The IL-23 inhibitor from AbbVie indicated for the treatment of moderately to severely active Crohn's disease (CD) in adults.1
US-MULT-230356
US-MULT-230356
The IL-23 inhibitor from AbbVie indicated for the treatment of moderately to severely active Crohn's disease (CD) in adults.1
Indications
Crohn's Disease: SKYRIZI is indicated for the treatment of moderately to severely active Crohn's disease in adults.
Plaque Psoriasis: SKYRIZI is indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.
Psoriatic Arthritis: SKYRIZI is indicated for the treatment of active psoriatic arthritis in adults.
Important Safety Information
Hypersensitivity Reactions
SKYRIZI® (risankizumab-rzaa) is contraindicated in patients with a history of serious hypersensitivity reaction to risankizumab-rzaa or any of the excipients. Serious hypersensitivity reactions, including anaphylaxis, have been reported with the use of SKYRIZI. If a serious hypersensitivity reaction occurs, discontinue SKYRIZI and initiate appropriate therapy immediately.
Infection
SKYRIZI may increase the risk of infection. Do not initiate treatment with SKYRIZI in patients with a clinically important active infection until it resolves or is adequately treated.
In patients with a chronic infection or a history of recurrent infection, consider the risks and benefits prior to prescribing SKYRIZI. Instruct patients to seek medical advice if signs or symptoms of clinically important infection occur. If a patient develops such an infection or is not responding to standard therapy, closely monitor and discontinue SKYRIZI until the infection resolves.
Tuberculosis (TB)
Prior to initiating treatment with SKYRIZI, evaluate for TB infection and consider treatment in patients with latent or active TB for whom an adequate course of treatment cannot be confirmed. Monitor patients for signs and symptoms of active TB during and after SKYRIZI treatment. Do not administer SKYRIZI to patients with active TB.
Hepatotoxicity in Treatment of Crohn’s Disease
Drug-induced liver injury was reported in a patient with Crohn’s disease who was hospitalized for a rash during induction dosing of SKYRIZI. For the treatment of Crohn’s disease, evaluate liver enzymes and bilirubin at baseline and during induction (12 weeks); monitor thereafter according to routine patient management. Consider an alternate treatment for patients with evidence of liver cirrhosis. Interrupt treatment if drug-induced liver injury is suspected, until this diagnosis is excluded. Instruct your patient to seek immediate medical attention if they experience symptoms suggestive of hepatic dysfunction.
Administration of Vaccines
Avoid use of live vaccines in patients treated with SKYRIZI. Medications that interact with the immune system may increase the risk of infection following administration of live vaccines. Prior to initiating SKYRIZI, complete all age-appropriate vaccinations according to current immunization guidelines.
Adverse Reactions
Most common (≥1%) adverse reactions associated with SKYRIZI in plaque psoriasis and psoriatic arthritis include upper respiratory infections, headache, fatigue, injection site reactions, and tinea infections.
In psoriatic arthritis phase 3 trials, the incidence of hepatic events was higher with SKYRIZI compared to placebo.
Most common (>3%) adverse reactions associated with SKYRIZI in Crohn’s disease are upper respiratory infections, headache, and arthralgia in induction and arthralgia, abdominal pain, injection site reactions, anemia, pyrexia, back pain, arthropathy, and urinary tract infection in maintenance.
Lipid Elevations: Increases from baseline and increases relative to placebo were observed at Week 4 and remained stable to Week 12 in patients treated with SKYRIZI in Crohn’s disease.
Dosage Forms and Strengths: SKYRIZI is available in a 150 mg/mL prefilled syringe and pen, and a 600 mg/10 mL single-dose vial for intravenous infusion.
INDICATIONS
Plaque Psoriasis: SKYRIZI is indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.
Psoriatic Arthritis: SKYRIZI is indicated for the treatment of active psoriatic arthritis in adults.
Crohn's Disease: SKYRIZI is indicated for the treatment of moderately to severely active Crohn's disease in adults.
Please see Full Prescribing Information.
US-SKZG-220547
REFERENCE
*As of January 2023.
†The total population in the ADVANCE and MOTIVATE studies includes patients dosed with risankizumab-rzaa 1200 mg IV, which did not demonstrate additional treatment benefit over the 600 mg dose and is not a recommended regimen.
aThe bio-naïve subpopulation includes patients who were bio‑exposed but did not have an inadequate response, loss of response, or intolerance to biologics (13%).
bPrior biologic failure includes inadequate response, loss of response, or intolerance to one or more biologics.
cThe bio-naïve subpopulation includes patients who were bio-exposed but did not have an inadequate response, loss of response, or intolerance to biologics (8%).
dClinical response was defined as a reduction of CDAI score ≥100 points from baseline.
CO-PRIMARY
ENDPOINTS
Endoscopic Responsea (>50% decrease in SES-CD) and Clinical Remissionb (CDAI <150) at Week 12
Endoscopic Responsea (>50% decrease in SES-CD) and Clinical Remissionb (CDAI <150) at Week 12
Endoscopic Responsea (>50% decrease in SES-CD) and Clinical Remissionb (CDAI <150) at Week 52
DURATION
12-week, randomized, double-blind, placebo-controlled, multi-center study
12-week, randomized, double-blind, placebo-controlled, multi-center study
52-week, randomized, double-blind, placebo-controlled, multi-center study
CONCOMITANT
THERAPIES
All patients may have received concomitant conventional therapies that included 5-aminosalicylates, immunomodulators, corticosteroids, and Crohn's-related antibiotics
All patients may have received concomitant conventional therapies that included 5-aminosalicylates, immunomodulators, corticosteroids, and Crohn's-related antibiotics
All patients may have received concomitant conventional therapies that included 5-aminosalicylates, immunomodulators, and Crohn's-related antibiotics
Patients taking corticosteroids at the start of FORTIFY had their therapy tapered
DOSING
IV infusion of SKYRIZI 600 mg, risankizumab-rzaa 1200 mgc or placebo at Weeks 0, 4, and 8
IV infusion of SKYRIZI 600 mg, risankizumab-rzaa 1200 mgc or placebo at Weeks 0, 4, and 8
Subcutaneous injection of SKYRIZI 180 mg, SKYRIZI 360 mg or placebo starting at Week 12 and every 8 weeks after
INCLUSION
CRITERIA
Moderately to severely active CD:
Moderately to severely active CD:
Moderately to severely active CD:
| ADVANCE N=850 |
|
|---|---|
| CO-PRIMARY ENDPOINTS |
Endoscopic Responsea (>50% decrease in SES-CD) and Clinical Remissionb (CDAI <150) at Week 12 |
| DURATION | 12-week, randomized, double-blind, placebo-controlled, multi-center study |
| CONCOMITANT THERAPIES |
All patients may have received concomitant conventional therapies that included 5-aminosalicylates, immunomodulators, corticosteroids, and Crohn's-related antibiotics |
| DOSING | IV infusion of SKYRIZI 600 mg, risankizumab-rzaa 1200 mgc or placebo, at Weeks 0, 4, and 8 |
| INCLUSION CRITERIA |
Moderately to severely active CD:
|
| MOTIVATE N=569 |
|
|---|---|
| CO-PRIMARY ENDPOINTS |
Endoscopic Responsea (>50% decrease in SES-CD) and Clinical Remissionb (CDAI <150) at Week 12 |
| DURATION | 12-week, randomized, double-blind, placebo-controlled, multi-center study |
| CONCOMITANT THERAPIES |
All patients may have received concomitant conventional therapies that included 5-aminosalicylates, immunomodulators, corticosteroids, and Crohn's-related antibiotics |
| DOSING | IV infusion of SKYRIZI 600 mg, risankizumab-rzaa 1200 mgc or placebo, at Weeks 0, 4, and 8 |
| INCLUSION CRITERIA |
Moderately to severely active CD:
|
| FORTIFY N=382 |
|
|---|---|
| CO-PRIMARY ENDPOINTS |
Endoscopic Responsea (>50% decrease in SES-CD) and Clinical Remissionb (CDAI <150) at Week 52 |
| DURATION | 52-week, randomized, double-blind, placebo-controlled, multi-center study |
| CONCOMITANT THERAPIES |
All patients may have received concomitant conventional therapies that included 5-aminosalicylates, immunomodulators, and Crohn's-related antibiotics Patients taking corticosteroids at the start of FORTIFY had their therapy tapered |
| DOSING | Subcutaneous injection of SKYRIZI 180 mg, SKYRIZI 360 mg or placebo starting at Week 12 and every 8 weeks after |
| INCLUSION CRITERIA |
Moderately to severely active CD:
|
aEndoscopic response was defined as a decrease in SES-CD >50% from baseline, or a decrease of at least 2 points for subjects with a baseline score of 4 and isolated ileal disease, based on central reading. The sections evaluated on endoscopy are the: rectum, sigmoid and left colon, transverse colon, right colon and ileum (per SES-CD assessment).
bClinical remission was defined as a CDAI score <150 points.
cThe 1200 mg IV induction dose did not demonstrate additional treatment benefit over the 600 mg IV dose and is not a recommended regimen.
dThe bio-naïve subpopulation includes patients who were bio‑exposed but did not have an inadequate response, loss of response, or intolerance to biologics (13%).
ePrior biologic failure includes inadequate response, loss of response, or intolerance to one or more biologics.
fClinical response was defined as a reduction of CDAI score ≥100 points from baseline.
APS=abdominal pain score; CD=Crohn's disease; CDAI=Crohn’s disease activity index; IV=intravenous; SC=subcutaneous; SES-CD=simple endoscopic score for Crohn’s disease; SF=stool frequency
References
US-SKZG-230070
Male, n (%)
88
(50)
189
(56)
Age (years),
mean (SD)
37.1
(13.4)
38.3
(13.3)
Disease duration
(years), mean (SD)
8.2
(7.1)
9.0
(8.8)
hs-CRP (mg/L),
median (IQR)
8.4
(2.8-21.9)
7.3
(2.8-21.8)
CDAI, mean (SD)
319.2
(59.4)
311.2
(62.4)
SES-CD, mean (SD)
13.8
(6.8)
14.7
(7.7)
Corticosteroid
use, n (%)
50
(29)
102
(30)
Biologics failure
history
0, n (%)
78
(45)
141
(42)
1, n (%)
41
(23)
100
(30)
>1, n (%)
56
(32)
95
(28)
Male, n (%)
99
(53)
92
(48)
Age (years),
mean (SD)
39.3
(13.5)
40.2
(13.6)
Disease duration
(years), mean (SD)
12.5
(9.7)
10.9
(7.7)
hs-CRP (mg/L),
median (IQR)
9.4
(3.6-28.2)
9.3
(3.5-23.0)
CDAI, mean (SD)
319.6
(69.8)
310.7
(63.6)
SES-CD, mean (SD)
15.0
(8.1)
14.4
(7.6)
Corticosteroid
use, n (%)
68
(36)
65
(34)
Biologics failure
history
0, n (%)
0
0
1, n (%)
88
(47)
92
(48)
>1, n (%)
99
(53)
99
(52)
FORTIFY |
Placebo
|
SKYRIZI
|
SKYRIZI
|
|
|---|---|---|---|---|
| BASELINE OF INDUCTION (ADVANCE, MOTIVATE) | ||||
Male, |
72 |
62 |
67 |
|
Age (years), |
38.0 |
39.2 |
36.2 |
|
Disease |
9.6 |
10.6 |
8.6 |
|
Baseline |
33 |
37 |
34 |
|
Baseline |
40 |
47 |
36 |
|
Biologics |
||||
0, n (%) |
31 |
40 |
34 |
|
1, n (%) |
49 |
34 |
42 |
|
>1, n (%) |
50 |
61 |
41 |
|
Baseline |
314.2 |
327.6 |
316.2 |
|
Baseline |
14.1 |
14.9 |
14.3 |
|
Baseline |
5.8 |
6.2 |
5.9 |
|
Baseline |
1.9 |
2.0 |
1.9 |
|
Baseline FCP (mg/kg), |
904.0 |
1666.0 |
1622.0 |
|
Baseline |
7.9 |
8.7 |
10.6 |
|
| Week 0 of Maintenance | ||||
CDAI at |
111.6 |
117.6 |
125.4 |
|
SES-CD at |
7.9 |
7.8 |
8.3 |
|
SF at |
1.4 |
2.1 |
1.9 |
|
APS at |
0.6 |
0.6 |
0.6 |
|
FCP at Week 0 (mg/kg), |
300.0 |
361 |
485.5 |
|
hs-CRP at Week 0 (mg/L), |
3.6 |
3.7 |
4.0 |
|
Disease duration (years), mean (SD)
9.6 (8.8)
9.3 (8.1)
Baseline immunomodulator use, n (%)
40 (24.4)
40 (28.4)
Baseline steroid use, n (%)
51 (31.1)
42 (29.8)
Biologics failure history
0, n (%)
41 (25.0)
39 (27.7)
1, n (%)
60 (36.6)
51 (36.2)
>1, n (%)
63 (38.4)
51 (36.2)
Baseline CDAI, mean (SD)
307.4 (64.9)
308.9 (61.1)
Baseline SES-CD, mean (SD)
14.0 (7.1)
14.3 (7.4)
Baseline SF, mean (SD)
5.8 (2.7)
5.9 (2.6)
Baseline APS, mean (SD)
1.9 (0.5)
1.8 (0.5)
Baseline FCP, median (min,max)
794.5
(30, 11378)
1543.0
(30, 14649)
Baseline hs-CRP, median (min,max) (mg/L)
7.6
(0.3, 181)
10.1
(0.3, 129)
CDAI at Week 0, mean (SD)
133.6 (80.6)
137.2 (67.7)
SES-CD at Week 0, mean (SD)
7.6
(0.3, 181)
8.5 (7.3)
SF at Week 0, mean (SD)
1.8 (1.8)
2.1 (1.8)
APS at Week 0, mean (SD)
0.7 (0.6)
0.7 (0.6)
FCP at Week 0, median (min,max) (mg/kg)
307
(30, 28013)
424
(30, 14804)
hs-CRP at Week 0, median (min,max) (mg/L)
4.1
(0.2, 53.4)
3.9
(0.2, 258)
Includes randomized subjects who received at least one dose of study drug, who had baseline eligible SES-CD ≥6 (≥4 for isolated ileal disease), and who received 12-week SKYRIZI IV treatment.
APS=abdominal pain score; CDAI=Crohn’s disease activity index; FCP=fecal calprotectin; hs-CRP=high-sensitivity C-reactive protein; IQR=interquartile range; IV=intravenous; SC=subcutaneous; SD=standard deviation; SES-CD=simple endoscopic score for Crohn’s disease; SF=stool frequency
References
US-SKZG-230070
Intention-to-treat 1A population, Non-responder imputation - COVID-19
Data Limitations: Data was not multiplicity controlled, and not powered to demonstrate statistical difference in treatment effect for SKYRIZI vs placebo (induction responders). No statistical or clinical conclusions can be made.
Clinical Remission: Defined as a CDAI score <150 points.
Placebo (Induction Responders): Patients who achieved CDAI clinical response (CR-100)* to SKYRIZI induction therapy and were randomized to receive placebo in the maintenance study.
*Clinical response was defined as a reduction of CDAI score ≥100 points from baseline.
CDAI=Crohn's disease activity index
REFERENCE
US-SKZD-210908