated using antimicrobials. If pouchitis is refractory to antimicrobials, screening for complications, such as cytomegalovirus (CMV) infection, is necessary. However, the optimal approach to management of pouchitis complicated by CMV infection is unclear. We report the case of a 41-year-old female patient with UC presenting with pouchitis associated with CMV infection; she had received subtotal colectomy/ileal pouch anal anastomosis (IPAA). She was admitted to hospital with persistent fever, epigastric discomfort, and watery diarrhea despite receiving antibiotics. Laboratory findings showed inflammation and reactivation of CMV infection accompanied by liver injury. The endoscopic findings showed inflammation of the pouch and ileal mucosa on the oral side with extensive and deep punched-out ulcers. Immunohistological staining of biopsy specimens from an ulcerated lesion demonstrated CMV infection. Therefore, we diagnosed the patient with pouchitis complicated by CMV infection. The patient was treated with ganciclovir and infliximab, which resolved her symptoms and led to the disappearance of CMV-positive cells. There has been no recurrence of pouchitis. CMV infection should be considered in patients with UC who develop refractory pouchitis.

Safety of Biological Therapy in Children With Inflammatory Bowel Disease.

Retrospective, observational, single-center, cohort study investigating the safety profile of biological therapy in children with inflammatory bowel disease (IBD). Retrospective, observational, cohort study of pediatric patients with IBD, receiving infliximab, adalimumab, vedolizumab, or ustekinumab for at least 2 months. Data related to the immediate and delayed adverse events (AEs) were collected, focusing on the reaction type and severity, the time of onset, the outcome and the temporary or definitive therapy discontinuation secondary to the AE. Number of suspected and confirmed coronavirus disease-209 (COVID-19) cases and their outcomes, as well as flu vaccination coverage were collected. One hundred eighty-five children were included (101 [55%] CD, 82 [44%] UC, and 2 [1%] IBDU): 149 received infliximab (IFX) (81%), 88 (48%) adalimumab (ADA), 18 (21%) vedolizumab, and 4 (2%) ustekinumab. The overall AE rates were 49%, 67% of whom likely medication-related. Eleven (6%) patients experienced more than 1 AE, 18 patients (10%) presented an immediate reaction, and 82 (45%) a delayed AE. Among the 90 patients experiencing at least 1 AE, 97% had mild-to-moderate AEs. Only 4 SAEs were reported (4%). Treatment discontinuation because of AE occurred in 25 patients (14%). Four COVID-19 cases were reported, all with a mild course. Our findings confirm a good safety profile of biologics. Infusion reactions to IFX administration remain one of the main issues, significantly linked to its immunogenicity and consequently with an impact on its efficacy and durability.

Pyoderma gangrenosum, acne, and unclassified inflammatory bowel disease syndrome

Abstract Rationale: Pyogenic arthritis, pyoderma gangrenosum (PG), and acne (PAPA) syndrome is an autosomal dominant inherited autoinflammatory syndrome. Recently, many subtypes of PAPA syndrome have been reported, such as PG, acne, and ulcerative colitis (PAC) syndrome. We present the rare case of a patient with intestinal lesions different from those seen in the patient with PAC syndrome. Patient concerns: A 22-year-old Japanese man was referred to our department for arthralgia, PG, and acne. He was diagnosed with inflammatory bowel disease 3 months after the first visit. Diagnoses: Synovial tissue from the patient's knee joint was poor in neutrophil infiltration, which did not indicate pyogenic arthritis. His symptoms resembled those of PAC syndrome; however, the macroscopic findings indicated unclassified inflammatory bowel disease rather than ulcerative colitis or Crohn's disease. We diagnosed him with PG, acne, and unclassified inflammatory bowel disease syndrome, which we propose to be a new subtype of PAPA syndrome. Interventions: Initially, the patient was treated with steroids, salazosulfapyridine, and enteral feeding, but arthralgia, acne, abdominal symptoms, and exacerbation of inflammatory reactions were still observed. Administration of adalimumab and granulocyte and monocyte adsorption apheresis therapy were not effective, and we elected to administer infliximab as an alternative treatment. Outcomes: All clinical symptoms except arthralgia improved after administration of infliximab. Lessons: We consider PG, acne, and unclassified inflammatory bowel disease to be a new subtype of PAPA syndrome complicated with unclassified inflammatory bowel disease, associated with autoinflammatory-related enterocolitis.

Tissue content of metalloproteinase-9 and collagen in the colon with and without fecal stream after intervention with infliximab in rats subjected to Hartmann's surgery.

ABSTRACTPurposeQuantify the tissue content of metalloproteinase-9 (MMP-9) and collagen in colic mucosa with and without intestinal transit after infliximab administration in rats subjected to Hartmann’s surgery.MethodsTwenty-two rats underwent colon diversion by Hartmann’s surgery. Animals were maintained with intestinal bypass for 12 weeks to induce development of diversion colitis (DC). Afterwards, animals were divided into three groups: first group received subcutaneous application of saline solution (SS) 0.9%, while the remaining two groups received infliximab subcutaneously at doses of 5 or 10 mg·kg–1·week–1 for five consecutive weeks. After the intervention, animals were sacrificed, removing the segments with and without intestinal transit. Diversion colitis was diagnosed by histological study, and its intensity was determined by a validated inflammatory scale. Tissue expression of MMP-9 was assessed byimmunohistochemistry, while total collagen was assessed by histochemistry. Tissue content of both was measuredby computerized morphometry.ResultsColon segments without intestinal transit had a higher degree of inflammation, which improved in animals treated with infliximab. Collagen content was always lower in those without intestinal transit. There was an increase in the collagen content in the colon without transit in animals treated with infliximab, primarily at a dose of 10 mg·kg–1·week–1. There was an increase in the content of MMP-9 in the colon without fecal transit, and a reduction was observed in animals treated with infliximab, regardless of the dose used.ConclusionsApplication of infliximab reduces inflammation, increases the total collagen content and decreases the content of MMP-9 in the colon without intestinal transit.

Infliximab Therapy for Children with Moderate to Severe Ulcerative Colitis: A Step-Up versus a Top-Down Strategy.

PurposeWe aimed to investigate clinical outcomes between top-down (TD) and conventional step-up (SU) therapies in pediatric patients with moderate to severe ulcerative colitis (UC).Materials and MethodsAll patients underwent clinical and endoscopic evaluation at diagnosis and 4 months and 1 year after treatment. Patients who started treatment with corticosteroid were grouped in the SU group, while those that initiated early infliximab (IFX) were grouped in the TD group. Among the SU group, patients who eventually changed to IFX treatment due to steroid resistance or dependency were included in the SU(R) group.ResultsIn total, 44 children with moderate to severe UC were included for analysis. Twenty-one patients were included in the SU group, 23 were included in the TD group, and 10 were enrolled in the SU(R) group. Relapse rates were 47.6% (10/21) in the SU group and 17.4% (4/23) in the TD group (p=0.033). Among relapsed patients, the durations from remission to relapse were 17.3 months (0.9–46.9) in the SU group and 24.3 months (1.8–44.9) in the TD group. There was no statistically significant difference in the sustained durations of remission after IFX administration between the SU(R) and TD groups [3.9 (1.4–6.3) and 2.3 (0.3–5.2) years, respectively (p>0.05)].ConclusionAccording to our study, early use of IFX without corticosteroid treatment for children with moderate to severe UC helps to lower relapse rates. We also found that IFX was a very effective treatment for pediatric UC, with a sustained duration of remission similar between TD and SU(R) groups.