Hair plays an important role in identity, self-perception, and psychosocial functioning. Hair loss can be a devastating experience that decreases self-esteem and feelings of personal attractiveness while also leading to depression and anxiety.^1,2 Although increasingly popular, surgical hair restoration, including hair transplantation, is costly and carries considerable risk.

Results of nonsurgical hair restoration are not immediate and may not be as dramatic; however, they do not carry the risks or recovery associated with surgical options. Treatments such as sex steroid hormone and biologic response modifiers have been used to inhibit hair miniaturization and stabilize hair loss in cases of androgenic alopecia (AGA).³ Currently, minoxidil and finasteride are the only US Food and Drug Administration (FDA)–approved medications for the treatment of hair loss; however, other nonsurgical treatment options have gained popularity, including dutasteride, spironolactone, low-level laser therapy (LLLT), platelet-rich plasma (PRP), microneedling, stem cells, and nutraceutical supplements. We provide an overview of these treatment options to help dermatologists select appropriate therapies for the treatment of alopecia (Table).

Minoxidil

Minoxidil has been known to improve hair growth for more than 40 years. Oral minoxidil was first introduced for hypertension in the 1970s with a common adverse effect of hypertrichosis; the 2% solution was marketed for AGA shortly thereafter in 1986.⁴ Minoxidil is a biologic response modifier that is thought to promote hair growth through vasodilation and stimulation of hair follicles into the growth phase.⁵ In animal studies, topical minoxidil has been shown to shorten telogen, prolong anagen, and increase hair follicle size.^6,7 More recently, topical minoxidil was shown to have anti-inflammatory effects by downregulating IL-1, which may confer an additional role in combatting alopecia.⁸

Minoxidil is FDA approved for treatment of AGA in men and women and often is used as first-line therapy.⁹ In 3 separate meta-analyses of topical minoxidil, it was shown to be more effective than placebo for treating AGA in men and women, with a notable increase in target area hair growth.¹⁰ A study of 777 male patients treated with topical minoxidil 2% found that 45% subjectively experienced new hair growth.¹¹ However, results may vary, and research indicates that higher concentrations are more effective. In a randomized, double-blind, placebo-controlled trial of 381 women with female pattern hair loss (FPHL), minoxidil solution 2% was found to be superior to placebo after 48 weeks, with average changes in nonvellus hair counts of 20.7/cm² in the minoxidil group vs 9.4/cm² in the placebo group.¹² In a separate meta-analysis, minoxidil solution 5% demonstrated superiority to both the 2% formulation and placebo with a mean change in nonvellus hair counts of 26.0/cm^2.13

Minoxidil also has demonstrated promising benefits in preventing chemotherapy-induced alopecia. Although oncologists most often use the scalp cooling method to prevent hair loss by decreasing perfusion and uptake of cytotoxic agents, cost may be prohibitive, as it is often not reimbursable by insurance companies.^14,15 On the other hand, minoxidil is easily procured over-the-counter and has been successfully used to decrease the duration of alopecia caused by chemotherapeutic agents such as fluorouracil, doxorubicin, and cyclophosphamide, as well as endocrine therapies used to treat breast cancer in women.^16-18 Minoxidil also has been used off label to treat other forms of alopecia, including alopecia areata, telogen effluvium, eyebrow hypotrichosis, and monilethrix; however, there is inconclusive evidence for its efficacy.^5,13,19

Compared to other nonsurgical treatments for hair loss, a meta-analysis found that minoxidil was associated with the highest rate of adverse effects (AEs).^16,17 Potential side effects include pruritus or burning at the application site; irritant or allergic contact dermatitis; hypertrichosis; and cardiovascular effects, which may be due to the vasodilatory mechanism of action of minoxidil.²⁰ One randomized double-blind study found that while topical minoxidil did not affect blood pressure, it increased heart rate by 3 to 5 beats per minute, caused considerable increases in left ventricular end-diastolic volume, an increase in cardiac output (by 0.751 min^-1), and an increase in left ventricular mass (by 5 g m^-2). The authors concluded that short-term use is safe in healthy individuals, but providers should ask about history of coronary artery disease to avoid potential cardiac side effects.²¹

Patients also should be advised that at least 6 months of minoxidil therapy may be necessary.¹¹ Furthermore, measurable hair changes may disappear within 3 months if the patient chooses to discontinue treatment.²² Finally, providers must consider patient perception of improvement and hair growth while on this medication. In one study, although investigator assessments of hair growth and hair count were increased with the use of minoxidil solution 5% compared to placebo, differences in patient assessment of hair growth were not significant at 48 weeks.²² Therefore, dermatologists should address patient expectations and consider additional treatments if necessary.

Finasteride

Finasteride is an oral medication that is FDA approved at a dose of 1 mg daily for the treatment of AGA in men. It competitively inhibits the type I and type II 5α-reductase enzymes, with a strong affinity for the type II enzyme, thereby inhibiting the conversion of testosterone to dihydrotestosterone (DHT), the potent androgen responsible for terminal hair follicle miniaturization and transformation of terminal hair into vellus hair.^21,23

Finasteride has demonstrated efficacy and high tolerability in large-scale, placebo-controlled, randomized trials with only rare complications of sexual dysfunction, supporting its status as a first-line agent.^24,25 One study found that in a population of 3177 Japanese men, an overall increase in hair growth was seen in 87.1% of men receiving oral finasteride 1 mg daily, with AEs such as decreased libido occurring in only 0.7% of patients.²⁶ However, postmarketing studies described more severe complications in men taking finasteride to treat AGA or benign prostatic hyperplasia, even after the discontinuation of medication, described as postfinasteride syndrome.^27,28 These side effects include decreased libido, reduction in penis size, gynecomastia, erectile dysfunction, and ejaculation disorder, in addition to psychologic impairments, including decreased concentration, depression, and suicidal ideation, presumably due to the role of 5α-reductase interacting with the γ-aminobutyric acid (GABA_A) receptor within the central nervous system.²⁹ The incidence of persistent erectile dysfunction was reported to be as low as 1.4% in a study assessing 11,909 men prescribed up to 5 mg once daily of finasteride to treat benign prostatic hyperplasia and AGA. The incidence was higher in patients using higher doses of finasteride and longer treatment courses as well as in patients with prostate disease.²⁹ These potential side effects should be discussed with male patients prior to prescribing finasteride.

Finasteride is not FDA approved for use in women and is considered category X in pregnancy due to animal studies that demonstrated external genital abnormalities in male fetuses exposed to type II 5α-reductase inhibitors.³⁰ Despite this potential teratogenicity, finasteride is prescribed off label to treat FPHL and hirsutism. A meta-analysis of 2683 women participating in 65 studies found that finasteride, when used at dosages of 0.5 to 5 mg daily, may improve FPHL and frontal fibrosing alopecia after 6 to 12 months.³⁰ However, available studies have used varying treatment methods, yielding differing results. For example, one randomized trial of 137 postmenopausal women with FPHL and normal androgen levels found no benefit with 1 mg daily³¹; however, another trial of 87 women with normal levels of androgens found that 5 mg daily of finasteride showed significant improvements in hair quantity and thickness after 12 months (P<.01).³² Further studies are needed to assess the appropriate female population that may benefit from use of finasteride. Premenopausal women interested in this therapy should be counseled about the risk of teratogenicity, as well as potential breast tenderness, loss of libido, and menstrual irregularities.³³ Furthermore, finasteride use in women may pose a theoretical risk of breast cancer, as DHT inhibition results in conversion of excess testosterone to estrogen, thereby altering the estrogen to androgen ratio.³⁴

Dutasteride

Dutasteride is 100-times more potent than finasteride as an inhibitor of type I 5α-reductase enzyme and 3-times more potent as an inhibitor of type I 5α-reductase enzyme.³⁵ Therefore, it has been hypothesized that dutasteride may be more effective than finasteride for restoring hair loss, though it is not yet FDA approved for this indication.

Research evaluating the efficacy of dutasteride is emerging. Randomized controlled trials in men with AGA are promising and suggest reversed hair miniaturization.³⁶ One randomized trial of 153 men found that dutasteride 0.5 mg daily was superior to placebo for the treatment of hair loss, as evidenced by an increase in hair counts in dutasteride patients (12.2/cm²) compared to controls (4.7/cm²). Furthermore, 0.5-mg dutasteride resulted in significantly increased new hair growth after 24 weeks compared to a placebo control (23/cm² vs 4/cm²; P<.05).³⁷

Dutasteride also is now being used off label to treat FPHL. Little evidence-based research exists regarding the use of dutasteride in women, though 1 case report described successful treatment of FPHL after 6 months of treatment with 0.5 mg daily of dutasteride in a 46-year-old woman who showed only minimal improvement on oral finasteride.³⁸

The side-effect profile is similar to finasteride, and research in the urologic literature demonstrated that the rate of AEs is comparable between the 2 drugs, with reports of sexual side effects occurring in 11% of patients taking dutasteride 0.5 mg daily vs 14% of patients taking finasteride 5 mg daily.³⁹ In the dermatologic literature, there was no statistically significant difference between the rate of AEs, specifically sexual AEs, in patients taking dutasteride 0.5 mg daily vs finasteride 1 mg daily.³⁶ Safety of dutasteride in women is not well established. The side-effect profile described for finasteride, including the risk of potential fetal anomalies, should be discussed with women receiving dutasteride therapy.

Spironolactone

Although topical minoxidil is still considered first-line therapy for women experiencing hair loss, spironolactone is growing in popularity as an off-label treatment of FPHL, though it is not FDA approved for this indication. Spironolactone is a synthetic steroid that has been used as a potassium-sparing diuretic for more than 60 years. Its primary metabolite, canrenone, competitively inhibits aldosterone.³⁷ It is FDA approved for the treatment of essential hypertension (25–100 mg), congestive heart failure (25 mg), diuretic-induced hypokalemia (25–100 mg), and primary hyperaldosteronism (100–400 mg).^37,40 Spironolactone was serendipitously discovered to treat hirsutism, acne, and seborrhea associated with polycystic ovary syndrome.⁴¹

Androgens are well studied in male pattern hair loss, and their role in FPHL is now becoming evident, with new research supporting the role of spironolactone as a useful antiandrogen.^42,43 An Australian open-label trial randomized 80 women with biopsy-proven FPHL to receive either spironolactone 200 mg daily or cyproterone acetate, an antiandrogen used abroad, including in European countries, in conjunction with an oral contraceptive pill for premenopausal women.⁴² Spironolactone was found to be as effective as the alternate regimen, with 44% of patients experiencing hair regrowth, 44% experiencing no progression of hair loss, and only 12% experiencing continued hair loss.⁴⁴ Spironolactone used in combination with minoxidil has been shown to demonstrate greater efficacy when compared to spironolactone alone.⁴⁵ One observational study of 100 women with FPHL found that once-daily capsules of minoxidil 0.25 mg combined with once daily spironolactone 25 mg was a safe and effective treatment of FPHL.⁴⁴ Spironolactone also is considered safe and effective to treat FPHL in postmenopausal women by inhibiting the relative androgen excess.⁴⁶

The starting dose for spironolactone usually is 25 mg twice daily and increased by 50 mg daily up to 200 mg daily as tolerated. Furthermore, results should be monitored for at least 6 months to assess efficacy accurately.⁴⁷ Side effects include headache, decreased libido, menstrual irregularities, orthostatic hypotension, fatigue, and hyperkalemia. Although hyperkalemia is a known side effect of spironolactone, one study of 974 male and female participants receiving spironolactone found that only 0.72% of participants experienced mild hyperkalemia (5.1–6.0 mEq/L) with no patients experiencing moderate or severe hyperkalemia. Regardless, providers may consider checking potassium levels within 4 to 8 weeks of initiating treatment with spironolactone.⁴⁸ Other potential AEs include gynecomastia and feminization; therefore, it is not recommended for use in men.⁴² Oral contraception is recommended to prevent pregnancy in premenopausal women, as spironolactone may cause feminization of the male fetus. Because of the antiandrogenic and progestogenic effects of spironolactone, there has been a theoretical concern for risk of inducing breast cancer, especially in postmenopausal women. However, a study conducted in the United Kingdom of more than 1 million female patients older than 55 years found that there was no increased risk of breast cancer in postmenopausal women.⁴⁹

Low-Level Laser Light Therapy

Low-level laser light therapy has been used to reduce pain, treat edema, and promote would healing for almost 50 years and is now one of the few FDA-cleared devices to treat alopecia. Low-level laser light therapy uses red beam or near-infrared nonthermal lasers at a wavelength of 600 to 1000 nm and from 5 to 500 mW. The exact mechanism of hair growth stimulation is not known; however, it is believed that LLLT accelerates mitosis, stimulates hair follicle stem cells to activate follicular keratinocytes, and alters cellular metabolism by inhibiting nitric oxide from cytochrome c oxidase.⁵⁰

Trials evaluating the efficacy of LLLT laser combs for the treatment of AGA have demonstrated notable improvements in hair density. For example, one sham device–controlled, double-blind clinical trial randomized 334 men and women to treatment with either an FDA-cleared laser comb vs sham devices.⁵¹ The treatment devices were used 3 times weekly for 26 weeks. Hair counts for those treated with the 7-, 9-, and 12-beam LLLT laser combs were significantly higher than the sham after 26 weeks (P<.05), without any serious AEs being reported.⁵¹ Another study in men with AGA proved similarly efficacious results using at-home LLLT therapy of 655 nm to the scalp every other day for 16 weeks (60 treatments).⁵² However, a 24-week randomized, double-blind, sham device–controlled, multicenter trial evaluating the LLLT helmet (combining 650-nm laser with 630- and 660-nm light-emitting diodes) among male and female patients with AGA failed to show promising results. Although mean (SD) hair thickness (12.6 [9.4] in LLLT group vs 3.9 [7.3] in control group [P=.01]) and hair density (17.2 [12.1] in LLLT group vs –2.1 [18.3] in control group [P=.003]) increased significantly, there was no significant difference in subject assessment of global appearance between the 2 groups.⁵³

Low-level laser light therapy devices are available both for use at home and in office, with 650- to 900-nm wavelengths at 5 mW being the recommended dose for men and women.⁵¹ With regard to AEs, the safety profile for LLLT is relatively favorable. Adverse events can include dry skin, pruritus, scalp tenderness, irritation, and a warm sensation at the treatment site.⁵²

Platelet-Rich Plasma

Originally used in the orthopedic literature to stimulate collagen growth, PRP has since been used in dermatology to promote hair regrowth by releasing platelet-derived growth factors, vascular endothelial growth factor, epidermal growth factor, insulinlike growth factor, and fibroblast growth factors to stimulate vascularization to the dermal papillary cells.^54,55 Platelet-rich plasma is derived from the supernatant of centrifuged whole blood and then injected in the dermis of the scalp to stimulate hair growth.

Although use of PRP is not approved or cleared by the FDA for treatment of hair loss, several studies have demonstrated the efficacy of autologous PRP use for treating AGA.⁵⁶ One pilot study of 19 male and female participants given a total of 5 PRP injections monthly for 3 months and subsequently at months 4 and 7 found a statistically significant improvement in mean hair density, hair diameter, and terminal-vellus hair ratio at 1-year follow-up (P<.05). Furthermore, histomorphometric evaluation demonstrated a decrease in perivascular inflammatory infiltrate.⁵⁷ On the other hand, 2 separate studies failed to show statistically significant improvements in hair growth after use of PRP.^58,59 Varying levels of success may be due in part to lack of a standard protocol for performing PRP injections. Studies comparing efficacy of different PRP administration regimens are emerging. A trial of 40 men and women found that subdermal PRP injections administered 3 times per month with booster injections administered 3 months later was more effective than other injection regimens, including once monthly injections.^58,59 Activators such as collagen, thrombin, 10% calcium chloride, and calcium gluconate may be added to the PRP serum to promote further growth factor secretion upon platelet activation.⁶⁰ However, different means of activation are used in different trials, potentially leading to varying results in clinical trials, with no one proven superior method.^61-63 The main drawback of PRP use is that there is no consensus regarding exact concentration, utility of activators, dosing parameters, depth of injection, or frequency of sessions.⁶⁰ Transient pain and erythema are the most common side effects of PRP injections, with no major AEs reported in the literature.⁶⁴

Microneedling

Microneedling is a minimally invasive procedure that uses needles to puncture the stratum corneum of the skin.⁶⁵ It was first used cosmetically more than 20 years ago due to its ability to increase collagen and elastin formation.⁵¹ Since its discovery, microneedling has been used to reduce the appearance of scars; augment transdermal drug delivery; and treat active acne vulgaris, melasma, hyperhidrosis, and alopecia.⁶⁵ Although there are numerous at-home and professional microneedling devices on the market, only one device has been FDA cleared thus far.

Microneedling is proposed to increase hair regrowth by triggering the wound healing response, which ultimately augments the release of platelet-derived and epidermal growth factors while also activating the hair bulge.⁶⁶ Treatment often is performed with a roller instrument that uses needles 0.5- to 2.5-mm long. Topical anesthetic cream may be applied prior to treatment.⁶⁷ The treated area is then washed and an antibiotic ointment is applied.⁵⁵ Management regimens typically require daily to weekly treatments with a total of 12 to 28 weeks to demonstrate an effect.

Microneedling has demonstrated efficacy in the treatment of hair loss, especially when combined with minoxidil. One study randomized 68 patients to undergo microneedling with minoxidil solution 5% twice daily compared to a control group of minoxidil solution 5% twice daily alone. After 12 weeks, patients treated with microneedling and minoxidil had significantly higher hair counts than the control group (P<.05).⁶⁸ It is speculated that microneedling increases penetration of topical medications, including minoxidil across the skin barrier, thereby enhancing absorption of large molecules.⁶⁶

Topical PRP has been used synergistically to augment the effects of microneedling. A trial randomized 93 patients with alopecia to receive minoxidil solution 5% alone, minoxidil solution 5% plus PRP, or microneedling with PRP.⁶⁹ Hair growth was appreciated in 26 of 31 patients treated with microneedling and PRP compared to 10 of 31 and 17 of 31 in the other 2 groups, respectively. However, when hair growth occurred in the minoxidil-treated group, it occurred faster, with changes in hair growth at 12 weeks compared to 26 weeks in the microneedling group.⁶⁹ When evaluating the efficacy of microneedling and PRP, it must be noted that there is no established leading protocol for treating hair loss, which may affect the success of the treatment.

The reported side-effect profile for microneedling and PRP injections has been favorable without any major AEs noted in clinical trials.^56,64,70 The possibility of bleeding, pain, erythema, and infection should be discussed with the patient nonetheless. More severe side effects such as allergic granulomatous reactions have been reported in the literature with the use of microneedling for facial rejuvenation.⁷¹

Stem Cells

Stem cell hair therapy is a new and promising area of research with the potential to treat alopecia. Although not yet FDA approved for this indication, human umbilical cord blood–derived mesenchymal stem cells (HUCB-MSCs) have received particular attention due to their proposed ability to promote tissue differentiation and repair, to replace aged and damaged hair cells, and to promote secretion of multiple growth factors.⁷² More recently, HUCB-MSCs have been shown to successfully differentiate into human hair follicles in vitro after 3 weeks of cell culture, establishing a method for high-speed and high-purity hair follicle cell differentiation with the hope of future injections to affected areas with hair loss.⁷³ Another study found that HUCB-MSCs enhanced growth of human follicular stem cells in vitro; the authors proposed an altered Wnt/β‐catenin and JAK/STAT pathway was responsible for improved growth of hair follicular cells.⁷⁴

Although umbilical cord blood is replete with the most rapidly dividing stem cells, autologous stem cells derived from the hair follicle or mononuclear cells also may be used to treat alopecia. One recent study randomized 40 patients with AGA and alopecia areata to receive 1 session of either autologous hair follicle or mononuclear cell–derived stem cell injections to the scalp.⁷⁵ Mononuclear cells were acquired from the upper iliac crest bone marrow of patients who were treated with granulocyte colony-stimulating factor 3 days prior to the procedure. Follicular stem cells were taken from 4-mm punch biopsies of the unaffected scalp. After 6 months, there was a notable improvement in hair growth confirmed by immunostaining and dermoscopy, without a significant difference between the forms of autologous stem cell source. Of note, 45% of study patients with alopecia areata showed recurrence of disease at 1-year follow-up. The most common AEs were scalp dermatitis in 20% of participants. Participants who underwent bone marrow biopsy experienced bone pain, hematoma, and granulocyte colony-stimulating factor–induced fatigue and chills.⁷⁵

Furthermore, the cost of stem cell therapy may be prohibitive. Therefore, although stem cell therapy is a novel and promising treatment for hair loss, future research is necessary to establish safety, efficacy, best practices, and accessibility.

Supplements

Patients failing routine treatments for alopecia may turn to holistic therapies. Nutrafol (Nutraceutical Wellness Inc), a novel nutraceutical product, is one such option that has been described for its anti-inflammatory, adaptogenic, antioxidant, and DHT-inhibiting properties. This supplement is not FDA approved or cleared, and large-scale clinical trials are lacking; however, one randomized controlled trial of 40 women with self-reported hair loss found a statistically significant increase in the number of terminal and vellus hair based on phototrichograms performed after 90 and 180 days (P=.009), with no AEs reported. This study, however, was limited by a small sample size.⁷⁶

Lamdapil (ISDIN) is another oral supplement being investigated for hair loss. It contains L-cystine amino acids; zinc; vitamins B₃, B₅, B₆; biotin; and the plant extract Serenoa repens.⁷¹Serenoa repens has reported activity inhibiting the enzyme 5α-reductase with the other vitamins, and amino acids are thought to maintain keratin and collagen growth in normal hair.⁷⁷ One randomized trial investigated use of Lamdapil capsules in a total of 70 patients, which included men with AGA and women experiencing telogen effluvium. For men, the anagen-telogen ratio increased in the Lamdapil-treated group by 23.4%, indicating that more hair was in the growing phase compared to placebo (P<.05). Women with telogen effluvium experienced a significantly greater improvement in the hair-pull test compared to placebo (P<.05).⁷⁷

Marine-derived nutraceutical substances also have been investigated for their role in treating hair loss. Viviscal, originally marketed under the name Hairgain, is one such supplement, which was shown to significantly reduce hair shedding at 3 and 6 months in a group of 96 premenopausal women diagnosed with subclinical hair thinning (P<.05). Additionally, phototrichogram images demonstrated a statistically significant increase in the mean velluslike hair diameter at 6 months compared to baseline.⁷⁸

Although nutraceutical products are not first-line therapy for hair loss, dermatologists may recommend these treatments in patients refusing prescription medications, specifically requesting a natural treatment, or in addition to a first-line agent such as minoxidil. It must be noted, however, that both supplements are new, and there is need for further investigation on their efficacy, safety, and dosing, as neither is FDA regulated.

Conclusion

Hair loss affects millions of Americans each year and has detrimental effects on self-esteem and psychosocial functioning. Nonsurgical treatment options will undoubtedly continue to intrigue patients, as they are often less costly and do not carry risks associated with surgery. Minoxidil, finasteride, and LLLT remain staples of therapy, with the strongest evidence supporting their safety and efficacy. Numerous other treatment options are emerging, including PRP, microneedling, mesenchymal and autologous stem cell therapy, and oral supplements, though further research must be conducted to establish dosing, safety, and best practices. Physicians must discuss patient preference and anticipated length of treatment when discussing alopecia treatment to maximize patient satisfaction.

Hair plays an important role in identity, self-perception, and psychosocial functioning. Hair loss can be a devastating experience that decreases self-esteem and feelings of personal attractiveness while also leading to depression and anxiety.^1,2 Although increasingly popular, surgical hair restoration, including hair transplantation, is costly and carries considerable risk.

Results of nonsurgical hair restoration are not immediate and may not be as dramatic; however, they do not carry the risks or recovery associated with surgical options. Treatments such as sex steroid hormone and biologic response modifiers have been used to inhibit hair miniaturization and stabilize hair loss in cases of androgenic alopecia (AGA).³ Currently, minoxidil and finasteride are the only US Food and Drug Administration (FDA)–approved medications for the treatment of hair loss; however, other nonsurgical treatment options have gained popularity, including dutasteride, spironolactone, low-level laser therapy (LLLT), platelet-rich plasma (PRP), microneedling, stem cells, and nutraceutical supplements. We provide an overview of these treatment options to help dermatologists select appropriate therapies for the treatment of alopecia (Table).

Minoxidil

Minoxidil has been known to improve hair growth for more than 40 years. Oral minoxidil was first introduced for hypertension in the 1970s with a common adverse effect of hypertrichosis; the 2% solution was marketed for AGA shortly thereafter in 1986.⁴ Minoxidil is a biologic response modifier that is thought to promote hair growth through vasodilation and stimulation of hair follicles into the growth phase.⁵ In animal studies, topical minoxidil has been shown to shorten telogen, prolong anagen, and increase hair follicle size.^6,7 More recently, topical minoxidil was shown to have anti-inflammatory effects by downregulating IL-1, which may confer an additional role in combatting alopecia.⁸

Minoxidil is FDA approved for treatment of AGA in men and women and often is used as first-line therapy.⁹ In 3 separate meta-analyses of topical minoxidil, it was shown to be more effective than placebo for treating AGA in men and women, with a notable increase in target area hair growth.¹⁰ A study of 777 male patients treated with topical minoxidil 2% found that 45% subjectively experienced new hair growth.¹¹ However, results may vary, and research indicates that higher concentrations are more effective. In a randomized, double-blind, placebo-controlled trial of 381 women with female pattern hair loss (FPHL), minoxidil solution 2% was found to be superior to placebo after 48 weeks, with average changes in nonvellus hair counts of 20.7/cm² in the minoxidil group vs 9.4/cm² in the placebo group.¹² In a separate meta-analysis, minoxidil solution 5% demonstrated superiority to both the 2% formulation and placebo with a mean change in nonvellus hair counts of 26.0/cm^2.13

Minoxidil also has demonstrated promising benefits in preventing chemotherapy-induced alopecia. Although oncologists most often use the scalp cooling method to prevent hair loss by decreasing perfusion and uptake of cytotoxic agents, cost may be prohibitive, as it is often not reimbursable by insurance companies.^14,15 On the other hand, minoxidil is easily procured over-the-counter and has been successfully used to decrease the duration of alopecia caused by chemotherapeutic agents such as fluorouracil, doxorubicin, and cyclophosphamide, as well as endocrine therapies used to treat breast cancer in women.^16-18 Minoxidil also has been used off label to treat other forms of alopecia, including alopecia areata, telogen effluvium, eyebrow hypotrichosis, and monilethrix; however, there is inconclusive evidence for its efficacy.^5,13,19

Compared to other nonsurgical treatments for hair loss, a meta-analysis found that minoxidil was associated with the highest rate of adverse effects (AEs).^16,17 Potential side effects include pruritus or burning at the application site; irritant or allergic contact dermatitis; hypertrichosis; and cardiovascular effects, which may be due to the vasodilatory mechanism of action of minoxidil.²⁰ One randomized double-blind study found that while topical minoxidil did not affect blood pressure, it increased heart rate by 3 to 5 beats per minute, caused considerable increases in left ventricular end-diastolic volume, an increase in cardiac output (by 0.751 min^-1), and an increase in left ventricular mass (by 5 g m^-2). The authors concluded that short-term use is safe in healthy individuals, but providers should ask about history of coronary artery disease to avoid potential cardiac side effects.²¹

Patients also should be advised that at least 6 months of minoxidil therapy may be necessary.¹¹ Furthermore, measurable hair changes may disappear within 3 months if the patient chooses to discontinue treatment.²² Finally, providers must consider patient perception of improvement and hair growth while on this medication. In one study, although investigator assessments of hair growth and hair count were increased with the use of minoxidil solution 5% compared to placebo, differences in patient assessment of hair growth were not significant at 48 weeks.²² Therefore, dermatologists should address patient expectations and consider additional treatments if necessary.

Finasteride

Finasteride is an oral medication that is FDA approved at a dose of 1 mg daily for the treatment of AGA in men. It competitively inhibits the type I and type II 5α-reductase enzymes, with a strong affinity for the type II enzyme, thereby inhibiting the conversion of testosterone to dihydrotestosterone (DHT), the potent androgen responsible for terminal hair follicle miniaturization and transformation of terminal hair into vellus hair.^21,23

Finasteride has demonstrated efficacy and high tolerability in large-scale, placebo-controlled, randomized trials with only rare complications of sexual dysfunction, supporting its status as a first-line agent.^24,25 One study found that in a population of 3177 Japanese men, an overall increase in hair growth was seen in 87.1% of men receiving oral finasteride 1 mg daily, with AEs such as decreased libido occurring in only 0.7% of patients.²⁶ However, postmarketing studies described more severe complications in men taking finasteride to treat AGA or benign prostatic hyperplasia, even after the discontinuation of medication, described as postfinasteride syndrome.^27,28 These side effects include decreased libido, reduction in penis size, gynecomastia, erectile dysfunction, and ejaculation disorder, in addition to psychologic impairments, including decreased concentration, depression, and suicidal ideation, presumably due to the role of 5α-reductase interacting with the γ-aminobutyric acid (GABA_A) receptor within the central nervous system.²⁹ The incidence of persistent erectile dysfunction was reported to be as low as 1.4% in a study assessing 11,909 men prescribed up to 5 mg once daily of finasteride to treat benign prostatic hyperplasia and AGA. The incidence was higher in patients using higher doses of finasteride and longer treatment courses as well as in patients with prostate disease.²⁹ These potential side effects should be discussed with male patients prior to prescribing finasteride.

Finasteride is not FDA approved for use in women and is considered category X in pregnancy due to animal studies that demonstrated external genital abnormalities in male fetuses exposed to type II 5α-reductase inhibitors.³⁰ Despite this potential teratogenicity, finasteride is prescribed off label to treat FPHL and hirsutism. A meta-analysis of 2683 women participating in 65 studies found that finasteride, when used at dosages of 0.5 to 5 mg daily, may improve FPHL and frontal fibrosing alopecia after 6 to 12 months.³⁰ However, available studies have used varying treatment methods, yielding differing results. For example, one randomized trial of 137 postmenopausal women with FPHL and normal androgen levels found no benefit with 1 mg daily³¹; however, another trial of 87 women with normal levels of androgens found that 5 mg daily of finasteride showed significant improvements in hair quantity and thickness after 12 months (P<.01).³² Further studies are needed to assess the appropriate female population that may benefit from use of finasteride. Premenopausal women interested in this therapy should be counseled about the risk of teratogenicity, as well as potential breast tenderness, loss of libido, and menstrual irregularities.³³ Furthermore, finasteride use in women may pose a theoretical risk of breast cancer, as DHT inhibition results in conversion of excess testosterone to estrogen, thereby altering the estrogen to androgen ratio.³⁴

Dutasteride

Dutasteride is 100-times more potent than finasteride as an inhibitor of type I 5α-reductase enzyme and 3-times more potent as an inhibitor of type I 5α-reductase enzyme.³⁵ Therefore, it has been hypothesized that dutasteride may be more effective than finasteride for restoring hair loss, though it is not yet FDA approved for this indication.

Research evaluating the efficacy of dutasteride is emerging. Randomized controlled trials in men with AGA are promising and suggest reversed hair miniaturization.³⁶ One randomized trial of 153 men found that dutasteride 0.5 mg daily was superior to placebo for the treatment of hair loss, as evidenced by an increase in hair counts in dutasteride patients (12.2/cm²) compared to controls (4.7/cm²). Furthermore, 0.5-mg dutasteride resulted in significantly increased new hair growth after 24 weeks compared to a placebo control (23/cm² vs 4/cm²; P<.05).³⁷

Dutasteride also is now being used off label to treat FPHL. Little evidence-based research exists regarding the use of dutasteride in women, though 1 case report described successful treatment of FPHL after 6 months of treatment with 0.5 mg daily of dutasteride in a 46-year-old woman who showed only minimal improvement on oral finasteride.³⁸

The side-effect profile is similar to finasteride, and research in the urologic literature demonstrated that the rate of AEs is comparable between the 2 drugs, with reports of sexual side effects occurring in 11% of patients taking dutasteride 0.5 mg daily vs 14% of patients taking finasteride 5 mg daily.³⁹ In the dermatologic literature, there was no statistically significant difference between the rate of AEs, specifically sexual AEs, in patients taking dutasteride 0.5 mg daily vs finasteride 1 mg daily.³⁶ Safety of dutasteride in women is not well established. The side-effect profile described for finasteride, including the risk of potential fetal anomalies, should be discussed with women receiving dutasteride therapy.

Spironolactone

Although topical minoxidil is still considered first-line therapy for women experiencing hair loss, spironolactone is growing in popularity as an off-label treatment of FPHL, though it is not FDA approved for this indication. Spironolactone is a synthetic steroid that has been used as a potassium-sparing diuretic for more than 60 years. Its primary metabolite, canrenone, competitively inhibits aldosterone.³⁷ It is FDA approved for the treatment of essential hypertension (25–100 mg), congestive heart failure (25 mg), diuretic-induced hypokalemia (25–100 mg), and primary hyperaldosteronism (100–400 mg).^37,40 Spironolactone was serendipitously discovered to treat hirsutism, acne, and seborrhea associated with polycystic ovary syndrome.⁴¹

Androgens are well studied in male pattern hair loss, and their role in FPHL is now becoming evident, with new research supporting the role of spironolactone as a useful antiandrogen.^42,43 An Australian open-label trial randomized 80 women with biopsy-proven FPHL to receive either spironolactone 200 mg daily or cyproterone acetate, an antiandrogen used abroad, including in European countries, in conjunction with an oral contraceptive pill for premenopausal women.⁴² Spironolactone was found to be as effective as the alternate regimen, with 44% of patients experiencing hair regrowth, 44% experiencing no progression of hair loss, and only 12% experiencing continued hair loss.⁴⁴ Spironolactone used in combination with minoxidil has been shown to demonstrate greater efficacy when compared to spironolactone alone.⁴⁵ One observational study of 100 women with FPHL found that once-daily capsules of minoxidil 0.25 mg combined with once daily spironolactone 25 mg was a safe and effective treatment of FPHL.⁴⁴ Spironolactone also is considered safe and effective to treat FPHL in postmenopausal women by inhibiting the relative androgen excess.⁴⁶

The starting dose for spironolactone usually is 25 mg twice daily and increased by 50 mg daily up to 200 mg daily as tolerated. Furthermore, results should be monitored for at least 6 months to assess efficacy accurately.⁴⁷ Side effects include headache, decreased libido, menstrual irregularities, orthostatic hypotension, fatigue, and hyperkalemia. Although hyperkalemia is a known side effect of spironolactone, one study of 974 male and female participants receiving spironolactone found that only 0.72% of participants experienced mild hyperkalemia (5.1–6.0 mEq/L) with no patients experiencing moderate or severe hyperkalemia. Regardless, providers may consider checking potassium levels within 4 to 8 weeks of initiating treatment with spironolactone.⁴⁸ Other potential AEs include gynecomastia and feminization; therefore, it is not recommended for use in men.⁴² Oral contraception is recommended to prevent pregnancy in premenopausal women, as spironolactone may cause feminization of the male fetus. Because of the antiandrogenic and progestogenic effects of spironolactone, there has been a theoretical concern for risk of inducing breast cancer, especially in postmenopausal women. However, a study conducted in the United Kingdom of more than 1 million female patients older than 55 years found that there was no increased risk of breast cancer in postmenopausal women.⁴⁹

Low-Level Laser Light Therapy

Low-level laser light therapy has been used to reduce pain, treat edema, and promote would healing for almost 50 years and is now one of the few FDA-cleared devices to treat alopecia. Low-level laser light therapy uses red beam or near-infrared nonthermal lasers at a wavelength of 600 to 1000 nm and from 5 to 500 mW. The exact mechanism of hair growth stimulation is not known; however, it is believed that LLLT accelerates mitosis, stimulates hair follicle stem cells to activate follicular keratinocytes, and alters cellular metabolism by inhibiting nitric oxide from cytochrome c oxidase.⁵⁰

Trials evaluating the efficacy of LLLT laser combs for the treatment of AGA have demonstrated notable improvements in hair density. For example, one sham device–controlled, double-blind clinical trial randomized 334 men and women to treatment with either an FDA-cleared laser comb vs sham devices.⁵¹ The treatment devices were used 3 times weekly for 26 weeks. Hair counts for those treated with the 7-, 9-, and 12-beam LLLT laser combs were significantly higher than the sham after 26 weeks (P<.05), without any serious AEs being reported.⁵¹ Another study in men with AGA proved similarly efficacious results using at-home LLLT therapy of 655 nm to the scalp every other day for 16 weeks (60 treatments).⁵² However, a 24-week randomized, double-blind, sham device–controlled, multicenter trial evaluating the LLLT helmet (combining 650-nm laser with 630- and 660-nm light-emitting diodes) among male and female patients with AGA failed to show promising results. Although mean (SD) hair thickness (12.6 [9.4] in LLLT group vs 3.9 [7.3] in control group [P=.01]) and hair density (17.2 [12.1] in LLLT group vs –2.1 [18.3] in control group [P=.003]) increased significantly, there was no significant difference in subject assessment of global appearance between the 2 groups.⁵³

Low-level laser light therapy devices are available both for use at home and in office, with 650- to 900-nm wavelengths at 5 mW being the recommended dose for men and women.⁵¹ With regard to AEs, the safety profile for LLLT is relatively favorable. Adverse events can include dry skin, pruritus, scalp tenderness, irritation, and a warm sensation at the treatment site.⁵²

Platelet-Rich Plasma

Originally used in the orthopedic literature to stimulate collagen growth, PRP has since been used in dermatology to promote hair regrowth by releasing platelet-derived growth factors, vascular endothelial growth factor, epidermal growth factor, insulinlike growth factor, and fibroblast growth factors to stimulate vascularization to the dermal papillary cells.^54,55 Platelet-rich plasma is derived from the supernatant of centrifuged whole blood and then injected in the dermis of the scalp to stimulate hair growth.

Although use of PRP is not approved or cleared by the FDA for treatment of hair loss, several studies have demonstrated the efficacy of autologous PRP use for treating AGA.⁵⁶ One pilot study of 19 male and female participants given a total of 5 PRP injections monthly for 3 months and subsequently at months 4 and 7 found a statistically significant improvement in mean hair density, hair diameter, and terminal-vellus hair ratio at 1-year follow-up (P<.05). Furthermore, histomorphometric evaluation demonstrated a decrease in perivascular inflammatory infiltrate.⁵⁷ On the other hand, 2 separate studies failed to show statistically significant improvements in hair growth after use of PRP.^58,59 Varying levels of success may be due in part to lack of a standard protocol for performing PRP injections. Studies comparing efficacy of different PRP administration regimens are emerging. A trial of 40 men and women found that subdermal PRP injections administered 3 times per month with booster injections administered 3 months later was more effective than other injection regimens, including once monthly injections.^58,59 Activators such as collagen, thrombin, 10% calcium chloride, and calcium gluconate may be added to the PRP serum to promote further growth factor secretion upon platelet activation.⁶⁰ However, different means of activation are used in different trials, potentially leading to varying results in clinical trials, with no one proven superior method.^61-63 The main drawback of PRP use is that there is no consensus regarding exact concentration, utility of activators, dosing parameters, depth of injection, or frequency of sessions.⁶⁰ Transient pain and erythema are the most common side effects of PRP injections, with no major AEs reported in the literature.⁶⁴

Microneedling

Microneedling is a minimally invasive procedure that uses needles to puncture the stratum corneum of the skin.⁶⁵ It was first used cosmetically more than 20 years ago due to its ability to increase collagen and elastin formation.⁵¹ Since its discovery, microneedling has been used to reduce the appearance of scars; augment transdermal drug delivery; and treat active acne vulgaris, melasma, hyperhidrosis, and alopecia.⁶⁵ Although there are numerous at-home and professional microneedling devices on the market, only one device has been FDA cleared thus far.

Microneedling is proposed to increase hair regrowth by triggering the wound healing response, which ultimately augments the release of platelet-derived and epidermal growth factors while also activating the hair bulge.⁶⁶ Treatment often is performed with a roller instrument that uses needles 0.5- to 2.5-mm long. Topical anesthetic cream may be applied prior to treatment.⁶⁷ The treated area is then washed and an antibiotic ointment is applied.⁵⁵ Management regimens typically require daily to weekly treatments with a total of 12 to 28 weeks to demonstrate an effect.

Microneedling has demonstrated efficacy in the treatment of hair loss, especially when combined with minoxidil. One study randomized 68 patients to undergo microneedling with minoxidil solution 5% twice daily compared to a control group of minoxidil solution 5% twice daily alone. After 12 weeks, patients treated with microneedling and minoxidil had significantly higher hair counts than the control group (P<.05).⁶⁸ It is speculated that microneedling increases penetration of topical medications, including minoxidil across the skin barrier, thereby enhancing absorption of large molecules.⁶⁶

Topical PRP has been used synergistically to augment the effects of microneedling. A trial randomized 93 patients with alopecia to receive minoxidil solution 5% alone, minoxidil solution 5% plus PRP, or microneedling with PRP.⁶⁹ Hair growth was appreciated in 26 of 31 patients treated with microneedling and PRP compared to 10 of 31 and 17 of 31 in the other 2 groups, respectively. However, when hair growth occurred in the minoxidil-treated group, it occurred faster, with changes in hair growth at 12 weeks compared to 26 weeks in the microneedling group.⁶⁹ When evaluating the efficacy of microneedling and PRP, it must be noted that there is no established leading protocol for treating hair loss, which may affect the success of the treatment.

The reported side-effect profile for microneedling and PRP injections has been favorable without any major AEs noted in clinical trials.^56,64,70 The possibility of bleeding, pain, erythema, and infection should be discussed with the patient nonetheless. More severe side effects such as allergic granulomatous reactions have been reported in the literature with the use of microneedling for facial rejuvenation.⁷¹

Stem Cells

Stem cell hair therapy is a new and promising area of research with the potential to treat alopecia. Although not yet FDA approved for this indication, human umbilical cord blood–derived mesenchymal stem cells (HUCB-MSCs) have received particular attention due to their proposed ability to promote tissue differentiation and repair, to replace aged and damaged hair cells, and to promote secretion of multiple growth factors.⁷² More recently, HUCB-MSCs have been shown to successfully differentiate into human hair follicles in vitro after 3 weeks of cell culture, establishing a method for high-speed and high-purity hair follicle cell differentiation with the hope of future injections to affected areas with hair loss.⁷³ Another study found that HUCB-MSCs enhanced growth of human follicular stem cells in vitro; the authors proposed an altered Wnt/β‐catenin and JAK/STAT pathway was responsible for improved growth of hair follicular cells.⁷⁴

Although umbilical cord blood is replete with the most rapidly dividing stem cells, autologous stem cells derived from the hair follicle or mononuclear cells also may be used to treat alopecia. One recent study randomized 40 patients with AGA and alopecia areata to receive 1 session of either autologous hair follicle or mononuclear cell–derived stem cell injections to the scalp.⁷⁵ Mononuclear cells were acquired from the upper iliac crest bone marrow of patients who were treated with granulocyte colony-stimulating factor 3 days prior to the procedure. Follicular stem cells were taken from 4-mm punch biopsies of the unaffected scalp. After 6 months, there was a notable improvement in hair growth confirmed by immunostaining and dermoscopy, without a significant difference between the forms of autologous stem cell source. Of note, 45% of study patients with alopecia areata showed recurrence of disease at 1-year follow-up. The most common AEs were scalp dermatitis in 20% of participants. Participants who underwent bone marrow biopsy experienced bone pain, hematoma, and granulocyte colony-stimulating factor–induced fatigue and chills.⁷⁵

Furthermore, the cost of stem cell therapy may be prohibitive. Therefore, although stem cell therapy is a novel and promising treatment for hair loss, future research is necessary to establish safety, efficacy, best practices, and accessibility.

Supplements

Patients failing routine treatments for alopecia may turn to holistic therapies. Nutrafol (Nutraceutical Wellness Inc), a novel nutraceutical product, is one such option that has been described for its anti-inflammatory, adaptogenic, antioxidant, and DHT-inhibiting properties. This supplement is not FDA approved or cleared, and large-scale clinical trials are lacking; however, one randomized controlled trial of 40 women with self-reported hair loss found a statistically significant increase in the number of terminal and vellus hair based on phototrichograms performed after 90 and 180 days (P=.009), with no AEs reported. This study, however, was limited by a small sample size.⁷⁶

Lamdapil (ISDIN) is another oral supplement being investigated for hair loss. It contains L-cystine amino acids; zinc; vitamins B₃, B₅, B₆; biotin; and the plant extract Serenoa repens.⁷¹Serenoa repens has reported activity inhibiting the enzyme 5α-reductase with the other vitamins, and amino acids are thought to maintain keratin and collagen growth in normal hair.⁷⁷ One randomized trial investigated use of Lamdapil capsules in a total of 70 patients, which included men with AGA and women experiencing telogen effluvium. For men, the anagen-telogen ratio increased in the Lamdapil-treated group by 23.4%, indicating that more hair was in the growing phase compared to placebo (P<.05). Women with telogen effluvium experienced a significantly greater improvement in the hair-pull test compared to placebo (P<.05).⁷⁷

Marine-derived nutraceutical substances also have been investigated for their role in treating hair loss. Viviscal, originally marketed under the name Hairgain, is one such supplement, which was shown to significantly reduce hair shedding at 3 and 6 months in a group of 96 premenopausal women diagnosed with subclinical hair thinning (P<.05). Additionally, phototrichogram images demonstrated a statistically significant increase in the mean velluslike hair diameter at 6 months compared to baseline.⁷⁸

Although nutraceutical products are not first-line therapy for hair loss, dermatologists may recommend these treatments in patients refusing prescription medications, specifically requesting a natural treatment, or in addition to a first-line agent such as minoxidil. It must be noted, however, that both supplements are new, and there is need for further investigation on their efficacy, safety, and dosing, as neither is FDA regulated.

Conclusion

Hair loss affects millions of Americans each year and has detrimental effects on self-esteem and psychosocial functioning. Nonsurgical treatment options will undoubtedly continue to intrigue patients, as they are often less costly and do not carry risks associated with surgery. Minoxidil, finasteride, and LLLT remain staples of therapy, with the strongest evidence supporting their safety and efficacy. Numerous other treatment options are emerging, including PRP, microneedling, mesenchymal and autologous stem cell therapy, and oral supplements, though further research must be conducted to establish dosing, safety, and best practices. Physicians must discuss patient preference and anticipated length of treatment when discussing alopecia treatment to maximize patient satisfaction.

Hair plays an important role in identity, self-perception, and psychosocial functioning. Hair loss can be a devastating experience that decreases self-esteem and feelings of personal attractiveness while also leading to depression and anxiety.^1,2 Although increasingly popular, surgical hair restoration, including hair transplantation, is costly and carries considerable risk.

Results of nonsurgical hair restoration are not immediate and may not be as dramatic; however, they do not carry the risks or recovery associated with surgical options. Treatments such as sex steroid hormone and biologic response modifiers have been used to inhibit hair miniaturization and stabilize hair loss in cases of androgenic alopecia (AGA).³ Currently, minoxidil and finasteride are the only US Food and Drug Administration (FDA)–approved medications for the treatment of hair loss; however, other nonsurgical treatment options have gained popularity, including dutasteride, spironolactone, low-level laser therapy (LLLT), platelet-rich plasma (PRP), microneedling, stem cells, and nutraceutical supplements. We provide an overview of these treatment options to help dermatologists select appropriate therapies for the treatment of alopecia (Table).

Minoxidil

Minoxidil has been known to improve hair growth for more than 40 years. Oral minoxidil was first introduced for hypertension in the 1970s with a common adverse effect of hypertrichosis; the 2% solution was marketed for AGA shortly thereafter in 1986.⁴ Minoxidil is a biologic response modifier that is thought to promote hair growth through vasodilation and stimulation of hair follicles into the growth phase.⁵ In animal studies, topical minoxidil has been shown to shorten telogen, prolong anagen, and increase hair follicle size.^6,7 More recently, topical minoxidil was shown to have anti-inflammatory effects by downregulating IL-1, which may confer an additional role in combatting alopecia.⁸

Minoxidil is FDA approved for treatment of AGA in men and women and often is used as first-line therapy.⁹ In 3 separate meta-analyses of topical minoxidil, it was shown to be more effective than placebo for treating AGA in men and women, with a notable increase in target area hair growth.¹⁰ A study of 777 male patients treated with topical minoxidil 2% found that 45% subjectively experienced new hair growth.¹¹ However, results may vary, and research indicates that higher concentrations are more effective. In a randomized, double-blind, placebo-controlled trial of 381 women with female pattern hair loss (FPHL), minoxidil solution 2% was found to be superior to placebo after 48 weeks, with average changes in nonvellus hair counts of 20.7/cm² in the minoxidil group vs 9.4/cm² in the placebo group.¹² In a separate meta-analysis, minoxidil solution 5% demonstrated superiority to both the 2% formulation and placebo with a mean change in nonvellus hair counts of 26.0/cm^2.13

Minoxidil also has demonstrated promising benefits in preventing chemotherapy-induced alopecia. Although oncologists most often use the scalp cooling method to prevent hair loss by decreasing perfusion and uptake of cytotoxic agents, cost may be prohibitive, as it is often not reimbursable by insurance companies.^14,15 On the other hand, minoxidil is easily procured over-the-counter and has been successfully used to decrease the duration of alopecia caused by chemotherapeutic agents such as fluorouracil, doxorubicin, and cyclophosphamide, as well as endocrine therapies used to treat breast cancer in women.^16-18 Minoxidil also has been used off label to treat other forms of alopecia, including alopecia areata, telogen effluvium, eyebrow hypotrichosis, and monilethrix; however, there is inconclusive evidence for its efficacy.^5,13,19

Compared to other nonsurgical treatments for hair loss, a meta-analysis found that minoxidil was associated with the highest rate of adverse effects (AEs).^16,17 Potential side effects include pruritus or burning at the application site; irritant or allergic contact dermatitis; hypertrichosis; and cardiovascular effects, which may be due to the vasodilatory mechanism of action of minoxidil.²⁰ One randomized double-blind study found that while topical minoxidil did not affect blood pressure, it increased heart rate by 3 to 5 beats per minute, caused considerable increases in left ventricular end-diastolic volume, an increase in cardiac output (by 0.751 min^-1), and an increase in left ventricular mass (by 5 g m^-2). The authors concluded that short-term use is safe in healthy individuals, but providers should ask about history of coronary artery disease to avoid potential cardiac side effects.²¹

Patients also should be advised that at least 6 months of minoxidil therapy may be necessary.¹¹ Furthermore, measurable hair changes may disappear within 3 months if the patient chooses to discontinue treatment.²² Finally, providers must consider patient perception of improvement and hair growth while on this medication. In one study, although investigator assessments of hair growth and hair count were increased with the use of minoxidil solution 5% compared to placebo, differences in patient assessment of hair growth were not significant at 48 weeks.²² Therefore, dermatologists should address patient expectations and consider additional treatments if necessary.

Finasteride

Finasteride is an oral medication that is FDA approved at a dose of 1 mg daily for the treatment of AGA in men. It competitively inhibits the type I and type II 5α-reductase enzymes, with a strong affinity for the type II enzyme, thereby inhibiting the conversion of testosterone to dihydrotestosterone (DHT), the potent androgen responsible for terminal hair follicle miniaturization and transformation of terminal hair into vellus hair.^21,23

Finasteride has demonstrated efficacy and high tolerability in large-scale, placebo-controlled, randomized trials with only rare complications of sexual dysfunction, supporting its status as a first-line agent.^24,25 One study found that in a population of 3177 Japanese men, an overall increase in hair growth was seen in 87.1% of men receiving oral finasteride 1 mg daily, with AEs such as decreased libido occurring in only 0.7% of patients.²⁶ However, postmarketing studies described more severe complications in men taking finasteride to treat AGA or benign prostatic hyperplasia, even after the discontinuation of medication, described as postfinasteride syndrome.^27,28 These side effects include decreased libido, reduction in penis size, gynecomastia, erectile dysfunction, and ejaculation disorder, in addition to psychologic impairments, including decreased concentration, depression, and suicidal ideation, presumably due to the role of 5α-reductase interacting with the γ-aminobutyric acid (GABA_A) receptor within the central nervous system.²⁹ The incidence of persistent erectile dysfunction was reported to be as low as 1.4% in a study assessing 11,909 men prescribed up to 5 mg once daily of finasteride to treat benign prostatic hyperplasia and AGA. The incidence was higher in patients using higher doses of finasteride and longer treatment courses as well as in patients with prostate disease.²⁹ These potential side effects should be discussed with male patients prior to prescribing finasteride.

Finasteride is not FDA approved for use in women and is considered category X in pregnancy due to animal studies that demonstrated external genital abnormalities in male fetuses exposed to type II 5α-reductase inhibitors.³⁰ Despite this potential teratogenicity, finasteride is prescribed off label to treat FPHL and hirsutism. A meta-analysis of 2683 women participating in 65 studies found that finasteride, when used at dosages of 0.5 to 5 mg daily, may improve FPHL and frontal fibrosing alopecia after 6 to 12 months.³⁰ However, available studies have used varying treatment methods, yielding differing results. For example, one randomized trial of 137 postmenopausal women with FPHL and normal androgen levels found no benefit with 1 mg daily³¹; however, another trial of 87 women with normal levels of androgens found that 5 mg daily of finasteride showed significant improvements in hair quantity and thickness after 12 months (P<.01).³² Further studies are needed to assess the appropriate female population that may benefit from use of finasteride. Premenopausal women interested in this therapy should be counseled about the risk of teratogenicity, as well as potential breast tenderness, loss of libido, and menstrual irregularities.³³ Furthermore, finasteride use in women may pose a theoretical risk of breast cancer, as DHT inhibition results in conversion of excess testosterone to estrogen, thereby altering the estrogen to androgen ratio.³⁴

Dutasteride

Dutasteride is 100-times more potent than finasteride as an inhibitor of type I 5α-reductase enzyme and 3-times more potent as an inhibitor of type I 5α-reductase enzyme.³⁵ Therefore, it has been hypothesized that dutasteride may be more effective than finasteride for restoring hair loss, though it is not yet FDA approved for this indication.

Research evaluating the efficacy of dutasteride is emerging. Randomized controlled trials in men with AGA are promising and suggest reversed hair miniaturization.³⁶ One randomized trial of 153 men found that dutasteride 0.5 mg daily was superior to placebo for the treatment of hair loss, as evidenced by an increase in hair counts in dutasteride patients (12.2/cm²) compared to controls (4.7/cm²). Furthermore, 0.5-mg dutasteride resulted in significantly increased new hair growth after 24 weeks compared to a placebo control (23/cm² vs 4/cm²; P<.05).³⁷

Dutasteride also is now being used off label to treat FPHL. Little evidence-based research exists regarding the use of dutasteride in women, though 1 case report described successful treatment of FPHL after 6 months of treatment with 0.5 mg daily of dutasteride in a 46-year-old woman who showed only minimal improvement on oral finasteride.³⁸

The side-effect profile is similar to finasteride, and research in the urologic literature demonstrated that the rate of AEs is comparable between the 2 drugs, with reports of sexual side effects occurring in 11% of patients taking dutasteride 0.5 mg daily vs 14% of patients taking finasteride 5 mg daily.³⁹ In the dermatologic literature, there was no statistically significant difference between the rate of AEs, specifically sexual AEs, in patients taking dutasteride 0.5 mg daily vs finasteride 1 mg daily.³⁶ Safety of dutasteride in women is not well established. The side-effect profile described for finasteride, including the risk of potential fetal anomalies, should be discussed with women receiving dutasteride therapy.

Spironolactone

Although topical minoxidil is still considered first-line therapy for women experiencing hair loss, spironolactone is growing in popularity as an off-label treatment of FPHL, though it is not FDA approved for this indication. Spironolactone is a synthetic steroid that has been used as a potassium-sparing diuretic for more than 60 years. Its primary metabolite, canrenone, competitively inhibits aldosterone.³⁷ It is FDA approved for the treatment of essential hypertension (25–100 mg), congestive heart failure (25 mg), diuretic-induced hypokalemia (25–100 mg), and primary hyperaldosteronism (100–400 mg).^37,40 Spironolactone was serendipitously discovered to treat hirsutism, acne, and seborrhea associated with polycystic ovary syndrome.⁴¹

Androgens are well studied in male pattern hair loss, and their role in FPHL is now becoming evident, with new research supporting the role of spironolactone as a useful antiandrogen.^42,43 An Australian open-label trial randomized 80 women with biopsy-proven FPHL to receive either spironolactone 200 mg daily or cyproterone acetate, an antiandrogen used abroad, including in European countries, in conjunction with an oral contraceptive pill for premenopausal women.⁴² Spironolactone was found to be as effective as the alternate regimen, with 44% of patients experiencing hair regrowth, 44% experiencing no progression of hair loss, and only 12% experiencing continued hair loss.⁴⁴ Spironolactone used in combination with minoxidil has been shown to demonstrate greater efficacy when compared to spironolactone alone.⁴⁵ One observational study of 100 women with FPHL found that once-daily capsules of minoxidil 0.25 mg combined with once daily spironolactone 25 mg was a safe and effective treatment of FPHL.⁴⁴ Spironolactone also is considered safe and effective to treat FPHL in postmenopausal women by inhibiting the relative androgen excess.⁴⁶

The starting dose for spironolactone usually is 25 mg twice daily and increased by 50 mg daily up to 200 mg daily as tolerated. Furthermore, results should be monitored for at least 6 months to assess efficacy accurately.⁴⁷ Side effects include headache, decreased libido, menstrual irregularities, orthostatic hypotension, fatigue, and hyperkalemia. Although hyperkalemia is a known side effect of spironolactone, one study of 974 male and female participants receiving spironolactone found that only 0.72% of participants experienced mild hyperkalemia (5.1–6.0 mEq/L) with no patients experiencing moderate or severe hyperkalemia. Regardless, providers may consider checking potassium levels within 4 to 8 weeks of initiating treatment with spironolactone.⁴⁸ Other potential AEs include gynecomastia and feminization; therefore, it is not recommended for use in men.⁴² Oral contraception is recommended to prevent pregnancy in premenopausal women, as spironolactone may cause feminization of the male fetus. Because of the antiandrogenic and progestogenic effects of spironolactone, there has been a theoretical concern for risk of inducing breast cancer, especially in postmenopausal women. However, a study conducted in the United Kingdom of more than 1 million female patients older than 55 years found that there was no increased risk of breast cancer in postmenopausal women.⁴⁹

Low-Level Laser Light Therapy

Low-level laser light therapy has been used to reduce pain, treat edema, and promote would healing for almost 50 years and is now one of the few FDA-cleared devices to treat alopecia. Low-level laser light therapy uses red beam or near-infrared nonthermal lasers at a wavelength of 600 to 1000 nm and from 5 to 500 mW. The exact mechanism of hair growth stimulation is not known; however, it is believed that LLLT accelerates mitosis, stimulates hair follicle stem cells to activate follicular keratinocytes, and alters cellular metabolism by inhibiting nitric oxide from cytochrome c oxidase.⁵⁰

Trials evaluating the efficacy of LLLT laser combs for the treatment of AGA have demonstrated notable improvements in hair density. For example, one sham device–controlled, double-blind clinical trial randomized 334 men and women to treatment with either an FDA-cleared laser comb vs sham devices.⁵¹ The treatment devices were used 3 times weekly for 26 weeks. Hair counts for those treated with the 7-, 9-, and 12-beam LLLT laser combs were significantly higher than the sham after 26 weeks (P<.05), without any serious AEs being reported.⁵¹ Another study in men with AGA proved similarly efficacious results using at-home LLLT therapy of 655 nm to the scalp every other day for 16 weeks (60 treatments).⁵² However, a 24-week randomized, double-blind, sham device–controlled, multicenter trial evaluating the LLLT helmet (combining 650-nm laser with 630- and 660-nm light-emitting diodes) among male and female patients with AGA failed to show promising results. Although mean (SD) hair thickness (12.6 [9.4] in LLLT group vs 3.9 [7.3] in control group [P=.01]) and hair density (17.2 [12.1] in LLLT group vs –2.1 [18.3] in control group [P=.003]) increased significantly, there was no significant difference in subject assessment of global appearance between the 2 groups.⁵³

Low-level laser light therapy devices are available both for use at home and in office, with 650- to 900-nm wavelengths at 5 mW being the recommended dose for men and women.⁵¹ With regard to AEs, the safety profile for LLLT is relatively favorable. Adverse events can include dry skin, pruritus, scalp tenderness, irritation, and a warm sensation at the treatment site.⁵²

Platelet-Rich Plasma

Originally used in the orthopedic literature to stimulate collagen growth, PRP has since been used in dermatology to promote hair regrowth by releasing platelet-derived growth factors, vascular endothelial growth factor, epidermal growth factor, insulinlike growth factor, and fibroblast growth factors to stimulate vascularization to the dermal papillary cells.^54,55 Platelet-rich plasma is derived from the supernatant of centrifuged whole blood and then injected in the dermis of the scalp to stimulate hair growth.

Although use of PRP is not approved or cleared by the FDA for treatment of hair loss, several studies have demonstrated the efficacy of autologous PRP use for treating AGA.⁵⁶ One pilot study of 19 male and female participants given a total of 5 PRP injections monthly for 3 months and subsequently at months 4 and 7 found a statistically significant improvement in mean hair density, hair diameter, and terminal-vellus hair ratio at 1-year follow-up (P<.05). Furthermore, histomorphometric evaluation demonstrated a decrease in perivascular inflammatory infiltrate.⁵⁷ On the other hand, 2 separate studies failed to show statistically significant improvements in hair growth after use of PRP.^58,59 Varying levels of success may be due in part to lack of a standard protocol for performing PRP injections. Studies comparing efficacy of different PRP administration regimens are emerging. A trial of 40 men and women found that subdermal PRP injections administered 3 times per month with booster injections administered 3 months later was more effective than other injection regimens, including once monthly injections.^58,59 Activators such as collagen, thrombin, 10% calcium chloride, and calcium gluconate may be added to the PRP serum to promote further growth factor secretion upon platelet activation.⁶⁰ However, different means of activation are used in different trials, potentially leading to varying results in clinical trials, with no one proven superior method.^61-63 The main drawback of PRP use is that there is no consensus regarding exact concentration, utility of activators, dosing parameters, depth of injection, or frequency of sessions.⁶⁰ Transient pain and erythema are the most common side effects of PRP injections, with no major AEs reported in the literature.⁶⁴

Microneedling

Microneedling is a minimally invasive procedure that uses needles to puncture the stratum corneum of the skin.⁶⁵ It was first used cosmetically more than 20 years ago due to its ability to increase collagen and elastin formation.⁵¹ Since its discovery, microneedling has been used to reduce the appearance of scars; augment transdermal drug delivery; and treat active acne vulgaris, melasma, hyperhidrosis, and alopecia.⁶⁵ Although there are numerous at-home and professional microneedling devices on the market, only one device has been FDA cleared thus far.

Microneedling is proposed to increase hair regrowth by triggering the wound healing response, which ultimately augments the release of platelet-derived and epidermal growth factors while also activating the hair bulge.⁶⁶ Treatment often is performed with a roller instrument that uses needles 0.5- to 2.5-mm long. Topical anesthetic cream may be applied prior to treatment.⁶⁷ The treated area is then washed and an antibiotic ointment is applied.⁵⁵ Management regimens typically require daily to weekly treatments with a total of 12 to 28 weeks to demonstrate an effect.

Microneedling has demonstrated efficacy in the treatment of hair loss, especially when combined with minoxidil. One study randomized 68 patients to undergo microneedling with minoxidil solution 5% twice daily compared to a control group of minoxidil solution 5% twice daily alone. After 12 weeks, patients treated with microneedling and minoxidil had significantly higher hair counts than the control group (P<.05).⁶⁸ It is speculated that microneedling increases penetration of topical medications, including minoxidil across the skin barrier, thereby enhancing absorption of large molecules.⁶⁶

Topical PRP has been used synergistically to augment the effects of microneedling. A trial randomized 93 patients with alopecia to receive minoxidil solution 5% alone, minoxidil solution 5% plus PRP, or microneedling with PRP.⁶⁹ Hair growth was appreciated in 26 of 31 patients treated with microneedling and PRP compared to 10 of 31 and 17 of 31 in the other 2 groups, respectively. However, when hair growth occurred in the minoxidil-treated group, it occurred faster, with changes in hair growth at 12 weeks compared to 26 weeks in the microneedling group.⁶⁹ When evaluating the efficacy of microneedling and PRP, it must be noted that there is no established leading protocol for treating hair loss, which may affect the success of the treatment.

The reported side-effect profile for microneedling and PRP injections has been favorable without any major AEs noted in clinical trials.^56,64,70 The possibility of bleeding, pain, erythema, and infection should be discussed with the patient nonetheless. More severe side effects such as allergic granulomatous reactions have been reported in the literature with the use of microneedling for facial rejuvenation.⁷¹

Stem Cells

Stem cell hair therapy is a new and promising area of research with the potential to treat alopecia. Although not yet FDA approved for this indication, human umbilical cord blood–derived mesenchymal stem cells (HUCB-MSCs) have received particular attention due to their proposed ability to promote tissue differentiation and repair, to replace aged and damaged hair cells, and to promote secretion of multiple growth factors.⁷² More recently, HUCB-MSCs have been shown to successfully differentiate into human hair follicles in vitro after 3 weeks of cell culture, establishing a method for high-speed and high-purity hair follicle cell differentiation with the hope of future injections to affected areas with hair loss.⁷³ Another study found that HUCB-MSCs enhanced growth of human follicular stem cells in vitro; the authors proposed an altered Wnt/β‐catenin and JAK/STAT pathway was responsible for improved growth of hair follicular cells.⁷⁴

Although umbilical cord blood is replete with the most rapidly dividing stem cells, autologous stem cells derived from the hair follicle or mononuclear cells also may be used to treat alopecia. One recent study randomized 40 patients with AGA and alopecia areata to receive 1 session of either autologous hair follicle or mononuclear cell–derived stem cell injections to the scalp.⁷⁵ Mononuclear cells were acquired from the upper iliac crest bone marrow of patients who were treated with granulocyte colony-stimulating factor 3 days prior to the procedure. Follicular stem cells were taken from 4-mm punch biopsies of the unaffected scalp. After 6 months, there was a notable improvement in hair growth confirmed by immunostaining and dermoscopy, without a significant difference between the forms of autologous stem cell source. Of note, 45% of study patients with alopecia areata showed recurrence of disease at 1-year follow-up. The most common AEs were scalp dermatitis in 20% of participants. Participants who underwent bone marrow biopsy experienced bone pain, hematoma, and granulocyte colony-stimulating factor–induced fatigue and chills.⁷⁵

Furthermore, the cost of stem cell therapy may be prohibitive. Therefore, although stem cell therapy is a novel and promising treatment for hair loss, future research is necessary to establish safety, efficacy, best practices, and accessibility.

Supplements

Patients failing routine treatments for alopecia may turn to holistic therapies. Nutrafol (Nutraceutical Wellness Inc), a novel nutraceutical product, is one such option that has been described for its anti-inflammatory, adaptogenic, antioxidant, and DHT-inhibiting properties. This supplement is not FDA approved or cleared, and large-scale clinical trials are lacking; however, one randomized controlled trial of 40 women with self-reported hair loss found a statistically significant increase in the number of terminal and vellus hair based on phototrichograms performed after 90 and 180 days (P=.009), with no AEs reported. This study, however, was limited by a small sample size.⁷⁶

Lamdapil (ISDIN) is another oral supplement being investigated for hair loss. It contains L-cystine amino acids; zinc; vitamins B₃, B₅, B₆; biotin; and the plant extract Serenoa repens.⁷¹Serenoa repens has reported activity inhibiting the enzyme 5α-reductase with the other vitamins, and amino acids are thought to maintain keratin and collagen growth in normal hair.⁷⁷ One randomized trial investigated use of Lamdapil capsules in a total of 70 patients, which included men with AGA and women experiencing telogen effluvium. For men, the anagen-telogen ratio increased in the Lamdapil-treated group by 23.4%, indicating that more hair was in the growing phase compared to placebo (P<.05). Women with telogen effluvium experienced a significantly greater improvement in the hair-pull test compared to placebo (P<.05).⁷⁷

Marine-derived nutraceutical substances also have been investigated for their role in treating hair loss. Viviscal, originally marketed under the name Hairgain, is one such supplement, which was shown to significantly reduce hair shedding at 3 and 6 months in a group of 96 premenopausal women diagnosed with subclinical hair thinning (P<.05). Additionally, phototrichogram images demonstrated a statistically significant increase in the mean velluslike hair diameter at 6 months compared to baseline.⁷⁸

Although nutraceutical products are not first-line therapy for hair loss, dermatologists may recommend these treatments in patients refusing prescription medications, specifically requesting a natural treatment, or in addition to a first-line agent such as minoxidil. It must be noted, however, that both supplements are new, and there is need for further investigation on their efficacy, safety, and dosing, as neither is FDA regulated.

Conclusion

Hair loss affects millions of Americans each year and has detrimental effects on self-esteem and psychosocial functioning. Nonsurgical treatment options will undoubtedly continue to intrigue patients, as they are often less costly and do not carry risks associated with surgery. Minoxidil, finasteride, and LLLT remain staples of therapy, with the strongest evidence supporting their safety and efficacy. Numerous other treatment options are emerging, including PRP, microneedling, mesenchymal and autologous stem cell therapy, and oral supplements, though further research must be conducted to establish dosing, safety, and best practices. Physicians must discuss patient preference and anticipated length of treatment when discussing alopecia treatment to maximize patient satisfaction.

MELBOURNE – The treatment of cancer-associated thrombosis may be complicated by increased bleeding risk in patients with gastrointestinal cancer, in whom direct oral anticoagulants may not be the ideal first choice, one expert reported at the International Society on Thrombosis and Haemostasis congress.

Agnes Y.Y. Lee, MD, medical director of the Thrombosis Program at Vancouver General Hospital and the University of British Columbia, spoke about the challenges and necessity of treating cancer-associated thrombosis, pointing out that about 20% of all cases of venous thromboembolism (VTE) are associated with cancer.

“In those with cancer, thrombosis can also interfere with cancer treatment, increases health care costs, and is extraordinarily burdensome to patients and their families,” she said. “Fortunately the most effective way to reduce this burden is to use anticoagulant therapy for prevention and treatment.”

While direct oral anticoagulants have been shown in several studies to be comparable to warfarin in treating most patients with thrombosis, Dr. Lee said there has been a question of how they compare in safety and efficacy to low-molecular-weight heparin in individuals with cancer.

Data from the Hokusai VTE Cancer trial, which compared oral edoxaban with subcutaneous dalteparin in patients with cancer, showed that the two treatments were comparable in time to first occurrence of thrombosis. However, the study did show a fourfold higher risk of bleeding with edoxaban, compared with that of dalteparin, among individuals with gastrointestinal cancers, a difference in bleeding rate that was not seen in patients with nongastrointestinal cancers, Dr. Lee said.

Dr. Lee pointed out that this study also showed a higher bleeding risk in patients with other bleeding risk factors, including those with primary or metastatic brain cancer.

“This study also showed that, when patients developed major bleeding, 60%-80% of them required hospitalization or an ICU stay, so major bleeding is a serious complication and certainly will increase the cost of therapy for these patients,” she said.

In the SELECT-D pilot study, which compared rivaroxaban with dalteparin in patients with cancer, there was a higher risk of bleeding for patients with esophageal or gastroesophageal cancers.

Bleeding risk is generally not well addressed in current guidelines on managing hemostasis in patients with malignancies, partly because it is difficult to quantify bleeding in these patients whose hemoglobin levels would be affected by their disease and their chemotherapy, Dr. Lee said in an interview.

“The bleeding events in cancer patients do get more complicated because there’s all this other noise in the background,” she said.

Commenting on her personal approach to treatment, Dr. Lee said she favors starting patients on low-molecular-weight heparin because it gives her time to understand patients, their disease, and their needs.

“A lot of patients arrive, and they can’t really tell me what their cancer is doing, they can’t really tell me what cancer therapy they’re going through,” she says. “And if they’re on a long list of drugs, then I have to talk to my pharmacist about whether there are drug-drug interactions.”

If patients were well managed on low-molecular-weight heparin without any bleeding, then Dr. Lee said she would consider switching them to direct oral anticoagulants.

Cochair of the session, Ingrid Pabinger, MD, from the Medical University of Vienna commented that vitamin K antagonists should not be forgotten because some patients are unable to afford low-molecular-weight heparin.

However Dr. Lee said these were last on the list for her because of the risk of drug-drug interactions, drug-food interactions, and the issues faced by patients experiencing vomiting or diarrhea with their chemotherapy.

Dr. Lee reported research funding, consultancies, and honoraria from the pharmaceutical sector.

MELBOURNE – The treatment of cancer-associated thrombosis may be complicated by increased bleeding risk in patients with gastrointestinal cancer, in whom direct oral anticoagulants may not be the ideal first choice, one expert reported at the International Society on Thrombosis and Haemostasis congress.

Agnes Y.Y. Lee, MD, medical director of the Thrombosis Program at Vancouver General Hospital and the University of British Columbia, spoke about the challenges and necessity of treating cancer-associated thrombosis, pointing out that about 20% of all cases of venous thromboembolism (VTE) are associated with cancer.

“In those with cancer, thrombosis can also interfere with cancer treatment, increases health care costs, and is extraordinarily burdensome to patients and their families,” she said. “Fortunately the most effective way to reduce this burden is to use anticoagulant therapy for prevention and treatment.”

While direct oral anticoagulants have been shown in several studies to be comparable to warfarin in treating most patients with thrombosis, Dr. Lee said there has been a question of how they compare in safety and efficacy to low-molecular-weight heparin in individuals with cancer.

Data from the Hokusai VTE Cancer trial, which compared oral edoxaban with subcutaneous dalteparin in patients with cancer, showed that the two treatments were comparable in time to first occurrence of thrombosis. However, the study did show a fourfold higher risk of bleeding with edoxaban, compared with that of dalteparin, among individuals with gastrointestinal cancers, a difference in bleeding rate that was not seen in patients with nongastrointestinal cancers, Dr. Lee said.

Dr. Lee pointed out that this study also showed a higher bleeding risk in patients with other bleeding risk factors, including those with primary or metastatic brain cancer.

“This study also showed that, when patients developed major bleeding, 60%-80% of them required hospitalization or an ICU stay, so major bleeding is a serious complication and certainly will increase the cost of therapy for these patients,” she said.

In the SELECT-D pilot study, which compared rivaroxaban with dalteparin in patients with cancer, there was a higher risk of bleeding for patients with esophageal or gastroesophageal cancers.

Bleeding risk is generally not well addressed in current guidelines on managing hemostasis in patients with malignancies, partly because it is difficult to quantify bleeding in these patients whose hemoglobin levels would be affected by their disease and their chemotherapy, Dr. Lee said in an interview.

“The bleeding events in cancer patients do get more complicated because there’s all this other noise in the background,” she said.

Commenting on her personal approach to treatment, Dr. Lee said she favors starting patients on low-molecular-weight heparin because it gives her time to understand patients, their disease, and their needs.

“A lot of patients arrive, and they can’t really tell me what their cancer is doing, they can’t really tell me what cancer therapy they’re going through,” she says. “And if they’re on a long list of drugs, then I have to talk to my pharmacist about whether there are drug-drug interactions.”

If patients were well managed on low-molecular-weight heparin without any bleeding, then Dr. Lee said she would consider switching them to direct oral anticoagulants.

Cochair of the session, Ingrid Pabinger, MD, from the Medical University of Vienna commented that vitamin K antagonists should not be forgotten because some patients are unable to afford low-molecular-weight heparin.

However Dr. Lee said these were last on the list for her because of the risk of drug-drug interactions, drug-food interactions, and the issues faced by patients experiencing vomiting or diarrhea with their chemotherapy.

Dr. Lee reported research funding, consultancies, and honoraria from the pharmaceutical sector.

MELBOURNE – The treatment of cancer-associated thrombosis may be complicated by increased bleeding risk in patients with gastrointestinal cancer, in whom direct oral anticoagulants may not be the ideal first choice, one expert reported at the International Society on Thrombosis and Haemostasis congress.

Agnes Y.Y. Lee, MD, medical director of the Thrombosis Program at Vancouver General Hospital and the University of British Columbia, spoke about the challenges and necessity of treating cancer-associated thrombosis, pointing out that about 20% of all cases of venous thromboembolism (VTE) are associated with cancer.

“In those with cancer, thrombosis can also interfere with cancer treatment, increases health care costs, and is extraordinarily burdensome to patients and their families,” she said. “Fortunately the most effective way to reduce this burden is to use anticoagulant therapy for prevention and treatment.”

While direct oral anticoagulants have been shown in several studies to be comparable to warfarin in treating most patients with thrombosis, Dr. Lee said there has been a question of how they compare in safety and efficacy to low-molecular-weight heparin in individuals with cancer.

Data from the Hokusai VTE Cancer trial, which compared oral edoxaban with subcutaneous dalteparin in patients with cancer, showed that the two treatments were comparable in time to first occurrence of thrombosis. However, the study did show a fourfold higher risk of bleeding with edoxaban, compared with that of dalteparin, among individuals with gastrointestinal cancers, a difference in bleeding rate that was not seen in patients with nongastrointestinal cancers, Dr. Lee said.

Dr. Lee pointed out that this study also showed a higher bleeding risk in patients with other bleeding risk factors, including those with primary or metastatic brain cancer.

“This study also showed that, when patients developed major bleeding, 60%-80% of them required hospitalization or an ICU stay, so major bleeding is a serious complication and certainly will increase the cost of therapy for these patients,” she said.

In the SELECT-D pilot study, which compared rivaroxaban with dalteparin in patients with cancer, there was a higher risk of bleeding for patients with esophageal or gastroesophageal cancers.

Bleeding risk is generally not well addressed in current guidelines on managing hemostasis in patients with malignancies, partly because it is difficult to quantify bleeding in these patients whose hemoglobin levels would be affected by their disease and their chemotherapy, Dr. Lee said in an interview.

“The bleeding events in cancer patients do get more complicated because there’s all this other noise in the background,” she said.

Commenting on her personal approach to treatment, Dr. Lee said she favors starting patients on low-molecular-weight heparin because it gives her time to understand patients, their disease, and their needs.

“A lot of patients arrive, and they can’t really tell me what their cancer is doing, they can’t really tell me what cancer therapy they’re going through,” she says. “And if they’re on a long list of drugs, then I have to talk to my pharmacist about whether there are drug-drug interactions.”

If patients were well managed on low-molecular-weight heparin without any bleeding, then Dr. Lee said she would consider switching them to direct oral anticoagulants.

Cochair of the session, Ingrid Pabinger, MD, from the Medical University of Vienna commented that vitamin K antagonists should not be forgotten because some patients are unable to afford low-molecular-weight heparin.

However Dr. Lee said these were last on the list for her because of the risk of drug-drug interactions, drug-food interactions, and the issues faced by patients experiencing vomiting or diarrhea with their chemotherapy.

Dr. Lee reported research funding, consultancies, and honoraria from the pharmaceutical sector.

NEWPORT BEACH, CALIF. – When it comes to acne in adult women, look past the jawline, beyond traditional medications, and toward greater control. That’s the message of a dermatologist who spoke at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

“We should be aiming to get our patients to clear or almost clear, and we have the tools necessary to help that happen,” said Linda Stein Gold, MD, director of dermatology research at Henry Ford Hospital in Detroit.

Research suggests that acne is more common in adult women than in men, a gap that widens after age 29 years, she noted. Acne appears to affect 51% of women aged 20-29 years, she said, and prevalence dips to 15% in women older than 50 years.

About 80% of cases continue from adolescence, compared with about 20% that are new-onset during adulthood, she said. According to studies, she added, “most adult women have acne on multiple different areas of their face, not just the jawline. It’s similar to what we see in the adolescent population.”

Dr. Stein Gold offered these tips about treatment in this group of patients:
 

Inflammation

Researchers now consider that “all acne is inflammatory acne.” Be aggressive with anti-inflammatory treatment, and “continue even after the lesion is resolved” if needed to prevent scarring.

Oral contraceptives (OCs)

OCs can be helpful, but “we have to proceed with caution,” she said. A 2012 Cochrane Library review of 31 trials found that six combination OCs (COCs) “evaluated in placebo-controlled trials are effective in reducing inflammatory and noninflammatory facial acne lesions. Few important and consistent differences were found between COC types in their effectiveness for treating acne,” the review concluded (Cochrane Database Syst Rev. 2012 Jul 11;[7]:CD004425).

Results take time, however, and it “can take 3 months to see an effect, and 6 months for full effect,” Dr. Stein Gold noted.

There are multiple contraindications to the use of OCs, and they’ve been linked – controversially – to an increased risk of blood clots and breast cancer. However, risk of thrombosis also spikes – to significantly higher levels than with OC use – during pregnancy and the postpartum period, she said.
 

Spironolactone

This antihypertensive drug can be helpful, Dr. Stein Gold noted, although the one study in a 2009 Cochrane review that had acne as an outcome failed to find evidence of efficacy versus placebo (Cochrane Database Syst Rev. 2009 Apr 15;[2]:CD000194). Be aware of the boxed warning about links to cancer in rat studies, and consider the risk of potassium elevation in certain populations, she added. Watch the dose: fewer side effects are seen at 50-100 mg daily, although they’re still common, and it can take 3 months or more for improvements to appear, she said.

Truncal acne

Patients may be hesitant to mention they have acne on their chest and back. “They may not tell you about it, and you may not ask about it but [some patients] expect you to know about it and treat it,” Dr. Stein Gold said. She referred to trifarotene, a topical retinoid cream that, although not yet approved, appears to be safe and effective in treating acne on the face and trunk in phase 3 studies.

“Some people will say the trunk will get too irritated if you put a retinoid on it. But it absolutely can be used on the chest and back. The first thing I say to my patients is to expect to have redness and scaling for first 2 weeks. People pay money for that. It’s a chemical peel! It’s okay to have some sloughing; use an oil-free moisturizer.”

Dr. Stein Gold disclosed relationships with Galderma, Foamix, and Sol Gel (investigator, consultant); Valeant (consultant, speaker); and Dermira (investigator, speaker).

SDEF and this news organization are owned by the same parent company.

NEWPORT BEACH, CALIF. – When it comes to acne in adult women, look past the jawline, beyond traditional medications, and toward greater control. That’s the message of a dermatologist who spoke at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

“We should be aiming to get our patients to clear or almost clear, and we have the tools necessary to help that happen,” said Linda Stein Gold, MD, director of dermatology research at Henry Ford Hospital in Detroit.

Research suggests that acne is more common in adult women than in men, a gap that widens after age 29 years, she noted. Acne appears to affect 51% of women aged 20-29 years, she said, and prevalence dips to 15% in women older than 50 years.

About 80% of cases continue from adolescence, compared with about 20% that are new-onset during adulthood, she said. According to studies, she added, “most adult women have acne on multiple different areas of their face, not just the jawline. It’s similar to what we see in the adolescent population.”

Dr. Stein Gold offered these tips about treatment in this group of patients:
 

Inflammation

Researchers now consider that “all acne is inflammatory acne.” Be aggressive with anti-inflammatory treatment, and “continue even after the lesion is resolved” if needed to prevent scarring.

Oral contraceptives (OCs)

OCs can be helpful, but “we have to proceed with caution,” she said. A 2012 Cochrane Library review of 31 trials found that six combination OCs (COCs) “evaluated in placebo-controlled trials are effective in reducing inflammatory and noninflammatory facial acne lesions. Few important and consistent differences were found between COC types in their effectiveness for treating acne,” the review concluded (Cochrane Database Syst Rev. 2012 Jul 11;[7]:CD004425).

Results take time, however, and it “can take 3 months to see an effect, and 6 months for full effect,” Dr. Stein Gold noted.

There are multiple contraindications to the use of OCs, and they’ve been linked – controversially – to an increased risk of blood clots and breast cancer. However, risk of thrombosis also spikes – to significantly higher levels than with OC use – during pregnancy and the postpartum period, she said.
 

Spironolactone

This antihypertensive drug can be helpful, Dr. Stein Gold noted, although the one study in a 2009 Cochrane review that had acne as an outcome failed to find evidence of efficacy versus placebo (Cochrane Database Syst Rev. 2009 Apr 15;[2]:CD000194). Be aware of the boxed warning about links to cancer in rat studies, and consider the risk of potassium elevation in certain populations, she added. Watch the dose: fewer side effects are seen at 50-100 mg daily, although they’re still common, and it can take 3 months or more for improvements to appear, she said.

Truncal acne

Patients may be hesitant to mention they have acne on their chest and back. “They may not tell you about it, and you may not ask about it but [some patients] expect you to know about it and treat it,” Dr. Stein Gold said. She referred to trifarotene, a topical retinoid cream that, although not yet approved, appears to be safe and effective in treating acne on the face and trunk in phase 3 studies.

“Some people will say the trunk will get too irritated if you put a retinoid on it. But it absolutely can be used on the chest and back. The first thing I say to my patients is to expect to have redness and scaling for first 2 weeks. People pay money for that. It’s a chemical peel! It’s okay to have some sloughing; use an oil-free moisturizer.”

Dr. Stein Gold disclosed relationships with Galderma, Foamix, and Sol Gel (investigator, consultant); Valeant (consultant, speaker); and Dermira (investigator, speaker).

SDEF and this news organization are owned by the same parent company.

NEWPORT BEACH, CALIF. – When it comes to acne in adult women, look past the jawline, beyond traditional medications, and toward greater control. That’s the message of a dermatologist who spoke at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

“We should be aiming to get our patients to clear or almost clear, and we have the tools necessary to help that happen,” said Linda Stein Gold, MD, director of dermatology research at Henry Ford Hospital in Detroit.

Research suggests that acne is more common in adult women than in men, a gap that widens after age 29 years, she noted. Acne appears to affect 51% of women aged 20-29 years, she said, and prevalence dips to 15% in women older than 50 years.

About 80% of cases continue from adolescence, compared with about 20% that are new-onset during adulthood, she said. According to studies, she added, “most adult women have acne on multiple different areas of their face, not just the jawline. It’s similar to what we see in the adolescent population.”

Dr. Stein Gold offered these tips about treatment in this group of patients:
 

Inflammation

Researchers now consider that “all acne is inflammatory acne.” Be aggressive with anti-inflammatory treatment, and “continue even after the lesion is resolved” if needed to prevent scarring.

Oral contraceptives (OCs)

OCs can be helpful, but “we have to proceed with caution,” she said. A 2012 Cochrane Library review of 31 trials found that six combination OCs (COCs) “evaluated in placebo-controlled trials are effective in reducing inflammatory and noninflammatory facial acne lesions. Few important and consistent differences were found between COC types in their effectiveness for treating acne,” the review concluded (Cochrane Database Syst Rev. 2012 Jul 11;[7]:CD004425).

Results take time, however, and it “can take 3 months to see an effect, and 6 months for full effect,” Dr. Stein Gold noted.

There are multiple contraindications to the use of OCs, and they’ve been linked – controversially – to an increased risk of blood clots and breast cancer. However, risk of thrombosis also spikes – to significantly higher levels than with OC use – during pregnancy and the postpartum period, she said.
 

Spironolactone

This antihypertensive drug can be helpful, Dr. Stein Gold noted, although the one study in a 2009 Cochrane review that had acne as an outcome failed to find evidence of efficacy versus placebo (Cochrane Database Syst Rev. 2009 Apr 15;[2]:CD000194). Be aware of the boxed warning about links to cancer in rat studies, and consider the risk of potassium elevation in certain populations, she added. Watch the dose: fewer side effects are seen at 50-100 mg daily, although they’re still common, and it can take 3 months or more for improvements to appear, she said.

Truncal acne

Patients may be hesitant to mention they have acne on their chest and back. “They may not tell you about it, and you may not ask about it but [some patients] expect you to know about it and treat it,” Dr. Stein Gold said. She referred to trifarotene, a topical retinoid cream that, although not yet approved, appears to be safe and effective in treating acne on the face and trunk in phase 3 studies.

“Some people will say the trunk will get too irritated if you put a retinoid on it. But it absolutely can be used on the chest and back. The first thing I say to my patients is to expect to have redness and scaling for first 2 weeks. People pay money for that. It’s a chemical peel! It’s okay to have some sloughing; use an oil-free moisturizer.”

Dr. Stein Gold disclosed relationships with Galderma, Foamix, and Sol Gel (investigator, consultant); Valeant (consultant, speaker); and Dermira (investigator, speaker).

SDEF and this news organization are owned by the same parent company.

MADRID – Tildrakizumab, a high-affinity anti–interleukin-23p19 monoclonal antibody, significantly improved joint and skin manifestations in patients with psoriatic arthritis in an ongoing phase 2b study.

Sara Freeman/MDedge News

“By week 24, all four doses of tildrakizumab were significantly more efficacious than placebo,” Philip J. Mease, MD, director of the division of rheumatology clinical research at Swedish Medical Center, Seattle, reported at the European Congress of Rheumatology. This included patient-rated pain, he observed.

Furthermore, “there was a clear separation between tildrakizumab and placebo as early as 8 weeks” for the trial’s primary endpoint, a 20% response rate on American College of Rheumatology criteria (ACR20) at 24 weeks.

The study (NCT02980692), which is projected to complete next year, was conducted to demonstrate the safety and efficacy of tildrakizumab in patients with active psoriatic arthritis. Tildrakizumab is already approved for the treatment of moderate to severe plaque psoriasis in multiple countries, Dr. Mease pointed out. Indeed, the drug – which is marketed as Ilumya in the United States and as Ilumetri in the Europe Union – was approved by the Food and Drug Administration in March last year based on the positive results of the phase 3 reSURFACE clinical trials program (Drugs. 2018;78[8]:845-9).

In presenting interim findings from the study, Dr. Mease observed that “it looked like shortening the dosing interval from Q12 to Q4 weeks for the 200-mg dose did not result in a measurable difference in skin or joint responses.”

The trial included 391 of 500 adult patients who were screened and then randomized to one of four tildrakizumab dosing groups or placebo; there were 78 patients treated with tildrakizumab 200 mg once every 4 weeks (Q4W) and 79 who were treated with tildrakizumab 200 mg once every 12 weeks (Q12W). A further 77 patients were treated with a 100 mg tildrakizumab dose Q12W, 78 patients with a 20 mg tildrakizumab dose Q12W, and 79 patients were treated with a placebo Q4W.

The mean age of patients included in the study was around 48 years. A total of 55% were female, and more than 96% were white. Across the groups, patients had a median of 7-8 tender joints and about 14-19 swollen joints, and 53%-70% had at least 3% psoriasis body surface area involvement.

The primary endpoint of ACR20 at 24 weeks was met by 79.5%, 77.2%, 71.4%, and 73.1% of patients in the tildrakizumab 200-mg Q4W, 200-mg Q12W, 100-mg Q12W, and 20-mg Q12W groups, and by 50.6% of the placebo-treated patients. “So even the very low dose had an effect,” Dr. Mease observed, also acknowledging the “very high placebo response.”

An ACR50 response was achieved by a respective 53.6%, 50.6%, 45.5%, 39.7%, 19.7%, and 24.1% of patients. ACR70 response rates were also “proportionately lower” than the ACR20 responses at around 25%-29% for the tildrakizumab groups and 16% for placebo.

“The skin scores were as expected quite high,” Dr. Mease said. The Psoriasis Area and Severity Index (PASI) 75 response rate was 79.6% in the tildrakizumab 200-mg Q12W group, 64.2% in the 200-mg Q4W group, 55.6% in the 100-mg Q12W group, 46.3% in the 20-mg Q12W group, and just 16.7% in the placebo group. The respective percentages of patients achieving a PASI 90 response rate were 50%, 47.2%, 38.9%, 36.6%, and 7.1%.

Patient pain assessment showed a clear reduction with tildrakizumab versus placebo treatment. “We see statistical separation between all of the tildrakizumab arms and placebo,” Dr. Mease said. “A greater than 50% response in pain is considered major clinical improvement, and that was achieved by all of the tildrakizumab arms.”

As for enthesitis, the mean change in Leeds Enthesitis Scores from baseline to week 24 were greater with all tildrakizumab doses than with placebo, although a high placebo response was again apparent.

“In general, the safety profile was very good for this agent,” Dr. Mease said. Any treatment-emergent adverse event (TEAE) occurred in 156 of 317 (49%) tildrakizumab-treated patients and in 34 of 70 (49%) placebo-treated patients. The rates of any severe TEAE were 2.2% for the tildrakizumab arms and 2.5% for placebo. Any TEAE related to treatment occurred in a respective 11.2% and 12.7%, but there were no discontinuations because of adverse events, nor were there any major cardiac adverse events, cases of malignancy, or deaths caused by TEAEs. There was a single serious infection, a case of tonsillitis, which occurred with tildrakizumab treatment.

In response to a question after his presentation, Dr. Measure noted: “In the psoriasis trials with this agent, even a single dose yielded a fairly meaningful PASI 75 responses out for extremely long periods of time, 6–12 months. So, it looks like the Q12 dosing is going to be reasonable and convenient for patients”. He also agreed with a comment that the more frequent dosing seemed to be linked to inferior responses in the skin.

The study was sponsored by Sun Pharmaceutical Industries. Dr. Mease has received research grants, consulting fees, and/or speaker fees from 15 pharmaceutical companies, including Sun Pharmaceutical Industries.

SOURCE: Mease PJ et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):77-9. Abstract LB0002, doi: 10.1136/annrheumdis-2019-eular.8669

MADRID – Tildrakizumab, a high-affinity anti–interleukin-23p19 monoclonal antibody, significantly improved joint and skin manifestations in patients with psoriatic arthritis in an ongoing phase 2b study.

Sara Freeman/MDedge News

“By week 24, all four doses of tildrakizumab were significantly more efficacious than placebo,” Philip J. Mease, MD, director of the division of rheumatology clinical research at Swedish Medical Center, Seattle, reported at the European Congress of Rheumatology. This included patient-rated pain, he observed.

Furthermore, “there was a clear separation between tildrakizumab and placebo as early as 8 weeks” for the trial’s primary endpoint, a 20% response rate on American College of Rheumatology criteria (ACR20) at 24 weeks.

The study (NCT02980692), which is projected to complete next year, was conducted to demonstrate the safety and efficacy of tildrakizumab in patients with active psoriatic arthritis. Tildrakizumab is already approved for the treatment of moderate to severe plaque psoriasis in multiple countries, Dr. Mease pointed out. Indeed, the drug – which is marketed as Ilumya in the United States and as Ilumetri in the Europe Union – was approved by the Food and Drug Administration in March last year based on the positive results of the phase 3 reSURFACE clinical trials program (Drugs. 2018;78[8]:845-9).

In presenting interim findings from the study, Dr. Mease observed that “it looked like shortening the dosing interval from Q12 to Q4 weeks for the 200-mg dose did not result in a measurable difference in skin or joint responses.”

The trial included 391 of 500 adult patients who were screened and then randomized to one of four tildrakizumab dosing groups or placebo; there were 78 patients treated with tildrakizumab 200 mg once every 4 weeks (Q4W) and 79 who were treated with tildrakizumab 200 mg once every 12 weeks (Q12W). A further 77 patients were treated with a 100 mg tildrakizumab dose Q12W, 78 patients with a 20 mg tildrakizumab dose Q12W, and 79 patients were treated with a placebo Q4W.

The mean age of patients included in the study was around 48 years. A total of 55% were female, and more than 96% were white. Across the groups, patients had a median of 7-8 tender joints and about 14-19 swollen joints, and 53%-70% had at least 3% psoriasis body surface area involvement.

The primary endpoint of ACR20 at 24 weeks was met by 79.5%, 77.2%, 71.4%, and 73.1% of patients in the tildrakizumab 200-mg Q4W, 200-mg Q12W, 100-mg Q12W, and 20-mg Q12W groups, and by 50.6% of the placebo-treated patients. “So even the very low dose had an effect,” Dr. Mease observed, also acknowledging the “very high placebo response.”

An ACR50 response was achieved by a respective 53.6%, 50.6%, 45.5%, 39.7%, 19.7%, and 24.1% of patients. ACR70 response rates were also “proportionately lower” than the ACR20 responses at around 25%-29% for the tildrakizumab groups and 16% for placebo.

“The skin scores were as expected quite high,” Dr. Mease said. The Psoriasis Area and Severity Index (PASI) 75 response rate was 79.6% in the tildrakizumab 200-mg Q12W group, 64.2% in the 200-mg Q4W group, 55.6% in the 100-mg Q12W group, 46.3% in the 20-mg Q12W group, and just 16.7% in the placebo group. The respective percentages of patients achieving a PASI 90 response rate were 50%, 47.2%, 38.9%, 36.6%, and 7.1%.

Patient pain assessment showed a clear reduction with tildrakizumab versus placebo treatment. “We see statistical separation between all of the tildrakizumab arms and placebo,” Dr. Mease said. “A greater than 50% response in pain is considered major clinical improvement, and that was achieved by all of the tildrakizumab arms.”

As for enthesitis, the mean change in Leeds Enthesitis Scores from baseline to week 24 were greater with all tildrakizumab doses than with placebo, although a high placebo response was again apparent.

“In general, the safety profile was very good for this agent,” Dr. Mease said. Any treatment-emergent adverse event (TEAE) occurred in 156 of 317 (49%) tildrakizumab-treated patients and in 34 of 70 (49%) placebo-treated patients. The rates of any severe TEAE were 2.2% for the tildrakizumab arms and 2.5% for placebo. Any TEAE related to treatment occurred in a respective 11.2% and 12.7%, but there were no discontinuations because of adverse events, nor were there any major cardiac adverse events, cases of malignancy, or deaths caused by TEAEs. There was a single serious infection, a case of tonsillitis, which occurred with tildrakizumab treatment.

In response to a question after his presentation, Dr. Measure noted: “In the psoriasis trials with this agent, even a single dose yielded a fairly meaningful PASI 75 responses out for extremely long periods of time, 6–12 months. So, it looks like the Q12 dosing is going to be reasonable and convenient for patients”. He also agreed with a comment that the more frequent dosing seemed to be linked to inferior responses in the skin.

The study was sponsored by Sun Pharmaceutical Industries. Dr. Mease has received research grants, consulting fees, and/or speaker fees from 15 pharmaceutical companies, including Sun Pharmaceutical Industries.

SOURCE: Mease PJ et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):77-9. Abstract LB0002, doi: 10.1136/annrheumdis-2019-eular.8669

MADRID – Tildrakizumab, a high-affinity anti–interleukin-23p19 monoclonal antibody, significantly improved joint and skin manifestations in patients with psoriatic arthritis in an ongoing phase 2b study.

Sara Freeman/MDedge News

“By week 24, all four doses of tildrakizumab were significantly more efficacious than placebo,” Philip J. Mease, MD, director of the division of rheumatology clinical research at Swedish Medical Center, Seattle, reported at the European Congress of Rheumatology. This included patient-rated pain, he observed.

Furthermore, “there was a clear separation between tildrakizumab and placebo as early as 8 weeks” for the trial’s primary endpoint, a 20% response rate on American College of Rheumatology criteria (ACR20) at 24 weeks.

The study (NCT02980692), which is projected to complete next year, was conducted to demonstrate the safety and efficacy of tildrakizumab in patients with active psoriatic arthritis. Tildrakizumab is already approved for the treatment of moderate to severe plaque psoriasis in multiple countries, Dr. Mease pointed out. Indeed, the drug – which is marketed as Ilumya in the United States and as Ilumetri in the Europe Union – was approved by the Food and Drug Administration in March last year based on the positive results of the phase 3 reSURFACE clinical trials program (Drugs. 2018;78[8]:845-9).

In presenting interim findings from the study, Dr. Mease observed that “it looked like shortening the dosing interval from Q12 to Q4 weeks for the 200-mg dose did not result in a measurable difference in skin or joint responses.”

The trial included 391 of 500 adult patients who were screened and then randomized to one of four tildrakizumab dosing groups or placebo; there were 78 patients treated with tildrakizumab 200 mg once every 4 weeks (Q4W) and 79 who were treated with tildrakizumab 200 mg once every 12 weeks (Q12W). A further 77 patients were treated with a 100 mg tildrakizumab dose Q12W, 78 patients with a 20 mg tildrakizumab dose Q12W, and 79 patients were treated with a placebo Q4W.

The mean age of patients included in the study was around 48 years. A total of 55% were female, and more than 96% were white. Across the groups, patients had a median of 7-8 tender joints and about 14-19 swollen joints, and 53%-70% had at least 3% psoriasis body surface area involvement.

The primary endpoint of ACR20 at 24 weeks was met by 79.5%, 77.2%, 71.4%, and 73.1% of patients in the tildrakizumab 200-mg Q4W, 200-mg Q12W, 100-mg Q12W, and 20-mg Q12W groups, and by 50.6% of the placebo-treated patients. “So even the very low dose had an effect,” Dr. Mease observed, also acknowledging the “very high placebo response.”

An ACR50 response was achieved by a respective 53.6%, 50.6%, 45.5%, 39.7%, 19.7%, and 24.1% of patients. ACR70 response rates were also “proportionately lower” than the ACR20 responses at around 25%-29% for the tildrakizumab groups and 16% for placebo.

“The skin scores were as expected quite high,” Dr. Mease said. The Psoriasis Area and Severity Index (PASI) 75 response rate was 79.6% in the tildrakizumab 200-mg Q12W group, 64.2% in the 200-mg Q4W group, 55.6% in the 100-mg Q12W group, 46.3% in the 20-mg Q12W group, and just 16.7% in the placebo group. The respective percentages of patients achieving a PASI 90 response rate were 50%, 47.2%, 38.9%, 36.6%, and 7.1%.

Patient pain assessment showed a clear reduction with tildrakizumab versus placebo treatment. “We see statistical separation between all of the tildrakizumab arms and placebo,” Dr. Mease said. “A greater than 50% response in pain is considered major clinical improvement, and that was achieved by all of the tildrakizumab arms.”

As for enthesitis, the mean change in Leeds Enthesitis Scores from baseline to week 24 were greater with all tildrakizumab doses than with placebo, although a high placebo response was again apparent.

“In general, the safety profile was very good for this agent,” Dr. Mease said. Any treatment-emergent adverse event (TEAE) occurred in 156 of 317 (49%) tildrakizumab-treated patients and in 34 of 70 (49%) placebo-treated patients. The rates of any severe TEAE were 2.2% for the tildrakizumab arms and 2.5% for placebo. Any TEAE related to treatment occurred in a respective 11.2% and 12.7%, but there were no discontinuations because of adverse events, nor were there any major cardiac adverse events, cases of malignancy, or deaths caused by TEAEs. There was a single serious infection, a case of tonsillitis, which occurred with tildrakizumab treatment.

In response to a question after his presentation, Dr. Measure noted: “In the psoriasis trials with this agent, even a single dose yielded a fairly meaningful PASI 75 responses out for extremely long periods of time, 6–12 months. So, it looks like the Q12 dosing is going to be reasonable and convenient for patients”. He also agreed with a comment that the more frequent dosing seemed to be linked to inferior responses in the skin.

The study was sponsored by Sun Pharmaceutical Industries. Dr. Mease has received research grants, consulting fees, and/or speaker fees from 15 pharmaceutical companies, including Sun Pharmaceutical Industries.

SOURCE: Mease PJ et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):77-9. Abstract LB0002, doi: 10.1136/annrheumdis-2019-eular.8669

Black individuals who develop type 2 diabetes are more likely than their white counterparts to develop dementia. Now, findings from a new study point to a possible preventive strategy: Putting older patients on metformin when they are diagnosed could reduce their risk for dementia by as much as 40%, whereas sulfonylureas do not seem to have such an effect.

The researchers did not examine cause and effect, so their findings are not conclusive, and very few women were included in the study. Still, the authors said that their data showing a 29% lower risk of dementia associated with metformin use in black patients aged 65-74 years, and a 40% lower risk in those aged 50-64 years, suggested that “this inexpensive, widely available treatment could be broadly prescribed to substantially reduce the risk of dementia in younger [black] patients with [type 2 diabetes]” (Ann Fam Med. 2019;17:352-62).

Previous findings have suggested that black patients with type 2 diabetes face a 10%-18% higher risk of dementia, compared with white patients (Diabetes Care. 2014; 37[4]:1009-15). Another study linked type 2 diabetes in middle-aged black patients to a 41% decrease in cognition per test results over 14 years. There was no such decrease in white patients (Neuroepidemiology. 2014;43[3-4]: 220-7).

For the new study, researchers led by Jeffrey F. Scherrer, PhD, of Saint Louis University tracked 73,761 patients aged 50 years or older from 2000-2001 (when they were free of dementia and not taking diabetes) to 2015. Among the patients, 86% were white and 14% were black. In the white and black groups, 97% and 95% were men, respectively, and 61% and 55% were obese, respectively.

All participants began metformin (76%) or sulfonylurea (24%) monotherapy after the baseline period. Guidelines recommend metformin as a first-line treatment for type 2 diabetes, whereas sulfonylureas are considered second-line drugs that should be added to metformin.

After adjustment for confounders such as socioeconomic status and other medical conditions, the researchers found a significantly lower risk of dementia in black patients who took metformin, compared with those taking a sulfonylurea (hazard ratio, 0.73; 95% confidence interval, 0.6-0.89). There was no difference between the drugs among white patients (HR, 0.96; 95% CI, 0.9-1.03, both P = .008)

The results were not statistically significant among age groups, but there were trends. In black patients, the dementia-lowering benefit was largest among those aged 50-64 years (HR, 0.6; 95% CI, 0.45-0.81), followed by those aged 65-74 years (HR, 0.71; 95% CI, 0.53-0.94), and there was no benefit among those aged at least 75 (HR, 1.17; 95% CI, 0.73-1.85) all P = .055. There was a slight benefit among white patients in one of the age groups – 65-74 years (HR, 0.9; 95% CI, 0.82-0.99; P = .315).

The authors suggested that the findings could have been the result of an effect of metformin to reduce vascular disease and chronic inflammation in black patients.

They also noted that further research is needed to identify the demographic and clinical subgroups in which metformin is most strongly associated with a reduction in the risk of dementia. In addition, they emphasized that clinical trials are needed to confirm the study findings.

The National Institutes of Health funded the study. The authors report no relevant disclosures.

SOURCE: Scherrer JF et al. Ann Fam Med. 2019;17:352-62.

Black individuals who develop type 2 diabetes are more likely than their white counterparts to develop dementia. Now, findings from a new study point to a possible preventive strategy: Putting older patients on metformin when they are diagnosed could reduce their risk for dementia by as much as 40%, whereas sulfonylureas do not seem to have such an effect.

The researchers did not examine cause and effect, so their findings are not conclusive, and very few women were included in the study. Still, the authors said that their data showing a 29% lower risk of dementia associated with metformin use in black patients aged 65-74 years, and a 40% lower risk in those aged 50-64 years, suggested that “this inexpensive, widely available treatment could be broadly prescribed to substantially reduce the risk of dementia in younger [black] patients with [type 2 diabetes]” (Ann Fam Med. 2019;17:352-62).

Previous findings have suggested that black patients with type 2 diabetes face a 10%-18% higher risk of dementia, compared with white patients (Diabetes Care. 2014; 37[4]:1009-15). Another study linked type 2 diabetes in middle-aged black patients to a 41% decrease in cognition per test results over 14 years. There was no such decrease in white patients (Neuroepidemiology. 2014;43[3-4]: 220-7).

For the new study, researchers led by Jeffrey F. Scherrer, PhD, of Saint Louis University tracked 73,761 patients aged 50 years or older from 2000-2001 (when they were free of dementia and not taking diabetes) to 2015. Among the patients, 86% were white and 14% were black. In the white and black groups, 97% and 95% were men, respectively, and 61% and 55% were obese, respectively.

All participants began metformin (76%) or sulfonylurea (24%) monotherapy after the baseline period. Guidelines recommend metformin as a first-line treatment for type 2 diabetes, whereas sulfonylureas are considered second-line drugs that should be added to metformin.

After adjustment for confounders such as socioeconomic status and other medical conditions, the researchers found a significantly lower risk of dementia in black patients who took metformin, compared with those taking a sulfonylurea (hazard ratio, 0.73; 95% confidence interval, 0.6-0.89). There was no difference between the drugs among white patients (HR, 0.96; 95% CI, 0.9-1.03, both P = .008)

The results were not statistically significant among age groups, but there were trends. In black patients, the dementia-lowering benefit was largest among those aged 50-64 years (HR, 0.6; 95% CI, 0.45-0.81), followed by those aged 65-74 years (HR, 0.71; 95% CI, 0.53-0.94), and there was no benefit among those aged at least 75 (HR, 1.17; 95% CI, 0.73-1.85) all P = .055. There was a slight benefit among white patients in one of the age groups – 65-74 years (HR, 0.9; 95% CI, 0.82-0.99; P = .315).

The authors suggested that the findings could have been the result of an effect of metformin to reduce vascular disease and chronic inflammation in black patients.

They also noted that further research is needed to identify the demographic and clinical subgroups in which metformin is most strongly associated with a reduction in the risk of dementia. In addition, they emphasized that clinical trials are needed to confirm the study findings.

The National Institutes of Health funded the study. The authors report no relevant disclosures.

SOURCE: Scherrer JF et al. Ann Fam Med. 2019;17:352-62.

Black individuals who develop type 2 diabetes are more likely than their white counterparts to develop dementia. Now, findings from a new study point to a possible preventive strategy: Putting older patients on metformin when they are diagnosed could reduce their risk for dementia by as much as 40%, whereas sulfonylureas do not seem to have such an effect.

The researchers did not examine cause and effect, so their findings are not conclusive, and very few women were included in the study. Still, the authors said that their data showing a 29% lower risk of dementia associated with metformin use in black patients aged 65-74 years, and a 40% lower risk in those aged 50-64 years, suggested that “this inexpensive, widely available treatment could be broadly prescribed to substantially reduce the risk of dementia in younger [black] patients with [type 2 diabetes]” (Ann Fam Med. 2019;17:352-62).

Previous findings have suggested that black patients with type 2 diabetes face a 10%-18% higher risk of dementia, compared with white patients (Diabetes Care. 2014; 37[4]:1009-15). Another study linked type 2 diabetes in middle-aged black patients to a 41% decrease in cognition per test results over 14 years. There was no such decrease in white patients (Neuroepidemiology. 2014;43[3-4]: 220-7).

For the new study, researchers led by Jeffrey F. Scherrer, PhD, of Saint Louis University tracked 73,761 patients aged 50 years or older from 2000-2001 (when they were free of dementia and not taking diabetes) to 2015. Among the patients, 86% were white and 14% were black. In the white and black groups, 97% and 95% were men, respectively, and 61% and 55% were obese, respectively.

All participants began metformin (76%) or sulfonylurea (24%) monotherapy after the baseline period. Guidelines recommend metformin as a first-line treatment for type 2 diabetes, whereas sulfonylureas are considered second-line drugs that should be added to metformin.

After adjustment for confounders such as socioeconomic status and other medical conditions, the researchers found a significantly lower risk of dementia in black patients who took metformin, compared with those taking a sulfonylurea (hazard ratio, 0.73; 95% confidence interval, 0.6-0.89). There was no difference between the drugs among white patients (HR, 0.96; 95% CI, 0.9-1.03, both P = .008)

The results were not statistically significant among age groups, but there were trends. In black patients, the dementia-lowering benefit was largest among those aged 50-64 years (HR, 0.6; 95% CI, 0.45-0.81), followed by those aged 65-74 years (HR, 0.71; 95% CI, 0.53-0.94), and there was no benefit among those aged at least 75 (HR, 1.17; 95% CI, 0.73-1.85) all P = .055. There was a slight benefit among white patients in one of the age groups – 65-74 years (HR, 0.9; 95% CI, 0.82-0.99; P = .315).

The authors suggested that the findings could have been the result of an effect of metformin to reduce vascular disease and chronic inflammation in black patients.

They also noted that further research is needed to identify the demographic and clinical subgroups in which metformin is most strongly associated with a reduction in the risk of dementia. In addition, they emphasized that clinical trials are needed to confirm the study findings.

The National Institutes of Health funded the study. The authors report no relevant disclosures.

SOURCE: Scherrer JF et al. Ann Fam Med. 2019;17:352-62.

Two-thirds of patients hospitalized with pneumonia received an excess duration of antibiotics, according to a recent study of more than 6,000 patients.

Longer antibiotic courses did not increase the survival rate or prevent any subsequent health care utilization, authors said; instead, they increased the risk of patient-reported adverse events.

The findings bolster a growing body of evidence showing that short-course therapy for pneumonia is safe and that longer durations are not only unnecessary, but “potentially harmful,” said Valerie M. Vaughn, MD, assistant professor of medicine at the University of Michigan, Ann Arbor, and coinvestigators.

“Reducing excess treatment durations should be a top priority for antibiotic stewardship nationally,” the investigators wrote in their report, which appears in the Annals of Internal Medicine.

The primary analysis of their retrospective cohort study included 6,481 individuals with pneumonia treated at 43 hospitals participating in a statewide quality initiative designed to improve care for hospitalized medical patients at risk of adverse events. About half of the patients were women, and the median age was 70 years. Nearly 60% had severe pneumonia.

The primary outcome of the study was the rate of excess antibiotic therapy duration beyond the shortest expected treatment duration consistent with guidelines. Patients with community-acquired pneumonia (CAP), representing about three-quarters of the study cohort, were expected to have a treatment duration of at least 5 days, while patients with health care–acquired pneumonia (HCAP) were expected to have at least 7 days of treatment.

Overall, 4,391 patients (67.8%) had antibiotic courses longer than the shortest effective duration, with a median duration of 8 days, and a median excess duration of 2 days, the researchers noted.

The great majority of excess days (93.2%) were due to antibiotic prescribed at discharge, according to Dr. Vaughn and colleagues.

Excess treatment duration was not linked to any improvement in 30-day mortality, readmission rates, or subsequent emergency department visits, they found.

In a telephone call at 30 days, 38% of patients treated to excess said they had gone to the doctor for an antibiotic-associated adverse event, compared with 31% who received appropriate-length courses (P = .003).

Odds of a patient-reported adverse event were increased by 5% for every excess treatment day, the investigators wrote.

Taken together, these findings have implications for patient care, research efforts, and future guidelines, according to Dr. Vaughn and coinvestigators.

“The next iteration of CAP and HCAP guidelines should explicitly recommend (rather than imply) that providers prescribe the shortest effective duration,” they said in a discussion of their study results.

Dr. Vaughn reported no disclosures related to the study. Coauthors reported grants from Blue Cross Blue Shield of Michigan and the Agency for Healthcare Research and Quality, personal fees from Wiley Publishing, and royalties from Wolters Kluwer Publishing and Oxford University Press, among other disclosures.

SOURCE: Vaughn VM et al. Ann Intern Med. 2019;171:153-63. doi: 10.7326/M18-3640.

Two-thirds of patients hospitalized with pneumonia received an excess duration of antibiotics, according to a recent study of more than 6,000 patients.

Longer antibiotic courses did not increase the survival rate or prevent any subsequent health care utilization, authors said; instead, they increased the risk of patient-reported adverse events.

The findings bolster a growing body of evidence showing that short-course therapy for pneumonia is safe and that longer durations are not only unnecessary, but “potentially harmful,” said Valerie M. Vaughn, MD, assistant professor of medicine at the University of Michigan, Ann Arbor, and coinvestigators.

“Reducing excess treatment durations should be a top priority for antibiotic stewardship nationally,” the investigators wrote in their report, which appears in the Annals of Internal Medicine.

The primary analysis of their retrospective cohort study included 6,481 individuals with pneumonia treated at 43 hospitals participating in a statewide quality initiative designed to improve care for hospitalized medical patients at risk of adverse events. About half of the patients were women, and the median age was 70 years. Nearly 60% had severe pneumonia.

The primary outcome of the study was the rate of excess antibiotic therapy duration beyond the shortest expected treatment duration consistent with guidelines. Patients with community-acquired pneumonia (CAP), representing about three-quarters of the study cohort, were expected to have a treatment duration of at least 5 days, while patients with health care–acquired pneumonia (HCAP) were expected to have at least 7 days of treatment.

Overall, 4,391 patients (67.8%) had antibiotic courses longer than the shortest effective duration, with a median duration of 8 days, and a median excess duration of 2 days, the researchers noted.

The great majority of excess days (93.2%) were due to antibiotic prescribed at discharge, according to Dr. Vaughn and colleagues.

Excess treatment duration was not linked to any improvement in 30-day mortality, readmission rates, or subsequent emergency department visits, they found.

In a telephone call at 30 days, 38% of patients treated to excess said they had gone to the doctor for an antibiotic-associated adverse event, compared with 31% who received appropriate-length courses (P = .003).

Odds of a patient-reported adverse event were increased by 5% for every excess treatment day, the investigators wrote.

Taken together, these findings have implications for patient care, research efforts, and future guidelines, according to Dr. Vaughn and coinvestigators.

“The next iteration of CAP and HCAP guidelines should explicitly recommend (rather than imply) that providers prescribe the shortest effective duration,” they said in a discussion of their study results.

Dr. Vaughn reported no disclosures related to the study. Coauthors reported grants from Blue Cross Blue Shield of Michigan and the Agency for Healthcare Research and Quality, personal fees from Wiley Publishing, and royalties from Wolters Kluwer Publishing and Oxford University Press, among other disclosures.

SOURCE: Vaughn VM et al. Ann Intern Med. 2019;171:153-63. doi: 10.7326/M18-3640.

Two-thirds of patients hospitalized with pneumonia received an excess duration of antibiotics, according to a recent study of more than 6,000 patients.

Longer antibiotic courses did not increase the survival rate or prevent any subsequent health care utilization, authors said; instead, they increased the risk of patient-reported adverse events.

The findings bolster a growing body of evidence showing that short-course therapy for pneumonia is safe and that longer durations are not only unnecessary, but “potentially harmful,” said Valerie M. Vaughn, MD, assistant professor of medicine at the University of Michigan, Ann Arbor, and coinvestigators.

“Reducing excess treatment durations should be a top priority for antibiotic stewardship nationally,” the investigators wrote in their report, which appears in the Annals of Internal Medicine.

The primary analysis of their retrospective cohort study included 6,481 individuals with pneumonia treated at 43 hospitals participating in a statewide quality initiative designed to improve care for hospitalized medical patients at risk of adverse events. About half of the patients were women, and the median age was 70 years. Nearly 60% had severe pneumonia.

The primary outcome of the study was the rate of excess antibiotic therapy duration beyond the shortest expected treatment duration consistent with guidelines. Patients with community-acquired pneumonia (CAP), representing about three-quarters of the study cohort, were expected to have a treatment duration of at least 5 days, while patients with health care–acquired pneumonia (HCAP) were expected to have at least 7 days of treatment.

Overall, 4,391 patients (67.8%) had antibiotic courses longer than the shortest effective duration, with a median duration of 8 days, and a median excess duration of 2 days, the researchers noted.

The great majority of excess days (93.2%) were due to antibiotic prescribed at discharge, according to Dr. Vaughn and colleagues.

Excess treatment duration was not linked to any improvement in 30-day mortality, readmission rates, or subsequent emergency department visits, they found.

In a telephone call at 30 days, 38% of patients treated to excess said they had gone to the doctor for an antibiotic-associated adverse event, compared with 31% who received appropriate-length courses (P = .003).

Odds of a patient-reported adverse event were increased by 5% for every excess treatment day, the investigators wrote.

Taken together, these findings have implications for patient care, research efforts, and future guidelines, according to Dr. Vaughn and coinvestigators.

“The next iteration of CAP and HCAP guidelines should explicitly recommend (rather than imply) that providers prescribe the shortest effective duration,” they said in a discussion of their study results.

Dr. Vaughn reported no disclosures related to the study. Coauthors reported grants from Blue Cross Blue Shield of Michigan and the Agency for Healthcare Research and Quality, personal fees from Wiley Publishing, and royalties from Wolters Kluwer Publishing and Oxford University Press, among other disclosures.

SOURCE: Vaughn VM et al. Ann Intern Med. 2019;171:153-63. doi: 10.7326/M18-3640.

Pregnancy management and outcomes have improved markedly for women with SLE over the past 2 decades, but there’s still progress to be made, research shows.

A retrospective cohort study led by rheumatologist Bella Mehta, MBBS, of the Hospital for Special Surgery in New York, and colleagues looked at data from the National Inpatient Sample database involving 93,820 pregnant women with SLE and 78,045,054 without SLE who were hospitalized in the United States between 1998 and 2015.

The results showed that over the 18-year study period, in-hospital maternal deaths per 100,000 admissions declined among patients with as well as those without SLE (442 vs. 13 for 1998-2000 and less than 50 vs. 10 for 2013-2015), although the decrease was greater in women with SLE (difference in trends, P less than .002).

Fetal mortality declined both for patients with SLE (268 deaths per 10,000 deliveries in 1998-2000 vs. 153 in 2013-2015) and those without SLE (72 deaths per 10,000 deliveries in 1998-2000 vs. 66 in 2013-2015).

“Although the decrease in fetal mortality seems somewhat greater in patients with SLE than those without it, the difference in trends is not statistically significant (P = .064),” the study authors noted in their paper, published in Annals of Internal Medicine.

Although patients with SLE in their study showed greater progress in rates of preeclampsia or eclampsia and length of stay, they still had worse outcomes in all measures when compared against women without SLE, the authors noted.

“Our study provides nationwide evidence that SLE pregnancy outcomes have become markedly better in the past 2 decades and continue to improve. However, SLE pregnancy risks remain high, and more work is needed to ensure good pregnancy outcomes among women with SLE,” they concluded.

Writing in an accompanying editorial, Megan E.B. Clowse, MD, of Duke University, Durham, N.C., noted that although the study findings of a progressive reduction in maternal mortality seemed very likely, the absolute decrease seen – from 140 maternal deaths per 100,000 births to fewer than 50 in 2013-2015 – warranted some reflection (Ann Intern Med. 2019;171:212-3. doi: 10.7326/M19-1667).

“SLE pregnancy management has not advanced within the past 5 years to an extent great enough to explain such a large drop in mortality,” she wrote.

There were also question marks around whether the NIS data should be used to analyze very rare events, such as maternal deaths in women with SLE. The SLE diagnosis in the database may also have included pregnancies in women who did not have SLE but instead had an elevated level of antinuclear antibody or lupus anticoagulant, which “may have diluted the frequency of poor outcomes,” Dr. Clowse wrote.

“For these reasons, I am concerned that the observed decline in maternal mortality may be an artifact, underestimating the ongoing risk of pregnancy for women with SLE,” Dr. Clowse wrote.

She added that recent analyses demonstrated that the use of hydroxychloroquine and aspirin in SLE pregnancy was not widespread.

“The inaugural reproductive health guidelines soon to be published by the American College of Rheumatology will have the potential to help expand state-of-the-art approaches to the management of pregnant women with SLE seen in everyday practice,” she concluded.

The study had no primary funding source and no conflicts of interest were declared. Dr. Mehta is supported by the C. Ronald MacKenzie Young Scientist Endowment Award. Dr. Clowse reported grants from GlaxoSmithKline and personal fees from UCB, both outside the submitted work.

SOURCE: Mehta B et al. Ann Intern Med. 2019;171:164-71. doi: 10.7326/M19-0120.

Pregnancy management and outcomes have improved markedly for women with SLE over the past 2 decades, but there’s still progress to be made, research shows.

A retrospective cohort study led by rheumatologist Bella Mehta, MBBS, of the Hospital for Special Surgery in New York, and colleagues looked at data from the National Inpatient Sample database involving 93,820 pregnant women with SLE and 78,045,054 without SLE who were hospitalized in the United States between 1998 and 2015.

The results showed that over the 18-year study period, in-hospital maternal deaths per 100,000 admissions declined among patients with as well as those without SLE (442 vs. 13 for 1998-2000 and less than 50 vs. 10 for 2013-2015), although the decrease was greater in women with SLE (difference in trends, P less than .002).

Fetal mortality declined both for patients with SLE (268 deaths per 10,000 deliveries in 1998-2000 vs. 153 in 2013-2015) and those without SLE (72 deaths per 10,000 deliveries in 1998-2000 vs. 66 in 2013-2015).

“Although the decrease in fetal mortality seems somewhat greater in patients with SLE than those without it, the difference in trends is not statistically significant (P = .064),” the study authors noted in their paper, published in Annals of Internal Medicine.

Although patients with SLE in their study showed greater progress in rates of preeclampsia or eclampsia and length of stay, they still had worse outcomes in all measures when compared against women without SLE, the authors noted.

“Our study provides nationwide evidence that SLE pregnancy outcomes have become markedly better in the past 2 decades and continue to improve. However, SLE pregnancy risks remain high, and more work is needed to ensure good pregnancy outcomes among women with SLE,” they concluded.

Writing in an accompanying editorial, Megan E.B. Clowse, MD, of Duke University, Durham, N.C., noted that although the study findings of a progressive reduction in maternal mortality seemed very likely, the absolute decrease seen – from 140 maternal deaths per 100,000 births to fewer than 50 in 2013-2015 – warranted some reflection (Ann Intern Med. 2019;171:212-3. doi: 10.7326/M19-1667).

“SLE pregnancy management has not advanced within the past 5 years to an extent great enough to explain such a large drop in mortality,” she wrote.

There were also question marks around whether the NIS data should be used to analyze very rare events, such as maternal deaths in women with SLE. The SLE diagnosis in the database may also have included pregnancies in women who did not have SLE but instead had an elevated level of antinuclear antibody or lupus anticoagulant, which “may have diluted the frequency of poor outcomes,” Dr. Clowse wrote.

“For these reasons, I am concerned that the observed decline in maternal mortality may be an artifact, underestimating the ongoing risk of pregnancy for women with SLE,” Dr. Clowse wrote.

She added that recent analyses demonstrated that the use of hydroxychloroquine and aspirin in SLE pregnancy was not widespread.

“The inaugural reproductive health guidelines soon to be published by the American College of Rheumatology will have the potential to help expand state-of-the-art approaches to the management of pregnant women with SLE seen in everyday practice,” she concluded.

The study had no primary funding source and no conflicts of interest were declared. Dr. Mehta is supported by the C. Ronald MacKenzie Young Scientist Endowment Award. Dr. Clowse reported grants from GlaxoSmithKline and personal fees from UCB, both outside the submitted work.

SOURCE: Mehta B et al. Ann Intern Med. 2019;171:164-71. doi: 10.7326/M19-0120.

Pregnancy management and outcomes have improved markedly for women with SLE over the past 2 decades, but there’s still progress to be made, research shows.

A retrospective cohort study led by rheumatologist Bella Mehta, MBBS, of the Hospital for Special Surgery in New York, and colleagues looked at data from the National Inpatient Sample database involving 93,820 pregnant women with SLE and 78,045,054 without SLE who were hospitalized in the United States between 1998 and 2015.

The results showed that over the 18-year study period, in-hospital maternal deaths per 100,000 admissions declined among patients with as well as those without SLE (442 vs. 13 for 1998-2000 and less than 50 vs. 10 for 2013-2015), although the decrease was greater in women with SLE (difference in trends, P less than .002).

Fetal mortality declined both for patients with SLE (268 deaths per 10,000 deliveries in 1998-2000 vs. 153 in 2013-2015) and those without SLE (72 deaths per 10,000 deliveries in 1998-2000 vs. 66 in 2013-2015).

“Although the decrease in fetal mortality seems somewhat greater in patients with SLE than those without it, the difference in trends is not statistically significant (P = .064),” the study authors noted in their paper, published in Annals of Internal Medicine.

Although patients with SLE in their study showed greater progress in rates of preeclampsia or eclampsia and length of stay, they still had worse outcomes in all measures when compared against women without SLE, the authors noted.

“Our study provides nationwide evidence that SLE pregnancy outcomes have become markedly better in the past 2 decades and continue to improve. However, SLE pregnancy risks remain high, and more work is needed to ensure good pregnancy outcomes among women with SLE,” they concluded.

Writing in an accompanying editorial, Megan E.B. Clowse, MD, of Duke University, Durham, N.C., noted that although the study findings of a progressive reduction in maternal mortality seemed very likely, the absolute decrease seen – from 140 maternal deaths per 100,000 births to fewer than 50 in 2013-2015 – warranted some reflection (Ann Intern Med. 2019;171:212-3. doi: 10.7326/M19-1667).

“SLE pregnancy management has not advanced within the past 5 years to an extent great enough to explain such a large drop in mortality,” she wrote.

There were also question marks around whether the NIS data should be used to analyze very rare events, such as maternal deaths in women with SLE. The SLE diagnosis in the database may also have included pregnancies in women who did not have SLE but instead had an elevated level of antinuclear antibody or lupus anticoagulant, which “may have diluted the frequency of poor outcomes,” Dr. Clowse wrote.

“For these reasons, I am concerned that the observed decline in maternal mortality may be an artifact, underestimating the ongoing risk of pregnancy for women with SLE,” Dr. Clowse wrote.

She added that recent analyses demonstrated that the use of hydroxychloroquine and aspirin in SLE pregnancy was not widespread.

“The inaugural reproductive health guidelines soon to be published by the American College of Rheumatology will have the potential to help expand state-of-the-art approaches to the management of pregnant women with SLE seen in everyday practice,” she concluded.

The study had no primary funding source and no conflicts of interest were declared. Dr. Mehta is supported by the C. Ronald MacKenzie Young Scientist Endowment Award. Dr. Clowse reported grants from GlaxoSmithKline and personal fees from UCB, both outside the submitted work.

SOURCE: Mehta B et al. Ann Intern Med. 2019;171:164-71. doi: 10.7326/M19-0120.

MADRID – Repeated antinuclear antibody testing after a negative result has limited use for the diagnosis of ANA-associated rheumatologic conditions, according to data from a multicenter, retrospective analysis that considered a 7-year period.

Sara Freeman/MDEdge News

Considering more than 7,875 repeated ANA tests in 4,887 patients, “the vast majority of results didn’t change,” Ai Li Yeo, MBBS, a PhD candidate, rheumatologist, and infectious disease fellow at Monash University, Melbourne, reported at the European Congress of Rheumatology.

ANA tests were repeated between 2 and as many as 45 times in individual patients, she reported, but the results of 79% of these tests remained unchanged – 45% of tests were persistently negative and 34% persistently positive using a cutoff titer of 1:160.

“Our study showed that there was a very low yield in repeating an ANA test for the diagnosis of ANA-associated rheumatological conditions unless there was evidence of evolving multisystem clinical features,” Dr. Yeo said.

Indeed, the positive predictive value was just 0.01. “So for a hundred patients staring off with a negative ANA results that on repeat testing became positive, the probability is that one patient will have a new ANA-associated rheumatological condition diagnosis,” Dr. Yeo said.

“ANA testing is frequently performed and is part of the classification criteria for autoimmune conditions such as lupus and scleroderma,” she observed. However, the test provides no information on the severity or activity of the disease, and the value of serial monitoring for such conditions is unclear.

“Minimizing unnecessary tests is a global health economic priority,” Dr. Yeo said. She noted that there are multiple initiatives in place to try to open a dialog about using health care resources most effectively, such as ‘Choosing Wisely’ set up by the American Board of Internal Medicine (ABIM) Foundation.

The aim of the present analysis was to calculate the cost of repeated ANA testing and to see if any change in the ANA result was associated with new diagnoses of ANA-associated rheumatological conditions.

The analysis considered more than 36,700 tests that were performed on samples from more than 28,800 patients within the Monash Health tertiary health network between 2011 and 2018. Of these, 22,657 (62%) had given a negative result and 14,058 (38%) had given a positive result.

“Not surprisingly, the age of those who tested positive was significantly higher than those who tested negative,” Dr. Yeo said (52.6 vs. 48.9 years; P less than .001). There was also a higher number of women than men tested, and women more often tested positive.

Around one-fifth of tests performed were repeat tests, of which 511 (6.5%) changed from being negative to positive over a median of 1.71 years.

“A small percentage of people alternated between results,” Dr. Yeo acknowledged, with 9.4% of people going from a positive to a negative result; 10.5% moving from a negative to a positive result, and 1.9% going from positive to negative to positive.

With repeated tests, just five new diagnoses of ANA-associated rheumatologic conditions were made: two cases of systemic lupus erythematosus (SLE), one case of scleroderma, and two cases of undifferentiated connective tissue disease. There was a range of ANA titers and patterns and evolving clinical features of a multisystem disease.

Based on the direct costs of ANA testing in her health care system, not performing repeated tests could yield significant savings, Dr. Yeo said, a 21.4% reduction, in fact, based on this analysis. The cost of an ANA test in Australia ranges from 15 to 46 euros, making the cost of all tests in this analysis 564,745 euros. Taking away the cost of all the single ANA tests performed (443,209 euros) gives a potential cost saving of more than 121,000 euros, she said.

“We now have an opportunity to prevent unnecessary ANA testing, Dr. Yeo said. “Ultimately, our aim is to change behavior at the start of the ordering cycle by educating medical students and doctors about inappropriate test ordering.”

The majority of repeated tests had been ordered by nonrheumatologists (82% of cases), and Dr. Yeo said that rheumatologists ordered repeat tests in 11% of cases. However, there was little information available in this retrospective analysis as to why the tests had been repeated.

The research was picked as one of the six best clinical abstracts at the meeting, out of a total of almost 5,000 submitted abstracts.

Dr. Yeo reported having no conflicts of interest.

SOURCE: Yeo AL et al. Ann Rheum Dis. Jun 2019;78(suppl 2):76-7, Abstract OP0020. doi: 10.1136/annrheumdis-2019-eular.4517.

MADRID – Repeated antinuclear antibody testing after a negative result has limited use for the diagnosis of ANA-associated rheumatologic conditions, according to data from a multicenter, retrospective analysis that considered a 7-year period.

Sara Freeman/MDEdge News

Considering more than 7,875 repeated ANA tests in 4,887 patients, “the vast majority of results didn’t change,” Ai Li Yeo, MBBS, a PhD candidate, rheumatologist, and infectious disease fellow at Monash University, Melbourne, reported at the European Congress of Rheumatology.

ANA tests were repeated between 2 and as many as 45 times in individual patients, she reported, but the results of 79% of these tests remained unchanged – 45% of tests were persistently negative and 34% persistently positive using a cutoff titer of 1:160.

“Our study showed that there was a very low yield in repeating an ANA test for the diagnosis of ANA-associated rheumatological conditions unless there was evidence of evolving multisystem clinical features,” Dr. Yeo said.

Indeed, the positive predictive value was just 0.01. “So for a hundred patients staring off with a negative ANA results that on repeat testing became positive, the probability is that one patient will have a new ANA-associated rheumatological condition diagnosis,” Dr. Yeo said.

“ANA testing is frequently performed and is part of the classification criteria for autoimmune conditions such as lupus and scleroderma,” she observed. However, the test provides no information on the severity or activity of the disease, and the value of serial monitoring for such conditions is unclear.

“Minimizing unnecessary tests is a global health economic priority,” Dr. Yeo said. She noted that there are multiple initiatives in place to try to open a dialog about using health care resources most effectively, such as ‘Choosing Wisely’ set up by the American Board of Internal Medicine (ABIM) Foundation.

The aim of the present analysis was to calculate the cost of repeated ANA testing and to see if any change in the ANA result was associated with new diagnoses of ANA-associated rheumatological conditions.

The analysis considered more than 36,700 tests that were performed on samples from more than 28,800 patients within the Monash Health tertiary health network between 2011 and 2018. Of these, 22,657 (62%) had given a negative result and 14,058 (38%) had given a positive result.

“Not surprisingly, the age of those who tested positive was significantly higher than those who tested negative,” Dr. Yeo said (52.6 vs. 48.9 years; P less than .001). There was also a higher number of women than men tested, and women more often tested positive.

Around one-fifth of tests performed were repeat tests, of which 511 (6.5%) changed from being negative to positive over a median of 1.71 years.

“A small percentage of people alternated between results,” Dr. Yeo acknowledged, with 9.4% of people going from a positive to a negative result; 10.5% moving from a negative to a positive result, and 1.9% going from positive to negative to positive.

With repeated tests, just five new diagnoses of ANA-associated rheumatologic conditions were made: two cases of systemic lupus erythematosus (SLE), one case of scleroderma, and two cases of undifferentiated connective tissue disease. There was a range of ANA titers and patterns and evolving clinical features of a multisystem disease.

Based on the direct costs of ANA testing in her health care system, not performing repeated tests could yield significant savings, Dr. Yeo said, a 21.4% reduction, in fact, based on this analysis. The cost of an ANA test in Australia ranges from 15 to 46 euros, making the cost of all tests in this analysis 564,745 euros. Taking away the cost of all the single ANA tests performed (443,209 euros) gives a potential cost saving of more than 121,000 euros, she said.

“We now have an opportunity to prevent unnecessary ANA testing, Dr. Yeo said. “Ultimately, our aim is to change behavior at the start of the ordering cycle by educating medical students and doctors about inappropriate test ordering.”

The majority of repeated tests had been ordered by nonrheumatologists (82% of cases), and Dr. Yeo said that rheumatologists ordered repeat tests in 11% of cases. However, there was little information available in this retrospective analysis as to why the tests had been repeated.

The research was picked as one of the six best clinical abstracts at the meeting, out of a total of almost 5,000 submitted abstracts.

Dr. Yeo reported having no conflicts of interest.

SOURCE: Yeo AL et al. Ann Rheum Dis. Jun 2019;78(suppl 2):76-7, Abstract OP0020. doi: 10.1136/annrheumdis-2019-eular.4517.

MADRID – Repeated antinuclear antibody testing after a negative result has limited use for the diagnosis of ANA-associated rheumatologic conditions, according to data from a multicenter, retrospective analysis that considered a 7-year period.

Sara Freeman/MDEdge News

Considering more than 7,875 repeated ANA tests in 4,887 patients, “the vast majority of results didn’t change,” Ai Li Yeo, MBBS, a PhD candidate, rheumatologist, and infectious disease fellow at Monash University, Melbourne, reported at the European Congress of Rheumatology.

ANA tests were repeated between 2 and as many as 45 times in individual patients, she reported, but the results of 79% of these tests remained unchanged – 45% of tests were persistently negative and 34% persistently positive using a cutoff titer of 1:160.

“Our study showed that there was a very low yield in repeating an ANA test for the diagnosis of ANA-associated rheumatological conditions unless there was evidence of evolving multisystem clinical features,” Dr. Yeo said.

Indeed, the positive predictive value was just 0.01. “So for a hundred patients staring off with a negative ANA results that on repeat testing became positive, the probability is that one patient will have a new ANA-associated rheumatological condition diagnosis,” Dr. Yeo said.

“ANA testing is frequently performed and is part of the classification criteria for autoimmune conditions such as lupus and scleroderma,” she observed. However, the test provides no information on the severity or activity of the disease, and the value of serial monitoring for such conditions is unclear.

“Minimizing unnecessary tests is a global health economic priority,” Dr. Yeo said. She noted that there are multiple initiatives in place to try to open a dialog about using health care resources most effectively, such as ‘Choosing Wisely’ set up by the American Board of Internal Medicine (ABIM) Foundation.

The aim of the present analysis was to calculate the cost of repeated ANA testing and to see if any change in the ANA result was associated with new diagnoses of ANA-associated rheumatological conditions.

The analysis considered more than 36,700 tests that were performed on samples from more than 28,800 patients within the Monash Health tertiary health network between 2011 and 2018. Of these, 22,657 (62%) had given a negative result and 14,058 (38%) had given a positive result.

“Not surprisingly, the age of those who tested positive was significantly higher than those who tested negative,” Dr. Yeo said (52.6 vs. 48.9 years; P less than .001). There was also a higher number of women than men tested, and women more often tested positive.

Around one-fifth of tests performed were repeat tests, of which 511 (6.5%) changed from being negative to positive over a median of 1.71 years.

“A small percentage of people alternated between results,” Dr. Yeo acknowledged, with 9.4% of people going from a positive to a negative result; 10.5% moving from a negative to a positive result, and 1.9% going from positive to negative to positive.

With repeated tests, just five new diagnoses of ANA-associated rheumatologic conditions were made: two cases of systemic lupus erythematosus (SLE), one case of scleroderma, and two cases of undifferentiated connective tissue disease. There was a range of ANA titers and patterns and evolving clinical features of a multisystem disease.

Based on the direct costs of ANA testing in her health care system, not performing repeated tests could yield significant savings, Dr. Yeo said, a 21.4% reduction, in fact, based on this analysis. The cost of an ANA test in Australia ranges from 15 to 46 euros, making the cost of all tests in this analysis 564,745 euros. Taking away the cost of all the single ANA tests performed (443,209 euros) gives a potential cost saving of more than 121,000 euros, she said.

“We now have an opportunity to prevent unnecessary ANA testing, Dr. Yeo said. “Ultimately, our aim is to change behavior at the start of the ordering cycle by educating medical students and doctors about inappropriate test ordering.”

The majority of repeated tests had been ordered by nonrheumatologists (82% of cases), and Dr. Yeo said that rheumatologists ordered repeat tests in 11% of cases. However, there was little information available in this retrospective analysis as to why the tests had been repeated.

The research was picked as one of the six best clinical abstracts at the meeting, out of a total of almost 5,000 submitted abstracts.

Dr. Yeo reported having no conflicts of interest.

SOURCE: Yeo AL et al. Ann Rheum Dis. Jun 2019;78(suppl 2):76-7, Abstract OP0020. doi: 10.1136/annrheumdis-2019-eular.4517.

The decision to undergo preimplantation genetic testing for aneuploidy is associated with a small but not unimportant amount of regret among some patients undergoing fertility treatment, research suggests.

In a report published in Human Reproduction, researchers did an anonymous survey of 69 patients undergoing their first cycle of autologous preimplantation genetic testing for aneuploidy (PGT-A) at a single fertility center.

“Despite the known distress associated with many aspects of assisted reproductive technology (ART) and the many opportunities for distress among patients pursuing PGT-A, little is known about the associated patient experience and psychological risks,” wrote Dr. Kara N. Goldman of New York University Langone Fertility Center, and coauthors.

“A ‘failure’ after PGT-A can present in many forms well before other IVF losses may be experienced: Embryos may not meet criteria for biopsy, PGT-A may result in an all-aneuploid embryo cohort, or a euploid embryo may fail to implant,” the authors continued.

The mean overall decision regret scale score was 8.5 on a scale of 0-100 – with a median of 0 – and 61% of respondents said they had no regrets about undergoing preimplantation genetic testing for aneuploidy; the remaining 39% reported “any degree of regret.”

This “one-third of respondents reported some degree of regret, suggesting an important opportunity for pretest counseling and support among patients pursuing PGT-A,” Dr. Goldman and associates emphasized.

Of the respondents who then underwent euploid embryo transfer, and who had a known pregnancy outcome, the 36 with an ongoing or delivered pregnancy had significantly less decision regret than the 24 who experienced a negative pregnancy test or a miscarriage.

The study found no differences in decision regret between those aged under or over 35 years of age, those with different levels of educational attainment, or between patients who paid exclusively out of pocket compared with those with any insurance coverage.

However, greater levels of decision regret were seen in patients who had experienced a longer time since retrieval of oocytes and those who said they would consider pregnancy with donor oocytes if they were unsuccessful with IVF and PGT-A.

“Completing a cycle of IVF with PGT-A and obtaining no usable, euploid embryos results in distress, but this distress must be weighed against the alternative scenario in which a patient invests valuable time, energy, and resources into a futile embryo transfer cycle resulting in a negative pregnancy test, miscarriage, or aneuploid gestation,” the authors wrote.

When assessing the dependence of the decision regret score on demographic factors, the researchers found that patients who had learned about PGT-A from their physicians, rather than from other sources such as friends or the Internet, had the highest levels of decision regret.

There was no external funding. One coauthor declared personal fees and other support from the fertility and pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Goldman KN et al. Hum Reprod. 2019 Jun 21. doi: 10.1093/humrep/dez080.

The decision to undergo preimplantation genetic testing for aneuploidy is associated with a small but not unimportant amount of regret among some patients undergoing fertility treatment, research suggests.

In a report published in Human Reproduction, researchers did an anonymous survey of 69 patients undergoing their first cycle of autologous preimplantation genetic testing for aneuploidy (PGT-A) at a single fertility center.

“Despite the known distress associated with many aspects of assisted reproductive technology (ART) and the many opportunities for distress among patients pursuing PGT-A, little is known about the associated patient experience and psychological risks,” wrote Dr. Kara N. Goldman of New York University Langone Fertility Center, and coauthors.

“A ‘failure’ after PGT-A can present in many forms well before other IVF losses may be experienced: Embryos may not meet criteria for biopsy, PGT-A may result in an all-aneuploid embryo cohort, or a euploid embryo may fail to implant,” the authors continued.

The mean overall decision regret scale score was 8.5 on a scale of 0-100 – with a median of 0 – and 61% of respondents said they had no regrets about undergoing preimplantation genetic testing for aneuploidy; the remaining 39% reported “any degree of regret.”

This “one-third of respondents reported some degree of regret, suggesting an important opportunity for pretest counseling and support among patients pursuing PGT-A,” Dr. Goldman and associates emphasized.

Of the respondents who then underwent euploid embryo transfer, and who had a known pregnancy outcome, the 36 with an ongoing or delivered pregnancy had significantly less decision regret than the 24 who experienced a negative pregnancy test or a miscarriage.

The study found no differences in decision regret between those aged under or over 35 years of age, those with different levels of educational attainment, or between patients who paid exclusively out of pocket compared with those with any insurance coverage.

However, greater levels of decision regret were seen in patients who had experienced a longer time since retrieval of oocytes and those who said they would consider pregnancy with donor oocytes if they were unsuccessful with IVF and PGT-A.

“Completing a cycle of IVF with PGT-A and obtaining no usable, euploid embryos results in distress, but this distress must be weighed against the alternative scenario in which a patient invests valuable time, energy, and resources into a futile embryo transfer cycle resulting in a negative pregnancy test, miscarriage, or aneuploid gestation,” the authors wrote.

When assessing the dependence of the decision regret score on demographic factors, the researchers found that patients who had learned about PGT-A from their physicians, rather than from other sources such as friends or the Internet, had the highest levels of decision regret.

There was no external funding. One coauthor declared personal fees and other support from the fertility and pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Goldman KN et al. Hum Reprod. 2019 Jun 21. doi: 10.1093/humrep/dez080.

The decision to undergo preimplantation genetic testing for aneuploidy is associated with a small but not unimportant amount of regret among some patients undergoing fertility treatment, research suggests.

In a report published in Human Reproduction, researchers did an anonymous survey of 69 patients undergoing their first cycle of autologous preimplantation genetic testing for aneuploidy (PGT-A) at a single fertility center.

“Despite the known distress associated with many aspects of assisted reproductive technology (ART) and the many opportunities for distress among patients pursuing PGT-A, little is known about the associated patient experience and psychological risks,” wrote Dr. Kara N. Goldman of New York University Langone Fertility Center, and coauthors.

“A ‘failure’ after PGT-A can present in many forms well before other IVF losses may be experienced: Embryos may not meet criteria for biopsy, PGT-A may result in an all-aneuploid embryo cohort, or a euploid embryo may fail to implant,” the authors continued.

The mean overall decision regret scale score was 8.5 on a scale of 0-100 – with a median of 0 – and 61% of respondents said they had no regrets about undergoing preimplantation genetic testing for aneuploidy; the remaining 39% reported “any degree of regret.”

This “one-third of respondents reported some degree of regret, suggesting an important opportunity for pretest counseling and support among patients pursuing PGT-A,” Dr. Goldman and associates emphasized.

Of the respondents who then underwent euploid embryo transfer, and who had a known pregnancy outcome, the 36 with an ongoing or delivered pregnancy had significantly less decision regret than the 24 who experienced a negative pregnancy test or a miscarriage.

The study found no differences in decision regret between those aged under or over 35 years of age, those with different levels of educational attainment, or between patients who paid exclusively out of pocket compared with those with any insurance coverage.

However, greater levels of decision regret were seen in patients who had experienced a longer time since retrieval of oocytes and those who said they would consider pregnancy with donor oocytes if they were unsuccessful with IVF and PGT-A.

“Completing a cycle of IVF with PGT-A and obtaining no usable, euploid embryos results in distress, but this distress must be weighed against the alternative scenario in which a patient invests valuable time, energy, and resources into a futile embryo transfer cycle resulting in a negative pregnancy test, miscarriage, or aneuploid gestation,” the authors wrote.

When assessing the dependence of the decision regret score on demographic factors, the researchers found that patients who had learned about PGT-A from their physicians, rather than from other sources such as friends or the Internet, had the highest levels of decision regret.

There was no external funding. One coauthor declared personal fees and other support from the fertility and pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Goldman KN et al. Hum Reprod. 2019 Jun 21. doi: 10.1093/humrep/dez080.

Each July, the largest gathering of pediatric hospitalists occurs, and 2019 is no different! This year, hospitalists who care for children will gather at Pediatric Hospital Medicine (PHM) in Seattle from July 25 to 28, with the goal of enhancing participants’ knowledge and competence in the areas of innovation, clinical medicine, education, health services, practice management, quality improvement, and research.

But what makes this year particularly special is the launch of the subspecialty exam for certification in pediatric hospital medicine coming later this fall, solidifying its growth and importance within hospital medicine and the entire health care landscape. The American Board of Pediatrics (ABP) has approved PHM as the newest board subspecialty with a 2-year fellowship accredited by the Accreditation Council for Graduate Medical Education (ACGME). This conference will be a great opportunity to join with others to review competencies for board review, as well as to network with those who are also navigating the road ahead.

During 2019, the Pediatric Hospitalist Special Interest Group (SIG) of SHM has been working tirelessly on several initiatives, including a revision of the Pediatric Hospital Medicine Core Competencies as well as additional work to develop Choosing Wisely 2.0 recommendations. These will help us ensure we are developing the best curricula for the next generation of pediatric hospitalists, while cutting back on unnecessary tests and procedures for those practicing today. Each of these initiatives, as well as the July conference, highlights the opportunities that we have within SHM to work with other like-minded providers who care for children. While we partner with all professionals across many organizations, like the American Academy of Pediatrics and the Academic Pediatric Association to name a few, I wanted to share my reflections on SHM and my appreciation for the “big tent” philosophy that has served us so well thus far.

Having an opportunity to sit on the board of SHM has allowed me a chance to really appreciate the efforts that this organization invests in all who care for patients in the hospital; we have an active group of advanced-practice providers, practice administrators, residents, students, academic hospitalists, and the list goes on and on. We collaborate with a number of spectacular societies dedicated to medical specialties, and we are always open to new ways of improving the methods of delivering care to patients, in hospitals, post-acute care facilities, homes – you name it! As health care delivery models continue to evolve, I believe we are well positioned to be leaders in the delivery of acute care medicine in the hospital and beyond.

I have also learned of happenings at the grassroots level by attending SHM chapter meetings across the United States. For example, the Hampton Roads Chapter led a great Point-of-Care Ultrasound (POCUS) workshop, and influenced by that, I shared an idea at home in Nashville – borrowing my son as a model to demonstrate ultrasound techniques that hospitalists can use to assist in clinical care. I hope you, as pediatric hospitalists, will see if you have a local chapter and attend a meeting; whether you are a member of SHM or not, you can mingle with those who provide acute care treatments to all your communities and share best practices. If you don’t see an SHM chapter close by, let’s get one going! SHM is here to help launch a chapter that can help bring your community together and provide education and networking closer to home.

If you can’t attend PHM in Seattle this year, I hope you will make every effort to be at PHM 2020, where our own SIG leader, Dr. Jeffrey Grill from Louisville, Ky., will be chairing the next rendition of this amazing conference. The SHM Meetings team led by Michelle Kann will be working tirelessly to make it a great event with continued growth in content and attendance.

Dr. Rehm is associate professor, pediatrics, and director, division of pediatric outreach medicine at Vanderbilt University and Monroe Carell Jr. Children’s Hospital at Vanderbilt, both in Nashville, Tenn. She is also a member of the SHM board of directors.

Each July, the largest gathering of pediatric hospitalists occurs, and 2019 is no different! This year, hospitalists who care for children will gather at Pediatric Hospital Medicine (PHM) in Seattle from July 25 to 28, with the goal of enhancing participants’ knowledge and competence in the areas of innovation, clinical medicine, education, health services, practice management, quality improvement, and research.

But what makes this year particularly special is the launch of the subspecialty exam for certification in pediatric hospital medicine coming later this fall, solidifying its growth and importance within hospital medicine and the entire health care landscape. The American Board of Pediatrics (ABP) has approved PHM as the newest board subspecialty with a 2-year fellowship accredited by the Accreditation Council for Graduate Medical Education (ACGME). This conference will be a great opportunity to join with others to review competencies for board review, as well as to network with those who are also navigating the road ahead.

During 2019, the Pediatric Hospitalist Special Interest Group (SIG) of SHM has been working tirelessly on several initiatives, including a revision of the Pediatric Hospital Medicine Core Competencies as well as additional work to develop Choosing Wisely 2.0 recommendations. These will help us ensure we are developing the best curricula for the next generation of pediatric hospitalists, while cutting back on unnecessary tests and procedures for those practicing today. Each of these initiatives, as well as the July conference, highlights the opportunities that we have within SHM to work with other like-minded providers who care for children. While we partner with all professionals across many organizations, like the American Academy of Pediatrics and the Academic Pediatric Association to name a few, I wanted to share my reflections on SHM and my appreciation for the “big tent” philosophy that has served us so well thus far.

Having an opportunity to sit on the board of SHM has allowed me a chance to really appreciate the efforts that this organization invests in all who care for patients in the hospital; we have an active group of advanced-practice providers, practice administrators, residents, students, academic hospitalists, and the list goes on and on. We collaborate with a number of spectacular societies dedicated to medical specialties, and we are always open to new ways of improving the methods of delivering care to patients, in hospitals, post-acute care facilities, homes – you name it! As health care delivery models continue to evolve, I believe we are well positioned to be leaders in the delivery of acute care medicine in the hospital and beyond.

I have also learned of happenings at the grassroots level by attending SHM chapter meetings across the United States. For example, the Hampton Roads Chapter led a great Point-of-Care Ultrasound (POCUS) workshop, and influenced by that, I shared an idea at home in Nashville – borrowing my son as a model to demonstrate ultrasound techniques that hospitalists can use to assist in clinical care. I hope you, as pediatric hospitalists, will see if you have a local chapter and attend a meeting; whether you are a member of SHM or not, you can mingle with those who provide acute care treatments to all your communities and share best practices. If you don’t see an SHM chapter close by, let’s get one going! SHM is here to help launch a chapter that can help bring your community together and provide education and networking closer to home.

If you can’t attend PHM in Seattle this year, I hope you will make every effort to be at PHM 2020, where our own SIG leader, Dr. Jeffrey Grill from Louisville, Ky., will be chairing the next rendition of this amazing conference. The SHM Meetings team led by Michelle Kann will be working tirelessly to make it a great event with continued growth in content and attendance.

Dr. Rehm is associate professor, pediatrics, and director, division of pediatric outreach medicine at Vanderbilt University and Monroe Carell Jr. Children’s Hospital at Vanderbilt, both in Nashville, Tenn. She is also a member of the SHM board of directors.

Each July, the largest gathering of pediatric hospitalists occurs, and 2019 is no different! This year, hospitalists who care for children will gather at Pediatric Hospital Medicine (PHM) in Seattle from July 25 to 28, with the goal of enhancing participants’ knowledge and competence in the areas of innovation, clinical medicine, education, health services, practice management, quality improvement, and research.

But what makes this year particularly special is the launch of the subspecialty exam for certification in pediatric hospital medicine coming later this fall, solidifying its growth and importance within hospital medicine and the entire health care landscape. The American Board of Pediatrics (ABP) has approved PHM as the newest board subspecialty with a 2-year fellowship accredited by the Accreditation Council for Graduate Medical Education (ACGME). This conference will be a great opportunity to join with others to review competencies for board review, as well as to network with those who are also navigating the road ahead.

During 2019, the Pediatric Hospitalist Special Interest Group (SIG) of SHM has been working tirelessly on several initiatives, including a revision of the Pediatric Hospital Medicine Core Competencies as well as additional work to develop Choosing Wisely 2.0 recommendations. These will help us ensure we are developing the best curricula for the next generation of pediatric hospitalists, while cutting back on unnecessary tests and procedures for those practicing today. Each of these initiatives, as well as the July conference, highlights the opportunities that we have within SHM to work with other like-minded providers who care for children. While we partner with all professionals across many organizations, like the American Academy of Pediatrics and the Academic Pediatric Association to name a few, I wanted to share my reflections on SHM and my appreciation for the “big tent” philosophy that has served us so well thus far.

Having an opportunity to sit on the board of SHM has allowed me a chance to really appreciate the efforts that this organization invests in all who care for patients in the hospital; we have an active group of advanced-practice providers, practice administrators, residents, students, academic hospitalists, and the list goes on and on. We collaborate with a number of spectacular societies dedicated to medical specialties, and we are always open to new ways of improving the methods of delivering care to patients, in hospitals, post-acute care facilities, homes – you name it! As health care delivery models continue to evolve, I believe we are well positioned to be leaders in the delivery of acute care medicine in the hospital and beyond.

I have also learned of happenings at the grassroots level by attending SHM chapter meetings across the United States. For example, the Hampton Roads Chapter led a great Point-of-Care Ultrasound (POCUS) workshop, and influenced by that, I shared an idea at home in Nashville – borrowing my son as a model to demonstrate ultrasound techniques that hospitalists can use to assist in clinical care. I hope you, as pediatric hospitalists, will see if you have a local chapter and attend a meeting; whether you are a member of SHM or not, you can mingle with those who provide acute care treatments to all your communities and share best practices. If you don’t see an SHM chapter close by, let’s get one going! SHM is here to help launch a chapter that can help bring your community together and provide education and networking closer to home.

If you can’t attend PHM in Seattle this year, I hope you will make every effort to be at PHM 2020, where our own SIG leader, Dr. Jeffrey Grill from Louisville, Ky., will be chairing the next rendition of this amazing conference. The SHM Meetings team led by Michelle Kann will be working tirelessly to make it a great event with continued growth in content and attendance.

Dr. Rehm is associate professor, pediatrics, and director, division of pediatric outreach medicine at Vanderbilt University and Monroe Carell Jr. Children’s Hospital at Vanderbilt, both in Nashville, Tenn. She is also a member of the SHM board of directors.