Evolving paradigm of psoriasis treatment with risankizumab
Although there is currently no cure for psoriasis, advances in biologic therapies have led to significant improvements in symptom control and better quality of life for patients. Dr Mimi Chang, Specialist in Dermatology & Venereology, Honorary Clinical Associate Professor from the Department of Medicine & Therapeutics, Chinese University of Hong Kong, talked to MIMS Doctor about the latest developments in biologic therapies and how they impact the management of psoriasis.
Psoriasis treatment overview
“Conventional therapies for psoriasis include topical agents, targeted or systemic phototherapies, and oral agents such as methotrexate, acitretin and cyclosporine,” said Chang. “Biologic therapies for psoriasis have been in use for more than 13 years in Hong Kong. These include the early-generation tumour necrosis factor alpha [TNF-α] inhibitors, interleukin [IL]-12/23 inhibitors and IL-17 inhibitors, and the latest-generation selective IL-23 inhibitors.” [Int J Mol Sci 2019;20:1475]
“According to guidelines of the British Association of Dermatologists, psoriasis patients are eligible for biologic therapy if they have a Dermatology Life Quality Index [DLQI] score of >10 plus extensive disease, defined as body surface area involvement >10 percent or Psoriasis Area and Severity Index [PASI] score of ≥10, or severe disease at local sites causing significant functional impairment and/or high levels of distress, such as on the face and hands,” she continued. [Br J Dermatol 2020, doi: 10.1111/bjd.19039]
Selective IL-23 inhibitors for psoriasis
“Selective IL-23 inhibitors [eg, guselkumab and risankizumab] are the latest-generation biologics that target the p19 subunit of the proinflammatory cytokine IL-23, leading to a decrease in proliferation of T helper 17 [Th17] cells and, in turn, a decrease in keratinocyte turnover, both of which are involved in the pathogenesis of psoriasis,” Chang explained. “Unlike IL-12/23 inhibitors, selective IL-23 inhibitors spare the non-pathogenic IL-12/T helper 1 [Th1] axis, which is important in protecting against infections and in tumour immune surveillance. Selective IL-23 inhibitors also act at a more upstream level than IL-17 inhibitors, and maintain the integrity of mucosal tissue.” [Psoriasis (Auckl) 2018;8:83-92; J Eur Acad Dermatol Venereol 2018;32:1111-1119]
Selective IL-23 inhibitors have demonstrated superior efficacy in the treatment of psoriasis compared with older-generation biologic therapies.
In the phase III, randomized, double-blind, placebo-controlled UltIMMa-1 and UltIMMa-2 trials, 997 patients with moderate-to-severe chronic plaque psoriasis were randomized to receive the selective IL-23 inhibitor risankizumab (150 mg), the IL-12/23 inhibitor ustekinumab (45 mg or 90 mg), or placebo. [Lancet 2018;392:650-661] An integrated analysis of the trials showed 90 percent improvement in PASI (PASI 90) in 75.1 percent vs 44.7 percent of patients on risankizumab vs ustekinumab at week 16. (Figure 1) [Lebwohl M, et al, AAD 2019, abstract P8108] The PASI 90 rate with risankizumab at week 16 was sustained at week 52 across subgroups (77.6–85.9 percent), including patients with psoriatic arthropathy, and biologic-naïve or biologic-experienced patients. Risankizumab was also effective regardless of prior treatment history, including in patients with prior biologic failure. [Foley P, et al, AAD 2019, abstract 9780]
“Meanwhile, the phase III IMMvent study [n=605] showed that risankizumab was superior to the TNF-α inhibitor adalimumab in rates of PASI 90 [72 percent vs 47 percent] and PASI 100 [40 percent vs 23 percent] at week 16,” noted Chang. [Lancet 2019;394:576-586] Furthermore, patients who achieved PASI 90 or PASI 100 had these responses sustained beyond week 136. [Reich K, et al, EADV 2019, poster 1713; Strober B, et al, EADV 2019, poster 1714; Leonardi C, et al, AAD 2020, poster 13883] After 4 weeks of treatment with risankizumab (ie, one dose), a mean PASI improvement of 58 percent was seen, indicative of a fast onset of efficacy. [Lebwohl M, et al, AAD 2019]
In the latest IMMerge study, a double-blind, placebo-controlled phase III study with head-to-head comparison of risankizumab vs the IL-17 inhibitor secukinumab, risankizumab demonstrated significantly higher rates of PASI 90 (87 percent vs 57 percent) and PASI 100 (66 perent vs 40 percent) vs secukinumab at week 52. (Figure 2) [Br J Dermatol 2020, doi: 10.1111/bjd.19341]
“In all studies, IL-23 inhibitors have shown low rates of adverse events [AEs] relative to TNF-α inhibitors, such as demyelinating disease and tuberculosis,” said Chang. “The most common AEs associated with IL-23 inhibitors included upper respiratory tract infections, headache, and injection site reactions. No new safety signals were reported in studies with longer follow-up.” [Curr Neurol Neurosci Rep 2017;17:36; Lancet 2018;392:650-661; Lancet 2019;394:576-586; Foley P, et al, AAD 2019, abstract 7980]
Treatment individualization is key
“As there is no cure at present, selection of treatment for psoriasis should be based on a balance of efficacy and safety,” Chang advised. “Each drug class has its own AE profile. Clinicians should individualize psoriasis treatment based on disease severity, comorbidities, previous treatments, efficacy, safety, contraindications, patient’s preferences and stage of life, and local reimbursement programmes, rather than prescribe treatment in a one-size-fits-all manner.”
“After loading, risankizumab is administered four times a year, making it a convenient option for patients. However, due to its relatively long half-life, adequate time is needed for risankizumab to be cleared from the body after temporary withdrawal for surgery or other reasons,” she noted. [Skyrizi Hong Kong Prescribing Information, May 2019] “With studies demonstrating its efficacy in patients with prior biologic failure, risankizumab would be a useful option for both biologic-naïve and biologic-experienced patients with moderate-to-severe chronic plaque psoriasis.” [Foley P, et al, AAD 2019, abstract 7980]
“Management of psoriasis has improved with advancements in biologic therapies, but the long-term efficacy and safety of these therapies still need to be monitored due to the withdrawal of a previous agent as a result of late fatal side effects,” Chang added. [https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/efalizumab-marketed-raptiva-information]