Safety of Tofacitinib in the Treatment of Rheumatoid Arthritis in Latin America Compared With the Rest of the World Population.
OBJECTIVE
Rheumatoid arthritis (RA) is a chronic, autoimmune disease characterized by joint destruction. Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. This post hoc analysis assessed the safety of tofacitinib in Latin American (LA) patients with RA versus the Rest of World (RoW) population.


METHODS
Data were pooled from 14 clinical studies of tofacitinib: six Phase 2, six Phase 3 and two long-term extension studies. Incidence rates (IRs; patients with events/100 patient-years of treatment exposure) were calculated for safety events of special interest combined across tofacitinib doses. 95% confidence intervals (CI) for IRs were calculated using the maximum likelihood method. Descriptive comparisons were made between LA and RoW (excluding LA) populations.


RESULTS
This analysis included data from 984 LA patients and 4687 RoW patients. IRs for safety events of special interest were generally similar between LA and RoW populations, with overlapping 95% CIs. IRs for discontinuation due to adverse events, serious infections, tuberculosis, all herpes zoster (HZ), serious HZ, malignancies (excluding non-melanoma skin cancer) and major adverse cardiovascular events were numerically lower for LA versus RoW patients; IR for mortality was numerically higher. No lymphoma was reported in the LA population versus eight cases in the RoW population. Exposure (extent and length) was lower in the LA population (2148.33 patient-years [mean = 2.18 years]) versus RoW (10515.68 patient-years [mean = 2.24 years]).


CONCLUSIONS
This analysis of pooled data from clinical studies of tofacitinib in patients with RA demonstrates that tofacitinib has a consistent safety profile across LA and RoW patient populations.
From the *Clínica Angloamericana, Lima, Peru; †Instituto Peruano del Hueso y la Articulación, Lima, Peru; ‡Hospital Nacional Alberto Sabogal, Bellavista, Callao, Peru; §Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina; ∥Organización Médica de Investigación, Buenos Aires, Argentina; ¶Section of Rheumatology, Department of Medicine, Hospital Dr I Pirovano, Ciudad Autónoma de Buenos Aires, Argentina; #Universidade Federal do Paraná, Curitiba, Brazil; **Centro de Investigación Clínica de Morelia, Morelia, México; ††Centro de Reumatología y Ortopedia, Barranquilla, Colombia; ‡‡Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, Colombia; §§Pfizer Inc., Lima, Peru; ∥∥Pfizer Inc., Buenos Aires, Argentina; ¶¶Pfizer Inc., Collegeville, PA, USA; ##Pfizer Inc., New York, NY, USA; and ***Pfizer Inc., Groton, CT, USA.
Oswaldo M
OM
Castañeda
Felix J
FJ
Romero
Ariel
A
Salinas
Gustavo
G
Citera
Eduardo
E
Mysler
Oscar
O
Rillo
Sebastiao C
SC
Radominski
Mario H
MH
Cardiel
Juan J
JJ
Jaller
Carlos
C
Alvarez-Moreno
Dario
D
Ponce de Leon
Graciela
G
Castelli
Erika G
EG
García
Kenneth
K
Kwok
Ricardo
R
Rojo
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000453:epidemiology; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000706:statistics & numerical data; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D000075242:Janus Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D007843:Latin America / Q000453:epidemiology; D000069451:Long Term Adverse Effects / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
D000075242:Janus Kinase Inhibitors; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib