KEEPsAKE findings boost risankizumab efficacy, safety for PsA

In individuals with psoriatic arthritis (PsA) who have inadequate response or intolerance to ≥1 csDMARD*, the monoclonal antibody risankizumab significantly improved manifestations of PsA, according to the 24-week findings of the phase III KEEPsAKE 1 trial.

“Currently available csDMARDs demonstrate variable efficacy in treating the diverse clinical manifestations of PsA, and additional therapeutic agents are needed to address the range of rheumatological and dermatological signs and symptoms of the disease,” said the researchers.

“[Our findings showed that] risankizumab … significantly improved the signs and symptoms of PsA, including joint symptoms, enthesitis and dactylitis, and skin and nail manifestations of psoriasis,” they continued.

A total of 964 participants (median age 52 years, 49.5 percent female) were randomized 1:1 to receive risankizumab 150 mg or placebo at weeks 0, 4, and 16 during the double-blind phase. The most common previously used csDMARD in >10 percent of patients was methotrexate (90 percent) followed by sulfasalazine (22 percent) and leflunomide (13 percent). [Ann Rheum Dis 2021;doi:10.1136/annrheumdis-2021-221019]

More patients on risankizumab vs placebo achieved the primary endpoint of ACR20** at week 24 (57 percent vs 34 percent), an improvement that was observed as early as week 4 (26 percent vs 14 percent; p≤0.001 for both).

A similar trend favouring risankizumab over placebo was also observed in most of the ranked secondary endpoints at week 24, such as PASI 90*** (52 percent vs 10 percent); minimal disease activity (25 percent vs 10 percent); changes HAQ-DI^# (mean, −0.31 vs −0.11), mNAPSI^## (mean,−9.8 vs −5.6), and PGA-F^### (mean, −0.8 vs −0.4); and resolution of enthesitis (48 percent vs 35 percent) and dactylitis (68 percent vs 51 percent; p<0.001 for all).

Collectively, these improvements support the potential of risankizumab to improve the various clinical manifestations and patient burden of PsA, the researchers noted.

The incidence of treatment-emergent adverse events (TEAEs) was similar between the risankizumab and placebo arms (40 percent and 39 percent), and most were mild or moderate in severity. Serious AE rates were similarly low between arms (2 percent vs 4 percent), as were the rates of drug discontinuation owing to TEAEs (0.8 percent in both arms).

The three injection site reactions reported with risankizumab were nonserious, as were the two cases of herpes zoster following risankizumab use. “[The herpes zoster cases] resolved with oral antiviral treatment and did not result in treatment discontinuation,” the researchers said.

Treat all facets of the disease

The impact of PsA on patients’ ability to function and emotional and psychological well-being impairs their quality of life (QoL), hence contributing to the individual and societal burden of the disease. [Ann Rheum Dis 2017;76:673-680; Ann Rheum Dis 2017;76:1495-1501] “[As such,] treating all facets of PsA is important to meaningfully improve patients’ QoL,” said the researchers.

The current findings support risankizumab’s mechanism of action, which has been established in previous studies. [Lancet 2020;395:1115-1125; Lancet 2020;395:1126-1136] “[Our findings imply that] risankizumab may provide an additional therapeutic option for patients in whom standard therapies are inadequate,” the researchers concluded.

The ongoing extension study shall further shed light on the long-term efficacy and safety of risankizumab. The KEEPsAKE 2 trial is assessing similar endpoints in patients who have had inadequate response or intolerance to biologic agents. [Ann Rheum Dis 2021;doi:10.1136/annrheumdis-2021-221048]