What are the second line treatment options for a patient with alopecia areata who has not responded to first line treatments?

Second-Line Treatment of Alopecia Areata

For patients with moderate to severe alopecia areata (>40% scalp hair loss) who have failed first-line treatments, JAK inhibitors (baricitinib or ritlecitinib) are now the preferred second-line option, demonstrating superior efficacy to all traditional therapies. 1

Treatment Algorithm Based on Disease Severity

For Moderate to Severe Disease (>40% scalp hair loss or extensive patchy disease refractory to conventional therapy):

JAK inhibitors should be initiated as second-line therapy after failure of intralesional corticosteroids or contact immunotherapy. 1 This represents a paradigm shift from older guidelines, as these are the first FDA-approved systemic treatments for alopecia areata with demonstrated superiority over traditional options. 1

• Before initiating JAK inhibitors: Ensure all needed live vaccines are administered, as they cannot be given during treatment. 1
• Critical safety screening required: Avoid in patients ≥65 years with cardiovascular risk factors, current or long-term smokers, history of cancer, or women contemplating pregnancy. 1

Traditional Second-Line Options (when JAK inhibitors are contraindicated or unavailable):

The following options have lower-quality evidence but remain alternatives:

Methotrexate (Level of Evidence 3):

• Dosing: 15-25 mg per week, with or without prednisolone 10-20 mg daily. 2
• Efficacy: In a retrospective review of 22 patients with alopecia totalis/universalis, 14 achieved complete regrowth (64%), including 3 of 6 treated with methotrexate alone. 2
• This represents the strongest evidence among traditional systemic options for severe disease.

Sulfasalazine (Level of Evidence 3):

• Dosing: 3 g daily orally for 6 months. 3
• Efficacy: In patients with severe alopecia areata (>40% hair loss), 25.6% achieved good response and 30.7% moderate response. 3
• Important caveat: Partial or complete relapse occurred in 67% of responders (10 of 15). 2
• Consider for persistent cases not responding to topical/intralesional corticosteroids, minoxidil, or PUVA. 3

Isoprinosine (Level of Evidence 2-):

• Evidence: An RCT in 32 patients with recalcitrant alopecia areata showed 50% complete remission at 12 weeks versus 0% with placebo. 2
• This represents the highest-quality controlled trial evidence among traditional second-line options, though availability may be limited.

Cyclosporine (Level of Evidence 3):

• Not recommended for severe disease: While evidence confirms it stimulates hair regrowth in some patients, the cosmetically worthwhile response rate is too low to justify the significant side-effect risks when given orally. 2, 1
• Topical tacrolimus showed no response in 11 patients treated for 24 weeks. 2

Adjunctive and Specialized Options

Excimer Laser Therapy (Level of Evidence 3):

• Protocol: 308-nm excimer laser twice weekly for 12 weeks. 2
• Efficacy: 60% response rate in treated patches, with no growth in untreated control patches. 2
• Consider for localized patchy disease as adjunct to systemic therapy.

For Eyelash Alopecia Specifically (Level of Evidence 2-):

• Latanoprost or bimatoprost topically: One study showed 45% achieved complete or moderate eyelash regrowth over 2 years, but conflicting results exist from shorter trials. 2

What NOT to Use

Biologic drugs (anti-TNF agents, alefacept) are ineffective for alopecia areata. 2 Multiple studies and case reports demonstrate no response to etanercept and alefacept, with some reports of alopecia areata actually occurring during anti-TNF therapy for other conditions. 2

Critical Counseling Points

• No treatment alters the long-term course of alopecia areata—all interventions only induce temporary hair growth. 4
• High relapse rates occur even with successful treatment, particularly with sulfasalazine (67% relapse rate). 2
• Disease duration >6 months predicts poor response: Patients with treatment duration exceeding 6 months have significantly lower probability of achieving >80% hair regrowth. 5
• Prognosis is poorest in long-standing extensive disease, with high failure rates across all treatment modalities. 4

Monitoring During Treatment

For JAK inhibitors specifically, counsel patients about increased risks of major adverse cardiovascular events and cancer in high-risk populations, and use extreme caution in patients with cancer history. 1