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  1. Article ; Online: Treatment decisions in axial spondyloarthritis daily clinical practice are more than treat-to-target.

    Bolt, Janne W / Aalbers, Caroline J / Walet, Laura / van Mens, Leonieke J J / van Denderen, Christiaan / van der Horst-Bruinsma, Irene / van Baarsen, Lisa G M / Landewé, Robert / van de Sande, Marleen G H

    Rheumatology (Oxford, England)

    2023  Volume 63, Issue 1, Page(s) 34–40

    Abstract: Objective: 'Treat-to-target principles' are advised for axial spondyloarthritis (axSpA), although a clear target is not yet defined and targets do not always reflect inflammation. Treat-to-target use and motives for treatment choices in clinics are ... ...

    Abstract Objective: 'Treat-to-target principles' are advised for axial spondyloarthritis (axSpA), although a clear target is not yet defined and targets do not always reflect inflammation. Treat-to-target use and motives for treatment choices in clinics are unknown. Therefore, we studied the presence of residual disease activity according physician's opinion, patient's opinion and composite indices and compared them to the subsequent treatment decisions.
    Methods: This cross-sectional multicentre study included 249 patients with a clinical diagnosis of axSpA ≥6 months. Remission and low disease activity according to the BASDAI (<1.9 and <3.5, respectively) and physician's and patient's opinion were assessed. Questionnaires included patient-reported outcomes and patients and physicians completed questions regarding treatment decisions.
    Results: A total of 115/249 (46%) patients were in remission according to the physician and 37% (n = 43) of these patients reached remission according to the BASDAI. In 51/83 (60%) of the patients with residual disease activity according to the physician and a BASDAI >3.5 the treatment was left unchanged, either because of low disease activity as rated by the physician [n = 15 (29%)] or because of a combination of low disease activity with non-inflammatory complaints or comorbidities [n = 11 (25%)]. Retrospective treat-to-target evaluations showed that treatments were most frequently intensified in patients with arthritis or inflammatory back pain and less often in patients with other (non-inflammatory) musculoskeletal comorbidities.
    Conclusion: This study shows that physicians do not always strictly apply treat-to-target in case of residual disease activity in axSpA. Usually, they accept low disease activity as satisfactory.
    MeSH term(s) Humans ; Spondylitis, Ankylosing/drug therapy ; Retrospective Studies ; Cross-Sectional Studies ; Inflammation ; Axial Spondyloarthritis ; Pain ; Spondylarthritis/diagnosis ; Spondylarthritis/drug therapy
    Language English
    Publishing date 2023-04-04
    Publishing country England
    Document type Multicenter Study ; Journal Article
    ZDB-ID 1464822-2
    ISSN 1462-0332 ; 1462-0324
    ISSN (online) 1462-0332
    ISSN 1462-0324
    DOI 10.1093/rheumatology/kead155
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Ultrasound-guided lymph node biopsy sampling to study the immunopathogenesis of rheumatoid arthritis: a well-tolerated valuable research tool.

    Fiechter, Renée H / Bolt, Janne W / van de Sande, Marleen G H / Aalbers, Caroline J / Landewé, Robert B M / Maas, Mario / Tas, Sander W / van Baarsen, Lisa G M

    Arthritis research & therapy

    2022  Volume 24, Issue 1, Page(s) 36

    Abstract: Background: Analyses of lymphoid organs are required to further elucidate the pathogenesis of inflammatory diseases like rheumatoid arthritis (RA). Yet, invasive tissue collection methods are scarcely applied, because they are often considered ... ...

    Abstract Background: Analyses of lymphoid organs are required to further elucidate the pathogenesis of inflammatory diseases like rheumatoid arthritis (RA). Yet, invasive tissue collection methods are scarcely applied, because they are often considered burdensome, although patients do not always consider invasive methods as a high burden. We aimed to investigate the perspectives of study participants undergoing ultrasound-guided inguinal lymph node (LN) needle biopsy sampling and determine the molecular and cellular quantity and quality of LN biopsies.
    Methods: Together with patient research partners, questionnaires were developed to evaluate the motives, expectations, and experiences of participants undergoing a LN biopsy. Healthy controls and RA(-risk) patients were asked to complete these questionnaires before and after the procedure. RNA and lymphocyte yields from obtained LN biopsies were also calculated.
    Results: We included 50 individuals, of which 43 (86%) reported their pre- and post-procedure experiences. The median reported pain on a 5-point Likert scale (1 not to 5 very painful) was 1. Interestingly, almost all (n = 32; 74%) study participants would undergo a second procedure and more than half (n = 23; 54%) would encourage others to take part in the LN biopsy study. Motives for current and future participation were mostly altruistic. Inguinal hematoma occurred frequently, but no other significant or unexpected complications ensued. The LN biopsies yielded sufficient and high-quality RNA and lymphocyte numbers.
    Conclusions: Ultrasound-guided inguinal LN biopsy sampling is well-tolerated, safe, and provides sufficient material for further molecular and cellular analyses. Our participants' positive experiences endorse the application of this research tool to further elucidate the pathogenesis of RA and other inflammatory diseases.
    MeSH term(s) Arthritis, Rheumatoid/diagnostic imaging ; Arthritis, Rheumatoid/immunology ; Arthritis, Rheumatoid/pathology ; Humans ; Lymph Nodes/diagnostic imaging ; Lymph Nodes/pathology ; Sentinel Lymph Node Biopsy/methods ; Ultrasonography
    Language English
    Publishing date 2022-02-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2107602-9
    ISSN 1478-6362 ; 1478-6354
    ISSN (online) 1478-6362
    ISSN 1478-6354
    DOI 10.1186/s13075-022-02728-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: More outreach for young scientists.

    Aalbers, Caroline J / Groen, Justus L / Sivapalaratnam, Suthesh

    Nature

    2010  Volume 467, Issue 7314, Page(s) 401

    MeSH term(s) Age Factors ; Community-Institutional Relations ; European Union ; Mentors ; Research Personnel
    Language English
    Publishing date 2010-09-23
    Publishing country England
    Document type Letter
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/467401a
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Advancements in adeno-associated viral gene therapy approaches: exploring a new horizon.

    Aalbers, Caroline J / Tak, Paul P / Vervoordeldonk, Margriet J

    F1000 medicine reports

    2011  Volume 3, Page(s) 17

    Abstract: Gene therapy is a promising new therapeutic strategy that has been explored in a wide variety of diseases, ranging from cancer to hemophilia, and ocular disorders to autoimmune diseases, among others. Proof of concept of gene transfer approaches has been ...

    Abstract Gene therapy is a promising new therapeutic strategy that has been explored in a wide variety of diseases, ranging from cancer to hemophilia, and ocular disorders to autoimmune diseases, among others. Proof of concept of gene transfer approaches has been shown in over 100 studies of animal models of disease, although only a few are under development for clinical application. The US Food and Drug Administration and the European Medicines Agency have not approved any viral human gene therapy products for sale so far, but the amount of gene-related research and development occurring in the United States and Europe continues to grow at a fast rate. This review summarizes the current status of developments in the field of viral gene therapy using adeno-associated virus as a vector, with a special focus on arthritis. For rheumatoid arthritis, and to a lesser extent for other immune-related inflammatory disorders, several cell and gene transfer approaches have been investigated at the preclinical level and a few have been implemented in clinical trials. Finally, both the potential and the hurdles that are faced during development of a viral gene therapy through to its clinical application are discussed.
    Language English
    Publishing date 2011-09-01
    Publishing country England
    Document type Journal Article
    ISSN 1757-5931
    ISSN (online) 1757-5931
    DOI 10.3410/M3-17
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Single-joint Assessment for the Evaluation of Intraarticular Treatment: Responsiveness and Discrimination of the Composite Change Index.

    Aalbers, Caroline J / Gerlag, Danielle M / Vervoordeldonk, Margriet J / Tak, Paul P / Landewé, Robert B

    The Journal of rheumatology

    2015  Volume 42, Issue 9, Page(s) 1672–1676

    Abstract: Objective: To investigate responsiveness, discrimination, and construct validity of a composite change index (CCI) for the assessment of single-joint involvement in inflammatory arthritis.: Methods: Evaluation of standardized response means (SRM), ... ...

    Abstract Objective: To investigate responsiveness, discrimination, and construct validity of a composite change index (CCI) for the assessment of single-joint involvement in inflammatory arthritis.
    Methods: Evaluation of standardized response means (SRM), Guyatt effect size, and Spearman rank correlation coefficient in a randomized controlled trial investigating the effect of an intraarticular etanercept injection.
    Results: The CCI showed a high SRM (1.68) and high Guyatt effect size (2.72). Both visual analog scale of pain and functionality had a moderate Guyatt effect size (2.06, 2.44) and high SRM (0.81, 0.97).
    Conclusion: This study supports the use of the CCI as a single-joint assessment after single-joint intervention.
    Clinical trial registration: NTR-1210.
    MeSH term(s) Antirheumatic Agents/administration & dosage ; Antirheumatic Agents/therapeutic use ; Arthritis, Psoriatic/drug therapy ; Arthritis, Psoriatic/pathology ; Arthritis, Rheumatoid/drug therapy ; Arthritis, Rheumatoid/pathology ; Disability Evaluation ; Double-Blind Method ; Etanercept/administration & dosage ; Etanercept/therapeutic use ; Humans ; Injections, Intra-Articular ; Knee Joint/pathology ; Treatment Outcome
    Chemical Substances Antirheumatic Agents ; Etanercept (OP401G7OJC)
    Language English
    Publishing date 2015-09
    Publishing country Canada
    Document type Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 194928-7
    ISSN 1499-2752 ; 0315-162X
    ISSN (online) 1499-2752
    ISSN 0315-162X
    DOI 10.3899/jrheum.140956
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Empty Capsids and Macrophage Inhibition/Depletion Increase rAAV Transgene Expression in Joints of Both Healthy and Arthritic Mice.

    Aalbers, Caroline J / Broekstra, Niels / van Geldorp, Mariska / Kramer, Emiel / Ramiro, Sofia / Tak, Paul P / Vervoordeldonk, Margriet J / Finn, Jonathan D

    Human gene therapy

    2017  Volume 28, Issue 2, Page(s) 168–178

    Abstract: Gene therapy has potential to treat rheumatic diseases; however, the presence of macrophages in the joint might hamper adeno-associated viral vector-mediated gene delivery. Here we demonstrate that in arthritic, but also in healthy, mice administration ... ...

    Abstract Gene therapy has potential to treat rheumatic diseases; however, the presence of macrophages in the joint might hamper adeno-associated viral vector-mediated gene delivery. Here we demonstrate that in arthritic, but also in healthy, mice administration of agents that influence macrophage activity/number and/or addition of empty decoy capsids substantially improve the efficacy of recombinant adeno-associated viral vector 5 transgene expression in the joint. Pretreatment with triamcinolone or clodronate liposomes improved luciferase expression over a period of 4 weeks. Similar results were seen when empty decoy capsids were added to full genome containing capsids in a 5:1 ratio. In a study to assess the duration of expression as well as to investigate the combination of these two approaches, we observed a synergistic enhancement of gene expression, sustained for at least 12 weeks. The enhancement of gene expression was independent of the route of administration of triamcinolone (intra-articular or intramuscular). In healthy mice it was demonstrated that the combination improved expression of the transgene significantly, in a serotype independent manner. These data have implications for future applications of gene therapy to the joint and for other tissues with an abundance of macrophages.
    MeSH term(s) Animals ; Arthritis/genetics ; Arthritis/therapy ; Capsid/metabolism ; Dependovirus/genetics ; Genetic Vectors/administration & dosage ; Joints/metabolism ; Joints/pathology ; Macrophages/cytology ; Macrophages/metabolism ; Mice ; Transgenes/physiology
    Language English
    Publishing date 2017-02
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1028152-6
    ISSN 1557-7422 ; 1043-0342
    ISSN (online) 1557-7422
    ISSN 1043-0342
    DOI 10.1089/hum.2016.036
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Interferon beta for rheumatoid arthritis: new clothes for an old kid on the block.

    Vervoordeldonk, Margriet J / Aalbers, Caroline J / Tak, Paul P

    Annals of the rheumatic diseases

    2009  Volume 68, Issue 2, Page(s) 157–158

    MeSH term(s) Animals ; Antirheumatic Agents/therapeutic use ; Arthritis, Rheumatoid/drug therapy ; Disease Models, Animal ; Drug Therapy, Combination ; Enzyme Inhibitors/therapeutic use ; Humans ; I-kappa B Kinase/antagonists & inhibitors ; I-kappa B Kinase/physiology ; Interferon-beta/therapeutic use
    Chemical Substances Antirheumatic Agents ; Enzyme Inhibitors ; Interferon-beta (77238-31-4) ; I-kappa B Kinase (EC 2.7.11.10)
    Language English
    Publishing date 2009-02
    Publishing country England
    Document type Comment ; Editorial
    ZDB-ID 7090-7
    ISSN 1468-2060 ; 0003-4967
    ISSN (online) 1468-2060
    ISSN 0003-4967
    DOI 10.1136/ard.2008.097899
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Preclinical Potency and Biodistribution Studies of an AAV 5 Vector Expressing Human Interferon-β (ART-I02) for Local Treatment of Patients with Rheumatoid Arthritis.

    Aalbers, Caroline J / Bevaart, Lisette / Loiler, Scott / de Cortie, Karin / Wright, J Fraser / Mingozzi, Federico / Tak, Paul P / Vervoordeldonk, Margriet J

    PloS one

    2015  Volume 10, Issue 6, Page(s) e0130612

    Abstract: Introduction: Proof of concept for local gene therapy for the treatment of arthritis with immunomodulatory cytokine interferon beta (IFN-β) has shown promising results in animal models of rheumatoid arthritis (RA). For the treatment of RA patients, we ... ...

    Abstract Introduction: Proof of concept for local gene therapy for the treatment of arthritis with immunomodulatory cytokine interferon beta (IFN-β) has shown promising results in animal models of rheumatoid arthritis (RA). For the treatment of RA patients, we engineered a recombinant adeno-associated serotype 5 vector (rAAV5) encoding human (h)IFN-β under control of a nuclear factor κB promoter (ART-I02).
    Methods: The potency of ART-I02 in vitro as well as biodistribution in vivo in arthritic animals was evaluated to characterize the vector prior to clinical application. ART-I02 expression and bioactivity after transduction was evaluated in fibroblast-like synoviocytes (FLS) from different species. Biodistribution of the vector after local injection was assessed in a rat adjuvant arthritis model through qPCR analysis of vector DNA. In vivo imaging was used to investigate transgene expression and kinetics in a mouse collagen induced arthritis model.
    Results: Transduction of RA FLS in vitro with ART-I02 resulted in high expression levels of bioactive hIFN-β. Transduction of FLS from rhesus monkeys, rodents and rabbits with ART-I02 showed high transgene expression, and hIFN-β proved bioactive in FLS from rhesus monkeys. Transgene expression and bioactivity in RA FLS were unaltered in the presence of methotrexate. In vivo, vector biodistribution analysis in rats after intra-articular injection of ART-I02 demonstrated that the majority of vector DNA remained in the joint (>93%). In vivo imaging in mice confirmed local expression of rAAV5 in the knee joint region and demonstrated rapid detectable and sustained expression up until 7 weeks.
    Conclusions: These data show that hIFN-β produced by RA FLS transduced with ART-I02 is bioactive and that intra-articular delivery of rAAV5 drives expression of a therapeutic transgene in the joint, with only limited biodistribution of vector DNA to other tissues, supporting progress towards a phase 1 clinical trial for the local treatment of arthritis in patients with RA.
    MeSH term(s) Animals ; Arthritis, Experimental/therapy ; Arthritis, Rheumatoid/drug therapy ; Arthritis, Rheumatoid/therapy ; Cells, Cultured ; Cytokines/biosynthesis ; Dependovirus/genetics ; Gene Expression/drug effects ; Genes, Synthetic ; Genetic Therapy ; Genetic Vectors/administration & dosage ; Genetic Vectors/genetics ; Genetic Vectors/pharmacokinetics ; Genetic Vectors/therapeutic use ; Humans ; Injections, Intra-Articular ; Interferon-beta/genetics ; Macaca mulatta ; Male ; Methotrexate/pharmacology ; Methotrexate/therapeutic use ; Mice ; Mice, Inbred DBA ; NF-kappa B/genetics ; Promoter Regions, Genetic/genetics ; Rabbits ; Rats ; Rats, Inbred Lew ; Specific Pathogen-Free Organisms ; Synovial Membrane/cytology ; Synovial Membrane/virology ; Tissue Distribution ; Transduction, Genetic
    Chemical Substances Cytokines ; NF-kappa B ; Interferon-beta (77238-31-4) ; Methotrexate (YL5FZ2Y5U1)
    Language English
    Publishing date 2015
    Publishing country United States
    Document type Comparative Study ; Journal Article
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0130612
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Safety, Biodistribution, and Efficacy of an AAV-5 Vector Encoding Human Interferon-Beta (ART-I02) Delivered via Intra-Articular Injection in Rhesus Monkeys with Collagen-Induced Arthritis.

    Bevaart, Lisette / Aalbers, Caroline J / Vierboom, Michel P M / Broekstra, Niels / Kondova, Ivanela / Breedveld, Elia / Hauck, Bernd / Wright, J Fraser / Tak, Paul Peter / Vervoordeldonk, Margriet J

    Human gene therapy. Clinical development

    2015  Volume 26, Issue 2, Page(s) 103–112

    Abstract: Preclinical studies to assess biodistribution, safety, and initial efficacy of ART-I02, an adeno-associated type 5 (rAAV5) vector expressing human interferon β (hIFN-β), were performed in a total of 24 rhesus monkeys with collagen-induced arthritis. All ... ...

    Abstract Preclinical studies to assess biodistribution, safety, and initial efficacy of ART-I02, an adeno-associated type 5 (rAAV5) vector expressing human interferon β (hIFN-β), were performed in a total of 24 rhesus monkeys with collagen-induced arthritis. All monkeys were naïve or showed limited neutralizing antibody (Nab) titers to AAV5 at the start of the study. Animals were injected with a single intra-articular dose of ART-I02 or placebo, consisting of 3.2×10(13) vg (Dose A=maximum feasible dose), 4.58×10(12) vg (Dose B), or placebo in the first affected finger joint, the ipsilateral knee, and ankle joint at the same time point. Animals were monitored for clinical parameters and well-being with a maximum of 4 weeks, with the option that the severity of arthritis could necessitate an earlier time point of sacrifice. No adverse events were noted after injection of ART-I02. No abnormalities were observed after histological evaluation of all organs. At both dose levels, immunohistochemical staining indicated expression of hIFN-β. In animals injected with Dose A, we observed stabilization or a reduction in swelling in the finger joint in which vector was administered. The highest copy numbers of vector DNA were detected in synovial tissue of the injected joint and the draining lymph node of the injected knee. High titers of Nab to rAAV5 were observed at the end of the study. Five monkeys developed an rAAV5-specific T-cell response. Two monkeys developed Nab to hIFN-β. In conclusion, intra-articular injection of ART-I02 was well-tolerated and did not induce adverse events. After administration of Dose A of ART-I02, we observed a beneficial effect on joint swelling, substantiated by decreased histological inflammation and bone erosion scores. A GMP vector for clinical application has been manufactured and is currently being tested in GLP rodent studies, with the aim to move forward to a clinical trial.
    MeSH term(s) Animals ; Ankle Joint/pathology ; Arthritis, Experimental/metabolism ; Arthritis, Experimental/pathology ; Arthritis, Experimental/therapy ; Dependovirus/genetics ; Female ; Finger Joint/pathology ; Genetic Therapy ; Genetic Vectors ; Humans ; Injections, Intra-Articular ; Interferon-beta/genetics ; Interferon-beta/metabolism ; Knee Joint/pathology ; Macaca mulatta ; Male ; Tissue Distribution ; Treatment Outcome
    Chemical Substances Interferon-beta (77238-31-4)
    Language English
    Publishing date 2015-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2768506-8
    ISSN 2324-8645 ; 2324-8637
    ISSN (online) 2324-8645
    ISSN 2324-8637
    DOI 10.1089/humc.2015.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Preclinical Potency and Biodistribution Studies of an AAV 5 Vector Expressing Human Interferon-β (ART-I02) for Local Treatment of Patients with Rheumatoid Arthritis.

    Caroline J Aalbers / Lisette Bevaart / Scott Loiler / Karin de Cortie / J Fraser Wright / Federico Mingozzi / Paul P Tak / Margriet J Vervoordeldonk

    PLoS ONE, Vol 10, Iss 6, p e

    2015  Volume 0130612

    Abstract: Proof of concept for local gene therapy for the treatment of arthritis with immunomodulatory cytokine interferon beta (IFN-β) has shown promising results in animal models of rheumatoid arthritis (RA). For the treatment of RA patients, we engineered a ... ...

    Abstract Proof of concept for local gene therapy for the treatment of arthritis with immunomodulatory cytokine interferon beta (IFN-β) has shown promising results in animal models of rheumatoid arthritis (RA). For the treatment of RA patients, we engineered a recombinant adeno-associated serotype 5 vector (rAAV5) encoding human (h)IFN-β under control of a nuclear factor κB promoter (ART-I02).The potency of ART-I02 in vitro as well as biodistribution in vivo in arthritic animals was evaluated to characterize the vector prior to clinical application. ART-I02 expression and bioactivity after transduction was evaluated in fibroblast-like synoviocytes (FLS) from different species. Biodistribution of the vector after local injection was assessed in a rat adjuvant arthritis model through qPCR analysis of vector DNA. In vivo imaging was used to investigate transgene expression and kinetics in a mouse collagen induced arthritis model.Transduction of RA FLS in vitro with ART-I02 resulted in high expression levels of bioactive hIFN-β. Transduction of FLS from rhesus monkeys, rodents and rabbits with ART-I02 showed high transgene expression, and hIFN-β proved bioactive in FLS from rhesus monkeys. Transgene expression and bioactivity in RA FLS were unaltered in the presence of methotrexate. In vivo, vector biodistribution analysis in rats after intra-articular injection of ART-I02 demonstrated that the majority of vector DNA remained in the joint (>93%). In vivo imaging in mice confirmed local expression of rAAV5 in the knee joint region and demonstrated rapid detectable and sustained expression up until 7 weeks.These data show that hIFN-β produced by RA FLS transduced with ART-I02 is bioactive and that intra-articular delivery of rAAV5 drives expression of a therapeutic transgene in the joint, with only limited biodistribution of vector DNA to other tissues, supporting progress towards a phase 1 clinical trial for the local treatment of arthritis in patients with RA.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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