EXECUTIVE SUMMARY

Four-year data from the ongoing multicenter, U.S.-based pivotal trial of the 52 mg Liletta levonorgestrel-releasing intrauterine device (IUD) indicate its safety and efficacy for four years of use in nulliparous and parous women, as well as in non-obese and obese women.

  • Liletta currently is approved for effective contraception for up to three years, based on an ongoing multicenter trial evaluating the product for up to seven years of use.
  • The use of long-acting reversible contraception (LARC) has increased in recent years, from 2.4% of all women using contraception in 2002 to 11.6% in 2013. There are now five LARC devices available in the United States: one single-rod etonogestrel implant and five brands of IUDs.

Four-year data from the ongoing multicenter, U.S.-based pivotal trial of the 52 mg Liletta levonorgestrel-releasing intrauterine device (IUD) indicate its safety and efficacy for four years of use in nulliparous and parous women, as well as in non-obese and obese women.1 The data were presented at the American College of Obstetricians and Gynecologists annual clinical and scientific meeting.

Liletta, marketed by Medicines360 of San Francisco and Actavis in Dublin, Ireland, currently is approved for effective contraception for up to three years, based on an ongoing multicenter trial evaluating the product for up to seven years of use. The current evaluation looked at four-year efficacy and safety data for the device.

In the current analysis, scientists enrolled and followed women ages 16-45, with women ages 36-45 receiving the device for safety evaluation only. Four-year pregnancy rates were assessed by Pearl Index and life-table analysis.

What Are the Findings?

Scientists report that successful IUD placement occurred in 1,568 (98%) women ages 16-35 and 146 (97%) women ages 36-45, including 1,011 (57.7%) nulliparous and 438 (25.1%) obese women. Among women ages 16-35 at enrollment, eight pregnancies occurred, including one following perforation and one following expulsion. Six (75%) pregnancies were ectopic. The eight pregnancies included three nulliparous women and one obese woman.

The Pearl Index in the first year was 0.15 (95% confidence interval [CI], 0.02-0.55). Cumulative life-table pregnancy rates through years two, three, and four were 0.49 (95% CI, 0.22-1.09), 0.60 (95% CI, 0.28-1.26), and 0.78 (95% CI, 0.37-1.60). Perforation following device placement occurred in two (0.1%) women; both were diagnosed within the first year. Expulsion was reported in 63 (3.7%) participants, most (50 [80.6%]) during the first year of use. Pelvic infection was diagnosed in 12 (0.7%) women. A total of 38 (2.2%) women discontinued use due to bleeding complaints.1

The data have been submitted to the Food and Drug Administration (FDA) for approval of Liletta for up to four years of use, said Jessica Grossman, MD, chief executive officer of Medicines360, in a statement accompanying the data release.

Looking Past Three Years of Use

The FDA evaluation of Liletta’s four-year data is ongoing, notes Anita Nelson, MD, professor and chair of the obstetrics and gynecology department at Western University of Health Sciences in Pomona, CA. Plans are to continue the device’s trial for seven years if the results remain promising, she says.

Data published late in 2016 indicate Liletta’s calculated levonorgestrel content and release rate curves support the continued evaluation of its contraceptive use for five or more years.2

Liletta has been updated with a single-handed inserter. The inserter features a locking mechanism within the cleft to keep the threads in place, a bendable tube to accommodate the anatomy of the patient during insertion, color-coded sliders to assist in loading the IUD and opening the arms during insertion, and the ability to reset the device for repeated attempts if the device is not loaded properly prior to insertion.

What Are the Options?

The use of long-acting reversible contraception (LARC) has increased in recent years, from 2.4% of all women using contraception in 2002 to 11.6% in 2013.3,4 There now are five LARC devices available in the United States: one single-rod etonogestrel implant (Nexplanon, Merck, Whitehouse Station, NJ) and five brands of IUDs. These include four levonorgestrel IUDs:

  • the 52 mg Mirena (Bayer HealthCare Pharmaceuticals, Whippany, NJ), approved for the treatment of heavy menstrual bleeding in IUD users and for five years of contraceptive use;
  • the 52 mg Liletta (Medicines360 and Actavis), approved for three years of contraceptive use;
  • the 13.5 mg Skyla (Bayer), approved for three years of contraceptive use; and
  • the 19.5 mg Kyleena (Bayer), approved for five years of contraceptive use.
  • The ParaGard copper-T IUD (Teva Women’s Health, Sellersville, PA) is approved for 10 years of contraceptive use.

Intrauterine contraceptives and the contraceptive implant offer top-tier pregnancy prevention, and their use is supported by the American College of Obstetricians and Gynecologists and the American Academy of Pediatrics. Both organizations have issued policy statements affirming that LARC methods are safe, effective, and appropriate options for teens.5,6 

REFERENCES

  1. Creinin MD. Four-year efficacy and safety of the LILETTA levonorgestrel intrauterine system. Presented at the 2017 American College of Obstetricians and Gynecologists Annual Clinical Meeting. San Diego, CA; May 2017.
  2. Creinin MD, Jansen R, Starr RM, et al. Levonorgestrel release rates over 5 years with the Liletta 52-mg intrauterine system. Contraception 2016;94:353-356.
  3. Finer LB, Jerman J, Kavanaugh ML. Changes in use of long-acting contraceptive methods in the United States, 2007-2009. Fertil Steril 2012;98:893-897.
  4. Daniels K, Daugherty J, Jones J. Current contraceptive status among women aged 15-44: United States, 2011-2013. NCHS Data Brief 2014;(173):1-8.
  5. Committee on Adolescent Health Care Long-Acting Reversible Contraception Working Group, American College of Obstetricians and Gynecologists. Committee Opinion #539. Adolescents and long-acting reversible contraception: Implants and intrauterine devices. Obstet Gynecol 2012;120:983-988.
  6. American Academy of Pediatrics, Committee on Adolescence. Policy statement: Contraception for adolescents. Pediatrics 2014;134:e1244-e1256.