Skyrizi (risankizumab-rzaa) - 4 indications

Scroll down for more information on each indication:

• for the treatment of plaque psoriasis; approved April 2019
• for the treatment of adults with active psoriatic arthritis; approved January of 2022
• for the treatment of adults with moderately to severely active Crohn's disease; approved June of 2022
• for the treatment of adults with moderately to severely active ulcerative colitis; approved June of 2024

General Information

Skyrizi (risankizumab-rzaa) is an interleukin-23 (IL-23) antagonist. IL-23 is involved in inflammation and is thought to be associated to several chronic immune-mediated diseases, including psoriasis.

Skyrizi is specifically indicated for:

• the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy
• the treatment of active psoriatic arthritis in adults
• for the treatment of adults with moderately to severely active Crohn's disease
• for the treatment of adults with moderately to severely active ulcerative colitis

Skyrizi is supplied as an injection for subcutaneous administration. Scroll down for recommended dosing/administration for each indication.

Mechanism of Action

Skyrizi (risankizumab-rzaa), an interleukin-23 antagonist, is a humanized immunoglobulin G1 (IgG1) monoclonal antibody. It selectively binds to the p19 subunit of human interleukin 23 (IL-23) cytokine and inhibits its interaction with the IL-23 receptor. IL-23 is a naturally occurring cytokine that is involved in inflammatory and immune responses. Risankizumab-rzaa inhibits the release of pro-inflammatory cytokines and chemokines.

Side Effects

Adverse effects associated with the use of Skyrizi may include, but are not limited to, the following:

Plaque Psoriasis and Psoriatic Arthritis: upper respiratory infections, headache, fatigue, injection site reactions, and tinea infections.

Crohn’s Disease: Induction: upper respiratory infections, headache, and arthralgia. Maintenance: arthralgia, abdominal pain, injection site reactions, anemia, pyrexia, back pain, arthropathy, and urinary tract infection.

Ulcerative Colitis: Induction: arthralgia. Maintenance: arthralgia, pyrexia, injection site reactions, and rash.

Skyrizi may also increase the risk of infection. Instruct patients to seek medical advice if signs or symptoms of clinically important infection occur. If such an infection develops, do not administer Syrizi until the infection resolves. Patients should be tested for tuberculosis prior to administration of Skyrizi.

Indication 1 - adults with plaque psoriasis

approved April of 2019

The recommended dose is 150 mg (two 75 mg injections) administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter.

The FDA approval of Skyrizi was based on AbbVie's global Phase 3 psoriasis program, which assessed the safety and efficacy of Skyrizi in adults with moderate to severe plaque psoriasis across four randomized, placebo and/or active-controlled pivotal studies: ultIMMa-1, ultIMMa-2, IMMhance and IMMvent. The co-primary endpoints of these studies were Psoriasis Area and Severity Index (PASI 90) and static Physician Global Assessment [sPGA] score of clear or almost clear [sPGA 0/1] at 16 weeks versus placebo.

In ULTIMMA-1 and ULTIMMA-2, 997 subjects were enrolled (including 598 subjects randomized to the Skyrizi 150 mg group, 200 subjects randomized to the placebo group, and 199 to the biologic active control group). Subjects received treatment at Weeks 0, 4, and every 12 weeks thereafter. In ultIMMa-1 and ultIMMa-2 at 16 weeks, PASI 90 was achieved in 75 percent of patients treated with Skyrizi, compared to 5 and 2 percent receiving placebo, respectively (p<0.001). PASI 100 was achieved in 36 and 51 percent of patients treated with Skyrizi, compared to 0 and 2 percent receiving placebo, respectively (p<0.001). At one year (52 weeks), 82 and 81 percent of patients treated with Skyrizi achieved PASI 90, and 56 and 60 percent achieved PASI 100, respectively (p<0.001). An integrated analysis of ultIMMa-1 and ultIMMa-2 showed most patients treated with Skyrizi who achieved PASI 90 and PASI 100 at week 16 maintained this response at one year (88 and 80 percent, respectively).

IMMHANCE enrolled 507 subjects (407 randomized to Skyrizi 150 mg and 100 to placebo). Subjects received treatment at Weeks 0, 4, and every 12 weeks thereafter. At Week 16, Skyrizi was superior to placebo on the co-primary endpoints of sPGA 0 or 1 (84% Skyrizi and 7% placebo) and PASI 90 (73% Skyrizi and 2% placebo). The respective response rates for Skyrizi and placebo at Week 16 were: sPGA 0 (46% Skyrizi and 1% placebo); PASI 100 (47% Skyrizi and 1% placebo); and PASI 75 (89% Skyrizi and 8% placebo).

IMMvent was a multinational, phase 3, randomized, double-blind, double-dummy, active-controlled trial – Part A, patients were randomized 1:1 to receive via subcutaneous injection RZB 150 mg at weeks 0 and 4 or ADA 80 mg at week 0 and 40 mg every 2 weeks from week 1 to week 15 (Figure 1) – Part B (weeks 16-44), patients initially randomized to receive ADA who achieved PASI 50 to <90 at week 16 were re-randomized 1:1 to receive RZB 150 mg at weeks 16, 20, and 32 or ADA 40 mg every 2 weeks up to week 41. Skyrizi demonstrated superiority versus adalimumab in the IMMvent study, with 72 percent of patients achieving PASI 90 compared to 47 percent of patients treated with adalimumab at Week 16 (p<0.001). Following re-randomization at Week 16, 66 percent of patients who started on adalimumab and switched to Skyrizi  achieved PASI 90, compared to 21 percent who continued on adalimumab at Week 44 (p<0.001). The co-primary endpoints of sPGA 0/1 and PASI 90 at Week 16 were met (p<0.001).

Indication 2 - adults with active psoriatic arthritis

approved January of 2022

The recommended dose is 150 mg (two 75 mg injections) administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter. Skyrizi may be administered alone or in combination with non-biologic disease-modifying antirheumatic drugs.

The FDA approval of Skyrizi for adults with active psoriatic arthritis was based on two pivotal studies, KEEPsAKE-1 and KEEPsAKE-2. The multicenter, randomized, double-blind, placebo-controlled studies were designed to evaluate the safety and efficacy of Skyrizi in adult patients with active psoriatic arthritis. KEEPsAKE-1 evaluated Skyrizi in patients who had an inadequate response or intolerance to at least one DMARD. KEEPsAKE-2 evaluated Skyrizi in patients who had an inadequate response or intolerance to biologic therapy and/or DMARDs. Patients were randomized to Skyrizi 150 mg or placebo followed by Skyrizi 150 mg at week 24 in the open-label extension. Patients randomized to Skyrizi received four maintenance doses a year, following two initiation doses. The primary endpoint for both studies was the achievement of ACR20 response at week 24. 

In KEEPsAKE-1 and KEEPsAKE-2, 57.3 percent and 51.3 percent of patients receiving Skyrizi achieved the primary endpoint of ACR20 response at week 24, respectively, versus 33.5 percent and 26.5 percent receiving placebo. Skyrizi also demonstrated improvements in ACR50 and ACR70 responses compared to placebo at week 24. Skyrizi also showed improvement in dactylitis and enthesitis - inflammation of fingers, toes and sites at which tendons or ligaments attach to bone.

Indication 3 - adults with moderately to severely active Crohn's disease

approved June of 2022

Obtain liver enzymes and bilirubin levels prior to initiating treatment. The recommended induction dosage is 600 mg administered by intravenous infusion over at least one hour at Week 0, Week 4, and Week 8. The recommended maintenance dosage is 360 mg administered by subcutaneous injection at Week 12, and every 8 weeks thereafter.

The FDA approval for Crohn’s disease was based on two induction and one maintenance clinical trials evaluating Skyrizi in moderately to severely active Crohn's disease: ADVANCE, MOTIVATE and FORTIFY. 

The co-primary endpoints of the clinical trials were endoscopic response and clinical remission. In the 12-week induction studies, ADVANCE and MOTIVATE, a significantly greater proportion of patients treated with Skyrizi achieved endoscopic response and clinical remission compared to placebo. As early as week 4, clinical response (defined as a 100-point reduction in CDAI) and clinical remission were achieved in a significantly greater proportion of patients receiving Skyrizi as compared to placebo. At week 12 the rates were 45% versus 25% (Skyrizi vs. placebo) and 60% vs. 37% (Skyrizi vs. placebo) for clinical remission and clinical response, respectively.

In the 52-week maintenance trial, FORTIFY, a significantly greater proportion of patients achieved the co-primary endpoints of endoscopic response and clinical remission as compared with the placebo group (risankizumab induction responders) after one year.

Indication 4 - adults with moderately to severely active ulcerative colitis

approved June of 2024

The recommended induction dosage is 1,200 mg administered by intravenous infusion over at least two hours at Week 0, Week 4, and Week 8. The recommended maintenance dosage is 180 mg or 360 mg administered by subcutaneous injection at Week 12, and every 8 weeks thereafter. Use the lowest effective dosage to maintain therapeutic response

FDA approval was supported by two Phase 3 clinical trials that evaluated Skyrizi for for the treatment of moderate to severe ulcerative colitis: a 12-week induction study, INSPIRE,1 and a 52-week maintenance study, COMMAND. Significantly more patients treated with risankizumab 1200 mg IV at week 12 in the induction study and 180 mg or 360 mg SC at week 52 in the maintenance study achieved the primary endpoint of clinical remission (per Adapted Mayo Score), compared to patients receiving placebo. Additionally, more risankizumab-treated patients in both the induction and maintenance studies achieved the key secondary endpoints of endoscopic improvement (endoscopic subscore ≤1 without evidence of friability) and histologic endoscopic mucosal improvement (HEMI, defined as endoscopic subscore ≤1 without evidence of friability and Geboes score ≤3.1) compared to placebo.