The IL-23 inhibitor from AbbVie indicated for the treatment of moderately to severely active Crohn's disease (CD) in adults.1
US-MULT-250253
INDICATIONS AND IMPORTANT SAFETY INFORMATION FOR SKYRIZI® (risankizumab-rzaa)1 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. Ulcerative Colitis: SKYRIZI is indicated for the treatment of moderately to severely active ulcerative colitis 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 Inflammatory Bowel 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 and ulcerative colitis, 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.
Most common (≥3%) adverse reactions associated with SKYRIZI in ulcerative colitis are arthralgia in induction, and arthralgia, pyrexia, injection site reactions, and rash 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. Lipid elevations observed in patients with ulcerative colitis were similar to those in Crohn's disease.
Dosage Forms and Strengths: SKYRIZI (risankizumab-rzaa) is available in a 150 mg/mL prefilled syringe and pen, a 600 mg/10 mL single-dose vial for intravenous infusion, and a 180 mg/1.2 mL or 360 mg/2.4 mL single-dose prefilled cartridge with on-body injector.
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.
Ulcerative Colitis: SKYRIZI is indicated for the treatment of moderately to severely active ulcerative colitis in adults.
Please see Full Prescribing Information.
US-SKZG-240258
REFERENCE
- SKYRIZI [package insert]. North Chicago, IL: AbbVie Inc.
largest phase 3 clinical program in crohn's disease TO DATE ACROSS INDICATION APPROVAL TRIALS*
1,419 PATIENTS ENROLLED ACROSS SKYRIZI TRIALS
‡Advanced therapy in Crohn's is defined as biologics.
*As of August 2024.
†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 advanced therapy-naïve subpopulation includes patients who were exposed to a biologic but did not have an inadequate response, loss of response, or intolerance to biologics (13%).
bPrior advanced therapy failure includes inadequate response, loss of response, or intolerance to one or more biologics.
cThe advanced therapy-naïve subpopulation includes patients who were exposed to a biologic 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.
Phase 3 Clinical program: Study Design Details1-5
ADVANCE
N=850
MOTIVATE
N=569
FORTIFY
N=382
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 mg,c or placebo at Weeks 0, 4, and 8
IV infusion of SKYRIZI 600 mg, risankizumab-rzaa 1200 mg,c 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
Crohn's disease:
- CDAI 220-450
- Average daily SF ≥4 or APS ≥2
- SES-CD ≥6 (≥4 for isolated ileitis), excluding the narrowing component
- 16-80 years old
- Advanced therapy naïved or advanced therapy failuree
Moderately to severely active
Crohn's disease:
- CDAI 220-450
- Average daily SF ≥4 or APS ≥2
- SES-CD ≥6 (≥4 for isolated ileitis), excluding the narrowing component
- 16-80 years old
- Advanced therapy failuree
Moderately to severely active
Crohn's disease:
- Entry and completion of ADVANCE or MOTIVATE. Completion includes the final endoscopy of ADVANCE or MOTIVATE
- Achieved Clinical Responsef in ADVANCE or MOTIVATE studies
| 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 mg,c or placebo, at Weeks 0, 4, and 8 |
| INCLUSION CRITERIA |
Moderately to severely active
|
| 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 mg,c or placebo, at Weeks 0, 4, and 8 |
| INCLUSION CRITERIA |
Moderately to severely active
|
| 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
|
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 advanced therapy-naïve subpopulation includes patients who were exposed to a biologic but did not have an inadequate response, loss of response, or intolerance to biologics (13%).
ePrior advanced therapy 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; CDAl=Crohn's disease activity index; IV=intravenous; SC=subcutaneous; SES-CD=simple endoscopic score for Crohn's disease; SF=stool frequency
References
- SKYRIZI [package insert]. North Chicago, IL: AbbVie Inc.
- D’Haens G, Panaccione R, Baert F, et al. Risankizumab as induction therapy for Crohn’s disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. Lancet. 2022;399(10340):2015-2030.
- Data on File, AbbVie Inc. ABVRRTI74525.
- Ferrante M, Panaccione R, Baert F, et al. Risankizumab as maintenance therapy for moderately to severely active Crohn’s disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. Lancet. 2022;399(10340):2031-2046.
- Daperno M, D’Haens G, Van Assche G, et al. Development and validation of a new, simplified endoscopic activity score for Crohn’s disease: the SES-CD. Gastrointestinal Endoscopy. 2004;60(4);505-512.
US-SKZG-240872
Phase 3 clinical program: baseline characteristics1,2
ADVANCE
Placebo
N=175
SKYRIZI 600 mg IV
N=336
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)
Disease location
lleal only, n (%)
19
(11)
52
(15)
Colonic only, n (%)
70
(40)
115
(34)
lleal-colonic, n (%)
86
(49)
169
(50)
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)
Advanced therapy*-failure history
0, n (%)
78
(45)
141
(42)
1, n (%)
41
(23)
100
(30)
>1, n (%)
56
(32)
95
(28)
MOTIVATE
Placebo
N=187
SKYRIZI 600 mg IV
N=191
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)
Disease location
lleal only, n (%)
26
(14)
33
(17)
Colonic only, n (%)
73
(39)
75
(39)
lleal-colonic, n (%)
88
(47)
83
(43)
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)
Advanced therapy*-failure history
0, n (%)
0
0
1, n (%)
88
(47)
92
(48)
>1, n (%)
99
(53)
99
(52)
FORTIFY |
Placebo
N=130 |
SKYRIZI
N=135 |
SKYRIZI
N=117 |
|
|---|---|---|---|---|
| BASELINE OF INDUCTION (ADVANCE, MOTIVATE) | ||||
Male, |
72 |
62 |
67 |
|
Age (years), |
38.0 |
39.2 |
36.2 |
|
Disease |
9.6 |
10.6 |
8.6 |
|
Disease location |
||||
lleal only, n (%) |
18 |
12 |
13 |
|
Colonic |
49 |
63 |
52 |
|
lleal-colonic, n (%) |
63 |
60 |
52 |
|
Baseline |
33 |
37 |
34 |
|
Baseline |
40 |
47 |
36 |
|
Advanced |
||||
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 |
7.3 |
7.8 |
8.3 |
|
SF at |
1.4 |
2.1 |
1.9 |
|
APS at |
0.6 |
0.6 |
0.6 |
|
FCP (mg/kg) at Week 0, |
300.0 |
361 |
485.5 |
|
hs-CRP (mg/L) at Week 0, |
3.6 |
3.7 |
4.0 |
|
FORTIFY
Placebo (Induction Responder)
N=164
SKYRIZI 360mg SC
N=141
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.
*Advanced therapy in Crohn’s is defined as biologics.
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
- D’Haens G, Panaccione R, Baert F, et al. Risankizumab as induction therapy for Crohn’s disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. Lancet. 2022;399(10340):2015-2030.
- Data on File, AbbVie Inc. ABVRRTI74525.
US-SKZG-240872
Maintenance of Clinical Remission (CDAI <150) Data at Week 52
of patients observed clinical remission at Week 12 of induction and at Week 52 of maintenance period1
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
- Data on File, AbbVie Inc. ABVRRTI74186.