Effect of Risankizumab on Patient-Reported Outcomes in Moderate to Severe Psoriasis: The UltIMMa-1 and UltIMMa-2 Randomized Clinical Trials

Abstract

Importance: Demonstrating the value of therapies from a patient's perspective is increasingly important for patient-centered care.

Objective: To compare patient-reported outcomes (PROs) with risankizumab vs ustekinumab and placebo in psoriasis symptoms, health-related quality of life (HRQL), and mental health among patients with moderate to severe psoriasis.

Design, setting, and participants: The UltIMMa-1 and UltIMMa-2 studies were replicate 52-week phase 3, randomized, multisite, double-blind, placebo-controlled and active comparator-controlled trials conducted in 139 sites (including hospitals, academic medical centers, clinical research units, and private practices) globally in Asia-Pacific, Japan, Europe, and North America. Adults (≥18 years) with moderate to severe chronic plaque psoriasis with body surface area (BSA) involvement of 10% or more, Psoriasis Area Severity Index (PASI) scores of 12 or higher, and static Physician's Global Assessment (sPGA) scores of 3 or higher were included.

Interventions: In each trial, patients were randomly assigned (3:1:1) to 150 mg of risankizumab, 45 mg or 90 mg of ustekinumab (weight-based per label) for 52 weeks, or matching placebo for 16 weeks followed by risankizumab.

Main outcomes and measures: Integrated data from 2 trials were used to compare Psoriasis Symptom Scale (PSS) (total score and item scores for pain, redness, itchiness, and burning), Dermatology Life Quality Index (DLQI), 5-level EuroQoL-5D (EQ-5D-5L), and Hospital Anxiety and Depression Scale (HADS), at baseline, week 16, and week 52.

Results: A total of 997 patients with moderate to severe chronic plaque psoriasis were analyzed. Across all arms, the mean age was 47.2 to 47.8 years and 68.3% (136/199 for ustekinumab) to 73.0% (146/200 for placebo) were men. Patients' characteristics and PROs were comparable across all treatment arms at baseline (n = 598, 199, 200 for risankizumab, ustekinumab, and placebo, respectively). At week 16, a significantly greater proportion of patients treated with risankizumab than those treated with ustekinumab or placebo achieved PSS = 0, indicating no psoriasis symptoms (30.3% [181/598], 15.1% [30/199], 1.0% [2/200], both P < .001), and DLQI = 0 or 1 indicating no impact on skin-related HRQL (66.2%, 44.7%, 6.0%, P < .001). Significantly greater proportions of patients treated with risankizumab achieved minimally clinically important difference (MCID) than ustekinumab or placebo for DLQI (94.5% [516/546], 85.1% [149/175], 35.6% [64/180]; both P < .001), EQ-5D-5L (41.7% [249/597] vs 31.5% [62/197], P = .01; vs 19.0% [38/200], P < .001), and HADS (anxiety: 69.1% [381/551] vs 57.1% [104/182], P = .004; vs 35.9% [66/184], P < .001; depression: 71.1% [354/598] vs 60.4% [96/159], P = .01; vs 37.1% [59/159], P < .001). At week 52, improvements in patients treated with risankizumab compared with those treated with ustekinumab were sustained for PSS, DLQI, and EQ-5D-5L.

Conclusions and relevance: Risankizumab significantly improved symptoms of moderate to severe psoriasis, improved HRQL, and reduced psychological distress compared with ustekinumab or placebo.

Trial registration: ClinicalTrials.gov Identifiers: NCT02684370 (UltIMMa-1) and NCT02684357 (UltIMMa-2).

Conflict of interest statement

Conflicts of Interest Disclosures: Dr Augustin has served as consultant to or paid speaker for clinical trials sponsored by companies that manufacture drugs used for the treatment of psoriasis, including AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, Centocor, Eli Lilly, GSK, Janssen-Cilag, Leo, Medac, Merck, MSD, Novartis, Pfizer, UCB and Xenoport. Dr Lambert serves as an investigator and/or consultant for AbbVie, Janssen, Lilly, Celgene, Novartis, Pfizer, and LEO Pharma. Dr Gordon has received honoraria for serving as a consultant and/or grants as an investigator from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermira, Eli Lilly, GlaxoSmithKline, Janssen, Leo, Novartis, Pfizer, Regeneron, Sanofi-Aventis, Sun, and UCB. Drs Joshi and Geng are employees of AbbVie and may own AbbVie stock or stock options. Drs Zema, Thompson, and Valdez are former employees of AbbVie and may own AbbVie stock or stock options. Drs Yang, Wu, and Garcia-Horton are employed by Analysis Group, which received payment from AbbVie to assist with the research process. No other conflicts are reported.

Figures

Figure 1.. Total Psoriasis Symptom Scale (PSS) Score Analyses

A, PSS Total score summary.Mean values are shown. The PSS total scores were exploratory outcomes in the trials. The last observation carried forward imputation was adopted for missing data. Risankizumab-treated patients had significantly lower PSS total scores compared with placebo-treated patients at week 4 through week 16 (P < .001) and ustekinumab-treated patients at week 4 through week 52 (P = .01 at week 4, P = .01 at week 8, P = .008 at week 12, and P < .001 at all other time points). B, PSS = 0 Responder Analysis. The nonresponder imputation (NRI) approach was used. PSS = 0 at week 16 was a ranked secondary outcome; all other time points were exploratory outcomes. A significantly greater proportion of risankizumab-treated patients achieved PSS = 0, compared with patients treated with placebo (P = .008 at week 4, P < .001 at all other time points) and those treated with ustekinumab (P = .02 at week 4, P = .03 at week 12, and P < .001 at all other time points). C, PSS = 0/1 responder analysis. NRI approach was used. PSS = 0/1 was an exploratory outcome. From week 12 through week 52, a significantly greater proportion of risankizumab-treated patients achieved PSS = 0/1 compared with ustekinumab-treated patients (P = .01 at week 12 and P < . 001 at week 16 through week 52).

Figure 2.. Psoriasis Symptom Scale (PSS) Items Scales Responder Analyses (Exploratory Outcomes)a

A, PSS pain. B, PSS redness. C, PSS itchiness. D, PSS burning. aSignificantly greater proportions of patients treated with risankizumab achieved a score of 0 or 1 on each of the PSS items at week 4 through week 16 compared with placebo. Compared with patients treated with ustekinumab, a significantly greater proportion of those treated with risankizumab achieved PSS pain = 0 (P < .001 from week 22 onward), PSS redness = 0 (P = .01 at week 4, P = .001 at week 8, P = .001 at week 12, and P < .001 at all other time points, PSS itchiness = 0 (P < .001 from week 16 onward), and PSS burning = 0 (P < .001 from week 28 onward).