Appeal type: Medical necessity
Decision: Overturned

Diagnosis: L63.0 - Alopecia (capitis) totalis
Treatment:  Xeljanz 5MG (milligrams)
The insurer denied the  Xeljanz 5MG (milligrams)
The denial is overturned

The patient is a female with alopecia totalis and loss of eyebrows and eyelashes. She is treated with topical and intralesional steroids, topical Squaric acid and anthralin. The patient's provider is requesting Xeljanz. The health plan denied the request as Xeljanz is not Food and Drug Administration approved for alopecia areata.

Yes, the proposed treatment with Xeljanz is medically necessary.

The patient is a female with alopecia totalis and loss of eyebrows and eyelashes.

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 Janus kinase inhibitor, which blocks interleukin (IL)-15 signaling. Interleukin-15 has a pivotal role in life and death of natural killer (NK) and CD8 (cluster of differentiation 8) memory T cells. Interleukin-15 signals through a heterotrimeric receptor involving the common gamma chain (c) shared with interleukin-2, interleukin-4, interleukin-7, interleukin-9, and interleukin-21, interleukin-2/interleukin-15 receptor (interleukin-15R) shared with interleukin-2 and a private interleukin-15R subunit. IFN- or CD40 (cluster of differentiation 40) ligand-stimulated dendritic cells coordinately express IL-15 and IL-15R. Cell surface IL-15R presents IL-15 in-trans to cells that express interleukin-2/interleukin-15R and c. Interleukin-15 is being used to treat patients with metastatic malignancy. However, 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 interleukin-15 action. Dysregulated 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 a published article. 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:

An 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 (SALT) 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 SALT score was 93% (mean 61%; 1%-100%) at an average of 6.5 months of treatment. Adverse events were mild (4).

Another study published 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 (5 milligrams [mg]) 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 (SALT) score with no significant adverse events (5).

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).

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 are an extremely distressing disease.  With further case reports of "off-label" uses of medications such as Xeljanz, more treatment options can become available.  Xeljanz is currently Food and Drug Administration-approved for rheumatoid arthritis and undergoing approval trials for psoriasis and psoriatic arthritis.  It is known to be safe and effective in the conditions for which it is Food and Drug Administration approved.  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.

The systematic review (13) performed a literature search to identify clinical trials and case reports, and concluded that several clinical studies have shown very promising results in the treatment of alopecia areata with oral formulas of Janus kinases inhibitors (JAKis). These agents do need chronic administration to maintain response. Topical formulations did not show satisfactory responses. The safety profile of these agents is described as favorable.

No, the health plan did not act reasonably, with sound medical judgment and in the best interest of the patient.