Psoriasis is an inflammatory immune-mediated chronic disease with significant impact on the individual’s physical, emotional and psychosocial wellbeing. The complex and heterogenous molecular genetic basis of psoriasis underlies the difficulty in disease management. Trial-and-error, frustrating treatment responses, relapses and drug-related adverse events (AE) are par for the course in a patient’s journey. In 2000, it was estimated that over 40,000 persons were affected by psoriasis in Singapore. While the local economic impact has not been formally evaluated, the annual cost from medical expenses and lost wages due to psoriasis in the U.S. was estimated at US$11.25 billion in 2008.
Current treatment landscape
In the last decade, developments in effective and well-tolerated biologic therapies have revolutionised the management of plaque psoriasis by enabling clinicians to treat underlying disease mechanisms. Prominently, the interleukin-17 (IL-17)/IL-23 axis has emerged as a primary signalling pathway leading to characteristic molecular, cellular and structural changes in psoriatic skin.
To date, three IL-23 inhibitors have been approved locally for the adult treatment of moderate-to-severe plaque psoriasis – ustekinumab (Stelara), guselkumab (Tremfya) and risankizumab (Skyrizi). Risankizumab was most recently approved by the Singapore’s Health Sciences Authority (HSA) in October 2021and is available in Singapore as 75mg/0.83mL and 150mg/mL preparations for subcutaneous injection. The recommended dosage is 150mg at Week 0 and Week 4, followed by every 12 weeks thereafter. Risankizumab is a humanised IgG1 monoclonal antibody that selectively binds to the p19 subunit of IL-23 which is responsible for the proliferation, maturation and maintenance of Th17 cells, and promotes the production of IL-17 cytokine. In-vitro, risankizumab was 2 to 3-fold more potent than guselkumab and 4 to 10-fold more potent than ustekinumab in inhibiting IL-23 signalling.
Efficacy and Safety Data
Four key Phase III trials in the setting of plaque psoriasis have demonstrated risankizumab’s efficacy over placebo, ustekinumab (dual IL-12/23 inhibitor) and adalimumab (anti-TNFα) with regard to the proportion of patients achieving ≥90% improvement from baseline in Psoriasis Area and Severity Index score (PASI 90) and a static Physician’s Global Assessment score of 0 or 1 (sPGA 0/1) at Week 165-7. The trials recruited adult patients ≥18 years of age with moderate to severe plaque psoriasis (with or without psoriatic arthritis (PsA)). The outcomes are briefly summarised in the table below.
| Population | Intervention vs Comparator(s) | Primary Efficacy Outcome(s) | Safety Outcomes |
| UltIMMa-1 (n=506)
Baseline (mean) Age: 48.0y BW: 88.5kg BSA involvement:26.4% DLQI: 13.0 28.7% women 34.3% were on prev biologic therapy |
VERSUS
|
At Week 16:
Superior efficacy was sustained through Weeks 52 vs ustekinumab |
|
| UltIMMa-2
(n=491) Baseline (mean) Age: 47.0y BW: 92.1kg BSA involvement:23.7% DLQI: 12.7 31.6% women 42.0% were on prev biologic therapy |
VERSUS
|
At Week 16:
Superior efficacy was sustained through Weeks 52 vs ustekinumab |
|
| IMMvent
(n=605) Baseline (mean) Age: 46.15y BW: 90.1kg BSA involvement:26% 30.0% women 38.0% were on prev biologic therapy |
VERSUS
At Week 16, adalimumab intermediate responders were re-randomised 1:1 to continue adalimumab (n=56) or to switch to risankizumab (n=53) |
At Week 16:
At Week 44: Among adalimumab intermediate responders, PASI 90 was achieved by 66% of the patients who switched to risankizumab and 21% of the patients continued on adalimumab (adjusted absolute difference 45.0%; p<0.0001) |
|
| IMMhance
(n=507) Baseline Median age: 51y Median BW: 89.7kg BSA involvement:26% 29.8% women 15.6% Asian 55.4% were on prev biologic therapy |
VERSUS
At Week 16, all patients received risankizumab. At Week 28, risankizumab patients with an sPGA score of 0/1 (n=336) were re-randomized 1:2 to continue the drug every 12 weeks (n=111) or switch to placebo i.e. treatment withdrawal (n=225). Patients with inadequate response to initial therapy (sPGA ≥2 at week 28) received open-label risankizumab every 12 weeks. At Week 32, patients who had responded to treatment but relapsed (sPGA≥3) were re-treated with open-label risankizumab. |
At Week 16:
At Week 52:
At Week 104:
|
|
To date, over 17 plaque psoriasis clinical trials have provided efficacy and safety evidence for up to 5.9 years of treatment with risankizumab. In addition to clinical improvements, patient-reported outcomes e.g. dermatology life quality index (DLQI) and psoriasis symptoms scale (PSS), which were evaluated as secondary endpoints also showed a positive impact with risankizumab treatment. From a safety perspective, integrated data has not provided signals for risankizumab use being associated with an increased risk of malignancy, major adverse cardiovascular events or serious opportunistic infections over that already associated with the pathophysiology of psoriasis or effects of comparable biologic therapies.
Overall, risankizumab proves to be a highly effective and durable therapeutic that contributes to a rising standard for psoriasis outcomes through resolution of skin lesions and joint manifestations and improvement in patient quality of life. Notwithstanding local regulatory approvals, use of risankizumab in other immune-mediated diseases (e.g. psoriatic arthritis, Crohn’s disease and ulcerative colitis) have also been investigated and successfully implemented in clinical practice globally.
