Review
Chemistry, Analytical
Kyungah Suh, Isaac Kyei, David S. Hage
Summary: Antibody-based therapeutic agents and other biopharmaceuticals are widely used in the treatment of various diseases. However, they may cause immune reactions that reduce the drug's efficacy and lead to side effects. The immunogenicity of biopharmaceuticals can be evaluated by detecting and measuring antidrug antibodies. This review discusses various methods for antidrug antibody detection and analysis, including immunoassays and antigen binding tests.
JOURNAL OF SEPARATION SCIENCE
(2022)
Article
Rheumatology
Sorwe Mojtahed Poor, Marina Henke, Thomas Ulshoefer, Michaela Koehm, Frank Behrens, Harald Burkhardt, Susanne Schiffmann
Summary: This study aimed to investigate the impact of concomitant MTX on ustekinumab (UST) levels and antidrug antibody (ADA) formation in PsA patients, as well as to evaluate the consequences in pharmacodynamics and pharmacokinetics. The results showed that concomitant MTX did not significantly affect the immunogenicity of UST, and ADA formation was not associated with UST safety, efficacy, or trough levels.
Review
Allergy
Ming-Li Chen, Tanawin Nopsopon, Ayobami Akenroye
Summary: This study aimed to determine the incidence of antidrug antibodies (ADAs) and their impact on clinical outcomes in patients with asthma receiving biologics. The results showed that the overall ADA incidence was 2.91%, with benralizumab having the highest incidence (8.35%) and omalizumab having the lowest incidence (0.00%). The subcutaneous route and longer dosing intervals were associated with higher ADA development.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2023)
Article
Biochemical Research Methods
Akane Omori, Tetsuo Sekino, Akira Ideno
Summary: In this study, a highly sensitive antibody bridging assay model was developed and successfully applied to the immunogenicity testing of oligonucleotide drugs. By utilizing probe alteration link self-assembly reactions as a signal amplifier, the bridging assay model achieved higher signal and improved analytical sensitivity.
Article
Biochemical Research Methods
Zhihua Jiang, John Kamerud, Zhiping You, Soma Basak, Elena Seletskaia, Gregory S. Steeno, Boris Gorovits
Summary: The study investigated the feasibility of singlicate analysis in ADA assay by comparing performance characteristics for duplicate and singlicate formats. The results showed that the assay parameters were comparable between singlicate and duplicate based assays, suggesting minimal impact of singlicate analysis on ADA assay with good duplicate precision. The study provided additional supportive evidence for the feasibility of singlicate-based analysis in ADA ligand binding assays.
Article
Biochemistry & Molecular Biology
Scott P. Henry, Cecilia Arfvidsson, Josh Arrington, Jasna Canadi, Dave Crowe, Shalini Gupta, Sabine Lohmann, Benoit Massonnet, Daniel Mytych, Tina Rogers, Hobart Rogers, Chris Stebbins, Craig Stovold, Daniela Verthelyi, Adam Vigil, Chi Xuan, Yuanxin Xu, Rosie Yu, Thomas Klem
Summary: This study summarizes the experience of the Oligonucleotide Safety Working Group in designing the immunogenicity assessment for therapeutic oligonucleotides, providing advice on assay development, clinical monitoring, and evaluation of the impact of immunogenicity on exposure, efficacy, and safety.
NUCLEIC ACID THERAPEUTICS
(2022)
Article
Medicine, General & Internal
Hyoun-Ah Kim, Sun-Kyung Lee, Sohee Oh, Eun Hye Park, Yong-Beom Park, Kichul Shin
Summary: This study aimed to investigate drug retention rates for various TNF inhibitors among Korean ankylosing spondylitis patients. Results showed that golimumab had a higher retention rate compared to other agents, with discontinuation primarily due to lack of efficacy and adverse events.
FRONTIERS IN MEDICINE
(2021)
Article
Rheumatology
Alejandro Ibanez-Costa, Carlos Perez-Sanchez, Alejandra Maria Patino-Trives, Maria Luque-Tevar, Pilar Font, Ivan Arias de la Rosa, Cristobal Roman-Rodriguez, Ma Carmen Abalos-Aguilera, Carmen Conde, Antonio Gonzalez, Sergio Pedraza-Arevalo, Mercedes del Rio-Moreno, Ricardo Blazquez-Encinas, Pedro Segui, Jerusalem Calvo, Rafaela Ortega Castro, Alejandro Escudero-Contreras, Nuria Barbarroja, Ma Angeles Aguirre, Justo P. Castano-Fuentes, Raul M. Luque, Eduardo Collantes-Estevez, Chary Lopez-Pedrera
Summary: This study identified altered expression of several splicing machinery elements in leucocytes of rheumatoid arthritis patients, with 8 elements equally affected in all leucocyte subtypes. These alterations could discriminate patients from healthy donors, classify high disease activity, recognize radiological involvement, and identify patients with atheroma plaques. The signature was also found in RA synovial fluid and ankle joints of arthritic mice, and could be reversed by anti-TNF therapy.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Rheumatology
Nafise Ghalandari, Maarten M. Immink, Esther Roeder, Patricia C. J. Bruijning-Verhagen, Hieronymus Smeele, Hubertina Crijns, Nicoline A. T. van der Maas, Mireille N. Bekker, Elisabeth A. M. Sanders, Radboud J. E. M. Dolhain
Summary: This pilot study investigated the impact of TNFis treatment in pregnant women with rheumatic disease on Tdap vaccine responses and maternal anti-pertussis IgG antibody levels in newborns. The results showed lower levels of maternal anti-pertussis antibodies in newborns during TNFis treatment.
Review
Rheumatology
John K. Botson, Herbert S. B. Baraf, Robert T. Keenan, John Albert, Karim R. Masri, Jeff Peterson, Christianne Yung, Brigid Freyne, Mona Amin, Abdul Abdellatif, Nehad Soloman, N. Lawrence Edwards, Vibeke Strand
Summary: Gout is a systemic disease that greatly impairs patients' quality of life and functionality. Adding an immunomodulator to pegloticase therapy for patients with uncontrolled gout can substantially improve treatment outcomes.
CURRENT RHEUMATOLOGY REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Florian Rissel, Yoann Cazaubon, Syrine Saffar, Romain Altwegg, Melanie Artasone, Claire Lozano, Thierry Vincent, Alexandre Jentzer
Summary: Therapeutic drug monitoring (TDM) is important for the treatment of inflammatory diseases. In this study, we evaluated the performance of different assays for drug and antidrug antibodies (ADA) measurement. The results showed that the four immunoassays (Promonitor, i-Track10®, ez-Track1, and Lisa Tracker® ELISA) performed well in drug and ADA measurement.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Rheumatology
Siri Lillegraven, Nina Paulshus Sundlisaeter, Anna-Birgitte Aga, Joseph Sexton, Inge Christoffer Olsen, Ase Stavland Lexberg, Tor Magne Madland, Hallvard Fremstad, Christian A. Hoili, Gunnstein Bakland, Cristina Spada, Hilde Haukeland, Inger Myrnes Hansen, Ellen Moholt, Till Uhlig, Daniel H. Solomon, Desiree Van der Heijde, Tore K. Kvien, Espen A. Haavardsholm
Summary: This study aimed to assess the effect of tapering tumor necrosis factor inhibitor (TNFi) to withdrawal compared with stable treatment on the risk of disease activity flares in patients with rheumatoid arthritis (RA) in remission for more than 1 year. The results showed that in the tapering TNFi group, 63% experienced a flare during 12 months, compared to 5% in the stable TNFi group. Therefore, tapering TNFi to discontinuation is not non-inferior to continued stable treatment.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Review
Immunology
XiaoQin Lu, Rui Hu, Lin Peng, MengSi Liu, Zhen Sun
Summary: "Seven biosimilars of adalimumab approved for rheumatoid arthritis treatment by FDA and/or EMA have shown similar efficacy, safety, and immunogenicity to adalimumab, with switching trials indicating no significant impact on these factors."
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Rheumatology
Seher Sener, Veysel Cam, Seza Ozen, Ezgi Deniz Batu
Summary: There is no consensus regarding the choice of biologic therapies and efficacy in juvenile dermatomyositis (JDM), but this review examines previous studies on biologic drug use in JDM patients. The most frequently used biologic drugs were rituximab (RTX) and tumor necrosis factor (TNF) inhibitors. RTX was preferred in severe skin involvement, while infliximab was preferred in calcinosis and adalimumab in skin involvement. Improvement was achieved in a significant percentage of treatments with RTX and anti-TNF drugs. Adverse events were observed in nearly half of the treatments. Controlled studies are needed to provide more evidence for the timing of biologic use in JDM treatment.
CLINICAL RHEUMATOLOGY
(2023)
Article
Medical Laboratory Technology
Maria Dorn-Rasmussen, Sine Buhl, Jorn Brynskov, Jakob T. Bay, Nils Bolstad, Tobias W. Klausen, David J. Warren, Mark A. Ainsworth, Casper Steenholdt
Summary: This study aimed to evaluate the relationship between IFX concentration and clinical and biochemical remission in inflammatory bowel disease, in order to implement therapeutic drug monitoring strategies. The results showed that an IFX concentration of 4.5 mcg/mL was associated with remission throughout the first year. Anti-IFX Abs were associated with low IFX levels and treatment failure.
THERAPEUTIC DRUG MONITORING
(2022)
Letter
Rheumatology
Lea C. Berkhout, Merel J. l'Ami, Gerrit Jan Wolbink, Theo Rispens
ANNALS OF THE RHEUMATIC DISEASES
(2021)
Article
Pharmacology & Pharmacy
Justin Jacobse, Wouter ten Voorde, Anushka Tandon, Stefan G. Romeijn, Hendrika W. Grievink, Koen van der Maaden, Michiel J. van Esdonk, Dirk Jan A. R. Moes, Floris Loeff, Karien Bloem, Annick de Vries, Theo Rispens, Gertjan Wolbink, Marieke de Kam, Dimitrios Ziagkos, Matthijs Moerland, Wim Jiskoot, Joke Bouwstra, Jacobus Burggraaf, Lenneke Schrier, Robert Rissmann, Rebecca ten Cate
Summary: This study evaluated the feasibility of intradermal administration of adalimumab using hollow microneedles. It was found that intradermal adalimumab injection was perceived as more painful compared to subcutaneous administration, but resulted in higher relative bioavailability and skin reactions. The study also showed similar safety and pharmacokinetic effects between intradermal and subcutaneous administration routes.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Mads Delbo Larsen, Erik L. de Graaf, Myrthe E. Sonneveld, H. Rosina Plomp, Jan Nouta, Willianne Hoepel, Hung-Jen Chen, Federica Linty, Remco Visser, Maximilian Brinkhaus, Tonci Sustic, Steven W. de Taeye, Arthur E. H. Bentlage, Suvi Toivonen, Carolien A. M. Koeleman, Susanna Sainio, Neeltje A. Kootstra, Philip J. M. Brouwer, Chiara Elisabeth Geyer, Ninotska I. L. Derksen, Gertjan Wolbink, Menno de Winther, Rogier W. Sanders, Marit J. van Gils, Sanne de Bruin, Alexander P. J. Vlaar, Theo Rispens, Jeroen den Dunnen, Hans L. Zaaijer, Manfred Wuhrer, C. Ellen van dDer Schoot, Gestur Vidarsson
Summary: This study reveals that afucosylated IgG antibodies are specifically formed against enveloped viruses, but not generally against other antigens. These antibodies enhance Fc gamma RIIIa responses, but also exacerbate cytokine storms and immune-mediated pathologies.
Article
Pediatrics
A. Nassar-Sheikh Rashid, D. Schonenberg-Meinema, S. C. Bergkamp, S. Bakhlakh, A. de Vries, T. Rispens, T. W. Kuijpers, G. Wolbink, J. M. van den Berg
Summary: Measurement of anti-TNF drug levels in children with JIA often leads to changes in treatment decisions, with some patients developing anti-drug antibodies that may result in low or undetectable drug levels. Additional research is needed to establish therapeutic drug ranges and pharmacokinetic curves for biologics in this patient population.
PEDIATRIC RHEUMATOLOGY
(2021)
Article
Cell Biology
Willianne Hoepel, Hung-Jen Chen, Chiara E. Geyer, Sona Allahverdiyeva, Xue D. Manz, Steven W. de Taeye, Jurjan Aman, Lynn Mes, Maurice Steenhuis, Guillermo R. Griffith, Peter Bonta, Philip J. M. Brouwer, Tom G. Caniels, Karlijn van der Straten, Korneliusz Golebski, Rene E. Jonkers, Mads D. Larsen, Federica Linty, Jan Nouta, Cindy P. A. A. van Roomen, Frank E. H. P. van Baarle, Cornelis M. van Drunen, Gertjan Wolbink, Alexander P. J. Vlaar, Godelieve J. de Bree, Rogier W. Sanders, Lisa Willemsen, Annette E. Neele, Diederik van de Beek, Theo Rispens, Manfred Wuhrer, Harm Jan Bogaard, Marit J. van Gils, Gestur Vidarsson, Menno de Winther, Jeroen den Dunnen
Summary: Patients diagnosed with COVID-19 tend to become critically ill around the activation of the adaptive immune response. Evidence shows that antibodies in serum may worsen the disease during seroconversion. High anti-spike IgG levels in critically ill patients with severe COVID-19 induce excessive inflammatory responses and may lead to pulmonary complications such as microvascular thrombosis.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Rheumatology
Nafise Ghalandari, Erik Kemper, Ineke (Hubertina) Crijns, Gertjan Wolbink, Theo Rispens, Hieronymus T. W. Smeele, Radboud J. E. M. Dolhain
Summary: Compliance with the EULAR-PtC guidelines results in absence or low levels of TNFi in cord blood, as demonstrated by the analysis of TNFi concentrations in maternal and cord blood samples from 111 patients enrolled in the study.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Medicine, Research & Experimental
Maike H. M. Wientjes, Sadaf Atiqi, Gerrit Jan Wolbink, Michael T. Nurmohamed, Maarten Boers, Theo Rispens, Annick de Vries, Ronald F. van Vollenhoven, Bart J. F. van den Bemt, Alfons A. den Broeder
Summary: This study investigates the clinical utility of therapeutic drug monitoring (TDM) in guiding treatment for patients with rheumatoid arthritis. It is the first blinded test-treatment trial using TDM in this context, with a unique design compared to previous TDM studies.
Article
Rheumatology
Laura Boekel, Maurice Steenhuis, Femke Hooijberg, Yaelle R. Besten, Zoe L. E. van Kempen, Laura Y. Kummer, Koos P. J. van Dam, Eileen W. Stalman, Erik H. Vogelzang, Olvi Cristianawati, Sofie Keijzer, Gestur Vidarsson, Alexandre E. Voskuyl, Luuk Wieske, Filip Eftimov, Ronald van Vollenhoven, Taco W. Kuijpers, S. Marieke van Ham, Sander W. Tas, Joep Killestein, Maarten Boers, Michael Nurmohamed, Theo Rispens, Gertjan Wolbink
Summary: This study found that older patients with autoimmune diseases on specific immunosuppressive drugs may have delayed antibody development after the first COVID-19 vaccination. However, second or repeated exposure to SARS-CoV-2, either through infection or vaccination, can improve humoral immunity in these patients. Delaying the second dose of COVID-19 vaccines in patients receiving immunosuppressive drugs should be avoided, and future studies including younger patients are needed to confirm the generalizability of the results.
LANCET RHEUMATOLOGY
(2021)
Editorial Material
Rheumatology
Laura Boekel, Laura Y. Kummer, Koos P. J. van Dam, Femke Hooijberg, Zoe van Kempen, Erik H. Vogelzang, Luuk Wieske, Filip Eftimov, Ronald van Vollenhoven, Taco W. Kuijpers, S. Marieke van Ham, Sander W. Tas, Joep Killestein, Maarten Boers, Mike T. Nurmohamed, Theo Rispens, Gertjan Wolbink
LANCET RHEUMATOLOGY
(2021)
Article
Rheumatology
J. Koers, N. I. L. Derksen, W. J. J. Falkenburg, P. Ooijevaar-de Heer, M. T. Nurmohamed, G. J. Wolbink, T. Rispens
Summary: This study found that anti-hinge antibodies (AHAs) and elevated levels of Fab glycosylation are present not only in patients with rheumatoid arthritis (RA), but also in healthy controls (HCs). These results suggest that extensive Fab glycosylation may develop in response to an inflammatory proteolytic microenvironment, but is not restricted to RA.
SCANDINAVIAN JOURNAL OF RHEUMATOLOGY
(2023)
Article
Clinical Neurology
Z. L. E. van Kempen, L. Wieske, E. W. Stalman, L. Y. L. Kummer, P. J. van Dam, A. G. Volkers, L. Boekel, A. A. Toorop, E. M. M. Strijbis, S. W. Tas, G. J. Wolbink, M. Lowenberg, C. van Sandt, A. ten Brinke, N. J. M. Verstegen, M. Steenhuis, T. W. Kuijpers, S. M. van Ham, T. Rispens, F. Eftimov, J. Killestein
Summary: This study found that MS patients treated with OCR had poorer humoral responses to the SARS-CoV-2 vaccine, with low B-cell counts and shorter time between infusion and vaccination negatively impacting the immune response. However, this did not completely prevent seroconversion. It is recommended that OCR-treated patients receive their first vaccination as soon as possible, and consideration should be given to timing of additional booster vaccinations based on B-cell count and time after last infusion.
MULTIPLE SCLEROSIS AND RELATED DISORDERS
(2022)
Letter
Rheumatology
Z. Layegh, F. Hooijberg, C. Bastida, A. D. R. Huitema, T. Rispens, C. G. Wolbink
CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
(2022)
Article
Rheumatology
I. Oomen, A. Nassar-Sheikh Rashid, A. H. M. Bouts, S. C. Gouw, T. W. Kuijpers, T. Rispens, A. de Vries, G. Wolbink, J. M. van den Berg, D. Schonenberg-Meinema
Summary: This study investigates the impact of anti-drug antibodies (ADA) on the pharmacokinetics and pharmacodynamics of rituximab (RTX) in children, and finds that ADA affects the concentration and efficacy of RTX, especially in patients with systemic lupus erythematosus (SLE).
CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
(2022)
Review
Rheumatology
L. Boekel, F. Hooijberg, E. H. Vogelzang, P. L. Klarenbeek, W. H. Bos, S. W. Tas, G. J. Wolbink
Summary: This article introduces a novel digital rheumatology research platform that can rapidly collect data and facilitate two-way communication between patients and researchers, making patients true research partners. The platform also implements blood collection methods in a large cohort of patients, with potential applications in both research and clinical care.
ARTHRITIS RESEARCH & THERAPY
(2021)