Appeal type: Experimental/Investigational
Decision: Upheld

Diagnosis: Atopic Dermatitis, Alopecia Areata
Treatment: Rinvoq
The insurer denied the Rinvoq.
The determination is upheld.

The patient has alopecia areata (AA), treated with topical steroids and intralesional steroids. He also has a diagnosis of atopic dermatitis. The provider is requesting Rinvoq. At issue is whether this is likely to be more beneficial than any standard treatment or treatments for the insured's life threatening or disabling condition or disease.

Rinvoq is not likely to be more beneficial than any standard treatment or treatments for the insured's life threatening or disabling condition or disease. There are no large scale studies with Rinvoq in the treatment of alopecia areata. Xeljanz and Ruxolitinib are the best studied. A large review examined Ninety-six mainly multicenter observational studies. Tofacitinib and ruxolitinib were mainly used for the three diseases, and also upadacitinib, abrocitinib, baricitinib, cerdulatinib, delgocitinib, gusacitinib for atopic dermatitis (AD), and baricitinib, PF-06700841, and PF-06651600 for AA. All patients with AD improved, whereas patients with vitiligo and patients with AA showed varied responses, including unresponsive cases (15). Rinvoq is not approved for alopecia areata. 

The janus kinase (JAK)-signal transducers and activators of transcription pathway is involved in downstream signaling of many proinflammatory cytokines, including those within the Th2 axis (e.g., interleukin (IL)-4, IL-5, and IL-13), and oral JAK inhibitors have emerged as a promising therapeutic class for atopic dermatitis (AD). Several recent clinical trials have investigated selective JAK1 inhibitors as monotherapy for moderate-to-severe AD, including recent promising results from a phase III study of abrocitinib and a phase II study of upadacitinib (Rinvoq).  The first generation of JAK inhibitors include tofacitinib, ruxolitinib, baricitinib, and oclacitinib, all of which are approved by the Food and Drug Administration (FDA) for use in humans, except for oclacitinib, which is approved for veterinary use. Second-generation agents have an increased selectivity to certain JAK isoforms; abrocitinib and upadacitinib are commonly referred to as 'selective JAK1 inhibitors' as they have greater selectivity to JAK1 compared to the other isoforms.
Rinvoq (upadacitinib) was evaluated in a 16-week, double-blind, placebo-controlled, parallel-group, dose-ranging portion of this 88-week trial in 8 countries.  Adults with moderate to severe disease and inadequate control by topical treatment were randomized 1:1:1:1, using an interactive response system and stratified geographically, to once-daily upadacitinib oral monotherapy 7.5, 15, or 30 milligrams (mg) or placebo.  The trial showed a 74% improvement (achievement of primary end point) at the 30 mg dose.  Half of the patients receiving the 30 mg dose of upadacitinib achieved clear or almost clear skin based on the Investigator Global Assessment (IGA) score and an improvement of at least 90% in Eczema Area and Severity Index (EASI) at week 16. Improvements in signs and symptoms of AD were shown after the first week in those receiving upadacitinib (7.5, 15, 30 mg), with a significant reduction in pruritus as well as clinical efficacy end points. There was no correlation between the occurrence of adverse events and dose of upadacitinib. Therefore, there were no safety concerns to preclude further investigation of upadacitinib for AD, and phase III trials are currently under way.  These agents offer a solution for patients who do not respond to Dupilumab or cannot tolerate Dupilumab side effects. It would therefore be more appropriate to undergo a trial of Dupixent before Rinvoq. The Rinvoq is not medically necessary at this time.