RARE DISEASE
Alopecia totalis
Alopecia totalis
Alopecia totalis
Drug discovery
4
drugs
With orphan designations
Overview
Alopecia totalis (AT) is a severe autoimmune subtype of alopecia areata characterized by complete scalp hair loss due to T-cell–mediated follicular destruction [6][13]. It affects 0.03% of the population, with <10% experiencing spontaneous regrowth [12][16]. Prognosis is poorer than localized AA, with frequent treatment resistance and relapses [6][11]. Management focuses on immune modulation, though sustained remission remains challenging [3][6].
Population
Affects ~0.03% globally, with rising prevalence [12][14]; 5%-10% of alopecia areata cases progress to AT/AU [2][9].
More common in children/young adults (mean onset <30 years) and those with family history (20% genetic link) [6][12][16].
Higher incidence in females (1.5–2:1 ratio) and Northeastern U.S. residents [2][14].
Burden
Psychological: 2–3x higher rates of depression/anxiety vs general population; social withdrawal common [4][9][10].
Economic: Annual healthcare costs ~70% higher than controls ($18,988 vs $11,030) [19]; frequent specialist visits (3.4 dermatology visits/year) [19].
Comorbidities: 20% have concurrent autoimmune disorders (thyroid disease, vitiligo, lupus) [6][9][13].
Therapies
First-line: Intralesional/topical corticosteroids ± adjunct minoxidil for maintenance [3][5].
Systemic agents: JAK inhibitors (baricitinib, ritlecitinib) show 50%+ regrowth in trials [3][8][18]; oral steroids for acute cases [5][11].
Advanced options: Contact immunotherapy (DPCP) or PUVA phototherapy, though relapse rates exceed 30% post-treatment [5][6].
Categories: rare skin diseases
Research Papers
541 drug discovery papers about Alopecia totalis, with 3 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
541 drug discovery papers about Alopecia totalis, with 3 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-17 | Alopecia areata: Emerging therapies and up-to-date management strategies.
Alopecia areata (AA) is an autoimmune hair disease with variable presentations necessitating individualized, stepwise management given patient age, extent of involvement, comorbidities, and treatment tolerability. Historically, severity was defined by percentage of scalp hair loss using the Severity of Alopecia Tool (SALT), with SALT≥50 defining severe disease and systemic therapy eligibility. Recently, severity assessment has expanded beyond scalp involvement with the AA Scale for Clinical Use (AASc), incorporating eyebrow/eyelash involvement, psychosocial impairment, and treatment response to better capture disease burden. First-line therapy for mild-to-moderate AA (SALT<50) includes topical or intralesional corticosteroids, often with topical or oral minoxidil. Observation may be appropriate in select cases given potential for spontaneous regrowth. FDA approval of oral Janus kinase inhibitors (JAKis) for severe AA (SALT≥50) has changed the therapeutic landscape. Selection among baricitinib, ritlecitinib, and deuruxolitinib is guided by patient age, safety considerations, comorbidities, laboratory monitoring, and insurance coverage. Switching between JAKis may still be beneficial after nonresponse to one agent. Adjunctive and alternative therapies include topical immunotherapy, systemic immunosuppressants, emerging biologic/targeted therapies, and procedural modalities, such as platelet-rich plasma, laser- and light-based therapies, and microneedling. This review synthesizes current evidence on AA treatment and offers a practical, contemporary framework for AA management.
2026-07-31 | Case Report: Repigmentation and complete hair regrowth in an 11-year-old preadolescent with alopecia totalis treated with a JAK inhibitor.
Alopecia areata (AA) is an autoimmune disease characterized by non-scarring hair loss. Janus kinase (JAK) inhibitors have emerged as effective therapeutic options for severe pediatric AA, though repigmentation of white hair during treatment remains rarely reported. Herein, we report an unusual case of complete hair regeneration with simultaneous white-to-black hair conversion in a child with severe AA following JAK inhibitor therapy. An 11-year-old girl presented with alopecia totalis (AT) persisting for two years. She initially received baricitinib for seven months, achieving SALT 65% with predominantly white and gray hair regrowth. After switching to ritlecitinib 50 mg/day, black hair emerged at 6 weeks, with complete hair regrowth and repigmentation at 6 months (SALT 0). The patient has now completed 12 months of ritlecitinib therapy with sustained response and stable pigmentation. Family Dermatology Life Quality Index (FDLQI) decreased from 18 to 4. No significant adverse effects were observed. This case suggests that prolonged JAK inhibition may facilitate both hair regrowth and pigment restoration in pediatric severe AA.
2026-07-29 | Efficacy and Safety of Oral Janus Kinase Inhibitors in Adults and Adolescents with Alopecia Areata: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.
Alopecia areata is an autoimmune disorder characterised by T-cell-mediated damage of hair follicles, resulting in non-scarring hair loss that can progress to complete scalp (alopecia totalis) or body hair loss (alopecia universalis). While long-term systemic options were historically limited, the emergence of Janus kinase (JAK) inhibitors has revolutionised the treatment of alopecia areata, even in patients with moderate-to-severe disease. We aimed to evaluate the efficacy and safety of oral JAK inhibitors compared with placebo in adults and adolescents with moderate-to-severe alopecia areata. MEDLINE, Embase and the Cochrane Central Register of Controlled Trials databases were searched from inception to 28 November, 2025. Randomised controlled trials evaluating oral JAK inhibitors in adolescents and adults (aged ≥12 years) with alopecia areata were included. Data extraction and risk of bias assessment were performed independently by multiple reviewers. Primary outcomes were the proportion of patients who achieved Severity of Alopecia Tool (SALT) scores of ≤10 and ≤20, and 50%, 75% and 90% reductions in SALT scores from baseline, as well as treatment-related adverse events (AEs). Data were synthesised using random-effects models to calculate odds ratios (ORs) and mean differences with 95% confidence intervals (CIs). Twelve randomised controlled trials involving 4141 participants (mean age 35.8 years, mean baseline SALT score 86.0) met the inclusion criteria. All trials enrolled adult participants, with the exception of one randomised controlled trial in which adolescents comprised 15% of the study population. Six trials were rated as having a low risk of bias, while six had "some concerns" primarily because of missing outcome data. Oral JAK inhibitors were significantly more effective than placebo across all primary efficacy endpoints. At week 24, the odds of achieving SALT ≤10 were 5.69 times higher for JAK inhibitors than placebo (95% CI 3.58-9.03); by week 36, this effect increased to an OR of 9.40 (95% CI 4.58-19.29). For SALT ≤20, the OR was 7.99 (95% CI 5.13-12.44) at week 24. Patients treated with oral JAK inhibitors were significantly more likely to achieve SALT50, SALT75 and SALT90 across all timepoints (weeks 12-36). Regarding safety, JAK inhibitors were associated with a higher risk of total AEs (OR 1.60; 95% CI 1.33-1.94), but no statistically significant difference was found for serious AEs (OR 1.04; 95% CI 0.69-1.57) or treatment discontinuation because of AEs (OR 1.22; 95% CI 0.84-1.76). Oral JAK inhibitors are effective in promoting scalp, eyebrow and eyelash hair regrowth in adults and adolescents with moderate-to-severe alopecia areata, with a trend of higher response rates at later timepoints across studies. The favourable safety profile of these agents is reassuring. Future research should prioritise head-to-head randomised controlled trials and long-term pharmacovigilance to define comparative efficacy and safety.
2026-06-30 | COMPARISON OF CLINICAL EFFICACY OF TOFACITINIB VERSUS METHOTREXATE IN SEVERE ALOPECIA AREATA, ALOPECIA TOTALIS, AND ALOPECIA UNIVERSALIS: A RANDOMIZED CONTROLLED TRIAL
Objective: To compare the 12-week clinical efficacy of oral tofacitinib with oral methotrexate in adults with severe alopecia areata, alopecia totalis, or alopecia universalis. Methods: This open-label, parallel-group randomized controlled trial was conducted in the Department of Dermatology, Medical Teaching Institution-Hayatabad Medical Complex, Peshawar, from 8 October 2024 to 8 March 2025. Seventy-eight adults aged 18-60 years were enrolled by consecutive non-probability sampling and allocated by blocked randomization (1:1) to tofacitinib 10 mg twice daily or methotrexate 0.2-0.4 mg/kg once weekly for 12 weeks. Participants receiving systemic alopecia therapy, pregnant or lactating women, and patients with renal, hepatic, or pulmonary disease were excluded. The trial was open-label; no allocation-concealment procedure was documented in the supplied records. Severity of Alopecia Tool (SALT) scores were measured at baseline and week 12. Efficacy was defined as a >50% reduction in SALT score. Ethical approval (No. 2141; 23 September 2024) and written informed consent were obtained. The trial was retrospectively registered (NCT07406204). Results: Baseline SALT scores were comparable between the tofacitinib and methotrexate groups (74.7 ± 9.5 vs 75.5 ± 8.7; p=0.68). At week 12, the mean SALT score was lower with tofacitinib (35.9 ± 11.2 vs 53.2 ± 9.5; p<0.001), and mean percentage improvement was greater (52.7 ± 10.2% vs 29.7 ± 9.5%; p<0.001). Efficacy was achieved by 23 (59.0%) and 1 (2.6%) participants, respectively (p<0.001). Conclusions: Oral tofacitinib demonstrated greater short-term efficacy than methotrexate over 12 weeks. The findings do not establish long-term safety, durability, relapse risk, or subtype-specific efficacy.
2026-06-25 | Alopecia totalis treated with constitutional medicine <i>Calcarea carbonica</i>: A case report
Introduction: Alopecia totalis is an autoimmune disease that causes hair loss anywhere in the body, but it most commonly affects the hair of the scalp. It occurs in people of all ages and affects 1–2% of the human population. The homoeopathic literature suggests that cases of alopecia totalis have been treated successfully with homoeopathic medicines. Case Summary: This case highlights the potential of the individualised homoeopathic remedy in promoting hair regrowth in alopecia totalis in a 14-yr old girl. The patient was prescribed Calcarea carbonica 200C, 2 doses on the basis of totality of symptoms and individualisation. This evidence-based case report shows how Homoeopathy can offer a promising alternative to conventional treatment in such cases.
2026-08-17 | Alopecia areata: Emerging therapies and up-to-date management strategies.
Alopecia areata (AA) is an autoimmune hair disease with variable presentations necessitating individualized, stepwise management given patient age, extent of involvement, comorbidities, and treatment tolerability. Historically, severity was defined by percentage of scalp hair loss using the Severity of Alopecia Tool (SALT), with SALT≥50 defining severe disease and systemic therapy eligibility. Recently, severity assessment has expanded beyond scalp involvement with the AA Scale for Clinical Use (AASc), incorporating eyebrow/eyelash involvement, psychosocial impairment, and treatment response to better capture disease burden. First-line therapy for mild-to-moderate AA (SALT<50) includes topical or intralesional corticosteroids, often with topical or oral minoxidil. Observation may be appropriate in select cases given potential for spontaneous regrowth. FDA approval of oral Janus kinase inhibitors (JAKis) for severe AA (SALT≥50) has changed the therapeutic landscape. Selection among baricitinib, ritlecitinib, and deuruxolitinib is guided by patient age, safety considerations, comorbidities, laboratory monitoring, and insurance coverage. Switching between JAKis may still be beneficial after nonresponse to one agent. Adjunctive and alternative therapies include topical immunotherapy, systemic immunosuppressants, emerging biologic/targeted therapies, and procedural modalities, such as platelet-rich plasma, laser- and light-based therapies, and microneedling. This review synthesizes current evidence on AA treatment and offers a practical, contemporary framework for AA management.
2026-07-31 | Case Report: Repigmentation and complete hair regrowth in an 11-year-old preadolescent with alopecia totalis treated with a JAK inhibitor.
Alopecia areata (AA) is an autoimmune disease characterized by non-scarring hair loss. Janus kinase (JAK) inhibitors have emerged as effective therapeutic options for severe pediatric AA, though repigmentation of white hair during treatment remains rarely reported. Herein, we report an unusual case of complete hair regeneration with simultaneous white-to-black hair conversion in a child with severe AA following JAK inhibitor therapy. An 11-year-old girl presented with alopecia totalis (AT) persisting for two years. She initially received baricitinib for seven months, achieving SALT 65% with predominantly white and gray hair regrowth. After switching to ritlecitinib 50 mg/day, black hair emerged at 6 weeks, with complete hair regrowth and repigmentation at 6 months (SALT 0). The patient has now completed 12 months of ritlecitinib therapy with sustained response and stable pigmentation. Family Dermatology Life Quality Index (FDLQI) decreased from 18 to 4. No significant adverse effects were observed. This case suggests that prolonged JAK inhibition may facilitate both hair regrowth and pigment restoration in pediatric severe AA.
2026-07-29 | Efficacy and Safety of Oral Janus Kinase Inhibitors in Adults and Adolescents with Alopecia Areata: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.
Alopecia areata is an autoimmune disorder characterised by T-cell-mediated damage of hair follicles, resulting in non-scarring hair loss that can progress to complete scalp (alopecia totalis) or body hair loss (alopecia universalis). While long-term systemic options were historically limited, the emergence of Janus kinase (JAK) inhibitors has revolutionised the treatment of alopecia areata, even in patients with moderate-to-severe disease. We aimed to evaluate the efficacy and safety of oral JAK inhibitors compared with placebo in adults and adolescents with moderate-to-severe alopecia areata. MEDLINE, Embase and the Cochrane Central Register of Controlled Trials databases were searched from inception to 28 November, 2025. Randomised controlled trials evaluating oral JAK inhibitors in adolescents and adults (aged ≥12 years) with alopecia areata were included. Data extraction and risk of bias assessment were performed independently by multiple reviewers. Primary outcomes were the proportion of patients who achieved Severity of Alopecia Tool (SALT) scores of ≤10 and ≤20, and 50%, 75% and 90% reductions in SALT scores from baseline, as well as treatment-related adverse events (AEs). Data were synthesised using random-effects models to calculate odds ratios (ORs) and mean differences with 95% confidence intervals (CIs). Twelve randomised controlled trials involving 4141 participants (mean age 35.8 years, mean baseline SALT score 86.0) met the inclusion criteria. All trials enrolled adult participants, with the exception of one randomised controlled trial in which adolescents comprised 15% of the study population. Six trials were rated as having a low risk of bias, while six had "some concerns" primarily because of missing outcome data. Oral JAK inhibitors were significantly more effective than placebo across all primary efficacy endpoints. At week 24, the odds of achieving SALT ≤10 were 5.69 times higher for JAK inhibitors than placebo (95% CI 3.58-9.03); by week 36, this effect increased to an OR of 9.40 (95% CI 4.58-19.29). For SALT ≤20, the OR was 7.99 (95% CI 5.13-12.44) at week 24. Patients treated with oral JAK inhibitors were significantly more likely to achieve SALT50, SALT75 and SALT90 across all timepoints (weeks 12-36). Regarding safety, JAK inhibitors were associated with a higher risk of total AEs (OR 1.60; 95% CI 1.33-1.94), but no statistically significant difference was found for serious AEs (OR 1.04; 95% CI 0.69-1.57) or treatment discontinuation because of AEs (OR 1.22; 95% CI 0.84-1.76). Oral JAK inhibitors are effective in promoting scalp, eyebrow and eyelash hair regrowth in adults and adolescents with moderate-to-severe alopecia areata, with a trend of higher response rates at later timepoints across studies. The favourable safety profile of these agents is reassuring. Future research should prioritise head-to-head randomised controlled trials and long-term pharmacovigilance to define comparative efficacy and safety.
2026-06-30 | COMPARISON OF CLINICAL EFFICACY OF TOFACITINIB VERSUS METHOTREXATE IN SEVERE ALOPECIA AREATA, ALOPECIA TOTALIS, AND ALOPECIA UNIVERSALIS: A RANDOMIZED CONTROLLED TRIAL
Objective: To compare the 12-week clinical efficacy of oral tofacitinib with oral methotrexate in adults with severe alopecia areata, alopecia totalis, or alopecia universalis. Methods: This open-label, parallel-group randomized controlled trial was conducted in the Department of Dermatology, Medical Teaching Institution-Hayatabad Medical Complex, Peshawar, from 8 October 2024 to 8 March 2025. Seventy-eight adults aged 18-60 years were enrolled by consecutive non-probability sampling and allocated by blocked randomization (1:1) to tofacitinib 10 mg twice daily or methotrexate 0.2-0.4 mg/kg once weekly for 12 weeks. Participants receiving systemic alopecia therapy, pregnant or lactating women, and patients with renal, hepatic, or pulmonary disease were excluded. The trial was open-label; no allocation-concealment procedure was documented in the supplied records. Severity of Alopecia Tool (SALT) scores were measured at baseline and week 12. Efficacy was defined as a >50% reduction in SALT score. Ethical approval (No. 2141; 23 September 2024) and written informed consent were obtained. The trial was retrospectively registered (NCT07406204). Results: Baseline SALT scores were comparable between the tofacitinib and methotrexate groups (74.7 ± 9.5 vs 75.5 ± 8.7; p=0.68). At week 12, the mean SALT score was lower with tofacitinib (35.9 ± 11.2 vs 53.2 ± 9.5; p<0.001), and mean percentage improvement was greater (52.7 ± 10.2% vs 29.7 ± 9.5%; p<0.001). Efficacy was achieved by 23 (59.0%) and 1 (2.6%) participants, respectively (p<0.001). Conclusions: Oral tofacitinib demonstrated greater short-term efficacy than methotrexate over 12 weeks. The findings do not establish long-term safety, durability, relapse risk, or subtype-specific efficacy.
2026-06-25 | Alopecia totalis treated with constitutional medicine <i>Calcarea carbonica</i>: A case report
Introduction: Alopecia totalis is an autoimmune disease that causes hair loss anywhere in the body, but it most commonly affects the hair of the scalp. It occurs in people of all ages and affects 1–2% of the human population. The homoeopathic literature suggests that cases of alopecia totalis have been treated successfully with homoeopathic medicines. Case Summary: This case highlights the potential of the individualised homoeopathic remedy in promoting hair regrowth in alopecia totalis in a 14-yr old girl. The patient was prescribed Calcarea carbonica 200C, 2 doses on the basis of totality of symptoms and individualisation. This evidence-based case report shows how Homoeopathy can offer a promising alternative to conventional treatment in such cases.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
4 orphan drug designations for Alopecia totalis.
4 orphan drug designations for Alopecia totalis.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
trafermin in combination with plasma and platelet rich plasma | other | FDA | 2017-12-21 | — | HCell, Inc. |
Diphencyprone | small molecules | EMA | 2006-06-29 | — | [INACTIVE] Orfagen |
Diphencyprone | small molecules | EMA | 2006-06-29 | — | [INACTIVE] Orfagen |
diphenylcyclopenone | small molecules | FDA | 2003-06-13 | — | Lloyd E. King, Jr. |
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