anti-IFX Ab Research Articles

Drug Levels Associated With Optimal Discrimination Between Remission and Nonremission and Comparison of Antibody Assays During First Year of Stable Infliximab Maintenance Therapy in Inflammatory Bowel Disease.

To implement therapeutic drug monitoring-based strategies for infliximab (IFX) in inflammatory bowel disease, the authors assessed IFX levels for optimal discrimination between remission and nonremission and compared assays for anti-IFX antibodies (Abs). The retrospective cohort comprised 163 bionaive patients with inflammatory bowel disease who received stable IFX maintenance therapy (5 mg/kg every 8 weeks [q8w]) for 1 year. The clinical and biochemical remission status was assessed at all infusions (weeks 14-22-30-38-46-54), and IFX and anti-IFX Abs were estimated using a time-resolved fluorometric assay (n = 690; 88% of infusions). Samples positive for anti-IFX Abs or IFX levels < limit of detection (n = 102) were analyzed by 2 binding assays [enzyme-linked immunosorbent assay (ELISA)] and functional reporter gene assay/drug-tolerant enzyme immunoassay. At all assessed time points, IFX levels were more than double in patients presenting clinical or biochemical remission. An IFX concentration of 4.5 mcg/mL was associated with clinical remission during the entire first year of therapy [sensitivity 54% (49-59), specificity 73% (67-78), AUCROC 0.65 (0.60-0.69), P < 0.0001]; these values were comparable with biochemical remission. Exploratory assessments for endoscopic remission (n = 131) were performed at the discretion of the treating physician. Anti-IFX Abs were associated with undetectable IFX and treatment failure [OR 2.9 (1.4-6.0), P < 0.01], irrespective of persistency or transiency. All performed assays detected anti-IFX Abs were picked up by all assays in ∼2/3 of samples. Binding assays demonstrated a higher sensitivity to anti-IFX Abs. IFX at ∼5 mcg/mL was associated with clinical and biochemical remission during the first year of maintenance therapy. During this phase of therapy, standard binding assays are appropriate for therapeutic drug monitoring.

Therapeutic thresholds and mechanisms for primary non-response to infliximab in inflammatory bowel disease

Background Primary non-response to infliximab (IFX) inherits a poor prognosis in inflammatory bowel disease (IBD). We explored underlying mechanisms and therapeutic thresholds in an effort to provide basis for optimizing therapy. Methods A prospectively followed cohort of 166 IBD patients having received standard IFX induction therapy (5 mg/kg at weeks 2, 6, and 14) had trough IFX and anti-IFX antibodies (Abs) retrospectively assessed at weeks 2 (n = 148) and 6 (n = 108). Circulating TNFα was measured in matched primary non-responders (n = 29) and responders (n = 21) at baseline and weeks 6 and 14. Clinical outcome at week 14 was supported by disease activity scores in half of patients. Results In all, 18 patients (11%) had primary non-response. Infliximab was consistently lower throughout the induction phase in non-responders as compared to responders (Week 2: IFX median 18.9 μg/mL vs. 23.3, p < .05. Week 6: 8.4 vs. 17.0, p < .05). Optimal IFX thresholds associated with response was 22.9 μg/mL at week 2 (sensitivity 51%, specificity 80%, AUCROC 0.67, p < .05) and 11.8 at week 6 (72%, 77%, 0.71, p < .05). Anti-IFX Abs occurred in 28% of primary non-responders and associated with low IFX and treatment failure (OR 13.7 [2.8–67.5], p < .01). Markers of disease activity (disease activity scores, albumin, CRP) also associated with low IFX. Circulating TNFα was higher throughout induction in non-responders with ulcerative colitis but not Crohn’s disease. Conclusion IBD patients with primary IFX failure generally have lower IFX trough than responders during early induction phase. Pharmacokinetic failure seems common in ulcerative colits, whereas pharmacodynamic failure appears common in Crohn’s disease.

A Role for Thiopurine Metabolites in the Synergism Between Thiopurines and Infliximab in Inflammatory Bowel Disease.

Interactions between principal cytotoxic thiopurine metabolites, that is 6-thioguanine nucleotides [6-TGN], and infliximab [IFX] and anti-IFX antibodies [Abs] may contribute to higher effectiveness of IFX-thiopurine combination therapy than monotherapies in inflammatory bowel disease. To examine if thiopurine metabolites influenced trough IFX and anti-IFX Abs, 89 patients previously assessed for anti-IFX Abs were included. To assess if IFX influenced thiopurine metabolites, eight patients who had responded to 12 weeks of intensified IFX at a constant thiopurine dosing were included. In the first cohort, IFX-thiopurine combination therapy reduced anti-IFX Ab detection [8/40; 20%] as compared with IFX monotherapy [22/49; 45%], odds ratio [OR] 0.31 [0.12-0.80], p < 0.05. 6-TGN was significantly lower in anti-IFX Ab-positive patients (50 pmol/8 × 108 red blood cells [RBC] vs 105, p < 0.01). All anti-IFX Ab-positive patients had 6-TGN < 117 pmol/8 × 108 RBC (sensitivity 100% [63-100], specificity 47% [29-65], area under the curveROC = 0.82, p < 0.01). Trough IFX was similar between anti-IFX Ab-negative patients in IFX monotherapy and IFX-thiopurine combination therapy [5.1 μg/mL vs 4.9, p = 0.76]. 6-TGN and IFX did not correlate [rP = 0.04, p = 0.83; rS = 0.02, p = 0.89, respectively]. In the second cohort, trough IFX increased during IFX intensification [ΔIFX median 6.5 μg/mL, p = 0.02], but 6-TGN was stable [6-TGN at Weeks 0, 4, 8, 12: 90 pmol/8 × 108 RBC, 93, 101, 90; p > 0.05]. Methylated mercaptopurine metabolite associations were consistently negative. Superior effect of IFX-thiopurine combination therapy over monotherapies partly relates to decrease in anti-IFX Abs, which associates with 6-TGN levels and has a lower therapeutic threshold than during thiopurine monotherapy. Additional benefit likely ascribes to synergy between different anti-inflammatory modes of action rather than direct drug interactions.

Infliximab Assay Used in Clinical Practice Validated for Measuring SB2 Infliximab Biosimilarʼs Serum Drug and Anti-drug Antibody Levels

Introduction: Study aimed to validate suitability of assays from THERADIAG (available in US via Miraca Life Sciences as InformTXTM, promoted as LISA-TRACKER (LT) outside of US) for monitoring of patients treated with Infliximab (IFX) biosimilar developed by Samsung Bioepis (SB2). LT has been developed to quantify IFX and Anti-IFX antibodies (Ab) in human serum/plasma for monitoring of patients treated with originator IFX (Remicade®). Methods: For IFX quantification, recombinant human TNFa on solid phase was used to catch IFX, and biotinylated anti-human-IgG for the detection step. For Anti-IFX quantification, IFX was coated on solid phase, and biotinylated IFX was used for the detection step. For both assays, conjugate and substrate were used before the reading of optical density (OD). Level of IFX or Anti-IFX was proportional to OD. 2 batches of SB2 were assessed. 3 human serum matrix were used to prepare spiked samples. 58clinical samples were collected from US patients treated with originator IFX. Inhibition assays were performed in using polyclonal Ab. Results:IFX ASSAY:SB2 spiked samples gave % of recovery between 81% and 105%. Coefficients of variation ranged from 2.2% to 10.3% for intra-run and from 4.4% to 12.7% for inter-run precision assay. Clinical samples with detectable levels of IFX spiked with SB2 or originator IFX gave similar results. IFX assay gave consistent results even if SB2 is quantified after storage of samples during 7 days at +2°C+8°C, or 3 days at room temperature, or after 5 freeze/thaw cycles. ANTI-IFX ASSAY:All clinical samples with a detectable level of Anti-IFX Ab were inhibited when originator IFX or SB2 were added to the samples. SB2 has the capacity to block detection of Anti-IFX Ab when added to detection reagent. Very good correlation was obtained when originator IFX or SB2 were used for reagents production: R2>0.97; 0.91 Conclusion: LT IFX assay gave high precision and accuracy for quantification of SB2. Behavior of SB2 and originator IFX in tested LT assays is similar. Results indicate that Anti-IFX Ab induced by SB2 should be detected with LT Anti-IFX assay. InformTXTM, or LT, are suitable for monitoring of patients treated with SB2. Study demonstrated that the assay can be used interchangeably for monitoring drug level and Anti-IFX for originator IFX and SB2.

Magnitude of Increased Infliximab Clearance Imposed by Anti-infliximab Antibodies in Crohn's Disease Is Determined by Their Concentration.

Antibodies (Abs) against infliximab (IFX) increase IFX clearance and can result in treatment failure and acute hypersensitivity reactions. However, interpretation of their clinical value is complicated by individual differences in Ab responses and methods used for quantification. The increase in IFX clearance imposed by anti-IFX Abs has generally been evaluated using a binary classification, i.e., positive or negative. This analysis aimed to investigate if anti-IFX Ab concentrations provide a more adequate prediction of alterations in clearance. Data originated from a clinical trial on Crohn's disease patients with IFX treatment failure. The trial was not originally designed for pharmacokinetic analysis. Therefore, published pharmacokinetic models were utilized as priors to enable covariate investigation. The impact of anti-IFX Abs on clearance was assessed using different mathematical relationships and exploiting information from two different quantification assays, measuring semi-quantitative "total" or "unbound neutralizing" concentrations of anti-IFX Ab, respectively. Inclusion of anti-IFX Ab status/concentration improved the model's performance for all investigated relationships. The anti-IFX Ab concentrations were superior to the binary classifications, indicating that the magnitude of increase in IFX clearance imposed by anti-IFX Abs closely relates to their concentration. Furthermore, total anti-IFX Ab concentrations appeared superior to the unbound neutralizing fraction in identifying high clearance individuals. Simulations showed that even at low concentrations, anti-IFX Abs lead to sub-therapeutic IFX concentrations, supporting a need of treatment interventions in all anti-IFX Ab positive patients. The developed model can serve as a basis for further investigations to refine treatment recommendations for patients with anti-IFX Abs.

Comparison of Commercially Available Assays for Infliximab Concentrations and Antibodies to Infliximab With Assays Developed at Janssen and Used in Clinical Studies of Remicade®: Iinfliximab in IBD Patients Presidential Poster

Introduction: Infliximab (IFX) concentrations and antibodies (Ab) to IFX (ATI) titers can be informative in assessing IBD response. In collaboration with KU Leuven, Sanquin, Dynacare and LabCorp, the accuracy and reliability of commercially available IFX and ATI assays were compared to assays used by Janssen for Remicade®(IFX) IBD studies. Methods: Samples were prepared by Janssen and shipped to labs. KU Leuven* and Dynacare used enzyme-linked immunosorbent assay (ELISA) to measure IFX and ATI. Sanquin used ELISA to measure IFX and a radioimmunoassay to measure ATI. LabCorp used electrochemiluminescence immunoassay (ECLIA) to measure IFX and ATI. Janssen used ELISA for IFX quantification, and ELISA (“old”) and ECLIA (“new”) for ATI assessments. Results:IFX Assays: Specificity: All assays were specific as they detected IFX, but not 5mg/mL of adalimumab, certolizumab pegol, golimumab or siltuximab. Selectivity: TNFa (0.5 - 50 ng/mL) did not interfere with IFX detection; ATI titers >10 interfered with IFX assessment. Accuracy: Confirmed by 3 independent measurements of IFX (0.125-20mg/mL) spiked sera from untreated IBD patients and with IFX measured in sera from IFX-treated IBD patients. Precision: IFX assays were precise, determined by inter-occasion reproducibility (2wks between assays; Dynacare assessed the same day). The correlation of Janssen IFX results to IFX results from Sanquin, Dynacare, KU Leuven, and LabCorp were 0.936, 0.945, 0.968 and 0.972, respectively. ATI assays: Specificity: Assays were specific in detecting anti-IFX Ab, and not affected by high titers of Ab against other monoclonal Ab drugs (ustekinumab and golimumab). Selectivity: Sanquin, LabCorp and new Janssen methods were drug tolerant (IFX >10ug/mL); ATI results from Dynacare and KU Leuven were affected by IFX concentrations at 2ug/mL or higher. Concentrations of free or bound TNFa (≤5ng/mL) did not interfere with ATI detection; a supraphysiologic TNFa concentration (50ng/mL) resulted in false positive results except Sanquin's. Precision: All assays were reproducible (2 wks between assays; Dynacare assessed samples same day). Conclusion: Results from all labs were similar and significantly correlated to the results of Janssen assays. These results may aid in interpretation of data from commercial assays and assays used in IBD clinical studies of Remicade (IFX).

Changes in serum trough levels of infliximab during treatment intensification but not in anti-infliximab antibody detection are associated with clinical outcomes after therapeutic failure in Crohn's disease.

Intensification of the infliximab (IFX) regimen is recommended if the treatment effect is inadequate. However, the rationale for this is not well defined as the underlying mechanisms vary. The aim of this study was to explore the association between changes in serum IFX and anti-IFX antibodies (Abs) after IFX intensification and clinical outcomes. We performed a post hoc analysis of a randomized clinical trial including 42 Crohn's disease patients with IFX treatment failure, all treated with an intensified IFX regimen (5mg/kg every 4 week) for 12 weeks. Trough serum IFX and anti-IFX Ab concentrations were measured by a homogeneous mobility shift binding assay (HMSA) and a functional cell-based reporter gene assay (RGA) at treatment failure and the end of the trial. Twenty-one patients (50%) regained clinical response on the intensified IFX regimen. The increase in serum trough levels of IFX during treatment intensification was higher among responders than non-responders (RGA, 8.8 versus 3.0 μg/mL, p = 0.035; HMSA, 9.9 versus 4.7 μg/mL, p = 0.040), and differentiated patients by clinical outcome (RGA, area under receiver operating characteristic curve [AUC] 0.75 [0.53-0.97], p = 0.035; HMSA, AUC 0.74 [0.53-0.95], p = 0.042). All responders exhibited an IFX increase ≥2.6 μg/mL (sensitivity 100%, specificity 50%). Anti-IFX Abs detected by HMSA in 13 patients (32%) were often non-functional and became undetectable during IFX intensification. However, even functional anti-IFX Abs detected by RGA in six patients (15%) became undetectable. Increase in IFX levels following treatment intensification was associated with improved clinical outcomes, indicating insufficient drug levels in a subgroup of patients. Anti-IFX Abs may become undetectable during treatment intensification, suggesting lowered production or the formation of immune complexes.

Clinical implications of measuring drug and anti-drug antibodies by different assays when optimizing infliximab treatment failure in Crohn's disease: post hoc analysis of a randomized controlled trial.

Cost-effective guidance of therapeutic strategy in Crohn's disease patients with secondary infliximab (IFX) treatment failure may be achieved by serum IFX and anti-IFX antibody (Ab) measurements by radioimmunoassay (RIA). This study investigated implications of using other techniques for this purpose. This is a post hoc analysis of randomized clinical trial including 66 Crohn's disease patients with IFX failure in whom IFX and anti-IFX Ab measurements by RIA had been used for therapeutic guidance. Samples were additionally assessed by enzyme-linked immunosorbent assay (ELISA), homogeneous mobility shift assay (HMSA), and functional cell-based reporter gene assay (RGA). IFX detection was comparable between assays (82% RIA, 76% ELISA, 88% HMSA, and 74% RGA), and it correlated significantly (Pearson's r=0.91-0.97, P<0.0001). However, IFX concentrations varied systematically between all pair of assays except RIA-RGA. Anti-IFX Ab detection was variable (27% RIA, 9% ELISA, 33% HMSA, and 11% RGA), but correlated significantly (Pearson's r=0.77-0.96; P<0.0001). Anti-IFX Abs detected by RIA and HMSA were often from sera without drug-neutralizing activity (RGA). Assays agreed on classification of underlying mechanism for treatment failure in most cases (79-94%). The majority (74-88%) failed IFX owing to pharmacodynamic problems, or had noninflammatory pathophysiology for symptoms resembling relapse. Applied threshold for therapeutic vs. subtherapeutic IFX level influenced classifications. The four different assays did not differ in terms of the ability to predict response to interventions defined by the algorithm. Despite variable analytical properties, common assays result in similar classifications and interventions in patients with IFX treatment failure, and with comparable clinical outcomes. Implications are, however, profound for the minority classified differently.

Comparison of Techniques for Monitoring Infliximab and Antibodies Against Infliximab in Crohn's Disease

Several techniques are used to measure infliximab (IFX) and anti-IFX antibodies (Abs) in Crohn's disease. The aim of this study was to compare different assays for this purpose. Fluid-phase radioimmunoassay (RIA), solid-phase enzyme-linked immunosorbent assay (ELISA), reporter gene assay (RGA), and enzyme immunoassay (EIA; anti-IFX Ab only) were assessed. IFX was added to pooled serum from 13 patients with inactive Crohn's disease to yield concentrations of 0, 1, 3, and 9 µg/mL. Anti-IFX Abs were assessed in 6 patients. IFX assessments: RIA and RGA had lower limit of detection than ELISA (0.07 µg/mL and 0.13 versus 0.26). Maximal inaccuracies were 39%, 24%, and 23%. Imprecisions (coefficients of variation) were ≤20% within IFX concentrations between 1 and 9 µg/mL. All assays showed linear correlations (R = 0.97-0.99), but sample concentrations differed by up to 1.55 µg/mL for RIA and RGA, 1.41 µg/mL for ELISA and RIA, and 0.48 µg/mL for ELISA and RGA (P < 0.05). Anti-IFX Ab assessments: RGA gave highly reproducible results (coefficients of variation ≤ 7%) compared with all others (24%-26%). All assays had linear correlations (R = 0.71-0.93), except ELISA versus RGA and EIA. Assays disagreed on anti-IFX Ab titers with mean difference -420 (-1200 to 210) in RGA and EIA, and up to 4500 (-2700 to 11,800) in RIA and RGA. A contributing factor to these discrepancies was inability of ELISA to detect IgG4 anti-IFX Abs. Performances of assays for IFX and anti-IFX Abs are comparable. However, IFX concentrations and anti-IFX Ab titers show systematic differences, and in individual patients, only the same assay should be used. Problems may arise when different assays are used to manage therapies in the same patient.

THU0215 Establishing Cut-Off of Infliximab and Anti-Infliximab Antibody Levels Using a Commercial Elisa in Patients with Rheumatoid Arthritis

BackgroundInpatients with rheumatoid arthritis (RA) the reasons for failure or loss of response to infliximab (IFX) are controversial, so far both IFX serum levels and the presence of antibodies (Ab)...

THU0282 Clinical efficacy to a second anti-tnf therapy is associated with the development of antibodies against the first anti-TNF therapy in patients with spondyloartrhitis

BackgroundSpondyloarthropathies (SpA) include a heterogeneous group of rheumatic diseases that mainly affect the axial skeleton and entheses. Despite the anti-TNF therapy has been demonstrated effective in SpA patients, about 30%...

Pre‐existing IgG antibodies cross‐reacting with the Fab region of infliximab predict efficacy and safety of infliximab therapy in inflammatory bowel disease

Infliximab (IFX) is a chimeric murine/human anti-TNF antibody (Ab) used for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Loss of response is common and associated with development of anti-IFX Abs during ongoing therapy. However, human anti-murine immunoglobulin Abs are common and may cross-react with the murine part of IFX. To investigate if Abs binding to IFX's Fab region (IFX-Fab) are present in IBD patients before exposure to IFX, and whether they predict efficacy and safety of IFX therapy. Observational, retrospective cohort study of patients with CD (n=29) and UC (n=22). Pre-treatment levels of IFX-Fab reactive IgG Abs were significantly lower in CD patients in remission after 1year of maintenance IFX (median 91mU/L, n=8) than in the rest of the patients (639mU/L, n=21; P<0.01), and lower than in patients with secondary loss of response in particular (692mU/L, n=7; P<0.01). A cut-off concentration of <439mU IFX-Fab reactive IgG Ab per litre comprised all patients who later obtained long-term sustained remission on IFX (sensitivity 100%, specificity 67%). Similar trends were observed in UC. The pre-treatment levels of IFX-Fab reactive IgG Abs were markedly higher in patients developing infusion reactions to IFX (1037mU/L, n=7) than in the remaining patients (349mU/L, n=44; P=0.036). IFX-Fab reactive IgG antibodies present in serum from IBD patients before infliximab therapy associate with lack of long-term efficacy and safety. Assessments of such antibodies may help clinicians to choose between treatment with infliximab and more humanised agents.

Clinical implications of variations in anti-infliximab antibody levels in patients with inflammatory bowel disease

The aim of the study was to investigate variations in anti-infliximab (IFX) antibody (Ab) levels and clinical implications thereof in patients with inflammatory bowel disease (IBD). A retrospective, explorative, single-center study of patients with IBD who developed anti-IFX Ab and in whom anti-IFX Ab were reassessed. IFX was administered to 316 patients; anti-IFX Ab was determined in 180 patients and detected in 83 (46%). During ongoing IFX maintenance therapy, anti-IFX Ab disappeared at later reassessment in two-thirds of patients with clinical response after median 4 (3-5) infusions. In contrast, anti-IFX Ab persisted in all patients without clinical response. Anti-IFX Ab appeared pharmacologically active, as IFX levels were high when anti-IFX Ab disappeared (median 3.7 μg/mL, interquartile range [IQR] 2.8-5.5), while undetectable or low when anti-IFX Ab persisted (median 0 μg/mL, IQR 0-0). In 56 patients, anti-IFX Ab were assessed after IFX discontinuation. The proportion of patients with anti-IFX Ab gradually declined over time, with a few patients having anti-IFX Ab up to about 4 years after initial assessment. No variables were associated with anti-IFX Ab disappearance in multivariate analysis. Discontinuation of IFX is advisable in patients with inadequate response and repeat positive anti-IFX Ab measurements. Anti-IFX Ab can persist for years after discontinuation, which could impact efficacy and safety at retreatment. Continued IFX treatment may, however, be considered in patients with clinical response and a single positive anti-IFX Ab measurement, as anti-IFX Ab disappears in two-thirds of these during continued treatment.

Severe infusion reactions to infliximab: aetiology, immunogenicity and risk factors in patients with inflammatory bowel disease

Infliximab (IFX) elicits acute severe infusion reactions in about 5% of patients with inflammatory bowel disease (IBD). To investigate the role of anti-IFX antibodies (Ab) and other risk factors. The study included all IBD patients treated with IFX at a Danish university hospital until 2010 either continuously (IFX every 4-12 weeks) or episodically (reinitiation after >12 weeks). Anti-IFX Ab were measured using radioimmunoassay. Twenty-five (8%) of 315 patients experienced acute severe infusion reactions. Univariate analysis showed that patients who reacted were younger at the time of diagnosis (19 vs. 26 years, P=0.013) and at first IFX infusion (28 vs. 35 years, P=0.012). Furthermore, they more often received episodic therapy (72% vs. 31%, P<0.001) and logistic regression revealed this as the only significant predictor of reactions (OR 5 [2-13]; P<0.001). IFX reinitiation after 6 months intermission further increased the risk (OR 8 [3-20], P<0.001). Most reactions (n=14, 88%) occurred at 2nd infusion in the 2nd treatment series (P=0.006). Anti-IFX IgG Ab were highly positive in 19 of 20 patients (95%) shortly after the reactions (median 84 U/mL). Anti-IFX IgG Ab measured prior to the retreatment series were negative in 7 of 11 patients tested (64%). Anti-IFX IgE Ab were negative in all patients with reactions. Acute severe infusion reactions were strongly associated with development of anti-IFX IgG Ab, but not with anti-IFX IgE Ab. The risk was particularly high at the 2nd infusion in retreatment series. Negative anti-IFX Ab before reinitiation did not rule out reactions.

Influence of anti-infliximab antibodies and residual infliximab concentrations on the occurrence of acquired drug resistance to infliximab in rheumatoid arthritis patients

Background Infliximab (IFX) can be immunogenic for humans and lead to the formation of antibodies against IFX (anti-IFX Ab), which could induce acquired IFX resistance. Objective To test whether the presence of anti-IFX Ab and residual circulating IFX levels are associated with acquired IFX resistance in RA. Methods A multivariate logistic regression was used to analyze the relationship between anti-IFX Ab, residual IFX concentrations, and acquired IFX resistance in a nested cohort within the Swiss RA registry (SCQM-RA). Results Sixty-four RA patients on longstanding IFX therapy were included; 24 with an acquired therapeutic resistance to IFX and 40 with continuous good response to IFX. The two groups had similar disease characteristics, but patients with acquired IFX resistance required significantly higher dosage of IFX (5.4 mg/kg versus 4.3 mg/kg, p = 0.02) and shorter infusion intervals (7.1 versus 8.7 weeks, p = 0.01) than long-term good responders. The presence of residual IFX tended to be associated with a decreased risk of acquired therapeutic resistance (OR 0.4 [95% CI: 0.1–1.5]), while the presence of anti-IFX Ab tended to be associated with an increased risk of acquired therapeutic resistance (OR: 1.8 [95% CI: 0.4 – 9.0]). The presence of either high anti-IFX Ab levels or low residual IFX concentrations was strongly associated with acquired therapeutic resistance to IFX (OR 5.9, 95% CI 1.3 – 26.6). However, just 42% of patients with acquired IFX resistance had either low IFX or high anti-IFX Ab levels. Conclusion These results suggest that the assessment of anti-IFX Ab and residual IFX levels is of limited value for individual patients in routine clinical care.