Trainer P J, Drake W M, Katznelson L, Freda P U, Herman-Bonert V, van der Lely A J, Dimaraki E V, Stewart P M, Friend K E, Vance M L, Besser G M, Scarlett J A, Thorner M O, Parkinson C, Klibanski A, Powell J S, Barkan A L, Sheppard M C, Malsonado M, Rose D R, Clemmons D R, Johannsson G, Bengtsson B A, Stavrou S, Kleinberg D L, Cook D M, Phillips L S, Bidlingmaier M, Strasburger C J, Hackett S, Zib K, Bennett W F, Davis R J
Christie Hospital, Manchester, United Kingdom.
N Engl J Med. 2000 Apr 20;342(16):1171-7. doi: 10.1056/NEJM200004203421604.
Patients with acromegaly are currently treated with surgery, radiation therapy, and drugs to reduce hypersecretion of growth hormone, but the treatments may be ineffective and have adverse effects. Pegvisomant is a genetically engineered growth hormone-receptor antagonist that blocks the action of growth hormone.
We conducted a 12-week, randomized, double-blind study of three daily doses of pegvisomant (10 mg, 15 mg, and 20 mg) and placebo, given subcutaneously, in 112 patients with acromegaly.
The mean (+/-SD) serum concentration of insulin-like growth factor I (IGF-I) decreased from base line by 4.0+/-16.8 percent in the placebo group, 26.7+/-27.9 percent in the group that received 10 mg of pegvisomant per day, 50.1+/-26.7 percent in the group that received 15 mg of pegvisomant per day, and 62.5+/-21.3 percent in the group that received 20 mg of pegvisomant per day (P<0.001 for the comparison of each pegvisomant group with placebo), and the concentrations became normal in 10 percent, 54 percent, 81 percent, and 89 percent of patients, respectively (P<0.001 for each comparison with placebo). Among patients treated with 15 mg or 20 mg of pegvisomant per day, there were significant decreases in ring size, soft-tissue swelling, the degree of excessive perspiration, and fatigue. The score fortotal symptoms and signs of acromegaly decreased significantly in all groups receiving pegvisomant (P< or =0.05). The incidence of adverse effects was similar in all groups.
On the basis of these preliminary results, treatment of patients who have acromegaly with a growth hormone-receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement.
目前，肢端肥大症患者接受手术、放射治疗和药物治疗以减少生长激素的过度分泌，但这些治疗可能无效且有不良反应。培维索孟是一种基因工程生长激素受体拮抗剂，可阻断生长激素的作用。
我们对112例肢端肥大症患者进行了一项为期12周的随机双盲研究，皮下注射三种每日剂量的培维索孟（10毫克、15毫克和20毫克）和安慰剂。
安慰剂组胰岛素样生长因子I（IGF-I）的平均（±标准差）血清浓度较基线水平下降了4.0±16.8%，每日接受10毫克培维索孟的组下降了26.7±27.9%，每日接受15毫克培维索孟的组下降了50.1±26.7%，每日接受20毫克培维索孟的组下降了62.5±21.3%（各培维索孟组与安慰剂组比较，P<0.001），分别有10%、54%、81%和89%的患者浓度恢复正常（与安慰剂组的每次比较，P<0.001）。在每日接受15毫克或20毫克培维索孟治疗的患者中，指环大小、软组织肿胀、多汗程度和疲劳程度均有显著下降。接受培维索孟治疗的所有组中，肢端肥大症的总症状和体征评分均显著下降（P≤0.05）。各组不良反应的发生率相似。
基于这些初步结果，用生长激素受体拮抗剂治疗肢端肥大症患者可降低血清IGF-I浓度并改善临床症状。
