Appeal type: Formulary Exception
Decision: Upheld

Diagnosis: Alopecia Unversalis.
Treatment: Formulary exception for Tofacitinib.
The insurer denied the formulary exception for Tofacitinib.
The denial is upheld.

The patient is a female with alopecia areata, treated with diprosone and anthralin. Her provider is requesting topical tofacitinib. The patient also has hair loss to eyes/face and body. The health plan requires use of formulary agents such as clobetasol, betamethasone and desoximetasone.

No, the health plan should not cover the formulary exception for Tofacitinib.

The formulary medications would also be effective and would not be expected to have adverse effects.

JAK (janus kinase) inhibitors are emerging as first line therapies for alopecia areata given their promising efficacy. 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% [percent] 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 inhibitor, which blocks IL (Interleukin) -15 signaling. IL-15 has a pivotal role in life and death of natural killer (NK) and CD8 (cluster of differentiation 8) memory T cells (lymphocytes). IL-15 signals through a heterotrimeric receptor involving the common gamma chain shared with IL-2, IL-4, IL-7, IL-9, and IL-21, IL-2/IL-15 receptor (R) shared with IL-2 and a private IL-15R subunit. IFN (interferon)- 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 IL-2/IL-15R and common gamma chain. 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 an article published approximately eight years ago. A patient with concomitant psoriasis and alopecia areata was treated with the medication, and serendipitously his alopecia areata reversed. Since then, further reports have emerged documenting its efficacy.

A phase I, 28 week prospective, placebo-controlled, double-blind study (Bokhari) in patients with alopecia universalis investigated hair regrowth with two topical JAK inhibitors, 2% tofacitinib and 1% ruxolitinib. Topical clobetasol dipropionate 0.005% was the active comparator while vehicle was used as the placebo control. Sixteen patients were recruited for the study. Six patients demonstrated partial hair regrowth in areas treated with 2% tofacitinib ointment applied twice daily. Five patients demonstrated partial hair regrowth in the areas treated with 1% ruxolitinib ointment. Ten patients demonstrated partial hair regrowth in the areas treated with clobetasol dipropionate 0.05% ointment. No regrowth was observed in the placebo treated area.

Therefore, given that the patient has not tried clobetasol and the efficacy of clobetasol was superior to topical tofacitinib in the above trial, the request is not medically necessary.