Näytönastekatsaukset

Risankizumab treatment in adult patients with active psoriatic arthritis: effectiveness and safety compared to placebo.

Näytönastekatsaukset

8.10.2024

Krista Nuotio

Level of evidence: A

Subcutaneous risankizumab treatment at the dose of 150 mg at weeks 0, 4 and 16 increases the proportion of patients with active psoriatic arthritis achieving the ACR20 response at week 16 (50–60%), when compared to placebo (25–35%), and it is safe.

Significantly higher ACR50 and ACR70 response rates were observed for risankizumab compared to placebo at week 24 as well, but it was observed more slowly. Follow-up time was relatively short, hence conclusions about long-term safety was not possible to draw.

Table 1. Description of the included studies
Reference	Study type	Population	Intervention and comparison	Outcomes	Risk of bias
«Kristensen LE, Keiserman M, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial. Ann Rheum Di»1	RCT, double-blind phase III multicenter study, KEEPsAKE 1 trial	Adults (≥18 years) with active PsA, IR, intolerance or contraindication to ≥1 csDMARD. No prior exposure to biologics was permitted. Patients were from 38 countries. Randomization 1:1.	RZM 150mg sc. at weeks 0, 4 and 16. vs. placebo	Primary outcome measure: ACR20 at week 24 Secondary outcome measures: HAQ-DI, PASI90, ACR20 at week 16, MDA, mNAPSI, PGA-F, resolution of enthesitis, resolution of dactylitis, PsA-mTSS, SF-36PCS, FACIT-Fatigue, ACR50/70.	Low
«Östör A, Van den Bosch F, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 2 trial. Ann Rheum Dis »2	RCT, double-blind phase III global multicenter study, KEEPsAKE 2 trial	Adults (≥18 years) with active PsA and IR or intolerance to biological agents and/or IR or intolerance to csDMARD-IRs. 23 countries, randomization 1:1.	RZM 150mg sc. at weeks 0, 4 and 16. vs. placebo	Primary outcome measure: ACR20 at week 24 Secondary outcome measures: HAD-QI, PASI90, ACR20 at week 16, MDA, SF-36PCS, FACIT-Fatigue score, ACR50, ACR70, resolution of enthesitis, resolution of dactylitis	Low
«Mease PJ, Kellner H, Morita A, et al. Long-Term Efficacy and Safety of Risankizumab in Patients with Active Psoriatic Arthritis: Results from a 76-Week Phase 2 Randomized Trial. Rheumatol Ther 2022;9(»3	RCT, double-blind, dose-ranging, phase 2, multicenter study	Adults (≥18 years) with active PsA and IR/intolerance to NSAIDs, csDMARDs or TNF-inhibitors. Exclusion: patients with major chronic inflammatory or connective tissue disease other than PsA or fibromyalgia or pts who received any therapeutic agent directly targeting IL-12/23, IL-23, or IL-17. 11 countries, randomization 2:2:2:1:2	Arm 1 (n=42): RZM 150 mg sc at weeks 0, 4, 8, 12, and 16 Arm 2 (n=42): RZM 150 mg sc at weeks 0, 4, and 16 (This dosing included in the present evidence review.) Arm 3 (n=39): RZM 150 mg sc at weeks 0 and 12 Arm 4 (n=20): RZM 75 mg sc at week 0 Arm 5 (n=42): PBO	Primary outcome measure: ACR20 at week 16 for pooled arms 1+2 and PBO Secondary outcome measures: ACR20, ACR50, ACR70 for all arms, PASI90, TJC68, SJC66, SF-36, SPARCC, mNAPSI, DAS28, LEI, MDA,	Low

RCT=randomized controlled trial; SR=systematic review; MA=meta-analysis; RZM=Risankizumab; PsA= psoriatic arthritis; PBO=placebo; ACR=American College of Rheumatology; ACR20= the proportion of patients who achieved ≥20% improvement in American College of Rheumatology criteria; DMARDs=disease-modifying antirheumatic drugs; cs= conventional synthetic; IR=inadequate response; PRISMA= Preferred Reporting Items for Systematic review and Meta-Analysis; HAQ-DI Health Assessment Questionnaire-Disability Index; PASI90=proportion of patients who achieved ≥90% reduction in Psoriasis Area and Severity Index 90; MDA=proportion of patients who achieved minimal disease activity; mNAPSI=change from baseline in modified Nail Psoriasis Severity Index; PGA-F=change from baseline in Physician's Global Assessment of Fingernail Psoriasis Score; PsA-mTSS=change from baseline in PsA-modified Total Sharp Score; SF-36PCS=change from baseline in 36-Item Short-Form Health Survey Physical Component Summary; FACIT-FAtigue score=change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Questionnaire

Table 2. Additional comments for included studies
Reference	Comments
«Kristensen LE, Keiserman M, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial. Ann Rheum Di»1	94% of study patients were white. The study continued as an open-label study until 204 weeks. 473 (97.9%) patients from RZM and 467 (97.1%) from PBO group completed the week 24 study visit. Most AEs reported in the RZM group were mild or moderate. The most frequently reported TEAE was upper respiratory tract infection (RZM, n=17 (7.6%); placebo, n=12 (5.5%)).
«Östör A, Van den Bosch F, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 2 trial. Ann Rheum Dis »2	96-97% of study patients were white. 215 (96.0%) patients from RZM and 199 (90.5%) from PBO group completed the week 24 study visit. One patient was randomised but never received the study drug and was excluded from the efficacy analyses; therefore, 443 patients were included in the full analysis set. The study continued as an opel-label study until 208 weeks.
«Mease PJ, Kellner H, Morita A, et al. Long-Term Efficacy and Safety of Risankizumab in Patients with Active Psoriatic Arthritis: Results from a 76-Week Phase 2 Randomized Trial. Rheumatol Ther 2022;9(»3	93.5% patients completed the 24-week core study (double-blinded randomized study). AbbVie and Boehringer Ingelheim funded the core study.

Results

Table 3. ACR20 at week 16
Reference	Number of studies and number of patients (I/C)	Follow-up time	Absolute number of events (%) I	Absolute number of events (%) C	Difference (95% CI)
1.	483/481	16 weeks	272 (56.3%)	161 (33.4%)	23.1% (16.8; 29.4)
2.	224/219	16 weeks	108 (48.3%)	55 (25.3%)	22.6% (13.9; 31.2)
3.	84/42	16 weeks	50 (59.5%)	15 (35.7%)	23.8% (9.3; 38.7)
Level of evidence: high

I= intervention; C=comparison; CI=confidence interval

Table 4. ACR50 at week 16-24
Reference	Number of studies and number of patients (I/C)	Follow-up time	Absolute number of events (%) I	Absolute number of events (%) C	Difference (95% CI)
1.	483/481	24 weeks	162 (33.4%)	54 (11.3%)	22.2% (17.3; 27.2)
2.	224/219	24 weeks	59 (26.3%)	20 (9.3%)	16.6% (9.7; 23.6)
3.	84/42	16 weeks	(23.8%)^*	(11.9%)^*	11.9%^*
Level of evidence: high

I= intervention; C=comparison; CI=confidence interval

^*Number and CI not reported

Table 5. ACR70 at week 24
Reference	Number of studies and number of patients (I/C)	Follow-up time	Absolute number of events (%) I	Absolute number of events (%) C	Difference (95% CI)
1.	483/481	24 weeks	74 (15.3%)	23 (4.7%)	10.5% (6.9; 14.2)
2.	224/219	24 weeks	27 (12.0%)	13 (5.9%)	6.0% (0.8; 11.3)
3.	84/42	16 weeks	(10.7%)^*	(0%)^*	10.7%^*
Level of evidence: high

I= intervention; C=comparison; CI=confidence interval

^*Number and CI not reported

Table 6. Any adverse event at week 24
Reference	Number of studies and number of patients (I/C)	Follow-up time	Absolute number of events (%) I	Absolute number of events (%) C	Difference (95% CI)
1.	483/481	24 weeks	195 (40.4%)	186 (38.7%)	1.7% (CI NR)
2.	224/219	24 weeks	124 (55.4%)	120 (54.8%)	0.6% (CI NR)
3.	84/42	24 weeks	49 (58.3%)	31 (73.8%)	-15.5% (CI NR)
Level of evidence: high

I= intervention; C=comparison; CI=confidence interval; NR=not reported

References

Kristensen LE, Keiserman M, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial. Ann Rheum Dis 2022;81(2):225-231 «PMID: 34911706»PubMed
Östör A, Van den Bosch F, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 2 trial. Ann Rheum Dis 2022;81(3):351-358 «PMID: 34815219»PubMed
Mease PJ, Kellner H, Morita A, et al. Long-Term Efficacy and Safety of Risankizumab in Patients with Active Psoriatic Arthritis: Results from a 76-Week Phase 2 Randomized Trial. Rheumatol Ther 2022;9(5):1361-1375 «PMID: 35931879»PubMed