Table 2.

Studies (clinical trials and RWEs) on risankizumab

Clinical trial
Authors, year	Study type	No. of prt	Study design (study groups)	Study period	Efficacy	Safety	Ref
Papp et al., 2017	Phase II, multicentre, randomized, dose-ranging trial Double-blind within risankizumab dose groups and single-blind (patients) with regard to drug	116	1)Single 18-mg SC dose of risankizumab at week 0 2)90-mg dose of risankizumab at weeks 0, 4, and 16 3)180-mg dose of risankizumab at weeks 0, 4, and 16 4)Ustekinumab 45 mg or 90 mg depending on body weight at weeks 0, 4, and 16	48 weeks	Week 12: PASI90 73% in 90-mg risankizumab, 81% in the 180-mg risankizumab versus 40% in ustekinumab. At least PASI75 was achieved in 63% in the 18-mg risankizumab, 98% in the 90-mg, and 88% in the 180-mg, as compared to 72% in ustekinumab Week 24: At least PASI75 was achieved in 53% of 18-mg risankizumab, 90% in the 90-mg, 88% in the 180-mg, compared to 70% in the ustekinumab	In the 18-mg and 90-mg risankizumab and the ustekinumab group 12%, 15%, and 8%, respectively had serious AEs, including 2 BCCs and 1 major cardiovascular adverse event. No serious AEs in the 180-mg risankizumab group were found	61
Gordon et al., 2018	Replicate phase III, randomized, placebo-controlled, and active comparator-controlled trial UltIMMa-1 and UltIMMa-2	997	1)150 mg risankizumab at weeks 0, 4, 16, 28, and 40 2)Ustekinumab based on weight (45 mg or 90 mg) at weeks 0, 4, 16, 28, and 40 3)Placebo at weeks 0 and 4 → 150 mg risankizumab at weeks 16, 28, and 40	52 weeks	Week 16: UltIMMa-1: PASI90 was achieved by 75.3% risankizumab group, 4.9% placebo group, and 42% of the ustekinumab group UltIMMa-2: PASI90 was achieved by 74.8% risankizumab group, 2% placebo group, and 47.5% of the ustekinumab group UltIMMa-1: sPGA 0 or 1 was achieved by 87.7% risankizumab group, 7.8% placebo, and 63% ustekinumab group UltIMMa-2: sPGA 0 or 1 was achieved by 83.7% risankizumab group, 5.1% placebo, and 61.6% ustekinumab group	Treatment-related AEs in UltIMMa-1 and UltIMMa-2 in risankizumab group were found in 49.7% and in 45.6%. Serious AEs were reported in 2.3% of patients on risankizumab in UltIMMa-1 and in 2% in UltIMMa-2	21
Ohtsuki et al., 2019	Phase II / III, randomized, double-blinded, placebo-controlled trial SustalMM	171 Japanese	1)75 mg risankizumab weeks 0, 4, 16, 28, and 40 2)150 mg risankizumab weeks 0, 4, 16, 28, and 40 3)Placebo weeks 0 and 4 → 75 mg risankizumab weeks 16, 28, and 40 4)Placebo weeks 0 and 4 → 150 mg risankizumab weeks 16, 28, and 40	52 weeks	Week 16: Risankizumab 75 and 150 mg superior versus placebo for PASI90 (75.9%, 74.5%, and 1.7%, respectively) (p < 0.001). PASI75 for risankizumab 75 and 150 mg were significantly higher than placebo (89.7%, 94.5%, and 8.6%, respectively) sPGA score of 0 or 1 was achieved by 86.2% and 92.7% versus 10.3% for risankizumab 75, 150 mg versus placebo Week 52: PASI90 and PASI100 were achieved by 86.2% and 43.1% in risankizumab 75 mg; 92.7% and 41.8% in the risankizumab 150 mg	The safety profile was consistent with previous trials, no new or unexpected safety events were found	72
Reich et al., 2019	Phase III, randomized, double-blind, active-comparator-controlled trial IMMvent	605	1)Risankizumab 150 mg week 0 and 4 2)Adalimumab 80 mg at randomization, then 40 every 2 weeks until week 15 Week 16: 1)Patients remained in risankizumab group (150 mg at week 16 and 28) 2)Adalimumab intermediate responders → re-randomized to continue 40 mg adalimumab every other week or switch to risankizumab 150 mg (week 16, 20, and 32). Responders to adalimumab (PASI90) remained on adalimumab every other week	44 weeks	Week 16: A significantly higher proportion of patients who were assigned to risankizumab achieved PASI90 and sPGA scores of clear or almost clear compared to adalimumab (72% versus 47% and 84% versus 60%, respectively) Week 44: Among adalimumab intermediate responders a larger proportion of patients that were rerandomized to risankizumab achieved PASI90, and PASI 100	In part A AEs occurred in 56% on risankizumab and 57% on adalimumab, with serious AE in 3% of risankizumab and 3% of adalimumab. The most frequently reported were viral upper respiratory tract infection, upper respiratory tract infection, and headache	63
Blauvelt et al., 2020	Phase III, randomized, double-blind, placebo-controlled trial IMMhance	507	1)Risankizumab 150 mg at weeks 0 and 4 2)Placebo at weeks 0 and 4 Week 16: All patients received risankizumab 150 mg Week 28: 1)Patients with risankizumab that achieved an sPGA of 0/1 were rerandomized to risankizumab or placebo every 12 weeks 2)Patients with an inadequate response to initial therapy received open-label risankizumab 150 mg every 12 weeks	104 weeks	Week 16: 73.2% patients in the risankizumab group achieved PASI90 versus 2% in placebo. 83.5% receiving risankizumab versus 7% receiving placebo achieved sPGA 0/1 scores Week 52: sPGA score of 0/1 was achieved by 87.4% of risankizumab versus 61.3% receiving placebo Week 104: the sPGA score of 0/1 was achieved by 81.1% receiving risankizumab versus 7.1% receiving placebo	Rates of treatment-related AEs were similar between risankizumab and placebo group (45.7% and 49%) in part A and remained stable over time	62
Warren et al., 2020	Phase III, multicentre, open-label, efficacy assessor-blinded, active-comparator trial IMMerge	327	1)Risankizumab 150 mg at week 0, 4, and every 12 weeks 2)Secukinumab 300 mg at weeks 0, 1, 2, 3, 4, and every 4 weeks	52 weeks	Week 16: Risankizumab was noninferior to secukinumab in proportion of patients achieving PASI90 (73.8% versus 65.6%) Week 52: PASI90 Risankizumab was superior to secukinumab (86.6% versus 57.1%, p < 0.001) PASI 100, sPGA 0/1, and PASI75 demonstrated superiority for risankizumab (p < 0.001)	AEs were reported in 71.3% of patients treated with risankizumab vs. 71.2% with secukinumab. Serious AEs were found in 5.5% and 3.7% with risankizumab and secukinumab, respectively Most common AEs with risankizumab were nasopharynhitis, upper respiratory tract infection, headache, arthralgia, diarrhoea, and bronchitis	64
Papp et al., 2021	Phase II, multicenter OLE trial Patients already treated in the 48-week, phase 2, double-blind, active comparator trial were included (Papp et al. 2017)	110	1)Risankizumab 90 mg every 12 weeks for at least 48 weeks If at week 12 < PASI90 was found → Risankizumab 150 mg every 12 weeks	48 weeks	74.1% achieved PASI90, whereas 98.1%, 91.7%, 53.7%, and 67.6% achieved PASI50, PASI75, PASI100, and sPGA 0/1, respectively	77.3% patients reported AEs. The most frequent were nasopharyngitis (17.3%), upper respiratory tract infection (13.6%), and arthralgia (10%)	71
Thaçi et al., 2021	Phase III, randomized, active-controlled, open-label study	120	1)Risankizumab 150 mg at weeks 0, 4, and 16 2)FAEs 30 QD from week 0 to week 2, then up to 240 mg, TID from week 3 to week 24 if PASI90 was not achieved	24	Week 24: PASI90 achieved by 83.3% of risankizumab group vs. 10% receiving FAEs PASI50 was achieved by 100% of risankizumab vs. 53.3% of FAEs	Serious AEs were reported by 3.51% of FAEs group and 1.67 of risankizumab group	65
Real world experience
Authors, year	Study type	No. of prt	Study design	Study period	Efficacy	Safety	Ref
Megna et al., 2020	Single-centre, retrospective study	8	Risankizumab at labelled dosage	16 weeks	Baseline mean PASI and BSA were 11.9 ± 5.5, and 22.9 ± 13.1, respectively. Week 16: 3.3 ± 1.7 and 7.5 ± 5 (p < 0.001 and p < 0.01), respectively. Mean baseline NAPSI reduced from 18.0 ± 8.5 to 7 ± 1.4. Palmo-plantar and scalp area showed a reduction of 67.5% and 99.9%	No AEs were reported	68
Bonifati et al., 2020	Prospective, real-world study	12 (9 guselkumab and 3 risankizumab)	1)Risankizumab at labelled dosage 2)Guselkumab at labelled dosage	24 weeks	PASI and PGA decreased significantly through the 24 weeks of treatment Week 12: all sites involved at baseline were free from psoriasis in 6 patients	No AEs were reported	73
Reddy et al., 2020	Observational, single-centre, retrospective study	41	1)Risankizumab at labelled dosage after failing guselkumab 2)Risankizumab + apremilast at labelled dosage after failing guselkumab 3)Risankizumab at labelled dosage without prior switch from guselkumab	Risankizumab after failing guselkumab 21.6 ± 10.4 weeks Risankizumab without guselkumab 18 ± 15.2 weeks	In the guselkumab failures BSA decreased from 28.5 to 5.9 with a 79.3% average decrease In the group without guselkumab treatment BSA decreased from 49.8 to 7.8 for an 84.3% decrease	NR	67
Hansel et al., 2020	Real-life multicenter study	57	Risankizumab at labelled dosage	16 weeks	49.1% reached PASI100, PASI90 was achieved by 63.2%, and PASI75 by 86%	1 patient experienced an upper respiratory tract infection	66
Kromer et al., 2020	Case report	1, 45-year-old woman	Risankizumab at labelled dosage	28 weeks	PASI at week 0: 12.8, week 11: 4.8, week 16: 3.8, and week 28:2.2	NR	74
Ruiz-Villaverde et al. 2020	Case report	1, 47-year-old male	Risankizumab at labelled dosage	56 weeks	Week 8: PASI 0, BSA 0, and sPGA 8	None	75
Tsuchida et al. 2021	Case report	1, 37-year-old man with recurrent colonic diverticulitis	Risankizumab at labelled dosage	48 weeks	PASI100 after a year of treatment	NR	69

Abbreviations: AEs, adverse events; BCC, basal cell carcinomas; FAEs: fumaric acid esters; PASI, Psoriasis Area Severity Index; prt, participants; QD, once a day; ref, reference; SC, subcutaneous; sPGA, static Physician Global Assessment; TID, three times a day (TID)