Safety Profile | SKYRIZI® (risankizumab-rzaa)

The IL-23 inhibitor from AbbVie indicated for the treatment of moderately to severely active Crohn's disease (CD) in adults.¹

WELL-STUDIED Safety Profile

UP TO ~7 Years of Clinical Experience ACROSS MULTIPLE INDICATIONS

Approved for 3 Indications: Starting with Plaque Psoriasis (Ps), Followed by Psoriatic Arthritis (PsA) and Crohn's Disease (CD)^1,2

Clinical Trials
Across Indications^2-6*^†

~135,000

Patients Prescribed
Worldwide since 2019
Starting with Ps^7‡

6,313

Patients Evaluated
Across Treatment Arms^2,8*^§

13,637

Patient-Years
of Exposure^2,8*^‖

*Safety data were evaluated for all patients receiving ≥1 dose of SKYRIZI from Phase 1-3 trials, including open-label extension and dose-ranging studies.

Safety Data Derived from the Largest Phase 3 Clinical Program in CD to Date^¶

2,059

Patient-Years of Exposure from CD Clinical Programs to Date⁸

SAFETY PROFILE

AEs THROUGH 12 WEEKS AEs THROUGH 12 WEEKS

AEs THROUGH 52 WEEKS AEs THROUGH 52 WEEKS

WELL-STUDIED SAFETY PROFILE

Week 12 Safety Data from
ADVANCE and MOTIVATE^3,9

	ADVANCE		MOTIVATE
Adverse Events (AEs), n (%)	Placebo IV N=186	SKYRIZI 600 mg IV N=373	Placebo IV N=207	SKYRIZI 600 mg IV N=206
Treatment-Emergent AEs
Any AE	105 (56)	210 (56)	137 (66)	98 (48)
Serious AE	28 (15)	27 (7)	26 (13)	10 (5)
AE Leading to Discontinuation of Study Drug*	14 (8)	9 (2)	17 (8)	2 (1)
Death	2 (1)	0	0	0
AEs of Special Interest
Infections
Infections	44 (24)	77 (21)	51 (25)	31 (15)
Serious Infection	7 (4)	3 (1)	5 (2)	1 (<1)
Opportunistic Infection (Excluding TB/Herpes Zoster)	0	0	3 (1)	0
Active TB	1 (1)	1 (<1)	0	0
Malignancy
Malignant Tumors	0	0	0	0
Malignancy (Excluding NMSC)	0	0	0	0
Cardiovascular Events
Adjudicated MACE^a	0	0	0	0
Other
Hypersensitivity (Serious Events Only)	0	1 (<1)	0	0
Adjudicated Anaphylactic Reaction	0	0	0	0
Hepatic Events	4 (2)	9 (2)	2 (1)	1 (<1)
Infusion-Related Reactions	1 (1)	4 (1)	3 (1)	1 (<1)

SKYRIZI IS CONTRAINDICATED IN PATIENTS WITH A HISTORY OF SERIOUS HYPERSENSITIVITY REACTION TO RISANKIZUMAB-RZAA OR ANY OF THE EXCIPIENTS.¹

In the treatment of CD, drug-induced liver injury during induction has been reported. Monitor liver enzymes and bilirubin levels at baseline and during induction, up to at least 12 weeks of treatment. Monitor thereafter according to routine patient management.¹

In the CD 12-week induction studies, the most common adverse reactions (>3% of patients and at a higher rate than placebo) include upper respiratory infections, headache and arthralgia.¹

WELL-STUDIED SAFETY PROFILE AND TOLERABILITY* WITH 2% OF PATIENTS IN ADVANCE AND 1% OF PATIENTS IN MOTIVATE DISCONTINUING THE TRIAL DUE TO ADVERSE EVENTS³

WELL-STUDIED SAFETY PROFILE

Week 52 Safety Data from
FORTIFY^1,3,10,11

	FORTIFY
	Non-randomized	Randomized
Adverse Events (AEs), % (E/100 PYs)	Continuous Placebo	Placebo (Induction Responder)	SKYRIZI 180 mg SC	SKYRIZI 360 mg SC
	N=81 PYs=60.5	N=143 PYs=124.4	N=155 PYs=149.4	N=142 PYs=134.8
Treatment-Emergent AEs
Any AE	75 (271.0)	71 (297.3)	69 (266.4)	70 (267.1)
Serious AE	16 (31.4)	10 (15.3)	11 (18.7)	13 (19.3)
AE Leading to Discontinuation of Study Drug*	6 (13.2)	2 (2.4)	2 (2.7)	3 (4.5)
Death	0	0	0	0
AEs of Special Interest
Infections
Infections	33 (66.1)	36 (60.3)	32 (50.2)	37 (60.8)
Serious Infection	4 (8.3)	2 (2.4)	3 (2.7)	6 (7.4)
Opportunistic Infection (Excluding TB/Herpes Zoster)	0	0	0	1 (0.7)
Active TB	0	0	0	0
Herpes Zoster	0	1 (0.8)	1 (1.3)	0
Malignancy
Malignant Tumors	0	1 (0.8)	0	0
Malignancy (Excluding NMSC)	0	0	0	0
Cardiovascular Events
Adjudicated MACE^a	0	1 (0.8)	0	1 (0.7)
Other
Hypersensitivity (Serious Events Only)	0	0	0	0
Adjudicated Anaphylactic Reaction	0	0	0	0
Hepatic Events	1 (1.7)	2 (2.4)	3 (4.7)	5 (6.7)
Injection Site Reaction	0	3 (4.8)	5 (10.0)	6 (13.4)

SKYRIZI IS CONTRAINDICATED IN PATIENTS WITH A HISTORY OF SERIOUS HYPERSENSITIVITY REACTION TO RISANKIZUMAB-RZAA OR ANY OF THE EXCIPIENTS.¹

In the treatment of CD, drug-induced liver injury during induction has been reported. Monitor liver enzymes and bilirubin levels at baseline and during induction, up to at least 12 weeks of treatment. Monitor thereafter according to routine patient management.¹

WELL-STUDIED SAFETY PROFILE AND TOLERABILITY* WITH 2% OF SKYRIZI 180 MG SC PATIENTS AND 3% OF SKYRIZI 360 MG SC PATIENTS DISCONTINUING THE TRIAL DUE TO ADVERSE EVENTS¹⁰

Continuous Placebo: Patients who responded to placebo in induction (CR-100)^† were not randomized and continued on placebo in maintenance. These patients were not included in the primary efficacy analysis.

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.

HAVE YOU SEEN THE ENDOSCOPIC
AND CLINICAL RESULTS?

EXPLORE EFFICACY

HAVE YOU SEEN SKYRIZI'S
DOSING SCHEDULE?

REVIEW DOSING

	PsA (WEEK 24) ACROSS 2 PIVOTAL TRIALS^1,2		Ps (WEEK 16) ACROSS 4 PIVOTAL TRIALS^3-5
	SKYRIZI^a N=707 % (n)	Placebo^a N=700 % (n)	SKYRIZI^b N=1,306 % (n)	Placebo^c N=300 % (n)
Any Serious Adverse Event	3.0 (21)	4.4 (31)	2.4 (31)	4.0 (12)
Any Infection	19.0 (134)	19.3 (135)	22.1 (288)	14.7 (44)
Serious Infections	1.0 (7)	1.6 (11)	0.4 (5)	0.3 (1)
Active TB	0.0	0.0	0.0	0.0
Any Malignancy	0.1 (1)	0.4 (3)	0.5 (6)	0.3 (1)
Malignancy (Excluding NMSC)	0 (0)	0.3 (2)	0.2 (3)	0 (0)
Adjudicated MACE	0.1 (1)	0 (0)	<0.1 (1)	0.3 (1)

	PsA (WEEK 52) ACROSS 2 PIVOTAL TRIALS¹		Ps (WEEK 52)²	Ps LONG-TERM (UP TO ~7 YEARS OF EXPOSURE)³
	KEEPsAKE-1	KEEPsAKE-2	INTEGRATED ANALYSIS OF 2 CLINICAL TRIALS	INTEGRATED ANALYSIS OF 17 CLINICAL TRIALS
	N=946 PYs=958.1 Events/100 PYs	N=419 PYs=509.7 Events/100 PYs	N=598 PYs=618.0 Events/100 PYs	N=3,197 PYs=9,982.6 Events/100 PYs
Any Serious Adverse Event	7.4	9.4	9.4	7.6
Serious Infections	2.8	2.0	1.8	1.2
Active TB	0.0	0.0	0.0	0.0
Any Malignancy	0.6	2.2	0.5	1.2
Malignancy (Excluding NMSC)	0.4	0.4	0.0	0.6
Adjudicated MACE	0.0	0.6	0.3	0.5

Adverse Reactions Reported in >3% of Subjects and at a Higher Rate than Placebo	Placebo N=143 n (%)	SKYRIZI 180 mg SC^a N=155 n (%)	SKYRIZI 360 mg SC^a N=142 n (%)
Adverse Drug Reactions
Arthralgia	12 (8.4)	13 (8.4)	13 (9.2)
Abdominal pain^b	6 (4.2)	9 (5.8)	12 (8.5)
Injection site reactions^c,d	4 (2.8)	7 (4.5)	8 (5.6)
Anemia	6 (4.2)	7 (4.5)	7 (4.9)
Pyrexia	4 (2.8)	4 (2.6)	7 (4.9)
Back pain	3 (2.1)	3 (1.9)	6 (4.2)
Arthropathy	2 (1.4)	1 (0.6)	5 (3.5)
Urinary tract infection	4 (2.8)	1 (0.6)	5 (3.5)

	ADVANCE N=850
CO-PRIMARY ENDPOINTS	Endoscopic Response^a (>50% decrease in SES-CD) and Clinical Remission^b (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 CD: CDAI 220-450 Average daily SF ≥4 or APS ≥2 SES-CD ≥6 (≥4 for isolated ileitis), exluding the narrowing component 16-80 years old Bio-naïve^d or biologic failure^e

	MOTIVATE N=569
CO-PRIMARY ENDPOINTS	Endoscopic Response^a (>50% decrease in SES-CD) and Clinical Remission^b (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 CD: CDAI 220-450 Average daily SF ≥4 or APS ≥2 SES-CD ≥6 (≥4 for isolated ileitis), exluding the narrowing component 16-80 years old Biologic failure^e

FORTIFY		Placebo (Induction Responder) N=130	SKYRIZI 180 mg SC N=135	SKYRIZI 360 mg SC N=117
BASELINE OF INDUCTION (ADVANCE, MOTIVATE)
	Male, n (%)	72 (55.4)	62 (45.9)	67 (57.3)
	Age (years), mean (SD)	38.0 (12.8)	39.2 (14.7)	36.2 (12.6)
	Disease duration (years), mean (SD)	9.6 (8.2)	10.6 (10.2)	8.6 (7.1)
	Baseline immunomodulatorimmuno- modulator use, n (%)	33 (25.4)	37 (27.4)	34 (29.1)
	Baseline steroid use, n (%)	40 (30.8)	47 (34.8)	36 (30.8)
	Biologics failure history
	0, n (%)	31 (23.8)	40 (29.6)	34 (29.1)
	1, n (%)	49 (37.7)	34 (25.2)	42 (35.9)
	>1, n (%)	50 (38.5)	61 (45.2)	41 (35.0)
	Baseline CDAI, mean (SD)	314.2 (64.2)	327.6 (68.2)	316.2 (59.6)
	Baseline SES-CD, mean (SD)	14.1 (7.1)	14.9 (7.2)	14.3 (7.0)
	Baseline SF, mean (SD)	5.8 (2.7)	6.2 (3.1)	5.9 (2.7)
	Baseline APS, mean (SD)	1.9 (0.5)	2.0 (0.4)	1.9 (0.5)
	Baseline FCP (mg/kg), median (min,max)	904.0 (30, 11378)	1666.0 (30, 28800)	1622.0 (30, 14649)
	Baseline hs-CRP (mg/L), median (min,max)	7.9 (0.3, 181)	8.7 (0.4, 151)	10.6 (0.3, 129)

Week 0 of Maintenance
	CDAI at Week 0, mean (SD)	111.6 (69.5)	117.6 (66.8)	125.4 (62.7)
	SES-CD at Week 0, mean (SD)	7.9 (6.4)	7.8 (6.4)	8.3 (7.3)
	SF at Week 0, mean (SD)	1.4 (1.7)	2.1 (1.9)	1.9 (1.7)
	APS at Week 0, mean (SD)	0.6 (0.5)	0.6 (0.5)	0.6 (0.5)
	FCP (mg/kg) at Week 0, median (min,max)	300.0 (30, 22912)	361 (30, 28800)	485.5 (30, 14804)
	hs-CRP (mg/L) at Week 0, median (min,max)	3.6 (0, 42)	3.7 (0, 48)	4.0 (0, 258)

WELL-STUDIED Safety Profile

UP TO ~7 Years of Clinical Experience ACROSS MULTIPLE INDICATIONS

Safety Data Derived from the Largest Phase 3 Clinical Program in CD to Date¶

Patient-Years of Exposure from CD Clinical Programs to Date8

WELL-STUDIED SAFETY PROFILE

SKYRIZI IS CONTRAINDICATED IN PATIENTS WITH A HISTORY OF SERIOUS HYPERSENSITIVITY REACTION TO RISANKIZUMAB-RZAA OR ANY OF THE EXCIPIENTS.1

In the treatment of CD, drug-induced liver injury during induction has been reported. Monitor liver enzymes and bilirubin levels at baseline and during induction, up to at least 12 weeks of treatment. Monitor thereafter according to routine patient management.1

In the CD 12-week induction studies, the most common adverse reactions (>3% of patients and at a higher rate than placebo) include upper respiratory infections, headache and arthralgia.1

WELL-STUDIED SAFETY PROFILE

SKYRIZI IS CONTRAINDICATED IN PATIENTS WITH A HISTORY OF SERIOUS HYPERSENSITIVITY REACTION TO RISANKIZUMAB-RZAA OR ANY OF THE EXCIPIENTS.1

In the treatment of CD, drug-induced liver injury during induction has been reported. Monitor liver enzymes and bilirubin levels at baseline and during induction, up to at least 12 weeks of treatment. Monitor thereafter according to routine patient management.1

IMPORTANT SAFETY INFORMATION AND INDICATIONS FOR SKYRIZI® (risankizumab-rzaa)1

ADVANCE N=850

MOTIVATE N=569

FORTIFY N=382

ADVANCE

Placebo N=175

SKYRIZI 600 mg IV N=336

MOTIVATE

Placebo N=187

SKYRIZI 600 mg IV N=191

FORTIFY

Placebo (Induction Responder) N=130

SKYRIZI 180 mg SC N=135

SKYRIZI 360 mg SC N=117

FORTIFY

Placebo (Induction Responder) N=164

SKYRIZI 360mg SC N=141

IMPORTANT SAFETY INFORMATION AND INDICATIONS FOR SKYRIZI® (risankizumab-rzaa)1

IMPORTANT SAFETY INFORMATION AND INDICATION FOR SKYRIZI® (risankizumab-rzaa)1

IMPORTANT SAFETY INFORMATION AND INDICATIONS FOR SKYRIZI® (risankizumab-rzaa)1

IMPORTANT SAFETY INFORMATION AND INDICATION FOR SKYRIZI® (risankizumab-rzaa)1

IMPORTANT SAFETY INFORMATION AND INDICATIONS FOR SKYRIZI® (risankizumab-rzaa)1

Safety Data Derived from the Largest Phase 3 Clinical Program in CD to Date^¶

Patient-Years of Exposure from CD Clinical Programs to Date⁸

SKYRIZI IS CONTRAINDICATED IN PATIENTS WITH A HISTORY OF SERIOUS HYPERSENSITIVITY REACTION TO RISANKIZUMAB-RZAA OR ANY OF THE EXCIPIENTS.¹

In the treatment of CD, drug-induced liver injury during induction has been reported. Monitor liver enzymes and bilirubin levels at baseline and during induction, up to at least 12 weeks of treatment. Monitor thereafter according to routine patient management.¹

In the CD 12-week induction studies, the most common adverse reactions (>3% of patients and at a higher rate than placebo) include upper respiratory infections, headache and arthralgia.¹

SKYRIZI IS CONTRAINDICATED IN PATIENTS WITH A HISTORY OF SERIOUS HYPERSENSITIVITY REACTION TO RISANKIZUMAB-RZAA OR ANY OF THE EXCIPIENTS.¹

In the treatment of CD, drug-induced liver injury during induction has been reported. Monitor liver enzymes and bilirubin levels at baseline and during induction, up to at least 12 weeks of treatment. Monitor thereafter according to routine patient management.¹

IMPORTANT SAFETY INFORMATION AND INDICATIONS FOR SKYRIZI® (risankizumab-rzaa)¹

ADVANCE
N=850

MOTIVATE
N=569

FORTIFY
N=382

Placebo
N=175

SKYRIZI 600 mg IV
N=336

Placebo
N=187

SKYRIZI 600 mg IV
N=191

Placebo
(Induction Responder)
N=130

SKYRIZI
180 mg SC
N=135

SKYRIZI
360 mg SC
N=117

Placebo (Induction Responder)
N=164

SKYRIZI 360mg SC
N=141

IMPORTANT SAFETY INFORMATION AND INDICATIONS FOR SKYRIZI® (risankizumab-rzaa)¹

IMPORTANT SAFETY INFORMATION AND INDICATION FOR SKYRIZI® (risankizumab-rzaa)¹

IMPORTANT SAFETY INFORMATION AND INDICATIONS FOR SKYRIZI® (risankizumab-rzaa)¹

IMPORTANT SAFETY INFORMATION AND INDICATION FOR SKYRIZI® (risankizumab-rzaa)¹

IMPORTANT SAFETY INFORMATION AND INDICATIONS FOR SKYRIZI® (risankizumab-rzaa)¹