Risankizumab trumps ustekinumab, placebo for moderate-to-severe psoriasis
The novel, humanized IgG1 monoclonal antibody risankizumab was superior to ustekinumab and placebo in reducing and potentially eliminating symptoms of moderate-to-severe chronic plaque psoriasis, according to two replicate phase III trials.
Apart from its quick onset and sustained long-term effects, risankizumab reduced psychological distress, leading to meaningful improvements in mental health and health-related quality of life (HRQoL), further boosting its promising potential in this setting, noted the researchers.
“Integrated data from [UltIMMa-1 and UltIMMa-2 reflect the] treatment efficacy [of risankizumab] over time from a patient’s perspective through patient-reported outcomes (PROs),” said the researchers. “In the era of patient-centred care … use of PROs is particularly relevant for chronic diseases such as psoriasis given the lifelong effect it has on patients.”
A total of 997 patients were randomized 3:1:1 to receive risankizumab 150 mg, ustekinumab 45 or 90 mg (weight-based), or matching placebo. Risankizumab and ustekinumab were given for 52 weeks; placebo was given for 16 weeks. [JAMA Dermatol 2020;doi:10.1001/jamadermatol.2020.3617]
Total PSS* score was significantly lower with risankizumab vs placebo as early as week 4 (mean, 4.3 to 7.4; p<0.001), which was sustained until week 16 (mean, 2.2 vs 8.0; p<0.001). Total PSS score was also lower with risankizumab vs ustekinumab at week 52 (mean, 1.2 vs 3.1; p<0.001).
A greater fraction of patients on risankizumab achieved PSS=0 (symptom-free) compared with patients on placebo at week 16 (30 percent vs 1 percent; p<0.001), and compared with those on ustekinumab at week 52 (p<0.001).
DLQI, HADS, EQ-5D-5L
At week 16, the percentages of MCID**-based DLQI*** (no impact on skin-related HRQoL) and HADS# responders were also greater with risankizumab compared with ustekinumab (94 percent vs 85 percent; p<0.001 [DLQI], 69 percent vs 57 percent; p=0.004 [HADS anxiety], and 71 percent vs 60 percent; p=0.01 [HADS depression]) and with placebo (94 percent vs 36 percent, 69 percent vs 36 percent, 71 percent vs 37 percent, respectively; p<0.001 for all).
The DLQI improvements with risankizumab vs ustekinumab were sustained by week 52 (96 percent vs 85 percent; p<0.001).
Multivariate analyses of the week-52 outcomes also favoured risankizumab over ustekinumab in terms of PSS=0 (odds ratio [OR], 2.69), MCID-based DLQI=0/1 (OR, 5.27), and DLQI (OR, 3.89; p<0.001 for all).
EQ-5D-5L## scores, although not a sensitive measurement for chronic plaque psoriasis, [Value Health 2013;16:1156-1162] improved in a significantly greater fraction of patients on risankizumab, both at week 16 (42 percent vs 32 percent; p=0.01 [vs ustekinumab] and 42 percent vs 19 percent; p<0.001 [vs placebo]) and at week 52 (44 percent vs 32 percent; p=0.002 [vs ustekinumab]).
Taken together, these PROs are essential for evaluating the efficacy of a certain treatment from a patient’s vantage point to augment data obtained from conventional assessments, noted the researchers.
Avoiding shame, stigma, stress
The appearance of plaque psoriasis may breed a sense of embarrassment, stigmatization, psychological distress, and eventual social isolation among afflicted patients. [Br J Dermatol 2005;153:1192-1199; J Investig Dermatol Symp Proc 2004;9:140-147; Dermatology 2006;212:123-127] “Its physical and psychosocial burden can substantially compromise social functioning, work and daily activity, and HRQoL of many patients with psoriasis, particularly those with moderate-to-severe disease,” said the researchers.
Overall, the findings underscore the potential of risankizumab to provide meaningful clinical and psychosocial benefits among individuals with moderate-to-severe psoriasis, they added.
The results also support available literature on other agents for plaque psoriasis which, despite having favourable outcomes, mostly reflect short-term results. [J Am Acad Dermatol 2015;73:400-409; Lancet 2015;386:541-551; J Dermatol Sci 2016;81:44-52; J Am Acad Dermatol 2017;76:405-417] “One of the strengths of the present study is the availability of longer timepoints at which PROs, including mental health impact, can be evaluated, allowing for both short- and long-term assessment,” noted the researchers.