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Meta-Analysis
. 2016 May;75(5):831-41.
doi: 10.1136/annrheumdis-2014-205847. Epub 2015 Apr 22.

Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme

Jeffrey R Curtis  1 , Eun Bong Lee  2 , Irina V Kaplan  3 , Kenneth Kwok  4 , Jamie Geier  4 , Birgitta Benda  5 , Koshika Soma  3 , Lisy Wang  3 , Richard Riese  3
Affiliations
Meta-Analysis

Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme

Jeffrey R Curtis et al. Ann Rheum Dis. 2016 May.

Abstract

Objectives: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). To further assess the potential role of Janus kinase inhibition in the development of malignancies, we performed an integrated analysis of data from the tofacitinib RA clinical development programme.

Methods: Malignancy data (up to 10 April 2013) were pooled from six phase II, six Phase III and two long-term extension (LTE) studies involving tofacitinib. In the phase II and III studies, patients with moderate-to-severe RA were randomised to various tofacitinib doses as monotherapy or with background non-biological disease-modifying antirheumatic drugs (DMARDs), mainly methotrexate. The LTE studies (tofacitinib 5 or 10 mg twice daily) enrolled patients from qualifying prior phase I, II and III index studies.

Results: Of 5671 tofacitinib-treated patients, 107 developed malignancies (excluding non-melanoma skin cancer (NMSC)). The most common malignancy was lung cancer (n=24) followed by breast cancer (n=19), lymphoma (n=10) and gastric cancer (n=6). The rate of malignancies by 6-month intervals of tofacitinib exposure indicates rates remained stable over time. Standardised incidence ratios (comparison with Surveillance, Epidemiology and End Results) for all malignancies (excluding NMSC) and selected malignancies (lung, breast, lymphoma, NMSC) were within the expected range of patients with moderate-to-severe RA.

Conclusions: The overall rates and types of malignancies observed in the tofacitinib clinical programme remained stable over time with increasing tofacitinib exposure.

Keywords: DMARDs (synthetic); Inflammation; Rheumatoid Arthritis; Treatment.

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Figures

Figure 1
Figure 1
Incidence rates (and 95% CIs) for (A) all malignancies (excluding non-melanoma skin cancer (NMSC)), including drug exposure data; (B) lung cancer; (C) breast cancer (female patients); (D) NMSC and (E) lymphoma for all active treatments including dose groups. ADA, adalimumab; LTE, long-term extension; N, total number of patients in that group exposed to the study treatment; n, number of unique patients with malignancy event in each treatment group; PBO, placebo.
Figure 1
Figure 1
Incidence rates (and 95% CIs) for (A) all malignancies (excluding non-melanoma skin cancer (NMSC)), including drug exposure data; (B) lung cancer; (C) breast cancer (female patients); (D) NMSC and (E) lymphoma for all active treatments including dose groups. ADA, adalimumab; LTE, long-term extension; N, total number of patients in that group exposed to the study treatment; n, number of unique patients with malignancy event in each treatment group; PBO, placebo.
Figure 1
Figure 1
Incidence rates (and 95% CIs) for (A) all malignancies (excluding non-melanoma skin cancer (NMSC)), including drug exposure data; (B) lung cancer; (C) breast cancer (female patients); (D) NMSC and (E) lymphoma for all active treatments including dose groups. ADA, adalimumab; LTE, long-term extension; N, total number of patients in that group exposed to the study treatment; n, number of unique patients with malignancy event in each treatment group; PBO, placebo.
Figure 2
Figure 2
Incidence rates (95% CI) per 6-month intervals for (A) all malignancies (excluding non-melanoma skin cancer (NMSC)); (B) lung cancer; (C) breast cancer (female patients); (D) NMSC and (E) age-adjusted and sex-adjusted standardised incidence ratios (95% CI) per 6-month intervals for all malignancies (excluding NMSC). pt-yr, patient-years; SEER, Surveillance Epidemiology and End Result; SIR, standardised incidence ratio as compared with SEER database.
Figure 2
Figure 2
Incidence rates (95% CI) per 6-month intervals for (A) all malignancies (excluding non-melanoma skin cancer (NMSC)); (B) lung cancer; (C) breast cancer (female patients); (D) NMSC and (E) age-adjusted and sex-adjusted standardised incidence ratios (95% CI) per 6-month intervals for all malignancies (excluding NMSC). pt-yr, patient-years; SEER, Surveillance Epidemiology and End Result; SIR, standardised incidence ratio as compared with SEER database.
Figure 2
Figure 2
Incidence rates (95% CI) per 6-month intervals for (A) all malignancies (excluding non-melanoma skin cancer (NMSC)); (B) lung cancer; (C) breast cancer (female patients); (D) NMSC and (E) age-adjusted and sex-adjusted standardised incidence ratios (95% CI) per 6-month intervals for all malignancies (excluding NMSC). pt-yr, patient-years; SEER, Surveillance Epidemiology and End Result; SIR, standardised incidence ratio as compared with SEER database.
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