Appeal type: Experimental/Investigational
Decision: Upheld

Diagnosis: Alopecia Areata. 
Treatment: Xeljanz 5 mg tablet. 

The insurer dened the Xeljanz 5 mg tablet. 
The determination is overturned. 

The patient has alopecia universalis (severe form of alopecia areata), treated with oral, topical and intralesional steroids. The patient had full regrowth of his entire body hair with Xeljanz. The provider is requesting continuation of Xeljanz. 

At issue is whether the Xeljanz 5 mg tablet is likely to be more beneficial than any standard treatment or treatments for the insured's life threatening or disabling condition or disease. 

Yes. Alopecia universalis is a severe form of alopecia areata (AA) involving total body hair loss - including eyelashes, groin, etc. Regrowth of hair rarely occurs. Treatment studies for any form of alopecia areata are difficult to perform because the disease has an unpredictable course, and much investigation is still needed. 
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 has now shown to be more beneficial than any of these other therapies. 

Xeljanz is a Jak-kinase inhibitor, which blocks interleukin (IL)-15 signaling. IL-15 has a pivotal role in life and death of natural killer (NK) and CD8 memory T cells. IL-15 signals through a heterotrimeric receptor involving the common gamma chain (yc) shared with IL-2, IL-4, IL-7, IL-9, and IL-21, IL-2/IL-15 receptor beta [] (IL-15R) shared with IL-2 and a private IL-15R subunit. interferon (IFN) or cluster of differentiation CD40 ligand-stimulated dendritic cells coordinately express IL-15 and IL-15R [alpha]. Cell surface IL-15R [alpha] presents IL-15 in-trans to cells that express IL-2/IL-15R and common gamma chain (yc). IL-15 is being used to treat patients with metastatic malignancy. However, IL-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-15 action. Dysregulated IL-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: 
- Published in January 2017, the adult study involved 65 patients, defined as those with alopecia totalis or alopecia universalis. 77% achieved a clinical response, with 58% of patients achieving greater than 50% change in severity of alopecia tool (SALT) score over 4 to 18 months of treatment. Patients with AA experienced a higher percent change in 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. 
- 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 score was 93% (mean 61%; 1%-100%) at an average of 6.5 months of treatment. Adverse events were mild. 
- Another study published in September 2016 was a 2-center, open-label, single-arm trial of 66 patients with AA with greater than (>) 50% scalp hair loss, alopecia totalis (AT), and alopecia universalis (AU). Tofacitinib (5 milligrams (mg)) was given twice daily for 3 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. 32% experienced 50% or greater improvement in SALT score with no significant adverse events. 
- 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. 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 (FDA)-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 FDA 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.