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Principal Investigator: Pamela Fitch Weiss
Organization: CHILDREN'S HOSP OF PHILADELPHIA
Fiscal Year: 2024
Award: $377,034
Funding agency: National Institute of Arthritis and Musculoskeletal and Skin Diseases
PROJECT SUMMARY
Across the world, spondyloarthritis (SpA) is the most common form of juvenile arthritis, accounting for as many
as one-third of all cases. Since the introduction of biologic disease modifying agents such as tumor necrosis
factor inhibitors (TNFi), inactive disease is a realistic goal for children with spondyloarthritis (SpA). However,
side effects of TNFi include increased risk of infection, psoriasis, demyelinating disorders, and malignancy.
Additionally, TNFi are expensive and may adversely impact patient’s and caregiver’s quality of life and anxiety.
Recently, the COVID-19 pandemic prompted numerous inquiries regarding whether being on a TNFi increased
the risk of becoming infected, and, if infected, whether being on a TNFi increased the risk of morbidity. In the
absence of definitive answers many families’ next question was, “Can we stop the medication?” We must
address two critical knowledge gaps to inform strategies for TNFi de-escalation in children with SpA. First, it is
unknown if subclinical imaging represents a risk for flare or whether it represents benign residual activity.
Presently, clinical equipoise exists in whether subclinical inflammation on pelvic MRI should impact treatment
decisions about children with SpA and axial disease because we do not know the prevalence or the clinical
relevance of these MRI findings. Second, the role of cellular biomarkers to predict flare after therapy de-
escalation in juvenile SpA is unknown. Prior studies in polyarticular juvenile arthritis have identified cellular
populations and biomarkers that can distinguish disease states that are highly associated with relapse. Similar
studies have not been done in juvenile SpA. Our objective is to test the association of immunologic, serologic
and imaging biomarkers with the risk of disease flare in children with SpA by leveraging the infrastructure and
resources of the parent trial, Biologic Abatement and Capturing Kids’ Outcomes and Flare Frequency in
Juvenile SpA (BACK-OFF JSpA) to perform mechanistic studies to address these critical knowledge gaps. This
application has 2 specific aims: 1) to test the ability of imaging biomarkers at the time of medication de-
escalation to predict subsequent flare in children with axial arthritis, and 2) to test the ability of cellular
biomarkers at the time of medication de-escalation to predict subsequent flare in all children with SpA. The
work proposed in this application will directly impact clinical care and significantly enhance the evidence base
that clinicians, families, and patients use to make decisions about whether or not to de-escalate biologic
therapy.
Terms: <(TNF)-α><0-11 years old><Abate><Accounting><Address><Adolescent><Adolescent Youth><After Care><After-Treatment><Aftercare><Age><Ancillary Study><Anxiety><Apoptosis><Apoptosis Pathway><Area><Arthritis><Back><Benign><Biological><Biological Agent><Biological Markers><Biological Products><Biological Response Modifier Therapy><Biological Therapy><CD152><CD152 Antigen><CD152 Gene><CD3><CD3 Antigens><CD3 Complex><CD3 molecule><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 years><CTLA 4><CTLA-4 Gene><CTLA4><CTLA4 gene><CTLA4-TM><Cachectin><Cancers><Cell Body><Cell Communication and Signaling><Cell Signaling><Cells><Child><Child Youth><Childhood><Children (0-21)><Chronic Childhood Arthritis><Clinical><Communities><Cytotoxic T-Lymphocyte Protein 4><Cytotoxic T-Lymphocyte-Associated Antigen 4><Cytotoxic T-Lymphocyte-Associated Protein 4><Cytotoxic T-Lymphocyte-Associated Serine Esterase-4><Data Bases><Data Reporting><Databases><Decision Making><Demyelinating Diseases><Demyelinating Disorders><Disease><Disorder><Dorsum><Dose><Drugs><Enrollment><Equipoise><Family><Flare><Frequencies><Funding><Gene Transcription><Genetic Transcription><Goals><History><Image><Immune><Immune Markers><Immunes><Immunochemical Immunologic><Immunologic><Immunologic Markers><Immunological><Immunologically><Immunologics><Inflammation><Inflammatory><Infrastructure><Intracellular Communication and Signaling><Juvenile Chronic Arthritis><Juvenile Chronic Polyarthritis><Juvenile Rheumatoid Arthritis><Knowledge><MAP kinase><MHC Receptor><MR Imaging><MR Tomography><MRI><MRIs><Macrophage-Derived TNF><Magnetic Resonance Imaging><Major Histocompatibility Complex Receptor><Malignant Neoplasms><Malignant Tumor><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Medication><Memory><Messenger RNA><Mitogen-Activated Protein Kinases><Monocyte-Derived TNF><Morbidity><Morbidity - disease rate><NIH Program Announcements><NMR Imaging><NMR Tomography><Nuclear><Nuclear Magnetic Resonance Imaging><OKT3 antigen><Outcome><PD 1><PD-1><PD1><Parents><Patients><Pelvic><Pelvic Region><Pelvis><Pharmaceutical Preparations><Phenotype><Population><Predictive Value><Prevalence><Process><Program Announcement><Programmed Cell Death><Protocol><Protocols documentation><Psoriasis><Public Health><RNA Expression><ROC Analyses><ROC Curve><Randomized><Receptor Activation><Recording of previous events><Relapse><Research><Research Resources><Residual><Residual state><Resources><Risk><Role><Role of Tob in T-cell activation><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><Sacroiliac Joint><Sacroiliac joint structure><Serology><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Signal Transduction><Signal Transduction Systems><Signaling><Spinal Arthritis><Spondylarthritis><T memory cell><T-Cell Activation Pathway><T-Cell Antigen Receptors><T-Cell Receptor><T-Cell Subsets><T-Lymphocyte Subsets><T3 Antigens><T3 Complex><T3 molecule><TNF><TNF A><TNF Alpha><TNF gene><TNF-α><TNFA><TNFα><Testing><Time><Transcription><Tumor Necrosis Factor><Tumor Necrosis Factor-alpha><Withdrawal><Withdrawing Treatments><Work><Zeugmatography><ages><arthritic><bio-markers><biologic><biologic marker><biological signal transduction><biological therapeutic><biological treatment><biologically based therapeutics><biologics><biomarker><biopharmaceutical><biotherapeutic agent><biotherapeutics><biotherapy><caregiver quality of life><clinical care><clinical predictors><clinical relevance><clinically relevant><cohort><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><cytokine><cytotoxic T-lymphocyte antigen 4><data base><data representation><data representations><de-myelinating diseases><de-myelinating disorders><demyelinating conditions><demyelination diseases><demyelination disorders><disease risk><disorder risk><drug/agent><enroll><evidence base><histories><imaging><imaging biomarker><imaging marker><imaging-based biological marker><imaging-based biomarker><imaging-based marker><immune check point><immune checkpoint><immune-based biomarkers><immunecheckpoint><immunological biomarkers><immunological markers><improved><infection risk><inhibitor><inhibitor drug><inhibitor therapeutic><inhibitor therapy><juvenile><juvenile arthritis><juvenile human><juvenile idiopathic arthritis><kids><mRNA><malignancy><memory T lymphocyte><neoplasm/cancer><parent><pediatric><point of care><post treatment><pragmatic randomized trial><predictive biomarkers><predictive marker><predictive molecular biomarker><programmed cell death 1><programmed cell death protein 1><programmed death 1><psoriasiform><psoriatic><quality of life for caregivers><randomisation><randomization><randomly assigned><receiver operating characteristic analyses><receiver operating characteristic curve><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><side effect><sle2><social role><spondyloarthritis><standard of care><systemic lupus erythematosus susceptibility 2><tool><youngster>