Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Severe Alopecia Areata
Treatment: Xeljanz 10mg Tablets, pre-service
The insurer denied the Xeljanz 10mg (milligrams) Tablets, pre-service
The denial is overturned.

The patient is a female with alopecia areata to the scalp and eyebrows, eyelashes. Her provider is requesting Xeljanz. The health plan denied the request, as alopecia areata is not a covered diagnosis for this treatment. This denial is being appealed.

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

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 SALT (Severity of Alopecia Tool) score over 4 to 18 months of treatment. Patients with AA (alopecia areata) experienced a higher percent change in SALT (Severity of Alopecia Tool) score than did patients with alopecia totalis or alopecia universalis (81.9% vs 59.0%). Tofacitinib was well tolerated, and there were no serious adverse events.

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

Another study published was a 2-center, open-label, single-arm trial of 66 patients with AA (alopecia areata) with > [greater than] 50% scalp hair loss, alopecia totalis (AT), and alopecia universalis (AU). Tofacitinib (5 milligrams) 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 (Severity of Alopecia Tool) 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 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 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 (United States 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.

Therefore, given the above, the treatment with Xeljanz is medically necessary.

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