Improved joint and patient-reported health assessments with pegloticase plus methotrexate co-therapy in patients with uncontrolled gout: 12-month exploratory outcomes of the MIRROR open-label trial.

Autor: Botson JK; Orthopedic Physicians Alaska, 3801 Lake Otis Parkway, Anchorage, AK, 99508, USA. jbotson@opaak.com., Obermeyer K; Horizon Therapeutics plc, Deerfield, IL, USA., LaMoreaux B; Horizon Therapeutics plc, Deerfield, IL, USA., Zhao L; Horizon Therapeutics plc, Deerfield, IL, USA., Weinblatt ME; Division of Rheumatology, Immunology and Immunity, Brigham and Women's Hospital, Boston, MA, USA., Peterson J; Western Washington Arthritis Clinic, Bothell, WA, USA.
Jazyk: angličtina
Zdroj: Arthritis research & therapy [Arthritis Res Ther] 2022 Dec 27; Vol. 24 (1), pp. 281. Date of Electronic Publication: 2022 Dec 27.
DOI: 10.1186/s13075-022-02979-4
Abstrakt: Background: Uncontrolled/refractory gout patients are recalcitrant/intolerant to oral urate-lowering therapies (ULTs), experiencing frequent gout flares, functionally limiting tophi, and low quality of life. Pegloticase lowers urate, but anti-pegloticase antibodies limit urate-lowering efficacy and increase infusion reaction (IR) risk. Immunomodulator + pegloticase co-administration may improve treatment response rates, with 79% of MIRROR open-label trial (MIRROR-OL, pegloticase + oral methotrexate) participants meeting 6-month response criteria. Exploratory outcomes from MIRROR-OL are described here.
Methods: Adults with uncontrolled gout (serum urate [SU] ≥ 6 mg/dL and ULT-intolerance/recalcitrance or functionally limiting tophi) were included. Oral methotrexate (15 mg/week) was administered 4 weeks before and during pegloticase treatment (biweekly 8 mg infusion, ≤ 52 weeks). Exploratory outcomes included change from baseline (CFB) in number of affected joints, Health Assessment Questionnaires (HAQs), and Gout Global Assessments.
Results: Fourteen patients received ≥ 1 pegloticase infusion, with 13 included in 52-week analyses (1 enrolled before treatment-extension amendment, exited at 24 weeks). Three patients prematurely exited due to SU rise; 10 completed 52-week evaluations (8 completed 52 weeks of co-therapy, 2 completed 24 weeks [met treatment goals]). At 52 weeks, SU averaged 1.1 ± 2.5 mg/dL, with improvements in HAQ pain and health (CFB: - 33.6 and - 0.7, respectively), Patient and Physician Global Assessments (CFB: - 4.6 and - 5.7, respectively), and joint involvement (CFB: - 5.6, - 8.4, - 6.0 tender, swollen, tophi-affected joints, respectively). Two patients underwent dual-energy computed tomography, showing concomitant monosodium urate volume reductions. All patients had ≥ 1 AE, with 92.9% experiencing acute flare. One mild IR ("cough") occurred and no new safety signals were identified.
Conclusion: Pegloticase + methotrexate co-therapy resulted in sustained SU-lowering with meaningful improvements in clinical measures, urate burden, and patient-reported outcomes.
Trial Registration: ClinicalTrials.gov (NCT03635957).
(© 2022. The Author(s).)
Databáze: MEDLINE
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