Psoriasis is a universal chronic immune-mediated skin disease, characterized by the eruption of reddish, silvery-scaled plaques, predominantly on the elbows, knees, scalp, and trunk. Clinical manifestations of skin lesions and coexisting comorbidities have substantial negative effect on quality of life.1–4

Psoriasis is a heterogenic disease with different genetic and clinical phenotypes. This is reflected in the prevalence of the disease in different geographic regions and ethnic groups. In the United States, the prevalence of psoriasis in adults 20 years or older is estimated to be 3.2%,5 while it is lower in Hispanics (1.6%) than in Caucasians (3.6%) and African Americans (1.9%).5 While the potential genetic factors may contribute to the different prevalence of psoriasis in different populations, it is still unclear whether these differences reflect a different immune pathogenesis among the populations which could lead to different responses to treatment.

Although evidence is lacking regarding the prevalence and characteristics of psoriasis in Latin America, the prevalence of psoriasis may be lower in Latin America, estimated at approximately 2%, than in Western countries.6 Studies are complicated by racial and ethnic heterogeneity of the Latin American population.6 A recent population-based cross-sectional survey evaluating psoriasis prevalence in Brazil interviewed 8947 inhabitants in all 26 Brazilian state capitals. The overall prevalence of psoriasis in the Brazilian population ranged from 1.10% to 1.51% with greater proportions in the South and Southeast regions.7 Further efforts are required to understand psoriasis and establish the effectiveness of treatments in Latin America.

Human genome studies have identified polymorphisms associated with psoriasis in many immune-related genes, which support the tenet that deregulated cytokine networks play a role in the initiation and pathophysiology of psoriasis.8–11 Studies have demonstrated a high level of efficacy in large proportions of patients with psoriasis with antibodies targeting interleukin-12/23, interleukin-17A, or interleukin-17 receptor (IL-17RA) subunit.12–22

In the phase 3, randomized UNCOVER-1, -2, and -3 studies, two different dose regimens of ixekizumab, a high-affinity anti-interleukin-17A antibody, were compared with placebo and/or a tumor necrosis factor blocker, etanercept (50mg twice weekly), in the treatment of plaque psoriasis.23,24 Both ixekizumab dose regimens had greater efficacy than placebo (UNCOVER-1, -2, and -3) and etanercept (UNCOVER-2 and -3) over the first 12-week induction phase.23,24 In the three phase 3 UNCOVER studies, ixekizumab was also shown to be effective through 60 weeks of treatment.24

The UNCOVER-3 study included patients from Argentina, Chile, and Mexico. The objective of this subgroup analysis was to evaluate the efficacy and safety of ixekizumab in Latin American patients with moderate-to-severe psoriasis in the UNCOVER-3 study.

In this subgroup analysis of the phase 3 UNCOVER-3 study, ixekizumab Q2W and Q4W, compared with placebo and etanercept, provided Latin American patients with moderate-to-severe psoriasis significant resolution of plaque psoriasis. At week 12, ixekizumab Q2W demonstrated higher rates than etanercept for achieving PASI 90 and PASI 100. Rapid onset efficacy with ixekizumab was noted: Latin American patients given ixekizumab Q2W or Q4W had significant differences in PASI 75 compared with those given etanercept as early as week 2. Long-term treatment with ixekizumab Q4W for up to 60 weeks continued to provide high resolution of plaques. The safety profile of ixekizumab was comparable in Latin American patients and the UNCOVER-3 safety population. Furthermore, there was no reactivation of tuberculosis, which is a particular safety concern within Latin America.

The results of this subgroup analysis support the notion, reported by other studies, that the general efficacy profile of anti-psoriasis treatment in Latin American patients is comparable to that of the general global psoriasis population. A subgroup analysis of an open-label, single-arm study confirmed the efficacy and safety of efalizumab in a Latin American population with moderate-to-severe psoriasis.25 In another subgroup analysis, the randomized, double-blind PRISTINE study showed that response rates to etanercept for patients with moderate-to-severe psoriasis from Asia, Central Europe, and Latin America were similar to those observed in the overall study population.26 Subgroup analysis in the longitudinal prospective international observational PSOLAR study showed that living in Latin America or Europe (vs North America) was significantly associated with achieving a Physician's Global Assessment score of 0/1 and improving DLQI with biological psoriasis therapy.27 Collectively, these studies suggest that, although genetic factors may contribute to the development of psoriasis in different populations, Latin American patients seem to respond similarly to treatment compared to general psoriasis study populations.

The observed safety profile for ixekizumab in Latin American patients during the induction period was consistent with its mechanism of action and the previously demonstrated safety profile for ixekizumab.16,23,24 The overall safety profile in Latin American patients was comparable to that in the UNCOVER-1, -2, and -3 populations.23,24 Similarly to the UNCOVER-2 and -3 populations,23 overall rates of TEAEs and infections for Latin American patients were more frequent in patients given ixekizumab than in those given etanercept or placebo. Although injection site reactions were among the most frequently reported adverse reactions among Latin American patients receiving ixekizumab at week 12, occurrences were similar for patients receiving etanercept and the majority were mild or moderate in severity and did not lead to discontinuation. Among Latin American patients who continued treatment with ixekizumab Q4W during the long-term extension period, nasopharyngitis and injection site reaction were the most common any-grade TEAEs reported, although overall they were mild to moderate, treatable, and did not lead to discontinuation of study drug. No cases of active tuberculosis occurred during the study.

The limitations of this subgroup analysis are that the study was neither designed nor powered to show significance in subgroups, such as ethnicity subgroups, and subgroups comprised relatively small sample sizes, thereby making accurate inferences challenging. Hence, these results should be interpreted with caution. Despite these limitations, this subgroup analysis suggests that both ixekizumab dosing regimens were effective for treating moderate-to-severe psoriasis in Latin American patients and that long-term treatment with ixekizumab Q4W results in high clearance of moderate-to-severe psoriasis with a tolerable safety profile.

This study was supported by Eli Lilly and Company.

Fernando Valenzuela was principal investigator for the UNCOVER-3 trial and has participated in advisory boards for AbbVie, Novartis, and Pfizer. Claudia de la Cruz Fernandez was principal investigator for the UNCOVER-3 trial and has participated in advisory boards for AbbVie, Janssen, Novartis, and Pfizer and received research support from AbbVie, Eli Lilly and Company, and Pfizer. Ricardo Luis Galimberti is a senior researcher at Novartis, Eli Lilly and Company, and AbbVie. Livia Goncalves is a full-time employee of Eli Lilly and Company. Sirel Gürbüz is a full-time employee of Eli Lilly and Company and is a minor owner of Lilly stocks and stock options. Ricardo Romiti has participated in advisory boards or as a consultant or speaker for, AbbVie, Galderma, Janssen, LEO Pharma, Eli Lilly and Company, MSD, Novartis, Pfizer and UCB Pharma. Missy McKean-Matthews has no conflict of interest.