Course Of Infliximab Research Articles

“Trident Sign” in Spinal Cord Lymphoma (P7-4.003)

<h3>Objective:</h3> N/A <h3>Background:</h3> Chronic, progressive myelopathies with longitudinally-extensive T2-hyperintense lesions and specific gadolinium enhancement patterns, such as the axial “trident sign” of enhancement, have shown to be strongly suggestive of spinal cord sarcoidosis. However, the sensitivity and specificity of such enhancement patterns are not known. <h3>Design/Methods:</h3> Case report with description of history, examination, laboratory values, and imaging findings. <h3>Results:</h3> A 50-year-old woman presented with progressive left spastic hemiparesis over three weeks. MRI of the cervical spine revealed a longitudinally-extensive T2-hyperintense lesion with linear dorsal subpial enhancement and an axial trident pattern of enhancement. Cerebrospinal fluid analysis revealed a pleocytosis with a white blood cell count 20 cells/mm³ (89% lymphocytes), protein of 50 mg/dL, and glucose of 59 mg/dL with negative oligoclonal bands, cytology, and flow cytometry. Aquaporin-4-IgG and Myelin Oligodendrocyte Glycoprotein-IgG in serum were negative. Whole-body FDG-PET revealed increased uptake in the cervical cord but no other areas of systemic hypermetabolism. She was treated with three courses of IV methylprednisolone but her weakness continued to progress. Repeat MRI two months after her initial presentation showed persistent enhancement. Her neurologic examination revealed left spastic hemiplegia and moderate weakness of her right upper extremity. Given the chronic, progressive myelopathy, persistent trident enhancement pattern suggestive of spinal cord sarcoidosis, and the potential risks involved with a cervical cord biopsy, a course of infliximab was trialed empirically. Despite this, she continued to worsen neurologically and developed hypercarbic respiratory failure. Spinal cord biopsy was pursued, ultimately revealing infiltration by diffuse large B-cell lymphoma. <h3>Conclusions:</h3> Spinal cord lymphoma should be considered in patients presenting with chronic, progressive myelopathy and can present with similar enhancement patterns as spinal cord sarcoidosis. Atypical clinical features, such as rapid and severe neurologic worsening despite immunosuppression, should raise suspicion for diagnoses other than spinal cord sarcoidosis to allow for earlier detection and expedited disease-directed treatment. <b>Disclosure:</b> Dr. Griffin has nothing to disclose. Dr. Toledano has nothing to disclose. The institution of Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Pharmacy times. The institution of Dr. Flanagan has received research support from Viela Bio. Dr. Flanagan has received research support from UCB. Dr. Flanagan has received publishing royalties from a publication relating to health care. Dr. Flanagan has a non-compensated relationship as a Member of medical Advisory Board with The MOG Project that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Journal of The Neurologic Sciences that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Neuroimmunology Reports that is relevant to AAN interests or activities. Dr. Mustafa has nothing to disclose.

Behçet's Disease-related Budd-Chiari Syndrome Successfully Managed with anti-TNF Antibody: A Case Report and Review of the Literature.

Behçet’s disease (BD) is multisystemic vasculitis with heterogeneous clinical manifestations. We describe the case of a 26-year-old man who presented with Budd–Chiari syndrome (BCS) related to BD. The patient received infliximab (IFX) due to the severity of vascular involvement. Subsequently, after IFX therapy, hospital-acquired pneumonia, trapped lung, and fungal infection of the lung and central nervous system developed as complications. The patient benefited from a second course of IFX and clinical remission was achieved following early identification and treatment of complications. Data on the presentation and prognosis of BCS related to BD are extremely limited. Our case report supports the growing evidence that anti-TNF antibody is a promising treatment for BD-related BCS.LEARNING POINTSBehçet’s disease-related Budd–Chiari syndrome is a rare form of vascular involvement that severely affects mortality.Behçet’s disease-related Budd–Chiari syndrome is frequently confused with idiopathic thrombosis and may be underdiagnosed.Infliximab could be a therapeutic option for refractory Behçet’s disease with major vascular involvement, but the increased risk of opportunistic infections should be kept in mind.

Risk factors for anti-drug antibody formation to infliximab: Secondary analyses of a randomised controlled trial.

BackgroundAnti‐drug antibodies (ADAb) frequently form early in the treatment course of infliximab and other tumour necrosis factor (TNF) inhibitors, leading to treatment failure and adverse events.ObjectiveTo identify risk factors for ADAb in the early phase of infliximab treatment.MethodsPatients (n = 410) with immune‐mediated inflammatory diseases who initiated infliximab treatment were included in the 38‐week Norwegian Drug Monitoring Trial (NOR‐DRUM) A and randomised 1:1 to therapeutic drug monitoring (TDM) or standard therapy. Serum levels of infliximab and ADAb were measured at each infusion. Possible risk factors for ADAb formation were assessed using logistic regression, adjusting for potential confounders.ResultsADAb were detected in 78 (19%) patients. A diagnosis of rheumatoid arthritis (RA) (odds ratio [OR], 1.9 [95% confidence interval [CI] 1.0–3.6]) and lifetime smoking (OR, 2.0 [CI 1.1–3.6]) were baseline risk factors, while baseline use of concomitant immunosuppressors (OR, 0.4 [CI 0.2–0.8]) and a diagnosis of spondyloarthritis (SpA) (OR, 0.4 [CI 0.2–0.8]) reduced the risk of ADAb. Higher disease activity during follow‐up (OR, 1.1 [CI 1.0–1.1]) and “drug holidays” of more than 11 weeks (OR, 4.1 [CI 1.2–13.8]) increased the risk of ADAb, whereas higher infliximab doses (OR, 0.1 [CI 0.0–0.3) and higher serum infliximab concentrations (OR, 0.7 [CI 0.6–0.8]) reduced the risk of immunogenicity.ConclusionSeveral risk factors for ADAb formation during early‐phase infliximab treatment were identified. This knowledge provides a basis for treatment strategies to mitigate the formation of ADAb and identify patients in whom these measures are of particular importance.

Relapse of Sarcoidosis After Lung Transplantation

<h3>Introduction</h3> Sarcoidosis is a systemic granulomatous disease of unknown etiology. It most commonly affects the lungs, lymph nodes and skin, but the eyes, liver, heart and central nervous system can also be involved. Lung involvement is present in almost all patients with sarcoidosis. Prognosis is generally benign with more than half of patients entering spontaneous remission. However, a third of patients exhibit progressive disease culminating in organ dysfunction. Although sarcoidosis is not among the most frequent causes for lung transplantation, this can be the only therapeutic alternative in this subset of patients. <h3>Case Report</h3> The authors present the case of a 48-year-old caucasian male patient, with no relevant medical history, who had been diagnosed with sarcoidosis since 2006. Thoracic lymph nodes and lung parenchyma were affected on presentation, and screening showed ocular involvement as well. The patient experienced a flare in 2015, with worsened dyspnea and decline in FEV1 and DLCO values, and was started on prednisolone and methotrexate. Clinical stability for the next three years allowed suspension of methotrexate in 2018, while maintaining low dose steroids. However, new clinical and functional decline, as well as detection of cardiac involvement, prompted a six month course of infliximab in 2019. Due to continued worsening of lung function tests (LFTs) and progression to lung fibrosis, the patient underwent bilateral lung transplantation in June 2020 without major complications, and was discharged a month later. He remained asymptomatic and follow-up LFTs were stable until February 2021, eight months after the transplant, when a new fall in FEV1 was noticed. Flexible bronchoscopy and transbronchial biopsies (TBB) were performed, revealing minimal acute rejection (A1) and granulomas compatible with sarcoidosis. Methylprednisolone pulse therapy was administered, followed by weaning. FEV1 levels improved in subsequent evaluations, although TBB performed three months later continued to show signs of sarcoidosis. <h3>Summary</h3> Allograft relapse of sarcoidosis is relatively common - Schultz et al have reported a recurrence rate of 30%. Research by Ionescu et al has showed the granulomas originate from the recipient. Recurrence of sarcoidosis does not seem to impact survival or lung function of lung transplant recipients. This case illustrates coexistence of both acute rejection and recurrent sarcoidosis.

Does Perianal Disease Influence the Efficacy of Combination Therapy in Crohn’s Disease?

Background: Perianal disease is associated with a disabling course of Crohn’s disease (CD). We aim to study the impact of perianal disease on CD remission rates, after a 1-year course of infliximab in combination therapy with azathioprine. Methods: This was a retrospective, single-center cohort study, including consecutive CD patients on combination therapy, followed for 1 year since induction. The outcome variable was split into clinical and endoscopic remissions. The correlation toward the outcome variable was assessed with univariate and multivariate analysis and a survival assessment, using SPSS software. Results: We assessed 74 CD patients, of whom 41 (55.4%) were female, with a mean age of 36 years. Thirty-nine percent of the patients presented perianal disease at diagnosis (n = 29). We documented 70.3% clinical and 47.2% endoscopic remissions. Several variables had statistical significance toward the outcomes (endoscopic and clinical remissions) in the univariate analysis. After adjusting for confoundment, patients with perianal disease presented an odds ratio (OR) of 0.201 for achieving endoscopic remission (CI: 0.054–0.75, p value 0.017) and an OR of 0.203 for achieving clinical remission (CI: 0.048–0.862, p value 0.031). Sixty-six patients (89.2%) presented an initial response to treatment, from whom, 20 (30.3%) exhibited at least 1 disease relapse (clinical and/or endoscopic). Patients with perianal disease presented higher probability of disease relapse, displaying statistically significant difference on Kaplan-Meier curves (Breslow p value 0.043). Conclusion: In the first year of combination therapy, perianal disease is associated with an 80% decrease in endoscopic and clinical remission rates and higher ratio of disease relapse.

Rapid weight gain in infliximab treated Crohn’s disease patients is sustained over time: real-life data over 12 months

Background Infliximab (IFX) is used in active Crohn’s disease for induction and maintenance of remission. There are scanty data on weight gain in IBD-patients under anti-TNF treatment. We investigated changes in weight and blood chemistry in anti-TNF-naïve Crohn’s disease patients during their first course of IFX. Methods Retrospective analysis of 110 patients (77 men, 33 women) aged 34 years (range 14–73), 54 with luminal and 56 with fistulising disease, given at least 3 infusions of IFX (range 3–11). Data regarding body weight, height, C-reactive protein (CRP), haemoglobin and S-albumin at baseline, before the third infusion, at three months and at 12 months were collected. Results At 6 weeks, 65 (59%) increased in weight, 73% and 76% at three and 12 months, respectively. There was an increase in median weight (1.7 kg, IQR = 3.1 kg) and BMI (0.5 kg/m2, IQR = 1.2 kg/m2) at 6 weeks, which persisted at three and 12 months (all p < .001). There was no difference between men and women. Young patients, patients with underweight or fistulising disease increased most in weight. Disease activity assessed by PGA and SES-CD decreased at all time points (p < .05). Increases in weight and BMI correlated with an increase in serum albumin and a decrease in CRP. Conclusion Approximately 60% of Crohn’s disease patients experience weight gain within the first six weeks of infliximab treatment. The weight increment correlates with improvements in inflammatory markers and disease activity. The causes of weight gain may be related to treatment induced metabolic changes and reduced inflammatory burden.

The role of ABO blood groups in Crohn's disease and in monitoring response to infliximab treatment.

The variation in ABO blood groups is reported to be associated with multiple diseases. Infliximab (IFX) has been widely used in the treatment of Crohn's disease (CD). We aim to investigate the distribution of ABO blood groups in Chinese patients with CD and to explore its impact on response to IFX. Patients with CD were consecutively recruited to the study between 2007 and 2014. CD patients receiving IFX therapy were followed for at least two years. In 293 patients with CD, most patients (40.6%) had blood type O (119/293). The odds ratio (OR) of CD in blood type O patients was 1.06 (95%CI: 0.6-1.86; p=0.84) compared to all other blood types. Among those CD patients, 107 patients received IFX treatment. One year after the first course of IFX, a significant association was found between the overall ABO system and outcomes of IFX treatment (p<0.001). CD patients with blood type AB (OR=4.42, 95% CI: 1.04-18.76; p=0.044) were more likely to achieve mucosal healing, while CD patients with blood type A had a high risk of losing response (OR=0.38, 95% CI: 0.15-0.96; p=0.040). ABO blood groups are not associated with prevalence of CD. Patients with blood type AB had a better response to IFX while those with blood type A appeared to have a risk of losing response to IFX.

Normalization of mucosal tumor necrosis factor-α: A new criterion for discontinuing infliximab therapy in ulcerative colitis

BackgroundBiological agents such as anti-tumor necrosis factor (TNF) induce remission in ulcerative colitis. There is however no consensus regarding the discontinuation of this treatment. AimThe aim of this study is to assess whether clinical parameters and mucosal cytokine mRNAs in healed colonic mucosa can predict long-term remission in ulcerative colitis following discontinuation of infliximab (IFX) therapy. MethodsThe prospective Tromsø Inflammatory Bowel Disease (IBD) Study is based on an intensified induction treatment algorithm with IFX to achieve disease remission. Following clinical and endoscopic remission, IFX treatment was discontinued, and follow-up until relapse was performed. Patients who achieved clinical and endoscopic remission following an induction course of IFX were included. Expression levels of TNF alpha (TNF), interferon gamma (IFNG), interleukin (IL) 6 (IL6), IL17A, IL23, and transforming growth factor beta (TGFB) were quantified by real-time PCR in mucosal biopsies obtained at colonoscopy. Remission was defined as Ulcerative Colitis Disease Activity Index (UCDAI) below 3, and an endoscopic sub-score of 0–1. Relapse was defined as UCDAI score >3 and endoscopic sub-score >1. Mucosal cytokine transcript levels from 20 non-IBD patients with a normal colonoscopy served as control group. ResultsOf the 45 patients included, twenty patients (44%) had normalized levels of mucosal TNF expression at the time of mucosal healing, whereas 35 of 42 (83%) had normalized IL17A expression levels, and 31 of 36 (86%) had normalized IFNG expression levels. The median time to relapse was 8months (range 4–12). Normalization of TNF gene expression predicted 20months (1–39) relapse-free survival after withdrawal of IFX compared to 5months (3–7) in the group with elevated TNF expression. Mucosal expression levels of IL17A, IL23, IFNG, TGFB, IL6 did not predict long-term remission (>12months) ConclusionNormalization of mucosal TNF predicts long-term remission after discontinuation of IFX.

Pulmonary artery involvement in Behçet׳s syndrome: Effects of anti-Tnf treatment

ObjectivesAnti-TNF agents are being increasingly used in patients with Behçet׳s syndrome (BS) when conventional immunosuppressives fail. However, experience with anti-TNF treatment on pulmonary artery involvement (PAI) of BS is limited. MethodsA chart review revealed 13 patients with PAI (all men) treated with anti-TNF agents (12 infliximab and 1 adalimumab) following an inadequate response to immunosuppressives for 12.2 ± 9.5 SD months and 2 male patients who developed PAI while receiving infliximab for large vein thrombosis for 10 months and for parenchymal central nervous system involvement for 2 years, respectively. ResultsThe first patient developing PAI while receiving infliximab responded to cyclophosphamide and prednisolone but the second died with hemoptysis within 1 month. At the end of the survey, 6 of the 13 patients with PAI were continuing these agents for 25.5 ± 16.2 SD months with good response, 4 stopped anti-TNF treatment after a mean of 23 ± 9.8 SD months after achieving clinical and radiologic response and 1 patient with good response went to another center after receiving infliximab for 10 months and the remaining 2 experienced serious infections (lung tuberculosis and aspergillosis) necessitating early withdrawal. Two patients relapsed within 3 years after stopping anti-TNF agents and concomitant azathioprine. One developed mesenteric vein thrombosis necessitating bowel resection and the second developed new PAI that was controlled with cyclophosphamide and prednisolone after short courses of infliximab, adalimumab, and canakinumab. ConclusionAnti-TNF treatment seems to be effective for refractory PAI of BS but may not prevent its development. Relapses can be seen after withdrawal. Caution is required for their serious adverse effects.

OP0065 Initial Infliximab is not Cost-Effective in Otherwise Actively Treated Early Rheumatoid Arthritis. the 2-Year Follow-Up Results of the Randomized Clinical Neo-Raco Trial

BackgroundIn most early rheumatoid arthritis (RA) patients, early remission and a non-progressive state of disease can be achieved when an initial treatment with a triple combination of disease modifying antirheumatic...

Herpes zoster in Crohn’s disease during treatment with infliximab

Infliximab is widely used in both inducing and maintaining remission of patients with Crohn's disease (CD). The efficacy of infliximab has been undoubtedly proven; however, various opportunistic infections have emerged. Herpes virus infections (being a type of opportunistic infection) in CD patients treated with infliximab alone with no other concomitant medications are, however, rare and have not aroused enough attention. Gastroenterologists have limited knowledge of the immunization status of patients with CD, and rarely do they take an adequate immunization history before immunosuppressive therapy. Here we report two herpes zoster (HZ) events in CD patients while using infliximab alone: in the first case, HZ occurred during the patient's 12th infusion for maintance therapy, and in the second case, HZ occurred during the patient's first course of infliximab after surgery for therapy of inducing remission. We hope to increase the gastroenterologists' awareness of this potential infection in CD patients during treatment with infliximab.

A case of a patient with stage III familial hidradenitis suppurativa treated with 3 courses of infliximab and died of metastatic squamous cell carcinoma.

Although rare, severe hidradenitis suppurativa (HS) of the anal, perianal, gluteal, thigh, and groin regions can evolve into squamous cell carcinoma (SCC). This usually does not occur until the HS has been present for more than 20 years. Malignant degeneration of HS in the axilla has not been reported. SCC has developed in dissecting cellulitis, acne conglobata, and pilonidal cysts (other members of the follicular tetrad). Whereas the male to female ratio of HS is 1:3, SCC in HS has a male to female ration of 5:1. The reasons behind malignant degeneration in HS are complex and might differ from the malignant degeneration causing Marjolin ulcers. It likely involves the presence of human papilloma virus (HPV) in affected areas (a rarity in the axilla), and impaired defensins, which combat HPV, in the skin of Hurley Stage III HS. In familial HS, the odds of developing SCC are likely greater because of independent loss-of-function mutations in the γ-secretase multiprotein complex, which regulates the Notch signaling pathway. Compromise of the Notch signaling pathway can undermine immune function and increase the risk of neoplastic development. Coincident SCC with use of tumor necrosis factor α blockers has been reported. I report a patient with long standing Hurley Stage III, familial HS, wwho developed metastatic SCC after 3 courses of infliximab and expired 11 months after the infliximab was started. A 47-year-old male presented with progressive HS since early adulthood. His stage III hidradenitis suppurativa (HS) involved his groin, legs buttocks, and perineal areas. Interestingly, his HS was familial; one daughter also suffered from HS. A pilonidal cyst had been excised in the past. He suffered from hypertension for which he took ramipril, 2.5 mg per day. He did not admit to smoking. He had undergone numerous surgeries and courses of clindamycin with rifampin and clindamycin with minocycline. He used pregablin among other stronger medications for pain control. He had also taken isotretinoin years before without substantial long-term benefit. The various treatments were palliative but the HS always returned. He expressed that the pain from his HS was not bearable. He decided in consultations with his doctors to try infliximab owing to the positive clinical data for its efficacy in HS. He took 3 courses of infliximab 500mg, each of which was followed by surgical debridement of the perineal and anal areas. At the 3rd surgical debridement his physician noted the presence of squamous cell carcinoma (SCC) on July 28, 2008. The infliximab was stopped. However, the patient developed the patient underwent scanning soon after that showed soon after that the SCC had metastasized. He expired in June of 2009.

Clinical course of infliximab treatment in korean pediatric ulcerative colitis patients: a single center experience.

PurposeInfliximab (IFX) is considered safe and effective for the treatment of ulcerative colitis (UC) in both adults and children. The aim of this study was to evaluate the short- and long-term clinical course of IFX in Korean children with UC.MethodsPediatric patients with UC who had received IFX infusions between November 2007 and May 2013 at Samsung Medical Center were retrospectively investigated. The clinical efficacy of IFX treatment was evaluated at 8 weeks (short term) and 54 weeks (long term) after the initiation of IFX treatment using the Pediatric Ulcerative Colitis Activity Index (PUCAI). The degree of response to IFX treatment was defined as complete response (PUCAI score=0), partial response (decrement of PUCAI score≥20 points), and non-response (decrement of PUCAI score <20 points). Adverse events associated with IFX treatment were also investigated.ResultsEleven pediatric patients with moderate to severe UC had received IFX. The remission rate after IFX treatment was 46% (5/11) and 82% (9/11) at 8 weeks and 54 weeks after IFX treatment, respectively. All patients who were steroid-dependent before treatment with IFX achieved remission at 54 weeks and were able to stop treatment with corticosteroids, while all steroid-refractory patients failed to achieve remission at 54 weeks after treatment with IFX.ConclusionResponse to IFX treatment after 8 weeks may predict a favorable long-term response to IFX treatment in Korean pediatric UC patients.

Infliximab Retreatment in Inflammatory Bowel Disease: A Single-center Experience

Purpose: Infliximab is an anti-tumor necrosis factor alpha (anti-TNF) agent used in Crohn's disease (CD) and ulcerative colitis (UC). Early data on episodic treatment with infliximab demonstrated increased risk of allergic reactions and reduced efficacy after interruptions in therapy. We aimed to characterize response rates and adverse events among patients with inflammatory bowel diseases (IBD) treated with a standardized infliximab retreatment protocol after a drug holiday. Methods: We retrospectively analyzed all cases of infliximab retreatment at a single tertiary care center, including individuals with both CD and UC, between 2011 and 2012. Re-treatment protocol included: prednisone taper, intravenous hydrocortisone, extended infusion duration, and initiation of concomitant immunomodulator when possible. We assessed the rationale for first discontinuation of infliximab, time interval since last infusion, adverse events associated with reinduction therapy, and overall response rates; defined as a.) clinical response with continuation of infliximab beyond induction therapy, and b.) clinical response with continuation of infliximab beyond 14 weeks. Results: A total of 19 patients underwent reinduction therapy with infliximab (n=17 with CD, n=2 with UC). Ages ranged from 20 to 72 years (mean 35.2 years), nine (47.4%) were female, five (26.3%) were smokers, and 13 (68.4%) had prior surgery. The interval between initial treatment and reinduction with infliximab ranged from 1 to 9 years (mean 4.7 years), and 15 (78.9%) were on other forms of immunosuppression prior to retreatment. A total of 13 (68.4%) had tried an alternate anti-TNF. The most common reason for discontinuation of first course of infliximab was patient preference (n=9, 47.4%). A total of 13 (68.4%) responded to reinduction at 6 weeks, with 12 (63.2%) meeting the endpoint of clinical response at week 14. Rates were higher for response at week 6 and 14 among those started on concomitant immunosuppression (72.7% and 63.6% respectively, as compared to 62.5% and 62.5% for those on no immunomodulator). There were three incidents of serious adverse events (SAEs), including two infusion reactions and one delayed serum sickness reaction. Of those with SAES, two (66.7%) had previously stopped infliximab due to preference, and one (33.3%) due to loss of response. Of these, two (66.7%) were on concomitant immunomodulators. Conclusion: We observed high re-treatment response rates with infliximab re-induction therapy in a group of individuals who largely initially stopped infliximab due to preference, although a substantial rate of severe adverse events occurred. Retreatment protocols should only be attempted with caution in a controlled setting.

Ten Years of Infliximab for Crohn’s Disease

Aim was to assess the long-term clinical efficacy of infliximab therapy in patients with Crohn's disease treated in a cohort of 2 tertiary referral centers in the Netherlands. All consecutive patients with Crohn's disease treated with infliximab were assessed. Endpoints were primary clinical efficacy, sustained benefit, efficacy of retreatment, surgical intervention rates, and safety. Sustained benefit was determined by Kaplan-Meier analysis. The estimated 5-year benefit was calculated. A total of 469 patients were included. Median follow-up length was 4.5 years (interquartile range, 2.7-6.8). Seventy patients (15%) had unsuccessful remission induction, and 316 patients received maintenance therapy. Scheduled maintenance regimen was successful in 169 of 276 (61%). Episodic maintenance therapy was successful in 19 of 40 patients (48%). Estimated 5-year sustained benefit was 55.7% (95% confidence interval, 48.8-62.6). Concomitant thiopurines were associated with improved sustained benefit. A second course of infliximab after previous discontinuation was prescribed in 131 patients with similar efficacy rates. Abdominal surgical intervention rate per 100 patient-years was significantly reduced after infliximab initiation in patients with a scheduled maintenance regime (reduction, 2.70; 95% confidence interval, -4.82 to -0.35; P = 0.018). Mortality and malignancy rates were 1.9% (0.39/100 patient-years) and 3.4% (0.70/100 patient-years), respectively. The present study shows an estimated 5-year sustained benefit of 55.7% in patients with Crohn's disease treated with infliximab maintenance therapy. Remission induction and maintenance were equally successful in patients starting infliximab and patients who temporarily stopped and were retreated. Long-term use of infliximab was safe and reduced the need for surgery in patients on scheduled maintenance therapy.

AB0464 Comparative efficacy of infliximab in patients with rheumatoid arthritis (RA) depending on a total dose (quantity of infusions)

ObjectivesTo estimate efficacy of infliximab (INF) in patients (pts) with RA depending on a total dose (quantity of infusions) of this biologic.MethodsThe cohort of 135 pts with active RA despite...

AB0172 Protection from articular damage by passive or active anti-TNF alpha immunotherapy in human-TNF alpha transgenic mice depends on anti-TNF alpha antibody levels

BackgroundIn human TNFα (hTNFα) transgenic mice (TTg), active anti-TNFα immunization with the kinoid of TNFα (TNF-K) induces polyclonal anti-hTNFα antibodies and results in amelioration of arthritis1,2,3Objectives1) To compare the efficacy...

Protection from articular damage by passive or active anti-tumour necrosis factor (TNF)-α immunotherapy in human TNF-α transgenic mice depends on anti-TNF-α antibody levels

Active anti-tumour necrosis factor (TNF)-α immunization with the kinoid of TNF-α (TNF-K) induces polyclonal anti-TNF-α antibodies and ameliorates arthritis in human TNF-α (hTNF-α) transgenic mice (TTg). We compared the efficacy of TNF-K to that of infliximab (IFX) and of TNF-K and IFX co-administration, and evaluated whether the titres of anti-hTNF-α antibodies induced by immunization were a determinant of TNF-K efficacy. Forty-eight TTg mice received one of the following treatments: TNF-K immunization (TNF-K group); weekly IFX throughout the study duration (IFXw0-15); TNF-K plus weekly IFX for 4 weeks (TNF-K + IFX); and weekly IFX for 4 weeks (IFXw0-4); PBS. Animals were killed at week 16. Anti-hTNF-α antibody titres and clinical and histological scores were compared. All TNF-K immunized mice (TNF-K and TNF-K + IFX) produced anti-hTNF-α antibodies. Titres were higher in TNF-K versus TNF-K + IFX (P < 0·001) and correlated inversely with histological inflammation (R = -0·78; P = 0·0001) and destruction (R = -0·67; P = 0·001). TNF-K + IFX had higher histological inflammation and destruction versus TNF-K (P < 0·05). A receiver operating characteristic (ROC) analysis of anti-hTNF-α antibody titres identified the criterion cut-off value to discriminate most effectively between the TNF-K and TNF-K + IFX groups. Mice with high versus low titres had less histological inflammation and destruction (P < 0·05). In a model of TNF-α-dependent arthritis, protection from articular damage by TNF-K correlates with the titres of induced anti-hTNF-α antibodies. The co-administration of TNF-K and a short course of infliximab does not result in less articular damage versus solely TNF-K, due probably to lower anti-hTNF-α antibody production. These results are relevant for future development of active anti-TNF-α immunization in human disease.

Infliximab for Crohn’s Disease: The First 500 Patients Followed Up Through 2009

The aim of this study was to assess the long-term usage patterns and safety of infliximab in patients with Crohn's disease in clinical practice. The medical records of 492 unselected patients treated with infliximab at Mayo Clinic were reviewed and abstracted for demographic features, usage patterns, and adverse events. The patients received a median of seven infusions and had a median follow-up of 6.3years. Twenty-eight patients (6%) were lost to follow-up, 63 patients (13%) had no clinical benefit, and 401 patients (80%) had partial or complete response. Of the responding patients, 114 (28%) received induction treatment only, 167 (42%) received initial episodic treatment (62 switched to scheduled maintenance treatment of whom 32 [42%] were still on infliximab at last follow-up), and 120 (30%) received scheduled maintenance treatment (56 patients [32%] still on infliximab at last follow-up). Three patients (0.6%) developed septic shock and six patients (1.5%) developed septicemia. One patient (0.2%) developed Mycobacterium avium complex. Histoplasmosis occurred in three patients (0.6%). The cumulative 10-year probability for developing cancer after infliximab was 9%. Among the 31 patients developing malignancies (6%), 15 (3%) had solid tumors, 11 (2%) had melanoma and non-melanoma skin cancers, three (0.6%) had lymphomas (0.6%), and two (0.4%) had leukemia. Overall 10-year survival after the final course of infliximab was 94%. Among the 28 deaths (6%), nine occurred within 12weeks of an infliximab infusion-two of these deaths were due to infections. Long-term follow-up of patients with Crohn's disease who were treated with infliximab initially between 1998 and 2002 showed persistence of therapy (due to clinical benefit) and an acceptable safety profile, despite the fact that less than one-third initially received three-dose induction followed by scheduled maintenance therapy. Infections and malignancy occurred at rates similar to those previously reported.

Systemic Mycobacterium avium Complex Infection During Antitumor Necrosis Factor‐α Therapy in Pediatric Crohn Disease

Systemic <i>Mycobacterium avium</i> Complex Infection During Antitumor Necrosis Factor‐α Therapy in Pediatric Crohn Disease