Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Alopecia
Treatment: Xeljanz 5 mg (milligrams)
The insurer denied the Xeljanz 5 mg.
The denial is overturned.

The patient is a female with alopecia totalis (AT), treated with intralesional steroids. Her provider is requesting Xeljanz. The health plan denied the request, as Xeljanz is not covered for this diagnosis.

Yes, the requested Xeljanz is medically necessary.

A wide range of treatments have been used for the management of alopecia areata (AA), 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 Janus Kinase (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) memory T cells. 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) 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 AA.

Tofacitinib first demonstrated efficacy in AA in the article published. A patient with concomitant psoriasis and AA 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 approximately five years ago, the adult study involved 65 patients, defined as those with AT or alopecia universalis (AU). 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 experienced a higher percent change in SALT score than did patients with AT or AU (81.9% vs 59.0%). Tofacitinib was well tolerated, and there were no serious adverse events.

The adolescent retrospective study, also published approximately five years ago, 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 approximately six years ago was a 2-center, open-label, single-arm trial of 66 patients with AA with > [greater than] 50% scalp hair loss, AT, and AU. Tofacitinib (5 mg [milligrams]) was given twice daily for 3 months. Endpoints included regrowth of scalp hair, as assessed by the 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.

Another recent case report outlined 8 adolescent patients ages 12-19 with AU. All patients experienced substantial regrowth of hair including body, eyebrow and eyelash hair and are still on Tofacitinib, with no adverse effects.

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

AA 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 FDA (United States 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 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.

The systematic review 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 AA with oral formulas of JAK. These agents do need chronic administration to maintain response. Topical formulations did not show satisfactory responses. The safety profile of these agents is evidenced to be favorable.

Therefore, given the support in current literature and lack of effective therapies for AA, Xeljanz is medically necessary.

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