Department of General Internal Medicine and Nephrology, Robert Bosch Hospital, Stuttgart, Germany.
School of Medicine, University of Split, Split, Croatia.
Nephrol Dial Transplant. 2023 Mar 31;38(4):982-991. doi: 10.1093/ndt/gfac206.
We previously reported that modified-release nicotinamide (NAMR) was superior to placebo in reducing serum phosphate concentrations over 12 weeks in a large cohort of haemodialysis patients with hyperphosphataemia. Here we report outcomes after 52 weeks of treatment.
NOPHOS was a phase 3, international, randomized, controlled, double-blind trial with a parallel group design. NAMR (250-1500 mg/day) was investigated in comparison to placebo as an add-on therapy to an individual therapy with approved phosphate binders.
In the intention-to-treat population (NAMR: n = 539; placebo: n = 183), serum phosphate was significantly lower in the NAMR group compared with the placebo group at week 24 (5.40 ± 1.55 versus 5.79 ± 1.37 mg/dl, P < .001) with a mean difference of -0.39 mg/dl [95% confidence interval (CI) -0.66 to -0.13], but was comparable between the groups at week 52 [mean difference -0.08 (95% CI -0.36-0.20)]. In the completer population (n = 358), statistical significance in favour of NAMR was reached at weeks 24 and 52. The treatment effect was reduced in patients with high baseline serum intact parathyroid hormone (iPTH) compared with patients with low baseline serum iPTH. Compliant patients in the NAMR group had a more pronounced and sustained reduction in serum phosphate than non-compliant patients. NAMR treatment was associated with a significantly increased risk of thrombocytopenia, pruritus, anaemia, and diarrhoea. Herpes zoster occurred exclusively in patients randomized to NAMR.
NAMR combined with phosphate binders significantly reduced serum phosphate over the first 24 weeks of treatment, but the treatment effect was not maintained up to week 52. Non-compliance may have contributed to reduced long-term efficacy. Several newly identified safety signals warrant further evaluation.
我们之前报道过，在一个接受血液透析且高磷血症的大型队列中，与安慰剂相比，改良释放烟酰胺（NAMR）在 12 周内降低血清磷酸盐浓度的效果更好。在此，我们报告 52 周治疗后的结果。
NOPHOS 是一项 3 期、国际、随机、对照、双盲试验，采用平行组设计。与安慰剂相比，NAMR（250-1500mg/天）作为批准的磷酸盐结合剂个体化治疗的附加治疗进行研究。
在意向治疗人群（NAMR：n=539；安慰剂：n=183）中，与安慰剂组相比，NAMR 组在第 24 周时血清磷酸盐显著降低（5.40±1.55 与 5.79±1.37mg/dl，P<0.001），平均差异为-0.39mg/dl（95%置信区间[CI]：-0.66 至 -0.13），但在第 52 周时两组间无差异[-0.08（95%CI：-0.36 至 0.20）]。在完成治疗人群（n=358）中，NAMR 在第 24 周和第 52 周均达到统计学意义。与低基线血清全段甲状旁腺激素（iPTH）相比，基线血清 iPTH 较高的患者治疗效果降低。NAMR 组中依从性好的患者血清磷酸盐降低更明显且持续，而非依从性患者则相反。NAMR 治疗与血小板减少症、瘙痒、贫血和腹泻的风险显著增加相关。单纯疱疹病毒感染仅发生在接受 NAMR 治疗的患者中。
NAMR 联合磷酸盐结合剂可显著降低治疗的前 24 周内的血清磷酸盐水平，但治疗效果在第 52 周时无法维持。不依从可能导致长期疗效降低。一些新出现的安全性信号需要进一步评估。
