Gouw Samantha C, van der Bom Johanna G, Marijke van den Berg H
Van Creveldlkiniek, University Medical Center Utrrecht, Utrecht, The Netherlands.
Blood. 2007 Jun 1;109(11):4648-54. doi: 10.1182/blood-2006-11-056291. Epub 2007 Feb 8.
The CANAL Study (Concerted Action on Neutralizing Antibodies in severe hemophilia A) was designed to describe the relationship between treatment characteristics and inhibitor development in previously untreated patients with severe hemophilia A. This multicenter retrospective cohort study investigated 366 consecutive patients born between 1990 and 2000. The outcome was clinically relevant inhibitor development, defined as the occurrence of at least 2 positive inhibitor titers combined with a decreased recovery. Eighty-seven (24%) patients developed inhibitors (69 high titer [19%]). The incidence of inhibitors appeared to be associated with age at first treatment, decreasing from 41% for those treated within the first month of age to 18% in those treated after 18 months; after adjustment for treatment intensity, this association largely disappeared. Surgical procedures and peak treatment moments at start of treatment increased inhibitor risk (relative risk [RR], 3.7; 95% confidence interval [CI], 2.0-7.1; and RR, 3.3; CI, 2.1-5.3, respectively). Regular prophylaxis was associated with a 60% lower risk than on-demand treatment (RR, 0.4; CI, 0.2-0.8). Our findings suggest that the previously reported associated between an early age at first exposure and the risk of inhibitor development is largely explained by early, intensive treatment. The latter appears to be an independent risk factor for inhibitor development. In addition, early, regular prophylaxis may protect patients with hemophilia against the development of inhibitors.
CANAL研究（重度A型血友病中和抗体协同行动）旨在描述重度A型血友病初治患者的治疗特征与抑制物产生之间的关系。这项多中心回顾性队列研究调查了1990年至2000年出生的366例连续患者。研究结果为临床相关抑制物产生，定义为至少出现2次阳性抑制物滴度且回收率降低。87例（24%）患者产生了抑制物（69例高滴度[19%]）。抑制物的发生率似乎与首次治疗时的年龄有关，从1月龄内接受治疗的患者中的41%降至18月龄后接受治疗的患者中的18%；在对治疗强度进行调整后，这种关联基本消失。手术操作和治疗开始时的高峰治疗时刻会增加抑制物风险（相对风险[RR]分别为3.7；95%置信区间[CI]为2.0 - 7.1；RR为3.3；CI为2.1 - 5.3）。规律预防治疗的风险比按需治疗低60%（RR为0.4；CI为0.2 - 0.8）。我们的研究结果表明，先前报道的首次暴露年龄与抑制物产生风险之间的关联很大程度上可由早期强化治疗来解释。后者似乎是抑制物产生的一个独立危险因素。此外，早期规律预防治疗可能会保护血友病患者不产生抑制物。
