Sebastião Cezar Radominski1, Mario Humberto Cardiel2, Gustavo Citera3, Annelise Goecke4, Juan Jose Jaller5, Andrea Barranjard Vannucci Lomonte6, Pedro Miranda7, Patricia Velez8, Daniel Xibillé9, Kenneth Kwok10, Ricardo Rojo11, Erika Gabriela García12. 1. Universidade Federal do Paraná, Curitiba, Brazil. 2. Centro de Investigación Clínica de Morelia, Morelia, Mexico. 3. Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina. 4. Instituto de Ciencias Biomédicas, Hospital Clínico de la Universidad de Chile, Santiago, Chile. 5. University Metropolitana, Barranquilla, Colombia. 6. Hospital Heliópolis, São Paulo, Brazil. 7. Centro de Estudios Reumatológicos, Santiago, Chile. 8. CIREISAS, Bogotá, Colombia. 9. Hospital General de Cuernavaca, Cuernavaca, Mexico. 10. Pfizer Inc, New York, NY, USA. 11. Pfizer Inc, Groton, CT, USA. Electronic address: Ricardo.Rojo@pfizer.com. 12. Pfizer Inc, Collegeville, PA, USA.
Abstract
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.
RCT Entities:
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.
Authors: Pedro Santos-Moreno; Susan Martinez; Linda Ibata; Laura Villarreal; Fernando Rodríguez-Florido; Manuel Rivero; Adriana Rojas-Villarraga; Claudio Galarza-Maldonado Journal: Biologics Date: 2022-07-13
Authors: Andrea B V Lomonte; Sebastião C Radominski; Flora M D Marcolino; Claiton V Brenol; Cristiano A F Zerbini; Erika G García; Ermeg L Akylbekova; Ricardo Rojo; Dario Ponce de Leon Journal: Medicine (Baltimore) Date: 2018-08 Impact factor: 1.817
Authors: Jorge Enrique Machado-Alba; Manuel E Machado-Duque; Andres Gaviria-Mendoza; Juan Manuel Reyes; Natalia Castaño Gamboa Journal: Clin Rheumatol Date: 2020-09-30 Impact factor: 2.980