EFFICACY OF COMPOUND BETAMETHASONE COMBINED WITH COMPOUND GLYCYRRHIZIN IN THE TREATMENT OF SEVERE ACTIVE ALOPECIA AREATA
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Acta Medica Mediterranea, 2020, 36: 347
EFFICACY OF COMPOUND BETAMETHASONE COMBINED WITH COMPOUND GLYCYRRHIZIN
IN THE TREATMENT OF SEVERE ACTIVE ALOPECIA AREATA
Youyu Sheng#, Jun Zhao#, Jingwen Ma, Sisi Qi, Ruiming Hu, Qinping Yang*
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China
#
These authors contributed equally to this work
ABSTRACT
Objective: To evaluate the efficacy of combination therapy with compound betamethasone and compound glycyrrhizin in the
treatment of severe active alopecia areata.
Methods: A monocentric controlled study with 100 patients was conducted in Huashan Hospital, Fudan University, Shanghai,
China. Patients with severe active alopecia areata (severity of alopecia tool score >50, and ongoing hair loss proved by positive
hair-pulling test) were randomized into two groups. Compound betamethasone was intramuscular injected every three weeks for four
times in each group, and combined with oral compound glycyrrhizin tablets for 24 weeks in the concurrent treatment group. Efficacy
was assessed by measuring the response rate during treatment, as well as the relapse rate off treatment.
Results: The efficacy rate at 24-weeks of the combination therapy group (72.00%) was significantly higher than that of mono-
therapy group (46.00%) (P=0.008). The efficacy rate at 36-weeks of the combination therapy group (50.00%) was significantly higher
than the monotherapy group (28.00%) (P=0.024). The relapse rate at 36-weeks of the combination therapy group (36.11%) was signif-
icantly lower than that of the monotherapy group (65.22%) (P=0.029). No severe adverse event was noted.
Conclusions: The combination treatment of compound betamethasone injection with compound glycyrrhizin tablet showed bet-
ter efficacy and durability of responses than single betamethasone treatment in severe active alopecia areata.
Keywords: Alopecia areata, treatment, compound betamethasone injection, compound glycyrrhizin tablet.
DOI: 10.19193/0393-6384_2020_1_53
Received November 30, 2018; Accepted February 20, 2019
Introduction effective way to treat severe active AA(2). However,
the unstable efficacy rate, high recurrence rate and
Alopecia areata (AA) is a common autoim- adverse effects of systemic glucocorticoid treatment
mune disease characterized by sudden hair loss with are disappointing. Glycyrrhizin, the primary active
a lifetime risk of 2.1% in ordinary people(1). About constituent of liquorice root, is commonly used in
14~25% of AA patients will develop into severe Asia to treat patients with chronic hepatitis. Further-
types, with more than 50% scalp area involved, in- more, glycyrrhizin has a wide range of pharmaco-
cluding multifocal patchy pattern, ophiasis type, logical action, including a steroid-like function and
alopecia totalis and alopecia universalis(2). These immunoregulation of T cells activation, which may
patients usually carry significant psychological bur- inhibit autoimmune reaction. The efficacy of glycyr-
dens due to poor prognosis and apparent appearance rhizin for the treatment of mild to moderate AA has
disturbance(3). Severe alopecia areata patients are less been confirmed by several studies(4-6). We conduct-
sensitive to conventional treatment. Although there is ed this randomized controlled study to evaluate the
still no consensus on the dosage, dosage form, meth- efficacy and safety of the combination therapy with
od and course of glucocorticoid administration in compound betamethasone and compound glycyrrhiz-
severe AA, systemic glucocorticoid is a routine and in in the treatment of severe active alopecia areata.348 Youyu Sheng, Jun Zhao et Al
Materials and methods Each injection contains 5mg betamethasone dipro-
pionate and 2mg betamethasone phosphate sodium.
Ethics statement The compound glycyrrhizin tablets were produced
The monocentric controlled study was approved by the Minophagen Pharmaceutical Co., Ltd (Ja-
by the ethics committee of Huashan Hospital, which pan). Each tablet contains 25 mg glycyrrhizin, 35mg
is affiliated with Fudan University. All participants aminoacetic acid and 25mg methionine.
provided their written informed consent to partici-
pate before enrolment. The study was performed at Patient’s assessment and outcomes definition
the dermatology outpatient clinic of Huashan Hospi- The patient’s basic information, including gen-
tal, which is affiliated with Fudan University, locat- der, age, disease duration, hereditary history and past
ed in Shanghai, China. medical history was recorded at the first visit. Fol-
low-up assessments were done once every 12 weeks
Participants to evaluate disease activity, severity, recovery and
In this monocentric randomized controlled potential reoccurrence of AA. Photographic doc-
clinical trial, we included 100 patients diagnosed umentation was done with a digital camera in four
with severe active alopecia areata at the dermatol- standardized views: frontal, occipital and both tem-
ogy outpatient clinic of Huashan Hospital, affiliated porals. Activity of the disease was determined by the
with Fudan University, between January 2016 and hair-pulling test and severity of the disease was eval-
September 2017. uated with the Severity of Alopecia Tool (SALT)(7).
The inclusion criteria were as follows: The SALT scores were noted at baseline, 12-weeks,
• 18-70 years old; 24-weeks and 36-weeks. Adverse events were also
• Multifocal patchy pattern or ophiasis pattern monitored at each visit.
alopecia areata with a bald surface exceeding 50% In this study, the primary efficacy indicator was
of the scalp, alopecia totalis (AT) and alopecia uni- a 24-week efficacy rate. Secondary efficacy indica-
versalis (AU); tors included:
• With present activity of the disease clinically • 12-week and 36-week efficacy rates;
corresponding to ongoing hair loss proved by posi- • Incidence of recurrence off treatment. Effica-
tive hair-pulling test or with a rapid progress to AT/ cy rate was defined as the proportion of good or com-
AU within 6 months; plete responders with 50% or greater hair regrowth
• Without other skin and other types of hair dis- from baseline based on the SALT score. Percentage
orders (androgenic alopecia, scarring alopecia, sec- of hair regrowth was evaluated every 12 weeks.
ondary syphilis, telogen effluvium); Patients with ≥95% hair regrowth were defined as
• Without major cardiovascular, liver, kidney or complete responders, ≥50% butEfficacy of compound betamethasone combined with compound glycyrrhizin in the treatment of... 349
principle. The analysis of safety was performed on Poor Partial Good Complete Efficacy
the safety set (SS), which included all subjects that Efficacy Response
(n/N)
Response
(n/N)
Response
(n/N)
Response
(n/N) Rate (%)
had used products at least once. Statistical analysis
Group A 17/50 15/50 15/50 3/50 36.00
was performed using the Chi-square test and the sig- 12-week
Group B 8/50 16/50 23/50 3/50 52.00
nificance level was set at p0.05) (Table 2).
Disease duration (month) 7.51±11.93 7.56±14.21
At the 36-week visit, relapse of AA occurred
Duration of progression
into severe AA (month) 2.84±2.41 2.58±1.99 in 15 good responders in Group A and 13 in Group
AT 5 6 B. Therefore, at the 36-week visit, only 28.00%
AU 14 14
of patients in Group A and 50.00% of patients in
AA types Multifocal patchy 21 18
Group B showed greater than 50% hair regrowth.
Ophiasis 3 5
The efficacy rate of combination therapy group
at 36-weeks was significantly higher than the
Acute diffuse AA 7 7
monotherapy group (P=0.024) (Table 2). To assess
the durability of treatment effectiveness, the relapse
No 26 28
Recurrent AA
Yes 24 22
rates of the two groups were evaluated at the 36-week
History
Yes 20 20
visit. The number of good and complete responders
of severe AA
No 30 30 at 24-weeks were calculated as denominators.
Family history
Yes 7 11 Relapse of AA occurred in 15 of 23 good responders
No 43 39 in Group A and 13 of 36 good responders in Group
S1 (case) 0 0 B, respectively. The relapse rate of the combination
S2 (case) 0 0 therapy group was significantly lower than the
Severity S3 (case) 19 20 monotherapy group (P=0.029) (Table 3).
S4 (case) 22 21 Good and350 Youyu Sheng, Jun Zhao et Al
Discussion Conclusion
Severe alopecia areata (AA) causes significant In conclusion, the combination treatment of
harm to a patient’s appearance and self-esteem. Up compound betamethasone injections with compound
to now, there is still no curable treatment for severe glycyrrhizin tablets showed better efficacy and du-
AA. Many patients have to wear wigs as a last choice rability of responses than single steroid treatment in
after a long course of the disease. Systematic steroids severe active alopecia areata.
were first applied in the treatment of severe AA in
1952(8). The efficacy of systematic steroids has been
supported by many studies in adults or children(9-14).
However, relapses and side effects are still unsolved
problems(15-17). Therefore, exploring effective com- References
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