Abortion drug is effective and safe, U.S. study says

The first U.S. study of the mifepristone/misoprostol regimen for medical abortion has found it highly effective,1 confirming the results of the original French studies2,3 and laying further groundwork for the eventual introduction of mifepristone in the United States.

The U.S. trial reported an efficacy rating of 92% up to 49 days following last menstrual period, comparable to the 95% efficacy rate commonly cited in the European experience, note researchers involved in the American study.

"Our findings confirm here in the United States, in our health care system, with our ethnic groups and mix of women, that we have similar results to what was found in Europe with this regimen," notes Ann Robbins, PhD, who served as the New York City-based Population Council's manager of the multi-center clinical trial.

While the publication of the U.S. clinical trial results offers further reinforcement of the safety and efficacy of mifepristone (formerly known as RU-486), perhaps the most important factor in bringing the drug to the U.S. market is securing a pharmaceutical firm to produce it.

The Population Council of New York City, which holds the U.S. patent for the drug, has appointed the Danco Group of San Diego as its licensee for manufacture and marketing of mifepristone. According to company spokes woman Heather O'Neill, the company has entered into talks with several entities and expects mifepristone to enter the U.S. market in 1999. (Review the problems encountered in the American debut of the drug in the following issues of Contraceptive Technology Update: January 1997, p. 11; April 1997, p. 51; and December 1997, p. 149.)

A total of 2,121 women age 18 and older took part in the U.S. study at 17 sites around the country. Trial centers included Planned Parenthood facilities, university hospitals, and freestanding clinics. The protocol called for the oral administration of 600 mg of mifepristone, followed by 400 mcg of misoprostol two days later.

The U.S. trial took a strict approach when defining failure of the medical abortion regimen, the study's authors say. They considered the method a failure if a woman chose medical abortion but subsequently had a surgical intervention during the study period.

Failure under that definition resulted if a surgical procedure was used for any of these reasons:

· The drugs failed to terminate a pregnancy.

· The patient asked for a surgical abortion. (For example, one woman had to leave town and could not return for the second visit. Other studies might consider women who withdraw from a trial as dropouts and exclude them from analysis.)

· The physician intervened, even though surgery (in hindsight) was not essential.

· The drugs caused a medical need to intervene.

· The abortion was incomplete, in that some tissue remained in the uterus, and the physician thought surgery was the best way to manage the situation.

· The abortion was not complete at day 15.

Provider experience key

Success rates with the mifepristone/misoprostol regimen rose as providers became more experienced with the drugs, report clinicians who participated in the U.S. trial.

When the clinical trials began in 1994, most U.S. providers and patients were used to the minimal amount of blood associated with traditional abortion techniques, remarks one of the study's investigators, Carolyn Westhoff, MD, DSc, medical director of family planning at Columbia Presby terian Medical Center and associate professor of clinical OB/GYN and public health at Columbia University, both in New York City. The mifepristone/misoprostol regimen, which produces a level of bleeding often similar to a heavy menstrual period, may have led at first to early intervention. By the end of the trial, though, providers had a better understanding of the bleeding involved with the regimen and were able to counsel women more effectively to achieve success.

For Westhoff, who has continued to study the drug through trials conducted by Abortion Rights Mobilization of New York City, intervention now is rarely enacted. "Basically, we are hardly intervening at all anymore because we now know how safe it is, we know how to answer the patients' questions, we know how to reassure them," she says.

Look to acceptability data from the U.S. study to be published this summer.4 Findings will show that the majority of women were satisfied with the mifepristone/misoprostol regimen, regardless of whether the outcome was successful, says one of the study's coauthors, Beverly Winikoff, MD, MPH, director of the Population Council's reproductive health programs.

Even for women who had surgical interventions, most of them reported they would try the method again and would recommend it to others, which is a finding similar to the European experience, Winikoff says.

"Even if the pills didn't work for them, it still allows women to have a little bit more control over what was happening to their bodies and participate a little bit more in their care," Westhoff says.

References

1. Spitz IM, Bardin CW, Benton L, et al. Early pregnancy termination with mifepristone and misoprostol in the United States. N Engl J Med 1998; 338:1,241-1,247.

2. Silvestre L, Dubois C, Renault M, et al. Voluntary interruption of pregnancy with mifepristone (RU 486) and a prostaglandin analogue. A large-scale French experience. N Engl J Med 1990; 322:645-648.

3. Peyron R, Aubeny E, Targosz V, et al. Early termination of pregnancy with mifepristone (RU486) and the orally active prostaglandin misoprostol. N Engl J Med 1993; 328:1,509-1,513.

4. Winikoff B, Ellertson C, Elul B, et al. Acceptability and feasibility of early pregnancy termination by mifepristone-misoprostol. In press 1998.