Session Information
Session Title: Rheumatoid Arthritis Treatment - Small Molecules, Biologics and Gene Therapy: Safety Issues
Session Type: Abstract Submissions (ACR)
Background/Purpose:
Tofacitinib is a novel, oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This analysis extended the evaluation of malignancies that occurred in the tofacitinib RA program from the Phase (P) 2, P3, and long-term extension (LTE) studies based on the data cut off of April 2013 (except where indicated).
Methods:
Data were pooled from 6 randomized P2, 6 randomized P3 studies and 2 open-label LTE studies. Patients (pts) in P3 and LTE (LTE pts rolled over from the P2 and P3 studies) studies were treated with tofacitinib 5 or 10 mg twice daily; P2 included additional dosages.
Results:
A total of 5674 patients (12669 pt-yr) received tofacitinib in the P2, P3 and LTE studies. One hundred and five pts receiving tofacitinib (all doses) reported malignancies (excluding non-melanoma skin cancer [NMSC]); the most common types of malignancies were lung and breast cancer. There were 10 lymphoma cases. The overall incidence rate (IR, events per 100 pt-yr) for all malignancies (excluding NMSC) and lymphomas were 0.83 (95% confidence interval [CI]: 0.69, 1.00) and 0.076 (0.04, 0.14), respectively. The IRs (95% CI) for all malignancies (excluding NMSC) broken down into 0-6, 6-12, 12-18, 18-24, 24-30, 30-36, 36-42, and >42 months based on exposure to study drug were 0.70 (0.44, 1.11), 0.62 (0.37, 1.05), 0.94 (0.59, 1.49), 1.04 (0.64, 1.66), 0.83 (0.47, 1.46), 1.00 (0.57, 1.76), 0.79 (0.36, 1.76), and 0.93 (0.46, 1.85), respectively. The standardized incidence ratios (SIRs) (95% CI) (as compared with the US Surveillance Epidemiology and End Result database) for all malignancies (excluding NMSC) and lymphomas were 1.07 (0.88, 1.30) and 2.58 (1.24, 4.74), respectively. The SIRs (95% CI) for lung and breast cancer were 1.93 (1.12, 3.09) and 0.71 (0.37, 1.24), respectively (data cut off April 2012). Thirty eight pts experienced NMSCs, for an IR of 0.45 (95% CI: 0.33, 0.62) (data cut off April 2012). By comparison, the IR of NMSC in patients treated with anti-TNF was 0.47 (0.37, 0.59) in a meta-analysis of randomized controlled trials1 and ranged from 0.23 to 0.35 in a meta-analysis of registries.2
Conclusion:
The malignancies that occurred in the tofacitinib RA program, including more than 12000 pt-yr of drug exposure, are consistent with the type and distribution of malignancies expected for patients with moderately to severely active RA. The IRs for all malignancies (excluding NMSC), lung cancer, breast cancer, and lymphomas are consistent with published estimates in RA patients treated with biologic and non-biologic DMARDs.3-6
References:
1. Askling J, et al. Pharmacoepidemiol Drug Saf 2011; 20: 119-30.
2. Mariette X, et al. Ann Rheum Dis 2011; 70: 1895-904.
3. Carmona L, et al. Semin Arthritis Rheum 2011; 41: 71-80.
4. Pallavicini FB, et al. Autoimmun Rev 2010; 9: 175-80.
5. Simon TA, et al. Ann Rheum Dis 2009; 68: 1819-26.
6. Wolfe F, Michaud K. Arthritis Rheum 2007; 56: 2886-95.
Disclosure:
X. Mariette,
Pfizer Inc,
5;
J. R. Curtis,
Roche/Genentech, UCB, Janssen, CORRONA, Amgen, Pfizer, BMS, Crescendo, AbbVie,
2,
Roche/Genentech, UCB, Janssen, CORRONA, Amgen, Pfizer, BMS, Crescendo, AbbVie,
5;
E. B. Lee,
Pfizer Inc,
5;
B. Benda,
Pfizer Inc,
1,
Pfizer Inc,
3;
I. Kaplan,
Pfizer Inc,
3,
Pfizer Inc,
1;
K. Soma,
Pfizer Inc,
1,
Pfizer Inc,
3;
R. Chew,
Pfizer Inc,
1,
Pfizer Inc,
3;
J. Geier,
Pfizer Inc,
1,
Pfizer Inc,
3;
L. Wang,
Pfizer Inc,
1,
Pfizer Inc,
3;
R. Riese,
Pfizer Inc,
1,
Pfizer Inc,
3.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tofacitinib-an-oral-janus-kinase-inhibitor-analysis-of-malignancies-across-the-rheumatoid-arthritis-clinical-program/