KEEPsAKE2 trial reveals potential of risankizumab for psoriatic arthritis

The humanized immunoglobulin G1 monoclonal antibody risankizumab led to significant improvements in patients with active psoriatic arthritis (PsA), including those with insufficient response or intolerance to one or two biologic therapies or to at least one DMARD*, according to the results of the phase III KEEPsAKE2 trial presented at EULAR 2021.

Despite advances in PsA treatments, there is still a substantial fraction of PsA patients who do not achieve favourable outcomes, hence the need for other therapeutic alternatives, noted Dr Andrew Östör from Monash University, Melbourne, Victoria, Australia. “KEEPsAKE2 met the primary and all ranked secondary endpoints.”

At week 24, the proportion of patients achieving the primary endpoint of ACR20** was nearly twice as high in the risankizumab vs the placebo arm (51.3 percent vs 26.5 percent; p≤0.001). This effect occurred early in the risankizumab arm at week 4 (19.6 percent vs 11.4 percent; p≤0.05), consistently improving through week 24. [EULAR 2021, abstract OP0228]

All secondary endpoints, be it ranked (changes in HAQ-DI, PASI 90, MDA, SF-36 PCS*** at week 24 and ACR20 at week 16; p<0.001 for all) or non-ranked (ACR50** and resolution of dactylitis [p<0.001 for both], ACR70** [p<0.05], and resolution of enthesitis [p<0.01] – all at week 24), were met with significant superiority with risankizumab vs placebo. Some responses also occurred early – around week 4 for PASI 90 and week 8 for the two non-ranked ACR variables.

“[PsA has various] manifestations, including skin [and] joint disease, enthesis, and dactylitis, as well as functional limitations and patient-reported outcomes that are really meaningful for patients,” Östör pointed out. The findings show that risankizumab outdid placebo in improving these signs and symptoms, including disease activity in the joints and skin.

Risankizumab was well-tolerated with no specific safety issues noted. Treatment-emergent adverse event rates were similar between the risankizumab and the placebo arms (55 percent for both). “Except for upper respiratory tract infection, no TEAE was reported for ≥5 percent of patients in either arm … [There were] no deaths in either arm or flags in relation to AEs of special interest,” said Östör. The safety profile correlated with those previously reported with risankizumab.

A step forward

KEEPsAKE2 randomized 444 patients (median age 52.5 years, 55 percent female) 1:1 to receive risankizumab 150 mg or placebo at weeks 0, 4, and 16. In the ensuing open-label extension phase from week 24, placebo recipients switched to risankizumab Q12W, while those on risankizumab continued their regimen. Nearly half of the participants had prior biologics (46 percent), while almost all had a history of conventional synthetic DMARD use (csDMARD; 95 percent). At baseline, 61 percent were on csDMARDs (predominantly methotrexate [47 percent]).

“Once [risankizumab] is licensed [for PsA], it will certainly be a significant step forward in the management of PsA … What was pleasing was that, whether you failed conventional or biologic DMARDs … you still gained statistically significant improvement,” said Östör. “[As such, risankizumab may] be used in a spectrum of patients … including those who are on ongoing background csDMARDs or even those who are not.”

While we have yet to see how risankizumab will fare in this patient setting in the longer term, at this point, the efficacy and safety responses are “certainly reassuring”, he added.