Background/Purpose: Tofacitinib is an oral JAK inhibitor for the treatment of RA. Real‑world data (RWD) complement clinical trial data in assessing long-term safety. We evaluated 5-year adverse event (AE) incidence rates (IRs) in new starters of tofacitinib vs biologic (b)DMARDs using cohorts from the US Corrona RA registry.

Methods: This prospective, observational 5-year study in the ongoing US Corrona RA registry routinely collected 9 predefined AE categories from participating physicians. Major cardiovascular adverse events (MACE), serious infectious events (SIE), and herpes zoster (HZ) were a priori identified as having ≥ 80% power to detect a hazard ratio (HR) of 2.0 (MACE, SIE) or 2.25 (HZ) between patients (pts) starting tofacitinib or bDMARDs between 6 Nov 2012 (US FDA approval) and 30 Jun 2017 (follow-up to 31 Dec 2017). A safety signal for pulmonary embolism and mortality was seen in the tofacitinib 10 mg twice daily arm of an FDA post-marketing study in RA designed to evaluate the long-term risk of MACE and malignancy. Pts in that ongoing, open-label, endpoint-driven study had to be ≥ 50 years of age, have ≥ 1 cardiovascular risk factor, and be on a stable dose of methotrexate to be eligible for enrollment. For MACE, SIE, and HZ analyses, baseline variables with a standardized difference > │0.10│ between cohorts, and a priori-selected-covariates (gender, age, line of therapy, history of AE of interest) were used to construct propensity scores (PS) to derive PS‑trimmed (primary) and PS‑matched (sensitivity) populations (ratio: max. 4 bDMARD:1 tofacitinib; caliper=0.05). Pts were followed from start until AE of interest, discontinuation and/or start of new therapy +90 days, death, or end of follow-up, whichever came first. IRs (no. of events/100 pt‑years [PY]) were estimated, and multivariable-adjusted Cox regression was used to estimate HRs comparing rates of first events between cohorts.

Results: In total, 1,544 tofacitinib (2,138.2 PY) and 7,083 bDMARD (9,904.9 PY) starters were included. PS‑trimming led to 1,117 tofacitinib and 5,542 bDMARD starters. MACE and SIE rates were similar in both cohorts (Figure 1a); adjusted HRs (95% confidence interval) were: MACE 0.60 (0.30, 1.18); SIEs 0.99 (0.72, 1.36; Figure 1b). Compared with bDMARDs, the HZ IR was higher with tofacitinib (Figure 1a) and the HZ HR was significantly increased (adjusted HR 2.12 [1.22, 3.66]; Figure 1b); all HZ events were non-serious with tofacitinib. Similar results were seen in PS-matched populations. Venous thromboembolic event (VTE) IRs were similar in both cohorts (Figure 2).

Conclusion: This is the first comparative analysis of RWD for tofacitinib and bDMARDs to use PS-trimmed and PS-matched analyses to adjust for channeling/prescribing patterns for newly approved therapies. Pts starting tofacitinib or bDMARDs had similar MACE, SIE, and VTE rates. Tofacitinib starters had higher HZ IRs vs bDMARD starters.

Acknowledgments: The authors thank Carol Etzel for her contributions. Sponsors: Corrona, LLC. Corrona is supported by contracted subscriptions with multiple companies. This was a Corrona/Pfizer collaboration with Pfizer financial support. Medical writing support was provided by Anthony G McCluskey of CMC Connect and funded by Pfizer Inc.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/post-approval-comparative-safety-study-of-tofacitinib-and-biologic-dmards-five%e2%80%91year-results-from-a-us-based-rheumatoid-arthritis-registry/