Description
Stelara is a monoclonal antibody that inhibits proteins that contribute to the overproduction of skin cells. It is a biologic drug that inhibits interleukin-12 and interleukin-23. Stelara is available in 45 mg and 90 mg subcutaneous dosage forms, as well as 130 mg single-dose vials. The vials are only used for the treatment of Crohn’s disease. Dosing varies per indication. In general, for adults with plaque psoriasis, for patients weighing less than or equal to 100 kg, the dose of Stelara is 45 mg administered subcutaneously at week 0 and 4, then 45 mg administered subcutaneously every 12 weeks thereafter. For those adults with plaque psoriasis weighing more than 100 kg, the dose is 90 mg subcutaneously at week 0 and 4, and then 90 mg subcutaneously every 12 weeks thereafter. For patients 12 years of age or older with plaque psoriasis, weight-based subcutaneous dosing is recommended (see package insert for details) and follows the same schedule (week 0 and 4, then 12 weeks thereafter). The recommended dose for psoriatic arthritis is 45 mg administered subcutaneously at week 0 and 4 and then 45 mg administered subcutaneously every 12 weeks thereafter. Those patients with coexistent moderate to severe plaque psoriasis who weigh over 100 kg should follow the plaque psoriasis dosing. Crohn’s disease is dosed with a weight-based intravenous loading dose at week 0 (see package insert for details) and then 90 mg subcutaneously every 8 weeks.

Plaque Psoriasis
Psoriasis is a common skin condition that is characterized by frequent episodes of redness, itching and thick, dry, silvery scales on the skin. It is most commonly seen on the trunk, elbows, knees, scalp, skin folds and fingernails. This condition can appear suddenly or gradually and may affect people of any age; it most commonly begins between the ages of 15 and 35. Psoriasis is not contagious. It is an inherited disorder related to an inflammatory response in which the immune system targets the body’s own cells. It may be severe in immunosuppressed people or those who have other autoimmune disorders such as rheumatoid arthritis. The diagnosis is based on the appearance of the skin. A skin biopsy or scraping and culture of the skin patch may be needed to rule out other disorders. If joint pain is present and persistent, an X-ray may be used to evaluate for psoriatic arthritis. Treatment is focused on control of the symptoms and prevention of secondary infections. Lesions that cover all or most of the body may be acutely painful and require hospitalization. The body loses vast quantities of fluid and becomes susceptible to severe secondary infections that can involve internal organs and even progress to septic shock.

Psoriatic Arthritis
Psoriatic arthritis is an inflammatory arthritis that occurs in individuals with psoriasis. The arthritic portion typically presents asymmetrically and the psoriasis may precede or follow joint involvement. The joints most commonly affected are the distal interphalangeal joints of the fingers and toes. Diagnosis of psoriatic arthritis requires both clinical and radiological observations. In patients with psoriatic arthritis, the arthritic remissions tend to be more frequent and complete than rheumatoid arthritis, but progression to chronic arthritis with crippling can occur. Treatment for psoriatic arthritis is similar to that of rheumatoid arthritis and includes disease modifying anti-rheumatic drugs, such as methotrexate. Phototherapy may also be an effective treatment option.

Crohn’s Disease
Crohn's disease is a chronic autoimmune disease that can affect any part of the gastrointestinal tract, but most commonly occurs in the ileum. As a result of the immune attack, the intestinal wall becomes thick, and deep ulcers may form. In addition to the bowel abnormalities, Crohn’s disease can also affect other organs in the body. Typically, first-line treatments such as corticosteroids, 6-MP and azathioprine are used to treat this condition.

Policy: 
Coverage of Stelara is provided when the criteria below are met and there has been a trial and failure of preferred therapy. 

Treatment with Stelara is considered MEDICALLY NECESSARY with documentation of inadequate response, intolerance or confirmed adverse event to preferred treatment for (individuals 18 years of age or greater):

• Psoriatic arthritis
  • ​​​Actively inflamed joints
• • Dactylitis
  • Enthesitis
  • Axial disease
  • Active skin and/or nail involvement
• Plaque psoriasis
  • One of the following:
    • Greater than or equal to 3% body surface area involvement
    • Severe scalp psoriasis
    • Palmoplantar (i.e., palms, soles), facial, or genital involvement
• • Patient is 6 years of age or older
  • Minimum duration of a 4-week trial and failure, contraindication, or intolerance to one of the following topical therapies:
    • Corticosteroids (e.g., betamethasone, clobetasol)
    • Vitamin D analogs (e.g., calcitriol, calcipotriene)
    • Tazarotene
    • Calcineurin inhibitors (e.g., tacrolimus, pimecrolimus)
    • Anthralin
    • Coal tar
• Crohn's disease after:
  •  
  • One of the following:
    • Frequent diarrhea and abdominal pain
    • At least 10% weight loss
    • Complications such as obstruction, fever, abdominal mass
    • Abnormal lab values (e.g., C-reactive protein [CRP])
    • CD Activity Index (CDAI) greater than 220
  • Trial and failure, contraindication or intolerance to at least one self-injectable tumor necrosis factor (TNF) blocker
  • Trial and failure, contraindication, or intolerance to treatment with at least one immunomodulator or corticosteroid (e.g., Purinethol (6-mercaptopurine), Imuran (azathioprine), Sandimmune (cyclosporine A), Prograf (tacrolimus), MTX (methotrexate))
• Ulcerative Colitis after:
  •  
  • One of the following:
    • Greater than 6 stools per day
    • Frequent blood in the stools
    • Frequent urgency
    • Presence of ulcers
    • Abnormal lab values (e.g., hemoglobin, ESR, CRP)
    • Dependent on, or refractory to, corticosteroids
  • Trial and failure, contraindication, or intolerance to treatment with at least one of the following:
    • Corticosteroid
    • Purinethol (6-mercaptopurine)
    • Imuran (azathioprine)
    • Aminosalicylates (e.g., mesalamine (Asacol, Pentasa, Rowasa), olsalazine (Dipentum), sulfasalazine (Azulfidine, Sulfazine))
  • Trial and failure, contraindication or intolerance to at least one self-injectable biologic agent

Prior to initiation of therapy, member must have testing for tuberculosis performed.

Rationale
Plaque Psoriasis
Stelara was evaluated for the treatment of plaque psoriasis in two multicenter, randomized, double-blind, placebo-controlled studies (Ps Study 1 and Ps Study 2). These studies enrolled 1,996 patients age 18 years of age and older with plaque psoriasis who had a minimum body surface area involvement of 10% and were candidates for phototherapy or systemic therapy. The patients were given either placebo, Stelara 45 mg or Stelara 90 mg. In both studies, the endpoints were the proportion of subjects who achieved at least a 75% reduction in the PASI score (PASI 75) from baseline to week 12 and treatment success on the Physician’s Global Assessment. In regard to the primary endpoints in Ps Study 1, 3% of placebo patients reached PASI 75 vs. 67% in the Stelara 45 mg group vs. 66% in the Stelara 90 mg group. In regard to the primary endpoints in Ps Study 2, 4% of placebo patients reached PASI 75 vs. 67% in the 45 mg group vs. 76% in the 90 mg group.

Stelara in adolescent subjects (12-17 years of age) with plaque psoriasis was studied in a multi-center, randomized, double-blind, placebo-controlled study. Subjects were randomized to receive Stelara or placebo. The endpoints were the proportion of patients who achieved a PGA score of 0 or 1, PASI 75, and PASI 90 at week 12. Subjects were followed for up to 60 weeks. In regard to PGA, 69.4% of the Stelara group achieved a PGA of 0 or 1 vs. 5.4% in the placebo group. In regard to PASI 75, 80.6% of the Stelara group achieved a PASI 75 vs. 10.8% in the placebo group. In regard to PASI 90, 61.1% of the Stelara group achieved PASI 90 vs. 5.4% in the placebo group.

Psoriatic Arthritis
Stelara was evaluated in psoriatic arthritis in two randomized, double-blind, placebo-controlled studies in adult patients with psoriatic arthritis despite therapy with non-steroidal anti-inflammatory drugs or disease modifying anti-rheumatic agents. These studies included 927 patients, and those patients were randomized to receive Stelara 45 mg, 90 mg, or placebo. The primary endpoint of the studies was the percentage of patients achieving ACR20 response at week 24. In both studies, a greater proportion of patients achieved ACR 20, ACR 50, and PASI 75 response in the Stelara 45 mg and 90 mg groups compared to placebo at week 24. In PsA study 1, ACR20 was achieved in 23% of placebo patients, 42% of Stelara 45 mg patients, and 50% of Stelara 90 mg patients. In PsA study 2, ACR20 was achieved in 20% of placebo patients, 44% of Stelara 45 mg patients, and 44% of Stelara 90 mg patients.

Crohn’s Disease
Stelara was evaluated in 3 randomized, double-blind, placebo-controlled clinical studies in adult patients with moderately to severely active Crohn’s disease. There were two 8-week intravenous induction studies (CD-1 and CD-2) followed by a 44-week subcutaneous randomized withdrawal maintenance study (CD-3) representing 52 weeks of therapy.

For CD-1 and CD-2, induction of clinical response at week 6 and clinical remission at week 8 was evaluated. CD-1 included patients who had failed or were intolerant to TNF inhibitors, while CD-2 included patients who were intolerant or had failed treatment with steroids, an immunomodulator, or both. There were 1,409 patients randomized in these two trials. The clinical response at week 6 for the placebo groups was 21% and 29% in trials CD-1 and CD-2, respectively. The clinical response at week 6 in the Stelara group was 34% and 56% for trials CD-1 and CD-2, respectively. The clinical remission at week 8 was 7% and 20% in the placebo groups for trials CD-1 and CD-2, respectively. The clinical remission at week 8 was 21% and 40% for trials CD-1 and CD-2, respectively. In these two studies, a greater proportion of patients treated with Stelara achieved clinical response at week 6 and clinical remission at week 8 compared to placebo. Clinical response and remission were significant as early as week 3 in Stelara-treated patients and continued to improve through week 8.

CD-3 (the maintenance study) evaluated 388 patients who achieved clinical response at week 8 of induction with Stelara in studies CD-1 and CD-2. Patients were randomized to receive subcutaneous Stelara 90 mg every 8 week of placebo for 44 weeks. At 52 weeks from initiation of the induction dose, 36% of placebo patients had reached a clinical remission vs. 53% of patients in the Stelara treatment group. At the same time point, 44% of placebo patients had a clinical response vs. 59% in the Stelara group. At week 44, 47% of patients who received Stelara were steroid-free and in clinical remission compared to 30% of patients in the placebo group.

References  

1. Ustekinumab (Stelara) [package insert]. Horsham, PA; Janssen Biotech, Inc., Revised September 2017.
2. U.S. Food and Drug Administration. Center for Drug Evaluation and Research. FDA Labeling Information. Ustekinumab (Stelara) http://www.fda.gov.  

Coding Section 

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive. 

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

"Current Procedural Terminology © American Medical Association. All Rights Reserved" 

History From 2018 Forward