Publications by authors named "Gerrit J Wolbink"

Monitoring belimumab concentrations in patients can be a valuable tool for assessing treatment response and for personalizing drug doses. Various assay formats may be used to measure concentrations of therapeutic monoclonal antibodies. A particularly useful format involves the use of anti-idiotype monoclonal antibodies, selected to be highly specific to the antibody of interest.

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  • The study explores how patients on immunosuppressants (ISPs) respond to SARS-CoV-2 infections compared to healthy controls, particularly looking at antibody levels post-infection.
  • Patients with immune-mediated inflammatory diseases (IMIDs) on different ISP therapies showed variable antibody responses, with those on anti-CD20 and sphingosine-1 phosphate therapies having lower antibody levels.
  • Despite lower antibody titers, the breakthrough infections in these patients were mostly mild, indicating that ISPs may not severely impede the overall immune response to SARS-CoV-2.
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Background: Rheumatoid factors (RFs) are autoantibodies that target the Fc region of IgG, and are found in patients with rheumatic diseases as well as in the healthy population. Many studies suggest that an immune trigger may (transiently) elicit RF responses. However, discrepancies between different studies make it difficult to determine if and to which degree RF reactivity can be triggered by vaccination or infection.

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Background: The noninflammatory immunoglobulin G4 (IgG4) is linked to tolerance and is unique to humans. Although poorly understood, prolonged antigenic stimulation and IL-4-signaling along the T helper 2-axis may be instrumental in IgG4 class switching. Recently, repeated SARS-CoV-2 mRNA vaccination has been linked to IgG4 skewing.

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Objectives: This study aims to assess current cardiovascular disease risk and prevalence of risk factors in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (SpA).

Methods: 2050 consecutive patients with inflammatory arthritis (IA) and 939 controls were included, with 1308 patients with RA, 356 patients with PsA and 386 patients with SpA. In a prospective cohort setting, questionnaires regarding previous cardiovascular events and risk factors were used to assess cardiovascular risk and prevalence in patients with IA by calculating ORs using logistic regression models.

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  • Millions of patients use TNF inhibitors for inflammatory diseases, but the effectiveness varies due to differences in how drugs are cleared from the body, which may be influenced by TNF-TNFi complexes.
  • Researchers focused on understanding how different types of TNF inhibitors, particularly their structural characteristics, affect the clearance and levels of TNF in patients with conditions like arthritis and ulcerative colitis.
  • Findings indicate that TNF levels are significantly higher with certolizumab compared to other inhibitors, and the ability of macrophages to internalize these complexes is linked to the antibody structure, impacting TNF's clearance rate but not its production.
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Background: Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressants (ISPs) may have impaired long-term humoral immune responses and increased disease activity after SARS-CoV-2 infection. We aimed to investigate long-term humoral immune responses against SARS-CoV-2 and increased disease activity after a primary SARS-CoV-2 infection in unvaccinated IMID patients on ISPs.

Methods: IMID patients on active treatment with ISPs and controls (i.

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  • The 'MHC-I-opathy' concept refers to a group of inflammatory diseases linked to the major histocompatibility complex class I, with recognized conditions including spondyloarthritis and psoriasis, all associated with specific genetic variants.
  • There is a significant challenge in understanding and treating these disorders due to differences in patient symptoms and insufficient research on the MHC-I pathway.
  • The text advocates for a collaborative approach involving diverse medical and research disciplines to standardize disease definitions, explore genetic factors, and improve therapeutic strategies, ultimately aiming to enhance patient care.
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  • * The acid-dissociation radioimmunoassay (ARIA) is a more reliable method but is difficult to implement due to the use of radioactive materials.
  • * A new technique called acid-dissociation lanthanide-fluorescence immunoassay (ALFIA) combines the benefits of ARIA with easier lab procedures, demonstrating high sensitivity and specificity for detecting anti-adalimumab ADAs in rheumatoid arthritis patients.
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For patients with immune-mediated inflammatory diseases (IMIDs), concerns exist about increased disease activity after vaccination. We aimed to assess changes in disease activity after SARS-CoV-2 vaccination in patients with IMIDs, and determine risk factors for increased disease activity. In this substudy of a prospective observational cohort study (Target-to-B!), we included patients with IMIDs who received a SARS-CoV-2 vaccine.

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Ocrelizumab, an anti-CD20 monoclonal antibody, counteracts induction of humoral immune responses after severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccinations in patients with multiple sclerosis (MS). We aimed to assess if serum ocrelizumab concentration measured at the time of vaccination could predict the humoral response after SARS-CoV-2 vaccination. In 52 patients with MS, we found ocrelizumab concentration at the time of vaccination to be a good predictor for SARS-CoV-2 IgG anti-RBD titers after vaccination (comparable to B-cell count).

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  • - The study investigates how specific immunosuppressive therapies affect the immune response to SARS-CoV-2 vaccination in patients with immune-mediated inflammatory disorders, focusing on the humoral immune response.
  • - Conducted in the Netherlands with over 3,200 participants, the research compares the immune responses of patients on immunosuppressants to controls, including healthy individuals and those without systemic immunosuppressants.
  • - Findings indicate that certain immunosuppressive treatments, like anti-CD20 therapy and S1P modulators, result in lower chances of achieving adequate immunity post-vaccination, regardless of the type of immune disorder present.
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  • A significant number of rheumatoid arthritis (RA) patients stop using tumor necrosis factor inhibitors (TNFi) due to lack of effectiveness or side effects, prompting the need for alternative treatments.
  • The ADDORA-switch trial is a 24-week study comparing two strategies for switching RA treatments after failure of adalimumab: one based on serum drug levels and the other on random assignment, with a focus on measuring disease activity over time.
  • This trial is unique as it's the first blinded test-treatment study using therapeutic drug monitoring (TDM) in RA, aiming to provide insights into the clinical value of TDM for guiding treatment decisions.
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Purpose: Tocilizumab is a humanized monoclonal antibody approved for rheumatoid arthritis treatment. In clinical practice, empirical dose-tapering strategies are implemented in patients showing sustained remission or low disease activity (LDA) to avoid overtreatment and reduce costs. Since rational adaptive-dosing algorithms taking the full pharmacokinetic (PK)/pharmacodynamic (PD) characteristics into account are currently lacking, we aimed to develop novel tapering strategies and compare them with currently used empirical ones.

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IgG4 antibodies are unique to humans. IgG4 is associated with tolerance during immunotherapy in allergy, but also with pathology, as in pemphigus vulgaris and IgG4-related disease. Its induction is largely restricted to nonmicrobial antigens, and requires repeated or prolonged antigenic stimulation, for reasons poorly understood.

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Ustekinumab is an effective treatment for psoriasis, but response varies between patients. The formation of anti-drug antibodies (ADAs) may explain part of this variation by reducing the free ustekinumab level. Currently, published analyses of the clinical impact of ADAs are incomplete.

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Tumor necrosis factor inhibitors (TNFi) have significantly improved treatment outcome of rheumatic diseases since their incorporation into treatment protocols two decades ago. Nevertheless, a substantial fraction of patients experiences either primary or secondary failure to TNFi due to ineffectiveness of the drug or adverse reactions. Secondary failure and adverse events can be related to the development of anti-drug antibodies (ADA).

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Objectives: Recently, we demonstrated that early low concentrations of circulating, adalimumab-bound TNF in RA patients treated with adalimumab was associated with future anti-drug antibody formation. Furthermore, low TNF was associated with less frequent baseline MTX use. This is remarkable, because of the anti-inflammatory effects of MTX and a potential inhibiting effect on cytokine production.

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Objectives: Tumour necrosis factor (TNF) inhibitors like certolizumab, elicit an immunogenic response leading to the formation of anti-drug antibodies (ADAs). We sought to mechanistically investigate the relationship between certolizumab concentrations, ADAs, and the effective TNF neutralising capacity in sera of rheumatoid arthritis (RA) patients. TNF neutralising capacity of certolizumab was compared to the neutralising capacity of adalimumab.

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Background: The aim of our study was to investigate the influence of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and body mass index (BMI) on circulating drug levels and clinical response to tumour necrosis factor inhibitor (TNFi) therapy in axial spondyloarthritis (axSpA) patients.

Methods: Prospective observational study during 1 year with 2 cohorts (Madrid and Amsterdam) including 180 axSpA patients treated with standard doses of infliximab or adalimumab. Patients were stratified by BMI, being 78 (43%) normal weight (18.

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Patients with rheumatoid arthritis (RA) can be successfully treated with tumor necrosis factor (TNF) inhibitors, including the monoclonal antibody adalimumab. Once in remission, a proportion of patients can successfully discontinue treatment, indicating that blocking TNF is no longer required for disease control. To explore the dynamics of circulating TNF during adalimumab treatment, we developed a competition enzyme-linked immunosorbent assay that can quantify TNF in the presence of large amounts of TNF inhibitor, i.

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Article Synopsis
  • - The study explores using the Mitra microsampler as an alternative to dried blood spot collection for monitoring biopharmaceutical concentrations, particularly therapeutic drugs.
  • - Researchers tested various therapeutic monoclonal antibodies in whole blood using both the Mitra microsampler and filter paper, analyzing concentrations with specific ELISAs.
  • - Results showed effective recovery rates for several therapeutic antibodies after storage for up to one month, establishing protocols for estimating drug concentrations from capillary blood samples.
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