Journal of Dermatological Treatment ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/ijdt20 Consistent response to guselkumab treatment between Hispanic and non-Hispanic patients with psoriasis: an analysis from VOYAGE 1 and VOYAGE 2 Luis Puig, Jashin J. Wu, Melinda J. Gooderham, Yin You, Yaung-Kaung Shen, Bruce Randazzo & Francisco Kerdel To cite this article: Luis Puig, Jashin J. Wu, Melinda J. Gooderham, Yin You, Yaung-Kaung Shen, Bruce Randazzo & Francisco Kerdel (2021) Consistent response to guselkumab treatment between Hispanic and non-Hispanic patients with psoriasis: an analysis from VOYAGE 1 and VOYAGE 2, Journal of Dermatological Treatment, 32:5, 484-491, DOI: 10.1080/09546634.2019.1679336 To link to this article: https://doi.org/10.1080/09546634.2019.1679336 © 2019 The Author(s). Published with Published online: 21 Oct 2019. license by Taylor and Francis Group, LLC Submit your article to this journal Article views: 1477 View related articles View Crossmark data Citing articles: 1 View citing articles Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=ijdt20 JOURNAL OF DERMATOLOGICAL TREATMENT 2021, VOL. 32, NO. 5, 484–491 https://doi.org/10.1080/09546634.2019.1679336 ARTICLE Consistent response to guselkumab treatment between Hispanic and non-Hispanic patients with psoriasis: an analysis from VOYAGE 1 and VOYAGE 2 Luis Puiga , Jashin J. Wub , Melinda J. Gooderhamc , Yin Youd, Yaung-Kaung Shend, Bruce Randazzoe and Francisco Kerdelf a Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; bDermatology Research and Education Foundation, Irvine, CA, USA; cSKiN Centre for Dermatology and Department of Medicine, Queen’s University, Peterborough, Ontario, Canada; dBiostatistics, Immunology, Janssen Research & Development, LLC, Spring House, PA, USA; eClinical Research, Janssen Research & Development, LLC, Spring House, PA, USA; fFlorida Academic Dermatology Centers, Coral Gables, FL, USA ABSTRACT ARTICLE HISTORY Introduction: In VOYAGE 1 (NCT02207231) and VOYAGE 2 (NCT02207244), guselkumab, an interleukin-23 Received 24 September 2019 blocker, was safe and effective in patients with moderate-to-severe plaque psoriasis. Accepted 4 October 2019 Methods: Patients who self-identified as Hispanic (n ¼ 117) or non-Hispanic (n ¼ 1686) were randomized KEYWORDS to guselkumab, placebo, or adalimumab. Efficacy assessments included Psoriasis Area and Severity Index Guselkumab; psoria- (PASI), Investigator’s Global Assessment (IGA), and Dermatology Life Quality Index (DLQI). sis; Hispanic Results: At week 16, treatment differences for guselkumab versus placebo in the Hispanic and non- Hispanic populations were 67.4 (95% confidence interval 50.4, 84.4) and 77.2 (73.5, 80.8) percentage points for IGA 0/1 and 59.2 (41.9, 76.4) and 69.2 (65.7, 72.7) percentage points for PASI 90, respectively. Treatment differences for guselkumab versus adalimumab were 25.9 (6.5, 45.3) and 17.5 (12.8, 22.3) per- centage points for IGA 0/1 and 21.4 (–0.1, 42.9) and 23.5 (18.2, 28.9) percentage points for PASI 90, respectively. Week 24 results were similar. Adverse event frequency was greater in adalimumab- versus guselkumab-treated patients in the Hispanic population only through weeks 16 and 28. In both popula- tions, DLQI 0/1 responses were greater in guselkumab-treated versus placebo- and adalimumab-treated patients at week 16 and versus adalimumab-treated patients at week 24. Conclusions: Guselkumab safety and efficacy were consistent between Hispanic and non-Hispanic populations. Guselkumab (TREMFYAV; Janssen Research & Development, R Introduction LLC, Spring House, PA, USA) is an interleukin-23 blocker approved Psoriasis is a common, chronic disease that negatively impacts for the treatment of moderate-to-severe plaque psoriasis. In glo- health-related quality of life (HRQoL) (1). Psoriasis affects many bal Phase 3 studies (VOYAGE 1 and VOYAGE 2), guselkumab was ethnic groups worldwide, with prevalence in the USA highest in well tolerated and demonstrated superior clinical activity com- Caucasians or non-Hispanic whites (3.6% to 3.7%), followed by pared with adalimumab (HUMIRAV; Abbott Laboratories, North R Black (2.0%) and Hispanic (1.6%) individuals (2,3). However, psoria- Chicago, IL, USA), a commonly used tumor necrosis factor-a sis is more frequently undiagnosed in nonwhite individuals, and inhibitor (14,15). We conducted an analysis of pooled data from therefore the prevalence of psoriasis in the Black and Hispanic VOYAGE 1 and VOYAGE 2 to compare efficacy and safety between populations is likely underestimated (4–6). The genetic susceptibil- Hispanic and non-Hispanic patients with psoriasis. ity of psoriasis also varies with ethnic groups, although differences are more commonly documented in the Asian population in con- trast to the Black and Hispanic populations (6). Materials and methods Psoriasis has generally been understudied in the Hispanic Patients population, despite the fact that people of Hispanic ethnicity are the largest ethnic minority in the USA, constituting 17.8% of the VOYAGE 1 and VOYAGE 2 were global studies conducted in the nation’s total population (7). The limited data available suggest USA, Canada, Poland, Czech Republic, Germany, Hungary, Spain, that, compared with patients who are non-Hispanic, psoriasis in Russia, Australia, South Korea, and Taiwan (VOYAGE 1 only). Both patients who are Hispanic is more severe (8,9), has a greater studies included patients 18 years of age who had moderate-to- impact on HRQoL (10), and may be undertreated (11). It is import- severe plaque psoriasis (Investigator’s Global Assessment [IGA] ant to further investigate the efficacy and safety of psoriasis treat- score 3, Psoriasis Area and Severity Index [PASI] score 12, and ment in this population, since few studies of biologic therapy for body surface area involvement 10%) for at least 6 months and the treatment of psoriasis in Hispanic patients have been pub- were candidates for systemic therapy or phototherapy. Full inclu- lished (9,10,12,13). sion and exclusion criteria have been previously published (14,15). CONTACT Luis Puig lpuig@santpau.cat Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Mas Casanovas 90, 08041 Barcelona, Spain ß 2019 The Author(s). Published with license by Taylor and Francis Group, LLC This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. JOURNAL OF DERMATOLOGICAL TREATMENT 485 For this post hoc analysis, patients were divided into self-identified populations from VOYAGE 1 and VOYAGE 2 were analyzed Hispanic and non-Hispanic subpopulations. All patients provided through week 28. written consent to participate in the studies. Statistical analyses Study design Efficacy and baseline characteristics analyses were based on all VOYAGE 1 and VOYAGE 2 were Phase 3, randomized, double- patients who were randomized at week 0 according to their blind, placebo- and active-comparator-controlled studies with assigned treatment. Safety analyses were based on patients who similar designs through week 28 (14,15). The design of both stud- received at least 1 dose of study agent according to the actual ies was identical through week 24; patients were randomized to treatment received during the study. The receive guselkumab 100 mg at weeks 0 and 4, then every 8 weeks; Cochran–Mantel–Haenszel chi-squared test stratified by study was placebo at weeks 0, 4, and 12, followed by guselkumab 100 mg at used to compare the proportion of patients responding to treat- weeks 16 and 20; or adalimumab 80 mg at week 0, 40 mg at week ment. Treatment differences and confidence intervals (CIs) were 1, and then 40 mg every 2 weeks through week 23 (Figure 1). The adjusted by study (VOYAGE 1 and VOYAGE 2) with timing of adalimumab administration between weeks 23 and 28 Cochran–Mantel–Haenszel. After the treatment failure rules were differed between studies. In VOYAGE 1, patients received adalimu- applied, the remaining missing data were handled using nonres- mab every 2 weeks through week 28, and in VOYAGE 2, patients ponder imputation. randomized to receive adalimumab did not receive any study drug from week 23 until week 28. Data from VOYAGE 1 and Results VOYAGE 2 were pooled so that outcomes in a relatively large population of Hispanic patients could be compared with out- Patient disposition and disease characteristics comes in non-Hispanic patients. Both study protocols were A total of 1803 patients were included in this analysis; 117 reviewed by an Institutional Review Board or Independent Ethics randomized patients (6.5%) self-identified as Hispanic (placebo ¼ Committee at participating sites and both VOYAGE 1 31, guselkumab ¼ 43, and adalimumab ¼ 43) and 1686 (93.5%) (NCT02207231) and VOYAGE 2 (NCT02207244) were registered at self-identified as non-Hispanic (placebo ¼ 387, guselkumab ¼ ClinicalTrials.gov. 769, and adalimumab ¼ 530) (Figure 2). The majority of patients (62.4%) who self-identified as Hispanic were recruited at study Study assessments sites within the USA, 13.7% were recruited at study sites in Spain, 10.3% were recruited at study sites in Poland, 6.0% were recruited The co-primary endpoints in VOYAGE 1 and VOYAGE 2 were an at study sites in Germany, 4.3% were recruited at study sites in IGA score of 0 (cleared) or 1 (minimal) (16) and 90% improve- Canada, and 1.7% each were recruited at study sites in Australia ment in the PASI score (17) from baseline (PASI 90) at week 16. and Russia. Secondary endpoints included 75% and 100% improvement in Baseline demographics were generally comparable between PASI score from baseline (PASI 75 and PASI 100) and a the Hispanic and non-Hispanic populations, although body weight Dermatology Life Quality Index (DLQI) score of 0 or 1 (DLQI 0/1; and body mass index (BMI) were slightly higher in the Hispanic no effect at all on patient’s HRQoL) (18). For this analysis, pooled population (Table 1). Overall, mean body weight was 93 kg for efficacy data for the Hispanic and non-Hispanic patient popula- Hispanic patients and 89 kg for non-Hispanic patients, and mean tions from VOYAGE 1 and VOYAGE 2 were analyzed at week 16 BMI was 31.8 kg/m2 and 29.4 kg/m2, respectively. Severity of dis- and week 24. ease at baseline was also comparable between the Hispanic and To evaluate safety, pooled data on treatment-emergent non-Hispanic populations; median body surface area with psoria- adverse events (TEAEs) for the Hispanic and non-Hispanic patient sis was 20.0% and 23.0%, respectively; mean PASI score was 20.2 Guselkumab 100 mg at weeks 0, 4, then q8w R Placebo at weeks 0, 4, and 12 Guselkumab 100 mg at weeks 16 and 20 Adalimumab 80 mg at week 0 → 40 mg at week 1, then q2w through week 23a Week 0 16 24 28 PE SE R = Randomization Figure 1. VOYAGE 1 and VOYAGE 2 study designs through week 28. aIn VOYAGE 1, patients randomized to receive adalimumab received adalimumab every 2 weeks through week 28. In VOYAGE 2, patients randomized to receive adalimumab did not receive any study drug from week 23 until week 28. PE: primary endpoint; q2w: every 2 weeks; q8w: every 8 weeks; SE: secondary endpoint. 486 L. PUIG ET AL. 2315 Screened 1829 Randomized a 26 Ethnicity not reported 418 Placebo 812 Guselkumab 573 Adalimumab 31 Hispanic 387 Non-Hispanic 43 Hispanic 769 Non-Hispanic 43 Hispanic 530 Non-Hispanic 1 discontinued 21 discontinued 1 discontinued 24 discontinued 3 discontinued 18 discontinued study agent study agent study agent study agent study agent study agent 1 Lack of 4 Adverse 1 Lost to 13 Adverse 1 Adverse 5 Adverse efficacy event follow-up event event event 5 Lack of 3 Lost to 1 Lost to 3 Lack of efficacy follow-up follow-up efficacy 2 Lost to 1 Patient 1 Protocol 2 Lost to follow-up withdrawal violation follow-up 9 Patient 3 Treatment non- 4 Patient withdrawal compliance withdrawal 1 Protocol 3 Protocol 3 Treatment non- violation violation compliance Placebo 1 Other 1 Protocol Crossover violation (week 16) Crossed-over to guselkumab Continued guselkumab Continued adalimumab 30 Hispanic 366 Non-Hispanic 42 Hispanic 745 Non-Hispanic 40 Hispanic 512 Non-Hispanic 2 discontinued 7 discontinued 2 discontinued 19 discontinued 3 discontinued 25 discontinued study agent study agent study agent study agent study agent study agent 1 Lost to 1 Adverse 1 Lost to 6 Adverse 1 Adverse 6 Adverse follow-up event follow-up event event event 1 Treatment non- 4 Patient 1 Patient 3 Lack of 1 Lack of 1 Pregnancy compliance withdrawal withdrawal efficacy efficacy 7 Lack of 1 Protocol 3 Lost to 1 Treatment non- efficacy violation follow-up compliance 4 Lost to 1 Other 3 Patient follow-up withdrawal 5 Patient 2 Treatment non- withdrawal compliance 1 Protocol 1 Protocol violation violation 1 Other 1 Other Continued through Week 28 Continued through Week 28 Continued through Week 28 28 Hispanic 359 Non-Hispanic 40 Hispanic 726 Non-Hispanic 37 Hispanic 487 Non-Hispanic Figure 2. Patient disposition of Hispanic and non-Hispanic patients in VOYAGE 1 and VOYAGE 2. and 21.9, respectively; 26.5% and 23.8% of patients, respectively, (Figure 5). At week 16, efficacy responses for guselkumab were had an IGA score of 4 (severe); and mean DLQI score was 14.1 greater than those for placebo and adalimumab in both popula- and 14.5, respectively. tions. Treatment differences for guselkumab versus placebo were At baseline, a smaller proportion of patients in the Hispanic significant for IGA 0/1 and PASI 90 responses (the co-primary end population had previously been treated with phototherapy (38.5% points) in both the Hispanic and non-Hispanic populations (all versus 57.2%, respectively) or nonbiologic systemic therapy p < .001); however, they were numerically lower in the Hispanic (47.0% versus 64.5%, respectively) than patients in the non- population (IGA 0/1: 67.4 [95% CI 50.4, 84.4] and 77.2 [95% CI Hispanic population. However, the proportion of patients who 73.5, 80.8] percentage points in the Hispanic and non-Hispanic had prior biologic therapy at baseline was comparable between populations, respectively; PASI 90: 59.2 [95% CI 41.9, 76.4] and populations (23.1% in the Hispanic population compared with 69.2 [95% CI 65.7, 72.7] percentage points in the Hispanic and 20.6% in the non-Hispanic population). non-Hispanic populations, respectively) (Figures 3 and 5). Treatment differences for guselkumab versus adalimumab at week 16 for the IGA 0/1 and PASI 90 responses were generally Efficacy comparable between populations (IGA 0/1: 25.9 [95% CI 6.5, 45.3] Treatment effects for IGA and PASI responses at week 16 and and 17.5 [95% CI 12.8, 22.3] percentage points in the Hispanic week 24 were generally consistent between the Hispanic and and non-Hispanic populations, respectively; PASI 90: 21.4 [95% CI non-Hispanic populations (Figures 3–5). The CIs for the treatment -0.1, 42.9] and 23.5 [95% CI 18.2, 28.9] percentage points in the differences across treatments for the Hispanic population were Hispanic and non-Hispanic populations, respectively) (Figures 3 wide and encompassed those of the non-Hispanic population and 5). Treatment differences for PASI 75 and PASI 100 responses JOURNAL OF DERMATOLOGICAL TREATMENT 487 Table 1. Summary of demographics and psoriasis disease characteristics at baseline in Hispanic and non-Hispanic patients in VOYAGE 1 and VOYAGE 2. Hispanic patients Non-Hispanic patients Placebo Guselkumab Adalimumab Total Placebo Guselkumab Adalimumab Total Randomized 31 43 43 117 387 769 530 1686 patients, n Age, years 46.6 ± 13.4 46.4 ± 11.8 36.6 ± 10.7 42.9 ± 12.7 43.7 ± 12.5 43.6 ± 12.4 43.6 ± 12.3 43.6 ± 12.4 Male, n (%) 23 (74.2) 29 (67.4) 25 (58.1) 77 (65.8) 266 (68.7) 550 (71.5) 388 (73.2) 1204 (71.4) Weight, kg 90.9 ± 25.8 93.4 ± 19.5 93.8 ± 27.6 92.9 ± 24.2 88.2 ± 21.6 89.0 ± 20.5 88.8 ± 20.8 88.7 ± 20.8 BMI, kg/m2 30.5 ± 7.0 32.1 ± 6.8 32.5 ± 9.4 31.8 ± 7.9 29.2 ± 6.7 29.5 ± 6.3 29.5 ± 6.1 29.4 ± 6.3 Race, n (%) White 29 (93.5) 40 (93.0) 38 (88.4) 107 (91.5) 318 (82.2) 618 (80.4) 432 (81.5) 1368 (81.1) Black 0 0 0 0 11 (2.8) 12 (1.6) 13 (2.5) 36 (2.1) Asian 0 0 1 (2.3) 1 (0.9) 50 (12.9) 122 (15.9) 82 (15.5) 254 (15.1) American 0 1 (2.3) 2 (4.7) 3 (2.6) 1 (0.3) 1 (0.1) 0 2 (0.1) Indian or Alaska Native Native 0 0 0 0 2 (0.5) 2 (0.3) 2 (0.4) 6 (0.4) Hawaiian or other Pacific Islander Other 2 (6.5) 2 (4.7) 2 (4.7) 6 (5.1) 3 (0.8) 10 (1.3) 0 13 (0.8) Multiple 0 0 0 0 2 (0.5) 4 (0.5) 1 (0.2) 7 (0.4) Duration of 13.4 ± 13.7 16.7 ± 13.5 14.3 ± 11.4 14.9 ± 12.8 18.1 ± 11.9 18.0 ± 12.1 17.5 ± 11.5 17.9 ± 11.8 psoriasis, years BSA, %, median 16.0 21.0 21.0 20.0 21.0 23.0 24.0 23.0 PASI score (0–72) 17.9 ± 6.2 21.8 ± 10.0 20.3 ± 7.1 20.2 ± 8.2 21.3 ± 8.4 22.0 ± 9.1 22.3 ± 9.1 21.9 ± 8.9 IGA score of 4 8 (25.8) 14 (32.6) 9 (20.9) 31 (26.5) 92 (23.8) 176 (22.9) 133 (25.1) 401 (23.8) (severe), n (%) DLQI score (0–30) 12.7 ± 6.9 14.5 ± 7.5 14.7 ± 7.2 14.1 ± 7.2 14.5 ± 7.3 14.4 ± 7.2 14.6 ± 7.1 14.5 ± 7.2 Prior psoriasis treatments (ever used), n (%) Phototherapya 7 (22.6) 18 (41.9) 20 (46.5) 45 (38.5) 214 (55.3) 458 (59.6) 291 (55.0) 963 (57.2) Nonbiologic 9 (29.0) 23 (53.5) 23 (53.5) 55 (47.0) 230 (59.4) 512 (66.6) 346 (65.3) 1088 (64.5) systemicsb Biologicsc 8 (25.8) 9 (20.9) 10 (23.3) 27 (23.1) 79 (20.4) 161 (20.9) 108 (20.4) 348 (20.6) Nonbiologic 15 (48.4) 28 (65.1) 29 (67.4) 72 (61.5) 258 (66.7) 556 (72.3) 378 (71.3) 1192 (70.7) systemics or biologics All values are mean ± standard deviation unless otherwise noted. a Psoralen and ultraviolet A (PUVA) or ultraviolet B (UVB); for non-Hispanic patients guselkumab n ¼ 768, adalimumab n ¼ 529, and total n ¼ 1684. b PUVA, methotrexate, cyclosporine, acitretin, apremilast, or tofacitinib. c Etanercept, infliximab, alefacept, efalizumab, ustekinumab, briakinumab, secukinumab, ixekizumab, or brodalumab. BMI: body mass index; BSA: body surface area; DLQI: Dermatology Life Quality Index; IGA: Investigator’s Global Assessment; n: number of patients; PASI: Psoriasis Area and Severity Index. Due to missing baseline values, the denominators to calculate the percentages may not always include all patients randomized at baseline. at week 16 were similar to those observed for the PASI 90 patients, and 39.0% of adalimumab-treated patients in the non- response at this time point for both populations (Figures 3 Hispanic population. Similar results were observed at week 24. and 5). The superior efficacy response with guselkumab versus adali- Safety mumab was maintained through week 24. Treatment differences for guselkumab versus adalimumab treatment remained signifi- Through week 16, the frequency of adverse events was compar- cant for IGA 0/1 and PASI 90 responses (all p  .036) and were able between guselkumab- and placebo-treated patients in both comparable between the Hispanic and non-Hispanic populations the Hispanic and non-Hispanic populations (Table 2). The fre- (IGA 0/1: 22.5 [95% CI 2.4, 42.6] and 20.5 [95% CI 15.6, 25.4] per- quency of adverse events was numerically greater in adalimumab- centage points in the Hispanic and non-Hispanic populations, treated patients compared with guselkumab-treated patients only respectively; PASI 90: 31.6 [95% CI 11.3, 51.8] and 23.4 [95% CI in the Hispanic population through week 16 and week 28. 18.2, 28.6] percentage points in the Hispanic and non-Hispanic Although no pattern accounted for the difference in the fre- populations, respectively) (Figures 4 and 5). Similar treatment dif- quency of events between guselkumab- and adalimumab-treated ferences were observed for PASI 75 and PASI 100 responses at patients in the Hispanic population at week 16 or week 28, the this time point (Figures 4 and 5). highest rates of adverse events in adalimumab-treated patients in The HRQoL improvement with treatment was comparable the Hispanic population were in the system organ class of infec- between the Hispanic and non-Hispanic populations (Figure 6). At tions and infestations. A greater proportion of adalimumab- week 16, DLQI 0/1 was achieved by 0% of placebo-treated treated Hispanic patients reported at least 1 infection and at least patients, 57.1% of guselkumab-treated patients, and 36.6% of ada- 1 infection requiring treatment compared with guselkumab- limumab-treated patients in the Hispanic population and by 4.0% treated Hispanic patients. Serious adverse events, major adverse of placebo-treated patients, 53.3% of guselkumab-treated cardiovascular events, malignancies other than nonmelanoma skin 488 L. PUIG ET AL. IGA 0/1 PASI 75 PASI 90 PASI 100 100 88.3 84.7 86.0 79.1 ** Proportion of patients (%) 80 * * 72.1 70.9 71.5 67.0 65.1 ** 58.1 60 * 48.5 46.5 40 34.9 35.5 * * * 18.6 18.5 20 12.9 * 12.9 * * 7.5 6.7 6.5 * ** 2.3 3.2 * 0.5 0 Placebo Guselkumab Adalimumab Hispanic (n = 31) Hispanic (n = 43) Hispanic (n = 43) Placebo Guselkumab Adalimumab Non-Hispanic (n = 387) Non-Hispanic (n = 769) Non-Hispanic (n = 530) Figure 3. Proportions of Hispanic and non-Hispanic patients in VOYAGE 1 and VOYAGE 2 who achieved an IGA score of 0 or 1 and PASI 75, PASI 90, and PASI 100 responses at week 16. p < .001; p < .05. p-values are versus guselkumab and based on Cochran–Mantel–Haenszel chi-squared test stratified by study. IGA: Investigator’s Global Assessment; PASI: Psoriasis Areas Severity Index. IGA 0/1 PASI 75 PASI 90 PASI 100 100 88.4 90.0 84.0 79.1 77.2 Proportion of patients (%) 80 * 74.4 71.9 * ** 65.1 ** 63.4 60 58.1 * 54.2 ** 46.5 44.2 44.1 40 * 25.6 25.3 20 0 Guselkumab Adalimumab Guselkumab Adalimumab Hispanic Hispanic Non-Hispanic Non-Hispanic (n = 43) (n = 43) (n = 769) (n = 530) Figure 4. Proportions of Hispanic and non-Hispanic patients in VOYAGE 1 and VOYAGE 2 who achieved an IGA score of 0 or 1 and PASI 75, PASI 90, and PASI 100 responses at week 24. p < .001; p < .05. p-values are versus guselkumab and based on Cochran–Mantel–Haenszel chi-squared test stratified by study. IGA: Investigator’s Global Assessment; PASI: Psoriasis Areas Severity Index. cancer, and nonmelanoma skin cancer occurred infrequently patients of other ethnicities; however, in our analysis, baseline dis- across all treatment groups in both the Hispanic and non- ease severity was generally comparable between the Hispanic and Hispanic populations through week 16 and week 28 (Table 2). non-Hispanic populations. It has also been reported that com- pared with non-Hispanic patients with the same severity of psoriasis, Hispanic patients are more likely to have a lower Discussion HRQoL (10). In this analysis, however, mean baseline DLQI scores Guselkumab, an interleukin-23 blocker, is approved for the treat- were comparable between the Hispanic and non-Hispanic popula- ment of moderate-to-severe plaque psoriasis. Taken together, the tions. Finally, review of data suggests that psoriasis may be pivotal guselkumab studies (VOYAGE 1 and VOYAGE 2) included undertreated in nonwhite individuals (5,11). In our analysis, 117 Hispanic patients and 1686 self-identified non-Hispanic fewer patients in the Hispanic population than in the non- patients. This pooled analysis of the Hispanic and non-Hispanic Hispanic population had received phototherapy and nonbiologi- populations in these studies adds to the limited literature on the cal systemic therapy at baseline; however, rates of prior biologic characteristics of psoriasis in Hispanic patients. Results from previ- treatment were comparable between populations. It should be ous studies that included Hispanic patients suggested that psoria- noted that the majority of Hispanic patients in this study (62.4%) sis is more severe in Hispanic (8,9) and Asian (10) patients than in were from the USA and that disease characteristics may not be JOURNAL OF DERMATOLOGICAL TREATMENT 489 Difference and 95% CI Difference (95% CI) p-value Week 16 IGA of 0 or 1 vs. Placebo Hispanic 67.4 (50.4, 84.4) < 0.001 Non-Hispanic 77.2 (73.5, 80.8) < 0.001 PASI 90 Hispanic 59.2 (41.9, 76.4) < 0.001 Non-Hispanic 69.2 (65.7, 72.7) < 0.001 Week 16 IGA of 0 or 1 vs. Adalimumab Hispanic 25.9 (6.5, 45.3) 0.015 Non-Hispanic 17.5 (12.8, 22.3) < 0.001 PASI 75 Hispanic 20.1 (2.8, 37.4) 0.030 Non-Hispanic 18.0 (13.5, 22.5) < 0.001 PASI 90 Hispanic 21.4 (-0.1, 42.9) 0.062 Non-Hispanic 23.5 (18.2, 28.9) < 0.001 PASI 100 Hispanic 17.7 (-0.5, 35.9) 0.083 Non-Hispanic 17.1 (12.3, 22.0) < 0.001 Week 24 IGA of 0 or 1 vs. Adalimumab Hispanic 22.5 (2.4, 42.6) 0.036 Non-Hispanic 20.5 (15.6, 25.4) < 0.001 PASI 75 Hispanic 23.8 (4.8, 42.8) 0.014 Non-Hispanic 18.4 (14.0, 22.8) < 0.001 PASI 90 Hispanic 31.6 (11.3, 51.8) 0.005 Non-Hispanic 23.4 (18.2, 28.6) < 0.001 PASI 100 Hispanic 19.0 (-1.0, 39.0) 0.083 Non-Hispanic 18.8 (13.6, ,24.0) < 0.001 -20 0 20 40 60 80 100 Placebo/Adalimumab Guselkumab better better Figure 5. Proportion differences and 95% confidence intervals in IGA and PASI responses at week 16 and week 24 for guselkumab-treated versus placebo- or adali- mumab-treated Hispanic and non-Hispanic patients in VOYAGE 1 and VOYAGE 2. Treatment differences and confidence intervals were adjusted by study (VOYAGE 1 and VOYAGE 2) with Cochran–Mantel–Haenszel. p-values are based on Cochran–Mantel–Haenszel chi-squared test stratified by study. CI: confidence interval; IGA: Investigator’s Global Assessment; PASI: Psoriasis Areas Severity Index. Week 16 Week 24 100 Proportion of patients (%) 80 59.5 59.0 60 57.1 53.3 * * ** 39.0 39.0 40.4 40 36.6 20 * * 4.0 0.0 0 Placebo Guselkumab Adalimumab Hispanic (n = 31) Hispanic (n = 43) Hispanic (n = 43) Placebo Guselkumab Adalimumab Non-Hispanic (n = 387) Non-Hispanic (n = 769) Non-Hispanic (n = 530) Figure 6. Proportions of Hispanic and non-Hispanic patients in VOYAGE 1 and VOYAGE 2 with a DLQI score of 0 or 1 at week 16 or week 24. p < .001; p < .05. p-values are versus guselkumab and based on Cochran–Mantel–Haenszel chi-squared test stratified by study. DLQI: Dermatology Life Quality Index. 490 L. PUIG ET AL. Table 2. Adverse events through week 16 and week 28 in Hispanic and non-Hispanic patients in VOYAGE 1 and VOYAGE 2. Week 16 Week 28 Hispanic patients Non-Hispanic patients Hispanic patients Non-Hispanic patients a Placebo Guselkumab Adalimumab Placebo Guselkumab Adalimumab Guselkumab Adalimumab Guselkumaba Adalimumab Patients randomized, n 31 43 42 387 767 530 43 42 767 530 Average duration of 16.1 16.0 16.0 15.9 16.2 16.1 27.5 27.5 27.8 27.6 follow-up, weeks 1 adverse event 12 (38.7) 16 (37.2) 22 (52.4) 182 (47.0) 380 (49.5) 262 (49.4) 19 (44.2) 30 (71.4) 469 (61.1) 338 (63.8) 1 serious adverse event 1 (3.2) 0 1 (2.4) 5 (1.3) 16 (2.1) 11 (2.1) 0 1 (2.4) 27 (3.5) 18 (3.4) 1 infection 5 (16.1) 5 (11.6) 12 (28.6) 84 (21.7) 181 (23.6) 128 (24.2) 8 (18.6) 22 (52.4) 265 (34.6) 189 (35.7) 1 infection requiring 3 (9.7) 0 5 (11.9) 27 (7.0) 55 (7.2) 37 (7.0) 0 9 (21.4) 86 (11.2) 59 (11.1) treatment MACEb 0 0 0 0 1 (0.1) 2 (0.4) 0 0 3 (0.4) 2 (0.4) Malignanciesc 0 0 0 0 0 0 0 0 2 (0.3) 0 Nonmelanoma skin cancer 0 0 0 0 1 (0.1) 0 0 0 2 (0.3) 1 (0.2) All values are n (%) unless otherwise noted. a The guselkumab column includes patients who were initially randomized to guselkumab at week 0 and does not include placebo crossover patients. b Defined as cardiovascular death, nonfatal myocardial infarction events, and nonfatal stroke events; all events observed were nonfatal myocardial infarction events. c Other than nonmelanoma skin cancer. MACE: major adverse cardiovascular events; n: number of patients. representative of the general Hispanic population in the rest of and VOYAGE 2 studies, the efficacy and safety of guselkumab the world. were generally comparable between the Hispanic and non- The efficacy of guselkumab treatment in patients with moder- Hispanic populations. These results suggest that the efficacy, ate-to-severe psoriasis was consistent between the Hispanic and safety, and resulting benefit/risk analyses of guselkumab are non-Hispanic populations in this analysis. Treatment differences applicable to Hispanic patients with moderate-to-severe psoriasis. were generally consistent between the populations for all efficacy endpoints at weeks 16 and 24, although the treatment differences for guselkumab versus placebo for IGA 0/1 and PASI responses Acknowledgements were numerically lower in the Hispanic population. However, the The authors thank Holly Capasso-Harris, Synchrogenix, a Certara CIs for the treatment effects in the Hispanic population were Company, Wilmington, DE; Cynthia Guzzo, Kelly Global Services, wide, as expected due to smaller sample size, and encompassed LLC, Troy, MI; and Cynthia Arnold, Janssen Scientific Affairs, LLC, those of the non-Hispanic population. Improvements in DLQI Spring House, PA for their support. scores with guselkumab treatment compared with placebo or adalimumab treatment at week 16 and adalimumab treatment at week 24 were also comparable between the populations. Disclosure statement Furthermore, guselkumab was generally well tolerated in the Dr. Puig has received consultancy and/or speaker’s honoraria from Hispanic and non-Hispanic populations, and no new safety con- and/or participated in clinical trials sponsored by AbbVie, Almirall, cerns emerged within the Hispanic population. However, it is not- Amgen, Baxalta, Biogen, Boehringer Ingelheim, Celgene, Gebro, able that through week 16 and week 28, the frequency of adverse Janssen, LEO Pharma, Eli Lilly, Merck-Serono, MSD, Mylan, events was greater in adalimumab-treated patients compared Novartis, Pfizer, Regeneron, Roche, Sandoz, Samsung-Bioepis, with guselkumab-treated patients in the Hispanic population only. The increase in adverse event rates for adalimumab was mostly Sanofi, and UCB. attributable to infection-related adverse events, including infec- Dr. Wu has been an investigator for AbbVie, Amgen, Eli Lilly, tions and infections requiring treatment. Janssen, and Novartis; a consultant for AbbVie, Almirall, Amgen, Limitations of this analysis include its duration of only Bristol-Myers Squibb, Celgene, Dermira, Dr. Reddy’s Laboratories, 28 weeks and the relatively small number of patients, which limits Eli Lilly, Janssen, LEO Pharma, Novartis, Promius Pharma, the precision of the results. In addition, the term ‘Hispanic’ is pri- Regeneron, Sun Pharmaceutical, UCB, and Valeant marily used within the USA to denote a person of Cuban, Pharmaceuticals North America LLC; and a speaker for AbbVie, Mexican, Puerto Rican, South or Central American, or other Celgene, Novartis, Regeneron, Sun Pharmaceutical, UCB, and Spanish culture or origin, regardless of race (19), and may be con- Valeant Pharmaceuticals North America LLC. fusing to patients in other countries. Therefore, because Hispanic Dr. Gooderham has been an investigator, speaker, advisory status was patient-reported, there is the possibility that patients board member, or consultant for AbbVie, Actelion Pharma, could be mis-identified. However, because of the considerable Amgen, Akros, Arcutis, Boehringer Ingelheim, Bristol-Myers size of the non-Hispanic population, this is not likely to affect Squibb, Celgene, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, results. It is interesting to note that of the 68 patients recruited in Janssen, Kyowa Kirin, LEO Pharma, Medimmune, Merck, Novartis, Spain, 23.5% self-identified as Hispanic and 76.5% self-identified Pfizer, Regeneron, Roche, Sanofi Genzyme, Sun Pharmaceuticals, as non-Hispanic, which was similar to what was observed in UCB, and Valeant Pharmaceuticals North America LLC. patients recruited in the USA (20.5% and 79.5%, respectively). Drs. You, Shen, and Randazzo are employed by Janssen Despite these limitations, considering the small number of pub- Research & Development, LLC and own stock in Johnson lished studies evaluating psoriasis in Hispanic patients (9,10,12,13), & Johnson. this analysis adds significantly to the literature covering biologics Dr. Kerdel has been an investigator (receiving grants) for for the treatment of psoriasis in this population. Actelion, Amgen, AbbVie, AstraZeneca, Janssen, Celgene, Dermira, In summary, in this analysis of a significant number of Hispanic Dr. Reddy’s, Eli Lilly, LEO Pharma, Menlo, Novartis, Ortho, Pfizer, patients with moderate-to-severe psoriasis from the VOYAGE 1 Regeneron, Sanofi, UCB, and X-Biotech; a speaker (receiving JOURNAL OF DERMATOLOGICAL TREATMENT 491 honoraria) for Actelion, Amgen, AbbVie, Janssen, Celgene, Eli Lilly, https://www.census.gov/content/dam/Census/newsroom/ Novartis, Pfizer, Ortho, Regeneron, Sanofi, and Valeant facts-for-features/2017/cb17-ff17.pdf. Pharmaceuticals North America LLC; and served on advisory 8. Abrouk M, Lee K, Brodsky M, et al. Ethnicity affects the pre- boards for Eli Lilly and Celgene. senting severity of psoriasis. J Am Acad Dermatol. 2017; 77(1):180–182. Funding 9. Adsit S, Zaldivar ER, Sofen H, et al. Secukinumab is effica- cious and safe in Hispanic patients with moderate-to-severe This work was supported by Janssen Research & Development, plaque psoriasis: pooled analysis of four Phase 3 trials. Adv LLC, including funding and guidance for the conduct of the Ther. 2017;34(6):1327–1339. research and the preparation of the article, including the collec- 10. Shah SK, Arthur A, Yang YC, et al. A retrospective study to tion, analysis, and interpretation of data; writing of the report; investigate racial and ethnic variations in the treatment of and the decision to submit the article for publication. psoriasis with etanercept. J Drugs Dermatol. 2011;10(8): 866–872. ORCID 11. Davis SA, Narahari S, Feldman SR, et al. Top dermatologic conditions in patients of color: an analysis of nationally rep- Luis Puig http://orcid.org/0000-0001-6083-0952 resentative data. J Drugs Dermatol. 2012;11(4):466–473. Jashin J. Wu http://orcid.org/0000-0002-1722-1892 12. McMichael A, Desai SR, Qureshi A, et al. Efficacy and safety Melinda J. Gooderham http://orcid.org/0000-0001-8926-0113 of brodalumab in patients with moderate-to-severe plaque Francisco Kerdel http://orcid.org/0000-0001-7242-8733 psoriasis and skin of color: Results from the pooled AMAGINE-2/-3 randomized trials. Am J Clin Dermatol. 2019; Data availability statement 20(2):267–276. 13. Stengel FM, Petri V, Campbell GA, et al. Control of moder- The data sharing policy of Janssen Pharmaceutical Companies of ate-to-severe plaque psoriasis with efalizumab: 24-week, Johnson & Johnson is available at https://www.janssen.com/clin- open-label, phase IIIb/IV Latin American study results. Arch ical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Drug Info. 2009;2(4):71–78. Access (YODA) Project site at http://yoda.yale.edu. 14. Blauvelt A, Papp KA, Griffiths CE, et al. 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