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.


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.


CONCLUSIONS
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.
Universidade Federal do Paraná, Curitiba, Brazil.
Sebastião Cezar
SC
Radominski
Centro de Investigación Clínica de Morelia, Morelia, Mexico.
Mario Humberto
MH
Cardiel
Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina.
Gustavo
G
Citera
Instituto de Ciencias Biomédicas, Hospital Clínico de la Universidad de Chile, Santiago, Chile.
Annelise
A
Goecke
University Metropolitana, Barranquilla, Colombia.
Juan Jose
JJ
Jaller
Hospital Heliópolis, São Paulo, Brazil.
Andrea Barranjard Vannucci
ABV
Lomonte
Centro de Estudios Reumatológicos, Santiago, Chile.
Pedro
P
Miranda
CIREISAS, Bogotá, Colombia.
Patricia
P
Velez
Hospital General de Cuernavaca, Cuernavaca, Mexico.
Daniel
D
Xibillé
Pfizer Inc, New York, NY, USA.
Kenneth
K
Kwok
Pfizer Inc, Groton, CT, USA. Electronic address: Ricardo.Rojo@pfizer.com.
Ricardo
R
Rojo
Pfizer Inc, Collegeville, PA, USA.
Erika Gabriela
EG
García
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D017326:Clinical Trials, Phase III as Topic; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000075242:Janus Kinase Inhibitors / Q000627:therapeutic use*; D007843:Latin America; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D055815:Young Adult
D018501:Antirheumatic Agents; D000075242:Janus Kinase Inhibitors; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib
Artritis reumatoide; Janus kinase; Kinasas Janus; Latin America; Latinoamérica; Rheumatoid arthritis; Tofacitinib