Signposts to the Promised Land in Alopecia Areata.

Clinical ImplicationsCosts associated with emerging therapies will require disease severity to be redefined.The Severity of Alopecia Tool score was not predictive of life quality.Patient-reported outcomes provide a more accurate depiction of diminished life quality. Costs associated with emerging therapies will require disease severity to be redefined.The Severity of Alopecia Tool score was not predictive of life quality.Patient-reported outcomes provide a more accurate depiction of diminished life quality. Alopecia areata (AA) is an autoimmune disease of the hair and nails. Although genotype alters the risk, the etiology remains unclear. AA typically presents as one or more hairless patches; however, full loss of scalp hair occurs in about 15% of patients (Cranwell et al., 2019Cranwell W.C. Lai V.W. Photiou L. Meah N. Wall D. Rathnayake D. et al.Treatment of alopecia areata: an Australian expert consensus statement.Australas J Dermatol. 2019; 60: 163-170Crossref PubMed Scopus (67) Google Scholar; Ikeda, 1965Ikeda T. A new classification of alopecia areata.Dermatologica. 1965; 131: 421-445Crossref PubMed Scopus (171) Google Scholar). The relative ease in semiobjectively quantifying the area of bald scalp has resulted in the Severity of Alopecia Tool (SALT) becoming the main measure of disease severity among physicians (Olsen and Canfield, 2016Olsen E.A. Hordinsky M.K. Price V.H. et al.Alopecia areata investigational assessment guidelines–Part II.J Am Acad Dermatol. 2004; 51 (440–7)Abstract Full Text Full Text PDF Google Scholar). However, Senna et al., 2022Senna M. Ko J. Glashofer M. Walker C. Ball S. Edson-Heredia E. et al.Predictors of QOL in patients with alopecia areata.J Invest Dermatol. 2022; 142: 2646-2650Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar have substantiated the intimation that the area of AA involvement does not necessarily predict the patients in most need of treatment. The SALT score, for example, does not include eyebrow and eyelash loss, which can result in significant functional impairment, allowing dust and sweat to enter the eyes. This study identifies the key data that connect functional loss to impact on QoL and link self-reported severity with QoL impact while showing that “SALT score alone was insufficient as a proxy for QoL impact.” As such, this translational study shifts the focus from the most objectively measurable outcomes of disease involvement toward the narrative that typically motivates a patient with AA to seek care: the impact on their QoL. Until recently, AA therapies were infrequently examined in randomized controlled trials, and primary efficacy endpoints were limited to the change in SALT score. However, this study comes at a time when industry-sponsored, randomized controlled trials have led to the licensing of the first disease-specific, systemic immunotherapy for AA in baricitinib by the Food and Drug Administration. Although the emergence of realistic therapeutic options is a watershed moment for patients with AA, significant questions regarding cost implications have been posed. As a result, the concept of AA severity as an arbiter of access to therapy is seeing renewed focus and increased scrutiny. The point prevalence of AA is in the order of 1‒2 per 1,000 people (Safavi, 1992Safavi K. Prevalence of alopecia areata in the First National Health and Nutrition Examination Survey.Arch Dermatol. 1992; 128: 702Crossref PubMed Scopus (188) Google Scholar). In the United States, with a population of almost 330 million, this equates to approximately 329,500‒659,000 people. Lifetime risk is estimated at 1.7‒2.1% on the basis of long-term United States data (Mirzoyev et al., 2014Mirzoyev S.A. Schrum A.G. Davis M.D.P. Torgerson R.R. Lifetime incidence risk of alopecia areata estimated at 2.1% by Rochester Epidemiology Project, 1990–2009.J Invest Dermatol. 2014; 134: 1141-1142Abstract Full Text Full Text PDF PubMed Scopus (193) Google Scholar; Safavi et al., 1995Safavi K.H. Muller S.A. Suman V.J. Moshell A.N. Melton 3rd, L.J. Incidence of alopecia areata in Olmsted County, Minnesota, 1975 through 1989.Mayo Clin Proc. 1995; 70: 628-633Abstract Full Text Full Text PDF PubMed Scopus (459) Google Scholar), suggesting that annually, approximately 2 per 10,000 are expected to develop AA for the first time. Globally, this would equate to roughly 1,550,600 new cases a year and with a relatively similar frequency among women as among men (Table 1). With approximately 40% of patients developing a single patch that resolves spontaneously within 6 months (Ikeda, 1965Ikeda T. A new classification of alopecia areata.Dermatologica. 1965; 131: 421-445Crossref PubMed Scopus (171) Google Scholar), it is likely that the true incidence and prevalence of AA is underestimated because many of those affected will not have accessed medical care.Table 1The Estimated Prevalence of AA and Associated Costs of Baricitinib Treatment According to List Price for Selected CountriesCountryEstimated Population (Millions)Estimated AA Population1Based on an estimated point prevalence of 0.1‒0.2% (Safavi, 1992)Estimated New AA Diagnoses Per Year2Based on an estimated lifetime risk of 1.7‒2.1% (0.02% per year) (Mirzoyev et al., 2014; Safavi et al., 1995)Estimated Cost of Bbaricitinib Treatment for all AA Per Year3Based on the list price of baricitinib ($2,497.20 per 30 days) if all estimated patients with AA were treated (Sinclair, 2022) ($ Millions)Estimated Cost of Baricitinib Treatment for AT/AU Per Year4Based on an estimated prevalence of total scalp loss of 15% of all patients with AA (Cranwell et al., 2019; Ikeda, 1965). ($ Millions)World7,7537,753,000‒15,506,0001,550,600471,11270,666Europe746.3746,300‒1,492,600149,26045,3496,802United States329.5329,500‒659,00065,90020,0223,003Australia25.725,700‒51,4005,1401,561234.2South Africa59.359,300‒118,60011,8603,603540.5United Kingdom67.267,200‒134,40013,4404,083612.5Ireland5.15,100‒10,2001,020309.946.5Abbreviations: AA, alopecia areata; AT, alopecia totalis; AU, alopecia universalis.1 Based on an estimated point prevalence of 0.1‒0.2% (Safavi, 1992Safavi K. Prevalence of alopecia areata in the First National Health and Nutrition Examination Survey.Arch Dermatol. 1992; 128: 702Crossref PubMed Scopus (188) Google Scholar)2 Based on an estimated lifetime risk of 1.7‒2.1% (0.02% per year) (Mirzoyev et al., 2014Mirzoyev S.A. Schrum A.G. Davis M.D.P. Torgerson R.R. Lifetime incidence risk of alopecia areata estimated at 2.1% by Rochester Epidemiology Project, 1990–2009.J Invest Dermatol. 2014; 134: 1141-1142Abstract Full Text Full Text PDF PubMed Scopus (193) Google Scholar; Safavi et al., 1995Safavi K.H. Muller S.A. Suman V.J. Moshell A.N. Melton 3rd, L.J. Incidence of alopecia areata in Olmsted County, Minnesota, 1975 through 1989.Mayo Clin Proc. 1995; 70: 628-633Abstract Full Text Full Text PDF PubMed Scopus (459) Google Scholar)3 Based on the list price of baricitinib ($2,497.20 per 30 days) if all estimated patients with AA were treated (Sinclair, 2022Sinclair R. Alopecia areata: progress, but who pays?.Br J Dermatol. 2022; 186: 206-207Crossref PubMed Scopus (2) Google Scholar)4 Based on an estimated prevalence of total scalp loss of 15% of all patients with AA (Cranwell et al., 2019Cranwell W.C. Lai V.W. Photiou L. Meah N. Wall D. Rathnayake D. et al.Treatment of alopecia areata: an Australian expert consensus statement.Australas J Dermatol. 2019; 60: 163-170Crossref PubMed Scopus (67) Google Scholar; Ikeda, 1965Ikeda T. A new classification of alopecia areata.Dermatologica. 1965; 131: 421-445Crossref PubMed Scopus (171) Google Scholar). Open table in a new tab Abbreviations: AA, alopecia areata; AT, alopecia totalis; AU, alopecia universalis. The question of reimbursement was recently addressed, speculating a potential cost of £4 billion annually in the United Kingdom alone to treat patients with baricitinib using recent epidemiological evidence of point prevalence and the list cost of baricitinib (Sinclair, 2022Sinclair R. Alopecia areata: progress, but who pays?.Br J Dermatol. 2022; 186: 206-207Crossref PubMed Scopus (2) Google Scholar). Although this figure assumes that all patients with AA would be treated, it poses the important question of how to define access criteria. Furthermore, focusing solely on the most extensively affected patients by SALT score (alopecia totalis or universalis) would still result in a cost of over £600 million annually. A recent systematic review and meta-analysis (SRMA) suggests a higher risk of depression and anxiety in patients with AA (Okhovat et al., 2019Okhovat J.P. Marks D.H. Manatis-Lornell A. Hagigeorges D. Locascio J.J. Senna M.M. Association between alopecia areata, anxiety, and depression: a systematic review and meta-analysis [e-pub ahead of print].J Am Acad Dermatol. 2019; (accessed September 7, 2022).https://doi.org/10.1016/j.jaad.2019.05.086Abstract Full Text PDF Scopus (31) Google Scholar), whereas a further SRMA identified significant impairment in health-related QoL but with more reliability and validity needed in the instruments used to collect these data. The onset of AA usually occurs before the age of 40, with the 30s representing patients’ most frequently affected decade. Given the social importance of this cohort, at the peak of their working age, there is a considerable need to better assess the unmet need to avoid negatively impacting the dependency ratio in a population. It is therefore interesting that Senna et al., 2022Senna M. Ko J. Glashofer M. Walker C. Ball S. Edson-Heredia E. et al.Predictors of QOL in patients with alopecia areata.J Invest Dermatol. 2022; 142: 2646-2650Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar have shown that SALT score was not associated with any of the Work Productivity and Activity Impairment. As such, there is a perfect storm—a prevalent disease, with a potentially marked impact on a cohort of patients at a critical period in their working life. There are emerging therapeutic options, but a disconnect between classic measures that might identify who should have access. This study reiterates the need to include eyebrow and eyelash compound measures of AA severity. There is also a call for change in clinical practice, by encouraging the recording of either patient perception of disease activity (mild, moderate, or severe) or, as favored by the authors, the Patient Global Impression of Severity scale. The latter, as noted by Senna et al., 2022Senna M. Ko J. Glashofer M. Walker C. Ball S. Edson-Heredia E. et al.Predictors of QOL in patients with alopecia areata.J Invest Dermatol. 2022; 142: 2646-2650Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar, is a validated scale recommended for incorporation in research and clinical settings. These would also be useful to include in patient registries, such as the Global Registry of Alopecia Areata Disease Severity and Treatment Safety (Wall et al., 2021Wall D. Meah N. York K. Bhoyrul B. Bokhari L. Abraham L.S. et al.A global eDelphi exercise to identify core domains and domain items for the development of a global registry of alopecia areata disease severity and treatment safety (GRASS).JAMA Dermatol. 2021; 157: 1-11Crossref PubMed Scopus (9) Google Scholar) At a crossroads in the story of AA, where the journey ahead now offers promise rather than bleak uncertainty, Senna et al., 2022Senna M. Ko J. Glashofer M. Walker C. Ball S. Edson-Heredia E. et al.Predictors of QOL in patients with alopecia areata.J Invest Dermatol. 2022; 142: 2646-2650Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar have, in this paper, created signposts toward a more patient-centric means of characterizing disease severity. Dmitri Wall: http://orcid.org/0000-0002-0107-4488 Huw Rees: http://orcid.org/0000-0003-2609-4474 Laita Bokhari: http://orcid.org/0000-0003-4522-2611 Nekma Meah: http://orcid.org/0000-0001-9466-6337 Katherine York: http://orcid.org/0000-0003-2905-4494 Rodney Sinclair: http://orcid.org/0000-0001-6751-1428 DW is a member of the Scientific Committee of the Irish Association of Dermatologists. DW has received personal fees (honoraria) from Janssen, consultancy fees from Eli-Lily, and nonfinancial support (travel fees/grant) from Pfizer. DW has received personal fees for consultancy from the not-for-profit company National and International Skin Registry Solutions. RS is the director and founder of Samson Clinical Pty. RS is a member of the advisory boards for Eli Lily, Pfizer, and Leo Pharmaceutical. RS is a member of the speaker bureau for AbbVie and Novartis. RS is the principal investigator in clinical trials for Amgen, Novartis, Arcutis Biotherapeutics, Aerotech, Merck, Celgene, Coherus BioSciences, Janssen, Regeneron, MedImmune, Glaxo Smith Kine, Samson Clinical, Behringer Ingelheim, Oncobiologics, Roche, Ascend, Dermira, AstraZeneca, Akesobio, Reistone Biopharma, UCB, Sanofi, Connect, Arena, Sun Pharma, Bristol Myer Squibb, and Galderma. Each of the authors has been involved in the establishment of the Global Registry of Alopecia Areata Disease Severity and Treatment Safety network, which has received funding from Pfizer. Predictors of QOL in Patients with Alopecia AreataJournal of Investigative DermatologyVol. 142Issue 10PreviewAlthough alopecia areata (AA) severity is often defined by the degree of scalp hair loss, its impact on QOL can also be a defining measure of severity. In this cross-sectional study (AA Disease Specific Program), 259 patients were surveyed for demographics, AA illness characteristics, QOL (Skindex-16 AA), and daily impairment (Work Productivity and Activity Impairment). The association between patient demographics and illness variables, the Skindex-16 AA scores, and the Work Productivity and Activity Impairment scores were analyzed using regression analyses. Full-Text PDF Open Access