Appeal type: Medical necessity
Decision: Upheld

Diagnosis: Ulcerative Pancolitis. 
Treatment: Xeljanz 10mg two times a day. 

The insurer denied the Xeljanz 10mg two times a day. 
The denial is upheld. 

The patient is an adult male with ulcerative pancolitis. He has failed Remicade and Entyvio. The patient was doing well on Entyvio monotherapy until approximately 10 months ago when Xeljanz was added. The patient has done well on this regimen. As such, the provider requests continuation of therapy as medically necessary given the patient's response to Xeljanz. 

The insurer denied the Xeljanz because the patient has not failed Humira or
demonstrated contraindication to Humira and because the records do not show that
Xeljanz will not be used with another biologic. 

No, the requested Xeljanz is not medically necessary. The literature does not
support using both Entyvio and Xeljanz together. 

Xeljanz (Tofacitinib) is an oral inhibitor of Janus kinases 1, 2, and 3, that the FDA
(Food and Drug Administration) approved for the treatment of adults with
moderately to severely active ulcerative colitis. In a double-blind, placebocontrolled, phase 2 trial, 194 adults with moderately to severely active ulcerative
colitis were randomly assigned to receive tofacitinib at a dose of 0.5 mg
(milligrams), 3 mg (milligrams), 10 mg (milligrams), or 15 mg (milligrams) or placebo
twice daily for 8 weeks. The primary outcome, clinical response at 8 weeks,
occurred in 32%, 48%, 61%, and 78% of patients receiving tofacitinib at a dose of
0.5 mg (milligrams), 3 mg (milligrams), 10 mg (milligrams) and 15 mg (milligrams), respectively, as compared with 42% of patients receiving placebo (Sandborn WJ, et al. N Engl J Med.). 

OCTAVE Induction 1 and 2 trials, were phase 3, randomized, double-blind,
placebo-controlled trial in adults with ulcerative colitis. In the OCTAVE Induction 1
and 2 trials, 598 and 541 patients, respectively, who had moderately to severely
active ulcerative colitis despite previous conventional therapy or therapy with a
tumor necrosis factor antagonist were randomly assigned to receive induction
therapy with tofacitinib (10 mg [milligrams] twice daily) or placebo for 8 weeks. The
OCTAVE Sustain trial, was a phase 3, randomized, double-blind, placebocontrolled which included 593 patients who had a clinical response to induction
therapy. Patients were randomly assigned to receive maintenance therapy with
tofacitinib (either 5 mg [milligrams] or 10 mg [milligrams] twice daily) or placebo for
52 weeks. 

In the OCTAVE Induction 1 trial, remission at 8 weeks occurred in 18.5% of the
patients in the tofacitinib group versus 8.2% in the placebo group; in the
OCTAVE Induction 2 trial, remission occurred in 16.6% versus 3.6%. In
the OCTAVE Sustain trial, remission at 52 weeks occurred in 34.3% of the patients
in the 5-mg (milligrams) tofacitinib group and 40.6% in the 10-mg (milligrams)
tofacitinib group versus 11.1% in the placebo group (Sandborn WJ, et al. N Engl J Med.). 

Vedolizumab is a drug that specifically targets the alpha 4 beta 7 integrin that is
selectively expressed on gut-homing T lymphocytes. Vedolizumab, by selectively
targeting the alpha 4 beta 7 integrin heterodimer is thought to specifically inhibit
lymphocyte migration within the gut and may not cross the blood-brain barrier. 

The United States Food and Drug Administration (FDA) approved
Entyvio (Vedolizumab) to treat adult patients with moderate to severe ulcerative
colitis and adult patients with moderate to severe Crohn's disease. Vedolizumab's
use in ulcerative colitis has been studied in a randomized, double-blind, placebocontrolled Phase III trial (GEMINI I trial). 47% of the Vedolizumab group versus
26% in the placebo group achieved clinical response, 17% in the
Vedolizumab group versus 5% in the placebo group achieved clinical
remission, and 41% in the Vedolizumab versus 25% in the placebo group
achieved mucosal healing. 

As such, at current time, the literature does not support using both Entyvio and
Xeljanz together. The requested Xeljanz is not medically necessary.