Speaker: Lida Rudnicka

Alopecia areata treatment approaches are evolving, particularly concerning new therapeutic possibilities. The assessment of disease severity primarily relies on the percentage of hair loss on the scalp. Severity of Alopecia Tool (SALT), with less than 20% scalp involvement classified as mild alopecia areata. In such cases, topical glucocorticoid steroids remain the first-line treatment, particularly for children, where occlusive methods can enhance effectiveness. Treatment should continue for several weeks to assess improvement, and guidelines recommend discontinuing corticosteroid therapy after six months if no response occurs. Intralesional corticosteroid injections are suggested for patients with a SALT score below 30 and above the age of 13 due to the significant psychological impact and pain associated with the procedure in younger patients. Furthermore, efficacy diminishes with increasing hair loss extent; thus, the consensus advises against intralesional treatment for those with SALT scores exceeding 30. 

For acute alopecia areata, glucocorticosteroids are preferred for their rapid action. Given the pressing need to halt ongoing hair loss, these agents provide immediate results. While specific recommendations regarding the type of steroid vary among clinicians, individual preferences dictate the choice. Following corticosteroid treatment, Janus kinase (JAK) inhibitors are recommended as the first-line systemic treatment (non-acute), as they are the only approved therapy for alopecia areata with substantial evidence from double-blind placebo-controlled clinical trials. In cases where JAK inhibitors are unavailable due to regulatory reasons or contraindications, cyclosporine is considered the second-line option, supported by expert consensus. The discussion has weighed the efficacy of cyclosporine against methotrexate, with a majority favoring cyclosporine. Other immunosuppressive agents, such as azathioprine, have limited data supporting their use, primarily relying on expert opinion rather than robust clinical evidence. Immunosuppressive medications may be administered in conjunction with glucocorticosteroids or as monotherapy. Expert opinions on the efficacy of minoxidil vary widely, with some asserting that it works well while others claim it has no effect. The need for larger, placebo-controlled trials is emphasized to clarify its role in treatment protocols.

Current approaches to steroid use, such as prednisone, dexamethasone, and triamcinolone, in the treatment of alopecia areata suggest a shift away from long-term glucocorticosteroid therapy. These medications are primarily used for initial treatment or in combination with immunosuppressive therapies rather than as standalone long-term solutions. There is no consensus on a singular approach; thus, practitioners may adopt varying strategies based on individual patient needs. Regarding JAK inhibitors, two have received approval in Europe (European Medicines Agency/ Food and Drug Administration): Ritlecitinib and Baricitinib. Ritlecitinib is dosed at 50 mg daily for both children and adults, while baricitinib is approved for 4 mg daily, with a lower of 2 mg for individuals over 62 or as maintenance dose. Additionally, deuruxolitinib, another JAK inhibitor, has been recently approved in the United States, but it is not yet available in Europe, with potential approval anticipated in 2026. Efficacy data from initial clinical trials indicate that approximately 38% to 43% of patients experience complete or near-complete hair regrowth with JAK inhibitors. Notably, response rates improve over time, with some patients being late responders. 

Early responders typically show significant regrowth by six months, while others may require up to 12 months for a notable response. A subset of patients, identified as late responders, may exhibit significant regrowth after two years of treatment. The delayed response to JAK inhibitors may be attributed to their mechanism of action, which influences telogen-phase hair follicles, necessitating several months for these follicles to transition back into the anagen phase of the hair growth cycle. Recommendations from the European Medicines Agency (EMA) address the duration of treatment for patients without observable regrowth, although specific guidelines were not detailed. According to the EMA and Food and drug. (FDA), if there is no hair regrowth observed by week 36, consideration should be given to discontinuing treatment, potentially switching to another JAK inhibitor or a different treatment modality. Adverse events associated with JAK inhibitors include headaches (6.6%) and acne (6.4%). Recent discussions suggest avoiding the term "acne" or "acneiform lesions" in favor of "folliculocentric rash," although the appearance may resemble acne. Common adverse events with baricitinib include hypercholesterolemia and headaches, with some patients reporting weight gain, though this is not statistically significant.

A comparative study between tofacitinib and tumor necrosis factor (TNF) inhibitors prompted the FDA and EMA to issue safety recommendations for baricitinib. Caution is advised when using baricitinib and other JAK inhibitors in patients aged 65 years and older, those with an increased risk of major cardiovascular events, smokers, or individuals at higher risk for cancer. While the reasons behind smoking's impact remain unclear, statistical data suggest higher adverse events in smokers compared to non-smokers. Generally, most treatment-emergent adverse events associated with ritlecitinib and baricitinib are mild to moderate. 

Long-term data indicate that approximately 60% of patients experience positive hair regrowth effects from JAK inhibitors, but responses may take several months. Trichoscopy can reveal regrowth approximately two months before it is clinically visible. JAK inhibitors are most effective in patients with a shorter duration of alopecia areata, particularly those with an episode duration of less than three years. However, successful regrowth has also been documented in patients with a history of alopecia areata lasting up to 40 years. Efficacy is significantly lower in cases of alopecia totalis and alopecia universalis, leading to expert consensus recommending the early initiation of JAK inhibitors in patients with moderate to severe alopecia areata. Long-term treatment is essential, as discontinuing therapy after achieving hair regrowth poses a high risk of relapse. Alopecia areata shares characteristics with psoriasis, emphasizing the importance of sustained treatment to maintain regrowth and prevent recurrence. The recommendation for tapering JAK inhibitor doses suggests a gradual reduction starting approximately two years after achieving full hair regrowth, followed by maintenance therapy. This approach necessitates long-term treatment. However, reimbursement for JAK inhibitors is not universally accessible, leading to alternative treatments such as cyclosporine or methotrexate.

Cyclosporine demonstrates initial efficacy similar to JAK inhibitors, with approximately 60% success in the early months. Nonetheless, the lack of long-term studies or extensive clinical trials limits its long-term applicability. Two dosing strategies exist: one recommends doses between 3 to 5 mg/kg/d, not exceeding 5 mg due to nephrotoxicity, while a low-dose approach often utilizes <2 mg/kg/d or100 mg/d. Although initial responses may be satisfactory, dose adjustments may be necessary over time as patients may experience hair loss after initial regrowth. Methotrexate presents additional complexities. A recent randomized clinical trial by Pascal Joly reported that only 2% of patients achieved complete or near-complete hair regrowth with methotrexate (15 mg/week). This limited efficacy raises concerns about recommending a treatment with such low success rates. Ongoing trials are awaited to provide further insights into methotrexate's potential in alopecia areata.

33, European Academy of Dermatology and Venereology Congress, 25-28 September 2024, Amsterdam