Skyrizi Performs Well in Phase 3 Studies of PsA

January 5, 2021

AbbVie’s Risankizumab (Skyrizi), an interleukin-23 (IL-23) inhibitor, is being evaluated as a treatment for adults with active psoriatic arthritis and several other immune-mediated diseases.

Two Phase 3 studies of Risankizumab (Skyrizi) show improvements in disease activity across joint and skin symptoms in patients with psoriatic arthritis.

KEEPsAKE-1 and KEEPsAKE-2 found that significantly more patients treated with risankizumab (150 mg) achieved the primary endpoint of ACR20 response at week 24 versus placebo.  In KEEPsAKE-1 and KEEPsAKE-2, 57 and 51 percent of patients receiving risankizumab achieved ACR20 response at week 24, respectively, versus 34 and 27 percent receiving placebo (p<0.001).

Full results from the studies will be presented at upcoming medical conferences and published in a peer-reviewed medical journal. Use of risankizumab in psoriatic arthritis is not approved and its safety and efficacy have not been evaluated by regulatory authorities.

Results of ranked secondary endpoints showed significant improvements in skin clearance (as measured by at least a 90 percent improvement in Psoriasis Area Severity Index [PASI 90]), physical function (as measured by the Health Assessment Questionnaire Disability Index [HAQ-DI]) and minimal disease activity (MDA) at week 24. 

These two Phase 3 studies evaluated risankizumab in adult patients with active psoriatic arthritis, and included patients who had responded inadequately or were intolerant to biologic therapy and/or non-biologic disease-modifying anti-rheumatic drugs (DMARDs).

"We are encouraged by these positive results showing the potential of risankizumab in psoriatic arthritis," says Michael Severino, M.D., vice chairman and president, AbbVie, in a news release. "These results underscore our commitment to research that can provide health care practitioners with important treatment options for patients with psoriatic disease."

KEEPsAKE-1 and KEEPsAKE-2 Results at Week 24*,1

KEEPsAKE-1

KEEPsAKE-2

Risankizumab 
150 mg
(n=483)

Placebo
(n=481)

Risankizumab 
150 mg
(n=224)

Placebo
(n=219)

ACR20a

57%

34%

51%

27%

ACR50a,f

33%

11%

26%

9%

ACR70a,f

15%

5%

12%

6%

PASI 90b

52%

10%

55%

10%

HAQ-DIc

-0.31

-0.11

-0.22

-0.05

MDAd

25%

10%

26%

11%

PsA-mTSSe,†

0.23

0.32

N/A

N/A

* In both studies, ACR20 at week 24 was the primary endpoint, and PASI 90, HAQ-DI and MDA at week 24 were ranked secondary endpoints. ACR20, PASI 90, HAQ-DI and MDA achieved p-values of <0.001. Not all ranked secondary endpoints are shown.

a ACR20/50/70 is defined as at least a 20 percent/50 percent/70 percent reduction from baseline in the number of both tender and swollen joint counts and equivalent improvement in three or more of the five American College of Rheumatology core set measures: patient assessments of pain, patient global assessment of disease activity, physical function, physician global assessment of disease activity and acute phase reactant.

b PASI 90 is defined as achievement of at least a 90 percent reduction in Psoriasis Area Severity Index. It was assessed in patients with a body surface area (BSA) ≥3 percent at baseline.

c HAQ-DI is defined as change in baseline in the Health Assessment Questionnaire Disability Index, which is a patient-reported questionnaire including categories of dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. It asks patients about the amount of difficulty they experience in these activities as well as the use of aids and/or devices. 

d MDA is defined as the fulfillment of 5 of 7 outcome measures: TJC ≤1; SJC ≤1; PASI ≤1 or BSA-Ps ≤3 percent; Patient's Assessment of Pain Numerical Rating Scale (NRS) ≤1.5; PtGA-Disease Activity NRS ≤2.0; HAQ-DI score ≤0.5; and LEI (Leeds Enthesitis Index) ≤1.

e PsA-mTSS is defined as a change in modified total Sharp score (mTSS) from baseline.

f ACR50 and ACR70 at week 24 were secondary endpoints and achieved nominal p-values of <0.05. These endpoints were not controlled for multiplicity. 

† PsA-mTSS at week 24 was a ranked secondary endpoint that did not reach statistical significance (p=0.496). It was not evaluated in KEEPsAKE-2.

In KEEPsAKE-1, the ranked secondary endpoint of PsA Sharp/van der Heijde Score (PsA-mTSS) was 0.23 and 0.32 at week 24 in the risankizumab and placebo groups, respectively (p=0.496 [note: a lower score denotes lower radiographic progression]).

In these studies, the safety profile of risankizumab through week 24 was generally consistent with safety findings in previous studies in psoriasis.Serious adverse events occurred in 2.5 percent and 4.0 percent of patients treated with risankizumab in KEEPsAKE-1 and KEEPsAKE-2, respectively, compared with 3.7 percent and 5.5 percent on placebo.1Rates of serious infections were similar between treatment groups (1.0 and 0.9 percent in risankizumab-treated patients in KEEPsAKE-1 and KEEPsAKE-2, respectively, and 1.2 and 2.3 percent in patients who received placebo). The rates of adverse events leading to discontinuation of the study drug were 0.8 percent and 0.9 percent of patients treated with risankizumab in KEEPsAKE-1 and KEEPsAKE-2, respectively, compared with 0.8 percent and 2.3 percent on placebo. In KEEPsAKE-1, there was one death in the risankizumab group not related to the study drug per investigator.1 There were no deaths reported in KEEPsAKE-2.

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