AB0398 COMPARATIVE SAFETY OF BIOLOGIC AND TARGETED SYNTHETIC DISEASE MODIFYING ANTI-RHEUMATIC DRUGS FOR CARDIOVASCULAR AND CANCER OUTCOMES IN RHEUMATOID ARTHRITIS

Background

The ORAL-surveillance trial showed a higher risk of major adverse cardiovascular events (MACE) and cancer in patients with rheumatoid arthritis (RA) taking tofacitinib, a Janus kinase inhibitor (JAKi), compared to those taking tumor necrosis factor alpha inhibitors (TNFi’s). However, little is known regarding the comparative safety of these two drug classes relative to non-TNFi biologics.

Objectives

To assess the comparative safety of TNFi’s, non-TNFi’s, and JAKi’s in RA patients for the risk of MACE (e.g., myocardial infarction, cardiac arrest, sudden death, stroke, percutaneous coronary intervention, and coronary artery bypass graft), cancer, deep vein thrombosis (DVT), and pulmonary embolism (PE).

Methods

We performed a retrospective cohort study using IBM Watson MarketScan databases (2012-2019) of RA patients 18-64 years of age who initiated treatment with TNFi’s, non-TNFi’s, or JAKi’s on or after January 2012. We used Cox Proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for developing MACE, cancer, DVT, and PE within 2 years of initiation in patients on non-TNFi’s or JAKi’s relative to TNFi’s, adjusting for multiple confounders, including age, gender, geographic region, year of initiating a biologic, Charlson Comorbidity Index, frailty status, healthcare utilization within 12 months prior to starting treatment (i.e., major infection requiring hospital admissions, general hospital admissions, outpatient visits, and emergency department visits), and RA severity (i.e. disease-modifying antirheumatic drug, nonsteroidal anti-inflammatory drug, glucocorticoid, and opioid fills 3 months prior to starting treatment).

Results

A total of 39,032 drug initiation events met eligibility criteria for our study (73.6% initiation of TNFi’s, 18.6% non-TNFi’s, and 7.80% JAKi’s). The mean age of the patients in each of the groups ranged from 47-49 years old; the majority were female. The mean follow-up time was 349 days for TNFi’s, 272 days for non-TNFi’s, and 266 days for JAKi’s. Non-TNFi’s were associated with an increased risk of MACE, cancer, and DVT, though the incidence of adverse health outcomes overall was still quite low (Table 1). In multivariable models, patients who started non-TNFi’s had a significantly higher risk of MACE (HR 1.75; 1.34-2.28), incident cancer (HR 2.06; 1.70-2.50), and DVT (HR 1.84; 1.45-2.32) compared to those who initiated TNFi’s. Patients who filled JAKi’s had a significantly higher risk of developing cancer compared to those who filled TNFi’s (HR 1.48; 1.09-2.03).

Conclusion

TNFi’s may be safer for RA treatment than non-TNFi’s and JAKi’s for RA in this generally younger and predominantly female population. However, since most RA patients initiate treatment with TNFi’s, results could be confounded by the possibility of more severe or prolonged disease in patients on non-TNFi’s and JAKi’s. These findings need to be replicated in other study populations. Future steps include looking at the risk conferred by individual non-TNFi’s towards these risks. Studies with longer follow-up are needed for better assessment of cancer risk among these drug classes.

Reference

[1] Ytterberg, S. R., Bhatt, D. L., Mikuls, T. R., Koch, G. G., Fleischmann, R., Rivas, J. L., Germino, R., Menon, S., Sun, Y., Wang, C., Shapiro, A. B., Kanik, K. S., Connell, C. A., & ORAL Surveillance Investigators (2022). Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis. The New England journal of medicine, 386(4), 316–326.

Acknowledgements

Research reported in this publication was supported by the National Institute of Arthritis And Musculoskeletal And Skin Diseases of the National Institutes of Health under Award Number K23AR079588 to Dr. Namrata Singh. This research was supported in part by the University of Washington Clinical Learning, Evidence, And Research (CLEAR) Center for Musculoskeletal Disorders, Administrative, Methodologic and Resource Cores and NIAMS/NIH grant P30AR072572.

Disclosure of Interests

Xavier Sendaydiego: None declared, Laura Gold: None declared, Jiha Lee: None declared, Radjiv Goulabchand Consultant of: NOVARTIS: involved in board concerning ITP management, Grant Hughes Employee of: Janssen Rheumatology Fellowship in Diagnostic and Therapeutic Disparities in Axial Spondyloarthritis: PI/Program Director, 7/1/2022 – 6/30/2023, Mathilde Pioro: None declared, James Andrews: None declared, Una Makris: None declared, Pradeep Suri: None declared, Jeffrey Jarvik: None declared, Jeffrey Sparks Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer, Grant/research support from: Bristol Myers Squibb, Siddharth Singh: None declared, Namrata Singh: None declared.