Elagolix shows promising results in the treatment of heavy menstrual bleeding associated with uterine fibroids

Oral elagolix either alone or with add-back therapy significantly reduces menstrual blood loss in 90% of pre-menopausal women with uterine fibroids reports the results of a new clinical trial published in November issue of Journal Obstetrics & Gynecology.

Elagolix is an oral gonadotropin-releasing hormone receptor antagonist and recently won FDA approval as the first and only oral drug for the management of severe pain associated with endometriosis.

This interventional, double-blind, randomized Phase 2b Study was conducted across five countries to evaluate the safety and efficacy of elagolix. Over a period of nearly 2.5 years, researchers enrolled 571 premenopausal women suffering from heavy menstrual blood loss and an ultrasound documented uterine fibroids.

These women were randomized to cohorts 1 (259) and 2 (308) and received 300 mg twice daily and 600 mg daily elgolix respectively. Each cohort has four arms: placebo, elagolix alone, elagolix with 0.5 mg estradiol/0.1 norethindrone acetate, and elagolix with 1.0 mg estradiol/0.5 mg norethindrone acetate.

The primary outcome measure was the percentage of women with a Menstrual Blood Loss (MBL) volume of < 80 mL at the last 28 days of the treatment cycle and a ≥ 50% Reduction in MBL volume from baseline to the final month.  The primary safety concern was the change in bone mineral density.

The average age of the participant was 43±5 years, and 70% were black.  Women in both cohorts demonstrated a significant reduction in menstrual blood loss and reached the primary endpoint in all three arms (all P<.001 vs. placebo). 

Elagolix arm showed a significant decrease in lumbar spine bone mineral density as compared to placebo, but add-on therapy with 1.0 mg estradiol/0.5 mg norethindrone acetate stopped the bone loss.

Dr. Bruce Carr, Professor of Obstetrics and Gynecology at UT Southwestern Medical Center and lead author on the study said the oral therapy offers new hope for patients suffering from menorrhagia with uterine fibroids for whom hysterectomy or myomectomy was the gold standard treatment. 

 “There are no orally approved drugs to decrease bleeding and prevent anemia in women with these tumors. Now, there is a medical option for this devastating disease that affects up to 75 percent of women,” he further added in a new release by UT Southwestern Medical Center.

A phase 3 ELARIS UF-EXTEND study of elagolix has also shown parallel results as the phase 2b trial and ELARIS UF-I and ELARIS UF-II phase 3 studies. AbbVie plans to include the ELARIS UF-EXTEND data as part of a submission for regulatory approval of elagolix for the treatment of uterine fibroids in 2019.

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UTSouthwestern Medical Center news release

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New approach to myomectomy: Transvaginal natural orifice transluminal endoscopic surgery

Natural orifice transluminal endoscopic surgery (NOTES) is a challenging minimally invasive procedure where ‘scarless’ abdominal surgeries are performed through an endoscope inserted through a natural orifice (mouth, anus, vagina, and urethra) and is considered as a less invasive approach to laparoscopic surgeries.

NOTES is considered a logical next step in the evolution of minimal invasive surgery, and the first NOTES procedure in humans is often considered to be a transgastric appendectomy performed in India in 2006 which was presented but not reported in manuscript form.

vNOTES is a natural orifice surgery performed through vaginal route. A look into history reveals that gynecologists have been performing colpotomies since years, adding their valuable experience towards NOTES surgeries and subsequent closure.

A recently published paper in January issue of Fertility and Sterility have demonstrated a new technique of performing myomectomy by this route and reports the technique and results of a small study involving 8 patients. Eight patients were treated transvaginally for intramural, subserosal, and pedunculated myomas.

The study was conducted at Gynecology department of a non-university teaching hospital in Belgium.

In case of the anterior myoma, anterior colpotomy was used to gain access to the peritoneal cavity, if the myoma was located posteriorly, a 2.5-cm posterior colpotomy was made under general anesthesia. The pouch of Douglas was opened and a vNOTES port was inserted transvaginally.

A pneumoperitoneum was created and the myoma was identified. With the use of conventional endoscopic instruments and a standard endoscope, all inserted through the vNOTES port, the uterine serosa was incised over the myoma and the myoma was resected. After achieving hemostasis, the uterine scar was sutured in two layers with the use of a standard absorbable suture or an autolocking suture.

 An adhesion-preventing barrier was applied over the uterine scar. The myoma was removed through the colpotomy in an endobag. The vNOTES port was removed and the colpotomy was sutured with the use of an absorbable suture.

The patients’ data collected included demographics, number of previous abdominal surgeries, myoma size, myoma weight, operating time, length of hospital stay, visual analog scale pain score, and serum hemoglobin drop.

All fibroids were successfully removed without any intraoperative or postoperative complications via vNOTES without converting to open or standard laparoscopic access. Patients were discharged within 24 hours, 2 of them went home in 12 hours.

In a developed setting, the surgical time can be reduced with the use of an autolocking suture and a commercially available vNOTES port, while in low resource setting it can be replaced by standard absorbable suture and a self-constructed gloveport, as clearly seen in the following video.

The authors concluded that vNOTES provides a new less invasive approach for the resection of myoma types 3–7 that are conventionally resected via laparotomy, laparoscopy, or transabdominal robotic surgery.

This was the first successful IDEAL (idea, development, exploration, assessment, long-term study) stage 1 study which confirmed the feasibility of vNOTES myomectomy. This novel approach not only provides a better cosmetic result than conventional laparoscopy but also improves patient comfort.

Larger studies are warranted in future. 

A new approach to ovarian cystectomy: Transvaginal natural orifice transluminal endoscopic surgery

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Here is the video of stepwise explanation of the technique.

Yet another warning from FDA against Removal of Uterine Fibroids with Ultrasonic Aspirators

FDA issued a guidance against use of Ultrasonic Surgical Aspirators for removal of uterine fibroids because of risk of unintended spread of uterine cancer in the process of suction by the aspirators, thereby, worsening the patient’s odds for survival.

Ultrasonic aspirators are multifunctional devices that break up and emulsify both hard and soft tissues with ultrasound energy and then suck them out of the body through a small incision. They're used by a wide variety of surgeons in both open and laparoscopic procedures, including the cytoreduction of advanced malignancies that can't be removed completely.

The FDA said that the device’s oscillating tip can disperse the tissue that it breaks up with ultrasonic waves, despite the fact that it is designed to suck up the tissue, and the risk of disseminating cancer cells is outweighed by the aspirator’s benefits, which include “more extensive tumor debulking, little or no collateral thermal damage, and the ability to avoid organ resection.”

However, when it comes to removing uterine fibroids, the risk of spreading occult cancer is not outweighed by the benefits, "particularly since there are alternative treatment options available," the FDA stated. The agency noted that there is "no reliable preoperative screening procedure to detect uterine sarcoma in women with presumed benign fibroids."

Under this guidance, the FDA also requires the manufacturers to add a contraindication label to labeling of the devices, with or without 510(k) clearances, within 120 days of the Oct. 30 release of the guidance: CONTRAINDICATION: This ultrasonic surgical aspirator device is not indicated for and should not be used for the fragmentation, emulsification, and aspiration of uterine fibroids.

ACOG has however openly opposed the FDA guidance against use of ultrasonic aspirators for fibroid removal by stating it to be “too rigid and eliminates patient choice.” ACOG also disagrees with FDA regarding existence of other safer alternatives to remove the fibroids and claims that abdominal hysterectomy carries more risk.

The US FDA  has already issued a communication discouraging the use of power morcellator was issued on April 17, 2014 and have resulted in 4% decline in rate of laparoscopic hysterectomies, says the results of cross sectional study published in forthcoming issue of Journal Obstetrics and Gynecology.

FDA issued the statement because of advocacy and anti-morcellator campaign by Amy Reed, MD, PhD, an anesthesiologist who died because of uterine leiomyosarcoma on Wednesday, May 24 at age of 44.

She underwent a laparoscopic hysterectomy in October 2013 for fibroid, but her undiagnosed, occult uterine leiomyosarcoma was upstaged because of dispersion in abdominal cavity by the use of power morcellator. Since then, the power morcellator is the focal point of a four-year debate that has divided the surgical field.

Based on an analysis of currently available data, the FDA has estimated that approximately 1 in 350 women who undergo hysterectomy or myomectomy for fibroids is found to have an unsuspected uterine sarcoma. 

FDA guidance PDF

Related articles:

Laparoscopic hysterectomies forleiomyomas on decline after FDA communication discouraging the use of power morcellator.

Debate escalates over morcellation ofuterine and fibroid specimens in Minimal Invasive Surgeries after FDA permits the marketing of PneumoLiner!

Power Morcellator: A Boon or Curse?Dr. Amy Reed, a staunch opponent of power morcellator loses battle to uterine cancer.

Laparoscopic hysterectomies for leiomyomas on decline after FDA communication discouraging the use of power morcellator.

The US FDA communication discouraging the use of power morcellator was issued on April 17, 2014 and have resulted in 4% decline in rate of laparoscopic hysterectomies, says the results of cross sectional study published in forthcoming issue of Journal Obstetrics and Gynecology.

FDA issued the statement because of advocacy and anti-morcellator campaign by Amy Reed, MD, PhD, an anesthesiologist who died because of uterine leiomyosarcoma on Wednesday, May 24 at age of 44.

She underwent a laparoscopic hysterectomy in October 2013 for fibroid, but her undiagnosed, occult uterine leiomyosarcoma was upstaged because of dispersion in abdominal cavity by the use of power morcellator. Since then, the power morcellator is the focal point of a four-year debate that has divided the surgical field.

The researchers examined data from 4 states inpatient and ambulatory surgery database for year 2013 to 2014, and compared the rates of laparoscopic hysterectomy 15 months before and 9 months after the FDA announcement.

Women with a diagnosis of leiomyomas who underwent hysterectomy or myomectomy were included in the analysis.

Total 77,637 hysterectomies and myomectomies were performed during that period. The rate of laparoscopic hysterectomies declined from 62% of all hysterectomies before to 58% afterward with an accompanying increase in abdominal hysterectomies of 8% from 71% to 79%.

The rate of myomectomies in women with leiomyoma remained the same as compared to hysterectomies.

On April 7, 2016 The U.S. Food and Drug Administration today permitted the marketing of the first tissue containment system for use with certain laparoscopic power morcellators to isolate uterine tissue that is not suspected to contain cancer.

"PneumoLiner is intended to contain morcellated tissue in the very limited patient population for whom power morcellation may be an appropriate therapeutic option - and only if patients have been appropriately informed of the risks," FDA deputy director William Maisel said in a news release.

"This new device does not change our position on the risks associated with power morcellation. We are continuing to warn against the use of power morcellators for the vast majority of women undergoing removal of the uterus or uterine fibroids," Dr Maisel added.

Based on an analysis of currently available data, the FDA has estimated that approximately 1 in 350 women who undergo hysterectomy or myomectomy for fibroids is found to have an unsuspected uterine sarcoma. 

ACOG statement on power morcellator 

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