Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Alopecia Areata
Treatment: Xeljanz
The insurer denied: Xeljanz
The denial is overturned.

The patient is an adult female with alopecia areata, treated with oral, topical and intralesional steroids.  The patient has responded well to Xeljanz. The provider is requesting continuation. 

The proposed treatment with Xeljanz is medically necessary.
The health plan denied the request as Xeljanz is not Food and Drug Administration (FDA) approved for alopecia areata.  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 (two percent or five percent), 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 interleukin (IL)-15 signaling.  Interleukin (IL)-15 has a pivotal role in life and death of natural killer (NK) and cluster of differentiation eight (CD8) memory T cells. Interleukin-15 is an inflammatory cytokine involved in immunological memory including that to self, thereby playing a role in autoimmune diseases. Dysregulated interleukin-15 expression was demonstrated in patients with rheumatoid arthritis, inflammatory bowel disease, psoriasis, celiac disease, and alopecia areata.

Published in 01/2017, the adult study involved 65 patients, defined as those with alopecia totalis or alopecia universalis.  Seventy-seven percent achieved a clinical response, with 58% of patients achieving greater than 50% change in Severity of Alopecia Tool score over four to 18 months of treatment. Patients with alopecia areata  experienced a higher percent change in Severity of Alopecia Tool (SALT) score than did patients with alopecia totalis or alopecia universalis (81.9% versus 59.0%). Tofacitinib was well tolerated, and there were no serious adverse events (3).

The adolescent retrospective study, also published in 01/2017, involved 13 patients, aged 12 to 17 years.  Nine patients experienced clinically significant hair regrowth. Median percent change in Severity of Alopecia Tool score was 93% (mean 61%; 1%-100%) at an average of 6.5 months of treatment. Adverse events were mild (4).

1)	Another study published in 09/2016 was a two-center, open-label, single-arm trial of 66 patients with alopecia areata with greater than (>) 50% scalp hair loss, alopecia totalis (AT), and alopecia universalis (AU). Tofacitinib (five milligrams) was given twice daily for three months. Endpoints included regrowth of scalp hair, as assessed by the severity of alopecia tool (SALT), duration of hair growth after completion of therapy, and disease transcriptome.  Thirty-two percent experienced 50% or greater improvement in Severity of Alopecia Tool score with no significant adverse events (5).

2)	Another recent case report outlined eight adolescent patients ages 12 to 19 with alopecia universalis.  All patient experienced substantial regrowth of hair including body, eyebrow and eyelash hair and are still on Tofacitinib, with no adverse effects (7).

3)	Several case reports have also documented substantial hair regrowth leading to reestablishment of eyelashes and other functional hair reducing incidence of corneal abrasions, etc.

Alopecia areata and its variants is an extremely distressing disease.  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.

Therefore given the support in current literature and lack of effective therapies for alopecia areata, and this patient's favorable response to therapy, Xeljanz is medically necessary.