Introduction Infliximab Research Articles

Body mass index influences infliximab post-infusion levels and correlates with prospective loss of response to the drug in a cohort of inflammatory bowel disease patients under maintenance therapy with Infliximab.

IntroductionInfliximab is an effective treatment for inflammatory bowel disease (IBD). Studies differ regarding the influence of body mass index (BMI) on the response to infliximab, with the majority of studies indicating that increased BMI may be associated with a poorer response to Infliximab. However, the pharmacokinetic mechanisms causing this have not yet been reported.AimsExamine the correlation between BMI/immunosuppressant use with clinical response, trough and post-infusion levels of infliximab, tumour necrosis factor-α(TNF-α) and anti-drug antibodies(ATI), and determine if these factors can predict future response.MethodsWe collected serum from 24 patients receiving Infliximab before and 30 minutes following infusion. Clinical parameters were collected retrospectively and prospectively. ELISA measurements of infliximab, TNF-α and ATI were performed.ResultsWe confirmed that patients with higher infliximab trough levels have a better response rate and that patients with an elevated BMI display a higher rate of loss of response (20%). Patients with a higher BMI had elevated post-infusion levels of infliximab. Additionally, the ratio of IFX/TNF-α trough levels correlated with clinical response to the following infusion.ConclusionThis study confirms that an elevated BMI is associated with a poorer response to infliximab. For the first time, we describe that a higher BMI correlates with higher post-infusion levels, however this does not correlate with a higher rate of response to the drug, suggesting that circulating drug levels do not correlate with tissue levels. Furthermore, in our small cohort of patients, we identified a possible predictive marker of future response to treatment which may be used to guide dose escalation and predict non-response to infliximab.

Nocardia cyriacigeorgica pneumonia in ulcerative colitis patient receiving infliximab despite TMP/SMX prophylaxis

Introduction Infliximab is an effective therapy for induction and maintenance of remission in patients with refractory ulcerative colitis (UC). Treatment with TNF-alpha inhibitors is associated with an increased risk of infection. In this case, we will discuss an uncommon cause of infection associated with infliximab therapy despite antibiotic prophylaxis. Case description 78-year-old man with history of UC maintained on infliximab infusion every 8-weeks was found to have pulmonary infiltrates on chest computed tomography (CT). His UC history was notable for recent Pneumocystis jiroveci pneumonia while on infliximab requiring intravenous Trimethoprim/Sulfamethoxazole (TMP/SMX) treatment for 21 days followed by single strength oral TMP/SMX for secondary prophylaxis. On evaluation, the patient endorsed weakness, generalized fatigue, and shortness of breath with activities. His lab was notable for mild anemia in the absence of leukocytosis. Result and conclusion Bronchoscopy was performed and bronchoalveolar lavage fluid was sent to the microbiology laboratory for culture. After 30 days of incubation, the culture returned partially acid fast, branching, Gram-positive rod shaped bacteria consistent with Nocardia cyriacigeorgica. The isolate was susceptible to TMP/SMX (0.25/4.75μg/Ml). Patient was started on therapeutic dose of oral TMP/SMX at 5 mg/kg of the trimethoprim component for 6 months. Infliximab was subsequently held. Repeat chest CT scan at 6 months showed resolution of patchy ground glass and nodular infiltrates. Take-home message This case highlights the importance of considering Nocardia infection in ulcerative colitis patients receiving infliximab therapy presenting with shortness of breath and new infiltrates on chest imaging. In addition, patients receiving prophylaxis with TMP/SMX are still at risk for this infection because the effectiveness of prophylactic doses of TMP/SMX in preventing disease remains unclear.

Clinical outcome after discontinuation of infliximab in patients with ulcerative colitis in deep remission

Abstract Introduction Infliximab (IFX) is effective in treating ulcerative colitis (UC) and in achieving mucosal healing (MH). Little is known about the role of mucosal healing (MH) in the subsequent evolution of the disease and the consequences of discontinuing treatment. Aims To evaluate the characteristics and evolution of patients with UC treated with IFX who discontinued treatment after disease remission. Methods Observational, prospective study of patients with moderate to severe UC, corticosteroid-resistant/corticosteroid-dependent, naive to anti-TNF. IFX administration regimen: 5 mg/kg at 0-2-6 weeks and every 8 weeks thereafter until week 54. In patients achieving MH, IFX was discontinued and the patients were followed-up for at least 20 months. Clinical remission (CR): Mayo score Results Of the 21 patients enrolled, 19 completed the study (colectomy, n = 1; non-responder, n = 1). Mean age: 47.8 years. UC: severe (n = 13) and moderate (n = 6); most patients (n = 11) were steroid-resistant; 57.8% received combined treatment with immunosuppressants, and 31.5% intensified treatment. Week 54: 16 patients (84.2%) showed clinical response, 13 (68.4%) showed CR, and 12 (63.2%) deep remission. Of these, 6 (25%) presented a new episode of UC, and in 3 (25%) IFX was restarted within 12 weeks of discontinuation, with all patients responding. Of the total sample, 91.7% remained IFX-free at week 8, and 75% at week 12, with no remission during follow-up. None of the patients required hospitalisation or surgery. Conclusions Half of patients with deep remission of UC with IFX therapy presented a new episode after treatment discontinuation, and in 25% IFX therapy was restarted.

OC-038 Making The Change: Switching to Infliximab Biosimilars for IBD at North Bristol NHS Trust

Introduction Infliximab biosimilars have been available since February 2015, however at the time there was limited guidance on how to introduce the products. The PLANETRA and PLANETAS studies demonstrate that biosimilars are equivalent in clinical efficacy when compared to Remicade®. From the 1st July 2015, the gastroenterology department at NBT introduced biosimilar infliximab making cost savings of £200,000. A 50:50 gain share agreement was negotiated with the local Clinical Commissioning Groups and these savings will be re-invested into Gastroenterology services. Here we describe how a multidisciplinary approach led to a safe transition to biosimilar infliximab. Methods An additional pharmacist was funded to implement the switch using projected savings from the gain share. Patients who were established on Remicade® were sent a letter with details of the proposed switch and given the opportunity to raise any concerns in a consultation with the specialist pharmacists in Gastroenterology. Verbal consent was obtained prior to switching to Inflectra®. Practical guidance for the prescribing and dispensing of biosimilar infliximab was circulated to clinicians and pharmacy staff. Educational sessions were provided to the Medical Day Case Unit nurses. Adverse events were reported via the Yellow card® Scheme and the Biologics Therapy Audit. From December 2015, patients were asked to complete a survey to explore their experiences leading up to and during the switch. We decided not to study clinical outcomes as the sample size is misrepresentative and the follow-up period too short to draw meaningful conclusions. Results In total, 64/65 patients consented to the switch. Following the switch, 7 patients discontinued treatment (2 post-surgery; 5 switched to alternative biologic). We received a 46% response rate to the survey. Patient feedback was largely positive. 83% of patients received the written correspondence; 93% reported that they understood the information leaflet in part (23%) or in full (70%). 96% had the opportunity to speak to pharmacist before their first infusion. Overall, 97% of patients were satisfied with the changeover process. Conclusion We have demonstrated how a multidisciplinary approach allowed the successful switch to a biosimilar within 3 months and the potential benefits to be had. The additional pharmacist post, funded by the projected gain share, will be made a substantive this year allowing for closer monitoring and optimisation of biologic treatment. This will lead to further cost savings through discontinuation of these drugs where appropriate. Since the completion of this project, the BSG has revised their statement to acknowledge that there is sufficient evidence to recommend use of biosimilar infliximab in IBD. Disclosure of Interest L. Chung: None Declared, B. Arnold: None Declared, R. Johnson: None Declared, M. Lockett Conflict with: sponsored by MSD to attend conference in 2016

Sa1972 Factors Influencing Infliximab and Adalimumab Antibody Formation and 6 Month Retrospective Follow up in a Tertiary IBD Centre

Introduction Infliximab(IFX) and adalimumab(Ada) are established treatments for IBD.However, immunogenicity can lead to anti-drug antibodies(ADAb) which is associated with a poor clinical response.Little is known regarding the factors which influence ADAb formation or the long term outcomes. Methods Patients with detectable ADAb between May 2012 and October 2014 were identified.Assays had been performed using LISA-Tracker DUO Kits which detects free drug levels(DLs) and ADAb only.Patients were analysed for disease phenotype, prior anti-TNF treatment and ADAb formation,and the use of concomitant immunomodulation(IM). Results 330 IFX DLs and ADAb levels from 199 patients and 143 Ada DLs and ADAb levels from 105 patients were analysed.21 positive ADAb, 19 IFX(9.5%) and 2 Ada(1.9%),were detected with a median ADAb of 141.8 U/ml(range 11–200),all DLs were >1.0μg/ml. 47.6% were male, age range 21–84,median 33.85.7% had Crohn’s Disease.In the majority of patients DL and ADAb were measured due to loss of response(66.7%). 6/19 patients who had IFX ADAb had prior exposure to IFX and 1 had prior exposure to Ada.Time to antibody detection ranged from 2–140 weeks(median 14).Of the 6 patients who had previous exposure to IFX,median time to ADAb detection was 6 weeks.Both patients who developed Ada ADAb had prior exposure to Ada,one also had prior exposure to IFX. 18/21 patients were prescribed concomitant IM(2 methotrexate, 16 thiopurines).8/16 on thiopurines had subtherapeutic TGNs( IFX ADAb group(n = 19):11 patients were switched to Ada, all of whom had a clinical response(mean HBI at week 26 = 2.1, no ADAb detected). 1 was switched out of class to vedolizumab and responded well. 3 stopped biologic treatment,1 patient continued on IFX at their own request and 1 patient was dose escalated but failed to respond. 2 patients had concomitant IM optimised,1 of whom on subsequent ADAb testing showed loss of ADAb. Ada ADAb group(n = 2):1 patient stopped anti-TNF due to recurrent infections and the other was lost to follow up. Conclusion 42.9% of patients with ADAb had been exposed to anti-TNF previously,all with a gap of >6 months prior to repeat exposure suggesting this is a risk factor for earlier ADAb formation. All patients switched to Ada from IFX responded well without developing ADAb,highlighting that switching to another anti-TNF is an acceptable option before switching out of class. Our use of concomitant IM is high but 50% of this cohort had subtherapeutic TGNs.The 2 patients in whom a thiopurine was optimised achieved clinical remission while remaining on IFX. However the level at which TGNs should be targeted in this context is still unclear Disclosure of Interest B. Warner: None Declared, E. Johnston: None Declared, J. Digby-Bell: None Declared, Z. Arkir: None Declared, N. Unsworth: None Declared, S. Anderson: None Declared, J. Sanderson: None Declared, P. Irving Grant/research support from: PI has been advisor to, in receipt of educational or research grants from, or invited lecturer for Abbvie, Falk, Ferring, Genetech, Hospira, Merck, Pharmacosmos, Shire, Takeda, Tillotts, Topivert, Vifor and Warner Chilcott, Paid instructor for: as above

Evolución clínica tras la suspensión de infliximab en pacientes con colitis ulcerosa en remisión profunda

IntroductionInfliximab (IFX) is effective in treating ulcerative colitis (UC) and in achieving mucosal healing (MH). Little is known about the role of mucosal healing (MH) in the subsequent evolution of the disease and the consequences of discontinuing treatment. AimsTo evaluate the characteristics and evolution of patients with UC treated with IFX who discontinued treatment after disease remission. MethodsObservational, prospective study of patients with moderate to severe UC, corticosteroid-resistant/corticosteroid-dependent, naïve to anti-TNF. IFX administration regimen: 5 mg/kg at 0-2-6 weeks and every 8 weeks thereafter until week 54. In patients achieving MH, IFX was discontinued and the patients were followed-up for at least 20 months. Clinical remission (CR): mayo score <2; Clinical response: decrease in mayo score of 3 points; MH: mayo score 0-1; Deep remission: patient with CR and MH. ResultsOf the 21 patients enrolled, 19 completed the study (colectomy, n = 1; non-responder, n = 1). Mean age: 47.8 years. UC: severe (n = 13) and moderate (n = 6); most patients (n = 11) were steroid-resistant; 57.8% received combined treatment with immunosuppressants, and 31.5% intensified treatment. Week 54: 16 patients (84.2%) showed clinical response, 13 (68.4%) showed CR, and 12 (63.2%) deep remission. Of these, 6 (25%) presented a new episode of UC, and in 3 (25%) IFX was restarted within 12 weeks of discontinuation, with all patients responding. Of the total sample, 91.7% remained IFX-free at week 8, and 75% at week 12, with no remission during follow-up. None of the patients required hospitalization or surgery. ConclusionsHalf of patients with deep remission of UC with IFX therapy presented a new episode after treatment discontinuation, and in 25% IFX therapy was restarted.

Discontinuation of infliximab therapy in patients with Crohn's disease in sustained complete remission (the STOP IT study): protocol for a double-blind, randomised, placebo-controlled, multicentre trial

IntroductionInfliximab (IFX), a monoclonal chimeric antibody against tumour necrosis factor (TNF) α, is effective for induction and maintenance of remission in moderate to severe Crohn's disease. Discontinuation of IFX maintenance...

PTU-072 Outcomes Of The Use Of Infliximab And Adalimumab In Patients With Crohn’s Disease At A District General Hospital

IntroductionInfliximab (IFX) and adalimumab (ADA) are licensed for the treatment of severe Crohn’s disease (CD). NICE recommends patients should receive these agents as a planned course of treatment for 12...

Utilidad clínica de la cuantificación de infliximab y anticuerpos antiquiméricos humanos

Introductioninfliximab (IFX), a chimeric antibody against tumour necrosis factor-alpha, is used in the treatment of patients with several inflammatory diseases, but it can lead to the formation of human anti-chimeric antibodies (HACA). HACA and low IFX serum levels have been associated with lack or loss of response, and infusion reactions. The usefulness of measuring the IFX and HACA concentrations is evaluated. Material and methodsIFX and HACA were measured using a relatively new ELISA technique in a cohort of 110 patients treated with IFX. Serum samples were collected immediately before patients were given the next drug infusion. The patients had received a median dose of 5mg/kg, with dose intervals adjusted to the patient's disease activity, usually every 8 weeks. The median number of infusions was 17. ResultsHACA were identified in 10 patients, and therapeutic IFX concentrations were observed in 37 patients. Eight out of 10 positive HACA patients had gastrointestinal disorders, and the therapy was discontinued in 9 of them. The concomitant use of immunosuppressants did not reduce the risk of HACA formation. Among 100 patients with no HACA, 79 continued on the same dose, 16 required a dose adjustment, 2 discontinued treatment, and 3 were switched to another biological agent. ConclusionsBlood IFX and HACA concentrations should be monitored in patients receiving IFX, as it may be useful to optimize dose regimens or avoid use of inadequate therapy.

PMO-227 Infliximab induction therapy alone for ulcerative colitis does not result in long term remission

IntroductionInfliximab (IFX) has demonstrated efficacy in moderate to severe ulcerative colitis (UC) with a reduction in short-term colectomy rates.1 In the UK, the National Institute for Health and Clinical Excellence...

PTU-102 Re-treatment with infliximab after a prolonged drug holiday in patients with Crohn's disease

IntroductionInfliximab (IFX) is a chimeric monoclonal antibody effective for inducing and maintaining remission in Crohn's disease. The safety and efficacy of retreatment with IFX after a short “drug holiday” was...

Predictors of response and loss of response to infliximab therapy for crohn's disease: a large UK single centre experience

IntroductionInfliximab (IFX) is licensed for use in Crohn's disease (CD) in the UK. Data from randomised controlled trials demonstrate that IFX is more effective than placebo at inducing remission of...

Infliximab rescue therapy for steroid refractory acute severe ulcerative colitis in the exeter ibd cohort

IntroductionInfliximab (IFX) has been shown to be efficacious in the treatment of steroid refractory acute severe ulcerative colitis (ASUC) with reduced rates of colectomy at index admission and at 3-year...