EXECUTIVE SUMMARY

The FDA has approved the Liletta levonorgestrel intrauterine device (IUD) for six years of effective use. The 52 mg device, similar in size to the Mirena IUD, was approved for the U.S. in February 2015.

Initially labeled for three years of effective use, Liletta gained FDA approval for five years’ effective use in 2018.

The manufacturers of Mirena also have filed for regulatory approval for an indication for six years of effective use.


Update your clinical practice: The FDA has approved the Liletta levonorgestrel intrauterine device (IUD) for six years of effective use. The 52 mg device, similar in size to the Mirena IUD, was approved for the U.S. market in February 2015. Initially labeled for three years of effective use, Liletta gained FDA approval for five years of effective use in 2018.

Liletta is the only hormonal IUD with FDA approval for use for more than five years, says Mitchell Creinin, MD, professor in the department of obstetrics and gynecology and director of family planning at the University of California, Davis in Sacramento. The approval comes as part of an ongoing 10-year study of the device, says Creinin, a co-author of the six-year efficacy and safety data.1

There may be more options: In October 2019, the manufacturers of Mirena filed a supplement New Drug Application to extend the device’s use to six years.

Study Fills Evidence Gap

Liletta’s current study publication assessed pregnancy rates through 72 months in women age 16-35 years at enrollment. Participants were women of various ages, races, and body mass index. The research supporting the approval of Liletta for seven years of effective use fills a “large gap” in clinical evidence on long-term IUD efficacy, says Creinin.

“While some reproductive health organizations recommend that published evidence supports use of a 52 mg IUD for up to seven years, those data are relatively flimsy,” states Creinin.

The 2016 study, which has served as the basis for the seven-year recommendation, compared rates of unintended pregnancy, method continuation, and reasons for removal among women using either the 52 mg levonorgestrel IUD or the copper T 380 A IUD. Designed as an open-label, seven-year randomized controlled trial, it included 20 centers, 11 of which were in China.2

Because women in Chinese centers experience rates of discontinuation, side effects, and efficacy that are very different than North American and European women, the data from non-Chinese centers is what would be relevant for evaluation, Creinin points out. Of the 601 women age 18-40 years at enrollment who used the levonorgestrel IUD for seven years, only 178 were non-Chinese, he states. The data set from the 2016 study also included women older than age 35 at enrollment, which is outside the standard age range of 35 years or less for FDA efficacy review, observes Creinin. Thus, the data on efficacy through seven years with zero pregnancies in years six and seven is based on 178 women, some of whom were too old for consideration if the FDA was reviewing the data, he states.

Liletta’s published six-year data show that during the study period, nine pregnancies occurred (none in year six) for a life-table pregnancy rate of 0.87 (95% confidence interval, .44-1.70). These findings suggest that adverse event rates remained low through six or more years of use, with two expulsions occurring in year six.1 The ongoing Liletta study, dubbed ACCESS IUS (A Comprehensive Contraceptive Efficacy and Safety Study of an IUS), has enrolled women at 25 U.S. study centers.

Safety Information for Long-Term Use

The Liletta study publication offers the first look at use for further than six years, notes Creinin. Since the safety data are for any safety outcome through the duration of IUD use, and the ACCESS IUS study enrollment now spans several years, some women were well past six years when data were prepared for the FDA submission for the current approval. A total of 191 women had completed seven years, and 121 had completed eight years of use at that point, Creinin observes. The first subject reached 10 years in December 2019.

Bleeding data for Liletta indicate maintenance of amenorrhea rates at about 40%, even into year six. Forty women (2.3%) discontinued due to bleeding complaints, with 75% of these discontinuations occurring in the first two years.1

Gathering data to support long-term use of IUDs is important for women’s health, states Creinin. “Every time an IUD needs to be removed and another one placed, that is an opportunity for a perforation, and can cause discomfort for women to have the procedure,” Creinin explains. “It is unfortunate that so many women had to endure removals and reinsertions that were unnecessary. ACCESS IUS is committed to getting information for women and providers on a more realistic possible duration of use.”

Co-investigator Carolyn Westhoff, MD, MSC, chief of the Division of Family Planning at Columbia University in New York City, agrees with Creinin’s assessment.

“I hear all the time from women that they want a reliable and long-term option for birth control that is reversible,” Westhoff said in a statement. “This groundbreaking trial has given healthcare providers the ability to confidently offer women the option of pregnancy prevention for up to six years.”3

REFERENCES

  1. Westhoff CL, Keder LM, Gangestad A, et al. Six-year contraceptive efficacy and continued safety of a levonorgestrel 52mg intrauterine system. Contraception 2019; doi:10.1016/j.contraception.2019.10.010.
  2. Rowe P, Farley T, Peregoudov A, et al. Safety and efficacy in parous women of a 52-mg levonorgestrel-medicated intrauterine device: A 7-year randomized comparative study with the TCu380A. Contraception 2016; 93:498-506.
  3. Medicines 360. FDA approves Medicines360’s Liletta (levonorgestrel-releasing intrauterine system) 52 mg to prevent pregnancy for up to six years, the longest approved duration of use of any hormonal IUDs. Oct. 28, 2019. Available at: https://bit.ly/2qIarjg.