Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Ulcerative Colitis. 
Treatment: Xeljanz 10mg (milligram) Tablet. 

The insurer denied: Xeljanz 10mg (milligram) Tablet. 
The denial is overturned. 

This patient is an adolescent male with ulcerative colitis.  The patient has tried and failed Entyvio, Inflectra, mesalamine, prednisone, Remicade, budesonide, and methotrexate.  The patient continues to have weight loss, abdominal pain, bloody stools, and diarrhea. The request is for Xeljanz. 

The proposed treatment with Xeljanz is medically necessary. 

Conventional therapeutic agents such as mercaptopurine (6-MP), azathioprine, or methotrexate take months to take effect. 
Xeljanz (Tofacitinib) is an oral inhibitor of Janus kinases I, II, and III, that the Food and Drug Administration (FDA) approved for the treatment of adults with moderately to severely active ulcerative colitis. In a double-blind, placebo-controlled, phase II trial, 194 adults with moderately to severely active ulcerative colitis were randomly assigned to receive tofacitinib at a dose of 0.5 milligrams (mg), three milligrams, ten milligrams, or 15 milligrams or placebo twice daily for eight weeks. The primary outcome, clinical response at eight weeks, occurred in 32%, 48%, 61%, and 78% of patients receiving tofacitinib at a dose of 0.5 milligrams (P=0.39), three milligrams (P=0.55), ten milligrams (P=0.10), and 15 milligrams (P<0.001), respectively, as compared with 42% of patients receiving placebo (Sandborn WJ, et al. N Engl J Med. 2012). 

OCTAVE Induction I and II trials, were phase III, randomized, double-blind, placebo-controlled trial in adults with ulcerative colitis. In the OCTAVE Induction I and II 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 (ten milligrams twice daily) or placebo for eight weeks. The OCTAVE Sustain trial, was a phase III, randomized, double-blind, placebo-controlled which included 593 patients who had a clinical response to induction therapy. Patients were randomly assigned to receive maintenance therapy with tofacitinib (either five milligrams or ten milligrams twice daily) or placebo for 52 weeks. In the OCTAVE Induction I trial, remission at eight weeks occurred in 18.5% of the patients in the tofacitinib group versus 8.2% in the placebo group (P=0.007); in the OCTAVE Induction II trial, remission occurred in 16.6% versus 3.6% (P<0.001). In the OCTAVE Sustain trial, remission at 52 weeks occurred in 34.3% of the patients in the five-milligram tofacitinib group and 40.6% in the ten-milligram tofacitinib group versus 11.1% in the placebo group (P<0.001 for both comparisons with placebo) (Sandborn WJ, et al. N Engl J Med. 2017.). 

In a retrospective single-center cohort study of consecutive hospitalized pediatric patients initiating tofacitinib for refractory ulcerative colitis from 2018-2021, eleven patients met inclusion criteria. All patients demonstrated non-response to both intravenous corticosteroids and anti-tumor necrosis factor (TNF) therapy prior to tofacitinib initiation. Eight of 11 patients remained colectomy-free at 90-days following hospital admission and six remained colectomy-free over median 182-day follow-up, including four of whom remained on tofacitinib (Constant BD et al). 

The health plan suggests use of conventional therapeutic agents.  However, given the patient's active symptoms, conventional therapeutic agents would not be indicated as per the American College of Gastroenterology (ACG) guidelines for the management of ulcerative colitis as these agents are used for maintenance of remission, and not induction of remission.  Given this patient's symptoms, the patient requires an agent that would induce remission.  The patient has failed all therapeutic class medications approved for ulcerative colitis in pediatrics.