Turok DK, Gero A, Simmons RG, et al. Levonorgestrel vs copper intrauterine devices for emergency contraception. N Engl J Med. 2021;384:335-344.

EXPERT COMMENTARY

Emergency contraception refers to therapies used to prevent pregnancy after inadequately protected intercourse.¹ Evidence-based forms of EC available in the United States include oral LNG, oral ulipristal acetate, and the copper IUD. The copper IUD provides not only EC but also highly effective contraception after placement.² The LNG-IUD has a favorable side effect profile compared with the copper IUD and is theorized to act as EC through direct interference with sperm and oviduct transport.³ Recently, Turok and colleagues conducted a noninferiority trial designed to investigate the EC effectiveness of the LNG-IUD compared with the copper IUD.³

Details of the study

Turok and colleagues recruited participants aged 18 to 35 who requested EC from 6 family planning clinics in Utah from 2016 to 2019. Participants who reported unprotected intercourse within the past 120 hours and who desired an IUD to prevent pregnancy for at least 1 year were randomly assigned to receive either the LNG-IUD or the copper IUD. Individuals were excluded from the trial if they had contraindications to IUD placement, were breastfeeding, had abnormal uterine bleeding, had irregular menses, were currently using highly effective contraception, or had recent EC use. Researchers determined pregnancy status at 1 month through a pregnancy test or clinical records review.

Results. Of 711 participants randomly assigned, 317 who received the LNG-IUD and 321 who received the copper IUD provided 1-month outcome data. Pregnancy 1 month after IUD placement occurred in 1 participant (0.3%) in the LNG-IUD group and in no participants in the copper IUD group (0%). The between-group difference of 0.3 percentage points was within the margin of noninferiority and was not significant.

Study strengths and limitations

This large, multicenter randomized controlled trial contributes novel information about the effectiveness and noninferiority of the LNG-IUD as EC. Unlike prior studies of oral EC, which commonly limited participants to 1 episode of unprotected intercourse, this trial enrolled women at potentially higher risk of pregnancy with multiple episodes of intercourse and found fewer pregnancies than expected. Randomization ensured equivalence between groups, with the exception of the reason for needing EC.

Study limitations include a higher than expected rate of loss to follow-up, requiring clinical records and survey data to confirm pregnancy status. After randomization, clinicians were unable to place IUDs in more than 5% of participants in both groups; noninferiority was demonstrated nonetheless. This study did not include participants receiving oral EC, so direct comparison of effectiveness is not possible. Pregnancy rates among IUD users in this study were favorable to rates reported in previous studies of oral EC.⁴

When choosing an IUD for contraception, more women select the LNG-IUD for its favorable side effect profile and reduction in menstrual bleeding. In this randomized IUD study, only 7% of eligible participants enrolled, potentially introducing selection bias. The majority who declined enrollment did not want an IUD. Previous studies that allowed participants to choose their IUD had higher enrollment rates. ● 

Turok DK, Gero A, Simmons RG, et al. Levonorgestrel vs copper intrauterine devices for emergency contraception. N Engl J Med. 2021;384:335-344.

EXPERT COMMENTARY

Emergency contraception refers to therapies used to prevent pregnancy after inadequately protected intercourse.¹ Evidence-based forms of EC available in the United States include oral LNG, oral ulipristal acetate, and the copper IUD. The copper IUD provides not only EC but also highly effective contraception after placement.² The LNG-IUD has a favorable side effect profile compared with the copper IUD and is theorized to act as EC through direct interference with sperm and oviduct transport.³ Recently, Turok and colleagues conducted a noninferiority trial designed to investigate the EC effectiveness of the LNG-IUD compared with the copper IUD.³

Details of the study

Turok and colleagues recruited participants aged 18 to 35 who requested EC from 6 family planning clinics in Utah from 2016 to 2019. Participants who reported unprotected intercourse within the past 120 hours and who desired an IUD to prevent pregnancy for at least 1 year were randomly assigned to receive either the LNG-IUD or the copper IUD. Individuals were excluded from the trial if they had contraindications to IUD placement, were breastfeeding, had abnormal uterine bleeding, had irregular menses, were currently using highly effective contraception, or had recent EC use. Researchers determined pregnancy status at 1 month through a pregnancy test or clinical records review.

Results. Of 711 participants randomly assigned, 317 who received the LNG-IUD and 321 who received the copper IUD provided 1-month outcome data. Pregnancy 1 month after IUD placement occurred in 1 participant (0.3%) in the LNG-IUD group and in no participants in the copper IUD group (0%). The between-group difference of 0.3 percentage points was within the margin of noninferiority and was not significant.

Study strengths and limitations

This large, multicenter randomized controlled trial contributes novel information about the effectiveness and noninferiority of the LNG-IUD as EC. Unlike prior studies of oral EC, which commonly limited participants to 1 episode of unprotected intercourse, this trial enrolled women at potentially higher risk of pregnancy with multiple episodes of intercourse and found fewer pregnancies than expected. Randomization ensured equivalence between groups, with the exception of the reason for needing EC.

Study limitations include a higher than expected rate of loss to follow-up, requiring clinical records and survey data to confirm pregnancy status. After randomization, clinicians were unable to place IUDs in more than 5% of participants in both groups; noninferiority was demonstrated nonetheless. This study did not include participants receiving oral EC, so direct comparison of effectiveness is not possible. Pregnancy rates among IUD users in this study were favorable to rates reported in previous studies of oral EC.⁴

When choosing an IUD for contraception, more women select the LNG-IUD for its favorable side effect profile and reduction in menstrual bleeding. In this randomized IUD study, only 7% of eligible participants enrolled, potentially introducing selection bias. The majority who declined enrollment did not want an IUD. Previous studies that allowed participants to choose their IUD had higher enrollment rates. ● 

Turok DK, Gero A, Simmons RG, et al. Levonorgestrel vs copper intrauterine devices for emergency contraception. N Engl J Med. 2021;384:335-344.

EXPERT COMMENTARY

Emergency contraception refers to therapies used to prevent pregnancy after inadequately protected intercourse.¹ Evidence-based forms of EC available in the United States include oral LNG, oral ulipristal acetate, and the copper IUD. The copper IUD provides not only EC but also highly effective contraception after placement.² The LNG-IUD has a favorable side effect profile compared with the copper IUD and is theorized to act as EC through direct interference with sperm and oviduct transport.³ Recently, Turok and colleagues conducted a noninferiority trial designed to investigate the EC effectiveness of the LNG-IUD compared with the copper IUD.³

Details of the study

Turok and colleagues recruited participants aged 18 to 35 who requested EC from 6 family planning clinics in Utah from 2016 to 2019. Participants who reported unprotected intercourse within the past 120 hours and who desired an IUD to prevent pregnancy for at least 1 year were randomly assigned to receive either the LNG-IUD or the copper IUD. Individuals were excluded from the trial if they had contraindications to IUD placement, were breastfeeding, had abnormal uterine bleeding, had irregular menses, were currently using highly effective contraception, or had recent EC use. Researchers determined pregnancy status at 1 month through a pregnancy test or clinical records review.

Results. Of 711 participants randomly assigned, 317 who received the LNG-IUD and 321 who received the copper IUD provided 1-month outcome data. Pregnancy 1 month after IUD placement occurred in 1 participant (0.3%) in the LNG-IUD group and in no participants in the copper IUD group (0%). The between-group difference of 0.3 percentage points was within the margin of noninferiority and was not significant.

Study strengths and limitations

This large, multicenter randomized controlled trial contributes novel information about the effectiveness and noninferiority of the LNG-IUD as EC. Unlike prior studies of oral EC, which commonly limited participants to 1 episode of unprotected intercourse, this trial enrolled women at potentially higher risk of pregnancy with multiple episodes of intercourse and found fewer pregnancies than expected. Randomization ensured equivalence between groups, with the exception of the reason for needing EC.

Study limitations include a higher than expected rate of loss to follow-up, requiring clinical records and survey data to confirm pregnancy status. After randomization, clinicians were unable to place IUDs in more than 5% of participants in both groups; noninferiority was demonstrated nonetheless. This study did not include participants receiving oral EC, so direct comparison of effectiveness is not possible. Pregnancy rates among IUD users in this study were favorable to rates reported in previous studies of oral EC.⁴

When choosing an IUD for contraception, more women select the LNG-IUD for its favorable side effect profile and reduction in menstrual bleeding. In this randomized IUD study, only 7% of eligible participants enrolled, potentially introducing selection bias. The majority who declined enrollment did not want an IUD. Previous studies that allowed participants to choose their IUD had higher enrollment rates. ● 

When gonadotropin-releasing hormone (GnRH) agonist and antagonist peptide medications were first approved for use in the 1980s and 1990s, the available agents could only be administered by injection or nasal spray. The innovative development of orally active, nonpeptide GnRH antagonists, including relugolix and elagolix (FIGURE 1), is a major breakthrough in women’s health. Orally active GnRH antagonists provide gynecologists with a unique way to regulate hypothalamic-pituitary-ovarian-uterus function. GnRH antagonists bind to the pituitary GnRH receptor, reducing pituitary secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In turn, reduction in LH and FSH suppresses ovarian follicle development, reducing ovarian secretion of estradiol and progesterone. The uterine endometrium becomes less active in response to low levels of estradiol and progesterone, resulting in oligomenorrhea or amenorrhea. The hypoestrogenic adverse effects of GnRH antagonist treatment, including bone loss and vasomotor symptoms can be minimized by adding back a low dose of estrogen and progestin, such as oral estradiol 1 mg and norethindrone acetate 0.5 mg.

Recently, the US Food and Drug Administration (FDA) approved oral relugolix combination therapy (Myfembree, Myovant Sciences and Pfizer Inc; relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg) once daily for the treatment of abnormal uterine bleeding (AUB) associated with uterine leiomyomata (fibroids) in premenopausal women for up to 24 months.¹ This editorial will focus on key clinical issues when using relugolix combination therapy.

Relugolix combination treatment is superior to placebo for AUB from fibroids

In 2 clinical trials, 770 women with symptomatic uterine fibroids were randomly assigned to 1 of 3 groups²:

• placebo for 24 weeks
• relugolix combination therapy (consisting of relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg) daily for 24 weeks
• relugolix monotherapy (40 mg daily for 12 weeks) followed by relugolix combination therapy for 12 additional weeks (delayed combination therapy group).

The women’s mean age was approximately 42 years, and they had a mean menstrual blood loss at baseline of approximately 230 mL and mean uterine volume by ultrasound measurement of 408 cm³.² Prior to entry into the study all the women had an endometrial biopsy and a transvaginal ultrasound study of the pelvis. Women with a baseline bone mineral density Z-score of less than -2.0 at the spine, total hip, or femoral neck were excluded from the study because of low bone mass.²

At 24 weeks of treatment, approximately 72% of the women in the relugolix combination therapy groups had less than 80 mL of menstrual blood volume loss and ≥50% reduction in menstrual blood loss from baseline compared with 17% of women in the placebo group.² At 8 weeks of treatment mean percent changes in menstrual blood loss from baseline were approximately 80% and 20% for the women receiving relugolix combination and placebo, respectively. Those differences persisted from 8 weeks through 24 weeks of treatment.¹ In the last 35 days of treatment, amenorrhea was reported by approximately 51% and 4.5% of women receiving relugolix combination or placebo treatment, respectively.² Compared with the placebo group, the relugolix combination groups reported significant improvement in bleeding and pelvic discomfort and had a higher hemoglobin concentration. Compared with placebo, relugolix combination treatment resulted in a greater percentage decrease in uterine volume (-12.9% vs +2.2%, respectively; P< .001).²

Continue to: Relugolix combination treatment is associated with fewer side effects than relugolix monotherapy...

Compared with relugolix combination therapy, women treated with relugolix monotherapy for 12 weeks followed by 12 weeks of relugolix combination therapy lost more bone density as measured by dual-energy X-ray absorptiometry and reported more vasomotor symptoms. This is an expected finding because GnRH antagonist monotherapy is known to significantly reduce ovarian estradiol and progesterone levels, causing bone loss and vasomotor symptoms. Relugolix combination treatment minimizes bone density loss and vasomotor symptoms because the combination of estradiol and norethindrone helps to preserve bone density and reduce hot flashes. Based on these and other findings, the FDA approved relugolix combination therapy for up to 24 months of treatment.¹

Contraindications

Contraindications to relugolix combination therapy include: 1) pregnancy, 2) undiagnosed abnormal uterine bleeding, 3) current or personal history of breast cancer or other hormone-sensitive cancer, 4) known osteoporosis, 5) liver disease, 6) high risk of thrombosis, and 7) hypersensitivity to components of the medication.¹

Adverse reactions

Serious adverse reactions were reported by 3.1% and 2.3% of women treated with the relugolix combination and placebo, respectively. Women taking relugolix combination reported the following adverse effects: 10.6% hot flashes, 6.3% AUB, 3.5% alopecia, and 3.1% decreased libido. Women taking placebo reported the following adverse effects: 6.6% hot flashes, 1.2% AUB, 0.8% alopecia, and 0.4% decreased libido. Among women taking relugolix combination, the following events occurred, each reported once by different women: myoma expulsion with menorrhagia, myoma prolapse without menorrhagia, cholecystitis, and pelvic pain.¹

Bone loss

In women taking relugolix combination or placebo for 6 months, lumbar spine bone density change from baseline, as measured by DEXA, were -0.23% and +0.18%, respectively.¹ After 12 months of relugolix combination treatment, lumbar spine bone density had decreased by -0.8% from baseline. These changes in lumbar bone density are minimal, and in my opinion of no clinical importance.

Reported mental health effects

Compared with placebo, more women taking relugolix combination reported depression, depressed mood, or mood swings (2.4% vs 0.8%), irritability (2.4% vs 0%), and anxiety (1.2% vs 0.8%).¹

Continue to: Options for the treatment of AUB caused by fibroids...

There are many options for the treatment of AUB caused by fibroids, including surgical, hormonal, and nonhormonal therapies. Women with bothersome fibroids strongly prefer to be involved in the decision-making process and select the treatment plan that is best for their situation.³ The patient’s preferences can be explored by discussing the main benefits and common complications and side effects of each treatment option.

Surgical options for the treatment of AUB caused by fibroids include, but are not limited to, hysterectomy (laparoscopic, vaginal, or laparotomy), myomectomy (hysteroscopic, laparoscopic, or laparotomy), uterine artery embolization, focused ultrasound surgery, radiofrequency ablation, cryomyolysis, endometrial ablation, and occlusion of the uterine arteries.⁴ The FIGO classification system provides a consensus nomenclature for describing fibroid location (see FIGURE 2).⁵ The selection of a treatment option is greatly influenced by the location of the fibroids in the uterus.⁶ Most experts recommend hysteroscopic myomectomy to treat Type 0 and Type 1 fibroids causing AUB.⁶ For Type 2 fibroids, hysteroscopic myomectomy, if technically feasible, is associated with a high rate of resolution of AUB with minimal complications. Hormonal treatment of Type 0 and Type 1 fibroids may result in red degeneration of the fibroid with significant menorrhagia.^7,8 In my practice, I generally advise patients that hysteroscopic myomectomy is the first-line treatment option for Types 0, 1, and 2 fibroids causing AUB.

New hormonal treatment adds options for women

Fibroids are the most common pelvic tumor of women. Women with fibroids often present for clinical care due to AUB, pelvic pain, and/or lower abdominal discomfort. For women with symptomatic fibroids it may be difficult to effectively complete employment-related tasks and home responsibilities. In one study, women with symptomatic fibroids reported that their symptoms negatively impacted approximately 20 hours per month of employment-related work and 12 hours per month of home responsibilities, reducing productivity in both settings.¹⁹ Relugolix combination therapy adds another important option for the hormonal treatment of the problems caused by these prevalent and bothersome tumors, improving health and the quality of contributions at work and home. ●

When gonadotropin-releasing hormone (GnRH) agonist and antagonist peptide medications were first approved for use in the 1980s and 1990s, the available agents could only be administered by injection or nasal spray. The innovative development of orally active, nonpeptide GnRH antagonists, including relugolix and elagolix (FIGURE 1), is a major breakthrough in women’s health. Orally active GnRH antagonists provide gynecologists with a unique way to regulate hypothalamic-pituitary-ovarian-uterus function. GnRH antagonists bind to the pituitary GnRH receptor, reducing pituitary secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In turn, reduction in LH and FSH suppresses ovarian follicle development, reducing ovarian secretion of estradiol and progesterone. The uterine endometrium becomes less active in response to low levels of estradiol and progesterone, resulting in oligomenorrhea or amenorrhea. The hypoestrogenic adverse effects of GnRH antagonist treatment, including bone loss and vasomotor symptoms can be minimized by adding back a low dose of estrogen and progestin, such as oral estradiol 1 mg and norethindrone acetate 0.5 mg.

Recently, the US Food and Drug Administration (FDA) approved oral relugolix combination therapy (Myfembree, Myovant Sciences and Pfizer Inc; relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg) once daily for the treatment of abnormal uterine bleeding (AUB) associated with uterine leiomyomata (fibroids) in premenopausal women for up to 24 months.¹ This editorial will focus on key clinical issues when using relugolix combination therapy.

Relugolix combination treatment is superior to placebo for AUB from fibroids

In 2 clinical trials, 770 women with symptomatic uterine fibroids were randomly assigned to 1 of 3 groups²:

• placebo for 24 weeks
• relugolix combination therapy (consisting of relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg) daily for 24 weeks
• relugolix monotherapy (40 mg daily for 12 weeks) followed by relugolix combination therapy for 12 additional weeks (delayed combination therapy group).

The women’s mean age was approximately 42 years, and they had a mean menstrual blood loss at baseline of approximately 230 mL and mean uterine volume by ultrasound measurement of 408 cm³.² Prior to entry into the study all the women had an endometrial biopsy and a transvaginal ultrasound study of the pelvis. Women with a baseline bone mineral density Z-score of less than -2.0 at the spine, total hip, or femoral neck were excluded from the study because of low bone mass.²

At 24 weeks of treatment, approximately 72% of the women in the relugolix combination therapy groups had less than 80 mL of menstrual blood volume loss and ≥50% reduction in menstrual blood loss from baseline compared with 17% of women in the placebo group.² At 8 weeks of treatment mean percent changes in menstrual blood loss from baseline were approximately 80% and 20% for the women receiving relugolix combination and placebo, respectively. Those differences persisted from 8 weeks through 24 weeks of treatment.¹ In the last 35 days of treatment, amenorrhea was reported by approximately 51% and 4.5% of women receiving relugolix combination or placebo treatment, respectively.² Compared with the placebo group, the relugolix combination groups reported significant improvement in bleeding and pelvic discomfort and had a higher hemoglobin concentration. Compared with placebo, relugolix combination treatment resulted in a greater percentage decrease in uterine volume (-12.9% vs +2.2%, respectively; P< .001).²

Continue to: Relugolix combination treatment is associated with fewer side effects than relugolix monotherapy...

Compared with relugolix combination therapy, women treated with relugolix monotherapy for 12 weeks followed by 12 weeks of relugolix combination therapy lost more bone density as measured by dual-energy X-ray absorptiometry and reported more vasomotor symptoms. This is an expected finding because GnRH antagonist monotherapy is known to significantly reduce ovarian estradiol and progesterone levels, causing bone loss and vasomotor symptoms. Relugolix combination treatment minimizes bone density loss and vasomotor symptoms because the combination of estradiol and norethindrone helps to preserve bone density and reduce hot flashes. Based on these and other findings, the FDA approved relugolix combination therapy for up to 24 months of treatment.¹

Contraindications

Contraindications to relugolix combination therapy include: 1) pregnancy, 2) undiagnosed abnormal uterine bleeding, 3) current or personal history of breast cancer or other hormone-sensitive cancer, 4) known osteoporosis, 5) liver disease, 6) high risk of thrombosis, and 7) hypersensitivity to components of the medication.¹

Adverse reactions

Serious adverse reactions were reported by 3.1% and 2.3% of women treated with the relugolix combination and placebo, respectively. Women taking relugolix combination reported the following adverse effects: 10.6% hot flashes, 6.3% AUB, 3.5% alopecia, and 3.1% decreased libido. Women taking placebo reported the following adverse effects: 6.6% hot flashes, 1.2% AUB, 0.8% alopecia, and 0.4% decreased libido. Among women taking relugolix combination, the following events occurred, each reported once by different women: myoma expulsion with menorrhagia, myoma prolapse without menorrhagia, cholecystitis, and pelvic pain.¹

Bone loss

In women taking relugolix combination or placebo for 6 months, lumbar spine bone density change from baseline, as measured by DEXA, were -0.23% and +0.18%, respectively.¹ After 12 months of relugolix combination treatment, lumbar spine bone density had decreased by -0.8% from baseline. These changes in lumbar bone density are minimal, and in my opinion of no clinical importance.

Reported mental health effects

Compared with placebo, more women taking relugolix combination reported depression, depressed mood, or mood swings (2.4% vs 0.8%), irritability (2.4% vs 0%), and anxiety (1.2% vs 0.8%).¹

Continue to: Options for the treatment of AUB caused by fibroids...

There are many options for the treatment of AUB caused by fibroids, including surgical, hormonal, and nonhormonal therapies. Women with bothersome fibroids strongly prefer to be involved in the decision-making process and select the treatment plan that is best for their situation.³ The patient’s preferences can be explored by discussing the main benefits and common complications and side effects of each treatment option.

Surgical options for the treatment of AUB caused by fibroids include, but are not limited to, hysterectomy (laparoscopic, vaginal, or laparotomy), myomectomy (hysteroscopic, laparoscopic, or laparotomy), uterine artery embolization, focused ultrasound surgery, radiofrequency ablation, cryomyolysis, endometrial ablation, and occlusion of the uterine arteries.⁴ The FIGO classification system provides a consensus nomenclature for describing fibroid location (see FIGURE 2).⁵ The selection of a treatment option is greatly influenced by the location of the fibroids in the uterus.⁶ Most experts recommend hysteroscopic myomectomy to treat Type 0 and Type 1 fibroids causing AUB.⁶ For Type 2 fibroids, hysteroscopic myomectomy, if technically feasible, is associated with a high rate of resolution of AUB with minimal complications. Hormonal treatment of Type 0 and Type 1 fibroids may result in red degeneration of the fibroid with significant menorrhagia.^7,8 In my practice, I generally advise patients that hysteroscopic myomectomy is the first-line treatment option for Types 0, 1, and 2 fibroids causing AUB.

New hormonal treatment adds options for women

Fibroids are the most common pelvic tumor of women. Women with fibroids often present for clinical care due to AUB, pelvic pain, and/or lower abdominal discomfort. For women with symptomatic fibroids it may be difficult to effectively complete employment-related tasks and home responsibilities. In one study, women with symptomatic fibroids reported that their symptoms negatively impacted approximately 20 hours per month of employment-related work and 12 hours per month of home responsibilities, reducing productivity in both settings.¹⁹ Relugolix combination therapy adds another important option for the hormonal treatment of the problems caused by these prevalent and bothersome tumors, improving health and the quality of contributions at work and home. ●

When gonadotropin-releasing hormone (GnRH) agonist and antagonist peptide medications were first approved for use in the 1980s and 1990s, the available agents could only be administered by injection or nasal spray. The innovative development of orally active, nonpeptide GnRH antagonists, including relugolix and elagolix (FIGURE 1), is a major breakthrough in women’s health. Orally active GnRH antagonists provide gynecologists with a unique way to regulate hypothalamic-pituitary-ovarian-uterus function. GnRH antagonists bind to the pituitary GnRH receptor, reducing pituitary secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In turn, reduction in LH and FSH suppresses ovarian follicle development, reducing ovarian secretion of estradiol and progesterone. The uterine endometrium becomes less active in response to low levels of estradiol and progesterone, resulting in oligomenorrhea or amenorrhea. The hypoestrogenic adverse effects of GnRH antagonist treatment, including bone loss and vasomotor symptoms can be minimized by adding back a low dose of estrogen and progestin, such as oral estradiol 1 mg and norethindrone acetate 0.5 mg.

Recently, the US Food and Drug Administration (FDA) approved oral relugolix combination therapy (Myfembree, Myovant Sciences and Pfizer Inc; relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg) once daily for the treatment of abnormal uterine bleeding (AUB) associated with uterine leiomyomata (fibroids) in premenopausal women for up to 24 months.¹ This editorial will focus on key clinical issues when using relugolix combination therapy.

Relugolix combination treatment is superior to placebo for AUB from fibroids

In 2 clinical trials, 770 women with symptomatic uterine fibroids were randomly assigned to 1 of 3 groups²:

• placebo for 24 weeks
• relugolix combination therapy (consisting of relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg) daily for 24 weeks
• relugolix monotherapy (40 mg daily for 12 weeks) followed by relugolix combination therapy for 12 additional weeks (delayed combination therapy group).

The women’s mean age was approximately 42 years, and they had a mean menstrual blood loss at baseline of approximately 230 mL and mean uterine volume by ultrasound measurement of 408 cm³.² Prior to entry into the study all the women had an endometrial biopsy and a transvaginal ultrasound study of the pelvis. Women with a baseline bone mineral density Z-score of less than -2.0 at the spine, total hip, or femoral neck were excluded from the study because of low bone mass.²

At 24 weeks of treatment, approximately 72% of the women in the relugolix combination therapy groups had less than 80 mL of menstrual blood volume loss and ≥50% reduction in menstrual blood loss from baseline compared with 17% of women in the placebo group.² At 8 weeks of treatment mean percent changes in menstrual blood loss from baseline were approximately 80% and 20% for the women receiving relugolix combination and placebo, respectively. Those differences persisted from 8 weeks through 24 weeks of treatment.¹ In the last 35 days of treatment, amenorrhea was reported by approximately 51% and 4.5% of women receiving relugolix combination or placebo treatment, respectively.² Compared with the placebo group, the relugolix combination groups reported significant improvement in bleeding and pelvic discomfort and had a higher hemoglobin concentration. Compared with placebo, relugolix combination treatment resulted in a greater percentage decrease in uterine volume (-12.9% vs +2.2%, respectively; P< .001).²

Continue to: Relugolix combination treatment is associated with fewer side effects than relugolix monotherapy...

Compared with relugolix combination therapy, women treated with relugolix monotherapy for 12 weeks followed by 12 weeks of relugolix combination therapy lost more bone density as measured by dual-energy X-ray absorptiometry and reported more vasomotor symptoms. This is an expected finding because GnRH antagonist monotherapy is known to significantly reduce ovarian estradiol and progesterone levels, causing bone loss and vasomotor symptoms. Relugolix combination treatment minimizes bone density loss and vasomotor symptoms because the combination of estradiol and norethindrone helps to preserve bone density and reduce hot flashes. Based on these and other findings, the FDA approved relugolix combination therapy for up to 24 months of treatment.¹

Contraindications

Contraindications to relugolix combination therapy include: 1) pregnancy, 2) undiagnosed abnormal uterine bleeding, 3) current or personal history of breast cancer or other hormone-sensitive cancer, 4) known osteoporosis, 5) liver disease, 6) high risk of thrombosis, and 7) hypersensitivity to components of the medication.¹

Adverse reactions

Serious adverse reactions were reported by 3.1% and 2.3% of women treated with the relugolix combination and placebo, respectively. Women taking relugolix combination reported the following adverse effects: 10.6% hot flashes, 6.3% AUB, 3.5% alopecia, and 3.1% decreased libido. Women taking placebo reported the following adverse effects: 6.6% hot flashes, 1.2% AUB, 0.8% alopecia, and 0.4% decreased libido. Among women taking relugolix combination, the following events occurred, each reported once by different women: myoma expulsion with menorrhagia, myoma prolapse without menorrhagia, cholecystitis, and pelvic pain.¹

Bone loss

In women taking relugolix combination or placebo for 6 months, lumbar spine bone density change from baseline, as measured by DEXA, were -0.23% and +0.18%, respectively.¹ After 12 months of relugolix combination treatment, lumbar spine bone density had decreased by -0.8% from baseline. These changes in lumbar bone density are minimal, and in my opinion of no clinical importance.

Reported mental health effects

Compared with placebo, more women taking relugolix combination reported depression, depressed mood, or mood swings (2.4% vs 0.8%), irritability (2.4% vs 0%), and anxiety (1.2% vs 0.8%).¹

Continue to: Options for the treatment of AUB caused by fibroids...

There are many options for the treatment of AUB caused by fibroids, including surgical, hormonal, and nonhormonal therapies. Women with bothersome fibroids strongly prefer to be involved in the decision-making process and select the treatment plan that is best for their situation.³ The patient’s preferences can be explored by discussing the main benefits and common complications and side effects of each treatment option.

Surgical options for the treatment of AUB caused by fibroids include, but are not limited to, hysterectomy (laparoscopic, vaginal, or laparotomy), myomectomy (hysteroscopic, laparoscopic, or laparotomy), uterine artery embolization, focused ultrasound surgery, radiofrequency ablation, cryomyolysis, endometrial ablation, and occlusion of the uterine arteries.⁴ The FIGO classification system provides a consensus nomenclature for describing fibroid location (see FIGURE 2).⁵ The selection of a treatment option is greatly influenced by the location of the fibroids in the uterus.⁶ Most experts recommend hysteroscopic myomectomy to treat Type 0 and Type 1 fibroids causing AUB.⁶ For Type 2 fibroids, hysteroscopic myomectomy, if technically feasible, is associated with a high rate of resolution of AUB with minimal complications. Hormonal treatment of Type 0 and Type 1 fibroids may result in red degeneration of the fibroid with significant menorrhagia.^7,8 In my practice, I generally advise patients that hysteroscopic myomectomy is the first-line treatment option for Types 0, 1, and 2 fibroids causing AUB.

New hormonal treatment adds options for women

Fibroids are the most common pelvic tumor of women. Women with fibroids often present for clinical care due to AUB, pelvic pain, and/or lower abdominal discomfort. For women with symptomatic fibroids it may be difficult to effectively complete employment-related tasks and home responsibilities. In one study, women with symptomatic fibroids reported that their symptoms negatively impacted approximately 20 hours per month of employment-related work and 12 hours per month of home responsibilities, reducing productivity in both settings.¹⁹ Relugolix combination therapy adds another important option for the hormonal treatment of the problems caused by these prevalent and bothersome tumors, improving health and the quality of contributions at work and home. ●

CASE Patient finds that follow-up ultrasonography is burdensome

Ms. MB presents to the clinic for dating ultrasonography and is diagnosed with a missed abortion measuring 7 weeks. After reviewing her management options, she elects for medication management. She receives mifepristone 200 mg and misoprostol 800 µg, with a plan to follow-up in clinic for repeat ultrasonography in a week. The day of her follow-up appointment, there is a large snowstorm. She calls her care team to ask if she needs to have a follow-up visit, as she is certain she has passed tissue and her bleeding is now minimal. She is told, however, that a follow-up ultrasonography is required, per clinic policy, to ensure successful management. Despite Ms. MB’s grief and the difficult travel conditions, she makes the arduous journey back to the clinic to complete the ultrasound.

Do all patients need an ultrasound after medication management of early pregnancy loss? Or is there an alternative follow-up option?

Early pregnancy loss (EPL) is a common pregnancy complication, and its management is a routine part of reproductive health care. In the clinically stable patient, EPL may be managed expectantly, surgically, or medically, based on the patient’s preference. For patients who select medication management, clear evidence supports that a combination regimen of mifepristone and misoprostol is more effective than treatment with misoprostol alone.^1,2 The data suggest that 91% of patients will experience expulsion of the gestational sac by 30 days with medication management.¹ Because a minority of patients will have a retained gestational sac despite medication therapy, follow-up ensures complete expulsion of pregnancy tissue.

In the United States, most follow-up protocols include an ultrasound examination, which often entails transvaginal ultrasonography. Returning to clinic for an additional ultrasound may be costly and inconvenient—and during a global pandemic medically risky. Further, it may undermine a fundamental principle in management of EPL: autonomy. Many patients who select medication management do so out of a desire to minimize interventions or procedures. Follow-up protocols that align with patient preferences for fewer interventions are critically important to the provision of patient-centered care. Additionally, the COVID-19 pandemic highlights the value of offering an alternative follow-up strategy that minimizes the need for additional visits to a clinic or hospital.

Lessons from medication abortion management

In many ways, follow-up after medication management of EPL is analogous to follow-up after medication abortion. In both cases, the goal of follow-up is to ensure that complete expulsion has occurred without complication and to identify patients with incomplete expulsion of pregnancy tissue who may benefit from further treatment with additional medication or uterine aspiration. A key difference in the management of EPL is that there is no concern for ongoing pregnancy.

Historically, follow-up transvaginal ultra­sonography was routinely performed after medication abortion to ensure complete expulsion of pregnancy.³ However, requiring patients to return to a health care facility for ultrasonography after abortion can be burdensome, both for patients and clinicians. To provide more accessible, patient-centered care, researchers have investigated alternative follow-up strategies for medication abortion that remove the necessity for ultrasonography. Guidelines from both the National Abortion Federation and the American College of Obstetricians and Gynecologists state that routine ultrasonography is not necessary after medication abortion.^4,5

Quantitative serum human chorionic gonadotropin (hCG) testing before treatment and at a follow-up visit is one reasonable strategy to ensure successful treatment. In one study of medication abortion patients, an 80% decrease in serum hCG was predictive of complete expulsion in 98.5% of patients.⁶ While this strategy avoids ultrasonography, it still necessitates a visit to a health care facility for a blood draw. As an alternative, substantial evidence now demonstrates the safety and feasibility of using a combination of clinical symptoms and urine pregnancy testing to confirm completed medication abortion. The evidence for follow-up using a combination of clinical symptoms and urine pregnancy testing is discussed below.

Continue to: Symptoms...

Symptoms. An assessment of symptoms alone, by the patient or clinician, is an important indicator of treatment success and can be completed easily via telephone. In one study of medication abortion with mifepristone and misoprostol, patients correctly predicted passage of a gestational sac 85% of the time based on symptoms alone.⁷ In another study, the combined clinical assessment from the patient and the clinician had a sensitivity of 96% and a specificity of 67% for predicting complete pregnancy expulsion.⁸ Finally, in an analysis of 931 patients after medication abortion, when both the patient and clinician believed that the gestational sac had passed, ultrasonography demonstrated complete expulsion 99% of the time.⁹

Urine pregnancy testing. Several studies have demonstrated that the addition of urine pregnancy testing to a clinical assessment of symptoms is a safe and effective follow-up strategy in medication abortion. Contemporary over-the-counter pregnancy tests are high-sensitivity tests that have an hCG detection threshold of 25 to 50 mIU/mL. As these tests are widely and commercially available in the United States, they can be a useful tool in follow-up strategies.

In a study by Chen and colleagues, patients seeking medication abortion were offered a choice of follow-up with ultrasonography at 1 week versus a combination of a 1-week phone call and a 4-week high-sensitivity urine pregnancy test. In this study, approximately 40% of patients opted for phone follow-up. The rates of incomplete abortion and loss to follow-up were similar between the 2 groups, highlighting the significant number of individuals interested in alternative models of follow-up and the efficacy of phone and urine testing specifically.¹⁰

In another study that evaluated the feasibility of a telephone and urine testing follow-up strategy, 97% of patients completed follow-up and all continuing pregnancies were diagnosed prior to the 4-week urine pregnancy test.⁸

In a hospital in Edinburgh, where a telephone-based symptom assessment in combination with a 2-week low-sensitivity pregnancy test (hCG detection threshold of 2,000 mIU/mL; not commercially available in the United States) is the standard of care for medication abortion follow-up, Michie and Cameron reported a sensitivity of 100% and a specificity of 88% to detect ongoing pregnancies.¹¹

Taken together, these data demonstrate that a combination of symptom assessment via telephone and home urine pregnancy testing (in addition to standard patient instructions and return precautions) is an appropriate strategy for medication abortion follow-up, and they suggest that similar strategies can be employed in the medication management of EPL.

To scan or not to scan?

Many published studies of EPL have used ultrasonography to confirm complete expulsion of pregnancy tissue; however, others have relied on either clinical evaluation or urine pregnancy testing to determine treatment success, using ultrasonography only as clinically indicated.^12-14 In their evaluation of medication management versus surgical management of miscarriage, Niinimäki and colleagues performed urine hCG testing at a 5- to 6-week follow-up visit to determine treatment success; ultrasonography was obtained only if the urine hCG test was positive. They demonstrated a treatment success rate of 90% with mifepristone and misoprostol treatment,¹² congruent with previously published results.

While a follow-up ultrasound scan may be helpful to accurately assess treatment efficacy in research protocols, it should not be considered necessary in clinical practice. Posttreatment imaging in an asymptomatic patient may place additional burden on the patient and health care system and may result in unnecessary intervention. Although treatment success is reliably defined by the absence of a gestational sac,^15,16 the finding of a thickened endometrium or presence of vascularity may result in the patient receiving an unnecessary aspiration or other intervention.

The evidence from the medication abortion literature suggests that a combination of a 1-week telephone call to assess patient symptoms in addition to a 4-week high-sensitivity pregnancy test is a reasonable alternative follow-up strategy. A similar strategy is already used in the United Kingdom, where current National Institute for Health and Care Excellence guidelines for follow-up after medication management of EPL recommend home pregnancy testing in 3 weeks unless the patient experiences worsening pain or bleeding symptoms.¹⁷

Time to rethink follow-up care

Follow-up care for EPL should be provided in a way that is sensitive to the needs and preferences of the patient and, if desired, minimizes additional health care visits, testing, or procedures. While some patients may prefer ultrasonography follow-up, it is important for the clinician to recognize that there are safe and effective alternatives. Patient preference guides the choice of EPL management; this logic extends to follow-up strategies. As we strive to provide evidence-based, patient-centered EPL care, there is no need for universal follow-up ultrasonography. ●

CASE Patient finds that follow-up ultrasonography is burdensome

Ms. MB presents to the clinic for dating ultrasonography and is diagnosed with a missed abortion measuring 7 weeks. After reviewing her management options, she elects for medication management. She receives mifepristone 200 mg and misoprostol 800 µg, with a plan to follow-up in clinic for repeat ultrasonography in a week. The day of her follow-up appointment, there is a large snowstorm. She calls her care team to ask if she needs to have a follow-up visit, as she is certain she has passed tissue and her bleeding is now minimal. She is told, however, that a follow-up ultrasonography is required, per clinic policy, to ensure successful management. Despite Ms. MB’s grief and the difficult travel conditions, she makes the arduous journey back to the clinic to complete the ultrasound.

Do all patients need an ultrasound after medication management of early pregnancy loss? Or is there an alternative follow-up option?

Early pregnancy loss (EPL) is a common pregnancy complication, and its management is a routine part of reproductive health care. In the clinically stable patient, EPL may be managed expectantly, surgically, or medically, based on the patient’s preference. For patients who select medication management, clear evidence supports that a combination regimen of mifepristone and misoprostol is more effective than treatment with misoprostol alone.^1,2 The data suggest that 91% of patients will experience expulsion of the gestational sac by 30 days with medication management.¹ Because a minority of patients will have a retained gestational sac despite medication therapy, follow-up ensures complete expulsion of pregnancy tissue.

In the United States, most follow-up protocols include an ultrasound examination, which often entails transvaginal ultrasonography. Returning to clinic for an additional ultrasound may be costly and inconvenient—and during a global pandemic medically risky. Further, it may undermine a fundamental principle in management of EPL: autonomy. Many patients who select medication management do so out of a desire to minimize interventions or procedures. Follow-up protocols that align with patient preferences for fewer interventions are critically important to the provision of patient-centered care. Additionally, the COVID-19 pandemic highlights the value of offering an alternative follow-up strategy that minimizes the need for additional visits to a clinic or hospital.

Lessons from medication abortion management

In many ways, follow-up after medication management of EPL is analogous to follow-up after medication abortion. In both cases, the goal of follow-up is to ensure that complete expulsion has occurred without complication and to identify patients with incomplete expulsion of pregnancy tissue who may benefit from further treatment with additional medication or uterine aspiration. A key difference in the management of EPL is that there is no concern for ongoing pregnancy.

Historically, follow-up transvaginal ultra­sonography was routinely performed after medication abortion to ensure complete expulsion of pregnancy.³ However, requiring patients to return to a health care facility for ultrasonography after abortion can be burdensome, both for patients and clinicians. To provide more accessible, patient-centered care, researchers have investigated alternative follow-up strategies for medication abortion that remove the necessity for ultrasonography. Guidelines from both the National Abortion Federation and the American College of Obstetricians and Gynecologists state that routine ultrasonography is not necessary after medication abortion.^4,5

Quantitative serum human chorionic gonadotropin (hCG) testing before treatment and at a follow-up visit is one reasonable strategy to ensure successful treatment. In one study of medication abortion patients, an 80% decrease in serum hCG was predictive of complete expulsion in 98.5% of patients.⁶ While this strategy avoids ultrasonography, it still necessitates a visit to a health care facility for a blood draw. As an alternative, substantial evidence now demonstrates the safety and feasibility of using a combination of clinical symptoms and urine pregnancy testing to confirm completed medication abortion. The evidence for follow-up using a combination of clinical symptoms and urine pregnancy testing is discussed below.

Continue to: Symptoms...

Symptoms. An assessment of symptoms alone, by the patient or clinician, is an important indicator of treatment success and can be completed easily via telephone. In one study of medication abortion with mifepristone and misoprostol, patients correctly predicted passage of a gestational sac 85% of the time based on symptoms alone.⁷ In another study, the combined clinical assessment from the patient and the clinician had a sensitivity of 96% and a specificity of 67% for predicting complete pregnancy expulsion.⁸ Finally, in an analysis of 931 patients after medication abortion, when both the patient and clinician believed that the gestational sac had passed, ultrasonography demonstrated complete expulsion 99% of the time.⁹

Urine pregnancy testing. Several studies have demonstrated that the addition of urine pregnancy testing to a clinical assessment of symptoms is a safe and effective follow-up strategy in medication abortion. Contemporary over-the-counter pregnancy tests are high-sensitivity tests that have an hCG detection threshold of 25 to 50 mIU/mL. As these tests are widely and commercially available in the United States, they can be a useful tool in follow-up strategies.

In a study by Chen and colleagues, patients seeking medication abortion were offered a choice of follow-up with ultrasonography at 1 week versus a combination of a 1-week phone call and a 4-week high-sensitivity urine pregnancy test. In this study, approximately 40% of patients opted for phone follow-up. The rates of incomplete abortion and loss to follow-up were similar between the 2 groups, highlighting the significant number of individuals interested in alternative models of follow-up and the efficacy of phone and urine testing specifically.¹⁰

In another study that evaluated the feasibility of a telephone and urine testing follow-up strategy, 97% of patients completed follow-up and all continuing pregnancies were diagnosed prior to the 4-week urine pregnancy test.⁸

In a hospital in Edinburgh, where a telephone-based symptom assessment in combination with a 2-week low-sensitivity pregnancy test (hCG detection threshold of 2,000 mIU/mL; not commercially available in the United States) is the standard of care for medication abortion follow-up, Michie and Cameron reported a sensitivity of 100% and a specificity of 88% to detect ongoing pregnancies.¹¹

Taken together, these data demonstrate that a combination of symptom assessment via telephone and home urine pregnancy testing (in addition to standard patient instructions and return precautions) is an appropriate strategy for medication abortion follow-up, and they suggest that similar strategies can be employed in the medication management of EPL.

To scan or not to scan?

Many published studies of EPL have used ultrasonography to confirm complete expulsion of pregnancy tissue; however, others have relied on either clinical evaluation or urine pregnancy testing to determine treatment success, using ultrasonography only as clinically indicated.^12-14 In their evaluation of medication management versus surgical management of miscarriage, Niinimäki and colleagues performed urine hCG testing at a 5- to 6-week follow-up visit to determine treatment success; ultrasonography was obtained only if the urine hCG test was positive. They demonstrated a treatment success rate of 90% with mifepristone and misoprostol treatment,¹² congruent with previously published results.

While a follow-up ultrasound scan may be helpful to accurately assess treatment efficacy in research protocols, it should not be considered necessary in clinical practice. Posttreatment imaging in an asymptomatic patient may place additional burden on the patient and health care system and may result in unnecessary intervention. Although treatment success is reliably defined by the absence of a gestational sac,^15,16 the finding of a thickened endometrium or presence of vascularity may result in the patient receiving an unnecessary aspiration or other intervention.

The evidence from the medication abortion literature suggests that a combination of a 1-week telephone call to assess patient symptoms in addition to a 4-week high-sensitivity pregnancy test is a reasonable alternative follow-up strategy. A similar strategy is already used in the United Kingdom, where current National Institute for Health and Care Excellence guidelines for follow-up after medication management of EPL recommend home pregnancy testing in 3 weeks unless the patient experiences worsening pain or bleeding symptoms.¹⁷

Time to rethink follow-up care

Follow-up care for EPL should be provided in a way that is sensitive to the needs and preferences of the patient and, if desired, minimizes additional health care visits, testing, or procedures. While some patients may prefer ultrasonography follow-up, it is important for the clinician to recognize that there are safe and effective alternatives. Patient preference guides the choice of EPL management; this logic extends to follow-up strategies. As we strive to provide evidence-based, patient-centered EPL care, there is no need for universal follow-up ultrasonography. ●

CASE Patient finds that follow-up ultrasonography is burdensome

Ms. MB presents to the clinic for dating ultrasonography and is diagnosed with a missed abortion measuring 7 weeks. After reviewing her management options, she elects for medication management. She receives mifepristone 200 mg and misoprostol 800 µg, with a plan to follow-up in clinic for repeat ultrasonography in a week. The day of her follow-up appointment, there is a large snowstorm. She calls her care team to ask if she needs to have a follow-up visit, as she is certain she has passed tissue and her bleeding is now minimal. She is told, however, that a follow-up ultrasonography is required, per clinic policy, to ensure successful management. Despite Ms. MB’s grief and the difficult travel conditions, she makes the arduous journey back to the clinic to complete the ultrasound.

Do all patients need an ultrasound after medication management of early pregnancy loss? Or is there an alternative follow-up option?

Early pregnancy loss (EPL) is a common pregnancy complication, and its management is a routine part of reproductive health care. In the clinically stable patient, EPL may be managed expectantly, surgically, or medically, based on the patient’s preference. For patients who select medication management, clear evidence supports that a combination regimen of mifepristone and misoprostol is more effective than treatment with misoprostol alone.^1,2 The data suggest that 91% of patients will experience expulsion of the gestational sac by 30 days with medication management.¹ Because a minority of patients will have a retained gestational sac despite medication therapy, follow-up ensures complete expulsion of pregnancy tissue.

In the United States, most follow-up protocols include an ultrasound examination, which often entails transvaginal ultrasonography. Returning to clinic for an additional ultrasound may be costly and inconvenient—and during a global pandemic medically risky. Further, it may undermine a fundamental principle in management of EPL: autonomy. Many patients who select medication management do so out of a desire to minimize interventions or procedures. Follow-up protocols that align with patient preferences for fewer interventions are critically important to the provision of patient-centered care. Additionally, the COVID-19 pandemic highlights the value of offering an alternative follow-up strategy that minimizes the need for additional visits to a clinic or hospital.

Lessons from medication abortion management

In many ways, follow-up after medication management of EPL is analogous to follow-up after medication abortion. In both cases, the goal of follow-up is to ensure that complete expulsion has occurred without complication and to identify patients with incomplete expulsion of pregnancy tissue who may benefit from further treatment with additional medication or uterine aspiration. A key difference in the management of EPL is that there is no concern for ongoing pregnancy.

Historically, follow-up transvaginal ultra­sonography was routinely performed after medication abortion to ensure complete expulsion of pregnancy.³ However, requiring patients to return to a health care facility for ultrasonography after abortion can be burdensome, both for patients and clinicians. To provide more accessible, patient-centered care, researchers have investigated alternative follow-up strategies for medication abortion that remove the necessity for ultrasonography. Guidelines from both the National Abortion Federation and the American College of Obstetricians and Gynecologists state that routine ultrasonography is not necessary after medication abortion.^4,5

Quantitative serum human chorionic gonadotropin (hCG) testing before treatment and at a follow-up visit is one reasonable strategy to ensure successful treatment. In one study of medication abortion patients, an 80% decrease in serum hCG was predictive of complete expulsion in 98.5% of patients.⁶ While this strategy avoids ultrasonography, it still necessitates a visit to a health care facility for a blood draw. As an alternative, substantial evidence now demonstrates the safety and feasibility of using a combination of clinical symptoms and urine pregnancy testing to confirm completed medication abortion. The evidence for follow-up using a combination of clinical symptoms and urine pregnancy testing is discussed below.

Continue to: Symptoms...

Symptoms. An assessment of symptoms alone, by the patient or clinician, is an important indicator of treatment success and can be completed easily via telephone. In one study of medication abortion with mifepristone and misoprostol, patients correctly predicted passage of a gestational sac 85% of the time based on symptoms alone.⁷ In another study, the combined clinical assessment from the patient and the clinician had a sensitivity of 96% and a specificity of 67% for predicting complete pregnancy expulsion.⁸ Finally, in an analysis of 931 patients after medication abortion, when both the patient and clinician believed that the gestational sac had passed, ultrasonography demonstrated complete expulsion 99% of the time.⁹

Urine pregnancy testing. Several studies have demonstrated that the addition of urine pregnancy testing to a clinical assessment of symptoms is a safe and effective follow-up strategy in medication abortion. Contemporary over-the-counter pregnancy tests are high-sensitivity tests that have an hCG detection threshold of 25 to 50 mIU/mL. As these tests are widely and commercially available in the United States, they can be a useful tool in follow-up strategies.

In a study by Chen and colleagues, patients seeking medication abortion were offered a choice of follow-up with ultrasonography at 1 week versus a combination of a 1-week phone call and a 4-week high-sensitivity urine pregnancy test. In this study, approximately 40% of patients opted for phone follow-up. The rates of incomplete abortion and loss to follow-up were similar between the 2 groups, highlighting the significant number of individuals interested in alternative models of follow-up and the efficacy of phone and urine testing specifically.¹⁰

In another study that evaluated the feasibility of a telephone and urine testing follow-up strategy, 97% of patients completed follow-up and all continuing pregnancies were diagnosed prior to the 4-week urine pregnancy test.⁸

In a hospital in Edinburgh, where a telephone-based symptom assessment in combination with a 2-week low-sensitivity pregnancy test (hCG detection threshold of 2,000 mIU/mL; not commercially available in the United States) is the standard of care for medication abortion follow-up, Michie and Cameron reported a sensitivity of 100% and a specificity of 88% to detect ongoing pregnancies.¹¹

Taken together, these data demonstrate that a combination of symptom assessment via telephone and home urine pregnancy testing (in addition to standard patient instructions and return precautions) is an appropriate strategy for medication abortion follow-up, and they suggest that similar strategies can be employed in the medication management of EPL.

To scan or not to scan?

Many published studies of EPL have used ultrasonography to confirm complete expulsion of pregnancy tissue; however, others have relied on either clinical evaluation or urine pregnancy testing to determine treatment success, using ultrasonography only as clinically indicated.^12-14 In their evaluation of medication management versus surgical management of miscarriage, Niinimäki and colleagues performed urine hCG testing at a 5- to 6-week follow-up visit to determine treatment success; ultrasonography was obtained only if the urine hCG test was positive. They demonstrated a treatment success rate of 90% with mifepristone and misoprostol treatment,¹² congruent with previously published results.

While a follow-up ultrasound scan may be helpful to accurately assess treatment efficacy in research protocols, it should not be considered necessary in clinical practice. Posttreatment imaging in an asymptomatic patient may place additional burden on the patient and health care system and may result in unnecessary intervention. Although treatment success is reliably defined by the absence of a gestational sac,^15,16 the finding of a thickened endometrium or presence of vascularity may result in the patient receiving an unnecessary aspiration or other intervention.

The evidence from the medication abortion literature suggests that a combination of a 1-week telephone call to assess patient symptoms in addition to a 4-week high-sensitivity pregnancy test is a reasonable alternative follow-up strategy. A similar strategy is already used in the United Kingdom, where current National Institute for Health and Care Excellence guidelines for follow-up after medication management of EPL recommend home pregnancy testing in 3 weeks unless the patient experiences worsening pain or bleeding symptoms.¹⁷

Time to rethink follow-up care

Follow-up care for EPL should be provided in a way that is sensitive to the needs and preferences of the patient and, if desired, minimizes additional health care visits, testing, or procedures. While some patients may prefer ultrasonography follow-up, it is important for the clinician to recognize that there are safe and effective alternatives. Patient preference guides the choice of EPL management; this logic extends to follow-up strategies. As we strive to provide evidence-based, patient-centered EPL care, there is no need for universal follow-up ultrasonography. ●

After a steep decline in the first months of the COVID-19 pandemic, youth with suicidal thoughts and behaviors visiting an emergency department (ED) resurged with an overrepresentation among girls and children without a prior psychiatric history, according to a cross-sectional study conducted at Kaiser Permanente Northern California.

JochenSchoenfeld/Thinkstock

The latest findings, published in JAMA Psychiatry, are highly consistent with Centers for Disease Control and Prevention data published a few months earlier in the Morbidity and Mortality Weekly Report that looked at these trends among young people aged 12-25 before and during the pandemic. In addition, the new data suggest that prevention efforts might be particularly helpful for these young people and their families.

“As suicide-related encounters have made up more ED volume during the pandemic, increasing ED-based interventions, staff trained in addressing emergency mental health needs, and aftercare resources may also be valuable in addressing the needs of this population,” wrote Kathryn K. Erickson-Ridout, MD, PhD, first author of the more recent study and an adjunct investigator with the Kaiser Permanente Division of Research, Oakland, Calif.

“While these results suggest many of our youth are coping well through the pandemic, we need to be vigilant as health care workers,” she said in an interview.

Dr. Ridout and associates evaluated suicide-related ED visits among children aged 5-17 years presenting to EDs in the Kaiser Permanente Northern California system. Four periods in 2020 were compared with the same four periods in 2019.

In the first period, March through May 2020, the incidence rate ratio (IRR) of suicide-related ED visits among children and adolescents fell more than 40% (IRR, 0.53; P < .001) relative to the same months in 2019. This is consistent with a broader decline in other types of ED visits during the beginning of the COVID-19 pandemic.

In the periods of June through August and September to Dec. 15, suicide-related ED visits increased, reaching prepandemic levels overall but with differences between genders. In girls, an increase in the first period reached significance (IRR, 1.19; P = .04) and then climbed even higher in the second (hazard ratio, 1.22; P < .001).
 

Youth present with no prior psychiatric history

Among boys, the increase relative to 2019 in the first period was modest and nonsignificant (IRR, 1.05; P = .26) In the second period, suicide-related ED visits fell and the difference relative to the same period in 2019 reached statistical significance (IRR, 0.81; P = .02).

Other characteristics of suicide-related ED visits during the pandemic were also different from those observed in 2019. One was an increase in visits from youth with no prior history of mental health or suicide-related outpatient visits.

“This finding may suggest that a youth’s first presentation to the ED for suicidal thoughts and behaviors differed during the pandemic, compared to prior to the pandemic,” Dr. Erickson-Ridout explained. “Mental health comorbidities first diagnosed at the ED encounter may suggest an increased complexity at first presentation.”

These data are remarkably similar to ED visits for suicide attempts that were reported by the CDC several months earlier. The CDC data were drawn from the National Syndromic Surveillance Program, which captures data from 71% of the EDs in the United States.

Measured from March 29 to April 25, 2020, ED visits for a suicide attempt declined by more than 25% in both girls and boys, but by early May, those visits were already starting to return to prepandemic levels, particularly among girls, according to the CDC report. When evaluated from July 26 through Aug. 22, 2020, the mean weekly ED visits for suspected suicide attempts had increased 26.2% among girls but only 10.8% among boys, compared with the same period in 2019.

‘More severe distress’ found among girls

In the most recent period evaluated, starting Feb. 21, 2021, and extending to March 20, there was a 50.6% increase among girls in the mean number of weekly ED visits for suspected suicide attempts, compared with the same period in 2019. For boys, the increase was 3.7%.

Higher rates of suicide attempts among girls have been reported by others independent of the COVID-19 pandemic, but the CDC investigators led by Ellen Yard, PhD, a researcher in the CDC’s National Center for Environmental Health, Chamblee, Ga., reported that others have also found greater suicide ideation and attempts by girls during the pandemic. This new report “suggests more severe distress among young females than has been identified in previous reports during the pandemic.”

Neither study was designed to isolate the reason or reasons for an increase in suicide-related ED visits overall or among girls specifically, but Dr. Yard and her coinvestigators speculated that social distancing and isolation during the COVID-19 pandemic might be affecting girls more.

The faster increase in suicide attempts among girls compared with boys “speaks to the importance of upstream prevention to prevent this group from becoming suicidal in the first place as well as improving suicide care both during and after ED visits,” said Dr. Yard, who was interviewed about this research.

For clinicians, she recommended “scaling up adoption of evidence-based best practice.” She cited two such resources from the National Action Alliance for Suicide Prevention (NAASP). One resource is the Best Practices in Care Transitions for Individuals with Suicide Risk: Inpatient Care to Outpatient Care; the other is called Recommended Standard Care. Both are available online for free from the NAASP.

Dr. Erickson-Ridout and Dr. Yard reported no potential conflicts of interest.

After a steep decline in the first months of the COVID-19 pandemic, youth with suicidal thoughts and behaviors visiting an emergency department (ED) resurged with an overrepresentation among girls and children without a prior psychiatric history, according to a cross-sectional study conducted at Kaiser Permanente Northern California.

JochenSchoenfeld/Thinkstock

The latest findings, published in JAMA Psychiatry, are highly consistent with Centers for Disease Control and Prevention data published a few months earlier in the Morbidity and Mortality Weekly Report that looked at these trends among young people aged 12-25 before and during the pandemic. In addition, the new data suggest that prevention efforts might be particularly helpful for these young people and their families.

“As suicide-related encounters have made up more ED volume during the pandemic, increasing ED-based interventions, staff trained in addressing emergency mental health needs, and aftercare resources may also be valuable in addressing the needs of this population,” wrote Kathryn K. Erickson-Ridout, MD, PhD, first author of the more recent study and an adjunct investigator with the Kaiser Permanente Division of Research, Oakland, Calif.

“While these results suggest many of our youth are coping well through the pandemic, we need to be vigilant as health care workers,” she said in an interview.

Dr. Ridout and associates evaluated suicide-related ED visits among children aged 5-17 years presenting to EDs in the Kaiser Permanente Northern California system. Four periods in 2020 were compared with the same four periods in 2019.

In the first period, March through May 2020, the incidence rate ratio (IRR) of suicide-related ED visits among children and adolescents fell more than 40% (IRR, 0.53; P < .001) relative to the same months in 2019. This is consistent with a broader decline in other types of ED visits during the beginning of the COVID-19 pandemic.

In the periods of June through August and September to Dec. 15, suicide-related ED visits increased, reaching prepandemic levels overall but with differences between genders. In girls, an increase in the first period reached significance (IRR, 1.19; P = .04) and then climbed even higher in the second (hazard ratio, 1.22; P < .001).
 

Youth present with no prior psychiatric history

Among boys, the increase relative to 2019 in the first period was modest and nonsignificant (IRR, 1.05; P = .26) In the second period, suicide-related ED visits fell and the difference relative to the same period in 2019 reached statistical significance (IRR, 0.81; P = .02).

Other characteristics of suicide-related ED visits during the pandemic were also different from those observed in 2019. One was an increase in visits from youth with no prior history of mental health or suicide-related outpatient visits.

“This finding may suggest that a youth’s first presentation to the ED for suicidal thoughts and behaviors differed during the pandemic, compared to prior to the pandemic,” Dr. Erickson-Ridout explained. “Mental health comorbidities first diagnosed at the ED encounter may suggest an increased complexity at first presentation.”

These data are remarkably similar to ED visits for suicide attempts that were reported by the CDC several months earlier. The CDC data were drawn from the National Syndromic Surveillance Program, which captures data from 71% of the EDs in the United States.

Measured from March 29 to April 25, 2020, ED visits for a suicide attempt declined by more than 25% in both girls and boys, but by early May, those visits were already starting to return to prepandemic levels, particularly among girls, according to the CDC report. When evaluated from July 26 through Aug. 22, 2020, the mean weekly ED visits for suspected suicide attempts had increased 26.2% among girls but only 10.8% among boys, compared with the same period in 2019.

‘More severe distress’ found among girls

In the most recent period evaluated, starting Feb. 21, 2021, and extending to March 20, there was a 50.6% increase among girls in the mean number of weekly ED visits for suspected suicide attempts, compared with the same period in 2019. For boys, the increase was 3.7%.

Higher rates of suicide attempts among girls have been reported by others independent of the COVID-19 pandemic, but the CDC investigators led by Ellen Yard, PhD, a researcher in the CDC’s National Center for Environmental Health, Chamblee, Ga., reported that others have also found greater suicide ideation and attempts by girls during the pandemic. This new report “suggests more severe distress among young females than has been identified in previous reports during the pandemic.”

Neither study was designed to isolate the reason or reasons for an increase in suicide-related ED visits overall or among girls specifically, but Dr. Yard and her coinvestigators speculated that social distancing and isolation during the COVID-19 pandemic might be affecting girls more.

The faster increase in suicide attempts among girls compared with boys “speaks to the importance of upstream prevention to prevent this group from becoming suicidal in the first place as well as improving suicide care both during and after ED visits,” said Dr. Yard, who was interviewed about this research.

For clinicians, she recommended “scaling up adoption of evidence-based best practice.” She cited two such resources from the National Action Alliance for Suicide Prevention (NAASP). One resource is the Best Practices in Care Transitions for Individuals with Suicide Risk: Inpatient Care to Outpatient Care; the other is called Recommended Standard Care. Both are available online for free from the NAASP.

Dr. Erickson-Ridout and Dr. Yard reported no potential conflicts of interest.

After a steep decline in the first months of the COVID-19 pandemic, youth with suicidal thoughts and behaviors visiting an emergency department (ED) resurged with an overrepresentation among girls and children without a prior psychiatric history, according to a cross-sectional study conducted at Kaiser Permanente Northern California.

JochenSchoenfeld/Thinkstock

The latest findings, published in JAMA Psychiatry, are highly consistent with Centers for Disease Control and Prevention data published a few months earlier in the Morbidity and Mortality Weekly Report that looked at these trends among young people aged 12-25 before and during the pandemic. In addition, the new data suggest that prevention efforts might be particularly helpful for these young people and their families.

“As suicide-related encounters have made up more ED volume during the pandemic, increasing ED-based interventions, staff trained in addressing emergency mental health needs, and aftercare resources may also be valuable in addressing the needs of this population,” wrote Kathryn K. Erickson-Ridout, MD, PhD, first author of the more recent study and an adjunct investigator with the Kaiser Permanente Division of Research, Oakland, Calif.

“While these results suggest many of our youth are coping well through the pandemic, we need to be vigilant as health care workers,” she said in an interview.

Dr. Ridout and associates evaluated suicide-related ED visits among children aged 5-17 years presenting to EDs in the Kaiser Permanente Northern California system. Four periods in 2020 were compared with the same four periods in 2019.

In the first period, March through May 2020, the incidence rate ratio (IRR) of suicide-related ED visits among children and adolescents fell more than 40% (IRR, 0.53; P < .001) relative to the same months in 2019. This is consistent with a broader decline in other types of ED visits during the beginning of the COVID-19 pandemic.

In the periods of June through August and September to Dec. 15, suicide-related ED visits increased, reaching prepandemic levels overall but with differences between genders. In girls, an increase in the first period reached significance (IRR, 1.19; P = .04) and then climbed even higher in the second (hazard ratio, 1.22; P < .001).
 

Youth present with no prior psychiatric history

Among boys, the increase relative to 2019 in the first period was modest and nonsignificant (IRR, 1.05; P = .26) In the second period, suicide-related ED visits fell and the difference relative to the same period in 2019 reached statistical significance (IRR, 0.81; P = .02).

Other characteristics of suicide-related ED visits during the pandemic were also different from those observed in 2019. One was an increase in visits from youth with no prior history of mental health or suicide-related outpatient visits.

“This finding may suggest that a youth’s first presentation to the ED for suicidal thoughts and behaviors differed during the pandemic, compared to prior to the pandemic,” Dr. Erickson-Ridout explained. “Mental health comorbidities first diagnosed at the ED encounter may suggest an increased complexity at first presentation.”

These data are remarkably similar to ED visits for suicide attempts that were reported by the CDC several months earlier. The CDC data were drawn from the National Syndromic Surveillance Program, which captures data from 71% of the EDs in the United States.

Measured from March 29 to April 25, 2020, ED visits for a suicide attempt declined by more than 25% in both girls and boys, but by early May, those visits were already starting to return to prepandemic levels, particularly among girls, according to the CDC report. When evaluated from July 26 through Aug. 22, 2020, the mean weekly ED visits for suspected suicide attempts had increased 26.2% among girls but only 10.8% among boys, compared with the same period in 2019.

‘More severe distress’ found among girls

In the most recent period evaluated, starting Feb. 21, 2021, and extending to March 20, there was a 50.6% increase among girls in the mean number of weekly ED visits for suspected suicide attempts, compared with the same period in 2019. For boys, the increase was 3.7%.

Higher rates of suicide attempts among girls have been reported by others independent of the COVID-19 pandemic, but the CDC investigators led by Ellen Yard, PhD, a researcher in the CDC’s National Center for Environmental Health, Chamblee, Ga., reported that others have also found greater suicide ideation and attempts by girls during the pandemic. This new report “suggests more severe distress among young females than has been identified in previous reports during the pandemic.”

Neither study was designed to isolate the reason or reasons for an increase in suicide-related ED visits overall or among girls specifically, but Dr. Yard and her coinvestigators speculated that social distancing and isolation during the COVID-19 pandemic might be affecting girls more.

The faster increase in suicide attempts among girls compared with boys “speaks to the importance of upstream prevention to prevent this group from becoming suicidal in the first place as well as improving suicide care both during and after ED visits,” said Dr. Yard, who was interviewed about this research.

For clinicians, she recommended “scaling up adoption of evidence-based best practice.” She cited two such resources from the National Action Alliance for Suicide Prevention (NAASP). One resource is the Best Practices in Care Transitions for Individuals with Suicide Risk: Inpatient Care to Outpatient Care; the other is called Recommended Standard Care. Both are available online for free from the NAASP.

Dr. Erickson-Ridout and Dr. Yard reported no potential conflicts of interest.

Among cancer patients with solid tumors, the response to the COVID-19 vaccine 6 months after receiving a second dose was as good as that of the general population, according to new findings from a case-control study.

The BNT162b2, or Pfizer-BioNTech, vaccine (Comirnaty) was previously shown to have good short-term efficacy, immunogenicity, and safety in cancer patients with solid tumors, but little is known about longer-term efficacy in this population, say the investigators.

They assessed responses 6 months after a second dose of the vaccine.

Serologic tests showed that 122 of 154 patients with solid tumors who were actively undergoing cancer treatment (79%) and 114 of 135 age-matched health care workers who served as control persons (84%) were seropositive at 6 months (P = .32).

Most (81%) of the patients with cancer who were seronegative were receiving chemotherapy, the researchers report.

One case of severe COVID-19 that required hospitalization occurred among the solid-tumor group; none occurred among the control persons, they also note.

The findings were published online on Sept. 2 in Cancer Discovery.

“In our study we saw that in all outcomes, including immunogenicity, infectivity rate throughout the 6-month period, and safety, patients with solid tumors depicted a similar trend as the general population,” commented lead author Irit Ben-Aharon, MD, PhD, director of the division of oncology at Rambam Health Care Campus, Haifa, Israel, in an American Association for Cancer Research press statement.

However, she and her coauthors stressed the importance of continuing to follow guidance, such as social distancing and mask wearing, for reducing COVID-19 transmission. “Due to uncertainty of the extended efficacy of the vaccine in the general population and recent reports on rising infection rates among vaccinated individuals, adherence to health care risk reduction recommendations is cardinal,” they write.

The mean age of the control persons in the study was 63 years, and the mean age of the case patients was 66 years. The most common cancers were gastrointestinal (36%), lung (23%), breast (17%), and genitourinary (11%). Treatment protocols included chemotherapy (62%), biological agents (36%), and immunotherapy (30%). Some patients received more than one type of treatment.

All of the reported adverse effects associated with vaccination had resolved at the time of follow-up.

These data can “help inform recommendations surrounding the prioritization of different groups for booster vaccines,” Dr. Ben-Aharon adds.

In fact, recently updated guidelines from the National Comprehensive Cancer Network state that cancer patients with solid tumors who are receiving treatment within 1 year of their initial vaccine dose should be prioritized for a booster vaccine.

The study was partially supported by the Israel Cancer Research Fund. Serologic testing of the control cohort was supported by the Ministry of Health, Israel. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Among cancer patients with solid tumors, the response to the COVID-19 vaccine 6 months after receiving a second dose was as good as that of the general population, according to new findings from a case-control study.

The BNT162b2, or Pfizer-BioNTech, vaccine (Comirnaty) was previously shown to have good short-term efficacy, immunogenicity, and safety in cancer patients with solid tumors, but little is known about longer-term efficacy in this population, say the investigators.

They assessed responses 6 months after a second dose of the vaccine.

Serologic tests showed that 122 of 154 patients with solid tumors who were actively undergoing cancer treatment (79%) and 114 of 135 age-matched health care workers who served as control persons (84%) were seropositive at 6 months (P = .32).

Most (81%) of the patients with cancer who were seronegative were receiving chemotherapy, the researchers report.

One case of severe COVID-19 that required hospitalization occurred among the solid-tumor group; none occurred among the control persons, they also note.

The findings were published online on Sept. 2 in Cancer Discovery.

“In our study we saw that in all outcomes, including immunogenicity, infectivity rate throughout the 6-month period, and safety, patients with solid tumors depicted a similar trend as the general population,” commented lead author Irit Ben-Aharon, MD, PhD, director of the division of oncology at Rambam Health Care Campus, Haifa, Israel, in an American Association for Cancer Research press statement.

However, she and her coauthors stressed the importance of continuing to follow guidance, such as social distancing and mask wearing, for reducing COVID-19 transmission. “Due to uncertainty of the extended efficacy of the vaccine in the general population and recent reports on rising infection rates among vaccinated individuals, adherence to health care risk reduction recommendations is cardinal,” they write.

The mean age of the control persons in the study was 63 years, and the mean age of the case patients was 66 years. The most common cancers were gastrointestinal (36%), lung (23%), breast (17%), and genitourinary (11%). Treatment protocols included chemotherapy (62%), biological agents (36%), and immunotherapy (30%). Some patients received more than one type of treatment.

All of the reported adverse effects associated with vaccination had resolved at the time of follow-up.

These data can “help inform recommendations surrounding the prioritization of different groups for booster vaccines,” Dr. Ben-Aharon adds.

In fact, recently updated guidelines from the National Comprehensive Cancer Network state that cancer patients with solid tumors who are receiving treatment within 1 year of their initial vaccine dose should be prioritized for a booster vaccine.

The study was partially supported by the Israel Cancer Research Fund. Serologic testing of the control cohort was supported by the Ministry of Health, Israel. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Among cancer patients with solid tumors, the response to the COVID-19 vaccine 6 months after receiving a second dose was as good as that of the general population, according to new findings from a case-control study.

The BNT162b2, or Pfizer-BioNTech, vaccine (Comirnaty) was previously shown to have good short-term efficacy, immunogenicity, and safety in cancer patients with solid tumors, but little is known about longer-term efficacy in this population, say the investigators.

They assessed responses 6 months after a second dose of the vaccine.

Serologic tests showed that 122 of 154 patients with solid tumors who were actively undergoing cancer treatment (79%) and 114 of 135 age-matched health care workers who served as control persons (84%) were seropositive at 6 months (P = .32).

Most (81%) of the patients with cancer who were seronegative were receiving chemotherapy, the researchers report.

One case of severe COVID-19 that required hospitalization occurred among the solid-tumor group; none occurred among the control persons, they also note.

The findings were published online on Sept. 2 in Cancer Discovery.

“In our study we saw that in all outcomes, including immunogenicity, infectivity rate throughout the 6-month period, and safety, patients with solid tumors depicted a similar trend as the general population,” commented lead author Irit Ben-Aharon, MD, PhD, director of the division of oncology at Rambam Health Care Campus, Haifa, Israel, in an American Association for Cancer Research press statement.

However, she and her coauthors stressed the importance of continuing to follow guidance, such as social distancing and mask wearing, for reducing COVID-19 transmission. “Due to uncertainty of the extended efficacy of the vaccine in the general population and recent reports on rising infection rates among vaccinated individuals, adherence to health care risk reduction recommendations is cardinal,” they write.

The mean age of the control persons in the study was 63 years, and the mean age of the case patients was 66 years. The most common cancers were gastrointestinal (36%), lung (23%), breast (17%), and genitourinary (11%). Treatment protocols included chemotherapy (62%), biological agents (36%), and immunotherapy (30%). Some patients received more than one type of treatment.

All of the reported adverse effects associated with vaccination had resolved at the time of follow-up.

These data can “help inform recommendations surrounding the prioritization of different groups for booster vaccines,” Dr. Ben-Aharon adds.

In fact, recently updated guidelines from the National Comprehensive Cancer Network state that cancer patients with solid tumors who are receiving treatment within 1 year of their initial vaccine dose should be prioritized for a booster vaccine.

The study was partially supported by the Israel Cancer Research Fund. Serologic testing of the control cohort was supported by the Ministry of Health, Israel. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Physicians caring for COVID-19 survivors should routinely check kidney function, which is often damaged by the SARS-CoV-2 virus months after both severe and milder cases, new research indicates.

The largest study to date with the longest follow-up of COVID-19-related kidney outcomes also found that every type of kidney problem, including end-stage kidney disease (ESKD), was far more common in COVID-19 survivors who were admitted to the ICU or experienced acute kidney injury (AKI) while hospitalized.

Researchers analyzed U.S. Veterans Health Administration data from more than 1.7 million patients, including more than 89,000 who tested positive for COVID-19, for the study, which was published online Sept. 1, 2021, in the Journal of the American Society of Nephrology.

The risk of kidney problems “is more robust or pronounced in people who have had severe infection, but present in even asymptomatic and mild disease, which shouldn’t be discounted. Those people represent the majority of those with COVID-19,” said senior author Ziyad Al-Aly, MD, of the Veteran Affairs St. Louis Health Care System.

“That’s why the results are important, because even in people with mild disease to start with, the risk of kidney problems is not trivial,” he told this news organization. “It’s smaller than in people who were in the ICU, but it’s not ... zero.”

Experts aren’t yet certain how COVID-19 can damage the kidneys, hypothesizing that several factors may be at play. The virus may directly infect kidney cells rich in ACE2 receptors, which are key to infection, said nephrologist F. Perry Wilson, MD, of Yale University, New Haven, Conn., and a member of Medscape’s advisory board.

Kidneys might also be particularly vulnerable to the inflammatory cascade or blood clotting often seen in COVID-19, Dr. Al-Aly and Wilson both suggested.
 

COVID-19 survivors more likely to have kidney damage than controls

“A lot of health systems either have or are establishing post-COVID care clinics, which we think should definitely incorporate a kidney component,” Dr. Al-Aly advised. “They should check patients’ blood and urine for kidney problems.”

This is particularly important because “kidney problems, for the most part, are painless and silent,” he added.

“Realizing 2 years down the road that someone has ESKD, where they need dialysis or a kidney transplant, is what we don’t want. We don’t want this to be unrecognized, uncared for, unattended to,” he said.

Dr. Al-Aly and colleagues evaluated VA health system records, including data from 89,216 patients who tested positive for COVID-19 between March 2020 and March 2021, as well as 1.7 million controls who did not have COVID-19. Over a median follow-up of about 5.5 months, participants’ estimated glomerular filtration rate and serum creatinine levels were tracked to assess kidney health and outcomes according to infection severity.

Results were striking, with COVID-19 survivors about one-third more likely than controls to have kidney damage or significant declines in kidney function between 1 and 6 months after infection. More than 4,700 COVID-19 survivors had lost at least 30% of their kidney function within a year, and these patients were 25% more likely to reach that level of decline than controls.

Additionally, COVID-19 survivors were nearly twice as likely to experience AKI and almost three times as likely to be diagnosed with ESKD as controls.
 

If your patient had COVID-19, ‘it’s reasonable to check kidney function’

“This information tells us that if your patient was sick with COVID-19 and comes for follow-up visits, it’s reasonable to check their kidney function,” Dr. Wilson, who was not involved with the research, told this news organization.

“Even for patients who were not hospitalized, if they were laid low or dehydrated ... it should be part of the post-COVID care package,” he said.

If just a fraction of the millions of COVID-19 survivors in the United States develop long-term kidney problems, the ripple effect on American health care could be substantial, Dr. Wilson and Dr. Al-Aly agreed.

“We’re still living in a pandemic, so it’s hard to tell the total impact,” Dr. Al-Aly said. “But this ultimately will contribute to a rise in burden of kidney disease. This and other long COVID manifestations are going to alter the landscape of clinical care and health care in the United States for a decade or more.”

Because renal problems can limit a patient’s treatment options for other major diseases, including diabetes and cancer, COVID-related kidney damage can ultimately impact survivability.

“There are a lot of medications you can’t use in people with advanced kidney problems,” Dr. Al-Aly said.

The main study limitation was that patients were mostly older White men (median age, 68 years), although more than 9,000 women were included in the VA data, Dr. Al-Aly noted. Additionally, controls were more likely to be younger, Black, living in long-term care, and have higher rates of chronic health conditions and medication use.

The experts agreed that ongoing research tracking kidney outcomes is crucial for years to come.

“We also need to be following a cohort of these patients as part of a research protocol where they come in every 6 months for a standard set of lab tests to really understand what’s going on with their kidneys,” Dr. Wilson said.

“Lastly – and a much tougher sell – is we need biopsies. It’s very hard to infer what’s going on in complex disease with the kidneys without biopsy tissue,” he added.

The study was funded by the American Society of Nephrology and the Department of Veterans Affairs. Dr. Al-Aly and Dr. Wilson reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Physicians caring for COVID-19 survivors should routinely check kidney function, which is often damaged by the SARS-CoV-2 virus months after both severe and milder cases, new research indicates.

The largest study to date with the longest follow-up of COVID-19-related kidney outcomes also found that every type of kidney problem, including end-stage kidney disease (ESKD), was far more common in COVID-19 survivors who were admitted to the ICU or experienced acute kidney injury (AKI) while hospitalized.

Researchers analyzed U.S. Veterans Health Administration data from more than 1.7 million patients, including more than 89,000 who tested positive for COVID-19, for the study, which was published online Sept. 1, 2021, in the Journal of the American Society of Nephrology.

The risk of kidney problems “is more robust or pronounced in people who have had severe infection, but present in even asymptomatic and mild disease, which shouldn’t be discounted. Those people represent the majority of those with COVID-19,” said senior author Ziyad Al-Aly, MD, of the Veteran Affairs St. Louis Health Care System.

“That’s why the results are important, because even in people with mild disease to start with, the risk of kidney problems is not trivial,” he told this news organization. “It’s smaller than in people who were in the ICU, but it’s not ... zero.”

Experts aren’t yet certain how COVID-19 can damage the kidneys, hypothesizing that several factors may be at play. The virus may directly infect kidney cells rich in ACE2 receptors, which are key to infection, said nephrologist F. Perry Wilson, MD, of Yale University, New Haven, Conn., and a member of Medscape’s advisory board.

Kidneys might also be particularly vulnerable to the inflammatory cascade or blood clotting often seen in COVID-19, Dr. Al-Aly and Wilson both suggested.
 

COVID-19 survivors more likely to have kidney damage than controls

“A lot of health systems either have or are establishing post-COVID care clinics, which we think should definitely incorporate a kidney component,” Dr. Al-Aly advised. “They should check patients’ blood and urine for kidney problems.”

This is particularly important because “kidney problems, for the most part, are painless and silent,” he added.

“Realizing 2 years down the road that someone has ESKD, where they need dialysis or a kidney transplant, is what we don’t want. We don’t want this to be unrecognized, uncared for, unattended to,” he said.

Dr. Al-Aly and colleagues evaluated VA health system records, including data from 89,216 patients who tested positive for COVID-19 between March 2020 and March 2021, as well as 1.7 million controls who did not have COVID-19. Over a median follow-up of about 5.5 months, participants’ estimated glomerular filtration rate and serum creatinine levels were tracked to assess kidney health and outcomes according to infection severity.

Results were striking, with COVID-19 survivors about one-third more likely than controls to have kidney damage or significant declines in kidney function between 1 and 6 months after infection. More than 4,700 COVID-19 survivors had lost at least 30% of their kidney function within a year, and these patients were 25% more likely to reach that level of decline than controls.

Additionally, COVID-19 survivors were nearly twice as likely to experience AKI and almost three times as likely to be diagnosed with ESKD as controls.
 

If your patient had COVID-19, ‘it’s reasonable to check kidney function’

“This information tells us that if your patient was sick with COVID-19 and comes for follow-up visits, it’s reasonable to check their kidney function,” Dr. Wilson, who was not involved with the research, told this news organization.

“Even for patients who were not hospitalized, if they were laid low or dehydrated ... it should be part of the post-COVID care package,” he said.

If just a fraction of the millions of COVID-19 survivors in the United States develop long-term kidney problems, the ripple effect on American health care could be substantial, Dr. Wilson and Dr. Al-Aly agreed.

“We’re still living in a pandemic, so it’s hard to tell the total impact,” Dr. Al-Aly said. “But this ultimately will contribute to a rise in burden of kidney disease. This and other long COVID manifestations are going to alter the landscape of clinical care and health care in the United States for a decade or more.”

Because renal problems can limit a patient’s treatment options for other major diseases, including diabetes and cancer, COVID-related kidney damage can ultimately impact survivability.

“There are a lot of medications you can’t use in people with advanced kidney problems,” Dr. Al-Aly said.

The main study limitation was that patients were mostly older White men (median age, 68 years), although more than 9,000 women were included in the VA data, Dr. Al-Aly noted. Additionally, controls were more likely to be younger, Black, living in long-term care, and have higher rates of chronic health conditions and medication use.

The experts agreed that ongoing research tracking kidney outcomes is crucial for years to come.

“We also need to be following a cohort of these patients as part of a research protocol where they come in every 6 months for a standard set of lab tests to really understand what’s going on with their kidneys,” Dr. Wilson said.

“Lastly – and a much tougher sell – is we need biopsies. It’s very hard to infer what’s going on in complex disease with the kidneys without biopsy tissue,” he added.

The study was funded by the American Society of Nephrology and the Department of Veterans Affairs. Dr. Al-Aly and Dr. Wilson reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Physicians caring for COVID-19 survivors should routinely check kidney function, which is often damaged by the SARS-CoV-2 virus months after both severe and milder cases, new research indicates.

The largest study to date with the longest follow-up of COVID-19-related kidney outcomes also found that every type of kidney problem, including end-stage kidney disease (ESKD), was far more common in COVID-19 survivors who were admitted to the ICU or experienced acute kidney injury (AKI) while hospitalized.

Researchers analyzed U.S. Veterans Health Administration data from more than 1.7 million patients, including more than 89,000 who tested positive for COVID-19, for the study, which was published online Sept. 1, 2021, in the Journal of the American Society of Nephrology.

The risk of kidney problems “is more robust or pronounced in people who have had severe infection, but present in even asymptomatic and mild disease, which shouldn’t be discounted. Those people represent the majority of those with COVID-19,” said senior author Ziyad Al-Aly, MD, of the Veteran Affairs St. Louis Health Care System.

“That’s why the results are important, because even in people with mild disease to start with, the risk of kidney problems is not trivial,” he told this news organization. “It’s smaller than in people who were in the ICU, but it’s not ... zero.”

Experts aren’t yet certain how COVID-19 can damage the kidneys, hypothesizing that several factors may be at play. The virus may directly infect kidney cells rich in ACE2 receptors, which are key to infection, said nephrologist F. Perry Wilson, MD, of Yale University, New Haven, Conn., and a member of Medscape’s advisory board.

Kidneys might also be particularly vulnerable to the inflammatory cascade or blood clotting often seen in COVID-19, Dr. Al-Aly and Wilson both suggested.
 

COVID-19 survivors more likely to have kidney damage than controls

“A lot of health systems either have or are establishing post-COVID care clinics, which we think should definitely incorporate a kidney component,” Dr. Al-Aly advised. “They should check patients’ blood and urine for kidney problems.”

This is particularly important because “kidney problems, for the most part, are painless and silent,” he added.

“Realizing 2 years down the road that someone has ESKD, where they need dialysis or a kidney transplant, is what we don’t want. We don’t want this to be unrecognized, uncared for, unattended to,” he said.

Dr. Al-Aly and colleagues evaluated VA health system records, including data from 89,216 patients who tested positive for COVID-19 between March 2020 and March 2021, as well as 1.7 million controls who did not have COVID-19. Over a median follow-up of about 5.5 months, participants’ estimated glomerular filtration rate and serum creatinine levels were tracked to assess kidney health and outcomes according to infection severity.

Results were striking, with COVID-19 survivors about one-third more likely than controls to have kidney damage or significant declines in kidney function between 1 and 6 months after infection. More than 4,700 COVID-19 survivors had lost at least 30% of their kidney function within a year, and these patients were 25% more likely to reach that level of decline than controls.

Additionally, COVID-19 survivors were nearly twice as likely to experience AKI and almost three times as likely to be diagnosed with ESKD as controls.
 

If your patient had COVID-19, ‘it’s reasonable to check kidney function’

“This information tells us that if your patient was sick with COVID-19 and comes for follow-up visits, it’s reasonable to check their kidney function,” Dr. Wilson, who was not involved with the research, told this news organization.

“Even for patients who were not hospitalized, if they were laid low or dehydrated ... it should be part of the post-COVID care package,” he said.

If just a fraction of the millions of COVID-19 survivors in the United States develop long-term kidney problems, the ripple effect on American health care could be substantial, Dr. Wilson and Dr. Al-Aly agreed.

“We’re still living in a pandemic, so it’s hard to tell the total impact,” Dr. Al-Aly said. “But this ultimately will contribute to a rise in burden of kidney disease. This and other long COVID manifestations are going to alter the landscape of clinical care and health care in the United States for a decade or more.”

Because renal problems can limit a patient’s treatment options for other major diseases, including diabetes and cancer, COVID-related kidney damage can ultimately impact survivability.

“There are a lot of medications you can’t use in people with advanced kidney problems,” Dr. Al-Aly said.

The main study limitation was that patients were mostly older White men (median age, 68 years), although more than 9,000 women were included in the VA data, Dr. Al-Aly noted. Additionally, controls were more likely to be younger, Black, living in long-term care, and have higher rates of chronic health conditions and medication use.

The experts agreed that ongoing research tracking kidney outcomes is crucial for years to come.

“We also need to be following a cohort of these patients as part of a research protocol where they come in every 6 months for a standard set of lab tests to really understand what’s going on with their kidneys,” Dr. Wilson said.

“Lastly – and a much tougher sell – is we need biopsies. It’s very hard to infer what’s going on in complex disease with the kidneys without biopsy tissue,” he added.

The study was funded by the American Society of Nephrology and the Department of Veterans Affairs. Dr. Al-Aly and Dr. Wilson reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

One month of dual antiplatelet therapy followed by 11 months of clopidogrel monotherapy failed to prove noninferiority to 12 unbroken months of DAPT for net clinical benefit in a multicenter Japanese trial that randomized more than 4,000 patients who underwent percutaneous coronary intervention (PCI) after a recent acute coronary syndrome episode.

© Astrid Gast/Thinkstock

The outcomes showed that while truncating DAPT duration could, as expected, cut major bleeding episodes roughly in half, it also led to a significant near doubling of myocardial infarction and showed a strong trend toward also increasing a composite tally of several types of ischemic events. These data were reported this week by Hirotoshi Watanabe, MD, PhD, at the virtual annual congress of the European Society of Cardiology. All study patients had undergone PCI with cobalt-chromium everolimus-eluting (CCEE) coronary stents (Xience).

These findings from the STOPDAPT-2 ACS trial highlighted the limits of minimizing DAPT after PCI in patients at high ischemic risk, such as after an acute coronary syndrome (ACS) event.

It also was a counterpoint to a somewhat similar study also reported at the congress, MASTER DAPT, which showed that 1 month of DAPT was noninferior to 3 or more months of DAPT for net clinical benefit in a distinctly different population of patients undergoing PCI (and using a different type of coronary stent) – those at high bleeding risk and with only about half the patients having had a recent ACS.

The results of STOPDAPT-2 ACS “do not support use of 1 month of DAPT followed by P2Y12 inhibitor monotherapy with clopidogrel compared with standard DAPT,” commented Robert A. Byrne, MBBCh, PhD, designated discussant for the report and professor at the RCSI University of Medicine and Health Sciences in Dublin.

“Although major bleeding was significantly reduced with this approach, there appeared to be a significant increase in adverse ischemic events, and there was a clear signal in relation to overall mortality, the ultimate arbiter of net clinical benefit,” added Dr. Byrne, who is also director of cardiology at Mater Private Hospital in Dublin.

He suggested that a mechanistic explanation for the signal of harm seem in STOPDAPT-2 ACS was the relatively low potency of clopidogrel (Plavix) as an antiplatelet agent, compared with other P2Y12 inhibitors such as prasugrel (Effient) and ticagrelor (Brilinta), as well as the genetically driven variability in response to clopidogrel that’s also absent with alternative agents.

These between-agent differences are of “particular clinical relevance in the early aftermath of an ACS event,” Dr. Byrne said.
 

12-month DAPT remains standard for PCI patients with recent ACS

The totality of clinical evidence “continues to support a standard 12-month duration of DAPT – using aspirin and either prasugrel or ticagrelor – as the preferred default approach,” Dr. Byrne concluded.

He acknowledged that an abbreviated duration of DAPT followed by P2Y12 inhibitor monotherapy “might be considered as an alternative.” In patients following an ACS event who do not have high risk for bleeding, he said, the minimum duration of DAPT should be at least 3 months and with preferential use of a more potent P2Y12 inhibitor.

Twelve months of DAPT treatment with aspirin and a P2Y12 inhibitor for patients following PCI “remains the standard of care in guidelines,” noted Marco Roffi, MD, a second discussant at the congress. But several questions remain, he added, such as which P2Y12 inhibitors work best and whether DAPT can be less than 12 months.

“The investigators [for STOPDAPT-2 ACS] pushed these questions to the limit with 1 month of DAPT and clopidogrel monotherapy,” said Dr. Roffi, professor and director of interventional cardiology at University Hospital, Geneva.

“This was a risky bet, and the investigators lost by not proving noninferiority and with excess ischemic events,” he commented.
 

First came STOPDAPT-2

Dr. Watanabe and colleagues designed STOPDAPT-2 ACS as a follow-up to their prior STOPDAPT-2 trial, which randomly assigned slightly more than 3000 patients at 90 Japanese centers to the identical two treatment options: 1 month of DAPT followed by 11 months of clopidogrel monotherapy or 12 months of DAPT, except the trial enrolled all types of patients undergoing PCI. This meant that a minority, 38%, had a recent ACS event, while the remaining patients had chronic coronary artery disease. As in STOPDAPT-2 ACS, all patients in STOPDAPT-2 had received a CCEE stent.

STOPDAPT-2 also used the same primary endpoint to tally net clinical benefit as STOPDAPT-2 ACS: cardiovascular death, MI, stroke of any type, definite stent thrombosis, or TIMI major or minor bleeding classification.

In STOPDAPT-2, using the mixed population with both recent ACS and chronic coronary disease, the regimen of 1 month of DAPT followed by 11 months of clopidogrel monotherapy was both noninferior to and superior to 12 months of DAPT, reducing the net adverse-event tally by 36% relative to 12-month DAPT and by an absolute reduction of 1.34%, as reported in 2019.

Despite this superiority, the results from STOPDAPT-2 had little impact on global practice, commented Kurt Huber, MD, professor and director of the cardiology ICU at the Medical University of Vienna.

“STOP-DAPT-2 did not give us a clear message with respect to reducing antiplatelet treatment after 1 month. I thought that for ACS patients 1 month might be too short,” Dr. Huber said during a press briefing.
 

Focusing on post-ACS

To directly address this issue, the investigators launched STOPDAPT-2 ACS, which used the same design as the preceding study but only enrolled patients soon after an ACS event. The trial included for its main analysis 3,008 newly enrolled patients with recent ACS, and 1,161 patients who had a recent ACS event and had been randomly assigned in STOPDAPT-2, creating a total study cohort for the new analysis of 4136 patients treated and followed for the study’s full 12 months.

The patients averaged 67 years old, 79% were men, and 30% had diabetes. About 56% had a recent ST-elevation MI, about 20% a recent non–ST-elevation MI, and the remaining 24% had unstable angina. For their unspecified P2Y12 inhibition, roughly half the patients received clopidogrel and the rest received prasugrel. Adherence to the two assigned treatment regimens was very good, with a very small number of patients not adhering to their assigned protocol.

The composite adverse event incidence over 12 months was 3.2% among those who received 1-month DAPT and 2.83% in those on DAPT for 12 months, a difference that failed to achieve the prespecified definition of noninferiority for 1-month DAPT, reported Dr. Watanabe, an interventional cardiologist at Kyoto University.

The ischemic event composite was 50% lower among those on 12-month DAPT, compared with 1 month of DAPT, a difference that just missed significance. The rate of MI was 91% higher with 1-month DAPT, compared with 12 months, a significant difference.

One-month DAPT also significantly reduced the primary measure of bleeding events – the combination of TIMI major and minor bleeds – by a significant 54%, compared with 12-month DAPT. A second metric of clinically meaningful bleeds, those that meet either the type 3 or 5 definition of the Bleeding Academic Research Consortium, were reduced by a significant 59% by 1-month DAPT, compared with 12 months of DAPT.

The new findings from STOPDAPT-2 ACS contrasted with those from MASTER DAPT, but in an explicable way that related to different patient types, different P2Y12 inhibitors, different treatment durations, and different stents.

“We’ve seen in MASTER DAPT that if you use the right stent and use ticagrelor for monotherapy there may be some ability to shorten DAPT, but we still do not know what would happen in patients with very high ischemic risk,” concluded Dr. Huber.

“A reduction in DAPT duration might work in patients without high bleeding risk, but I would exclude patients with very high ischemic risk,” he added. “I also can’t tell you whether 1 month or 3 months is the right approach, and I think clopidogrel is not the right drug to use for monotherapy after ACS.”

STOPDAPT-2 and STOPDAPT-2 ACS were both sponsored by Abbott Vascular, which markets the CCEE (Xience) stents used in both studies. Dr. Watanabe has received lecture fees from Abbott and from Daiichi-Sankyo. Dr. Byrne has received research funding from Abbott Vascular as well as from Biosensors, Biotronik, and Boston Scientific. Roffi has received research funding from Biotronik, Boston Scientific, GE Healthcare, Medtronic, and Terumo. Dr. Huber has received lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Pfizer, Sanofi-Aventis, and The Medicines Company.

A version of this article first appeared on Medscape.com.

One month of dual antiplatelet therapy followed by 11 months of clopidogrel monotherapy failed to prove noninferiority to 12 unbroken months of DAPT for net clinical benefit in a multicenter Japanese trial that randomized more than 4,000 patients who underwent percutaneous coronary intervention (PCI) after a recent acute coronary syndrome episode.

© Astrid Gast/Thinkstock

The outcomes showed that while truncating DAPT duration could, as expected, cut major bleeding episodes roughly in half, it also led to a significant near doubling of myocardial infarction and showed a strong trend toward also increasing a composite tally of several types of ischemic events. These data were reported this week by Hirotoshi Watanabe, MD, PhD, at the virtual annual congress of the European Society of Cardiology. All study patients had undergone PCI with cobalt-chromium everolimus-eluting (CCEE) coronary stents (Xience).

These findings from the STOPDAPT-2 ACS trial highlighted the limits of minimizing DAPT after PCI in patients at high ischemic risk, such as after an acute coronary syndrome (ACS) event.

It also was a counterpoint to a somewhat similar study also reported at the congress, MASTER DAPT, which showed that 1 month of DAPT was noninferior to 3 or more months of DAPT for net clinical benefit in a distinctly different population of patients undergoing PCI (and using a different type of coronary stent) – those at high bleeding risk and with only about half the patients having had a recent ACS.

The results of STOPDAPT-2 ACS “do not support use of 1 month of DAPT followed by P2Y12 inhibitor monotherapy with clopidogrel compared with standard DAPT,” commented Robert A. Byrne, MBBCh, PhD, designated discussant for the report and professor at the RCSI University of Medicine and Health Sciences in Dublin.

“Although major bleeding was significantly reduced with this approach, there appeared to be a significant increase in adverse ischemic events, and there was a clear signal in relation to overall mortality, the ultimate arbiter of net clinical benefit,” added Dr. Byrne, who is also director of cardiology at Mater Private Hospital in Dublin.

He suggested that a mechanistic explanation for the signal of harm seem in STOPDAPT-2 ACS was the relatively low potency of clopidogrel (Plavix) as an antiplatelet agent, compared with other P2Y12 inhibitors such as prasugrel (Effient) and ticagrelor (Brilinta), as well as the genetically driven variability in response to clopidogrel that’s also absent with alternative agents.

These between-agent differences are of “particular clinical relevance in the early aftermath of an ACS event,” Dr. Byrne said.
 

12-month DAPT remains standard for PCI patients with recent ACS

The totality of clinical evidence “continues to support a standard 12-month duration of DAPT – using aspirin and either prasugrel or ticagrelor – as the preferred default approach,” Dr. Byrne concluded.

He acknowledged that an abbreviated duration of DAPT followed by P2Y12 inhibitor monotherapy “might be considered as an alternative.” In patients following an ACS event who do not have high risk for bleeding, he said, the minimum duration of DAPT should be at least 3 months and with preferential use of a more potent P2Y12 inhibitor.

Twelve months of DAPT treatment with aspirin and a P2Y12 inhibitor for patients following PCI “remains the standard of care in guidelines,” noted Marco Roffi, MD, a second discussant at the congress. But several questions remain, he added, such as which P2Y12 inhibitors work best and whether DAPT can be less than 12 months.

“The investigators [for STOPDAPT-2 ACS] pushed these questions to the limit with 1 month of DAPT and clopidogrel monotherapy,” said Dr. Roffi, professor and director of interventional cardiology at University Hospital, Geneva.

“This was a risky bet, and the investigators lost by not proving noninferiority and with excess ischemic events,” he commented.
 

First came STOPDAPT-2

Dr. Watanabe and colleagues designed STOPDAPT-2 ACS as a follow-up to their prior STOPDAPT-2 trial, which randomly assigned slightly more than 3000 patients at 90 Japanese centers to the identical two treatment options: 1 month of DAPT followed by 11 months of clopidogrel monotherapy or 12 months of DAPT, except the trial enrolled all types of patients undergoing PCI. This meant that a minority, 38%, had a recent ACS event, while the remaining patients had chronic coronary artery disease. As in STOPDAPT-2 ACS, all patients in STOPDAPT-2 had received a CCEE stent.

STOPDAPT-2 also used the same primary endpoint to tally net clinical benefit as STOPDAPT-2 ACS: cardiovascular death, MI, stroke of any type, definite stent thrombosis, or TIMI major or minor bleeding classification.

In STOPDAPT-2, using the mixed population with both recent ACS and chronic coronary disease, the regimen of 1 month of DAPT followed by 11 months of clopidogrel monotherapy was both noninferior to and superior to 12 months of DAPT, reducing the net adverse-event tally by 36% relative to 12-month DAPT and by an absolute reduction of 1.34%, as reported in 2019.

Despite this superiority, the results from STOPDAPT-2 had little impact on global practice, commented Kurt Huber, MD, professor and director of the cardiology ICU at the Medical University of Vienna.

“STOP-DAPT-2 did not give us a clear message with respect to reducing antiplatelet treatment after 1 month. I thought that for ACS patients 1 month might be too short,” Dr. Huber said during a press briefing.
 

Focusing on post-ACS

To directly address this issue, the investigators launched STOPDAPT-2 ACS, which used the same design as the preceding study but only enrolled patients soon after an ACS event. The trial included for its main analysis 3,008 newly enrolled patients with recent ACS, and 1,161 patients who had a recent ACS event and had been randomly assigned in STOPDAPT-2, creating a total study cohort for the new analysis of 4136 patients treated and followed for the study’s full 12 months.

The patients averaged 67 years old, 79% were men, and 30% had diabetes. About 56% had a recent ST-elevation MI, about 20% a recent non–ST-elevation MI, and the remaining 24% had unstable angina. For their unspecified P2Y12 inhibition, roughly half the patients received clopidogrel and the rest received prasugrel. Adherence to the two assigned treatment regimens was very good, with a very small number of patients not adhering to their assigned protocol.

The composite adverse event incidence over 12 months was 3.2% among those who received 1-month DAPT and 2.83% in those on DAPT for 12 months, a difference that failed to achieve the prespecified definition of noninferiority for 1-month DAPT, reported Dr. Watanabe, an interventional cardiologist at Kyoto University.

The ischemic event composite was 50% lower among those on 12-month DAPT, compared with 1 month of DAPT, a difference that just missed significance. The rate of MI was 91% higher with 1-month DAPT, compared with 12 months, a significant difference.

One-month DAPT also significantly reduced the primary measure of bleeding events – the combination of TIMI major and minor bleeds – by a significant 54%, compared with 12-month DAPT. A second metric of clinically meaningful bleeds, those that meet either the type 3 or 5 definition of the Bleeding Academic Research Consortium, were reduced by a significant 59% by 1-month DAPT, compared with 12 months of DAPT.

The new findings from STOPDAPT-2 ACS contrasted with those from MASTER DAPT, but in an explicable way that related to different patient types, different P2Y12 inhibitors, different treatment durations, and different stents.

“We’ve seen in MASTER DAPT that if you use the right stent and use ticagrelor for monotherapy there may be some ability to shorten DAPT, but we still do not know what would happen in patients with very high ischemic risk,” concluded Dr. Huber.

“A reduction in DAPT duration might work in patients without high bleeding risk, but I would exclude patients with very high ischemic risk,” he added. “I also can’t tell you whether 1 month or 3 months is the right approach, and I think clopidogrel is not the right drug to use for monotherapy after ACS.”

STOPDAPT-2 and STOPDAPT-2 ACS were both sponsored by Abbott Vascular, which markets the CCEE (Xience) stents used in both studies. Dr. Watanabe has received lecture fees from Abbott and from Daiichi-Sankyo. Dr. Byrne has received research funding from Abbott Vascular as well as from Biosensors, Biotronik, and Boston Scientific. Roffi has received research funding from Biotronik, Boston Scientific, GE Healthcare, Medtronic, and Terumo. Dr. Huber has received lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Pfizer, Sanofi-Aventis, and The Medicines Company.

A version of this article first appeared on Medscape.com.

One month of dual antiplatelet therapy followed by 11 months of clopidogrel monotherapy failed to prove noninferiority to 12 unbroken months of DAPT for net clinical benefit in a multicenter Japanese trial that randomized more than 4,000 patients who underwent percutaneous coronary intervention (PCI) after a recent acute coronary syndrome episode.

© Astrid Gast/Thinkstock

The outcomes showed that while truncating DAPT duration could, as expected, cut major bleeding episodes roughly in half, it also led to a significant near doubling of myocardial infarction and showed a strong trend toward also increasing a composite tally of several types of ischemic events. These data were reported this week by Hirotoshi Watanabe, MD, PhD, at the virtual annual congress of the European Society of Cardiology. All study patients had undergone PCI with cobalt-chromium everolimus-eluting (CCEE) coronary stents (Xience).

These findings from the STOPDAPT-2 ACS trial highlighted the limits of minimizing DAPT after PCI in patients at high ischemic risk, such as after an acute coronary syndrome (ACS) event.

It also was a counterpoint to a somewhat similar study also reported at the congress, MASTER DAPT, which showed that 1 month of DAPT was noninferior to 3 or more months of DAPT for net clinical benefit in a distinctly different population of patients undergoing PCI (and using a different type of coronary stent) – those at high bleeding risk and with only about half the patients having had a recent ACS.

The results of STOPDAPT-2 ACS “do not support use of 1 month of DAPT followed by P2Y12 inhibitor monotherapy with clopidogrel compared with standard DAPT,” commented Robert A. Byrne, MBBCh, PhD, designated discussant for the report and professor at the RCSI University of Medicine and Health Sciences in Dublin.

“Although major bleeding was significantly reduced with this approach, there appeared to be a significant increase in adverse ischemic events, and there was a clear signal in relation to overall mortality, the ultimate arbiter of net clinical benefit,” added Dr. Byrne, who is also director of cardiology at Mater Private Hospital in Dublin.

He suggested that a mechanistic explanation for the signal of harm seem in STOPDAPT-2 ACS was the relatively low potency of clopidogrel (Plavix) as an antiplatelet agent, compared with other P2Y12 inhibitors such as prasugrel (Effient) and ticagrelor (Brilinta), as well as the genetically driven variability in response to clopidogrel that’s also absent with alternative agents.

These between-agent differences are of “particular clinical relevance in the early aftermath of an ACS event,” Dr. Byrne said.
 

12-month DAPT remains standard for PCI patients with recent ACS

The totality of clinical evidence “continues to support a standard 12-month duration of DAPT – using aspirin and either prasugrel or ticagrelor – as the preferred default approach,” Dr. Byrne concluded.

He acknowledged that an abbreviated duration of DAPT followed by P2Y12 inhibitor monotherapy “might be considered as an alternative.” In patients following an ACS event who do not have high risk for bleeding, he said, the minimum duration of DAPT should be at least 3 months and with preferential use of a more potent P2Y12 inhibitor.

Twelve months of DAPT treatment with aspirin and a P2Y12 inhibitor for patients following PCI “remains the standard of care in guidelines,” noted Marco Roffi, MD, a second discussant at the congress. But several questions remain, he added, such as which P2Y12 inhibitors work best and whether DAPT can be less than 12 months.

“The investigators [for STOPDAPT-2 ACS] pushed these questions to the limit with 1 month of DAPT and clopidogrel monotherapy,” said Dr. Roffi, professor and director of interventional cardiology at University Hospital, Geneva.

“This was a risky bet, and the investigators lost by not proving noninferiority and with excess ischemic events,” he commented.
 

First came STOPDAPT-2

Dr. Watanabe and colleagues designed STOPDAPT-2 ACS as a follow-up to their prior STOPDAPT-2 trial, which randomly assigned slightly more than 3000 patients at 90 Japanese centers to the identical two treatment options: 1 month of DAPT followed by 11 months of clopidogrel monotherapy or 12 months of DAPT, except the trial enrolled all types of patients undergoing PCI. This meant that a minority, 38%, had a recent ACS event, while the remaining patients had chronic coronary artery disease. As in STOPDAPT-2 ACS, all patients in STOPDAPT-2 had received a CCEE stent.

STOPDAPT-2 also used the same primary endpoint to tally net clinical benefit as STOPDAPT-2 ACS: cardiovascular death, MI, stroke of any type, definite stent thrombosis, or TIMI major or minor bleeding classification.

In STOPDAPT-2, using the mixed population with both recent ACS and chronic coronary disease, the regimen of 1 month of DAPT followed by 11 months of clopidogrel monotherapy was both noninferior to and superior to 12 months of DAPT, reducing the net adverse-event tally by 36% relative to 12-month DAPT and by an absolute reduction of 1.34%, as reported in 2019.

Despite this superiority, the results from STOPDAPT-2 had little impact on global practice, commented Kurt Huber, MD, professor and director of the cardiology ICU at the Medical University of Vienna.

“STOP-DAPT-2 did not give us a clear message with respect to reducing antiplatelet treatment after 1 month. I thought that for ACS patients 1 month might be too short,” Dr. Huber said during a press briefing.
 

Focusing on post-ACS

To directly address this issue, the investigators launched STOPDAPT-2 ACS, which used the same design as the preceding study but only enrolled patients soon after an ACS event. The trial included for its main analysis 3,008 newly enrolled patients with recent ACS, and 1,161 patients who had a recent ACS event and had been randomly assigned in STOPDAPT-2, creating a total study cohort for the new analysis of 4136 patients treated and followed for the study’s full 12 months.

The patients averaged 67 years old, 79% were men, and 30% had diabetes. About 56% had a recent ST-elevation MI, about 20% a recent non–ST-elevation MI, and the remaining 24% had unstable angina. For their unspecified P2Y12 inhibition, roughly half the patients received clopidogrel and the rest received prasugrel. Adherence to the two assigned treatment regimens was very good, with a very small number of patients not adhering to their assigned protocol.

The composite adverse event incidence over 12 months was 3.2% among those who received 1-month DAPT and 2.83% in those on DAPT for 12 months, a difference that failed to achieve the prespecified definition of noninferiority for 1-month DAPT, reported Dr. Watanabe, an interventional cardiologist at Kyoto University.

The ischemic event composite was 50% lower among those on 12-month DAPT, compared with 1 month of DAPT, a difference that just missed significance. The rate of MI was 91% higher with 1-month DAPT, compared with 12 months, a significant difference.

One-month DAPT also significantly reduced the primary measure of bleeding events – the combination of TIMI major and minor bleeds – by a significant 54%, compared with 12-month DAPT. A second metric of clinically meaningful bleeds, those that meet either the type 3 or 5 definition of the Bleeding Academic Research Consortium, were reduced by a significant 59% by 1-month DAPT, compared with 12 months of DAPT.

The new findings from STOPDAPT-2 ACS contrasted with those from MASTER DAPT, but in an explicable way that related to different patient types, different P2Y12 inhibitors, different treatment durations, and different stents.

“We’ve seen in MASTER DAPT that if you use the right stent and use ticagrelor for monotherapy there may be some ability to shorten DAPT, but we still do not know what would happen in patients with very high ischemic risk,” concluded Dr. Huber.

“A reduction in DAPT duration might work in patients without high bleeding risk, but I would exclude patients with very high ischemic risk,” he added. “I also can’t tell you whether 1 month or 3 months is the right approach, and I think clopidogrel is not the right drug to use for monotherapy after ACS.”

STOPDAPT-2 and STOPDAPT-2 ACS were both sponsored by Abbott Vascular, which markets the CCEE (Xience) stents used in both studies. Dr. Watanabe has received lecture fees from Abbott and from Daiichi-Sankyo. Dr. Byrne has received research funding from Abbott Vascular as well as from Biosensors, Biotronik, and Boston Scientific. Roffi has received research funding from Biotronik, Boston Scientific, GE Healthcare, Medtronic, and Terumo. Dr. Huber has received lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Pfizer, Sanofi-Aventis, and The Medicines Company.

A version of this article first appeared on Medscape.com.

ANSWER

The correct answer is that new hairs growing in to replace those lost from alopecia areata tend to be white (choice “b”). They usually regain their normal color, eventually.

DISCUSSION

Alopecia areata is an autoimmune phenomenon implying an increased tendency to develop other autoimmune diseases (eg, vitiligo [choice “a”], which can appear initially in the scalp).

This case turned out to be simple but had the potential to be far more serious. The biopsy of the dark patch showed benign seborrheic keratosis, but it was possible that another section could have demonstrated features of melanoma (choice “c”). When present, melanoma can occasionally trigger an immune response that destroys pigment cells in hair follicles, causing the hairs to lose their pigment. This is why the entire dark patch was later excised. Fortunately, the pathology report ruled out melanoma.

While it has been reported that stress can cause hair to turn gray (choice “d”), there were better (and more accurate) explanations for this patient’s presentation.

This case, though fairly straightforward, serves as a reminder that it is our job as clinicians to connect the dots to rule out worst-case scenarios.

Outcome

This patient’s hair all grew back, regaining its normal color, without any treatment.

ANSWER

The correct answer is that new hairs growing in to replace those lost from alopecia areata tend to be white (choice “b”). They usually regain their normal color, eventually.

DISCUSSION

Alopecia areata is an autoimmune phenomenon implying an increased tendency to develop other autoimmune diseases (eg, vitiligo [choice “a”], which can appear initially in the scalp).

This case turned out to be simple but had the potential to be far more serious. The biopsy of the dark patch showed benign seborrheic keratosis, but it was possible that another section could have demonstrated features of melanoma (choice “c”). When present, melanoma can occasionally trigger an immune response that destroys pigment cells in hair follicles, causing the hairs to lose their pigment. This is why the entire dark patch was later excised. Fortunately, the pathology report ruled out melanoma.

While it has been reported that stress can cause hair to turn gray (choice “d”), there were better (and more accurate) explanations for this patient’s presentation.

This case, though fairly straightforward, serves as a reminder that it is our job as clinicians to connect the dots to rule out worst-case scenarios.

Outcome

This patient’s hair all grew back, regaining its normal color, without any treatment.

ANSWER

The correct answer is that new hairs growing in to replace those lost from alopecia areata tend to be white (choice “b”). They usually regain their normal color, eventually.

DISCUSSION

Alopecia areata is an autoimmune phenomenon implying an increased tendency to develop other autoimmune diseases (eg, vitiligo [choice “a”], which can appear initially in the scalp).

This case turned out to be simple but had the potential to be far more serious. The biopsy of the dark patch showed benign seborrheic keratosis, but it was possible that another section could have demonstrated features of melanoma (choice “c”). When present, melanoma can occasionally trigger an immune response that destroys pigment cells in hair follicles, causing the hairs to lose their pigment. This is why the entire dark patch was later excised. Fortunately, the pathology report ruled out melanoma.

While it has been reported that stress can cause hair to turn gray (choice “d”), there were better (and more accurate) explanations for this patient’s presentation.

This case, though fairly straightforward, serves as a reminder that it is our job as clinicians to connect the dots to rule out worst-case scenarios.

Outcome

This patient’s hair all grew back, regaining its normal color, without any treatment.

Consumer advocacy group Public Citizen filed a lawsuit on Sept. 8 on behalf of the Post-Finasteride Syndrome Foundation (PFSF) against the Food and Drug Administration for the agency’s failure to act on a petition submitted by the foundation 4 years ago.

The September 2017 petition requested that the FDA take the popular hair-loss drug (1 mg finasteride, Propecia) off the market because of evidence of serious risk of patient injury, including depression and suicidal ideation. 

As an alternative, PFSF requested that the FDA require the drug’s manufacturers revise the safety information on the labeling and add boxed warnings to disclose the potential for side effects, another of which is erectile dysfunction.

Public Citizen points to a recent analysis of the VigiBase global database, which tracks adverse effects from global pharmacovigilance agencies, lists 356 reports of suicidality and 2,926 reports of psychological adverse events in finasteride users. Yet, 4 years after submitting the petition, the FDA has neither granted nor denied it.

The lawsuit claims that FDA has acted unlawfully in failing to act on PFSF’s petition, and further cites “88 cases of completed suicide associated with finasteride use” per data from the VigiBase database.

“On the same day that PFSF submitted the petition, FDA’s docket management division acknowledged receipt and assigned the petition a docket number,” Michael Kirkpatrick, the Public Citizen attorney serving as lead counsel for PFSF, told this news organization.

Yet, to date, “there has been no substantive response to the petition. The lawsuit filed today seeks to force FDA to issue a decision on PFSF’s petition,” Mr. Kirkpatrick said.

“The FDA needs to act in a timely way to protect the public from the risks associated with use of Propecia. The FDA’s failure to act exposes consumers to potentially life-threatening harm,” he added in a statement.

The complaint filed today by Public Citizen in the U.S. District Court for the District of Columbia is available online. 

This news organization reached out to the FDA for comment but did not receive a response by press time.
 

A version of this article first appeared on Medscape.com.

Consumer advocacy group Public Citizen filed a lawsuit on Sept. 8 on behalf of the Post-Finasteride Syndrome Foundation (PFSF) against the Food and Drug Administration for the agency’s failure to act on a petition submitted by the foundation 4 years ago.

The September 2017 petition requested that the FDA take the popular hair-loss drug (1 mg finasteride, Propecia) off the market because of evidence of serious risk of patient injury, including depression and suicidal ideation. 

As an alternative, PFSF requested that the FDA require the drug’s manufacturers revise the safety information on the labeling and add boxed warnings to disclose the potential for side effects, another of which is erectile dysfunction.

Public Citizen points to a recent analysis of the VigiBase global database, which tracks adverse effects from global pharmacovigilance agencies, lists 356 reports of suicidality and 2,926 reports of psychological adverse events in finasteride users. Yet, 4 years after submitting the petition, the FDA has neither granted nor denied it.

The lawsuit claims that FDA has acted unlawfully in failing to act on PFSF’s petition, and further cites “88 cases of completed suicide associated with finasteride use” per data from the VigiBase database.

“On the same day that PFSF submitted the petition, FDA’s docket management division acknowledged receipt and assigned the petition a docket number,” Michael Kirkpatrick, the Public Citizen attorney serving as lead counsel for PFSF, told this news organization.

Yet, to date, “there has been no substantive response to the petition. The lawsuit filed today seeks to force FDA to issue a decision on PFSF’s petition,” Mr. Kirkpatrick said.

“The FDA needs to act in a timely way to protect the public from the risks associated with use of Propecia. The FDA’s failure to act exposes consumers to potentially life-threatening harm,” he added in a statement.

The complaint filed today by Public Citizen in the U.S. District Court for the District of Columbia is available online. 

This news organization reached out to the FDA for comment but did not receive a response by press time.
 

A version of this article first appeared on Medscape.com.

Consumer advocacy group Public Citizen filed a lawsuit on Sept. 8 on behalf of the Post-Finasteride Syndrome Foundation (PFSF) against the Food and Drug Administration for the agency’s failure to act on a petition submitted by the foundation 4 years ago.

The September 2017 petition requested that the FDA take the popular hair-loss drug (1 mg finasteride, Propecia) off the market because of evidence of serious risk of patient injury, including depression and suicidal ideation. 

As an alternative, PFSF requested that the FDA require the drug’s manufacturers revise the safety information on the labeling and add boxed warnings to disclose the potential for side effects, another of which is erectile dysfunction.

Public Citizen points to a recent analysis of the VigiBase global database, which tracks adverse effects from global pharmacovigilance agencies, lists 356 reports of suicidality and 2,926 reports of psychological adverse events in finasteride users. Yet, 4 years after submitting the petition, the FDA has neither granted nor denied it.

The lawsuit claims that FDA has acted unlawfully in failing to act on PFSF’s petition, and further cites “88 cases of completed suicide associated with finasteride use” per data from the VigiBase database.

“On the same day that PFSF submitted the petition, FDA’s docket management division acknowledged receipt and assigned the petition a docket number,” Michael Kirkpatrick, the Public Citizen attorney serving as lead counsel for PFSF, told this news organization.

Yet, to date, “there has been no substantive response to the petition. The lawsuit filed today seeks to force FDA to issue a decision on PFSF’s petition,” Mr. Kirkpatrick said.

“The FDA needs to act in a timely way to protect the public from the risks associated with use of Propecia. The FDA’s failure to act exposes consumers to potentially life-threatening harm,” he added in a statement.

The complaint filed today by Public Citizen in the U.S. District Court for the District of Columbia is available online. 

This news organization reached out to the FDA for comment but did not receive a response by press time.
 

A version of this article first appeared on Medscape.com.

When the Food and Drug Administration approved Semglee, the first interchangeable biosimilar insulin, the agency pitched it as having the potential to be less costly than insulins currently on the market, but lack of transparency in pharmaceutical pricing has left analysts and advocates guessing whether it will indeed be a source of relief.

iStock/ThinkStock

Semglee (Mylan Pharmaceuticals), first approved as a biosimilar in June 2020, costs about $100 a vial.

But receiving the “interchangeable designation” in July 2021, the first for any insulin, now allows Semglee to be substituted for the branded Lantus (insulin glargine, Sanofi) at the pharmacy without the need for a separate prescription, the same way as generic medicines.

A spokesperson for Viatris – Mylan’s parent company told this news organization that the interchangeable, with its new labeling, will be “introduced before the end of the year,” but it would not give any more details.

“Additional information, including pricing information, for interchangeable biosimilar Semglee will be provided at the time of product launch,” said the spokesperson.
 

Even at $100 a vial, it is not cheap

Ian Devaney, a spokesman for the advocacy group T1 International, said the organization is optimistic, given that “another player has been able to enter into a space that has for so long been dominated by Eli Lilly, Novo Nordisk, and Sanofi.” Increased competition “will help drive down the overall costs of insulin,” Mr. Devaney said in an interview. But, he added, for many people, especially in low-income countries, Semglee’s launch will have little to no impact on price.

Even at $100 a vial in the United States, “this is not an insignificant amount of money and presents a very difficult financial challenge for those dependent on insulin to survive,” he said.

A current Semglee user agreed, sharing her story with this news organization via T1 International. “My son uses three to five vials of long-acting insulin per month, and I use one to three vials per month,” said the woman, who prefers to remain anonymous. “If we were to lose Medicaid, we would still be paying up to $800 out of pocket monthly to survive, and that’s not even counting fast-acting insulin or other supplies. While $100 a vial may be cheaper, these costs are still outrageous.”

The woman also noted that, while new competitors are welcome, they also have been disruptive. After her doctor switched her to Semglee, she was notified that it was on back order. “It took a week to get it filled, and when it finally came in, it was in short supply,” she said, noting that she and her son received one Semglee pen each, “well short of the three and five each we were expecting.”
 

U.S. pricing is all ‘smoke and mirrors’

Sara W. Koblitz, a food and drug law attorney with Hyman Phelps in Washington, D.C., noted in a blog post that interchangeable Semglee will likely be awarded a year of marketing exclusivity, which will block other interchangeable competitors from entering the market during that time.

With no competition, “Mylan can price Semglee only slightly less than Lantus and still take market share, only marginally reducing costs to consumers,” she wrote.

Jing Luo, MD, MPH, an assistant professor of medicine at the University of Pittsburgh, who has studied insulin access and costs, said that having just one interchangeable on the market might not be enough to drive insulin costs down.

And, he told this news organization, “there’s even a possibility that Semglee prices will go up, but hopefully that will not be the case.”

Manufacturers like Mylan can also offer confidential discounts and rebates to pharmacy benefit managers (PBMs), health plans, and health plan sponsors (usually large companies that are self-insured) that make it difficult to assess the true cost, said David Steinberg, PharmD, director of pharmacy insights at Scripta Insights. The Wellesley, Mass.–based company advises self-insured employers on how to optimize pharmacy benefits.

When it comes to pricing, “it’s a lot of smoke and mirrors,” Dr. Steinberg said in an interview.

Dr. Steinberg also noted that some PBMs might choose to continue contracts with Sanofi that offer rebates for Lantus, leaving Semglee in a less-preferred position on a formulary, which could increase how much the patient pays at the pharmacy counter. 

Medicare and Medicaid, however, can put Semglee in the top-tier preferred formulary position. Most Medicaid plans cover Semglee, but it appears that Medicare has not added coverage yet.
 

Does current pricing predict the future?

The currently marketed Semglee has an average wholesale price (AWP) that is one third of Lantus’, and about half of what is published for Basaglar (insulin glargine, Eli Lilly), a “follow-on biologic” approved in 2015 that is similar to Lantus, Dr. Steinberg said.

The AWP is often cited by analysts when talking about costs. The AWP of the current Semglee 10-mL vial is $118.38; the Lantus 10-mL vial is $340.27, said Steinberg.

Five prefilled Semglee pens (each 3 mL) are $177.58; for Lantus, the AWP for five 3-mL pens is $510.37.

Dr. Luo said he has seen a box of Semglee pens retail between $177 and $195, compared with about $500 retail for the Lantus pens.

Currently, people with commercial insurance can get Semglee for $0-75 a month, for up to a year, using the company’s savings program.

Steinberg said it’s possible that Mylan could increase the list price for the interchangeable Semglee, but that move could backfire. “I think their goal initially is to get market share,” he said.

After Basaglar came on the market – in late 2016 – the price of Lantus came down significantly over the next few years, according to a 2019 study by Dr. Luo’s colleagues at the University of Pittsburgh.

But Basaglar has not hung on to market share, according to Scott Strumello, a person with autoimmune type 1 diabetes who tweets and blogs about insulin and other issues.

In early August, Mr. Strumello tweeted some Lilly data that showed U.S. sales of Basaglar declined 42% in the first two quarters of 2021, compared with the same period in 2020.

Dr. Steinberg noted that the decline may have to do with rebates being given to PBMs by competitors Sanofi and Novo Nordisk. Sanofi “is very aggressive when it comes to pricing with their PBM partners,” he said.

While Mr. Devaney said people with diabetes are hopeful that Semglee can break the big three manufacturers’ monopoly, he added: “We don’t see Semglee as something that is solving the root cause of the insulin price crisis, which is high list prices and pharmaceutical industry greed.”

A version of this article first appeared on Medscape.com.

When the Food and Drug Administration approved Semglee, the first interchangeable biosimilar insulin, the agency pitched it as having the potential to be less costly than insulins currently on the market, but lack of transparency in pharmaceutical pricing has left analysts and advocates guessing whether it will indeed be a source of relief.

iStock/ThinkStock

Semglee (Mylan Pharmaceuticals), first approved as a biosimilar in June 2020, costs about $100 a vial.

But receiving the “interchangeable designation” in July 2021, the first for any insulin, now allows Semglee to be substituted for the branded Lantus (insulin glargine, Sanofi) at the pharmacy without the need for a separate prescription, the same way as generic medicines.

A spokesperson for Viatris – Mylan’s parent company told this news organization that the interchangeable, with its new labeling, will be “introduced before the end of the year,” but it would not give any more details.

“Additional information, including pricing information, for interchangeable biosimilar Semglee will be provided at the time of product launch,” said the spokesperson.
 

Even at $100 a vial, it is not cheap

Ian Devaney, a spokesman for the advocacy group T1 International, said the organization is optimistic, given that “another player has been able to enter into a space that has for so long been dominated by Eli Lilly, Novo Nordisk, and Sanofi.” Increased competition “will help drive down the overall costs of insulin,” Mr. Devaney said in an interview. But, he added, for many people, especially in low-income countries, Semglee’s launch will have little to no impact on price.

Even at $100 a vial in the United States, “this is not an insignificant amount of money and presents a very difficult financial challenge for those dependent on insulin to survive,” he said.

A current Semglee user agreed, sharing her story with this news organization via T1 International. “My son uses three to five vials of long-acting insulin per month, and I use one to three vials per month,” said the woman, who prefers to remain anonymous. “If we were to lose Medicaid, we would still be paying up to $800 out of pocket monthly to survive, and that’s not even counting fast-acting insulin or other supplies. While $100 a vial may be cheaper, these costs are still outrageous.”

The woman also noted that, while new competitors are welcome, they also have been disruptive. After her doctor switched her to Semglee, she was notified that it was on back order. “It took a week to get it filled, and when it finally came in, it was in short supply,” she said, noting that she and her son received one Semglee pen each, “well short of the three and five each we were expecting.”
 

U.S. pricing is all ‘smoke and mirrors’

Sara W. Koblitz, a food and drug law attorney with Hyman Phelps in Washington, D.C., noted in a blog post that interchangeable Semglee will likely be awarded a year of marketing exclusivity, which will block other interchangeable competitors from entering the market during that time.

With no competition, “Mylan can price Semglee only slightly less than Lantus and still take market share, only marginally reducing costs to consumers,” she wrote.

Jing Luo, MD, MPH, an assistant professor of medicine at the University of Pittsburgh, who has studied insulin access and costs, said that having just one interchangeable on the market might not be enough to drive insulin costs down.

And, he told this news organization, “there’s even a possibility that Semglee prices will go up, but hopefully that will not be the case.”

Manufacturers like Mylan can also offer confidential discounts and rebates to pharmacy benefit managers (PBMs), health plans, and health plan sponsors (usually large companies that are self-insured) that make it difficult to assess the true cost, said David Steinberg, PharmD, director of pharmacy insights at Scripta Insights. The Wellesley, Mass.–based company advises self-insured employers on how to optimize pharmacy benefits.

When it comes to pricing, “it’s a lot of smoke and mirrors,” Dr. Steinberg said in an interview.

Dr. Steinberg also noted that some PBMs might choose to continue contracts with Sanofi that offer rebates for Lantus, leaving Semglee in a less-preferred position on a formulary, which could increase how much the patient pays at the pharmacy counter. 

Medicare and Medicaid, however, can put Semglee in the top-tier preferred formulary position. Most Medicaid plans cover Semglee, but it appears that Medicare has not added coverage yet.
 

Does current pricing predict the future?

The currently marketed Semglee has an average wholesale price (AWP) that is one third of Lantus’, and about half of what is published for Basaglar (insulin glargine, Eli Lilly), a “follow-on biologic” approved in 2015 that is similar to Lantus, Dr. Steinberg said.

The AWP is often cited by analysts when talking about costs. The AWP of the current Semglee 10-mL vial is $118.38; the Lantus 10-mL vial is $340.27, said Steinberg.

Five prefilled Semglee pens (each 3 mL) are $177.58; for Lantus, the AWP for five 3-mL pens is $510.37.

Dr. Luo said he has seen a box of Semglee pens retail between $177 and $195, compared with about $500 retail for the Lantus pens.

Currently, people with commercial insurance can get Semglee for $0-75 a month, for up to a year, using the company’s savings program.

Steinberg said it’s possible that Mylan could increase the list price for the interchangeable Semglee, but that move could backfire. “I think their goal initially is to get market share,” he said.

After Basaglar came on the market – in late 2016 – the price of Lantus came down significantly over the next few years, according to a 2019 study by Dr. Luo’s colleagues at the University of Pittsburgh.

But Basaglar has not hung on to market share, according to Scott Strumello, a person with autoimmune type 1 diabetes who tweets and blogs about insulin and other issues.

In early August, Mr. Strumello tweeted some Lilly data that showed U.S. sales of Basaglar declined 42% in the first two quarters of 2021, compared with the same period in 2020.

Dr. Steinberg noted that the decline may have to do with rebates being given to PBMs by competitors Sanofi and Novo Nordisk. Sanofi “is very aggressive when it comes to pricing with their PBM partners,” he said.

While Mr. Devaney said people with diabetes are hopeful that Semglee can break the big three manufacturers’ monopoly, he added: “We don’t see Semglee as something that is solving the root cause of the insulin price crisis, which is high list prices and pharmaceutical industry greed.”

A version of this article first appeared on Medscape.com.

When the Food and Drug Administration approved Semglee, the first interchangeable biosimilar insulin, the agency pitched it as having the potential to be less costly than insulins currently on the market, but lack of transparency in pharmaceutical pricing has left analysts and advocates guessing whether it will indeed be a source of relief.

iStock/ThinkStock

Semglee (Mylan Pharmaceuticals), first approved as a biosimilar in June 2020, costs about $100 a vial.

But receiving the “interchangeable designation” in July 2021, the first for any insulin, now allows Semglee to be substituted for the branded Lantus (insulin glargine, Sanofi) at the pharmacy without the need for a separate prescription, the same way as generic medicines.

A spokesperson for Viatris – Mylan’s parent company told this news organization that the interchangeable, with its new labeling, will be “introduced before the end of the year,” but it would not give any more details.

“Additional information, including pricing information, for interchangeable biosimilar Semglee will be provided at the time of product launch,” said the spokesperson.
 

Even at $100 a vial, it is not cheap

Ian Devaney, a spokesman for the advocacy group T1 International, said the organization is optimistic, given that “another player has been able to enter into a space that has for so long been dominated by Eli Lilly, Novo Nordisk, and Sanofi.” Increased competition “will help drive down the overall costs of insulin,” Mr. Devaney said in an interview. But, he added, for many people, especially in low-income countries, Semglee’s launch will have little to no impact on price.

Even at $100 a vial in the United States, “this is not an insignificant amount of money and presents a very difficult financial challenge for those dependent on insulin to survive,” he said.

A current Semglee user agreed, sharing her story with this news organization via T1 International. “My son uses three to five vials of long-acting insulin per month, and I use one to three vials per month,” said the woman, who prefers to remain anonymous. “If we were to lose Medicaid, we would still be paying up to $800 out of pocket monthly to survive, and that’s not even counting fast-acting insulin or other supplies. While $100 a vial may be cheaper, these costs are still outrageous.”

The woman also noted that, while new competitors are welcome, they also have been disruptive. After her doctor switched her to Semglee, she was notified that it was on back order. “It took a week to get it filled, and when it finally came in, it was in short supply,” she said, noting that she and her son received one Semglee pen each, “well short of the three and five each we were expecting.”
 

U.S. pricing is all ‘smoke and mirrors’

Sara W. Koblitz, a food and drug law attorney with Hyman Phelps in Washington, D.C., noted in a blog post that interchangeable Semglee will likely be awarded a year of marketing exclusivity, which will block other interchangeable competitors from entering the market during that time.

With no competition, “Mylan can price Semglee only slightly less than Lantus and still take market share, only marginally reducing costs to consumers,” she wrote.

Jing Luo, MD, MPH, an assistant professor of medicine at the University of Pittsburgh, who has studied insulin access and costs, said that having just one interchangeable on the market might not be enough to drive insulin costs down.

And, he told this news organization, “there’s even a possibility that Semglee prices will go up, but hopefully that will not be the case.”

Manufacturers like Mylan can also offer confidential discounts and rebates to pharmacy benefit managers (PBMs), health plans, and health plan sponsors (usually large companies that are self-insured) that make it difficult to assess the true cost, said David Steinberg, PharmD, director of pharmacy insights at Scripta Insights. The Wellesley, Mass.–based company advises self-insured employers on how to optimize pharmacy benefits.

When it comes to pricing, “it’s a lot of smoke and mirrors,” Dr. Steinberg said in an interview.

Dr. Steinberg also noted that some PBMs might choose to continue contracts with Sanofi that offer rebates for Lantus, leaving Semglee in a less-preferred position on a formulary, which could increase how much the patient pays at the pharmacy counter. 

Medicare and Medicaid, however, can put Semglee in the top-tier preferred formulary position. Most Medicaid plans cover Semglee, but it appears that Medicare has not added coverage yet.
 

Does current pricing predict the future?

The currently marketed Semglee has an average wholesale price (AWP) that is one third of Lantus’, and about half of what is published for Basaglar (insulin glargine, Eli Lilly), a “follow-on biologic” approved in 2015 that is similar to Lantus, Dr. Steinberg said.

The AWP is often cited by analysts when talking about costs. The AWP of the current Semglee 10-mL vial is $118.38; the Lantus 10-mL vial is $340.27, said Steinberg.

Five prefilled Semglee pens (each 3 mL) are $177.58; for Lantus, the AWP for five 3-mL pens is $510.37.

Dr. Luo said he has seen a box of Semglee pens retail between $177 and $195, compared with about $500 retail for the Lantus pens.

Currently, people with commercial insurance can get Semglee for $0-75 a month, for up to a year, using the company’s savings program.

Steinberg said it’s possible that Mylan could increase the list price for the interchangeable Semglee, but that move could backfire. “I think their goal initially is to get market share,” he said.

After Basaglar came on the market – in late 2016 – the price of Lantus came down significantly over the next few years, according to a 2019 study by Dr. Luo’s colleagues at the University of Pittsburgh.

But Basaglar has not hung on to market share, according to Scott Strumello, a person with autoimmune type 1 diabetes who tweets and blogs about insulin and other issues.

In early August, Mr. Strumello tweeted some Lilly data that showed U.S. sales of Basaglar declined 42% in the first two quarters of 2021, compared with the same period in 2020.

Dr. Steinberg noted that the decline may have to do with rebates being given to PBMs by competitors Sanofi and Novo Nordisk. Sanofi “is very aggressive when it comes to pricing with their PBM partners,” he said.

While Mr. Devaney said people with diabetes are hopeful that Semglee can break the big three manufacturers’ monopoly, he added: “We don’t see Semglee as something that is solving the root cause of the insulin price crisis, which is high list prices and pharmaceutical industry greed.”

A version of this article first appeared on Medscape.com.