Tofacitinib, an oral Janus kinase inhibitor, for the treatment of Latin American patients with rheumatoid arthritis: Pooled efficacy and safety analyses of Phase 3 and long-term extension studies.

OBJECTIVE: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We assessed tofacitinib efficacy and safety in the Latin American (LA) subpopulation of global Phase 3 and long-term extension (LTE) studies. MATERIALS AND METHODS: Data from LA patients with RA and inadequate response to disease-modifying antirheumatic drugs (DMARDs) were pooled across five Phase 3 studies. Phase 3 patients received tofacitinib 5 or 10mg twice daily (BID), adalimumab or placebo; patients in the single LTE study received tofacitinib 5 or 10mg BID; treatments were administered alone or with conventional synthetic DMARDs. Efficacy was reported up to 12 months (Phase 3) and 36 months (LTE) by American College of Rheumatology (ACR) 20/50/70 response rates, Disease Activity Score (DAS)28-4(erythrocyte sedimentation rate [ESR]) and Health Assessment Questionnaire-Disability Index (HAQ-DI). Incidence rates (IRs; patients with event/100 patient-years) of adverse events (AEs) of special interest were reported. RESULTS: The Phase 3 studies randomized 496 LA patients; the LTE study enrolled 756 LA patients from Phase 2 and Phase 3. In the Phase 3 studies, patients who received tofacitinib 5 and 10mg BID showed improvements vs placebo at Month 3 in ACR20 (68.9% and 75.7% vs 35.6%), ACR50 (45.8% and 49.7% vs 20.7%) and ACR70 (17.5% and 23.1% vs 6.9%) responses, mean change from baseline in HAQ-DI (-0.6 and -0.8 vs -0.3) and DAS28-4(ESR) score (-2.3 and -2.4 vs -1.4). The improvements were sustained up to Month 36 in the LTE study. In the Phase 3 studies, IRs with tofacitinib 5 and 10mg BID and placebo were 7.99, 6.57 and 9.84, respectively, for SAEs, and 3.87, 5.28 and 3.26 for discontinuation due to AEs. IRs of AEs of special interest in tofacitinib-treated LA patients were similar to the global population. CONCLUSION: In Phase 3 and LTE studies in LA patients with RA, tofacitinib demonstrated efficacy up to 36 months with a manageable safety profile up to 60 months, consistent with the overall tofacitinib study population.

[Cost-effectiveness analysis of etanercept compared with other biologic therapies in the treatment of rheumatoid arthritis]. / Etanercept y otras terapias biológicas en artritis reumatoide. Un análisis de costo-efectividad.

OBJECTIVE: to conduct cost-effectiveness analysis of etanercept compared with other biologic therapies in the treatment of moderate or severe rheumatoid arthritis in patients with previous unresponse to immune selective anti-inflammatory derivatives failure. METHODS: a pharmacoeconomic model based on decision analysis to assess the clinical outcome after giving etanercept, infliximab, adalimumab or tocilizumab to treat moderate or severe rheumatoid arthritis was employed. Effectiveness of medications was assessed with improvement rates of 20 % or 70 % of the parameters established by the American College of Rheumatology (ACR 20 and ACR 70). RESULTS: the model showed that etanercept had the most effective therapeutic response rate: 79.7 % for ACR 20 and 31.4 % for ACR 70, compared with the response to other treatments. Also, etanercept had the lowest cost ($149,629.10 per patient) and had the most cost-effective average ($187,740.40 for clinical success for ACR 20 and $476,525.80 for clinical success for ACR 70) than the other biologic therapies. CONCLUSIONS: we demonstrated that treatment with etanercept is more effective and less expensive compared to the other drugs, thus making it more efficient therapeutic option both in terms of means and incremental cost-effectiveness ratios for the treatment of rheumatoid arthritis.

Objetivo: analizar la relación costo-efectividad del etanercept en comparación con otras terapias biológicas para tratar la artritis reumatoide moderada o severa en pacientes con falla previa a fármacos antirreumáticos modificadores de la enfermedad. Métodos: se empleó un modelo farmacoeconómico basado en el análisis de decisiones para valorar la evolución clínica con etanercept, infliximab, adalimumab o tocilizumab para tratar artritis reumatoide moderada o severa. Los parámetros de efectividad fueron las tasas de mejoría igual o superior a 20 % (ACR 20) y de mejoría igual o superior a 70 % (ACR 70). Resultados: etanercept tuvo la mayor efectividad terapéutica: en 79.7 % de los pacientes se observó una ACR 20 y en 31.4 %, una ACR 70. También tuvo el menor costo asociado ($149 629.1 por paciente) y fue más costo-efectiva ($187 740.4 por éxito clínico para obtener ACR 20 y $476 525.8 por éxito clínico para obtener ACR 70) que las demás terapias biológicas. Conclusiones: el etanercept fue el fármaco más efectivo y menos costoso, por lo que resulta la opción terapéutica más eficiente, desde el punto de vista de la relación costo-efectividad media y en términos incrementales para el tratamiento de la artritis reumatoide.

Cost Utility of Sirolimus versus Tacrolimus for the Primary Prevention of Graft Rejection in Renal Transplant Recipients in Mexico.

OBJECTIVE: Therapies for end-stage renal disease improve quality of life, and survival. In Mexico, clinicians often must choose between different therapies without the availability of comparative outcomes evaluation. The present study evaluates the comparative cost-utility of sirolimus (SIR) versus tacrolimus (TAC) for the primary prevention of graft rejection in renal transplant recipients in Mexico. METHODS: We used modeling techniques to estimate the cost-effectiveness of SIR versus TAC to prevent graft rejection in patients with end-stage renal disease in the Mexican setting. The model estimates the cost of quality-adjusted life-year (QALY) per patient. We applied a 20-year horizon (1-year Markov cycles). Cost-effectiveness was expressed in terms of cost per QALY. All costs are presented in 2011 US dollars. Probabilistic sensitivity analyses were conducted. RESULTS: The total cost for the SIR treatment arm over the 20-year duration of the model is estimated to be $136,778. This compares with $142,624 for the TAC treatment arm, resulting in an incremental cost of SIR compared with that of TAC of-$5,846. Over 20 years, SIR was estimated to have 8.18 QALYs compared with 7.33 QALYs for TAC. The resulting incremental utility of SIR compared with that of TAC is 0.84 QALY gained. SIR is estimated to be both less costly and more effective than TAC, indicating that it is the dominant strategy. Notably, results suggest that SIR has a 78% probability of being dominant over the TAC strategy and a 100% probability of having an incremental cost-effectiveness ratio at or below $10,064 (1 GDP) per QALY. CONCLUSIONS: These analyses suggest that in the Mexican setting, the use of SIR in place of TAC for the prevention of graft rejection in this population is likely to be cost saving.