NEW YORK (Reuters Health) – In patients with Kawasaki disease, initial treatment with a combination of intravenous immunoglobulin (IVIG) and ulinastatin reduces the occurrence of coronary artery lesions and the number of patients who need additional rescue treatment, a retrospective study from Japan suggests.

Ulinastatin is a urinary trypsin inhibitor that protects tissues and organs from neutrophil-mediated injury. It’s been used for the treatment of circulatory shock, septic shock and acute respiratory distress syndrome and Kawasaki disease.

In Kawasaki disease, it’s been used mainly as rescue therapy for patients refractory to conventional initial treatment (in the US and Japan, mainly aspirin and IVIG).

The new study suggests that “intensive initial treatment is the most effective strategy to reduce the occurrence of coronary artery lesions and ulinastatin is an effective candidate for this strategy,” Dr. Takashi Kanai, MD, of the department of pediatrics, National Defense Medical College, Saitama, Japan, told Reuters Health.

In a report online in Circulation, Dr. Kanai and colleagues note that markedly activated neutrophils or higher plasma levels of neutrophil elastase play a role in the poor response to IVIG and the formation of coronary artery lesions, which occurs in more than 10% of patients.

They hypothesized that ulinastatin would reduce the occurrence of coronary artery lesions by both direct and indirect suppression of neutrophils.

They reviewed the clinical records of 1,547 patients treated for Kawasaki disease between 1998 and 2009 at 14 hospitals in the Saitama and Gunma prefectures in Japan; 369 received ulinastatin, with aspirin and IVIG, as initial treatment and 1178 received only aspirin and IVIG (control group).

Ulinastatin was given by intravenous infusion (15,000 units/kg/day in three divided doses) until C-reactive protein levels normalized.

There were no adverse events associated with ulinastatin and the occurrence of coronary artery lesions was significantly lower in the ulinastatin group than the control group (3% [12 of 369] vs 7% [80 of 1178]). The crude odds ratio was 0.46.

The odds ratio was 0.32 after adjusting for sex, initial IVIG dose (1 or 2 g/kg) and Gunma score, a validated predictive score for IVIG unresponsiveness.

The researchers say ulinastatin was particularly beneficial in the subgroup of patients at high risk for coronary artery lesions due to a high Gunma risk score between 7 and 11 points (range 0 to 11 points).

In this subgroup, coronary artery lesions developed in 5 of 69 who received ulinastatin (7%) versus 39 of 141 (28%) who did not; the crude odds ratio was 0.20 and the adjusted odds ratio was 0.21.

Most coronary artery lesions occurred in patients who required additional rescue treatment. This supports several previous reports and it suggests that “success of initial treatment is crucial for the prevention of coronary artery lesions,” the investigators say.

“More importantly,” they found that the proportion of patients who required additional rescue treatment was significantly lower in the ulinastatin group than in the control group (13% [48 of 369] vs 22% [262 of 1178]). “To date, no additional rescue treatments have been reported to reduce the occurrence of coronary artery lesions ultimately,” Dr. Kanai told Reuters Health.

The researchers say a randomized prospective trial to confirm the clinical benefits of ulinastatin seen in this retrospective study is needed, and they are planning to conduct such as trial, Dr. Kanai said.

Reference:

Ulinastatin, a Urinary Trypsin Inhibitor, for the Initial Treatment of Patients With Kawasaki Disease

Circulation 2011;124.