Background/Purpose: Real-world evidence (RWE) is key to understanding post-approval long-term safety of medications. Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. A prospective observational 5-year study, embedded within the US Corrona RA registry, was initiated to evaluate the safety of tofacitinib after US Food and Drug Administration approval on Nov 6, 2012. The objective of this analysis was to compare 5-year incidence rates (IRs) of malignancy and mortality in patients (pts) initiating tofacitinib vs biologic (b)DMARDs using US Corrona RA registry cohorts.

Methods: This prospective, observational 5-year study derived from the ongoing US Corrona RA registry routinely collects structured safety data on serious adverse events (AEs) and AEs of interest from investigators. IRs (no. of events/100 pt-years [PY]) of total cancer (excluding non-melanoma skin cancer [NMSC]), NMSC, and death were compared using propensity score (PS) methods to adjust for non-random treatment assignment among RA pts who newly initiated tofacitinib (US approved dose 5 mg twice daily) or a bDMARD regardless of dose/schedule between Nov 6, 2012 and July 31, 2018 (follow‑up through Jan 31, 2019). Sufficient malignancy and mortality events occurred to provide 80% power to detect a hazard ratio (HR) of 2.0. Baseline variables with standardized difference >│0.10│ between cohorts and a priori selected covariates (gender, age, line of therapy, history of AE of interest) were used to derive PS-trimmed (primary analysis) and PS-matched populations (ratio: max. 4 bDMARD:1 tofacitinib; caliper=0.05). Analyses used a ‘once exposed, always exposed’ approach following patients from therapy initiation until an AE of interest, loss to follow-up, or end of data collection period, whichever came first; follow-up continued if a patient discontinued or switched therapy. Multivariable-adjusted Cox regression was used to estimate HRs of first events between cohorts.

Results: In total, 1999 tofacitinib (4505.62 PY) and 6354 bDMARD (16670.84 PY) initiators were included. Following PS trimming, analyses for total cancer excluding NMSC, NMSC, and death, respectively, included 1420/1419/1419 tofacitinib initiators, and 4820/4820/4821 bDMARD initiators. Of tofacitinib and bDMARD initiators, respectively, 88% and 59% had prior bDMARD use. IRs of all three outcomes were similar in both cohorts; the adjusted HR (95% confidence interval [CI]) was 1.04 (0.68, 1.61) for total cancer excluding NMSC, 1.02 (0.69, 1.50) for NMSC, and 1.0 (0.62, 1.63) for death (Figure 1). Similar results were observed in PS-matched populations.

Conclusion: To our knowledge, this is the first comparative RWE for tofacitinib and bDMARDs to use PS-trimmed/matched analyses to adjust for channeling/prescribing patterns. RA pts initiating tofacitinib or bDMARDs had similar rates of total cancer excluding NMSC, NMSC, and death.

Acknowledgment: The authors thank Carol Etzel for her contributions. Study sponsored by Corrona, LLC; analysis funded by Pfizer Inc. Corrona is supported by contracted subscriptions with multiple companies. Medical writing support was provided by Michelle Karpman, PhD of Corrona, LLC and Jennifer Stewart, PhD of CMC Connect and funded by Pfizer Inc.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/comparison-of-malignancy-and-mortality-rates-between-tofacitinib-and-biologic-dmards-in-clinical-practice-five-year-results-from-a-us-based-rheumatoid-arthritis-registry/