Discontinuation Of Infliximab Research Articles

Infliximab Tissue Concentrations in Patients With Stable Ulcerative Colitis Are Correlated With More Durable Infliximab-associated Disease Remission.

We aimed to determine the correlation between tissue and plasma infliximab concentrations in an outpatient ulcerative colitis (UC) cohort based on histologic disease activity in addition to their relationship with long-term clinical outcomes. We assessed intraparticipant variability in infliximab concentrations between adjacent intestinal samples and the correlation between disease activity and tumor necrosis factor-α (TNF-α). A prospective cohort study was conducted in participants with UC receiving infliximab. Blood and 2 sigmoid colon biopsies were obtained at the index colonoscopy for infliximab and TNF-α quantification. Histological disease activity was assessed. Participants were followed for 2 years for the occurrence of hospitalization, surgery, disease relapse, and infliximab discontinuation. A positive correlation was observed between mean plasma and uninflamed tissue infliximab concentrations only (Rs = 0.75, P = .0071). Lower mean tissue infliximab concentrations correlated with a shorter time to disease relapse vs those with higher mean tissue concentrations (Rs = 0.77, P = .032). This was not seen when using plasma infliximab concentrations. Additionally, no significant intraparticipant variability of infliximab concentrations was observed for all participants independent of disease activity. Neither plasma nor tissue TNF-α correlated with disease activity. These findings support data generated in patients with Crohn's disease: plasma infliximab concentrations are reflective of infliximab exposure in tissue in the UC patient in remission, but not for those with active disease. Increasing tissue concentrations in the noninflamed tissues may improve durability of infliximab. Neither plasma nor tissue TNF-α appear to correlate with UC disease activity. Larger follow-up studies would be of benefit.

Does the introduction of an infliximab biosimilar always result in savings for hospitals? A descriptive study using real-world data

BackgroundBiosimilars are biologic drugs that have the potential to increase the efficiency of healthcare spending and curb drug-related cost increases. However, their introduction into hospital formularies through initiatives such as non-medical switching must be carefully orchestrated so as not to cause treatment discontinuation or result in increased health resource utilization, such as additional visits or laboratory tests, among others. This retrospective cohort study aims to assess the impact of the introduction of CT-P13 on the healthcare expenditures of patients who were treated with originator infliximab or CT-P13.MethodsGastroenterology, immunoallergology and rheumatology patients treated between September 2017 and December 2020 at a university hospital in Western Switzerland were included and divided into seven cohorts, based on their treatment pathway (i.e., use and discontinuation of CT-P13 and/or originator infliximab). Costs in Swiss francs were obtained from the hospital's cost accounting department and length of stay was extracted from inpatient records. Comparisons of costs and length of stay between cohorts were calculated by bootstrapping.ResultsSixty immunoallergology, 84 rheumatology and 114 gastroenterology patients were included. Inpatient and outpatient costs averaged (sd) CHF 1,611 (1,020) per hospital day and CHF 4,991 (6,931) per infusion, respectively. The mean (sd) length of stay was 20 (28) days. Although immunoallergology and rheumatology patients had higher average costs than gastroenterology patients, differences in costs and length of stay were not formally explained by treatment pathway. Differences in health resource utilization were marginal.ConclusionsThe introduction of CT-P13 and the disruption of patient treatment management were not associated with differences in average outpatient and inpatient costs and length of stay, in contrast to the results reported in the rest of the literature. Future research should focus on the cost-effectiveness of non-medical switching policies and the potential benefits for patients.

Outcomes of a mandatory non-medical switch of infliximab to a biosimilar for inflammatory bowel disease in British Columbia, Canada

Abstract Background Despite infliximab biosimilars becoming widely used in inflammatory bowel disease (IBD) patients, real-world non-medical switching is sparse. A biosimilar non-medical switch was launched in British Columbia in 2019, the first Canadian province to do so, from Remicade to an approved biosimilar (CT-P13 or SB2). Aims This study aims to obtain real-world evidence evaluating the clinical outcomes of non-medical switching from Remicade to the infliximab biosimilars. Methods This is a retrospective observational study of stable IBD patients from the IBD Centre of BC who underwent the non-medical infliximab switch. The primary outcome is treatment continuation at 12 ± 2 months post-switch. Secondary outcomes include frequency of loss of response, adverse events, and immunogenicity within the first 12 months post-switch. A control group of patients maintained on the originator served as a comparison. Results Patients in the biosimilar switch group (n = 264) and originator group (n = 99), show similar demographics and disease characteristics. There was no difference in infliximab continuation between the biosimilar group (94.9%) and the originator group (90.1%) (P = 0.18). Reasons for discontinuation of infliximab included loss of response (4.04% vs 4.91%), immunogenicity (1.01% vs 0.75%), or adverse effect (1.01% vs 2.3%) in the infliximab originator vs biosimilar switch group, respectively. Similarly, no differences in safety or efficacy were observed between patients switched to CT-P13 or SB2. Conclusions Non-medical biosimilar switch of infliximab demonstrates similar clinical outcomes compared to originator molecule continuation for therapy of IBD. These data support the safety and efficacy of non-medical infliximab switching in IBD patients.

Clinical consequences of infliximab immunogenicity and the effect of proactive therapeutic drug monitoring: exploratory analyses of the randomised, controlled NOR-DRUM trials

Antidrug antibodies to TNF inhibitors might affect clinical outcomes. Proactive therapeutic drug monitoring allows for early detection of antidrug antibodies and might reduce negative clinical consequences. We aimed to explore how antidrug antibodies to the TNF inhibitor infliximab influence treatment outcomes, and to assess the effect of proactive therapeutic drug monitoring. This was a predefined exploratory analysis of data from the randomised, controlled NOR-DRUM trials. The trials were conducted in rheumatology, gastroenterology, and dermatology departments at 21 Norwegian hospitals. Adult patients (aged 18-75 years) with immune-mediated inflammatory diseases were randomly assigned to proactive therapeutic drug monitoring or standard infliximab dosing in the NOR-DRUM A trial (30-week follow-up) and the NOR-DRUM B trial (52-week follow-up). Antidrug antibodies were assessed with a drug-sensitive assay before each infusion. The outcomes of remission (at week 30), disease worsening (during 52 weeks), infusion reactions, and infliximab discontinuation were assessed according to the presence of antidrug antibodies and use of therapeutic drug monitoring. Between March 1, 2017, and Dec 12, 2019, 616 patients were included in the NOR-DRUM trials, of whom 615 had at least one serum infliximab and antidrug antibody assessment and were included in the present analyses. Mean age was 45 years (IQR 32-56), 305 (50%) patients were women, and 310 (50%) patients were men. Antidrug antibodies were detected in 147 (24%) patients. Remission at week 30 occurred in 25 (35%) of 72 patients with antidrug antibodies and 180 (54%) of 335 without antidrug antibodies (risk ratio 0·62 [95% CI 0·45-0·86]; p=0·0037). In patients with antidrug antibodies compared with patients without antidrug antibodies, higher rates were found for: disease worsening over 52 weeks (0·76 per person-year vs 0· 35 per person-year, hazard ratio [HR] 2·02 [95% CI 1·33-3·07]; p=0·0009), infusion reactions (0·16 per person-year vs 0·03 per person-year, HR 17·02 [6·98-41·47]; p<0·0001), and infliximab discontinuation (1·00 per person-year vs 0·20 per person-year, HR 6·64 [4·84-9·11]; p<0·0001). These associations were more pronounced in patients with high concentrations of antidrug antibodies than in those with low concentrations of antidrug antibodies. Independent of antibody status, therapeutic drug monitoring was associated with a lower risk of disease worsening (HR 0·41 [0·29-0·59]; p=0·0001) or an infusion reaction (HR 0·30 [0·12-0·73]; p=0·0076), and was associated with an increase in the rate of infliximab discontinuation (HR 1·37 [1·02-1·83]; p=0·037). In patients where antidrug antibodies were detected, remission was less likely to be reached and sustained, and infusion reaction or discontinuation of infliximab was more likely. Timely detection of antidrug antibodies by proactive therapeutic drug monitoring facilitated treatment decisions that reduced the negative consequences, both regarding infliximab effectiveness and safety. This highlights the role of proactive therapeutic drug monitoring in optimising infliximab therapy. Inter-regional KLINBEFORSK grants and South-Eastern Norway Regional Health Authority grants.

P766 No difference in progression of disability 2 years after stopping infliximab or immunosuppressant vs. continuing combination therapy in patients with CD in sustained steroid-free remission: a subanalysis of SPARE

Abstract Background In the SPARE trial, the discontinuation of infliximab (IFX) in patients with Crohn’s disease (CD) in sustained remission under combination therapy (IFX and immunosuppressant therapy), was associated with a significantly higher relapse rate than when continuing combination therapy or discontinuing immunosuppressant therapy. However, a high proportion of patients rapidly recover remission when resuming treatment. The impact of this treatment strategy on functional disability, a major endpoint in assessing CD progression, has been poorly studied. We aimed to compare the evolution of the IBD-disability index (IBD-DI) in patients continuing combination therapy, discontinuing IFX or immunosuppressant therapy. Methods The study of the evolution of the IBD-DI in the 3 groups (combination, IFX withdrawal, immunosuppressant withdrawal), between baseline and the end of study (2 years), was a pre-defined secondary endpoint of the trial. Changes in scores (between baseline and the end of study) were compared using Wilcoxon tests between the arms “combination group” versus “IFX withdrawal group” and between “immunosuppressant withdrawal group” versus “IFX withdrawal group”. Results IBD-DI was available at baseline and at the end of study for 153 patients out of the 211 randomised in the SPARE trial between November 2015 and April 2019 (46 in the combination group, 55 in the IFX withdrawal group, and 52 in the immunosuppressant withdrawal group) and those were included in the analysis. Table 1 summarizes baseline characteristics of these patients. 30 patients had a relapse (6 [13%] of 46 in the combination group, 19 [34.5%] of 55 in the IFX withdrawal group, 5 [9.6%] of 52 in the immunosuppressant withdrawal group). Of 23 patients who had a relapse and were retreated or optimised according to protocol, remission was achieved in 21 patients (1 of 2 in the combination group, 18 of 19 in the IFX withdrawal group, and 2 of 2 in the immunosuppressant withdrawal group). The median IBD-DI at baseline was 12.5 (IQR, 5.36-21.43), without significant differences between the 3 groups. Figure 1 shows changes in the IBD-DI between baseline and the end of study in the 3 groups. There was no significant difference in terms of changes in IBD-DI between the arms "combination group" and "IFX withdrawal group" (p=0.56), or between the arms "immunosuppressant withdrawal group” and "IFX withdrawal group" (p=0.29). Conclusion In patients with CD in sustained steroid-free remission under combination therapy with IFX and immunosuppressant therapy, there was no difference in progression of disability over 2 years between those who continued combination therapy, stopped IFX or stopped the immunosuppressant with the possibility of recycling the medication after a relapse.

P1070 Utilization of HLA-DQA1*05 haplotype testing in routine clinical practice to stratify advanced therapies: A prospective pilot study

Abstract Background A potential association between HLA-DQA1*05 allele and development of anti-drug antibodies in Anti-TNF treated Crohn’s Disease patients is reported in the PANTS study. The utility of stratifying treatment based on the HLA-DQA1*05 status has not been evaluated in a biomarker stratified clinical trial and there are no prospective studies evaluating the impact of using HLADQA1*05 in routine clinical practice to decide on monotherapy versus combo therapy while initiating on anti-TNFs. We aimed to determine the impact of carriage of HLADQA1*05 allele to guide the need for concomitant immunomodulators in IBD patients planned for Infliximab therapy. Methods In our prospective study, 97 adult IBD patients were included. All patients were screened for HLADQ2 haplotype as part of their routine pre-biologic screen. Stratification was done according to the presence of HLA-DQA1*05 haplotype. HLADQA1*05 positive patients were assigned combo therapy with Infliximab combined with either methotrexate or azathioprine. HLADQA1*05 negative patients were given infliximab monotherapy unless another indication for concomitant immunomodulation was present. Patients were followed for a minimum of one year after drug initiation. Primary outcome was drug persistence, expressed as time to discontinuation of infliximab, segregated by the treatment decision based on HLA-DQA1*05 status. Secondary outcomes were proportion of patients developing anti-drug antibodies and time to antibody development. Statistical analysis was done using Kaplan-Meier curves and log-rank test. Results Baseline characteristics are detailed in Table 1. HLA-DQA1*05 was positive in 41/97(42%) of patients and combo therapy was offered to 33/41(80%) of those patients. Immunomodulators were avoided in 39/97(40.2%) patients representing the subset of patients with negative HLADQA*105 to whom no immunomodulator was offered. There was no statistically significant difference in drug persistence rates between the groups treated based on HLA-DQA*105 status. 54/97(55.6%) of the patients developed anti-infliximab antibodies during their follow-up (25/41(60.9 %) in HLA positive and 29/56 (51.7%) in HLA negative). Neutralizing drug antibodies with absent drug levels were detected in 15/97(15.5%) of patients (8/41(19.5%) in HLA positive, 7/56(12.5%) in HLA negative). The median time to antibody development was 33.5 weeks (IQR 22-46.7). Conclusion This is the first prospective study suggesting HLA-DQA1*05 haplotype testing can be used in routine clinical practice to stratify therapy based on the need for immunomodulators in infliximab treated IBD patients. HLA-DQA1*05 negative patients may be started on monotherapy with potential for improving safety and reducing costs of immunomodulator monitoring.

P1058 Safety and effectiveness of subcutaneous infliximab formulation in difficult-to-treat Crohn’s Disease patients with previous exposure to intravenous infliximab: A case-series

Abstract Background Despite the increased therapeutic armamentarium for Crohn’s Disease (CD), a relevant proportion of patients fail to respond to multiple therapies and ultimately require surgery. Intravenous (IV) infliximab (IFX) reinduction after a drug holiday is associated with reduced drug efficacy and both acute and delayed infusion reactions, due to immunological mechanisms and development of antidrug antibodies, and is currently contraindicated. Recently, a subcutaneous (SC) formulation of IFX has been developed, demonstrating equal efficacy and safety with a better immunogenicity profile (i.e. biobetter). This study evaluated the safety and effectiveness of retreatment with SC IFX in CD patients previously exposed to IV IFX. Methods Data were retrospectively collected through the Electronic Medical Record. Patients included were IV IFX-experienced and subsequently treated with SC formulation after a period of drug holiday ≥ 1 year. Collected data included demographics, disease characteristics and activity, current and previous treatment, adverse events, and reasons for previous anti-TNFα discontinuation. Results 12 patients with CD were included. Mean age at diagnosis and disease duration were 16.2 (±6.7 SD) and 15.6 years (±7.4 SD) respectively. All patients had failed at least three biologics, and 7 patients underwent previous surgery. The main reason for IV IFX discontinuation was secondary failure (4 patients, 33%). Median time from IV suspension to SC treatment start was 106.5 months (IQR=98.5) with median treatment duration of 24 (IQR=37.5) and 7.5 (IQR=4.5) months for IV and SC IFX respectively. SC IFX was introduced as an add-on dual biologic therapy in 5 patients (3 treated with Ustekinumab, 2 with Vedolizumab). Overall, one adverse event with SC IFX was reported: a grade 2 serum sickness reaction, which led to treatment discontinuation. No immediate allergic reactions were reported. 10 patients had at least 6 months of follow-up. Median HBI reduction at 6 months from SC IFX begin was significant (p&amp;lt;0.05), varying from 7.5 (IQR=3.5) to 3.5 (IQR=4). C-Reactive Protein levels normalized in 3 (38%) patients, reduced in 2 (25%), and remained stable in 3 (38%). Faecal calprotectin normalized in 2 (29%) patients, reduced in 1 (14%), remained stable in 2 (29%), and increased in 2 (29%). At 6 months steroid free remission rate (HBI≤4) was 66%. Conclusion This is the first report showing that SC IFX reinduction in CD patients previously exposed to IV IFX is safe, even after a long drug holiday. It might be regarded as a rescue option in difficult-to-treat patients, either alone or combined with other immunosuppressants.

Pediatric IBD Patients Treated With Infliximab and Proactive Drug Monitoring Benefit From Early Concomitant Immunomodulatory Therapy: A Retrospective Analysis of a 10-Year Real-Life Cohort.

Limited approval of second-line treatments in pediatric inflammatory bowel disease (pIBD) necessitates optimized use of infliximab (IFX) with proactive therapeutic drug monitoring (TDM). We investigated whether early combo-therapy with an immunomodulator (IMM) provides additional benefit. In the retrospectively reviewed medical records of all children treated with IFX and proactive TDM between 2013 and 2022, IMMearly (IMM ≤3 months since IFX start) was evaluated against IMMother/no (late/short or no IMM) over follow-up of 3 to 60 months. Kaplan-Meier analysis was used to analyze time to loss of response (LOR) with IFX discontinuation or time to antibodies-to-IFX (ATI) development. Three hundred fifteen patients with pIBD were reviewed; of those, 127 with 2855 visits were included (77 CD, 50 UC/IBD-unclassified). Sixty patients received IMMearly, 20 patients IMMother, and 47 had IFX monotherapy. Median follow-up time was 30 and 26 months for IMMearly and IMMother/no, respectively, with comparable proactive TDM. Infliximab treatment persistence was 68% after 60 months. Loss of response was observed in 7 IMMearly and 15 IMMother/no patients (P = .16). Early combo-therapy significantly delayed LOR with IFX discontinuation (median LOR free interval IMMearly 30 months vs IMMother/no 9 months, P = .01). Patients with IMMother/no were 10-, 3- and 2-times more likely to experience LOR with IFX discontinuation after 1, 3, and 5 years, respectively. There were no significant group differences regarding the presence of any positive (>10 arbitrary units per milliliter [AU/mL]) or high (>100 AU/mL) ATI, median ATI concentrations, and ATI-free interval. Early IMM combo-therapy in proactively monitored patients with pIBD significantly prolonged the median LOR free interval compared with late/short or no IMM treatment.

Real-world impact of infliximab precision-guided dosing on management of patients with IBD.

Evaluate the clinical utility of a precision-guided dosing test for infliximab (IFX) and its impact on treatment decision-making for inflammatory bowel disease (IBD). Prospective, multisite, clinical experience program. Health care providers were given access to PredictrPK IFX, a precision-guided dosing test, for their patients with IBD on maintenance IFX therapy. Blood samples were drawn 20 to 56 days post infusion. A Bayesian data assimilation tool used clinical and serologic data to generate individual pharmacokinetic profiles and forecast trough IFX. Results were reported to providers to aid in-therapy management decisions and the decision-making process was assessed through questionnaires. Relationships between forecasted IFX concentration, disease activity, and therapy management decisions were analyzed by logistic regression. PredictrPK IFX was used for 275 patients with IBD by 37 providers. In 58% of cases, providers modified treatment plans based on the results, including dose modifications (41%; of these, one-third decreased dose) and discontinuation (8%) of IFX. Of the 42% where treatment was not modified, 97.5% had IFX levels of 5 µg/mL or greater. Patients with IFX concentrations less than 5 µg/mL were 3 and 7.3 times more likely to have active disease or discontinue IFX, respectively. There was unanimous agreement among providers who completed a postprogram survey that PredictrPK IFX was beneficial in guiding treatment decisions and added more value to their practice than routine therapeutic drug monitoring. PredictrPK IFX enables earlier and more precise dose optimization of IFX in patients with IBD, exerting a substantial impact on treatment decisions that may result in improved health outcomes and overall cost savings.

Serum Concentrations of Infliximab and IL-6 for Predicting One-Year Discontinuation of Infliximab Treatment Owing to Secondary Non-response in Patients with Rheumatoid Arthritis.

Secondary non-response to infliximab (IFX) occurs in some patients with rheumatoid arthritis (RA). Although therapeutic drug monitoring (TDM) is a useful tool to optimize IFX therapy, it is unclear whether it can help to identify the risk of secondary non-response. This study aimed to explore the utility of serum levels of IFX or other biomarkers to predict IFX discontinuation owing to secondary non-response. A single-center, retrospective study was conducted using the Kyoto University Rheumatoid Arthritis Management Alliance cohort database between 2011 and 2020. Serum IFX levels were measured using liquid chromatography-tandem mass spectrometry. An electrochemiluminescence assay was used to quantify serum levels of tumor necrosis factor-α and interleukin-6 and detect anti-drug antibodies. Eighty-four out of 310 patients were eligible for this study. The cutoff levels of biomarkers were determined by receiver operating characteristic analysis. IFX persistence was similar between groups stratified using IFX levels, tumor necrosis factor-α levels, interleukin-6 levels, and anti-drug antibodies positivity. The group with lower IFX and higher interleukin-6 levels had the worst therapy persistence (p = 0.017) and the most frequent disease worsening (90.0%, p < 0.001). Evaluating both interleukin-6 and IFX levels, not just IFX alone, enabled us to identify patients at risk of discontinuing IFX treatment. These findings support the utility of measuring IFX and interleukin-6 levels for successful maintenance therapy for RA.

HLA-DQA1*05 and upstream variants of PPARGC1B are associated with infliximab persistence in Japanese Crohn's disease patients.

Recently, the HLA-DQA1*05 (rs2097432) genetic variation has been reported to be linked to early infliximab (IFX) treatment failure in the Caucasian Crohn's disease (CD) population, but that evidence is scarce in the Asian population. This study aimed to investigate the relationship between rs2097432 and the cumulative discontinuation-free time of IFX (IFX persistence) in 189 Japanese biologics-naive CD patients. We also performed a genome-wide association study (GWAS) to discover novel genetic predictors for IFX persistence. The C allele of rs2097432 significantly increased the risk of early discontinuation of IFX [Hazard ratio (HR) = 2.23 and P-value = 0.026]. In GWAS, one locus tagged by rs73277969, located upstream of PPARGC1B which attenuates macrophage-mediated inflammation, reached genome-wide significance (HR = 6.04 and P-value = 7.93E-9). Pathway analysis suggested association of signaling by PDGF and FCGR activation signaling with IFX persistence (P-value = 8.56E-5 and 5.80E-4, respectively).

Infliximab for vascular involvement in Behçet's syndrome

ObjectiveVascular involvement is an important cause of morbidity and mortality in patients with Behçet's syndrome (BS). We aimed to survey the efficacy and safety of infliximab (IFX) in BS patients with vascular involvement followed in a dedicated tertiary center. MethodsCharts of all BS patients who used IFX for vascular involvement between 2004 and 2022 were reviewed. Primary endpoint was remission at Month 6, defined as lack of new clinical symptoms and findings associated with vascular lesion, lack of worsening of the primary vascular lesion and a new vascular lesion on imaging, and CRP < 10 mg/L. Relapse was defined as development of a new vascular lesion or recurrence of the preexisting vascular lesion. ResultsAmong the 127 patients (102 men, mean age at IFX initiation: 35.8 ± 9.0 years) treated with IFX, 110 (87%) had received IFX for remission induction and 87 of these (79%) were already on immunosuppressives when the vascular lesion requiring IFX developed. The remission rate was 73% (93/127) at Month 6 and 63% (80/127) at Month 12. Seventeen patients experienced relapses. Remission rates were better among patients with pulmonary artery involvement and venous thrombosis compared to patients with non-pulmonary artery involvement and venous ulcers. Fourteen patients had adverse events leading to IFX discontinuation and 4 had died due to lung adenocarcinoma, sepsis, and pulmonary hypertension-related right heart failure due to pulmonary artery thrombosis (n = 2). ConclusionInfliximab seems to be effective in majority of BS patients with vascular involvement, even in those who are refractory to immunosuppressives and glucocorticoids.

Discontinuation of infliximab in patients with Crohn's disease on combination therapy.

Discontinuation of infliximab in patients with Crohn's disease on combination therapy.

Definition of a therapeutic range for predicting long-term infliximab response in patients with inflammatory bowel disease

IntroductionMonitoring plasma levels of Infliximab plays an important role in optimising treatment in patients with inflammatory bowel disease (IBD). The aim of the following study has been to determine the predictive potential of monitoring infliximab plasma levels for sustained clinical response and evaluate its usefulness to improve treatment efficacy and symptom control, in patients with IBD. MethodsThis single-centre retrospective study (2017–2019) included patients diagnosed with IBD treated with infliximab. Serum levels and the occurrence of drug-associated immunogenicity were analysed at Week 8 post-induction and 6, 12 and 24 months. Clinical parameters and inflammatory markers were recorded such as subjective global assessment (SGA), C-reactive protein (CRP) and faecal calprotectin (FC). Factors associated with early discontinuation and dose intensification of infliximab were determined. ResultsMultivariate analysis determined that IFX concentrations>7μg/mL at week 8, and at 6 months, are associated with inflammatory remission (p=0.046, 0.045). IFX>7μg/mL at 12 months predicted remission at 18 months of treatment (p=0.006). IFX values>3μg/mL at 12 months are associated with stable SGA at 18 months (p=0.001). Such values at 18 months are associated with stable SGA at 24 months (p=0.044). Conclusions and relevanceThe predictive potential of monitoring IFX plasma levels as a strategy to evaluate sustained long-term clinical response was confirmed. Our results highlight the importance of its introduction into routine clinical practice to enable early identification of non-responders, treatment optimisation, relapse prevention and improve long-term therapy maintenance.

P753 Comparing long-term outcomes in inflammatory bowel disease patients between switch and non-switch cohorts: no differences in infliximab persistence or safety outcomes after 54 months

Abstract Background Switching patients with inflammatory bowel disease (IBD) from originator to biosimilar infliximab has been demonstrated to be non-inferior to continuing originator infliximab by several studies. However, data comparing treatment outcomes beyond 12-months across switch and non-switch cohorts specific to IBD patients remains comparatively underreported. Here we report long-term (&amp;gt;48 weeks) treatment outcomes of the SAME study, a large-scale parallel cohort study of Australian IBD patients who underwent non-medical switching from originator to biosimilar (CT-P13) (n=204) or continued originator infliximab (n=141). Methods The SAME study was a multi-centre, prospective parallel cohort non-inferiority study across seven Australian hospitals over 48 weeks undertaken between May 2017 to October 2019. The data that we present here is the long-term extension study, obtained retrospectively, which sought to compare long-term infliximab persistence beyond 48 weeks across switch and non-switch cohorts. This study included five of the original seven sites, three of which switched from originator to biosimilar infliximab. The primary outcome was infliximab persistence, defined as the proportion of originator or biosimilar infliximab treated patients from the original cohort at last follow up. Secondary outcomes included disease worsening requiring infliximab dose escalation or discontinuation, rates of adverse events, and development of antibodies to infliximab (&amp;gt;10ng/mL). Results Data from 263 (90 Ulcerative colitis and 173 Crohn’s disease) of 345 (76%) patients enrolled in the original SAME study were included with median follow up of 54.2 months (IQR 46.1-59.3). At last follow-up, 103 (65.5%) and 68 (64.2%) patients across the switch and non-switch cohorts (p = 0.8) remained on infliximab. There were no differences in the proportions that discontinued infliximab due to clinical or biochemical worsening of disease (21.7 v 23.6%, p = 0.72); required infliximab dose escalation (35.2 v 32.4%, p=0.8); developed antibodies to infliximab (5.3 vs 11.3%, p = 0.09) or experienced drug related adverse events (7.8 vs 8.3%, p = 0.8) between switch and non-switch cohorts, at last follow-up. Conclusion Long-term infliximab persistence was similar between switch and non-switch cohorts after a median of 54 months. This study represent one of the longest ‘real-world’ comparisons between switch and non-switch cohorts specific to IBD, and should provide reassurance to clinicians and patients alike.

P410 Long-term persistence and safety of biological drugs in patients with Inflammatory Bowel Disease. Differences between women and men: SEXEII study of ENEIDA

Abstract Background Female sex has been associated with a worse response to anti-TNF drugs and with discontinuation of these drugs in immune-mediated diseases. Data in Inflammatory Bowel Disease (IBD) are unclear. The aims of study are to assess possible differences in long-term treatment persistence and safety of biological drugs between women and men with IBD. Methods Multicenter observational study carried out with data from the ENEIDA registry. Patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) who receive or have received biological drugs, and have had a minimum treatment follow-up of 6 months, were included. We evaluated the first biological treatment used in the patient. Statistic analysis; Regression logistic models were used for safety evaluation. Kaplan-Meier curves, Log-Rank test and COX regression were used to treatment persistance. Results A total of 51,595 patients with IBD were evaluated [ 25,947 with CD (13238 men and 12709 women) and 25,648 with UC (13596 men and 12052 women)]. Mean follow up of 13 years. Biologic use: 28.7% of the evaluated patients had been treated with at least one biologic drug. Biologics use in UC was less common in women than in men (15.5% vs. 17.2%, OR (95%CI): 0.88 (0.81-0.94), p= 0.001) and there were no differences between sexes in CD ( 45.7% in men, 44.7% in women). Infliximab (IFX) and adalimumab (ADA) were the most used drugs (in 8914 and 5269 patients, respectively). Safety evaluation. Women suffered more frequently adverse effects to IFX and ADA than men, being the withdrawal of IFX and ADA due to adverse effects also significantly more frequent in women than in men. Biological treatment persistence in patients with IBD was longer in men than in women [median 3.1 years vs. 2.3 years, p &amp;lt; 0.001]. Female sex was a risk factor of biologic discontinuation [adjusted hazard ratio [aHR] (95%CI): 1.20 (1.14-1.25), p&amp;lt;0.001]. Combotherapy with thiopurines and CD were protective factors for discontinuation [ combotherapy; aHR (95%CI): 0.46 ( 0.44-0.48), p&amp;lt;0.001; CD aHR (95%CI): 0.78 (0.74-0.82), p &amp;lt; 0.001]. In the analysis of each specific biological drug, female sex was identified as independent predictor for discontinuation of IFX [aHR (95%CI) 1.21; 1.13-1.30, p&amp;lt;0.001] and ADA [aHR (95%CI) 1.24; 1.14-1.35, p&amp;lt;0.001] in patients with CD and of IFX in patients with UC [aHR (95%CI): 1.16; 1.05-1.28, p=0.004]. Figure 1. Conclusion 1.The use of biologics in ulcerative colitis seems to be higher in men than in women. 2. Female sex is an independent risk factor for the development of adverse effects to IFX and ADA and for the discontinuation of these drugs. 3. The long-term persistence of IFX and ADA (as first biological treatments) is low, being higher in men compared to women.

Ten-year follow-up of infliximab treatment for uveitis in Behçet disease patients: A multicenter retrospective study.

To evaluate 10-year outcome of infliximab (IFX) treatment for uveitis in Behçet disease (BD) patients using a standardized follow-up protocol. Retrospective longitudinal cohort study. 140 BD uveitis patients treated with IFX enrolled in our previous study. Medical records were reviewed for demographic information, duration of IFX treatment, number of ocular attacks before IFX initiation, best corrected visual acuity (VA) at baseline and 1, 2, 3, 4, 5, and 10 years after IFX initiation, uveitis recurrence after IFX initiation and main anatomical site, concomitant therapies, and adverse events (AEs). 10-year IFX continuation rate and change in LogMAR VA. Of 140 BD patients, 106 (75.7%) continued IFX treatment for 10 years. LogMAR VA improved gradually after initiation of IFX, and the improvement reached statistical significance from 2 years of treatment. Thereafter, significant improvement compared with baseline was maintained until 10 years, despite a slight deterioration of logMAR VA from 5 years. However, eyes with worse baseline decimal VA < 0.1 showed no significant improvement from baseline to 10 years. Uveitis recurred after IFX initiation in 50 patients (recurrence group) and did not recur in 56 (non-recurrence group). Ocular attacks/year before IFX initiation was significantly higher in the recurrence group (2.82 ± 3.81) than in the non-recurrence group (1.84 ± 1.78). In the recurrence group, uveitis recurred within 1 year in 58% and within 2 years in 74%. Seventeen patients (34%) had recurrent anterior uveitis, 17 (34%) had posterior uveitis, and 16 (32%) had panuveitis, with no significant difference in VA outcome. In addition, logMAR VA at 10 years did not differ between the recurrence and non-recurrence groups. AEs occurred among 43 patients (30.7%), and 24 (17.1%) resulted in IFX discontinuation before 10 years. Among BD patients with uveitis who initiated IFX, approximately 75% continued treatment for 10 years, and their VA improved significantly and was maintained for 10 years. Uveitis recurred in one-half of the patients, but visual acuity did not differ significantly from the patients without recurrence.

Discontinuation of infliximab treatment in patients with inflammatory bowel disease who retransitioned to originator and those who remained on biosimilar.

Many patients with inflammatory bowel disease (IBD) have transitioned from an infliximab originator to a biosimilar. However, some patients retransition to the originator (i.e. stop biosimilar and reinitiate the originator). Whether this sign of potential unsatisfactory treatment response is specifically related to the infliximab biosimilar or the patient and/or the disease including patients' beliefs on the biosimilar is unclear. We aimed to compare the risk of and reasons for infliximab discontinuation between retransitioned patients and those remaining on biosimilar. Non-interventional, multicentre cohort study. IBD patients who transitioned from infliximab originator to biosimilar between January 2015 and September 2019 in two Dutch hospitals were eligible for this study. Retransitioned patients (retransitioning cohort) were matched with patients remaining on biosimilar (biosimilar remainder cohort). Reasons for discontinuation were categorised as the unwanted response (i.e. loss of effect or adverse events) or remission. Risk of unwanted discontinuation was compared using Cox proportional hazards models. Patients in the retransitioning cohort (n = 44) were younger (median age 39.9 versus 44.0 years), more often female (65.9% versus 48.9%) and had shorter dosing intervals (median 48.5 versus 56.0 days) than in the biosimilar remainder cohort (n = 127). Infliximab discontinuation due to unwanted response was 22.7% in the retransitioning and 13.4% in the biosimilar remainder cohort, and due to remission was 2.3% and 9.4%, respectively. Retransitioned patients are at increased risk of discontinuing due to unwanted response compared with biosimilar remainder patients (adjusted HR 3.7, 95% CI: 1.0-13.9). Patients who retransitioned due to an increase in objective disease markers had higher discontinuation rates than patients who retransitioned due to symptoms only (66.7% versus 23.7%). Retransitioned patients are at increased risk of infliximab discontinuation due to unwanted response. Retransitioning appeared related to the patient and/or disease and not the product. Clinicians might switch patients opting for retransitioning to other treatment regimens.

A CASE OF SECONDARY ORGANIZING PNEUMONIA FROM INFLIXIMAB

A CASE OF SECONDARY ORGANIZING PNEUMONIA FROM INFLIXIMAB

Flare-up of mucocutaneous leishmaniasis following infliximab discontinuation and antiparasitic therapy in a patient with juvenile idiopathic arthritis.

A 25-year-old patient had been treated for 4 years with infliximab for JIA. He was admitted for nodular and erythematosquamous lesions of the face and ears that had been evolving for 1 year (Fig. 1A). A skin biopsy with PCR allowed the diagnosis of Leishmania infantum mucocutaneous leishmaniasis (MCL). There was no visceral involvement. The patient lived in the south of France and had not travelled to another endemic area. Infliximab was discontinued and, 10 weeks after the last infusion, treatment with liposomal amphotericin-B 18 mg/kg was initiated. On the third day of treatment, he had a sudden but transient worsening of the lesions (Fig. 1B). One month later, he had complete response to the disease and infliximab was reintroduced (Fig. 1C). No recurrence occurred at a 6-month follow-up. TNFα mediates immune control of Leishmania infection but is also responsible for induced tissue damage. About 50 cases of MCL/cutaneous leishmaniasis have been reported in patients with anti-TNFα in the Mediterranean basin [1]. We report the first case of paradoxical worsening of MCL, which could be explained in two ways: immune restoration following anti-TNFα discontinuation, leading to inflammatory tissue destruction, as has been described in HIV-infected patients with leishmaniasis after highly active antiretroviral therapy (HAART) introduction [2]; and/or a ‘pseudo-Herxheimer’ type reaction related to Leishmania lysis.