Speaker: Lidia Rudnicka
In the treatment of alopecia areata, particularly in the context of JAK inhibitors, the main factor influencing treatment decisions is the disease severity, primarily assessed using the Severity of Alopecia Tool (SALT) score, which measures the percentage of scalp hair loss. Despite disease activity, comorbidities, and psychological burden, the SALT score remains the cornerstone of clinical decision-making and reimbursement. Experts generally agree that systemic therapy should be initiated for patients with a SALT score of 20 or greater, as this level of hair loss significantly impacts the patient's quality of life. However, some specialists propose that a SALT score of 50 might be a more appropriate threshold, given the availability of clinical data supporting this score, while acknowledging that there is a lack of clinical trials specifically for SALT 20. The rationale for treating patients with a SALT score of 20 lies in the progressive nature of alopecia areata; the disease can advance rapidly, making regrowth increasingly difficult. Data indicate that more severe forms of the condition, such as alopecia totalis or universalis, correlate with a lower likelihood of treatment response. Thus, timely intervention is critical, as shown in studies involving treatments like baricitinib.
For acute alopecia areata, glucocorticosteroids are recommended due to their rapid effectiveness. For both acute and chronic cases, JAK inhibitors such as ritlecitinib and baricitinib are used. Ritlecitinib, primarily targeting JAK3, is often described as a kinase inhibitor due to its broader mechanism of action. It is administered at a dose of 50 mg/day for adults and children aged 12 years and older. Baricitinib, which affects JAK1 and JAK2, is administered at four milligrams. In older patients or those with cardiovascular risk factors, a starting dose of two milligrams may be considered, with the option to increase to four milligrams if necessary. Recently approved drug Deuroxolitinib, which received FDA approval, is administered at a dose of 2x 8 mg/day for adults. The efficacy of these JAK inhibitors varies, with pooled data showing response rates between 50% and 64% after one year of treatment. However, it is important to note that around 40% of patients may not respond to these therapies, highlighting the inability to predict treatment outcomes accurately.
The common characteristic of all JAK inhibitors is that the onset of treatment efficacy is relatively late, particularly in patients with alopecia areata. These inhibitors tend to be more effective in individuals with a shorter duration since their last episode of hair regrowth. It is crucial to clarify to patients that the count starts from the previous regrowth of terminal hairs, not merely from the appearance of vellus hairs. Moreover, patients with alopecia totalis and alopecia universalis are less likely to respond to treatment. Patients often expect to see the first signs of regrowth within a few weeks, as they might have experienced with corticosteroids or cyclosporine. However, this is not the case with JAK inhibitors. For instance, early responders to ritlecitinib typically achieve a SALT score of 20 or less by month nine, while late responders may see good results by month 24. This long waiting period can pose a problem, especially considering the product information suggests discontinuation of treatment if no significant improvement is observed within 36 weeks, which is less than a year. Current understanding indicates that it may take longer for some patients to see positive outcomes.
On average, regrowth is observed after approximately three to four months, but delayed regrowth is common. Importantly, among those who respond to JAK inhibitors, a high percentage—90 to 93%—maintain their hair after two years, which is a significant advantage compared to treatments like glucocorticosteroids or cyclosporine. Nonetheless, a subset of patients does not respond to therapy, leading to the consideration of switching to a different JAK inhibitor as a potential solution.
A case history from our department illustrates these challenges. A patient with alopecia areata, who had undergone various treatments without success, was eventually eligible for reimbursement for JAK inhibitors. Initial trichoscopy revealed signs of active hair loss, and despite attempts to add minoxidil, no hair regrowth was observed. With the 36-week deadline approaching, we decided to introduce a low dose of corticosteroids. This led to notable hair regrowth, beginning with beard development, followed by the regrowth of eyebrows and eyelashes over time. It is important to note that combining JAK inhibitors with glucocorticoids is considered off-label and lacks comprehensive documentation. Although there is a mild suggestion in clinical consensus for this combination, it is not formally recommended. Clinicians must make treatment decisions based on individual patient circumstances, including the presence of hair regrowth.
The question of when a patient with alopecia areata can discontinue treatment is often one of the most challenging inquiries a clinician faces. Ulrike Blume-Peytavi, a prominent expert in hair diseases, likens alopecia areata to psoriasis, noting that discontinuation of therapy frequently leads to relapse. As a general guideline, after two to three years of successful treatment, clinicians might consider a gradual reduction of the JAK inhibitor dose, with the understanding that it may be necessary to increase the dose again in the event of a relapse. This process is typically more complex than initiating treatment. Many patients are interested in using tofacitinib, particularly since it is available at a low cost outside of Europe. Although case series suggest that tofacitinib may be effective for alopecia areata, this indication is not formally approved.
Additionally, significant safety concerns are associated with tofacitinib, highlighted by the black box warning in the United States and cautionary statements from the European Medicines Agency. Given these risks and the priority of patient safety, I do not personally recommend tofacitinib for alopecia areata. While we aspire for all patients to access JAK inhibitors, numerous individuals may face challenges obtaining them due to a lack of reimbursement or contraindications. Therefore, it is imperative to have alternative treatment options available for these patients. As previously mentioned, options for second-line therapy include cyclosporine, with a recommended dose ranging from 3 to 5 mg/kg per day. There are indications that lower doses, below 2 mg, might also be effective. My clinical practice typically begins with a daily dose of 100 mg, adjusting as necessary based on patient response. The response rates to cyclosporine are generally favorable; however, the data supporting its use are largely derived from case reports and small studies rather than large clinical trials.
Another treatment option is methotrexate, which has a long history, having been first approved in 1953. It was not until 2006 that its efficacy in alopecia areata was investigated, with a study by Pascal Joly demonstrating that approximately 50% of patients treated with methotrexate monotherapy experienced hair regrowth. This finding has sparked considerable discussion among experts, leading to a range of studies with variable results regarding methotrexate's effectiveness in this condition. In a recent double-blind, randomized clinical trial by Pascal Joly, the efficacy of methotrexate for alopecia areata was evaluated. The study demonstrated that complete or nearly complete hair regrowth occurred in 0% of patients receiving a placebo and only 2% in those treated with methotrexate alone. However, adding oral prednisone to the treatment regimen significantly increased the response rate, yielding a regrowth rate of 20-31%. This presents a considerable challenge in patient communication; conveying a mere 2% chance of regrowth may lead to dissatisfaction and prompt patients to seek alternative medical opinions.
Clinicians have observed variable responses to methotrexate in their patients, highlighting the subjectivity and variability inherent in treatment outcomes. Furthermore, a recent study from Krakow, Poland, indicated that patients receiving low-dose methotrexate for conditions such as morphea or psoriasis experienced a 30% incidence of telogen effluvium, complicating the assessment of hair loss in those already receiving the drug. Therefore, clinicians must differentiate between relapse of alopecia areata and potential drug-induced hair shedding when patients report hair loss after starting methotrexate. Methotrexate, which was administered at a dose of 15 mg/week and up to 25 mg for responders, typically leads to initial hair regrowth after 3 months, with complete regrowth occurring within 6 to 12 months. The psychological impact of alopecia areata on patients cannot be overstated, as studies show that over 60% of individuals make significant life decisions, including those related to relationships, education, and careers, based on their health and hair loss experiences. Given this substantial emotional burden, early initiation of treatment is paramount.
In conclusion, two JAK inhibitors are currently approved for alopecia areata, marking a shift in therapeutic strategies. It is essential to set realistic expectations regarding the delayed response to treatments. Methotrexate and cyclosporine, which, while considered off-label, remain standard therapeutic options. Additionally, there is an observable trend away from long-term monotherapy with corticosteroids in the management of this condition. Despite the advancements brought about by JAK inhibitors in treating severe alopecia areata, there remain challenges in managing patients with SALT scores between 21-49 due to a lack of clinical trial data. Consequently, treatment decisions for this group often rely on expert opinion, raising concerns about reimbursement from payers based solely on these recommendations.
33, European Academy of Dermatology and Venereology Congress, 25-28 September 2024, Amsterdam.Top of Form
