• Depending on the condition being treated, some improvement is usually within 3 weeks of a Stelara dose.
• It may take up to 8 weeks to see a response in some people.
• For Crohn's disease: 41 to 51% of adults had experienced a CDAI 70 by week 3. After 44 weeks, 47% of patients were in clinical remission and corticosteroid free.
• For ulcerative colitis: 19% of adults given Stelara achieved clinical remission by week 8. By week 44, 45% of patients had achieved clinical remission and 74% experienced a clinical response.
• For psoriasis: 66-76% of adults achieved a PASI75 after 12 weeks.
• For psoriatic arthritis: 44%-50% of adults achieved an ACR20 after 24 weeks treatment and 9%-14% achieved an ACR70.
• Stelara reduces disease activity in most people; however, less achieve remission.

What is Stelara?

Stelara (ustekinumab) is a targeted treatment that reduces inflammation and may be used in the treatment of:

• Plaque psoriasis in adults and children who are at least 6 years old
• Psoriatic arthritis in adults, sometimes in combination with methotrexate
• Active psoriatic arthritis in children who are at least 6 years old
• Moderate-to-severe Crohn's disease in adults after other medicines have failed
• Moderate-to-severe ulcerative colitis in adults.

Stelara is administered by injection, under the skin (subcutaneous). The dosage and frequency of administration depend on the condition being treated. After appropriate training, people can be taught how to self-administer Stelara or caregivers shown how to give it to another person.

How long before Stelara starts to work?

The onset of effect of Stelara depends on the condition being treated.

Crohn's disease

Crohn’s disease improvement is measured using the Crohn’s Disease Activity Index (CDAI). This looks at various signs, symptoms, and other variables present over the past seven days and assigns a severity score.

Clinical response in two published trials was defined as a reduction in CDAI score of greater than or equal to 100 points or a CDAI score of less than 150 at week 6 and clinical remission as a CDAI score of less than 150 at week 8.

• By week 3, 41 to 51% had experienced a CDAI score of at least 70. This improved to 44 to 65% by week 6.
• 34 to 56% of patients achieved a CDAI100 at week 6 with Stelara and by week 8, 21 to 40% had achieved clinical remission (CDAI150). By week 8 response rates had improved to 38-58%.
• At week 44, 47% of patients receiving Stelara were in clinical remission and corticosteroid free compared with only 30% receiving placebo.

Ulcerative colitis

Trials of Stelara in patients with ulcerative colitis (UC) used the Mayo score to determine the effectiveness of treatment. The Mayo score is a combined endoscopic (a tool that looks into the small bowel) and clinical scale to assess the severity of UC.

The following trial reports have been published:

• 19% of patients given Stelara (6mg/kg/dose) achieved clinical remission (defined as a Mayo score of 0 or 1 by week 8) compared with only 7% of those receiving placebo ( a pretend pill) in a study of 961 patients with ulcerative colitis. The patients had to have failed previous treatment with corticosteroids, immunomodulators, or at least one biologic.
• A clinical response (defined as at least a 30% difference in Mayo score or an improvement of at least 2 points) was experienced in 58% of those receiving Stelara compared with 31% receiving placebo.
• In another study, 45% of patients achieved clinical remission (defined as a Mayo score of 0 or 1 after 44 weeks) compared with only 26% receiving placebo. 74% experience a clinical response after 44 weeks.

Psoriasis

For psoriasis, the response is measured using the Psoriasis Area and Severity Index (PASI) score. The PASI 75 is a 75% reduction in the PASI score from baseline, after 12 weeks of therapy.

• A PASI75 was experienced in 66% to 76% of participants in two studies (Ps Study 1 and Ps study 2)
• 59% to 73% were reported to have cleared or minimal psoriatic plaques remaining.

Psoriatic arthritis

For psoriatic arthritis, the American College of Rheumatology (ACR) responder criteria is used.

This assesses several variables, such as the number of tender and number of swollen joints, patient global assessment, physician global assessment, functional ability measure visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).

The percentage (20, 50, or 70) is an indication of the amount of improvement.

• An ACR of 20% was reported in 44%-50% of patients given 90mg Stelara and 42% to 44% of patients given Stelara 45mg after 24 weeks of treatment.
• An ACR of 50% was reported in 23%-28% of patients given 90mg Stelara and 17% to 25% of patients given Stelara 45mg after 24 weeks of treatment.
• An ACR of 70% was reported in 9%-14% of patients given 90mg Stelara and 7% to 12% of patients given Stelara 45mg after 24 weeks of treatment.

How does Stelara work?

Stelara (ustekinumab) is a monoclonal antibody.

Monoclonal antibodies are man-made proteins that act like human antibodies in the immune system. They are a type of “targeted” treatment. Targeted treatments attach only to specific proteins in the body.

Stelara binds to the p40 protein subunit that is used by two cytokines, IL-12 and IL-23. Cytokines are signaling substances that help control immunity, inflammation, and the manufacture of blood cells.

By binding to this protein, Stelara disrupts the interaction of these two cytokines which have been identified as being important contributors to chronic inflammation that is a hallmark of Crohn’s disease and ulcerative colitis. These cytokines are also present in skin lesions associated with psoriasis and in the joints of people with psoriatic arthritis.