eligibility_summary
Adults ≥18 with ACR gout, poorly controlled: SU ≥6 mg/dL,XOI failure/contraindication,≥1 tophus or ≥2 flares/yr, prior pegloticase failure, normal G6PD, stop ULT, effective contraception if WOCBP. Exclude: G6PD deficiency, eGFR<30/dialysis, CHF/arrhythmia/ACS or BP>160/100, cancer (active/≤5y), infections, severe pegloticase reaction, HBV/HCV/HIV+, pregnancy, MTX/steroid intolerance, AST/ALT>2×ULN or liver disease, cytopenias, alcohol>1/day, pulmonary disease, recent rituximab/MTX.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Trial tests rituximab pretreatment to recapture response to standard methotrexate + pegloticase in poorly controlled tophaceous gout with prior pegloticase failure. Interventions and mechanisms: 1) Rituximab (biologic chimeric monoclonal antibody): targets CD20 on B cells, depleting B cells to suppress humoral immunity and reduce anti-pegloticase antibodies. 2) Methotrexate (oral antimetabolite/immunomodulator): inhibits folate-dependent pathways and promotes anti-inflammatory adenosine signaling, reducing lymphocyte proliferation and anti-drug antibody formation. 3) Pegloticase (PEGylated recombinant enzyme/uricase): converts uric acid to allantoin, lowering serum urate. Targeted cells/pathways: CD20+ B cells, humoral immune/anti-drug antibody pathways, lymphocyte proliferation (folate/adenosine), urate oxidation/purine metabolism.