Appeal type: Experimental/Investigational
Decision: Upheld

Diagnosis: Alopecia Areata.
Treatment: Xeljanz 10MG (milligram) Tablet.

The insurer denied Xeljanz 10MG (milligram) Tablet.  The denial is overturned.

The patient is an adult female. She is noted to have alopecia areata, with over 40% (percent) scalp hair loss. She has been treated with oral, topical and intralesional steroids. Her provider is requesting Xeljanz. The health plan denied coverage, as Xeljanz is not FDA (United States Food and Drug Administration)-approved for alopecia areata. The denial is being appealed.

The health plan should cover the treatment with Xeljanz.

A wide range of treatments have been used for the management of alopecia areata, most of which are not highly effective. Treatments include topical or intralesional corticosteroids, topical minoxidil (2% or 5%), topical anthralin, systemic corticosteroids, cyclosporine, and other immunosuppressants. A dependable and safe treatment for extensive disease (totalis or universalis) has yet to be found. Given the rarity of the disease, large randomized controlled trials are extremely difficult.
Xeljanz is a Jak-kinase inhibitor, which blocks IL (Interleukin)-15 signaling. IL (Interleukin)-15 has a pivotal role in life and death of natural killer (NK) and CD8 (cluster of differentiation 8) memory T cells. IL (Interleukin)-15 signals through a heterotrimeric receptor involving the common gamma chain (yc) shared with IL (Interleukin)-2, IL (Interleukin)-4, IL (Interleukin)-7, IL (Interleukin)-9, and IL (Interleukin)-21, IL (Interleukin)-2/IL (Interleukin)-15 receptor (IL-15R) shared with IL (Interleukin)-2 and a private IL (Interleukin)-15R (receptor) subunit. IFN (interferon)- or CD40 (cluster of differentiation 40) ligand-stimulated dendritic cells coordinately express IL (Interleukin)-15 and IL (Interleukin)-15R (receptor). Cell surface IL (Interleukin)-15R (receptor) presents IL (Interleukin)-15 in-trans to cells that express IL (Interleukin)-2/IL (Interleukin)-15R (receptor) and yc (common gamma chain) IL (Interleukin)-15 is being used to treat patients with metastatic malignancy. However, IL (Interleukin)-15 is an inflammatory cytokine involved in immunological memory including that to self, thereby playing a role in autoimmune diseases. These insights provide the scientific basis for clinical strategies directed toward diminishing IL (Interleukin)-15 action. Dysregulated IL (Interleukin)-15 expression was demonstrated in patients with rheumatoid arthritis, inflammatory bowel disease, psoriasis, celiac disease, and alopecia areata. Tofacitinib first demonstrated efficacy in alopecia areata in the article published in 2014. A patient 
with concomitant psoriasis and alopecia areata was treated with the medication and serendipitously his alopecia areata reversed. Since then, further case reports have emerged documenting its efficacy, which has led to the very recently published retrospective studies involving adults and adolescents, as well as others, summarized below:  1) Published in January 2017, the adult study involved 65 patients, defined as those with alopecia totalis or alopecia universalis (10). 77% achieved a clinical response, with 58% of patients achieving greater than 50% change in SALT (Severity of Alopecia Tool) score over 4 to 18 months of treatment. Patients with AA (alopecia areata) experienced a higher percent change in SALT (Severity of Alopecia Tool) score than did patients with alopecia totalis or alopecia universalis (81.9% vs 59.0%). Tofacitinib was well tolerated, and there were no serious adverse events.  2) The adolescent retrospective study, also published in January 2017, involved 13 patients, aged 12 to 17 years. Nine patients experienced clinically significant hair regrowth. Median percent change in SALT (Severity of Alopecia Tool) score was 93% (mean 61%; 1%-100%) at an average of 6.5 months of treatment. Adverse events were mild.

Alopecia areata and its variants is an extremely distressing disease. With further case reports of "off-label" uses of medications such as Xeljanz, more treatment options can become available. Biologic medications as a whole have many off label uses, leading to better outcomes in rare diseases for which large, randomized trials are not readily available.