- Email: [email protected]
Response of alopecia areata of the beard to oral tofacitinib
Journal Pre-proof Response of alopecia areata of the beard to oral tofacitinib Karolina Louisa Suzanna Kerkemeyer, MBBS (Honours), BHlthSci, Jared Marc John, MBBS, MPH, Rodney Sinclair, MBBS, MD, FACD, Bevin Bhoyrul, MBBS, MRCP PII:
S0190-9622(19)32981-0
DOI:
https://doi.org/10.1016/j.jaad.2019.10.058
Reference:
YMJD 13958
To appear in:
Journal of the American Academy of Dermatology
Received Date: 24 September 2019 Revised Date:
16 October 2019
Accepted Date: 23 October 2019
Please cite this article as: Suzanna Kerkemeyer KL, John JM, Sinclair R, Bhoyrul B, Response of alopecia areata of the beard to oral tofacitinib, Journal of the American Academy of Dermatology (2019), doi: https://doi.org/10.1016/j.jaad.2019.10.058. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier on behalf of the American Academy of Dermatology, Inc.
1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42
Article type: Research letter Title of article: Response of alopecia areata of the beard to oral tofacitinib Authors: Karolina Louisa Suzanna Kerkemeyer, MBBS (Honours), BHlthSci,1 Jared Marc John, MBBS, MPH,1 Rodney Sinclair, MBBS, MD, FACD,1 and Bevin Bhoyrul, MBBS, MRCP1 1 Sinclair Dermatology, East Melbourne, Victoria Corresponding author: Name – Dr Karolina Louisa Suzanna Kerkemeyer; Postal address – Level 3, 2 Wellington Parade East Melbourne, Victoria 3002; Business telephone number – +61 3 9654 2426; Business fax number – +61 3 9650 9944; Email address – [email protected] Funding sources: Dr Bhoyrul was supported by The Geoffrey Dowling Fellowship from the British Association of Dermatologists. Conflict(s) of interest statement: Professor Sinclair has professional services associated with Leo Pharma, Amgen, Novartis, Merck & Co., Celgene, Coherus Biosciences, Janssen, Regeneron, MedImmune, GlaxoSmithKline, Cutanea, Samson Clinical, Boehringer Ingelheim, Pfizer, MSD, Oncobiologics, Roche, Eli Lilly and Company, Bayer, and Sun Pharma. Reprint requests: Dr Karolina Louisa Suzanna Kerkemeyer Text word count: 500 words Number of references: 5 Number of tables: 2 Number of figures: 0 Keywords: Beard; alopecia areata; alopecia areata of the beard; tofacitinib; JAK inhibitor; JAK pathway
2 43
Alopecia areata of the beard (BAA) affects 28% of men with alopecia areata (AA).1
44
Janus kinase (JAK) inhibitors have recently emerged as a promising targeted
45
treatment for AA. While most studies have focused on scalp hair regrowth, there is, to
46
our knowledge, only one case report documenting beard regrowth with ruxolitinib in a
47
patient with alopecia universalis (AU).3
48 49
We retrospectively reviewed the records of all male patients with scalp alopecia
50
areata (SAA) who were treated with oral tofacitinib at a specialist hair clinic between
51
July 2016 and August 2019. The inclusion criteria for this study were age ≥18 years,
52
BAA and treatment with oral tofacitinib for ≥3 months. The Severity of Alopecia
53
Tool (SALT) score was used to quantify scalp hair loss. Beard regrowth (none, partial
54
or complete) was measured by an independent observer evaluation of global
55
photographs. Data entry and analysis were performed using IBM SPSS Statistics v24.
56 57
45 patients met the inclusion criteria (Table I). Nineteen men had total beard loss, 24
58
had multiple discrete patches, and two had a solitary patch of BAA. Ten men
59
achieved complete beard regrowth after 5.0–28.0 months of treatment (mean 16.0)
60
(Table II). The mean disease duration among complete beard responders was 93.2
61
months (range 12.0–252.0). 60% of men who achieved complete beard regrowth also
62
achieved complete scalp hair regrowth. Of the 19 patients with partial beard regrowth,
63
15 achieved partial and one achieved complete scalp hair regrowth. Of 16 patients
64
with no beard regrowth, 14 had no regrowth and two had partial regrowth of scalp
65
hair.
66
3 67
There were no serious adverse events. Mild adverse events were seen in 10 patients
68
and included upper respiratory infections, elevated liver transaminases, fatigue and
69
acne. None required treatment cessation or dose modification.
70 71
BAA is associated with a high prevalence of anxiety and depressive symptoms.1-3
72
Some religions e.g. Islam, Orthodox Judaism and Sikhism require adult males to grow
73
a full beard.3 One of our patients regularly competes in beard championships, and the
74
loss of >50% of his beard as a result of BAA caused significant distress, see Figure 1
75
(available at https://data.mendeley.com/datasets/nh2h672rhc/1).
76 77
Our results demonstrate a strong correlation between the extent of beard and scalp
78
hair regrowth, suggesting that these hair-bearing sites may respond similarly to oral
79
tofacitinib. In contrast to SAA studies which showed an inverse association between
80
disease duration and treatment response, no such association was observed in our
81
BAA cohort.4,5 On the contrary, patients with complete beard regrowth had a longer
82
mean disease duration. The age of the patient, BAA phenotype (patchy or total beard
83
loss) and duration of treatment did not influence the degree of beard response. As
84
with our BAA cohort, age did not predict improvement in SALT score in 90 patients
85
with severe SAA treated with oral tofacitinib.4
86 87
Our findings suggest that oral tofacitinib might be a promising therapeutic option for
88
patients with BAA. We suggest that prospective clinical trials evaluating oral JAK
89
inhibitors in AA should seek to include beard assessment in their protocols to
90
determine their effectiveness for the treatment of BAA.
91
4 92 93 94 95
References 1. Cervantes J, Fertig RM, Maddy A, et al. Alopecia areata of the beard: a review of the literature. Am J Clin Dermatol. 2017;18:789-796. 2. Saceda-Corralo D, Grimalt R, Fernández-Crehuet P, et al. Beard alopecia
96
areata: a multicentre review of 55 patients. J Eur Acad Dermatol Venereol.
97
2017;31:187-192.
98
3. Ramot Y, Zlotogorski. Complete regrowth of beard hair with ruxolitinib in an
99
alopecia universalis patient. Skin Appendage Disord. 2018;4:122-124.
100
4. Liu LY, Craiglow BG, Dai F, et al. Tofacitinib for the treatment of severe
101
alopecia areata and variants: a study of 90 patients. J Am Acad Dermatol.
102
2016;76:22-28.
103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126
5. Phan K, Sebaratnam DF. JAK inhibitors for alopecia areata: a systematic review and meta-analysis. J Eur Acad Dermatol Venereol. 2019;33:850-856.
5 127
Abbreviation and acronym list
128
Alopecia areata of the beard = BAA
129
Alopecia areata = AA
130
Alopecia totalis = AT
131
Alopecia universalis = AU
132
Janus kinase = JAK
133
Mg = milligram
134
Scalp alopecia areata = SAA
135
Severity of Alopecia Tool = SALT
136
SD = standard deviation
137 138 139 140 141 142 143 144 145 146 147 148 149 150 151
6 152 Table 1. Patient demographics and clinical characteristics (n = 45) Findings N (%) Mean ± SD Age (years) 38.6 ± 12.8 AA subtype: Solitary patch 6 (13.3) Multiple patches 13 (28.9) Diffuse 8 (17.8) AT 4 (8.9) AU 14 (31.1) SALT score pre-tofacitinib 62.0 ± 38.9 SALT score post-tofacitinib 41.7 ± 38.5 BAA subtype: Solitary patch 2 (4.5) Multiple patches 24 (53.3) Total beard loss 19 (42.2) Duration of BAA (months)† 61.2 ± 74.1 Dose of oral tofacitinib (mg) 7.2 ± 4.0 Duration of oral tofacitinib treatment (months) 15.5 ± 13.8 1 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 1
Median (Range) 36.0 (20.0–67.0)
69.0 (2.0–100.0) 29.0 (0.0–100.0)
28.0 (3.0–324.0) 7.5 (1.0–20.0) 13.0 (3.0–86.0)
AA, Alopecia areata; AT, Alopecia totalis; AU, Alopecia universalis; SD, Standard deviation; SALT, Severity of Alopecia Tool; BAA, Alopecia areata of the beard; Mg, milligram †Duration of current episode of BAA not documented in six patients
7 180
Table 2. Response to treatment with oral tofacitinib (n = 45) Degree of beard regrowth None Partial Complete Number of patients (%) 16 (35.6) 19 (42.2) 10 (22.2) BAA subtype, N (%): Solitary patch 2 (4.5) 0 (0.0) 0 (0.0) Multiple patches 8 (17.8) 9 (20.0) 7 (15.6) Total beard loss 6 (13.3) 10 (22.2) 3 (6.7) Degree of scalp hair regrowth, N (%): None 14 (31.1) 3 (6.7) 1 (2.2) Partial 2 (4.5) 15 (33.3) 3 (6.7) Complete 0 (0.0) 1 (2.2) 6 (13.3) Duration of BAA (months), mean ± 58.1 ± 78.5 45.1 ± 58.1 93.2 ± 72.5 SD 181 2
2
BAA, Alopecia areata of the beard; N; count value; SD, Standard deviation
S0190-9622(19)32981-0
DOI:
https://doi.org/10.1016/j.jaad.2019.10.058
Reference:
YMJD 13958
To appear in:
Journal of the American Academy of Dermatology
Received Date: 24 September 2019 Revised Date:
16 October 2019
Accepted Date: 23 October 2019
Please cite this article as: Suzanna Kerkemeyer KL, John JM, Sinclair R, Bhoyrul B, Response of alopecia areata of the beard to oral tofacitinib, Journal of the American Academy of Dermatology (2019), doi: https://doi.org/10.1016/j.jaad.2019.10.058. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier on behalf of the American Academy of Dermatology, Inc.
1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42
Article type: Research letter Title of article: Response of alopecia areata of the beard to oral tofacitinib Authors: Karolina Louisa Suzanna Kerkemeyer, MBBS (Honours), BHlthSci,1 Jared Marc John, MBBS, MPH,1 Rodney Sinclair, MBBS, MD, FACD,1 and Bevin Bhoyrul, MBBS, MRCP1 1 Sinclair Dermatology, East Melbourne, Victoria Corresponding author: Name – Dr Karolina Louisa Suzanna Kerkemeyer; Postal address – Level 3, 2 Wellington Parade East Melbourne, Victoria 3002; Business telephone number – +61 3 9654 2426; Business fax number – +61 3 9650 9944; Email address – [email protected] Funding sources: Dr Bhoyrul was supported by The Geoffrey Dowling Fellowship from the British Association of Dermatologists. Conflict(s) of interest statement: Professor Sinclair has professional services associated with Leo Pharma, Amgen, Novartis, Merck & Co., Celgene, Coherus Biosciences, Janssen, Regeneron, MedImmune, GlaxoSmithKline, Cutanea, Samson Clinical, Boehringer Ingelheim, Pfizer, MSD, Oncobiologics, Roche, Eli Lilly and Company, Bayer, and Sun Pharma. Reprint requests: Dr Karolina Louisa Suzanna Kerkemeyer Text word count: 500 words Number of references: 5 Number of tables: 2 Number of figures: 0 Keywords: Beard; alopecia areata; alopecia areata of the beard; tofacitinib; JAK inhibitor; JAK pathway
2 43
Alopecia areata of the beard (BAA) affects 28% of men with alopecia areata (AA).1
44
Janus kinase (JAK) inhibitors have recently emerged as a promising targeted
45
treatment for AA. While most studies have focused on scalp hair regrowth, there is, to
46
our knowledge, only one case report documenting beard regrowth with ruxolitinib in a
47
patient with alopecia universalis (AU).3
48 49
We retrospectively reviewed the records of all male patients with scalp alopecia
50
areata (SAA) who were treated with oral tofacitinib at a specialist hair clinic between
51
July 2016 and August 2019. The inclusion criteria for this study were age ≥18 years,
52
BAA and treatment with oral tofacitinib for ≥3 months. The Severity of Alopecia
53
Tool (SALT) score was used to quantify scalp hair loss. Beard regrowth (none, partial
54
or complete) was measured by an independent observer evaluation of global
55
photographs. Data entry and analysis were performed using IBM SPSS Statistics v24.
56 57
45 patients met the inclusion criteria (Table I). Nineteen men had total beard loss, 24
58
had multiple discrete patches, and two had a solitary patch of BAA. Ten men
59
achieved complete beard regrowth after 5.0–28.0 months of treatment (mean 16.0)
60
(Table II). The mean disease duration among complete beard responders was 93.2
61
months (range 12.0–252.0). 60% of men who achieved complete beard regrowth also
62
achieved complete scalp hair regrowth. Of the 19 patients with partial beard regrowth,
63
15 achieved partial and one achieved complete scalp hair regrowth. Of 16 patients
64
with no beard regrowth, 14 had no regrowth and two had partial regrowth of scalp
65
hair.
66
3 67
There were no serious adverse events. Mild adverse events were seen in 10 patients
68
and included upper respiratory infections, elevated liver transaminases, fatigue and
69
acne. None required treatment cessation or dose modification.
70 71
BAA is associated with a high prevalence of anxiety and depressive symptoms.1-3
72
Some religions e.g. Islam, Orthodox Judaism and Sikhism require adult males to grow
73
a full beard.3 One of our patients regularly competes in beard championships, and the
74
loss of >50% of his beard as a result of BAA caused significant distress, see Figure 1
75
(available at https://data.mendeley.com/datasets/nh2h672rhc/1).
76 77
Our results demonstrate a strong correlation between the extent of beard and scalp
78
hair regrowth, suggesting that these hair-bearing sites may respond similarly to oral
79
tofacitinib. In contrast to SAA studies which showed an inverse association between
80
disease duration and treatment response, no such association was observed in our
81
BAA cohort.4,5 On the contrary, patients with complete beard regrowth had a longer
82
mean disease duration. The age of the patient, BAA phenotype (patchy or total beard
83
loss) and duration of treatment did not influence the degree of beard response. As
84
with our BAA cohort, age did not predict improvement in SALT score in 90 patients
85
with severe SAA treated with oral tofacitinib.4
86 87
Our findings suggest that oral tofacitinib might be a promising therapeutic option for
88
patients with BAA. We suggest that prospective clinical trials evaluating oral JAK
89
inhibitors in AA should seek to include beard assessment in their protocols to
90
determine their effectiveness for the treatment of BAA.
91
4 92 93 94 95
References 1. Cervantes J, Fertig RM, Maddy A, et al. Alopecia areata of the beard: a review of the literature. Am J Clin Dermatol. 2017;18:789-796. 2. Saceda-Corralo D, Grimalt R, Fernández-Crehuet P, et al. Beard alopecia
96
areata: a multicentre review of 55 patients. J Eur Acad Dermatol Venereol.
97
2017;31:187-192.
98
3. Ramot Y, Zlotogorski. Complete regrowth of beard hair with ruxolitinib in an
99
alopecia universalis patient. Skin Appendage Disord. 2018;4:122-124.
100
4. Liu LY, Craiglow BG, Dai F, et al. Tofacitinib for the treatment of severe
101
alopecia areata and variants: a study of 90 patients. J Am Acad Dermatol.
102
2016;76:22-28.
103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126
5. Phan K, Sebaratnam DF. JAK inhibitors for alopecia areata: a systematic review and meta-analysis. J Eur Acad Dermatol Venereol. 2019;33:850-856.
5 127
Abbreviation and acronym list
128
Alopecia areata of the beard = BAA
129
Alopecia areata = AA
130
Alopecia totalis = AT
131
Alopecia universalis = AU
132
Janus kinase = JAK
133
Mg = milligram
134
Scalp alopecia areata = SAA
135
Severity of Alopecia Tool = SALT
136
SD = standard deviation
137 138 139 140 141 142 143 144 145 146 147 148 149 150 151
6 152 Table 1. Patient demographics and clinical characteristics (n = 45) Findings N (%) Mean ± SD Age (years) 38.6 ± 12.8 AA subtype: Solitary patch 6 (13.3) Multiple patches 13 (28.9) Diffuse 8 (17.8) AT 4 (8.9) AU 14 (31.1) SALT score pre-tofacitinib 62.0 ± 38.9 SALT score post-tofacitinib 41.7 ± 38.5 BAA subtype: Solitary patch 2 (4.5) Multiple patches 24 (53.3) Total beard loss 19 (42.2) Duration of BAA (months)† 61.2 ± 74.1 Dose of oral tofacitinib (mg) 7.2 ± 4.0 Duration of oral tofacitinib treatment (months) 15.5 ± 13.8 1 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 1
Median (Range) 36.0 (20.0–67.0)
69.0 (2.0–100.0) 29.0 (0.0–100.0)
28.0 (3.0–324.0) 7.5 (1.0–20.0) 13.0 (3.0–86.0)
AA, Alopecia areata; AT, Alopecia totalis; AU, Alopecia universalis; SD, Standard deviation; SALT, Severity of Alopecia Tool; BAA, Alopecia areata of the beard; Mg, milligram †Duration of current episode of BAA not documented in six patients
7 180
Table 2. Response to treatment with oral tofacitinib (n = 45) Degree of beard regrowth None Partial Complete Number of patients (%) 16 (35.6) 19 (42.2) 10 (22.2) BAA subtype, N (%): Solitary patch 2 (4.5) 0 (0.0) 0 (0.0) Multiple patches 8 (17.8) 9 (20.0) 7 (15.6) Total beard loss 6 (13.3) 10 (22.2) 3 (6.7) Degree of scalp hair regrowth, N (%): None 14 (31.1) 3 (6.7) 1 (2.2) Partial 2 (4.5) 15 (33.3) 3 (6.7) Complete 0 (0.0) 1 (2.2) 6 (13.3) Duration of BAA (months), mean ± 58.1 ± 78.5 45.1 ± 58.1 93.2 ± 72.5 SD 181 2
2
BAA, Alopecia areata of the beard; N; count value; SD, Standard deviation