Mar Issue 17 65 App Suresh Vedantham: Pill that shrinks uterine Profile fibroids gathers early data Page 26 Ulipristal acetate has become the first oral therapy to show positive phase III esultsr for the treatment of uterine fibroids. In early 2017, it demonstrated efficacy and safety in the Michael Dake: treatment of uterine fibroids in two US pivotal studies. TEVAR’s dirty secret hree prominent physicians Page 28 who are strong advocates Tfor treating uterine fibroids using embolization: gynaecologist Bruce McLucas (California, USA) Lutonix AV results and interventional radiologists Jim Spies (Washington, DC, USA) provide tailwind for and Jon Moss (Glasgow, UK) tell Interventional News about how drug-coated balloons drugs will constantly nip at the heels of interventional treatments, and in dysfunctional how it is their side-effect profile that will determine whether patients will arteriovenous fistula tolerate their use. Ulipristal acetate is an treatment investigational drug for the medical treatment of uterine fibroids. It is Scott Trerotola presented the first release a selective progesterone receptor of eight-month data from the Lutonix AV modulator that acts directly on the trial at the Leipzig Interventional Course progesterone receptors in three target (LINC; 24–27 January, Leipzig, Germany) tissues: the endometrium; uterine Uterine fibromyoma and showed that the drug-coated balloon fibroids; and the pituitary gland. (Lutonix 035 AV from Bard) is linked with a Mclucas, who is founder of the In fact, leuprolide now markets a Richter announced positive results significantly higher target lesion patency Fibroid Treatment Collective and three month injection, rather than a from Venus II, the second of two and far fewer reinterventions to maintain whose team performed the first monthly one. We, who treat myoma pivotal phase III clinical trials the opening in a wide variety of failing fibroid embolization in the USA in patients know the reason. [With this evaluating the efficacy and safety arteriovenous fistulas than standard 1994, says: “Ulipristal acetate, a drug] Patients were forced into a of ulipristal acetate in women with angioplasty. Nine-month data from the drug marketed in the USA to prevent menopausal state, similar to patients abnormal bleeding due to uterine trial will be presented at the Society of implantation and pregnancy, is the whose ovaries are abruptly removed. fibroids. A new drug application Interventional Radiology’s annual scientific latest of several medical therapies They would simply refuse to come filing for ulipristal acetate is planned meeting (4–9 March Washington, DC, USA) to be touted for control of uterine back for a second injection. And so for the second half of 2017, a press and 12-month data will be presented at the myomata. Historically, we have it is with ulipristal. Amenorrhea, release states. Charing Cross International Symposium seen progesterone implants, or hot flushes and headaches are all Venus II was a multicentre, (25–28 April, London, UK). intrauterine devices reported to reported side-effects in the current randomised, double-blind, impede, if not shrink, myomata. series. And once patients stop taking placebo-controlled clinical trial in ommenting on fistulas in a prospective, Progesterone, a balancing hormone their medication, their myomata, premenopausal women in North the significance randomised, multicentre to oestrogen, might logically rebound and grow. Most of our America between 18 and 50 years of C of the data, fashion. A lot of things perform that function. More patients have tried, and given up age who had cyclic abnormal uterine Trerotola (University of [different technologies] recently, leuprolide, an injectable on hormonal therapies, before bleeding and one or more discrete Pennsylvania Medical have been tried; this oestrogen agonist, showed promise presenting to our practice. When uterine fibroids of any size and Center, Philadelphia, is the first one that has as a treatment to reduce myomata a medical therapy comes along location observable by transvaginal USA) said: “This is worked.” by as much as 35%. So why even without the crippling side-effects ultrasound. Patients also had to have the first trial in the 51 The Lutonix AV study promote a procedure such as uterine of current options, I will be there to follicle-stimulating hormone ≤20 years since fistulas have is a prospective, global, artery embolization when we have recommend it over even minimally mIU/mL, and uterine volume ≤20 been created to look multicentre, randomised, a pill? In a word, the side-effects of invasive treatments. That day has not weeks by exam. Eligible patients at an intervention for controlled study de- all of these treatments, and more, come with ulipristal.” were randomised to ulipristal acetate lesions within native Continued on page 8 are intolerable to most patients. In January, Allergan and Gedeon Continued on page 2 2 Embolization March 2017 Pill that shrinks uterine fibroids gathers early data Continued from page 1 5mg, 10mg or placebo for two separate 12-week treatment courses followed by a 12-week treatment-free follow-up period. The study randomised 432 patients so that 162 patients received ulipristal acetate 5mg, 157 patients received 10mg of the oral therapy, and 113 patients received a placebo. The average age of patients enrolled was 41 years and 67% of enrolled patients were black/African Americans. The study met all the co- primary and secondary endpoints with both ulipristal treatment arms achieving statistically significant results over placebo Bruce McLucas Jon Moss Jim Spies (p<0.0001). The co-primary efficacy endpoints were percentage of patients with Greater Glasgow and Clyde and a term eg. with respect to cardiovascular given cyclically? What is the impact of the absence of uterine bleeding and time to lead investigator on the randomised health and cancer? Will women be medication on future fertility? It will be absence of uterine bleeding on treatment controlled FEMME (embolization vs. happy to take this drug long term? We important to have a better understanding of during course one (12-week duration). myomectomy) and REST (embolization now need to compare this interesting its safety and side-effect profile in a larger Significantly more patients in the 10mg vs. surgery) trials, has encountered drug with the existing invasive option population. Finally, what will be the cost group (54.8%) and the 5mg group (42%) patients who have been treated with so that women can make an informed of the drug in the United States, where new achieved absence of bleeding compared to this potential new treatment for uterine choice. Finally, any new treatment must drug costs are typically very steep. High those in the placebo group (0%). fibroids. “As an interventional radiologist prove to be cost-effective in the UK costs may cause insurance companies to More patients in the 10mg group I have used ulipristal acetate usually as and will not receive National Institute deny coverage, limiting the number of (55.4%) and the 5mg group (34.6%) a temporary stopgap for patients who for Health and Care Excellence (NICE) women who may benefit from it.” achieved absence of bleeding within 10 are awaiting embolization. It shrinks the approval without it.” What about the larger picture of drugs days after treatment initiation in the first fibroids and usually stops menstruation. Ulipristal acetate exerts a direct effect being developed for conditions that course of treatment compared to placebo In the UK, we can now prescribe three on the endometrium (suppressing uterine are currently treated by intervention. (0%). Significantly more patients in the 12 week courses each separated by two bleeding) and direct action on fibroid Is this the way medicine is likely to 10mg group (57.3%) and the 5mg group break through bleeds, so approximately size by decreasing the formation of go? “Without a shadow of doubt,” says (40.5%) achieved absence of bleeding a one-year course. Obviously for women new fibroid cells and promoting fibroid Moss. “Years ago, a physician once told compared to placebo (8%) in the second approaching menopause it might prove cell death. The safety and efficacy of me his job was to put the surgeon out course of treatment. The improvement to be a definitive treatment,” he told ulipristal acetate has been evaluated in of business. The demise of peptic ulcer from baseline in the UFS-QOL revised Interventional News. two phase III US studies of more than surgery is a perfect example of how a activities subscale was significantly Moss outlined some of the questions 589 adult women of reproductive age. drug (antibiotics in this case) can totally greater in the 10mg group (56.7%) and that he would like to see answered Spies, chairman and chief of service, replace surgical treatment. Of course, it the 5mg group (48.3%) compared to regarding ulipristal acetate: “The data Georgetown University Medical Center, is never completely clear-cut and some placebo (13%). are interesting and support similar and a past president of the Society of women may still prefer an invasive The most common adverse events findings previously published in the Interventional Radiology reiterates Moss’ procedure (hysterectomy, myomectomy (≥5%) on ulipristal acetate treatment New England Journal of Medicine by concerns about the ulipristal acetate’s safety or embolization) rather than take a pill were hot flush, headache, fatigue, and Donnez et al. The main question is: profile. “Selective progesterone receptor until menopause,” he adds. nausea in the combined period of first what is the role of this drug? Other modulators have been under development Spies says: “I think all medical course of treatment and first off-treatment questions are: is it going to be a long- for many years and this appears to be the technologies leapfrog each other— interval. The most common adverse event term option for women? What are the first to have sufficient data for consideration interventions have supplanted (≥5%) on ulipristal acetate treatment was long-term safety issues? What effect by the US FDA for approval.