Advances in Alopecia Areata Treatment and Assessment

National Alopecia Areata Foundation (NAAF) Board of Directors member Dr Brett King updates us on what is new and evolving in the care of patients with alopecia areata (AA) in this interview with The Dermatologist. Every September, NAAF celebrates AA Awareness Month, recognizing all those affected by the disease. Visit https://www.naaf.org/awareness-month for more information.

The Dermatologist: Can you briefly review the new treatments for AA?

Dr King: Until recently, there were no approved treatments for AA and no reliably effective treatments for moderate to severe disease. Dermatologists sometimes used oral corticosteroids, methotrexate, and cyclosporine to treat moderate to severe AA, but these medications are very rarely helpful, not to mention that oral corticosteroids and cyclosporine cannot be used long term due to significant adverse events, which means there was tremendous unmet need.

In June 2022, the oral Janus kinase (JAK) inhibitor baricitinib was approved by the US Food and Drug Administration for adults with severe AA,¹ marking a historic event for dermatology and people living with this often awful disease. Finally, there was treatment. Then 1 year later, in June 2023, the JAK inhibitor ritlecitinib was approved for adults and adolescents with severe AA,² marking another historic event, a treatment option for patients aged 12 years and older.

It is amazing how quickly the treatment landscape is advancing, and in 2024 we will hopefully see approval of a third JAK inhibitor, deuruxolitinib. At last, we have emerged from the desert, and there is not just a little water to drink but a rich oasis.

The Dermatologist: Can you explain how AA is classified and why it is classified that way?

Dr King: Because we did not have reliably effective treatments for AA until recently, our thinking about disease severity classification did not significantly evolve since at least 1902 when the terms patchy AA, alopecia totalis, alopecia universalis, and ophiasis could be found in the literature.³

Then, in 2004, a group of AA experts published the Severity of Alopecia Tool (SALT),⁴ an instrument for assessing scalp hair loss (SALT score 0=no scalp hair loss, SALT score 100=100% scalp hair loss). While SALT was used little, if at all, for a decade afterward, its critical importance was realized immediately when clinical trials of JAK inhibitors began in 2014.

In 2020, publication of work with AA experts and patients with AA gave us both a disease severity scale, the AA-IGA, and the treatment goal in recent clinical trials. In the AA-IGA, there is none (0% scalp hair loss), limited AA (1%–20% scalp hair loss), moderate AA (21%–49% scalp hair loss), severe AA (50%–94% scalp hair loss), and very severe AA (95%–100% scalp hair loss).

To conduct a clinical trial properly, one needs to know what matters to patients. In other words, what is a clinically meaningful change for patients during treatment? In developing the AA-IGA, we learned that successful treatment of patients with ≥50% scalp hair loss (baseline SALT score ≥50) would be hair regrowth resulting in ≤20% scalp hair loss (SALT score ≤20).⁵

This work gives context to recent clinical trials of JAK inhibitors, which have enrolled patients with a baseline SALT score ≥50, or severe AA. The primary endpoint in these trials of severe AA is a SALT score ≤20.

The Dermatologist: How is the assessment of AA severity changing?

Dr King: Scalp hair loss is often, maybe even usually, a central feature of AA, and so it makes sense that the amount of scalp hair loss has been the focus of severity assessment. Recognizing, however, that there are other features besides extent of scalp hair loss that should be considered in disease severity,⁶ a group of experts came together to devise a more complete approach to severity assessment. This work culminated in the AA Scale (AASc), published in 2021.⁷

The AASc is anchored in the extent of scalp hair loss (parallel to the AA-IGA) but also accounts for the involvement of eyebrows and eyelashes, inadequate treatment response, rapidly progressing disease, and the negative psychosocial impact of AA. The mild or moderate AA severity rating increases by 1 level if 1 or more of the following is present: negative impact on psychosocial functioning resulting from AA, noticeable involvement of eyebrows and/or eyelashes, inadequate response after at least 6 months of treatment, and a diffuse (multifocal) positive hair pull test consistent with rapidly progressing AA.

The AASc acknowledges that the patient with mild or moderate scalp hair loss may have moderate or severe disease, respectively, related to other disease features that are present. It is easy to use in clinic and is an important advancement because AA is not unidimensional, and we need to be more expansive in the way we evaluate patients.

The Dermatologist: Why it is important for dermatologists to see AA patients?

Dr King: AA and other hair loss disorders are dermatologic disorders, and dermatologists should be adept at recognizing and caring for patients with these conditions.

Patients with severe AA have long felt dismissed by their doctors, and it was said that AA was cosmetic. This is absurd considering the abnormal distortion of appearance that occurs when large patches of hair loss happen or when there is significant eyebrow loss. In the past, when there were no effective treatments, it was challenging to care for these patients. Not having effective treatment to offer, dermatologists said things like, “At least it is just hair” or “At least you have a nice-shaped head” or “That wig looks good.” While meaning well, these words do not acknowledge the often awful experience of patients with AA.

Imagine your physical appearance (or even worse, your child’s) changing over days or weeks until you no longer recognize yourself and others do not recognize you either. Imagine appearing gravely ill but not being sick.^8,9 AA causes profound sadness that sometimes becomes depression. It causes anxiety.¹⁰ People withdraw from life. It is awful.

The availability of treatments will change all of this. Dermatologists will become comfortable treating patients, and I am hopeful that this comfort will lead to acknowledging patients’ experiences; it is hugely important to them.

The Dermatologist: With September being AA Awareness Month, are there any additional tips or insights you would like to share with your colleagues?

Dr King: Think about oral minoxidil for AA. While this medicine has garnered a lot of attention recently for the treatment of androgenetic alopecia, a clinical trial of oral minoxidil published in 1987 showed that almost 20% of patients, most with moderate to severe AA, treated with minoxidil 5 mg twice daily had a cosmetically acceptable result.¹¹ This led me to begin using it in combination with JAK inhibitors for AA, and results of a small retrospective series of patients from my clinic suggest that most patients treated with oral minoxidil in combination with JAK inhibitors achieve near-complete scalp hair regrowth.¹² Indeed, the majority of my patients taking JAK inhibitors are also taking oral minoxidil. And I have many other patients with AA taking oral minoxidil monotherapy.

With recent advancements, the care of patients with AA has changed forever and so has dermatology. JAK inhibitors have made this possible, creating remarkable awareness of AA among the public and the pharmaceutical industry. Presently, there are multiple clinical trials in AA happening, not just of JAK inhibitors but also medications with other mechanisms of action. We have a lot to celebrate.

References

1. King B, Ohyama M, Kwon O, et al. Two phase 3 trials of baricitinib for alopecia areata. N Engl J Med. 2022;386(18):1687-1699. doi:10.1056/NEJMoa2110343
2. King B, Zhang X, Harcha WG, et al. Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomized, double-blind, multicentre, phase 2b-3 trial. Lancet. 2023;401(10387):1518-1529. doi:10.1016/S0140- 6736(23)00222-2
3. Déhu P. Pelade. In: Besnier E, Brocq L, Jacquet L, eds.Dermatological Practice: Treatise on Applied Dermatology. Masson Et Cie; 1904:647-714.
4. Olsen EA, Hordinsky MK, Price VH, et al. Alopecia areata investigational assessment guidelines—part II. National Alopecia Areata Foundation. J Am Acad Dermatol. 2004;51(3):440-447. doi:10.1016/j.jaad.2003.09.032
5. Wyrwich KW, Kitchen H, Knight S, et al. The Alopecia Areata Investigator Global Assessment (AA-IGA) scale: a measure for evaluating clinically meaningful success in clinical trials. Br J Dermatol. 2020;183(4):702-709. doi:10.1111/ bjd.18883
6. King BA, Senna MM, Ohyama M, et al. Defining severity in alopecia areata: cur- rent perspectives and a multidimensional framework. Dermatol Ther (Heidelb). 2022;12(4):825-834. doi:10.1007/s13555-022-00711-3
7. King BA, Mesinkovska NA, Craiglow B, et al. Development of the alopecia areata scale for clinical use: results of an academic-industry collaborative effort. J Am Acad Dermatol. 2022;86(2):359-364. doi:10.1016/j.jaad.2021.08.043
8. Craiglow BG, Borges KA, King BA. The close resemblance of patients with severe alopecia areata and those with cancer: what hair tells us about wellness—or grave illness. J Am Acad Dermatol. 2022;86(3):e125-e126. doi:10.1016/j. jaad.2021.10.031
9. Creadore A, Manjaly P, Li SJ, et al. Evaluation of stigma toward individuals with alopecia. JAMA Dermatol. 2021;157(4):392-398. doi:10.1001/jamadermatol.2020.5732
10. Mesinkovska NA, King B, Mirmirani P, Ko J, Cassella J. Burden of illness in alo- pecia areata: a cross-sectional online survey study. J Invest Dermatol Symp Proc. 2020;20(1):S62-S68. doi:10.1016/j.jisp.2020.05.007
11. Fiedler-Weiss VC, Rumsfield J, Buys CM, West DP, Wendrow A. Evaluation of oral minoxidil in the treatment of alopecia areata. Arch Dermatol. 1987;123(11):1488-1490.
12. Wambier CG, Craiglow BG, King BA. Combination tofacitinib and oral minoxidil treatment for severe alopecia areata. J Am Acad Dermatol. 2021;85(3):743-745. doi:10.1016/j.jaad.2019.08.080