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.
| Reference | Study type | Population | Intervention and comparison | Outcomes | Risk of bias |
|---|---|---|---|---|---|
| «Kristensen LE, Keiserman M, Papp K, et al. Efficac...»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 ...»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 Ef...»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
| Reference | Comments |
|---|---|
| «Kristensen LE, Keiserman M, Papp K, et al. Efficac...»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 ...»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 Ef...»3 | 93.5% patients completed the 24-week core study (double-blinded randomized study). AbbVie and Boehringer Ingelheim funded the core study. |
Results
| 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
| 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
| 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
| 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