Dermatol Ther (Heidelb) (2021) 11:1265–1275 https://doi.org/10.1007/s13555-021-00545-5 ORIGINAL RESEARCH Dermatology Life Quality Index in Patients with Moderate-to-Severe Plaque Psoriasis Treated with Brodalumab or Ustekinumab Jo Lambert . Jes Birger Hansen . Anne Sohrt . Luis Puig Received: January 29, 2021 / Accepted: April 29, 2021 / Published online: May 14, 2021 Ó The Author(s) 2021 ABSTRACT ustekinumab group. A significantly greater reduction (improvement) in DLQI score from Introduction: Targeted biological therapies for baseline was observed in the brodalumab group psoriasis have resulted in significant benefits, compared with the ustekinumab group at weeks with therapeutic goals such as clear or almost 4 [least-squares (LS) mean difference - 2.9, 95% clear skin accompanied by improvements in confidence interval [CI] - 3.6 to - 2.2; health-related quality of life (HRQoL). The p \ 0.001), 12 (LS mean difference - 0.85, 95% objective of this study was to compare the CI - 1.5 to - 0.2; p = 0.01) and 52 (LS mean effects of 52 weeks of treatment with bro- difference - 0.94, 95% CI - 1.6 to - 0.2; dalumab or ustekinumab on HRQoL in patients p = 0.009)]. Significantly greater proportions of with moderate-to-severe plaque psoriasis. patients treated with brodalumab achieved a Methods: Data were pooled from two ran- DLQI score of 0 at weeks 4 (15.0 vs. 5.4%; p \ domised controlled phase 3 trials (AMAGINE-2 0.0001), 12 (37.5 vs. 28.0%; p = 0.0140) and 52 and -3) which included patients with moderate- (46.3 vs. 30.3%; p \ 0.0001), or of B 1 [DLQI (0/ to-severe plaque psoriasis treated with bro- 1): 33.9 vs. 15.4%, 59.9 vs. 45.6% and 54.9 vs. dalumab 210 mg or ustekinumab 45 or 90 mg 39.8%, respectively; all p \ 0.0001]. Similar for 52 weeks. HRQoL outcomes were measured results were observed using the DLQI-R scoring using the Dermatology Life Quality Index system. Significantly more patients achieved a C (DLQI) as well as the DLQI-Relevant (DLQI-R) 4 or C 5 improvement in DLQI with bro- version which excludes ‘not relevant’ responses. dalumab compared to ustekinumab at weeks 4 Results: A total of 929 patients were included, and 52. Treatment with brodalumab was asso- 339 in the brodalumab group and 590 in the ciated with significantly more patients achiev- ing a DLQI of 0 compared to ustekinumab for all domains after 4 and 52 weeks. J. Lambert Conclusion: Brodalumab was associated with a Department of Dermatology, Ghent University Hospital, Ghent, Belgium significantly greater improvement in HRQoL compared to ustekinumab in patients with J. B. Hansen  A. Sohrt moderate-to-severe psoriasis. LEO Pharma A/S, Ballerup, Denmark L. Puig (&) Keywords: Brodalumab; Pharmacology; Department of Dermatology, Hospital de la Santa Creu i Sant Pau–Universitat Autònoma de Barcelona Psoriasis; Quality of life; Ustekinumab (UAB), Barcelona, Spain e-mail: LPuig@santpau.cat 1266 Dermatol Ther (Heidelb) (2021) 11:1265–1275 life, social activity and work functioning. The Key Summary Points use of targeted biological therapies has resulted in significant improvements in the treatment of Both ustekinumab and brodalumab have psoriasis with therapeutic goals, such as clear or been associated with significantly almost clear skin, attainable for many patients. improved health-related quality of life in These improvements in clinical efficacy have patients with moderate-to-severe been associated with significant benefits in the psoriasis, as measured by the Dermatology self-reported HRQoL of patients [1]. Life Quality Index (DLQI). Brodalumab Biological treatments include ustekinumab, has also been shown to provide superior which targets the interleukin (IL)-12/23 path- skin clearance to ustekinumab in patients way and, more recently, IL-17 inhibitors, with moderate-to-severe plaque psoriasis including secukinumab and ixekizumab, which in randomised controlled trials. bind to the IL-17 ligand, and brodalumab, which binds to the IL-17 receptor A and inhibits In an analysis of data pooled from two the action of multiple pro-inflammatory IL-17 randomised, controlled, phase 3 trials of family cytokines. Both ustekinumab and bro- patients with moderate-to-severe plaque dalumab have been associated with signifi- psoriasis, a significantly greater reduction cantly improved HRQoL in patients with (improvement) in DLQI score from moderate-to-severe psoriasis, as measured by baseline was observed with brodalumab the Dermatology Life Quality Index (DLQI) compared to ustekinumab at weeks 4, 12 [2–5]. Previous studies have suggested that IL-17 and 52. inhibition with secukinumab or ixekizumab is More patients treated with brodalumab associated with greater improvements in skin than ustekinumab achieved a DLQI score clearance and HRQoL than ustekinumab [6–8]. of 0 or 0/1. Brodalumab has also been shown to provide superior skin clearance to ustekinumab in Brodalumab was associated with a patients with moderate-to-severe plaque psori- significantly greater improvement in asis in two 1-year randomised controlled trials HRQoL compared to ustekinumab in (AMAGINE-2 and AMAGINE-3) [9]. However, patients with moderate-to-severe the comparative effects of brodalumab and psoriasis. ustekinumab on HRQoL from these trials have not previously been reported. Here, we report the effects of 1-year of treatment with brodalumab or ustekinumab on the HRQoL in patients with moderate-to-severe DIGITAL FEATURES plaque psoriasis enrolled in the AMAGINE-2 and AMAGINE-3 phase 3 trials. This article is published with digital features, including a summary slide, to facilitate under- standing of the article. To view digital features METHODS for this article go to https://doi.org/10.6084/ AMAGINE-2 and AMAGINE-3 were two multi- m9.figshare.14501088. centre, randomised, double-blind, placebo- controlled and active comparator-controlled INTRODUCTION phase 3 trials [9]. In both trials, patients were randomised (2:2:1:1) to brodalumab 210 mg or Psoriasis can have a substantial negative impact 140 mg, ustekinumab (45 mg for patients with a on the health-related quality of life (HRQoL) of body weight B 100 kg and 90 mg for patients, affecting emotional well-being and patients [ 100 kg) or placebo. At week 12, interfering with daily activities, including home patients originally randomised to brodalumab Dermatol Ther (Heidelb) (2021) 11:1265–1275 1267 underwent repeat randomisation (2:2:2:1) to NNRs have previously been observed among brodalumab 210 mg every 2 weeks, 140 mg patients with psoriasis, and concerns have been every 2 weeks, 140 mg every 4 weeks or 140 mg raised regarding the potential for NRRs to lead every 8 weeks. Full details of these studies have to a lower DLQI and thus the patient being been previously reported [9]. The present anal- categorised as having a higher quality of life ysis was focused on the on-label dosages for than may be the case [10]. An adjusted scoring brodalumab so only those patients randomised system for the DLQI that is intended to correct to brodalumab 210 mg for the entire 52 weeks for bias in the NRR option (DLQI-R) has been were included. proposed [11]. The DLQI-R was also used to Patients eligible for enrolment were aged determine proportions of patients achieving 18–75 years and candidates for biologic therapy DLQI 0/1 in a post-hoc analysis. for stable moderate-to-severe plaque psoriasis (minimum disease duration of 6 months) with a Statistical Analysis psoriasis area and severity index (PASI) score of C 12, a physician’s global assessment (PGA) All binary endpoints were analysed and com- score of C 3, and involvement of C 10% of body pared between treatments by odds ratios (ORs) surface area. The institutional review board and 95% confidence intervals (CIs) calculated (IRB) at each participating centre approved the using a Cochran-Mantel–Haenszel Chi-squared study protocols (list of IRBs is given in the test stratified by total body weight at baseline Acknowledgements). Both studies were con- (B or [ 100 kg), prior biologic use, geographic ducted in accordance with the Helsinki Decla- region and baseline DLQI score (B or [ me- ration of 1964, and its later amendments and all dian). Missing data for binary endpoints were relevant regional regulations. All patients pro- accounted for by non-responder imputation vided written informed consent. (NRI). HRQoL was assessed using the DLQI, a ten- For continuous outcomes, an analysis of item measure assessing a patient’s self-assess- covariance model adjusting for total body ment of their quality of life and problems weight at week 12 (B or [ 100 kg), week 12 associated with dermatological disease. DLQI static PGA (sPGA) response (0, C 1), study and total scores range from 0 to 30, with lower treatment was used. Last observation carried scores indicating better dermatology-specific forward (LOCF) method was used to impute quality of life and a score of 0 or 1 both repre- missing data. sentative of no disease effect at all on HRQoL. In The full analysis set included all patients the present study, the DLQI questionnaire was randomly assigned to treatment with at least completed by patients at baseline and every 4 one efficacy assessment after randomisation. weeks during the 52-week treatment period. All statistical analyses were performed using Endpoints included changes in mean DLQI and SAS version 9.4 or higher (SAS Institute Inc., changes in the six individual domains (symp- Cary, NC, USA). toms and feelings, daily activities, leisure, work and school, personal relationships and treat- ment), percentage of patients achieving DLQI RESULTS total scores of 0 and B 1 (0/1) at weeks 12 and 52, patients achieving a C 4- or C 5-point A total of 929 patients were included in the improvement in DLQI from baseline and area- present analysis, 339 in the brodalumab 210 mg under-the-curve (AUC) for DLQI 0/1. group and 590 in the ustekinumab group. Of the ten items of the DLQI, eight include Baseline demographic and clinical characteris- ‘not relevant’ as a possible response, meaning tics were similar across both groups (Table 1). patients do not consider that the item is appli- DLQI at baseline was similar in both treatment cable to their lifestyle. In the original DLQI, a groups, with mean [± standard deviation (SD)] ‘not relevant’ response (NRR) is scored as having scores of 14.8 ± 7.3 in the brodalumab group no impact on the patient’s HRQoL. High rates of and 14.9 ± 7.3 in the ustekinumab group. 1268 Dermatol Ther (Heidelb) (2021) 11:1265–1275 Table 1 Baseline characteristics of patients Fig. 1 Proportions of patients achieving DLQI score of 0 c (a) or 0/1 (b) or a DLQI-R score of 0/1 (c) per visit with Baseline characteristic Brodalumab Ustekinumab brodalumab or ustekinumab (full analysis set, non-respon- (n = 339) (n = 590) der imputation). DLQI Dermatology Life Quality Index, Age, years 44.5 (13.4) 45.1 (13.0) DLQI-R adjusted DLQI correcting for bias in the ‘not relevant’ response (NRR), Q2W once every 2 weeks Male, n (%) 230 (67.8) 404 (68.5) Weight, kg 90.4 (24.2) 91.0 (22.9) Race, white, n (%) 308 (90.9) 532 (90.2) 10.4 ± 7.0 vs. - 7.5 ± 6.3; least-squares (LS) mean difference - 2.9, 95% CI - 3.6 to - 2.2; Disease duration, years 17.3 (11.7) 18.6 (12.2) p \ 0.001], 12 [- 11.7 ± 7.8 vs. - 10.9 ± 7.2; Body surface area 27.0 (16.2) 27.6 (18.6) LS mean difference - 0.85, 95% CI - 1.5 to involvement, % - 0.2; p = 0.01] and 52 [- 12.1 ± 8.1 vs. - 11.2 ± 7.7; LS mean difference - 0.94, 95% Psoriasis area and 20.4 (7.9) 20.0 (8.4) CI - 1.6 to - 0.2; p = 0.009]. severity index (PASI) Significantly greater proportions of patients score treated with brodalumab achieved a DLQI score Dermatology Life 14.8 (7.3) 14.9 (7.3) of 0 at week 4 compared with ustekinumab- Quality Index (DLQI) treated patients (15.0 vs. 5.4%; OR 2.95, 95% CI 1.82–4.79; p \ 0.0001) and this difference score remained significant at weeks 12 (37.5 vs. Nail Psoriasis Severity 9.3 (3.6) 9.9 (3.6) 28.0%; OR 1.45, 95% CI 1.08–1.95; p = 0.0140) Index (NAPSI) score and 52 (46.3 vs. 30.3%; OR 2.08, 95% CI 1.55–2.78; p \ 0.0001]) (Fig. 1a). Similarly, Psoriasis Symptom 19.1 (7.0) 18.7 (6.9) among patients with a DLQI score [ 1 at base- Inventory (PSI) score line, more patients in the brodalumab group Psoriatic arthritis, n (%) 79 (23.3) 110 (18.6) than ustekinumab group achieved a DLQI score of 0/1 at weeks 4 (33.9 vs. 15.4%; OR 2.82, 95% Systemic treatment- 144 (42.5) 246 (41.7) CI 2.01–3.95; p \ 0.0001), 12 (59.9 vs. 45.6%; naı̈ve, n (%) OR 1.74, 95% CI 1.32–2.31; p \ 0.0001) and 52 Previous non-biologic 99 (29.2) 188 (31.9) (54.9% vs. 39.8%; OR 1.90, 95% CI 1.43–2.53; systemic treatment, p \ 0.0001) (Fig. 1b). The AUC for patients n (%) achieving DLQI 0/1 was significantly higher for those receiving brodalumab than for those on Previous biologic 50 (14.8) 95 (16.1) ustekinumab (53.1 vs. 39.7%; AUC ratio 1.34; without failure, n (%) p \ 0.0001) (Fig. 2). Previous biologic failure, 46 (13.6) 61 (10.3) An analysis using the adjusted DLQI-R scor- ing system showed generally similar results for n (%) the proportions of patients achieving DLQI-R All data are presented as the mean with the standard 0/1, although there was a slightly lower pro- deviation (SD) in parentheses unless otherwise indicated portion of patients achieving DLQI-R 0/1 com- pared to DLQI 0/1 (Fig. 1c). NRRs were most frequent for the sport (13.5%), working/study- ing (11.6%) and sexual difficulties (10.1%) Mean individual domain scores were also simi- items, with other items having 1.2–3.6% NRRs. lar between groups at baseline. As with the unadjusted DLQI, a significantly A significantly greater reduction (improve- higher proportion of patients achieved DLQI-R ment) in DLQI score from baseline was observed 0/1 with brodalumab than ustekinumab at in the brodalumab group compared with the weeks 4 (30.1 vs. 12.2%; OR 3.00, 95% CI ustekinumab group at weeks 4 [mean ± SD - 2.10–4.29; p \ 0.0001), 12 (55.5 vs. 41.4%; OR Dermatol Ther (Heidelb) (2021) 11:1265–1275 1269 1270 Dermatol Ther (Heidelb) (2021) 11:1265–1275 Fig. 2 The AUC for DLQI score 0/1 with brodalumab or ustekinumab. AUC = 100% would mean 100% of patients achieve and maintain DLQI 0/1 from week 0 to week 52 (ideal response). AUC Area-under-the-curve 1.75, 95% CI 1.32–2.32; p \ 0.0001) and 52 weeks 4 (83.6 vs. 67.7%; OR 2.73, 95% CI (52.2 vs. 37.8%; OR 1.88, 95% CI 1.41–2.50; 1.87–3.99; p \ 0.0001), 12 (88.2 vs. 86.4%; OR p \ 0.0001). 1.24, 95% CI 0.80–1.92; p = 0.3384) and 52 Among patients with baseline DLQI C 4, (62.8 vs. 48.5%; OR 1.88, 95% CI 1.40–2.54; significantly more achieved a C 4-point p \ 0.0001). improvement with brodalumab compared with Treatment with brodalumab was associated ustekinumab at week 4 and week 52, although with significantly more patients achieving DLQI not at week 12 (Fig. 3). A similar pattern was 0 compared to ustekinumab for the domains of seen among patients with baseline DLQI C 5 at symptoms and feelings, daily activities, leisure Fig. 3 Patients achieving an improvement in DLQI of C 4 points with brodalumab and ustekinumab at 4, 12 and 52 weeks (full analysis set, non-responder imputation). CI Confidence interval, OR odds ratio Dermatol Ther (Heidelb) (2021) 11:1265–1275 1271 Fig. 4 Patients achieving DLQI 0 for individual domains with brodalumab and ustekinumab at 4, 12 and 52 weeks (full analysis set, non-responder imputation) and treatment after 4, 12 and 52 weeks (Fig. 4). patients with moderate-to-severe psoriasis, with Proportions of patients achieving DLQI 0 were complete or near complete skin clearance now a also significantly higher with brodalumab ver- realistic treatment goal. However, patients with sus ustekinumab for work and school and per- psoriasis and their physicians may differ sonal relationships at weeks 4 and 52 but were regarding how much importance they place on not significantly different between groups at different treatment outcomes [14]. To be clini- week 12. cally meaningful for patients, objective improvements in symptoms, such as those reported by PASI, need to be accompanied by DISCUSSION improvements in subjective self-reported HRQoL measures, including the DLQI. Psoriasis represents a considerable burden for Several studies have previously reported that patients, often resulting in feelings of embar- both brodalumab and ustekinumab improve rassment and anxiety and poor self-esteem and HRQoL. In a phase II, randomised, placebo- limiting daily, social and work-related activities controlled clinical study of 198 patients with [12, 13]. Biological treatments such as bro- moderate-to-severe psoriasis, clinically mean- dalumab and ustekinumab have resulted in ingful improvements in DLQI were observed as significant improvements in outcomes for early as week 4 following initiation of treatment 1272 Dermatol Ther (Heidelb) (2021) 11:1265–1275 with brodalumab [4]. DLQI scores were signifi- More patients who achieved PASI 100 (complete cantly improved across all domains at week 12. resolution of all disease) than PASI 90 to \ 100 In a 5-year open-label extension of this study, also achieved DLQI 0/1 (83.5 vs. 64.3%) [19]. In treatment with brodalumab resulted in sub- the previous phase II trial of brodalumab, stantial improvements in HRQoL, with over patients who achieved total skin clearance (PASI two-thirds of patients achieving DLQI 0/1 from 100) reported greater HRQoL improvements week 12 through to week 264 [15]. Ustek- than those who were responders but were not inumab has also been associated with signifi- clear of disease (PASI 75 to \ 100) [20]. In cant improvements in HRQoL as measured by addition, more patients achieved a DLQI score the DLQI [2, 3], which have been reported to be of 0 in the PASI 90 to \ 100 and PASI 100 maintained for up to 3 years of treatment [16]. groups compared with the PASI 75 to \ 90 Ustekinumab was also associated with a sus- group [21]. However, Abrouk et al. reported no tained improvement in DLQI among 489 significant differences in DLQI between patients patients with psoriasis after transitioning from achieving PASI 75 or PASI 90 in an analysis of methotrexate [17]. However, DLQI improve- two ustekinumab clinical trials [22]. In a real- ments with ustekinumab have been reported to world setting, improvements in PASI were be less than those with the IL-17 inhibitors observed to be only weakly to moderately secukinumab or ixekizumab [7, 8]. associated with improvements in DLQI in In the present study, improvements in patients treated with ustekinumab [23]. Simi- HRQoL were significantly greater with bro- larly, data from the Danish National Registry dalumab than with ustekinumab. Also, mean also suggested that the correlation between DLQI scores were lower, and more patients PASI and DLQI is weak to moderate and varies achieved a DLQI of 0 or 0/1 with brodalumab at over time [24]. More research is needed to weeks 4, 12 and 52, indicating a more rapid confirm the correlation between PASI and DLQI improvement in HRQoL with the difference outcomes, especially outside of clinical trials. being maintained over 1 year of treatment. Of the ten questions of the DLQI, eight offer More patients also achieved a C 4-point an NRR option that is scored as if the item had improvement with brodalumab compared with no impact on patients, as a value of 0 is counted ustekinumab, which is the recommended min- for an NRR response. This can mean it is more imal clinically important difference of the DLQI difficult for these patients to fulfil the DLQI [ [18]. The cumulative benefit of brodalumab 10 criterion required to access biologic treat- over ustekinumab regarding HRQoL was con- ment in some clinical guidelines. Female gen- firmed by the AUC ratio for DLQI 0/1 of 1.34. der, older age and more severe disease have Improvements were also seen in each individual previously been associated with more NRRs DLQI domain. [10]. To address this, a new scoring formula Improvement in quality of life tends to be (DLQI-R) that adjusts the total score for the associated with high skin clearance scores [15]. number of NRRs has been proposed [11]. In our PASI and DLQI are closely correlated, with a analysis, the use of DLQI-R did not have a major substantial improvement in clinical efficacy effect on the proportions of patients achieving associated with improved HRQoL in patients DLQI 0/1. For both treatments, the proportions with moderate-to-severe psoriasis, and a signif- of patients achieving DLQI 0/1 was slightly icant difference in DLQI score of 0/1 between lower using DLQI-R than DLQI, which is the PASI 75 and PASI \ 90 responders (C 75% and opposite effect to that previously reported [10]. \90% reduction in PASI scores from baseline, Most NRRs occurred in the sport, sexual diffi- excellent to even better disease improvement, culties and working/studying items of the DLQI, respectively) and PASI 90 responders [1]. In a which is consistent with previous findings. separate analysis of the AMAGINE-2 and -3 tri- However, the proportions of reported NRRs als, a significant association was observed were lower in our analysis than previously between the PASI response level and achieve- reported; for example, the domain with the ment of DLQI 0/1, regardless of treatment arm. highest proportion of NRRs, sport, had 13.5% Dermatol Ther (Heidelb) (2021) 11:1265–1275 1273 NNRs compared with 28.4% reported by Rencz Lambert has received consultancy/speaker’s et al. [10]. The model was originally developed honoraria from and/or participated in clinical based on data collected in cross-sectional anal- trials sponsored by Abbvie, Almirall, Amgen, yses and it is possible that patients enrolled in ArgenX, Celgene, Janssen, BIOCAD, LEO clinical trials may be less likely to include ‘not Pharma, Lilly, Novartis, Pfizer, Sanofi, and UCB. relevant’ as a response. If this is the case, the use Lluı́s Puig has received consultancy/speaker’s of DLQI-R may be less useful in a clinical trial honoraria from and/or participated in clinical setting than when used to help guide treatment trials sponsored by Abbvie, Almirall, Amgen, decisions in clinical practice. Further validation Baxalta, Biogen, Boehringer Ingelheim, Cel- in clinical trials and clinical practice is required. gene, Gebro, Janssen, JS BIOCAD, LEO Pharma, One possible limitation of this analysis is Lilly, Merck-Serono, MSD, Mylan, Novartis, that the original AMAGINE-2 and -3 studies Pfizer, Regeneron, Roche, Sandoz, Samsung- were conducted between 2012 and 2014. Bioepis, Sanofi, and UCB. Advances in treatment and greater disease awareness among patients in the ensuing years Compliance with Ethics Guidelines. An may have resulted in increased expectations of institutional review board approved the study complete skin clearance and improvements in protocol for each participating center. These HRQoL. This may need to be taken into con- were: Research Review Board, Inc. Richmond sideration if comparing these DLQI results with Hill, ON, Canada; Health Research Ethics Board those of more recent studies. However, this of Alberta Clinical Trials Committee, Edmon- would not have impacted on the comparative ton, AB, Canada; Eticka Komise Fakultni aspect of this trial. nemocnice Kralovske Vinohrady, Praha, Czech In conclusion, brodalumab treatment pro- Republic; Eticka Komise Fakultni nemocnice vided significant improvement in self-reported Kralovske Vinohrady, Brno, Czech Republic; HRQoL in patients with moderate-to-severe Eticka Komise Fakultni nemocnice, Praha Czech psoriasis compared with ustekinumab. Republic; Eticka Komise Fakultni nemocnice Kralovske Vinohrady, Usti nad Labem, Czech Republic; Eticka Komise Fakultni nemocnice, Novy Jicin, Czech Republic; Eticka Komise ACKNOWLEDGEMENTS Fakultni nemocnice, Jihlava, Czech Republic; Comité de Protection des Personnes Ile de Funding. This analysis and manuscript France IV - Hôpital Saint Louis, Paris, France; development, including Rapid Service Fee, was Egeszsegugyi Tudomanyos Tanacs, Klinikai Far- funded by Leo Pharma A/S. makologiai Etikai Bizottsaga, Budapest, Hun- gary; Academisch Medisch Centrum, Authorship. All named authors meet the Amsterdam, the Netherlands; Komisja Bioety- International Committee of Medical Journal czna przy Okregowej Izbie Lekarskiej w Lodzi, Editors (ICMJE) criteria for authorship for this Lodz, Poland; Comissao de Etica para a Investi- article, take responsibility for the integrity of gacao Clinica (CEIC), Lisboa, Portugal; CEIC the work as a whole, and have given their Fundacio de Gestio Sanitaria Hospital de la approval for this version to be published. Santa Creu i Sant Pau, Barcelona, Spain; University of California Davis Institutional Medical Writing and Editorial Assis- Review Board, Sacramento, CA, USA; Schulman tance. Medical writing and editorial assistance Associates IRB, Cincinnati, OH, USA; Oregon were provided by Andy Bond of Spirit Medical Health and Science University Research Integ- Communications Group Ltd., funded by Leo rity Office,Portland, OR, USA; Western Institu- Pharma A/S. tional Review Board, Puyallup, WA, USA; Northwestern University IRB, Chicago, IL, USA; Disclosures. Anne Sohrt and Jes Birger University of Michigan Medical School IRB, Hansen are employees of Leo Pharma A/S. Jo Ann Arbor, MI, USA; Partners Human Research 1274 Dermatol Ther (Heidelb) (2021) 11:1265–1275 Committee/Partners Human Research Office, Open Access. This article is licensed under a Boston, MA, USA; NorthShore University Creative Commons Attribution-NonCommer- HealthSystem IRB, Evanston, IL, USA; Duke cial 4.0 International License, which permits University Health System IRB, Durham, NC, any non-commercial use, sharing, adaptation, USA; University of California Irvine Office of distribution and reproduction in any medium Research IRB, Irvine, CA, USA; Kaiser Perma- or format, as long as you give appropriate credit nente Southern California IRB, Pasadena, CA, to the original author(s) and the source, provide USA; New York Harbor Health Care System a link to the Creative Commons licence, and Subcommittee for Human Studies, New York, indicate if changes were made. The images or NY, USA; Tulane University Human Research other third party material in this article are Protection Office, New Orleans, LA, USA; included in the article’s Creative Commons Ethikkommission Nordwest- und Zen- licence, unless indicated otherwise in a credit tralschweiz (EKNZ), Basel, Switzerland; Com- line to the material. If material is not included mission cantonale d’éthique de la recherche sur in the article’s Creative Commons licence and l’être humain, Lausanne, Switzerland; Kan- your intended use is not permitted by statutory tonale Ethikkommission, Zürich, Switzerland; regulation or exceeds the permitted use, you Ethikkommission des Fachbereichs Medizin, will need to obtain permission directly from the Frankfurt am Main, Germany; Probity Medical copyright holder. To view a copy of this licence, Research Corporation, Waterloo, ON, Canada; visit http://creativecommons.org/licenses/by- Washington University School of Medicine, nc/4.0/. Human Research Protection Office, St. Louis, MO, USA; Comite de Protection des Personnes Sud Ouest et Outre Mer I et II, Toulouse, France; Commission centrale d’ethique des Hopitaux REFERENCES Universitaires de Geneve, Geneva, Switzerland; Komisja Bioetyczna przy Okregowej Izbie 1. Puig L, Thom H, Mollon P, et al. Clear or almost Lekarskiej, Krakow, Poland; Comite de Protec- clear skin improves the quality of life in patients with moderate-to-severe psoriasis: a systematic tion des Personnes Sud Est II Hopital Edouard review and meta-analysis. J Eur Acad Dermatol Herriot, Lyon, France; Creighton University Venereol. 2017;31(2):213–20. IRB, Omaha, NE, USA; University of California at San Francisco, Committee of Human 2. Lebwohl M, Papp K, Han C, et al. Ustekinumab improves health-related quality of life in patients Research, San Francisco, CA, USA; University of with moderate-to-severe psoriasis: results from the California at San Diego, Human Research Pro- PHOENIX 1 trial. Br J Dermatol. 2010;162(1): tections Program, La Jolla, CA, USA; Medicor 137–46. Research Inc, Sudbury, ON, Canada; Capital 3. Langley RG, Feldman SR, Han C, et al. Ustekinumab District Health Authority Research Ethics Board, significantly improves symptoms of anxiety, Halifax, NS, Canada; University Hospitals of depression, and skin-related quality of life in Cleveland IRB, Cleveland, OH, USA; Kantonale patients with moderate-to-severe psoriasis: results Ethikkommission Bern, Bern, Switzerland. Both from a randomized, double-blind, placebo-con- trolled phase III trial. J Am Acad Dermatol. studies were performed in accordance with the 2010;63(3):457–65. Helsinki Declaration of 1964, and its later amendments. All subjects provided informed 4. Gordon KB, Kimball AB, Chau D, et al. Impact of consent to participate in the study. brodalumab treatment on psoriasis symptoms and health-related quality of life: use of a novel patient- reported outcome measure the Psoriasis Symptom Data Availability. The datasets generated Inventory. Br J Dermatol. 2014;170(3):705–15. during and/or analysed during the current study are available from the corresponding 5. Papp KA, Gordon KB, Langley RG, et al. Impact of author on reasonable request. previous biologic use on the efficacy and safety of brodalumab and ustekinumab in patients with moderate-to-severe plaque psoriasis: integrated analysis of the randomized controlled trials Dermatol Ther (Heidelb) (2021) 11:1265–1275 1275 AMAGINE-2 and AMAGINE-3. Br J Dermatol. 16. Kimball AB, Gordon KB, Fakharzadeh S, et al. Long- 2018;179:320–8. term efficacy of ustekinumab in patients with moderate-to-severe psoriasis: results from the 6. Blauvelt A, Reich K, Tsai TF, et al. Secukinumab is PHOENIX 1 trial through up to 3 years. Br J Der- superior to ustekinumab in clearing skin of subjects matol. 2012;166(4):861–72. with moderate-to-severe plaque psoriasis up to 1 year: Results from the CLEAR study. J Am Acad 17. Augustin M, Blome C, Paul C, et al. Quality of life Dermatol. 2017;76(1):60-69.e9. and patient benefit following transition from methotrexate to ustekinumab in psoriasis. J Eur 7. Reich K, Pinter A, Lacour JP, et al. Comparison of Acad Dermatol Venereol. 2017;31(2):294–303. ixekizumab with ustekinumab in moderate-to-sev- ere psoriasis: 24-week results from IXORA-S, a phase 18. Basra MK, Salek MS, Camilleri L, et al. Determining III study. Br J Dermatol. 2017;177(4):1014–23. the minimal clinically important difference and responsiveness of the Dermatology Life Quality 8. Puig L, Augustin M, Blauvelt A, et al. Effect of Index (DLQI): further data. Dermatology. 2015;230: secukinumab on quality of life and psoriasis-related 27–33. symptoms: a comparative analysis versus ustek- inumab from the CLEAR 52-week study. J Am Acad 19. Warren RB, Hansen JB, Reich K, et al. Complete Dermatol. 2018;78(4):741–8. clearance and psoriasis area and severity index response for brodalumab and ustekinumab in 9. Lebwohl M, Strober B, Menter A, et al. Phase 3 AMAGINE-2 and -3. J Eur Acad Dermatol Venereol. studies comparing brodalumab with ustekinumab 2020. https://doi.org/10.1111/jdv.16816.10.1111/ in psoriasis. N Engl J Med. 2015;373(14):1318–28. jdv.16816. 10. Rencz F, Poór AK, Péntek M, et al. A detailed anal- 20. Viswanathan HN, Chau D, Milmont CE, et al. Total ysis of ‘‘not relevant’’ responses on the DLQI in skin clearance results in improvements in health- psoriasis: potential biases in treatment decisions. related quality of life and reduced symptom severity J Eur Acad Dermatol Venereol. 2018;32(5):783–90. among patients with moderate to severe psoriasis. J Dermatolog Treat. 2015;26(3):235–9. 11. Rencz F, Gulácsi L, Péntek M, et al. Proposal of a new scoring formula for the Dermatology Life 21. Revicki DA, Jin Y, Wilson HD, et al. Reliability and Quality Index in psoriasis. Br J Dermatol. validity of the psoriasis symptom inventory in 2018;179(5):1102–8. patients with moderate-to-severe psoriasis. J Der- matolog Treat. 2014;25(1):8–14. 12. Kimball AB, Jacobson C, Weiss S, et al. The psy- chosocial burden of psoriasis. Am J Clin Dermatol. 22. Abrouk M, Nakamura M, Zhu TH, et al. The impact 2005;6(6):383–92. of PASI 75 and PASI 90 on quality of life in mod- erate to severe psoriasis patients. J Dermatolog 13. Augustin M, Radtke MA. Quality of life in psoriasis Treat. 2017;28(6):488–91. patients. Expert Rev Pharmacoecon Outcomes Res. 2014;14(4):559–68. 23. Hesselvig JH, Egeberg A, Loft ND, et al. Correlation between dermatology life quality index and psori- 14. Strober BE, van der Walt JM, Armstrong AW, et al. asis area and severity index in patients with psori- Clinical goals and barriers to effective psoriasis care. asis treated with ustekinumab. Acta Derm Venereol. Dermatol Ther (Heidelb). 2019;9:5–18. 2018;98(3):335–9. 15. Lebwohl MG, Blauvelt A, Menter A, et al. Efficacy, 24. Loft ND, Egeberg A, Rasmussen MK, et al. Patient- safety, and patient-reported outcomes in patients reported outcomes during treatment in patients with moderate-to-severe plaque psoriasis treated with moderate-to-severe psoriasis: a Danish with brodalumab for 5 years in a long-term, open- nationwide study. Acta Derm Venereol. label, phase II study. Am J Clin Dermatol. 2019;99(13):1224–30. 2019;20(6):863–71.