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Study Designs

LIMMitless Open Label Extension Study Design to 4.5 years2

LIMMitless OLE Study Design2

LIMMitless is an ongoing phase 3, single-arm, multicentre, international, open-label extension in which all patients received SKYRIZI (150 mg) every 12 weeks. The 232 week analysis included patients who were initially randomized to receive SKYRIZI (150 mg) in 1 of 5 base phase II/III studies. Results from 232 week interim analysis including integrated data from five phase 2/3 studies (UltIMMA-1, UltIMMa-2, SustaIMM, IMMvent, and NCT03255382) and the LIMMitless study. Efficacy was assessed every 12 weeks by PASI 90, PASI 100, sPGA 0/1, mean PASI percent improvement. Quality of life was assessed every 24 weeks by DLQI 0/1.

Adapted from Papp K, et al. 2021.

RZB, risankizumab; PASI, Psoriasis Area Severity Index; sPGA, static Physicians Global Assessment, DLQI; Dermatology Life Quality Index.

Efficacy was assessed every 12 weeks by:

− PASI 90

− PASI 100

− sPGA 0/1

− Mean PASI percent improvement

Quality of life was assessed every 24 weeks by:

− DLQI 0/1

Safety was assessed via adverse event monitoring through the cutoff date for this analysis (Mar 26, 2020)

LIMMitless OLE baseline demographicsa2

Adapted from Papp K, et al. 2020.

aBaseline at the start of base study.
bDiagnosed or suspected.
cBased on N = 838 as this information was not collected in NCT03255382.
BSA, body surface area, DLQI, Dermatology Life Quality Index; PASI, Psoriasis Area and Severity Index; sPGA, static Physician’s Global Assessment; TNF, tumor necrosis factor.
Results from 172 week interim analysis including integrated data from five phase 2/3 studies (UltIMMA-1, UltIMMa-2, SustaIMM, IMMvent, and NCT03255382)2-5 and the LIMMitless study).

 

IMMerge Phase III Study3,4

IMMerge Study Design

A phase III, global, multicentre, randomised, open-label, efficacy assessor-blinded, active comparator study to evaluate the safety and efficacy of risankizumab vs secukinumab in adults with moderate to severe plaque psoriasis.

Adapted from Warren et al. 2020

A total of 327 subjects were randomised 1:1 to SKYRIZI (n=164) (150 mg), given as two 75-mg subcutaneous injections at baseline, 4 weeks later, and every 12 weeks thereafter, or secukinumab (n=163) (300 mg) given as two 150-mg subcutaneous injections, at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks thereafter.


PASI, Psoriasis Area Severity Index

Co-primary endpoints

  • PASI 90 at Week 52 (superiority): Proportion of patients who achieved PASI 90 response at Week 52 vs secukinumab.
  • PASI 90 at Week 16 (noninferiority): Proportion of patients who achieved PASI 90 response at Week 16 vs secukinumab.

Co-primary endpoints were met. 

Ranked secondary endpoints

  • PASI 100 at Week 52 vs secukinumab
  • PASI 75 at Week 52 vs secukinumab
  • sPGA 0/1 at Week 52 vs secukinumab

All ranked secondary endpoints were met.

PASI, Psoriasis Severity Index; sPGA, static Physicians' Global Assessment.

IMMerge baseline demographics3,4

Key demographics and baseline characteristics were generally balanced between treatment groups and consistent with the pivotal UltIMMa-1 and UltIMMa-2 trials.5

Adapted from Warren et al, 20203

sPGA, static Physician Global Assessment; PASI, Psoriasis and Severity Index; PsO, Psoriasis.

UltiMMa-1 and UltiMMa-2 Phase III studies and open label extension study5

UltIMMa-1: n=506, UltIMMa-2: n=491

Efficacy and safety of SKYRIZI in adults with moderate to severe plaque psoriasis in 2 replicate double-blind, randomised, placebo controlled and ustekinumab controlled Phase III clinical trials. 

 

 

Part A (baseline to Week 16): Patients received either SKYRIZI 150mg, ustekinumab 45/90mg, or placebo. 

Part B (Weeks 16 to 52): SKYRIZI and ustekinumab patients continued on treatment 

Study design 

UltIMMa-1 and Ult!MMa-2 were replicate Phase Ill, randomised, double-blind, placebo-controlled and active comparator-controlled trials done at 139 sites. Eligible patients were 18 years or older, with moderate to severe chronic plaque psoriasis. In each study, patients were stratified by weight and previous exposure to TNF inhibitor and randomly assigned (3:1:1) by use of interactive response technology to receive 150mg risankizumab, 45mg or 90mg ustekinumab (weight-based per label), or placebo. 

*Dosing of ustekinumab was 90mg for patients weighing over 100kg.
OLE, open-label extension; PASI, Psoriasis Area Severity Index; PBO, Placebo; sPGA, static Physicians' Global Assessment; TNF, tumour necrosis factor; UST, ustekinumab.

Co-primary endpoints:
Co-primary endpoints were proportions of patients achieving PASI 90 and sPGA 0 or 1 at Week 16 with SKYRIZI vs. placebo. Both co-primary endpoints were met (P<0.0001).


Ranked secondary endpoints:
1st sPGA 0 (clear) at Week 16 vs. placebo
2nd PASI 100 at Week 16 vs. placebo 3rd DLQI 0 or 1 at Week 16 vs. placebo 4th PSS 0 at Week 16 vs. placebo
5th PASI 90 at Week 16 vs. placebo
6th sPGA 0/1 (clear or almost clear) at Week 16 vs. ustekinumab
7th PASI 100 at Week 16 vs. ustekinumab
8th sPGA 0 (clear) at Week 16 vs. ustekinumab
9th PASI 90 at Week 52 vs. ustekinumab 10th PASI 100 at Week 52 vs. ustekinumab
11th sPGA 0 (clear) at Week 52 vs. ustekinumab
12th PASI 75 at Week 12 vs. ustekinumab
13th sPGA 0/1 (clear or almost clear) at Week 12 vs. ustekinumab
14th DLQI 0 or 1 at Week 16 vs. ustekinumab
15th Change from baseline in PSS at Week 16 vs. placebo

All ranked secondary endpoints were met.

*Dosing of ustekinumab was 90mg for patients weighing over 100kg.
OLE, open-label extension; PASI, Psoriasis Area Severity Index; PSS, psoriasis symptom scale; PBO, Placebo; sPGA, static Physicians' Global Assessment; TNF, tumour necrosis factor; UST, ustekinumab.

UltiMMa-1 and UltiMMa-2 OLE baseline demographics5

*Stratlflcation factors for randomisation. Data are mean (SD) or n (%) unless otherwise specified. 
BMI, body mass index; BSA. body surface area; DLOI, Dermatology Life Quality Index; PASI, Psoriasis Area and Severity Index; SD. standard deviation; sPGA. static Physician's Global Assessment; TNFi. tumour necrosis factor inhibitor. 

IMMvent Phase III study6

Efficacy and safety of SKYRIZI compared with adalimumab in patients with moderate to severe plaque psoriasis.

Part A (baseline to Week 16): Patients received either SKYRIZI 150mg or adalimumab (80mg at baseline, 40mg at Week 1, and then EOW). 

Part B (Weeks 16 to 44): SKYRIZI patients continued on treatment. Adalimumab group, dependent on PASI response: 

• PASI <50 switched to SKYRIZI 

• PASI 50 <PASI 90 (rerandomised to either SKYRIZI or adalimumab) 

• PASI 90 continued with adalimumab

EOW, every other week; OLE, open-label extension; PASI, Psoriasis Area Severity Index; sPGA, static Physicians' Global Assessment. 

Co-primary endpoints:

Co-primary endpoints for Part A were PASI 90 and sPGA 0/1 at week 16 with SKYRIZI vs. adalimumab. 

Primary endpoint for Part B was PASI 90 at Week 44 with SKYRIZI vs. adalimumab among those with PASI 50 - <PASI 90 after 16 weeks of adalimumab treatment. 

Co-primary and primary endpoints were met for both Part A and Part B (P<0.0001 ). 

Ranked secondary endpoints: 

  • PASI 75 at Week 16 with SKYRIZI vs. adalimumab 
  • PASI 100 at Weeks 16 and 44 with SKYRIZI vs. adalirnumab. 

All ranked endpoints were met (P<0.001) 

EOW, every other week; OLE, open-label extension; PASI, Psoriasis Area Severity Index; sPGA, static Physicians· Global Assessment. 

Patient subgroups in the IMMvent pivotal trial6

*Stratification factors for randomisation. 
BMI, body mass Index; BSA. body surface area; PASI, Psoriasis Area and Severity Index; SD, standard deviation; sPGA. static Physician's Global Assessment; TNFi. tumour necrosis factor Inhibitor. 

KEEPsAKE-1 and KEEPsAKE-2: study design7

Two randomized, double-blind, placebo-controlled studies assessing the safety and efficacy of 1,407 patients (964 in KEEPsAKE-1 and 443 in KEEPsAKE-2) ≥18 years old with active PsA.

 

SKYRIZI is dosed 150 mg at Week 0, Week 4, and every 12 weeks thereafter. At week 24 when the placebo cohort were switched over to SKYRIZI, loading doses were not administered and patients were immediately switched to 12 weekly dosing.

Study design7

In the two randomized, double-blind, placebo-controlled KEEPsAKE-1 and KEEPsAKE-2 studies, patients had a diagnosis of PsA ≥6 months based on Classification Criteria for Psoriatic Arthritis (CASPAR), a median duration of PsA of 4.9 years at baseline, ≥5 tender joints and ≥5 swollen joints, and active plaque psoriasis or nail psoriasis at baseline. 55.9% of subjects had ≥3% body surface area with active plaque psoriasis. 63.4% and 27.9% of subjects had enthesitis and dactylitis, respectively. 

In KEEPsAKE-1, all subjects had a previous inadequate response or intolerance to nonbiologic DMARD therapy and were biologic naïve. In KEEPsAKE-2, 53.5% of subjects had a previous inadequate response or intolerance to nonbiologic DMARD therapy and 46.5% of subjects had a previous inadequate response or intolerance to biologic therapy.

In both studies, subjects were randomized to receive SKYRIZI 150 mg or placebo at Weeks 0, 4, and 16. Starting from Week 28, all subjects received SKYRIZI every 12 weeks. Both studies include a long-term extension for up to an additional 204 weeks. 59.6% of subjects from both studies were receiving concomitant MTX, 11.6% were receiving concomitant nonbiologic DMARDs other than MTX, and 28.9% were receiving SKYRIZI monotherapy. SKYRIZI was dosed 150 mg at Week 0, Week 4, and every 12 weeks thereafter.*Dosing of ustekinumab was 90mg for patients weighing over 100kg.

ACR20, ≥20% improvement in American College of Rheumatology score; q12w, every 12 weeks; SC, subcutaneous; SJC, swollen joint count; TJC, tender joint count.

KEEPsAKE 17,8

Primary endpoint:

  • ACR 20 at week 24

Secondary endpoints:

  • Change in HAQ-DI at week 24
  • PASI 90 at week 24a
  • ACR20 at week 16
  • MDA at week 24
  • Change in mNAPSI at week 24
  • Change in PGA-F at week 24
  • Resolution of Enthesitisb
  • Resolution of Dactylitisc
  • Change in PsA-mTSS at week 24
  • Change in SF-36 PCS at week 24
  • Change in FACIT-Fatigue at week 24
  • ACR50 at week 24
  • ACR70 at week 24

 

KEEPsAKE 27,9

Primary endpoint:

  • ACR 20 at week 24

Secondary endpoints:

  • Change in HAQ-DI at week 24
  • PASI 90 at week 24a
  • ACR20 at week 16
  • MDA at week 24
  • Change in SF-36 PCS at week 24
  • Change in FACIT-Fatigue at week 24
  • ACR50 at week 24
  • ACR70 at week 24
  • Resolution of Enthesitisb
  • Resolution of Dactylitisc

 

a Among patients with ≥ 3% BSA affected by psoriasis at baseline.
b LEI used to assess the presence or absence of enthesitis.
c LDI used to assess the presence or absence of dactylitis.

ACR, American College of Rheumatology criteria; HAQ-DI, Health Assessment Questionnaire-Disability Index; PASI, Psoriasis Area and Severity Index; MDA, minimal disease activity; SF-36, 36-Item Short Form Health Survey Physical Component Summary; FACIT-Fatigue, Functional Assessment of Chronic Illness Therapy Fatigue Questionnaire.

Patient demographics and baseline characteristics7

BMI, body mass index; BSA, body surface area; HAQ-DI, Health Assessment Questionnaire-Disability Index; MDA, minimal disease activity; PASI, Psoriasis Area and Severity Index; PsA, psoriatic arthritis.

References

  1. SKYRIZI: Summary of Product Characteristics.
  2. Papp K, et al. Long-Term Efficacy and Safety of Risankizumab for the Treatment of Moderate-to-Severe Plaque Psoriasis: Interim Analysis of the LIMMitless Open-Label Extension Trial Beyond 3.5 Years of Follow-Up. Poster 1354. Presented at the 30th European Academy of Dermatology and Venereology Congress, 29 September–2 October 2021, EADV Virtual Congress.
  3. Warren RB et al. Risankizumab vs Secukinumab in Patients with Moderate-to-Severe Plaque Psoriasis: A Phase 3 Trial, Presented at AAD 2020.
  4. Risankizumab versus secukinumab for subjects with moderate to severe plaque psoriasis. ClinicalTrials.gov identifier: NCT03478787. Updated September 20, 2019. Accessed March 2, 2020. https://clinicaltrials.gov/ct2/show/NCT03478787.
  5. Gordon KB et al. Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials. Lancet 2018;392: 650-661.
  6. Reich K et al. Risankizumab compared with adalimumab in patients with moderate-to-severe plaque psoriasis (IMMvent): a randomised, double-blind, active-comparator-controlled phase 3 trial. Lancet 2019; 394: 576-586.
  7. Kristensen LE et al. Efficacy and Safety of Risankizumab for Active Psoriatic Arthritis: 52-Week Results From the KEEPsAKE 1 and KEEPsAKE 2 Trials. Oral presentation EADV 30th Congress 2021 - Anniversary Edition 29 Sept – 2 Oct 2021.
  8. A Study Comparing Risankizumab to Placebo in Participants With Active Psoriatic Arthritis (PsA) Who Have a History of Inadequate Response to or Intolerance to at Least One Disease Modifying Anti-Rheumatic Drug (DMARD) Therapy (KEEPsAKE 1). Available at: https://clinicaltrials.gov/ct2/show/NCT03675308?term=keepsake+1&draw=2&rank=1. Accessed: November 2021. 
  9. A Study Comparing Risankizumab to Placebo in Participants With Active Psoriatic Arthritis Including Those Who Have a History of Inadequate Response or Intolerance to Biologic Therapy(Ies) (KEEPsAKE2). Available at: https://clinicaltrials.gov/ct2/show/NCT03671148?term=keepsake+1&draw=2&rank=2. Accessed: November 2021.

UK-RISN-210507. Date of preparation: November 2021. 


SKYRIZI® (risankizumab) is indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy.1
SKYRIZI® (risankizumab) alone or in combination with methotrexate, is indicated for the treatment of active psoriatic arthritis in adults who have had an inadequate response or who have been intolerant to one or more disease-modifying antirheumatic drugs.1
The recommended dose of SKYRIZI is 150mg administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter.
SKYRIZI is intended for use under the guidance and supervision of a physician experienced in the diagnosis and treatment of psoriasis.
Some patients may not be suitable for SKYRIZI. You are advised to read the Prescribing Information (which can be found on tab above). Please also refer to the SKYRIZI Summary of Product Characteristics for important information including special warnings/precautions for use and summary of adverse reactions.
Study design information can be found on the Study Design page.

Adverse events should be reported. Reporting forms and information can be found at yellowcard.mhra.gov.uk.
Adverse events should also be reported to AbbVie on GBPV@abbvie.com