Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: Integrated analysis of data from the global clinical trials

Stanley B. Cohen, Yoshiya Tanaka, Xavier Mariette, Jeffrey R. Curtis, Eun Bong Lee, Peter Nash, Kevin Winthrop, Christina Charles-Schoeman, Krishan Thirunavukkarasu, Ryan DeMasi, Jamie Geier, Kenneth Kwok, Lisy Wang, Richard Riese, Jürgen Wollenhaupt

Research output: Contribution to journalArticle

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Abstract

Objectives: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We report an integrated safety summary of tofacitinib from two phase I, nine phase II, six phase III and two long-term extension studies in adult patients with active RA. Methods: Data were pooled for all tofacitinib-treated patients (data cut-off: 31 March 2015). Incidence rates (IRs; patients with event/100 patient-years) and 95% CIs are reported for adverse events (AEs) of interest. Results: 6194 patients received tofacitinib for a total 19 406 patient-years' exposure; median exposure was 3.4 patient-years. IR (95% CI) for serious AEs was 9.4 (9.0 to 9.9); IR for serious infections was 2.7 (2.5 to 3.0). IR for (all) herpes zoster was 3.9 (3.6 to 4.2); IR for disseminated or multidermatomal herpes zoster was 0.3 (0.2 to 0.4). IR for opportunistic infections (excluding tuberculosis) was 0.3 (0.2 to 0.4) and was 0.2 (0.1 to 0.3) for tuberculosis. IR for malignancies (excluding non-melanoma skin cancer (NMSC)) was 0.9 (0.8 to 1.0); NMSC IR was 0.6 (0.5 to 0.7). IR for gastrointestinal perforations was 0.1 (0.1 to 0.2). Analysis of IR for serious infections, herpes zoster and malignancies by 6-month intervals did not reveal any notable increase in IR with longer-duration tofacitinib exposure. Conclusion: This analysis of tofacitinib exposure up to 8.5 years allowed estimation of safety events with improved precision versus previous tofacitinib reports. AEs were generally stable over time; no new safety signals were observed compared with previous tofacitinib reports.

Original languageEnglish (US)
Pages (from-to)1253-1262
Number of pages10
JournalAnnals of the Rheumatic Diseases
Volume76
Issue number7
DOIs
StatePublished - Jul 1 2017

Fingerprint

Rheumatoid Arthritis
Clinical Trials
Safety
Herpes Zoster
Skin Neoplasms
Therapeutics
Skin
Tuberculosis
Janus Kinases
tofacitinib
Opportunistic Infections
Infection
Neoplasms
Incidence

Keywords

  • Cardiovascular Disease
  • Infections
  • Rheumatoid Arthritis
  • Treatment
  • Tuberculosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years : Integrated analysis of data from the global clinical trials. / Cohen, Stanley B.; Tanaka, Yoshiya; Mariette, Xavier; Curtis, Jeffrey R.; Lee, Eun Bong; Nash, Peter; Winthrop, Kevin; Charles-Schoeman, Christina; Thirunavukkarasu, Krishan; DeMasi, Ryan; Geier, Jamie; Kwok, Kenneth; Wang, Lisy; Riese, Richard; Wollenhaupt, Jürgen.

In: Annals of the Rheumatic Diseases, Vol. 76, No. 7, 01.07.2017, p. 1253-1262.

Research output: Contribution to journalArticle

Cohen, SB, Tanaka, Y, Mariette, X, Curtis, JR, Lee, EB, Nash, P, Winthrop, K, Charles-Schoeman, C, Thirunavukkarasu, K, DeMasi, R, Geier, J, Kwok, K, Wang, L, Riese, R & Wollenhaupt, J 2017, 'Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: Integrated analysis of data from the global clinical trials', Annals of the Rheumatic Diseases, vol. 76, no. 7, pp. 1253-1262. https://doi.org/10.1136/annrheumdis-2016-210457
Cohen, Stanley B. ; Tanaka, Yoshiya ; Mariette, Xavier ; Curtis, Jeffrey R. ; Lee, Eun Bong ; Nash, Peter ; Winthrop, Kevin ; Charles-Schoeman, Christina ; Thirunavukkarasu, Krishan ; DeMasi, Ryan ; Geier, Jamie ; Kwok, Kenneth ; Wang, Lisy ; Riese, Richard ; Wollenhaupt, Jürgen. / Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years : Integrated analysis of data from the global clinical trials. In: Annals of the Rheumatic Diseases. 2017 ; Vol. 76, No. 7. pp. 1253-1262.
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abstract = "Objectives: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We report an integrated safety summary of tofacitinib from two phase I, nine phase II, six phase III and two long-term extension studies in adult patients with active RA. Methods: Data were pooled for all tofacitinib-treated patients (data cut-off: 31 March 2015). Incidence rates (IRs; patients with event/100 patient-years) and 95{\%} CIs are reported for adverse events (AEs) of interest. Results: 6194 patients received tofacitinib for a total 19 406 patient-years' exposure; median exposure was 3.4 patient-years. IR (95{\%} CI) for serious AEs was 9.4 (9.0 to 9.9); IR for serious infections was 2.7 (2.5 to 3.0). IR for (all) herpes zoster was 3.9 (3.6 to 4.2); IR for disseminated or multidermatomal herpes zoster was 0.3 (0.2 to 0.4). IR for opportunistic infections (excluding tuberculosis) was 0.3 (0.2 to 0.4) and was 0.2 (0.1 to 0.3) for tuberculosis. IR for malignancies (excluding non-melanoma skin cancer (NMSC)) was 0.9 (0.8 to 1.0); NMSC IR was 0.6 (0.5 to 0.7). IR for gastrointestinal perforations was 0.1 (0.1 to 0.2). Analysis of IR for serious infections, herpes zoster and malignancies by 6-month intervals did not reveal any notable increase in IR with longer-duration tofacitinib exposure. Conclusion: This analysis of tofacitinib exposure up to 8.5 years allowed estimation of safety events with improved precision versus previous tofacitinib reports. AEs were generally stable over time; no new safety signals were observed compared with previous tofacitinib reports.",
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T2 - Integrated analysis of data from the global clinical trials

AU - Cohen, Stanley B.

AU - Tanaka, Yoshiya

AU - Mariette, Xavier

AU - Curtis, Jeffrey R.

AU - Lee, Eun Bong

AU - Nash, Peter

AU - Winthrop, Kevin

AU - Charles-Schoeman, Christina

AU - Thirunavukkarasu, Krishan

AU - DeMasi, Ryan

AU - Geier, Jamie

AU - Kwok, Kenneth

AU - Wang, Lisy

AU - Riese, Richard

AU - Wollenhaupt, Jürgen

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N2 - Objectives: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We report an integrated safety summary of tofacitinib from two phase I, nine phase II, six phase III and two long-term extension studies in adult patients with active RA. Methods: Data were pooled for all tofacitinib-treated patients (data cut-off: 31 March 2015). Incidence rates (IRs; patients with event/100 patient-years) and 95% CIs are reported for adverse events (AEs) of interest. Results: 6194 patients received tofacitinib for a total 19 406 patient-years' exposure; median exposure was 3.4 patient-years. IR (95% CI) for serious AEs was 9.4 (9.0 to 9.9); IR for serious infections was 2.7 (2.5 to 3.0). IR for (all) herpes zoster was 3.9 (3.6 to 4.2); IR for disseminated or multidermatomal herpes zoster was 0.3 (0.2 to 0.4). IR for opportunistic infections (excluding tuberculosis) was 0.3 (0.2 to 0.4) and was 0.2 (0.1 to 0.3) for tuberculosis. IR for malignancies (excluding non-melanoma skin cancer (NMSC)) was 0.9 (0.8 to 1.0); NMSC IR was 0.6 (0.5 to 0.7). IR for gastrointestinal perforations was 0.1 (0.1 to 0.2). Analysis of IR for serious infections, herpes zoster and malignancies by 6-month intervals did not reveal any notable increase in IR with longer-duration tofacitinib exposure. Conclusion: This analysis of tofacitinib exposure up to 8.5 years allowed estimation of safety events with improved precision versus previous tofacitinib reports. AEs were generally stable over time; no new safety signals were observed compared with previous tofacitinib reports.

AB - Objectives: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We report an integrated safety summary of tofacitinib from two phase I, nine phase II, six phase III and two long-term extension studies in adult patients with active RA. Methods: Data were pooled for all tofacitinib-treated patients (data cut-off: 31 March 2015). Incidence rates (IRs; patients with event/100 patient-years) and 95% CIs are reported for adverse events (AEs) of interest. Results: 6194 patients received tofacitinib for a total 19 406 patient-years' exposure; median exposure was 3.4 patient-years. IR (95% CI) for serious AEs was 9.4 (9.0 to 9.9); IR for serious infections was 2.7 (2.5 to 3.0). IR for (all) herpes zoster was 3.9 (3.6 to 4.2); IR for disseminated or multidermatomal herpes zoster was 0.3 (0.2 to 0.4). IR for opportunistic infections (excluding tuberculosis) was 0.3 (0.2 to 0.4) and was 0.2 (0.1 to 0.3) for tuberculosis. IR for malignancies (excluding non-melanoma skin cancer (NMSC)) was 0.9 (0.8 to 1.0); NMSC IR was 0.6 (0.5 to 0.7). IR for gastrointestinal perforations was 0.1 (0.1 to 0.2). Analysis of IR for serious infections, herpes zoster and malignancies by 6-month intervals did not reveal any notable increase in IR with longer-duration tofacitinib exposure. Conclusion: This analysis of tofacitinib exposure up to 8.5 years allowed estimation of safety events with improved precision versus previous tofacitinib reports. AEs were generally stable over time; no new safety signals were observed compared with previous tofacitinib reports.

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KW - Infections

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