Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis: Subgroup analysis of Latin American patients in the phase 3 randomized UNCOVER-3 study / Comparación de ixekizumab y etanercept o placebo en la psoriasis de moderada a grave: análisis del subgrupo de pacientes latinoamericanos de la fase 3 del estudio aleatorizado UNCOVER-3

Background and objectives: Ixekizumab demonstrated greater efficacy than placebo and etanercept in UNCOVER-3. Subgroup analysis of Latin American patients was performed. We report 12-week and 60-week data. Patients and methods: Analysis included 102 Latin American patients randomized to receive placebo (n = 14), etanercept 50 mg twice weekly (n=30), or ixekizumab 160-mg starting dose followed by 80 mg every 2 weeks (Q2W; n = 29) or every 4 weeks (Q4W; n = 29). At week 12, patients maintaining efficacy response and adequate overall safety were assigned, at the discretion of the investigator, to long-term extension with ixekizumab Q4W. Results: At week 12, Psoriasis Area and Severity Index (PASI) 100 scores were 0%, 20.0% (p = 0.075 vs placebo), 62.1% (p < 0.001 vs placebo; p = 0.001 vs etanercept), and 48.3% (p = 0.002 vs placebo; p = 0.023 vs etanercept) for placebo, etanercept, ixekizumab Q2W, and ixekizumab Q4W, respectively. Among patients who continued therapy up to week 60 (n = 97), PASI 100 scores were 71.4%, 60.0%, 77.8%, and 57.7% for patients who received induction placebo, etanercept, ixekizumab Q2W, and ixekizumab Q4W, respectively (non-responder imputation). By week 60, ≥1 serious adverse event was experienced by 7.1% (n = 1/14), 3.3% (n = 1/30), 14.8% (n = 4/27), and 0% (n = 0/26) of patients who received induction placebo, etanercept, ixekizumab Q2W, and ixekizumab Q4W, respectively. There were no cases of active tuberculosis with ixekizumab treatment through 60 weeks. Conclusions: In Latin American patients, both ixekizumab dosing regimens demonstrated greater efficacy than etanercept for treating psoriasis over 12 weeks. The safety profile of ixekizumab through 60 weeks was well tolerated and consistent with the overall profile (AU)

Antecedentes y objetivos: Ixekizumab demostró una mayor eficacia que el placebo y etanercept en el estudio UNCOVER-3. Tras realizar un análisis del subgrupo de pacientes latinoamericanos, se presentan los resultados transcurridas 12 y 60 semanas. Pacientes y métodos: El análisis incluyó a 102 pacientes latinoamericanos aleatorizados para la administración de placebo (n=14), etanercept 50 mg 2 veces por semana (n = 30), o ixekizumab 160mg como dosis inicial y 80mg cada 2 semanas (Q2W; n=29) o 4 semanas (Q4W; n = 29). A la semana 12 los pacientes con buena respuesta de eficacia y ausencia de efectos adversos fueron asignados al tratamiento de ampliación a largo plazo con ixekizumab Q4W, a discreción del investigador. Resultados: A las 12 semanas las puntuaciones del PASI fueron del 0%, 20% (p = 0,075 vs placebo), 62,1% (p < 0,001 vs placebo; p = 0,001 vs etanercept) y 48,3% (p = 0,002 vs placebo; p = 0,023 vs etanercept) para placebo, etanercept, ixekizumab Q2W, e ixekizumab Q4W, respectivamente. Entre los pacientes que prosiguieron la terapia hasta la semana 60 (n = 97) las puntuaciones PASI 100 fueron del 71,4%, 60%, 77,8%, y 57,7% para los pacientes a quienes se administró placebo de inducción, etanercept, ixekizumab Q2W e ixekizumab Q4W, respectivamente (imputación del no respondedor). En la semana 60 ≥1 presentaron reacción adversa grave el 7,1% (n = 1/14), 3,3% (n = 1/30), 14,8% (n = 4/27) y 0% (n = 0/26) de los pacientes a quienes se administró placebo, etanercept, ixekizumab Q2W e ixekizumab Q4W, respectivamente. No se produjeron casos de tuberculosis activa con el tratamiento de ixekizumab a lo largo de las 60 semanas. Conclusiones: En los pacientes latinoamericanos ambos regímenes de dosificación de ixekizumab demostraron mayor eficacia que etanercept para el tratamiento de la psoriasis durante 12 semanas. En cuanto al perfil de seguridad, ixekizumab a lo largo de 60 semanas fue bien tolerado y consistente con el perfil general (AU)

Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis: Subgroup analysis of Latin American patients in the phase 3 randomized UNCOVER-3 study.

BACKGROUND AND OBJECTIVES: Ixekizumab demonstrated greater efficacy than placebo and etanercept in UNCOVER-3. Subgroup analysis of Latin American patients was performed. We report 12-week and 60-week data. PATIENTS AND METHODS: Analysis included 102 Latin American patients randomized to receive placebo (n=14), etanercept 50mg twice weekly (n=30), or ixekizumab 160-mg starting dose followed by 80mg every 2 weeks (Q2W; n=29) or every 4 weeks (Q4W; n=29). At week 12, patients maintaining efficacy response and adequate overall safety were assigned, at the discretion of the investigator, to long-term extension with ixekizumab Q4W. RESULTS: At week 12, Psoriasis Area and Severity Index (PASI) 100 scores were 0%, 20.0% (p=0.075 vs placebo), 62.1% (p<0.001 vs placebo; p=0.001 vs etanercept), and 48.3% (p=0.002 vs placebo; p=0.023 vs etanercept) for placebo, etanercept, ixekizumab Q2W, and ixekizumab Q4W, respectively. Among patients who continued therapy up to week 60 (n=97), PASI 100 scores were 71.4%, 60.0%, 77.8%, and 57.7% for patients who received induction placebo, etanercept, ixekizumab Q2W, and ixekizumab Q4W, respectively (non-responder imputation). By week 60, ≥1 serious adverse event was experienced by 7.1% (n=1/14), 3.3% (n=1/30), 14.8% (n=4/27), and 0% (n=0/26) of patients who received induction placebo, etanercept, ixekizumab Q2W, and ixekizumab Q4W, respectively. There were no cases of active tuberculosis with ixekizumab treatment through 60 weeks. CONCLUSIONS: In Latin American patients, both ixekizumab dosing regimens demonstrated greater efficacy than etanercept for treating psoriasis over 12 weeks. The safety profile of ixekizumab through 60 weeks was well tolerated and consistent with the overall profile.

Normal transcutaneous oxygen pressure in skin after radiation therapy for cancer.

BACKGROUND: Chronic deleterious changes in human skin after radiation therapy often have been ascribed to progressive ischemia (decreased blood supply and oxygenation). Recent studies suggest, however, that damaged irradiated skin is not ischemic. Transcutaneous oxygen pressure (TCPO2), that accurately reflects skin oxygenation, was studied in 100 patients who had undergone prior extensive radiation therapy for cancer. METHODS: In the 100 patients, the mean time since radiation was 7.86 +/- 10.56 years (mean, +/- SD) (range, 1-58 years). Radiation skin effects were graded (0-4+), and TCPO2 was measured in irradiated and control nonirradiated sites, with patients first breathing room air, then 100% O2 6 l/min for 10 minutes. Data were stratified according to skin grades, sex, time since irradiation, site, type, and dose of radiation. RESULTS: The mean TCPO2 in patients breathing room air was 52.0 17.8 mm Hg (mean +/- SD) for all irradiated skin, compared with 131.8 +/- 51.1 at the same irradiated sites in response to oxygen breathing (P < 0.0001); the mean TCPO2 for normal, nonirradiated skin was 56.5 +/- 12.6 when patients were breathing room air, compared with 151.5 +/- 48.1 when breathing 100% oxygen (P < 0.0001). Higher skin damage grades correlated with increasing time after radiation therapy. However, neither increasing time after irradiation nor grade of skin damage correlated with TCPO2, which was normal in 88% of the patients. CONCLUSIONS: Human skin, even many decades after radiation therapy, retains normal tissue oxygenation and TCPO2 response to inspired oxygen. Postradiation scarring, poor healing, and rare ulceration are not solely due to ischemia and may be caused by other radiation effects, such as permanent changes in fibroblasts.