Is alopecia a known adverse effect of ruxolitinib (Jakafi) and how should it be evaluated and managed in a patient experiencing hair thinning after starting therapy?

Ruxolitinib and Alopecia: Evaluation and Management

Ruxolitinib Does NOT Cause Alopecia as an Adverse Effect

Alopecia is not a recognized adverse effect of ruxolitinib (Jakafi); rather, oral ruxolitinib is an investigational treatment that induces hair regrowth in patients with moderate-to-severe alopecia areata. 1

The NCCN guidelines for myeloproliferative neoplasms, which include comprehensive monitoring recommendations for ruxolitinib therapy, do not list alopecia or hair loss among the adverse effects requiring surveillance or management. 2 The primary hematologic toxicities requiring monitoring are thrombocytopenia, anemia, and neutropenia, managed through dose reduction or interruption. 2

Ruxolitinib as Treatment FOR Alopecia Areata

Oral Ruxolitinib Efficacy

• Oral ruxolitinib 20 mg twice daily induces remarkable hair regrowth in 75% of patients with moderate-to-severe alopecia areata, with average regrowth of 92% after 3-6 months of treatment. 1

• In comparative studies, oral ruxolitinib 20 mg twice daily achieved a mean change in Severity of Alopecia Tool (SALT) score of 93.8 ± 3.25 in patients with more than 30% scalp hair loss, alopecia totalis, or alopecia universalis. 3

• Ruxolitinib demonstrates a shorter duration to initial hair regrowth compared to tofacitinib, though final outcomes are similar between the two JAK inhibitors. 3

• Approximately two-thirds of patients experience relapse after discontinuation of oral JAK inhibitor therapy, highlighting the need for continued treatment. 3

Topical Ruxolitinib Limitations

• Topical ruxolitinib 1.5% cream failed to demonstrate significant efficacy in a randomized, vehicle-controlled phase 2 study of patients with 25-100% hair loss by SALT score. 4

• Case reports of topical ruxolitinib treatment failure in alopecia areata suggest that extensive disease requires oral rather than topical administration for adequate therapeutic effect. 5

Safety Profile

• Oral ruxolitinib is well tolerated in alopecia areata patients, with no serious adverse effects reported in clinical trials at 20 mg twice daily dosing. 3, 1

• Gene expression profiling demonstrates treatment-related downregulation of inflammatory markers, including cytotoxic T lymphocyte signatures and interferon response genes, with upregulation of hair-specific markers. 1

Clinical Approach to Hair Thinning in a Patient on Ruxolitinib

Differential Diagnosis

If a patient on ruxolitinib for myeloproliferative neoplasm develops hair thinning, consider alternative etiologies:

• Telogen effluvium secondary to systemic illness, stress, or the underlying myeloproliferative disorder itself
• Androgenetic alopecia (pattern hair loss affecting temples, vertex, and mid-frontal scalp with preserved occipital and lateral hair) 6
• Alopecia areata (round or oval patches of complete hair loss, short broken hairs with tapered ends, yellow dots on dermoscopy) 7
• Anemia-related hair changes from the underlying disease or ruxolitinib-induced anemia 2

Evaluation Strategy

• Examine the pattern of hair loss: diffuse thinning versus patchy versus patterned distribution 7, 6

• Perform dermoscopy to identify yellow dots (alopecia areata), miniaturized hairs (androgenetic alopecia), or other diagnostic features 7

• Review complete blood count, as ruxolitinib commonly causes anemia requiring dose modification or transfusion support 2

• Consider skin biopsy only when early scarring alopecia is a concern or diagnosis remains uncertain 7

Management Based on Etiology

For androgenetic alopecia: Initiate oral finasteride 1 mg daily and topical minoxidil 5% twice daily, as these are the only FDA-approved treatments proven to halt progression. 6

For alopecia areata with limited patchy disease: Intralesional triamcinolone acetonide (5-10 mg/mL) achieves 62% full regrowth in patients with fewer than five patches less than 3 cm in diameter. 7

For telogen effluvium: Address underlying triggers, optimize management of the myeloproliferative neoplasm, and correct anemia through transfusion or dose adjustment per NCCN guidelines. 2

Critical Pitfall to Avoid

Do not attribute hair loss to ruxolitinib as a drug side effect without thorough evaluation, as this may delay diagnosis and treatment of the actual underlying cause. The drug label and clinical guidelines do not recognize alopecia as an adverse effect of ruxolitinib therapy for myeloproliferative neoplasms. 2