Antibodies In Clinical Practice Research Articles

Analysis of thyroid stimulating immunoglobulins vs conventional TSH-receptor antibodies in clinical practice

Analysis of thyroid stimulating immunoglobulins vs conventional TSH-receptor antibodies in clinical practice

Real World Prescribing: Use of Anti-Amyloid Antibodies in Clinical Practice

Anti-amyloid antibody therapy is now available for clinical use in MCI due to Alzheimer's disease and mild Alzheimer's dementia. This symposium will focus on clinical aspects of screening, prescribing and safety monitoring. The first talk will address patient eligibility and therapy implementation. The speaker will discuss disease staging and how to recognize neuroimaging abnormalities and concomitant medications that would exclude patient from eligibility. The speaker will explore use of CSF or amyloid PET to confirm amyloid pathology and use of ApoE genotyping to assess ARIA risk. There will be emphasis on ways to provide treatment specific education to patients and their care partners. Lastly, the speaker will demonstrate infusions orders and utilization of CMS registry for Medicare coverage.The second talk will move to management issues once a patient starts receiving antibody therapy, such as identifying and treating infusion reactions. Our neurologist speaker will define and review the edema and hemorrhage subtypes of Amyloid-Related Imaging Abnormalities (ARIA-E and ARIA-H respectively). The speaker will recommend MRI monitoring schedule and provide strategies to reduce risk and manage ARIA.The final talk will utilize case studies to demonstrate best practices. The speakers will share lessons learned from their collective expertise. The panel acknowledges two different providers on the care spectrum - one being a treating provider and one being a referring provider. Referring providers will learn to create a comprehensive referral, ensuring efficient treatment transition.At time of submission, there are pending issues relevant to this symposium. Commercial insurance and Medicare Advantage plans are currently clarifying their position on drug coverage and patient registry requirement. CMS has proposed a coverage pathway for amyloid PET scans, currently in an open-comment period. There could be an introduction of an AD blood test, but it is unclear if would be acceptable for pathology confirmation. The speakers will address these updates.

Changing Trends in B-Cell Non-Hodgkin Lymphoma Treatment: The Role of Novel Monoclonal Antibodies in Clinical Practice.

We are currently witnessing a dramatic shift in our approach to the treatment of B-cell non-Hodgkin lymphoma (B-NHL). In the evolving clinical landscape, novel treatments for this clinically heterogeneous disease span a wide range of interventions, encompassing targeted agents, cell therapy approaches, and novel monoclonal antibodies (NMABs). Among these, the latter are likely to exert the most profound impact due to their distinctive high efficacy and versatile applicability. NMABs represent a heterogeneous group of agents, including naked antibodies, immunotoxins, and T-cell-engaging molecules. In recent times, several NMABs have either gained regulatory approval or are on the verge of introduction into clinical practice, addressing multiple therapeutic indications and treatment regimens. Their anticipated impact is expected to be broad, initially in the context of relapsed/refractory (R/R) disease and subsequently extending to early treatment lines. The scope of this review is to provide a comprehensive overview of the biological characteristics, clinical properties, efficacy, and toxicity profiles of NMABs that have recently been introduced or are nearing integration into clinical practice.

Clinical Significance of Different Profiles of anti-Ro Antibodies in Connective Tissue Diseases.

Anti-Ro60 and anti-Ro52 antibodies are associated with different connective tissue diseases (CTDs). However, the clinical significance of anti-Ro antibodies is not always consistent among different global regions. The aim of this study was to investigate the clinical characteristics of patients with anti-Ro antibodies. A total of 1596 inpatients with anti-Ro antibodies were included in the study. Demographic, clinical, and serological data were compared between individuals with different profiles of anti-Ro antibodies: patients with anti-Ro52 antibodies alone, patients with anti-Ro60 antibodies alone, and patients with combined anti-Ro52 and anti-Ro60 antibodies. Of the 1596 patients, 1362 (85.3%) were female, the mean age was 45.5 years, and systemic lupus erythematosus (SLE) (46.0%) and Sjogren's syndrome (SS) (19.0%) were the most common CTD diagnoses. Among the patients with anti-Ro52 antibodies alone, idiopathic inflammatory myopathy (18.8%) and SLE (17.6%) were the most common CTD diagnoses. The coexistent autoantibodies of this group were significantly lower compared with those of the other two groups, while the presence of anti-Jo1 antibodies were significantly higher compared with those of the other two groups (3.7% vs. 0.6% vs. 1.9%, p = 0.029). In addition, the patients with isolated anti-Ro52 antibodies were more likely to suffer from interstitial lung disease (35.5% vs. 11.3% vs. 13.7%, p < 10-4) and pulmonary arterial hypertension (10.1% vs. 5.3% vs. 3.6%, p = 0.001) compared with the other two groups of patients. Compared with patients with isolated anti-Ro52 or anti-Ro60 antibodies, the patients with combined anti-Ro52 and anti-Ro60 antibodies were more likely to suffer from xerophthalmia and xerostomia. Furthermore, hypocomplementemia, hyperglobulinemia, and proteinuria were particularly prevalent in patients with anti-Ro60 antibodies. Different profiles of anti-Ro antibodies were significantly associated with clinical phenotypic features in CTDs, indicating the potential diagnostic and prognostic value of these antibodies in clinical practice.

Development and Validation of Analytical Methods to Determine the Prolonged in-use Stability of Anticancer Monoclonal Antibodies in Clinical Practice

Background/purpose: Personalized dosing of monoclonal antibodies (mAbs) based on body weight and surface area may result in leftovers that need to be discarded due to the absence of stability data. After manufacturing, these mAbs undergo extensive quality control with a panel of methods. With some of these similar methods, these mAbs could be tested to see if stability is maintained after the opening of the pharmaceutical product vial and dilution for administration in a daily clinical setting. Prolonged in-use stability may reduce unnecessary waste and minimize the financial loss of these expensive drugs. Methods: Previously, based on extensive literature research, a complementary panel of methods was selected including visual inspection colour, apparency and, clarity (CAC), size exclusion chromatography (SEC), enzyme-linked immunosorbent assay (ELISA), dynamic light scattering (DLS), thermal denaturation (Tm), and aggregation (Tagg) determination, pH and dye ingress method. We evaluated, developed, and validated these methods with respect to the accuracy, precision, reproducibility, stability-indicating capability, carry-over, limit of quantification (LOQ) and limit of detection (LOD) for nivolumab and pembrolizumab as prototype anticancer mAbs. Results: Analytical results show that stability can be determined from a physiochemical, biological, and microbiological point of view with the selected methods. Forced degradation studies showed that even small instabilities can be detected using the panel of methods together, therefore the stability-indicating capability has been established. CAC shows mainly aggregation and discolouration. SEC shows aggregation and fragmentation/degradation, DLS gives information about turbidity and soluble aggregates, Tm and Tagg give information changes intra- and inter conformational changes, respectively, in the mAb molecule. ELISA shows potential loss in bioactivity and the pH of the sample is essential to the chemical composition of the mAb molecules in the solution. Conclusion: A panel of analytical methods was selected, enabling in-use stability determination of anticancer mAbs. This panel will be used in future studies to determine the prolonged use of leftover anticancer mAb products and infusion solutions, starting with nivolumab and pembrolizumab.

The Utility of Myositis Specific Antibodies in Clinical Practice.

Fifteen myositis-specific antibodies have been described and characterized over the past 40 years. Approximately two thirds of patients with idiopathic inflammatory myositis have a myositis-specific antibody and only rarely more than one. Assays to detect them are now widely available within clinical practice. We describe the original description and clinical phenotype of the myositis-specific antibodies, forming the antisynthetase syndrome group, anti-MDA-5 and rapidly progressive interstitial lung disease, anti-SRP/HMGCR and necrotizing myositis, anti-TIF-1γ/NXP-2 and malignancy, anti-SAE and esophageal disease, and anti-Mi-2 and classic dermatomyositis skin disease. Clinical practice is likely to be refined, with diagnosis and classification of the idiopathic inflammatory myositides based primarily on myositis-specific antibody, rather than directed by muscle histology or the broader clinical characteristics of polymyositis and dermatomyositis. All patients newly presenting with idiopathic inflammatory myositis should be routinely screened for myositis-specific antibodies. A positive result will usefully provide diagnostic and prognostic information, guide selection of therapy, and prompt surveillance for potential organ involvement and other features, such as cancer, throughout the disease course.

Serological testing for SARS-CoV-2 antibodies in clinical practice: A comparative diagnostic accuracy study.

BackgroundSerological tests are a powerful tool in the monitoring of infectious diseases and the detection of host immunity. However, manufacturers often provide diagnostic accuracy data generated through biased studies, and the performance in clinical practice is essentially unclear.ObjectivesWe aimed to determine the diagnostic accuracy of various serological testing strategies for (a) identification of patients with previous coronavirus disease‐2019 (COVID‐19) and (b) prediction of neutralizing antibodies against SARS‐CoV‐2 in real‐life clinical settings.MethodsWe prospectively included 2573 consecutive health‐care workers and 1085 inpatients with suspected or possible previous COVID‐19 at a Swiss University Hospital. Various serological immunoassays based on different analytical techniques (enzyme‐linked immunosorbent assays, ELISA; chemiluminescence immunoassay, CLIA; electrochemiluminescence immunoassay, ECLIA; and lateral flow immunoassay, LFI), epitopes of SARS‐CoV‐2 (nucleocapsid, N; receptor‐binding domain, RBD; extended RBD, RBD+; S1 or S2 domain of the spike [S] protein, S1/S2), and antibody subtypes (IgG, pan‐Ig) were conducted. A positive real‐time PCR test from a nasopharyngeal swab was defined as previous COVID‐19. Neutralization assays with live SARS‐CoV‐2 were performed in a subgroup of patients to assess neutralization activity (n = 201).ResultsThe sensitivity to detect patients with previous COVID‐19 was ≥85% in anti‐N ECLIA (86.8%) and anti‐S1 ELISA (86.2%). Sensitivity was 84.7% in anti‐S1/S2 CLIA, 84.0% in anti‐RBD+LFI, 81.0% in anti‐N CLIA, 79.2% in anti‐RBD ELISA, and 65.6% in anti‐N ELISA. The specificity was 98.4% in anti‐N ECLIA, 98.3% in anti‐N CLIA, 98.2% in anti‐S1 ELISA, 97.7% in anti‐N ELISA, 97.6% in anti‐S1/S2 CLIA, 97.2% in anti‐RBD ELISA, and 96.1% in anti‐RBD+LFI.The sensitivity to detect neutralizing antibodies was ≥85% in anti‐S1 ELISA (92.7%), anti‐N ECLIA (91.7%), anti‐S1/S2 CLIA (90.3%), anti‐RBD+LFI (87.9%), and anti‐RBD ELISA (85.8%). Sensitivity was 84.1% in anti‐N CLIA and 66.2% in anti‐N ELISA. The specificity was ≥97% in anti‐N CLIA (100%), anti‐S1/S2 CLIA (97.7%), and anti‐RBD+LFI (97.9%). Specificity was 95.9% in anti‐RBD ELISA, 93.0% in anti‐N ECLIA, 92% in anti‐S1 ELISA, and 65.3% in anti‐N ELISA. Diagnostic accuracy measures were consistent among subgroups.ConclusionsThe diagnostic accuracy of serological tests for SARS‐CoV‐2 antibodies varied remarkably in clinical practice, and the sensitivity to identify patients with previous COVID‐19 deviated substantially from the manufacturer's specifications. The data presented here should be considered when using such tests to estimate the infection burden within a specific population and determine the likelihood of protection against re‐infection.

Real-World Multicenter Experience with Mepolizumab and Benralizumab in the Treatment of Uncontrolled Severe Eosinophilic Asthma Over 12 Months.

PurposeTreatment of severe eosinophilic asthma (SEA) has been revolutionized by the development of monoclonal antibodies targeting underlying immunological pathways of eosinophilic asthma. Two of the most frequently used antibodies in clinical practice are mepolizumab, targeting interleukin (IL) 5 and benralizumab, targeting the IL5 receptor alpha. The comparative treatment efficacy of these antibodies remains unclear, particularly regarding long-term outcomes.Patients and MethodsIn this multicenter, retrospective study, we included 123 patients treated with mepolizumab and 64 patients treated with benralizumab for 12 months at one of three study sites in Germany. Data were collected at baseline and after 6 and 12 months of therapy. Endpoints were changes in pulmonary function (PF), exacerbation rate, oral corticosteroid (OCS) use and dose, asthma control test (ACT) score and fractional exhaled nitric oxide (FeNO) levels.ResultsBoth mepolizumab and benralizumab led to significant improvements in PF with an increase in median forced expiratory volume (FEV1) after 12 months from 59% to 74% for mepolizumab and 63% to 72% for benralizumab. Treatment also led to significant improvements in ACT scores after 12 months (mepolizumab: 13 [interquartile range (IQR) 9–17] to 19 [IQR 15–23]; benralizumab: 12 [IQR 9–16] to 22 [IQR 16–25]) as well as a reduction of mean OCS dose (mepolizumab 8 mg [IQR 5–12.5 mg] median prednisolone equivalent at baseline to 5 mg [IQR 3–7.5 mg]; benralizumab 7.5 mg [IQR 5–15 mg] to 5 mg [IQR 2–10 mg]). The exacerbation rates were reduced significantly, irrespective of the treatment. Overall, changes were similar after 6 and 12 months of therapy.ConclusionBoth mepolizumab and benralizumab are highly effective in the long-term treatment of SEA, with no clinically relevant differences in outcomes after 12 months of therapy. In both groups, improvements were similar after 6 and 12 months of therapy, underlining the feasibility of early treatment evaluation.

Potential false-positive reasons for SARS-CoV-2 antibody testing and its solution.

Coronavirus disease 2019 (COVID‐19) has brought a huge impact on global health and the economy. Early diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is essential for epidemic prevention and control. The detection of SARS‐CoV‐2 antibodies is an important criterion for diagnosing COVID‐19. However, SARS‐CoV‐2 antibody testing also has certain false positives causing confusion in clinical diagnosis. This article summarizes the causes of false‐positive detection of SARS‐CoV‐2 antibodies in clinical practice. The results indicate that the most common endogenous interferences include rheumatoid factor, heterophile antibodies, human anti‐animal antibodies, lysozyme, complement, and cross‐antigens. The exogenous interference is mainly incomplete coagulation of the specimen, contamination of the specimen, and insufficient optimization of the diagnostic kit's reaction system.

Anti-Ro52 antibodies in clinical practice: A single-centre experience.

To analyse the clinical significance of anti-Ro52 autoantibodies that target TRIM21 protein and occur in a variety of connective tissue diseases (CTD), 4782 cases with blood tested positive for anti-Ro52 antibodies between January 2016 and September 2017 in Drum Tower Hospital were enrolled. Anti-Ro52 and anti-Ro60 were measured using the immunoblotting method together with antibodies against other extractable nuclear antigens at the time of the patient's first visit. In this cohort, females accounted for the majority of all subjects (75.9%) and the average age was 47.25years old. About 97.4% were diagnosed as having various diseases, in which around 2/3 were CTDs. The incidence of CTD in patients with merely anti-Ro52 was lower than those with both anti-Ro52 and anti-Ro60 (54.7% vs 85.5% for all patients and 53.3% vs 87.1% for inpatients, both P<.0001). Amongst CTDs, the incidence of systemic lupus erythematosus was significantly decreased, while the incidence of inflammatory myositis as well as undifferentiated connective tissue diseases was increased in anti-Ro52 single-positive group. For patients with either CTDs or non-CTDs, respiratory involvement was more common in patients with merely anti-Ro52 (67.6% vs 34.7%, P<.0001 and 53.2% vs 36.3%, P<.01). Sub-analysis revealed that both interstitial lung disease and pulmonary infection were related to anti-Ro52 in CTD inpatients (P<.0001 and P<.05). Our study shows that anti-Ro52 could occur in various clinical conditions. These antibodies may appear in the early stage of CTD with the lung an important target organ, thus their presence warrants long-term follow-up.

Therapeutic Monoclonal Antibodies in Clinical Practice against Cancer.

The importance of monoclonal antibodies in oncology has increased drastically following the discovery of Milstein and Kohler. Since the first approval of the monoclonal antibody, i.e. Rituximab in 1997 by the FDA, there was a decline in further applications but this number has significantly increased over the last three decades for various therapeutic applications due to the lesser side effects in comparison to the traditional chemotherapy methods. Presently, numerous monoclonal antibodies have been approved and many are in queue for approval as a strong therapeutic agent for treating hematologic malignancies and solid tumors. The main target checkpoints for the monoclonal antibodies against cancer cells include EGFR, VEGF, CD and tyrosine kinase which are overexpressed in malignant cells. Other immune checkpoints like CTLA-4, PD-1 and PD-1 receptors targeted by the recently developed antibodies increase the capability of the immune system in destroying the cancerous cells. Here, in this review, the mechanism of action, uses and target points of the approved mAbs against cancer have been summarized.

Bispecific Antibodies in Clinical Practice and Clinical Trials (Literature Review)

Therapeutic monoclonal antibodies have long been an effective tool deployed by physicians of different specialties, particularly by oncologists. Bispecific antibodies opened up new horizons in the treatment of cancer as they allow to involve a patient’s endogenous immunity in his or her fight against tumor. The present review covers all the formats and strategies used in engineering of bispecific antibodies which reached the stage of clinical trials and also focuses on the available results of these clinical trials.

Prevalence and Significance of Non-conventional Antiphospholipid Antibodies in Patients With Clinical APS Criteria.

Background: The biological diagnostics of antiphospholipid syndrome (APS) takes into account the persistent positivity for anticardiolipin and/or anti-β2GP1 antibodies and/or presence of lupus anticoagulant (LA). However, some non-conventional antiphospholipid antibodies have emerged that could help in the diagnosis of APS.Objectives: To study the potential usefulness of non-conventional antiphospholipid antibodies in clinical practice.Methods: Eighty-seven patients, aged from 15 to 92 years were included and classified in following groups: 41 patients positive for the conventional antibodies with clinical criterion of APS (31 with primary APS and 10 secondary), 17 seronegative APS (SNAPS) patients (i.e., persistent negativity for the conventional antibodies with a strong clinical suspicion of APS), 11 asymptomatic antiphospholipid antibodies carriers (i.e., persistent positivity for the conventional antibodies without clinical evidence of APS), and 18 patients presenting with a first thrombotic or obstetrical event. IgG and IgM were detected to the following antigens: phosphatidylserine/prothrombin (PS/PT) by ELISA, and phosphatidic acid, phosphatidyl-ethanolamine, phosphatidyl-glycerol, phosphatidyl-inositol, phosphatidylserine, annexin V, prothrombin by immunodot. Anti-β2GP1 IgA, and anti-β2GP1 domain 1 IgG were detected by chemiluminescence.Results: Positivity for the non-conventional antibodies was correlated with APS severity; patients with catastrophic APS (CAPS) being positive for 10.7 (Median, Range: 5–14) non-conventional antibodies. 9/17 seronegative patients were positive for at least one of non-conventional antibodies. A study of non-supervised hierarchical clustering of all markers revealed that anti-PS/PT antibodies showed high correlation with the presence of LA. All patients with APS triple positivity (highest risk profile) exhibited also persistent positivity for anti-PS/PT antibodies.Conclusions: Our data obtained from a prospective cohort constituted mainly by patients with primary APS, suggest that non-conventional APS antibodies may be useful for patients classified as SNAPS. They demonstrate the potential value of aPS/PT antibodies as a strong marker of APS. We propose that anti-PS/PT antibodies could be a surrogate APS biological marker of LA to classify in high-risk profile patients treated by direct oral anticoagulants (DOACs), in whom LA detection cannot be achieved.

P074 Infliximab trough level and antibodies in clinical practice in pediatric inflammatory bowel diseases

P074 Infliximab trough level and antibodies in clinical practice in pediatric inflammatory bowel diseases

Immunomodulators targeting the PD-1/PD-L1 protein-protein interaction: From antibodies to small molecules.

Cancer immunotherapy has made great strides in the recent decade, especially in the area of immune checkpoint blockade. The outstanding efficacy, prolonged durability of effect, and rapid assimilation of anti-PD-1 and anti-PD-L1 monoclonal antibodies in clinical practice have been nothing short of a medical breakthrough in the treatment of numerous malignancies. The major advantages of these therapeutic antibodies over their small molecule counterparts have been their high binding affinity and target specificity. However, antibodies do have their flaws including immune-related toxicities, inadequate pharmacokinetics and tumor penetration, and high cost burden to manufacturers and consumers. These limitations hinder broader clinical applications of the antibodies and have heightened interests in developing the alternative small molecule platform that includes peptidomimetics and peptides to target the PD-1/PD-L1 immune checkpoint system. The progress on these small molecule alternatives has been relatively slow compared to that of the antibodies. Fortunately, recent structural studies of the interactions among PD-1, PD-L1, and their respective antibodies have revealed key hotspots on PD-1 and PD-L1 that may facilitate drug discovery efforts for small molecule immunotherapeutics. This review is intended to discuss key concepts in immuno-oncology, describe the successes and shortcomings of PD-1/PD-L1 antibody-based therapies, and to highlight the recent development of small molecule inhibitors of the PD-1/PD-L1 protein-protein interaction.

Anti-GAD antibodies in a cohort of neuropsychiatric patients

ObjectiveAntiglutamate decarboxylase (anti-GAD) antibodies are associated with several neurological manifestations, like epilepsy and movement disorders. However, in daily neurological practice, it remains hard to define when to test for anti-GAD antibodies in patients with neurologic and/or psychiatric symptoms. Therefore, here, we report the patient characteristics of a large retrospective cohort of patients tested for anti-GAD antibodies in clinical practice and compare the characteristics of anti-GAD positive and anti-GAD negative patients. MethodsWe blindly assessed relevant clinical symptoms and comorbidities and functional outcome with the modified Rankin Scale (mRS) in a retrospective observational cohort of all patients in which the decision to assess anti-GAD levels had been made based solely on the presence of possible associated neurological and/or psychiatric symptoms (N=119). ResultsOut of 119 patients, 17 (14.3%) were anti-GAD positive. The anti-GAD positive patients had a median age of 30years (range: 3–64; 2 children). They all had epilepsy, with 8 (47%) patients reporting cognitive complaints. Psychiatric symptoms were less prevalent in anti-GAD positive patients, only 1 anti-GAD positive patient (6%) versus 34 anti-GAD negative patients (33%) reported psychiatric symptoms (p=0.021). The most frequent comorbidity of anti-GAD positive patients was diabetes mellitus type 1 (n=8). Twelve (71%) and 13 (78%) of the anti-GAD positive patients were functionally independent at the time of diagnosis and after one year, respectively (mRS score: 0 to 2). There was no significant difference in functional status at any time during follow-up compared with the anti-GAD negative group. ConclusionAntiglutamate decarboxylase (anti-GAD) antibodies relate to epilepsy with or without cognitive complaints. However, psychiatric symptoms were almost absent in anti-GAD positive patients, and the presence of anti-GAD antibodies contributed little to the prognosis in our cohort.

Detection of Anti-Domain I β-2 Glycoprotein I Antibodies as New Potential Target in Antiphospholipid Syndrome Diagnosis

Anti-cardiolipin antibodies (ACL) and anti-β-2-glycoprotein I antibodies (anti-2GPI) represent two out of three laboratory criteria for detection of antiphospholipid syndrome (APS). The domain I (DI) in anti-β-2-glycoprotein I is a new target for better identification of antibodies and may be associated with thrombotic risk in antiphospholipid syndrome. Anti-β2GPI antibodies specifically reacting with DI have a particular clinical importance being more commonly detected among patients with APS and other autoimmune diseases. This observation implies that compared with antibodies targeting the whole molecule, anti-DI antibodies have higher specificity for APS. Routine testing for anti- DI antibodies in clinical practice can be used for an easy differentiation of subjects carrying clinically meaningful anti- β2GPI antibodies from those individuals with a benign autoantibody profile. The aim of our study was to determine the significance of the domain I in the anti-β-2-glycoprotein I as a new biomarker for determining thrombotic risk in antiphospholipid syndrome. We investigate the DI anti-β2GPI on a group of 74 patients with antiphospholipid syndrome diagnosis. All patients have positive antibodies in at least one class ACL and anti-β2GPI antibodies. We detect DI anti-β2GPI positivity in 21 samples in our group. The thrombotic complications had been observed in 21 from 74 patients. The incidence of thrombotic complications in the total group was established as 28.4%, in comparison to the group DI anti-β2GPI positive with the incidence of thrombotic complications 57%. Performing of assay improved a positive predictive value from 25% pre-test to 68% for patients with positive test. The new chemiluminescent method for detection of DI anti-β2GPI shows a better compliance with clinical outcome than the actual diagnostic scheme.

Anti-tumor necrosis factor drug therapy: The usefulness of monitoring drug levels and anti-drug antibodies in clinical practice

Anti-tumor necrosis factor drug therapy: The usefulness of monitoring drug levels and anti-drug antibodies in clinical practice

PTU-075 Utility of measuring adalimumab drug levels and anti-drug antibodies in clinical practice: a large IBD referral centre experience

Introduction The development of adalimumab (Ada) drug and antibody testing has allowed a personalised approach to complex inflammatory bowel disease (IBD) treatment. We present our 2-year experience at a tertiary IBD referral centre. Method All Ada drug and antibody levels carried out at Guy’s and St. Thomas’ Hospital were analysed. The indications for carrying out levels, the subsequent changes in management and the long-term patient outcomes were evaluated. Results 143 levels were carried out on 105 patients from October 2012 to October 2014. The median value was 5 µg/ml (range 0- >8 µg/ml). 74 levels (52%) were done on patients who had symptoms indicative of loss of response (LOR). 13 patients, all with no detectable antibodies had their dose increased, 10 of these patients had low levels ( 5 levels (4%) were measured after induction (week 12–14) resulting in 1 patient with a low level (3.5 µg/ml) and clinically active disease escalating to 40 mg weekly with good response. 38 levels (27%) were done as part of annual reassessment resulting in only 2 changes in management: 1 patient had dose de-escalation from weekly to every other week due to levels >8 µg/ml and the other had their dose increased to weekly due to low levels (1.4 µg/ml). The remaining levels were done to aid decisions regarding discontinuation of concomitant immunosuppressant (1%), dose de-escalation (11%) and discontinuation of Ada (2%), or to assess response to dose escalation (3%). 39 (27%) of the levels were sub therapeutic in 32 patients. In the 30 patients that did not have antibodies to Ada, 13 patients underwent dose escalation. Ada antibodies were detected in only 2 patients (1%). 1 patient, who had previously had a reaction to infliximab continued on Ada with minimal improvement in her symptoms. The other patient was lost to follow-up shortly after the levels were tested. Conclusion Measuring Ada levels in our cohort resulted in a change of management for 25% of patients, a percentage similar to that seen for infliximab. The majority of patients with LOR who had sub therapeutic levels responded well to Ada dose escalation. Antidrug antibody development is infrequent in our cohort of patients. Disclosure of interest B. Warner: None Declared, E. Johnston: None Declared, J. Digby-Bell: None Declared, N. Unsworth: None Declared, S. Anderson: None Declared, J. Sanderson: None Declared, Z. Arkir: None Declared, P. Irving Speaker Bureau of: MSD, Abbvie and Takeda.

PWE-038 Utility of measuring infliximab drug levels and anti-drug antibodies in clinical practice: a large ibd referral centre experience

<h3>Introduction</h3> The development of infliximab (IFX) drug level and anti-drug antibody (ADA) testing has allowed a personalised approach to IFX use in inflammatory bowel disease (IBD). We present our 2-year experience at a tertiary IBD centre. <h3>Method</h3> All IFX drug and ADA levels measured in patients managed at the Guy’s and St. Thomas’ IBD centre were reviewed. Indications for carrying out drug levels, subsequent changes in management and long-term outcomes were evaluated. <h3>Results</h3> 330 levels were measured in 199 patients from May 2012 to October 2014. Median IFX levels were 4.1 (range 0- &gt;8 µg/ml). 109 (33%) levels were sub therapeutic (≤2.0 µg/ml), of which 61 patients were symptomatic. This resulted in a change in management in 44 (72%) of those patients. ADA were detected in 22 tests (7%) from 19 patients. 12 patients were switched to adalimumab of which 11 continue (median 11 months follow-up) and 1 was a primary non-responder. 4 patients continued on IFX but were optimised on thiopurines, only 1 of which had a subsequent improvement in disease activity. 1 patient stopped anti-TNF therapy due to demyelination, and 2 discontinued anti-TNF to take part in clinical trials. 121 levels (37%) were measured in patients with loss of response (LOR) of whom 50 (41%) had sub therapeutic levels (&lt;2.0 µg/ml). 27 patients, all with no detectable antibodies, underwent dose escalation. 32 levels (10%) were measured at week 14 after standard induction of IFX resulting in 3 patients being switched to adalimumab (Ada) due to significant antibody detection (&gt;200 U/ml) and 1 patient having their dose increased to 10 mg/kg due to borderline levels (2.0 µg/ml) along with poor clinical response. 97 levels (29%) were measured as part of annual reassessment resulting in only 8 changes in management. 1 patient with levels &gt;8 µg/ml had a de-escalation from 10 to 5 mg/kg and 3 had their dose increased due to low levels. As a result of inactive disease, 4 out of the 81 patients with therapeutic IFX levels were able to be withdrawn. The remaining levels were measured after a change in dose of IFX (17%) or for consideration of: withdrawal of concomitant immunosuppression (1%), dose reduction (3%) and withdrawal from IFX (3%). <h3>Conclusion</h3> IFX drug and antibody level testing is being increasingly used in clinical practice. The benefits seem greatest in patients with LOR although our understanding of their utility in other circumstances is increasing. <h3>Disclosure of interest</h3> E. Johnston: None Declared, B. Warner: None Declared, J. Digby-Bell: None Declared, N. Unsworth: None Declared, S. Anderson: None Declared, J. Sanderson: None Declared, Z. Arkir: None Declared, P. Irving Speaker Bureau of: MSD, Abbvie and Takeda.