The COMPARE head-to-head, randomized controlled trial of SEL-212 (pegadricase plus rapamycin-containing nanoparticle, ImmTOR™) versus pegloticase for refractory gout.

Autor:	Baraf HSB; Rheumatology, Center for Rheumatology and Bone Research, Wheaton, MD, USA.; Rheumatology, George Washington University, Washington DC, USA., Khanna PP; Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA., Kivitz AJ; Department of Rheumatology, Altoona Center for Clinical Research, Duncansville, PA, USA., Strand V; Division of Immunology/Rheumatology, Stanford University School of Medicine, Palo Alto, CA, USA., Choi HK; Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, USA., Terkeltaub R; Rheumatology, Allergy and Immunology Division, San Diego VA Healthcare Service and UCSD, San Diego, CA, USA., Dalbeth N; Bone and Joint Research Group, Department of Medicine, University of Auckland, Auckland, New Zealand., DeHaan W; Selecta Biosciences, Watertown, MA, USA., Azeem R; Selecta Biosciences, Watertown, MA, USA., Traber PG; Selecta Biosciences, Watertown, MA, USA., Keenan RT; Duke University School of Medicine, Durham, NC, USA.; Arthrosi Therapeutics, San Diego, CA, USA.
Jazyk:	angličtina
Zdroj:	Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2024 Apr 02; Vol. 63 (4), pp. 1058-1067.
DOI:	10.1093/rheumatology/kead333
Abstrakt:	Objectives: Serum urate (SU) lowering with PEGylated uricases in gout can reduce flares and tophi. However, treatment-emergent anti-drug antibodies adversely affect safety and efficacy and the currently approved PEGylated uricase pegloticase requires twice-monthly infusions. Investigational SEL-212 therapy aims to promote uricase-specific tolerance via monthly sequential infusions of a proprietary rapamycin-containing nanoparticle (ImmTOR) and pegadricase. Methods: COMPARE was a randomized, phase 2, open-label trial of SEL-212 vs pegloticase in adults with refractory gout. SEL-212 [ImmTOR (0.15 mg/kg) and pegadricase (0.2 mg/kg)] was infused monthly or pegloticase (8 mg) twice monthly for 6 months. The primary endpoint was the proportion of participants with SU <6 mg/dl for ≥80% of the time during 3 and 6 months. Secondary outcomes were mean SU, gout flares, number of tender and/or swollen joints and safety. Results: During months 3 and 6 combined, numerically more participants achieved and maintained a SU <6 mg/dl for ≥80% of the time with SEL-212 vs pegloticase (53.0% vs 46.0%, P = 0.181). The percentage reductions in SU levels were statistically greater during months 3 and 6 with SEL-212 vs pegloticase (-73.79% and -47.96%, P = 0.0161). Reductions in gout flare incidence and number of tender and/or swollen joints were comparable between treatments. There were numerical differences between the most common treatment-related adverse events of interest with SEL-212 and pegloticase: gout flares (60.2% vs 50.6%), infections (25.3% vs 18.4%) and infusion-related reactions (15.7% vs 11.5%), respectively. Stomatitis (and related terms) was experienced by eight participants (9.6%) with SEL-212 and none with pegloticase. Stomatitis, a known event for rapamycin, was associated with ImmTOR only. Conclusions: SEL-212 efficacy and tolerability were comparable to pegloticase in refractory gout. This was associated with a substantial reduction in treatment burden with SEL-212 due to decreased infusion frequency vs pegloticase. Clinical Trial Registration: NCT03905512. (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
Databáze:	MEDLINE
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