Arash Mostaghimi, MD, MPH

Panelists discuss the efficacy and safety data for ritlecitinib and deuruxolitinib in treating alopecia areata, highlighting that ritlecitinib achieved SALT scores of ≤20 in 23% of patients at week 24 compared to 1.6% in the placebo group, while deuruxolitinib showed SALT scores of ≤20 in 42.5% (8mg BID ) and 56.8% (12mg BID) of patients, with treatment-emergent adverse events primarily being mild to moderate, including upper respiratory tract infections and headaches for ritlecitinib, and headache and acne for deuruxolitinib.

Assessing Risk and Safety of JAK Inhibitors

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    i.SALT≤20 at week 24 was achieved by 23% (50mg QD) and 1.6% (placebo) of patients; SALT≤10 at week 24 was achieved by 13.4% (50 mg QD) and 1.5% (placebo) of patients. 

    ii. TEAEs were reported by 75% of patients on 50 mg QD ritlecitinib and 71% on placebo group. Discontinuations were reported by 2% of patients in both groups. Most common AEs (occurred in ≥10% of patients) were upper respiratory tract infection, nasopharyngitis, and headache. b.	Deuruxolitinib (n=706, King 2024): 

    iii. SALT ≤20 after 24 weeks was achieved by 42.5% (8 mg BID), 56.8% (12mg BID), 1.8% (placebo) of patients with partial hair loss and by 20.1% (8 mg BID), 29.5% (12 mg BID), 0% (placebo) of patients with complete or near-complete hair loss. 

    iv. TEAEs related to study drug were reported by 31.3% (8 mg BID), 34.9% (12 mg BID), 22.1% (placebo). Most TEAEs were mild to moderate. Headache, acne, and increased blood creatinine phosphokinase were the most common TEAEs (occurred in ≥5% patients). No heart-related AEs were reported.

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Ritlecitinib and deuruxolitinib are being evaluated for their efficacy in treating hair loss. Ritlecitinib showed modest improvement in SALT scores at 24 weeks, with a higher incidence of treatment-emergent adverse events (TEAEs) compared to placebo. Deuruxolitinib demonstrated more significant improvements in SALT scores, particularly at higher doses, with a lower incidence of TEAEs compared to ritlecitinib. Common adverse events for both drugs included upper respiratory tract infections and headaches, with deuruxolitinib also causing acne and increased blood creatinine phosphokinase levels.

Panelists discuss their clinical experiences with Janus kinase (JAK) inhibitors for treating alopecia, noting observed differences in outcomes and tolerability among various systemic JAK inhibitors, while highlighting the advantages of these therapies over traditional local and systemic treatment options.

Real-World Clinical Experience With JAK Inhibitors

What has been your clinical experience with JAK inhibitors for treatment of alopecia?

    a. Have you observed differences in outcomes and/or tolerability with using   different systemic JAK inhibitors?

What are the advantages of using systemic JAK inhibitor therapies compared with traditional local or systemic therapies?

JAK inhibitors have shown promise in treating alopecia, offering a novel approach compared to traditional therapies. Clinicians have observed varying outcomes and tolerability among different systemic JAK inhibitors, with some patients responding better to specific agents. Systemic JAK inhibitors provide advantages over traditional therapies, including more targeted action and potential for improved efficacy in severe cases. However, considerations regarding side effects and long-term safety remain crucial. The choice of JAK inhibitor may depend on individual patient factors, including previous treatment responses and specific alopecia subtype.

Panelists discuss the long-term study results for baricitinib in alopecia areata, noting that nearly 90% of patients maintained a SALT score of ≤20 from week 52 to week 104, with over 70% achieving a SALT score of ≤10, while also addressing the reported treatment-emergent adverse events (TEAEs), which were mostly mild to moderate, with common events including COVID-19 infection and upper respiratory tract infections.

Review of FDA Approved JAK Inhibitors for Alopecia Areata

a. Baricitinib (n=194, long term study, Senna 2024): 

    i. Close to 90% of patients maintained SALT ≤20 from week 52 to week 104; SALT ≤10 was achieved by over 70% of patients; clinician- and patient-reported outcomes measurements for eyebrow and eyelash showed increase in response rates between weeks 52 and 104. 

    ii.TEAEs were reported in 76% of patients taking baricitinib. Most TEAEs were mild to moderate. Most common TEAEs (occurred in ≥5% patients) were COVID-19 infection, upper respiratory tract infection, and headache. One event of major adverse cardiovascular event was reported (<0.1% incidence rate).

Baricitinib, in a long-term study involving 194 patients, demonstrated significant efficacy in maintaining hair regrowth, with nearly 90% achieving a SALT score of ≤20 and over 70% achieving a SALT score of ≤10 from week 52 to week 104. Both clinician- and patient-reported outcomes for eyebrow and eyelash regrowth improved during this period. Treatment-emergent adverse events (TEAEs) were reported in 76% of patients, predominantly mild to moderate, with the most common being COVID-19 infection, upper respiratory tract infection, and headache. A single major adverse cardiovascular event was noted.

Panelists discuss the differences in mechanisms of action among the FDA-approved Janus kinase (JAK) inhibitors for alopecia, including baricitinib, deuruxolitinib, and ritlecitinib, and explore how selective inhibition differs from pan-inhibition in influencing treatment efficacy.

JAK Inhibition in the Treatment of Alopecia Areata

Three JAK inhibitors are FDA-approved for the treatment of alopecia: baricitinib and deuruxolitinib (JAK1/2 inhibitors), and ritlecitinib (selective JAK3 and TEC inhibitor). Can you talk about the differences in mechanisms of action and how they might influence treatment efficacy for alopecia?

How does selective inhibition differ from pan-inhibition?

JAK inhibitors, including baricitinib, deuruxolitinib, and ritlecitinib, are FDA-approved for alopecia treatment, each with distinct mechanisms of action. Baricitinib and deuruxolitinib target JAK1/2, while ritlecitinib selectively inhibits JAK3 and TEC. These differences in selectivity may influence treatment efficacy and safety profiles. Selective inhibition targets specific JAK pathways, potentially reducing off-target effects, whereas pan-inhibition affects multiple JAK pathways, which may increase efficacy but also the risk of adverse effects. Understanding these distinctions is crucial for optimizing therapeutic strategies in alopecia management.

Arash Mostaghimi, MD, MPH

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