Department of Medicine, University of Auckland, M&HS Building 507, 28 Park Ave. Grafton, 1023 Auckland, New Zealand.
Orthopedic Physicians Alaska, 3801 Lake Otis Parkway, 99508 Anchorage, AK, United States.
Joint Bone Spine. 2024 Jul;91(4):105715. doi: 10.1016/j.jbspin.2024.105715. Epub 2024 Mar 4.
Monosodium-urate (MSU) crystal deposits can be visualized and quantified with dual-energy CT (DECT). Pegloticase lowers serum urate (SU) in uncontrolled gout patients, with methotrexate (MTX) co-therapy recommended to increase SU-lowering response rate and decrease infusion reaction risk. The literature on serial DECT-imaging during pegloticase+MTX co-therapy is sparse, with only 2 prior cases of rapid MSU deposition depletion with subsequent bone-erosion remodeling reported from a small open-label trial. Here, we report DECT findings during pegloticase treatment in a larger number of patients from a randomized controlled trial to confirm bone-erosion remodeling that follows MSU depletion with pegloticase. The influence of length-of-therapy is also explored.
Patients received pegloticase (8mg every 2weeks)+MTX (15mg/week orally) or pegloticase+placebo (PBO) during the MIRROR RCT trial. A subset underwent DECT-imaging on Day1 (first pegloticase infusion) and at Weeks 14, 24, and 52. Patients with paired baseline-Week 52 images were included. Imaged regions with baseline MSU-crystal volume (V)<0.5cm were excluded to minimize artifact contributions. V and bone-erosion remodeling were assessed.
Eight patients (6 MTX, 2 PBO) were included. Included patients had received 52weeks (5 MTX), 42weeks (1 PBO), and 6weeks (1 MTX, 1 PBO) of pegloticase therapy. Patients who prematurely discontinued pegloticase maintained SU<6mg/dL on allopurinol (n=2)/febuxostat (n=1). At Week 52, V had markedly decreased in both the pegloticase+MTX and pegloticase+PBO treatment groups, with faster depletion during pegloticase therapy. Bone-erosion remodeling was observed in 29/42 (69%) evaluated erosions: 29 (69%) size decrease, 4 (9.5%) recortication, 3 (7.1%) new bone formation.
Rapid V depletion during pegloticase therapy was observed with concomitant bone remodeling within 1year. Following pegloticase discontinuation, V reduction slowed or stopped even when SU was maintained<6mg/dL with oral ULT.
NCT03994731.
尿酸单钠盐（MSU）晶体沉积物可以通过双能 CT（DECT）进行可视化和定量。培戈洛酶降低未经控制的痛风患者的血清尿酸（SU），建议与甲氨蝶呤（MTX）联合治疗以提高 SU 降低反应率并降低输注反应风险。关于培戈洛酶联合 MTX 治疗期间的连续 DECT 成像的文献很少，仅从小型开放标签试验中报告了 2 例先前的 MSU 沉积迅速耗尽和随后的骨侵蚀重塑的病例。在这里，我们报告了一项更大规模的随机对照试验中接受培戈洛酶治疗的患者的 DECT 结果，以确认培戈洛酶治疗后 MSU 耗尽引起的骨侵蚀重塑。还探讨了治疗时间长度的影响。
患者在 MIRROR RCT 试验中接受培戈洛酶（每 2 周 8mg）+MTX（每周 15mg 口服）或培戈洛酶+安慰剂（PBO）治疗。亚组在第 1 天（第一次培戈洛酶输注）和第 14、24 和 52 周进行 DECT 成像。纳入了具有基线至第 52 周配对图像的患者。排除基线 MSU 晶体体积（V）<0.5cm 的成像区域，以最大程度地减少伪影的影响。评估了 V 和骨侵蚀重塑。
纳入了 8 名患者（6 名 MTX，2 名 PBO）。纳入的患者接受了 52 周（5 名 MTX）、42 周（1 名 PBO）和 6 周（1 名 MTX，1 名 PBO）的培戈洛酶治疗。提前停止培戈洛酶治疗的患者在所有嘌呤醇（n=2）/非布索坦（n=1）上均保持 SU<6mg/dL。在第 52 周时，培戈洛酶+MTX 和培戈洛酶+PBO 治疗组的 V 均明显降低，培戈洛酶治疗期间的消耗更快。在 29/42（69%）评估的侵蚀中观察到骨侵蚀重塑：29 个（69%）大小减小，4 个（9.5%）再皮质化，3 个（7.1%）新骨形成。
在 1 年内观察到培戈洛酶治疗期间 V 的快速消耗，同时伴有骨重塑。培戈洛酶停药后，即使 SU 维持在<6mg/dL 以下，使用口服 ULT，V 的减少也会减慢或停止。
NCT03994731。
