聚乙二醇化尿酸酶联合或不联合甲氨蝶呤治疗期间的生活质量和临床痛风评估：MIRROR随机对照试验的探索性结果。
Quality of life and clinical gout assessments during pegloticase with and without methotrexate co-therapy: MIRROR randomized controlled trial exploratory findings.
作者信息
Botson John, Obermeyer Katie, LaMoreaux Brian, Padnick-Silver Lissa, Verma Supra, Weinblatt Michael E, Peterson Jeff
机构信息
Rheumatology and Bone Health Management, Orthopaedic Physicians Alaska, Anchorage, AK, USA.
US Medical Rare Disease, Amgen, Inc., Thousand Oaks, CA, USA.
出版信息
Rheumatol Adv Pract. 2024 Nov 29;8(4):rkae145. doi: 10.1093/rap/rkae145. eCollection 2024.
OBJECTIVES
Pegloticase lowers serum urate (SU) but is limited by anti-drug antibodies. Methotrexate (MTX) co-administration increases urate-lowering response rate and decreases infusion reaction risk. This is of importance in uncontrolled gout patients who have few treatment options and highly impacted quality of life (QOL). Here, we report exploratory QOL/clinical endpoints of MIRROR RCT (NCT03994731).
METHODS
Patients with uncontrolled gout (sUA ≥ 7 mg/dl, urate-lowering tehraoy (ULT) failure/intolerance, and ≥1 gout sign/symptom [≥1 tophus, ≥2 flares in past year, chronic gouty arthritis]) were administered pegloticase (biweekly 8 mg infusion; 52 weeks) with oral MTX (15 mg/week) or placebo co-therapy. Key exploratory outcomes included change from baseline (CFB) in Physician Global Assessment of Gout [PhGA, score: 0-10], CFB in tender/swollen joint counts [TJC/SJC, score: 0-68/0-66], and gout chronic response rate (GCR50, GCR70; 50%/70% reduction in ≥3 of TJC, SJC, HAQ-Health, HAQ-Pain). Least-square mean (±S.E.) CFB to week 52 was estimated using a mixed model for repeated measures.
RESULTS
In total, 100 patients were randomized to pegloticase + MTX; 52 to pegloticase + PBO. At baseline, patients had poor overall health (HAQ-Health [MTX, PBO]: 44.9 ± 28.6, 39.1 ± 27.4; PhGA: 5.5 ± 2.1, 5.4 ± 2.2) and many affected joints (TJC: 5.4 ± 7.8, 6.7 ± 8.4; SJC: 8.3 ± 12.2, 11.0 ± 15.9). QOL progressively improved during treatment, with similar CFB at week 52 in MTX vs. PBO groups in PhGA (-4.2 ± 0.2 vs. -3.8 ± 0.3) and TJC/SJC (-6.1 ± 0.5 vs. -7.0 ± 0.8/-5.1 ± 0.4 vs. -6.0 ± 0.6). However, at week 52, more MTX patients met GCR50 (58.0% vs. 38.5%) and GCR70 (52.0% vs. 30.8%) criteria.
CONCLUSION
In the MIRROR RCT, pegloticase treatment with or without MTX co-therapy led to meaningful clinical/QOL improvements in uncontrolled gout patients. However, patients receiving MTX co-therapy had greater benefits because of a higher sustained SU-lowering rate (60.0% vs. 30.8% in the PBO group at week 52).
TRIAL REGISTRATION
ClinicalTrials.gov, http://clinicaltrials.gov, NCT03994731.
目的
培戈洛酶可降低血清尿酸盐（SU），但受抗药抗体限制。联合使用甲氨蝶呤（MTX）可提高降尿酸反应率并降低输液反应风险。这对于治疗选择有限且生活质量（QOL）受严重影响的痛风控制不佳患者具有重要意义。在此，我们报告MIRROR随机对照试验（RCT，NCT03994731）的探索性生活质量/临床终点。
方法
痛风控制不佳的患者（血清尿酸≥7mg/dl，降尿酸治疗（ULT）失败/不耐受，且有≥1个痛风体征/症状[≥1个痛风石，过去一年≥2次发作，慢性痛风性关节炎]）接受培戈洛酶（每两周静脉输注8mg；共52周）联合口服MTX（15mg/周）或安慰剂治疗。主要探索性结局包括痛风医生整体评估[PhGA，评分：0 - 10]较基线的变化（CFB）、压痛/肿胀关节计数较基线的变化[TJC/SJC，评分：0 - 68/0 - 66]以及痛风慢性反应率（GCR50、GCR70；TJC、SJC、健康状况HAQ、疼痛状况HAQ中≥3项降低50%/70%）。使用重复测量混合模型估计至第52周的最小二乘均值（±标准误）CFB。
结果
总共100例患者随机分组接受培戈洛酶 + MTX治疗；52例接受培戈洛酶 + 安慰剂（PBO）治疗。基线时，患者整体健康状况较差（健康状况HAQ[MTX，PBO]：44.9±28.6，39.1±27.4；PhGA：5.5±2.1，5.4±2.2）且受累关节较多（TJC：5.4±7.8，6.7±8.4；SJC：8.3±12.2，11.0±15.9）。治疗期间生活质量逐渐改善，在第52周时，MTX组与PBO组在PhGA（-4.2±0.2对-3.8±0.3）和TJC/SJC（-6.1±0.5对-7.0±0.8/-5.1±0.4对-6.0±0.6）方面的CFB相似。然而，在第52周时，更多接受MTX治疗的患者达到GCR50（58.0%对38.5%）和GCR70（52.0%对30.8%）标准。
结论
在MIRROR随机对照试验中，培戈洛酶单独或联合MTX治疗可使痛风控制不佳患者的临床/生活质量得到有意义的改善。然而，接受MTX联合治疗的患者获益更大，因为其SU持续降低率更高（第52周时PBO组为30.8%，MTX组为60.0%）。
试验注册
ClinicalTrials.gov，http://clinicaltrials.gov，NCT03994731
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