Lymphoma in the Tofacitinib Rheumatoid Arthritis Clinical Development Program.
Arthritis Care Res (Hoboken)
; 70(5): 685-694, 2018 05.
Article
em En
| MEDLINE
| ID: mdl-28941219
ABSTRACT
OBJECTIVE:
Tofacitinib is an oral JAK inhibitor indicated for the treatment of rheumatoid arthritis (RA). We characterized lymphoma events in the tofacitinib RA clinical development program.METHODS:
Lymphoma events (up to March 2015) were identified from 19 tofacitinib studies (2 phase I, 9 phase II, 6 phase III, and 2 long-term extension) of patients with moderate to severe RA. Patients in these studies received tofacitinib dosed at 1-30 mg twice daily or 20 mg once daily, as monotherapy or with conventional synthetic disease-modifying antirheumatic drugs. Lymphoma incidence rates (IRs; number of patients with events/100 patient-years) and standardized incidence ratios (SIRs) were calculated. A descriptive case-matched control analysis (14) was performed to identify potential risk factors for lymphoma.RESULTS:
A total of 6,194 patients received tofacitinib (19,406 patient-years of exposure, 3.4 years median treatment duration). Nineteen lymphomas occurred (IR 0.10 [95% confidence interval (95% CI) 0.06-0.15]), with no increase observed with time of exposure. The age- and sex-adjusted SIR of lymphoma was 2.62 (95% CI 1.58-4.09) (Surveillance, Epidemiology, and End Results [SEER] program database). The clinical characteristics of the 19 lymphomas were typical for the RA population. Three lymphomas were positive for Epstein-Barr virus, 8 were negative, 2 were equivocal, and 6 were untested. Numerically, more lymphoma cases had a history of Sjögren's syndrome and were positive for anti-cyclic citrullinated protein and rheumatoid factor at baseline versus matched controls. The mean corticosteroid dose was higher for lymphoma cases versus controls.CONCLUSION:
In the tofacitinib RA clinical development program, lymphoma rates were stable over time and there were minimal differences in the baseline characteristics of patients with and without lymphoma.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Piperidinas
/
Artrite Reumatoide
/
Pirimidinas
/
Pirróis
/
Janus Quinase 3
/
Linfoma
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Arthritis Care Res (Hoboken)
Assunto da revista:
REUMATOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
França