Long-term Safety of Risankizumab From 17 Clinical Trials in Patients With Moderate-to-severe Plaque Psoriasis

K.B. Gordon; M. Lebwohl; K.A. Papp; H. Bachelez; J.J. Wu; R.G. Langley; A. Blauvelt; B. Kaplan; M. Shah; Y. Zhao; R. Sinvhal; K. Reich

Disclosures

The British Journal of Dermatology. 2022;186(3):466-475.

Abstract and Introduction

Abstract

Background: Risankizumab has demonstrated efficacy and safety in patients with moderate-to-severe plaque psoriasis in randomized clinical trials.

Objectives: To evaluate safety data from risankizumab psoriasis phase I–III clinical trials.

Methods: Short-term safety (through week 16) was analysed using integrated data from five phase II and III clinical trials. Long-term safety was evaluated using integrated data from 17 phase I–III completed and ongoing trials.

Results: Short-term safety analyses included 1306 patients receiving risankizumab 150 mg and 300 patients receiving placebo [402·2 and 92·0 patient-years (PY) of exposure, respectively]. Long-term analyses included 3072 risankizumab-treated patients (exposure: 7927 PY). The median (excluding four outliers) treatment duration was 2·9 years (range 2 days to 5·9 years). Exposure-adjusted adverse event rates did not increase with long-term treatment (318 vs. 171 events per 100 PY for short- and long-term analyses). With long-term risankizumab treatment, rates of serious adverse events were 7·8 per 100 PY, serious infections 1·2 per 100 PY, nonmelanoma skin cancer (NMSC) 0·7 per 100 PY, malignant tumours excluding NMSC 0·5 per 100 PY, and adjudicated major adverse cardiovascular events 0·3 per 100 PY, with no important identified risks. Limitations include that the study inclusion and exclusion criteria varied and that three studies enrolled ≤ 50 patients.

Conclusions: Risankizumab demonstrated a favourable safety profile over short- and long-term treatment in patients with moderate-to-severe psoriasis.

Introduction

Psoriasis is a chronic, systemic disease that has possible associations with psychiatric, arthritic, cardiometabolic and malignant comorbidities.^[1,2] Most patients treated with biologic agents require continuous long-term treatment to achieve disease control.^[3,4] Owing to the immunomodulatory nature of biologics, it has been suggested that patients treated with biologics may be more susceptible to opportunistic and other infections.^[5]

Risankizumab is a selective interleukin (IL)-23 inhibitor^[6] that binds to the p19 subunit of IL-23, preventing interaction with the IL-23 receptor. Risankizumab has been shown to be well tolerated and efficacious in patients with moderate-to-severe plaque psoriasis^[3,7–9] and is approved for the treatment of moderate-to-severe plaque psoriasis in over 70 countries, including the USA, Canada, Japan and in Europe.^[10,11] Here we report safety for up to 5·9 years of treatment with risankizumab using integrated data from 17 completed or ongoing clinical trials in plaque psoriasis.

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Table 1. Baseline demographic and disease characteristics
	Week 16 placebo (n = 300)	Week 16 RZB 150 mg (n = 1306)^a	Long-term all RZB (n = 3072)^a,b
Sex
Male	219 (73·0)	908 (69·5)	2129 (69·3)
Female	81 (27·0)	398 (30·5)	943 (30·7)
Age (years)
Median (range)	48 (19–85)	48 (18–84)	48·0 (18–85)
< 65	261 (87·0)	1165 (89·2)	2712 (88·3)
65–74	35 (11·7)	124 (9·5)	322 (10·5)
≥ 75	4 (1·3)	17 (1·3)	38 (1·2)
Body mass index (kg m⁻²)^c
Median (range)	29·8 (17·0–51·4)	29·9 (15·0–67·0)	29·3 (15·0–92·7)
< 25	62 (20·7)	282 (21·6)	708 (23·1)
25–30 (overweight)	91 (30·3)	400 (30·6)	972 (31·7)
≥ 30 (obese)	147 (49·0)	624 (47·8)	1391 (45·3)
Race
White	240 (80·0)	1020 (78·1)	2406 (78·3)
Asian	50 (16·7)	216 (16·5)	522 (17·0)
Black/African American	5 (1·7)	49 (3·8)	101 (3·3)
American Indian/Alaska Native	3 (1·0)	11 (0·8)	21 (0·7)
Native Hawaiian/Pacific Islander	2 (0·7)	4 (0·3)	11 (0·4)
Other	0 (0·0)	6 (0·5)	11 (0·4)
Weight (kg)^c
≤ 100	211 (70·3)	931 (71·3)	2225 (72·5)
> 100	89 (29·7)	375 (28·7)	846 (27·5)
Hypertension	4 (1·3)	38 (2·9)	266 (8·7)
Hyperlipidaemia	9 (3·0)	53 (4·1)	180 (5·9)
Diabetes	5 (1·7)	23 (1·8)	115 (3·7)
Prior TNFi use
Yes	83 (27·7)	328 (25·1)	543 (17·7)
No	217 (72·3)	978 (74·9)	2529 (82·3)
Prior biologics
0	167 (55·7)	736 (56·4)	1889 (61·5)
≥ 1	133 (44·3)	570 (43·6)	1183 (38·5)

The data are presented as n (%) unless stated otherwise. RZB, risankizumab; TNFi, tumour necrosis factor inhibitor. ^aDifferences in baseline demographic and clinical characteristics for the short- and long-term analysis sets are the result of pooling data from several different studies. ^bTreatment duration and exposure calculations include data from four patients from ongoing trials with erroneous dosing dates that overestimate their treatment duration and exposure; the range excluding the four outliers was 2 days to 5·9 years. ^cMissing data for one patient in the long-term cohort.

Table 2. Treatment-emergent adverse events (TEAEs) overall and TEAEs in areas of safety interest per 100 person-years (PY): 16-week and long-term analyses
	Week 16^a		Long term^a All RZB^b (n = 3072; 7927 PY)
	Placebo (n = 300; 92·0 PY)	RZB 150 mg (n = 1306; 402 PY)	Long term^a All RZB^b (n = 3072; 7927 PY)
	Events (events per 100 PY)
Overall AEs	261 (284)	1279 (318)	13 548 (171)
Most common AEs^c
Nasopharyngitis^d	1 (1·1)	7 (1·7)	1333 (16·8)
Viral upper respiratory tract infection^d	14 (15·2)	86 (21·4)	62 (0·8)
Upper respiratory tract infection	9 (9·8)	63 (15·7)	724 (9·1)
Arthralgia	10 (10·9)	35 (8·7)	284 (3·6)
Headache	6 (6·5)	46 (11·4)	275 (3·5)
Injection-site reaction	5 (5·4)	26 (6·5)	256 (3·2)
Hypertension	6 (6·5)	15 (3·7)	236 (3·0)
Serious AEs	16 (17·4)	40 (9·9)	617 (7·8)
Serious AEs related to study drug^e	1 (1·1)	6 (1·5)	82 (1·0)
AEs leading to discontinuation	9 (9·8)	11 (2·7)	136 (1·7)
AEs leading to death	0	1 (0·2)	17 (0·2)
AEs in areas of safety interest	Events (events per 100 PY; 95% confidence interval)
Serious infections	1 (1·1; < 0·1–6·1)	7 (1·7; 0·7–3·6)	97 (1·2; 1·0–1·5)
Depression	2 (2·2; 0·3–7·9)	4 (1·0; 0·3–2·6)	56 (0·7; 0·5–0·9)
NMSC	1 (1·1; < 0·1–6·1)	3 (0·7; 0·2–2·2)	54 (0·7; 0·5–0·9)
Malignant tumours excluding NMSC	0 (0; 0–3·3)	3 (0·7; 0·2–2·2)	42 (0·5; 0·4–0·7)
Adjudicated MACE	1 (1·1; < 0·1–6·1)	1 (0·2; < 0·1–1·4)	20 (0·3; 0·2–0·4)
Suicidal ideation and behaviour	1 (1·1; < 0·1–6·1)	2 (0·5; < 0·1–1·8)	7 (< 0·1; < 0·1–0·2)
Serious hypersensitivity	0	0	4 (< 0·1; < 0·1–0·1)^f

AE, adverse event; MACE, major adverse cardiovascular event; NMSC, nonmelanoma skin cancer; RZB, risankizumab. ^aWeek 16 (five-study pool) and long term (17-study pool) represent different pools of patients with varying lengths of treatment exposure included in the long-term set. RZB events counted in the week 16 column are also included in the long-term column. ^bTreatment duration and exposure calculations include data from four patients from ongoing trials with erroneous dosing dates that overestimate their treatment duration and exposure. ^cAEs with at least three events per 100 PY in the long-term analysis set. ^dThe lower-level symptoms of cold, cold symptoms, common cold syndrome, febrile cold including influenza-like illness, head cold and pyrexial cold were coded to the preferred term 'viral upper respiratory tract infection' in MedDRA version 20.0 in the 16-week analysis and to 'nasopharyngitis' using MedDRA version 22.1 in the long-term analysis. ^eAs assessed by the investigator. ^fOne case each of erythema multiforme (attributed to an antibiotic), Stevens–Johnson syndrome (chlorpromazine), hypersensitivity (hair dye application) and eczema.

Appendix 1

Conflicts of Interest

K.B.G. has received honoraria for serving as a consultant for and/or grants as an investigator from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermira, Eli Lilly, GlaxoSmithKline, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi-Aventis, Sun and UCB Pharma. M.L. is an employee of Mount Sinai and has received grants as an investigator from AbbVie, Amgen, Arcutis, Avotres Therapeutics, Boehringer Ingelheim, Dermavant Sciences, Eli Lilly, Incyte, Janssen Research & Development LLC, Ortho Dermatologics, Regeneron and UCB Inc.; and is a consultant for Aditum Bio, Almirall, AltruBio Inc., AnaptysBio, Arcutis Inc., Aristea Therapeutics, Arrive Technologies, Avotres Therapeutics, BiomX, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant Sciences, Dr. Reddy's Laboratories, Evelo Biosciences, Evommune Inc., Facilitation of International Dermatologic Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Helsinn Therapeutics, Hexima Ltd., LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer, Seanergy and Verrica. K.A.P. has received honoraria or fees for serving on advisory boards from AbbVie, Amgen, Bausch Health, Baxalta, Baxter, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, Janssen, LEO Pharma, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Sanofi Genzyme, Stiefel, Sun Pharma, UCB and Valeant; has received honoraria or fees as a speaker for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Kyowa Hakko Kirin, LEO Pharma, Merck Serono, Novartis, Pfizer, Sanofi Genzyme, UCB and Valeant; has received honoraria or fees as a consultant for AbbVie, Amgen, Arcutis, Astellas, Avillion, Bausch Health, Baxalta, Baxter, Boehringer Ingelheim, Botanix, Bristol Myers Squibb, Celgene, Coherus, Dermavant, Dermira, Eli Lilly, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa Hakko Kirin, LEO Pharma, Meiji Sika Pharma, MedImmune, Merck Serono, Merck Sharp & Dohme, Mitsubishi, Novartis, Pfizer, Regeneron, Roche, Samsung Bioepis, Sanofi Genzyme, Stiefel, Sun Pharma, Takeda, UCB and Valeant; and has received grants as principal investigator from AbbVie, Amgen, Arcutis, Astellas, Avillion, Bausch Health, Baxalta, Baxter, Boehringer Ingelheim, Botanix, Bristol Myers Squibb, Celgene, Coherus, Dermavant, Dermira, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa Hakko Kirin, LEO Pharma, MedImmune, Meiji Sika Pharma, Merck Serono, Merck Sharp & Dohme, Mitsubishi, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Stiefel, Sun Pharma, Takeda, UCB and Valeant. H.B. has received honoraria or fees for serving on advisory boards or as a speaker or consultant, and grants as an investigator from AbbVie, Almirall, Amgen, Anaptysbio, Avillion, Biocad, Boehringer Ingelheim, Celgene, Dermavant, Eli Lilly, Innovaderm, Janssen, Kyowa Kirin, LEO Pharma, Mylan, Novartis, Pfizer, Sun Pharmaceuticals and UCB. J.J.W. is or has been an investigator, consultant or speaker for AbbVie, Almirall, Amgen, Arcutis, Aristea Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Dr. Reddy's Laboratories, Eli Lilly, Galderma, Janssen, LEO Pharma, Mindera, Novartis, Regeneron, Sanofi Genzyme, Solius, Sun Pharma, UCB, Valeant Pharmaceuticals North America LLC and Zerigo Health. R.G.L. has served as principal investigator, served on the scientific advisory board or provided a lecture for AbbVie, Amgen, Boehringer Ingelheim, Celgene, LEO, Lilly, Merck, Novartis, Pfizer and UCB. A.B. has served as a scientific adviser and/or clinical study investigator for AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly and Company, Evommune, Forte, Galderma, Incyte, Janssen, Landos, LEO, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma and UCB Pharma. B.K., M.S., Y.Z. and R.S. are full-time salaried employees of AbbVie and may own stock or options. K.R. has served as an adviser and/or paid speaker for and/or participated in clinical trials sponsored by AbbVie, Affibody, Almirall, Amgen, Avillion, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Centocor, Covagen, Dermira, Forward Pharma, Fresenius Medical Care, Galapagos, Galderma, GlaxoSmithKline, Janssen-Cilag, Kyowa Kirin, LEO, Lilly, Medac, Merck Sharp & Dohme, Miltenyi Biotec, Novartis, Ocean Pharma, Pfizer, Regeneron, Samsung Bioepis, Sanofi, Sun Pharma, Takeda, UCB, Valeant and Xenoport.

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Long-term Safety of Risankizumab From 17 Clinical Trials in Patients With Moderate-to-severe Plaque Psoriasis

Abstract and Introduction

Abstract

Introduction

Tables

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Authors and Disclosures

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Appendix 1

Conflicts of Interest

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