Effect of etanercept therapy on psoriasis symptoms in patients from Latin America, Central Europe, and Asia: a subset analysis of the PRISTINE trial

The details of the PRISTINE trial have been previously published [8]. Briefly, patients ≥18 years of age with stable moderate-to-severe plaque psoriasis were randomized to receive 50 mg etanercept subcutaneously either once weekly (QW) or twice weekly (BIW) for 12 weeks, after which all patients received open-label, 50 mg etanercept subcutaneously QW for an additional 12 weeks, i.e. QW/QW or QW/BIW dosing groups (Fig. 1). Concomitant methotrexate was allowed (≤20 mg/week) if doses were stable from at least 28 days prior to baseline through the end of study. Only mild topical corticosteroids were permitted on scalp, axillae and groin for first 12 weeks; topical medications (corticosteroids of all potencies, vitamin D analogues and combination products) were allowed as needed, at physician’s discretion, during the second 12 weeks, consistent with therapeutic practice. Of the 273 patients enrolled in the PRISTINE trial, 171 patients were eligible for this subset analysis.

The study protocol was reviewed and approved by an independent Ethics Committee prior to initiation. The study was conducted in compliance with the ethical principles of the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice Guidelines. The PRISTINE trial is registered on ClinicalTrials.gov, identifier NCT00663052.

Primary efficacy was measured as the proportion of patients achieving 50 %, 75 %, or 90 % improvement in Psoriasais Area and Severity Index (PASI), PASI 50, PASI 75, and PASI 90, respectively, at weeks 8, 12, and 24. Other efficacy endpoints included the percentage of patients who achieved a status of “clear” or “almost clear” on the Physician’s Global Assessment (PGA) of psoriasis, time to achieving PGA first “clear” or “almost clear” status, and percentage reduction in affected body surface area (BSA). Health-related quality of life (HRQoL) measures included Dermatology Life Quality Index (DLQI) [9], EuroQoL-5 Dimension (EQ-5D™) [10, 11], Work Productivity and Activity Impairment scale (WPAI) [12] and Functional Activity in Chronic Therapy (FACIT) [13].

For continuous efficacy parameters, treatment groups were compared in 1-way analysis of variance for baseline parameters or in analysis of covariance models of week 12/24 change from baseline parameters with treatment group as a factor and baseline measurement as a covariate. For dichotomous or categorical parameters, Fisher’s exact test was used. The last observation was carried forward for patients for whom data were not available at any time point.

Of the 273 patients enrolled in the PRISTINE trial, all 171 patients from Asia (Taiwan, n = 25; Thailand, n = 22), Central Europe (Czech Republic, n = 12; Hungary, n = 50), and Latin America (Argentina, n = 28; Mexico, n = 34) were included in the analysis. Since the number of patients from each region was small, they were pooled together for this subset analysis (Fig. 2).

The baseline demographics were similar between the etanercept 50 mg QW/QW and BIW/QW treatment groups (Table 1). In addition, the history of psoriasis, the extent of the disease, the presence and duration of psoriatic arthritis, and baseline HRQoL measures were also similar between the two groups of patients (Table 1). The baseline characteristics of the patients in this subset were comparable to those from the overall PRISTINE population (Table 2).

There were more patients achieving PASI 50, PASI 75, and PASI 90 in the group that received etanercept 50 mg BIW than in the group that received etanercept 50 mg QW over the time course of the study (Fig. 3). Statistically significant difference between the two treatment groups was evident as early as week 4 in PASI 50. Statistically significant difference in PASI 75 was observed by week 8 and in PASI 90 by week 12 (Fig. 3). After 12 weeks of treatment, i.e. at the end of the blinded phase of the study, 72 %, 40 % and 14 % of patients in the QW/QW group and 92 %, 67 % and 32 % in the BIW/QW group achieved PASI 50, PASI 75 and PASI 90, respectively. Kaplan-Meier estimates of the proportions of patients achieving first PASI 50, PASI 75 and PASI 90 responses by weeks 8, 12 and 24 also indicate a strong beneficial response in both treatment groups (Table 3). Improvements from baseline were also observed in PGA and BSA scores (p < 0.0001) at weeks 12 and 24 in both treatment groups (Fig. 4). By week 12, 36 % and 56 % of patients in the QW/QW and BIW/QW groups, respectively, exhibited a PGA status of clear or almost clear (Table 4). By week 24, the number of patients with clear or almost clear status increased to 57 % and 71 % in the QW/QW and BIW/QW groups, respectively. For the achievement of first PGA of clear/almost clear response, there was a statistically significant difference between the time-to-event curves for the QW/QW and BIW/QW treatment arms (p = 0.0112) and a significantly higher median time-to-response for the QW/QW group (113 days; 95 % confidence interval [CI]: 85–141) compared with the BIW/QW group (85 days; 95 % CI: 59–86). The efficacy parameters are summarized in Table 4.

Statistically significant (p < 0.001) improvements from baseline in all measures of HRQoL were observed in both treatment groups by week 12 and were maintained to week 24 (Table 5). In addition, the difference in the observed improvement in DLQI and EQ-5D scores at week 12 between the two treatment groups was statistically significant (p < 0.05).

Individual safety analysis by country or region was not performed since the trial was designed to randomize all enrolled patients and not stratified by geographic location. The complete safety data for the PRISTINE trial have been reported before [8]. Briefly, etanercept was well tolerated. The most commonly reported (≥5 % of patients) treatment-emergent adverse events were nasopharyngitis, headache, elevated blood insulin, diarrhea, injection-site erythema, pharyngitis, arthralgia, fatigue and injection-site reaction. Seven patients of 273 (2.6 %) reported serious adverse events and nine patients discontinued treatment due to an adverse event. There was no incidence of tuberculosis, opportunistic infections, or deaths reported.