Levonorgestrel intrauterine system is safe and efficacious for contraception over a 5-year period, data from a phase III trial found.
Pearl Indices, or the number of unintentional pregnancies, for years 1 and 5 were 0.15 (95% CI 0.02-0.55) and 0.20 (95% CI 0.01-1.13) pregnancies per 100 women-years, respectively, reported Stephanie B. Teal, MD, of the University of Colorado in Aurora, and colleagues.
Cumulative life-table pregnancy rate was 0.92% (95% CI 0.46-1.82%) through 5 years, the authors wrote in Obstetrics and Gynecology.
While discontinuation for adverse events occurred in almost 20% of participants, only about 2% discontinued due to bleeding events, and pelvic infection was diagnosed in less than 1% of participants, they noted.
The authors noted that the levonorgestrel 52-mg intrauterine system was approved by the FDA in 2013 for 3 years of contraception, and 4-year approval for the system was granted in October 2017. With this data, the company, Medicines360, is now trying for a 5-year contraceptive indication, the authors said.
The researchers examined data from 1,751 nulliparous and parous women ages 16-45 who were interested in contraception at 29 centers in the U.S. Participants received a novel levonorgestrel 52-mg intrauterine system and after year 1, study visits occurred every 6 months, with a phone call at the 3-month point between visits, the authors said.
Successful intrauterine system placement occurred in 1,1714 women, including 1,568 women ages 16-35, and 146 ages 36-45; there were 1,538 in the efficacy evaluation portion of the trial.
Overall, there were nine pregnancies occurring in four nulliparous and five parous participants, and six of these were ectopic pregnancies.
Examining safety, the analysis included patients who used the system for up to, or beyond 7 years. Participants ages 16-35 were significantly more likely to have new or worsening acne, dyspareunia, pelvic pain, and dysmenorrhea, while older participants were likely to report new or worsening weight increases, Teal and co-authors said.
Of the 18.8% of participants who discontinued treatment due to an adverse event, partial or complete expulsion was the most common for those with successful insertion (3.8%), although the researchers noted that the rates of expulsion did not differ between participants ages 16-35 and 36-45.
Bleeding symptoms were among the most common non-expulsion adverse event that led to at least 0.5% of participants requesting discontinuation during more than 7 years of intrauterine system use, the researchers added.
They noted one death that occurred during the first year of use, but it was the result of a preexisting illness and was not related to the intrauterine system.
Teal and colleagues added that this is an ongoing trial, and the plan is to evaluate the levonorgestrel 52-mg intrauterine system for up to 10 years of continuous use. “Use of the same product for a longer period of time would allow for fewer procedures, which will both decrease healthcare costs and result in less discomfort and risk for females to endure,” the team concluded.
The study was supported by Medicines360.
Teal disclosed support from Merck & Co., and her institution received support from Bayer Health Care, Medicines360, Merck, and Sebela.
Other co-authors disclosed financial relationships with Allergan, Bayer, Pharanest, Teva, Bioceptive, Bayer HealthCare, Cooper Surgical, Medicines360, Merck, Sebela, Antiva, Chemo, Invovio, Mithra, Lupin, Estetra, Gedeon Richter, Icebreaker Health, Daré Bioscience, and HRA Pharma.