Tumor Necrosis Factor-Alpha Inhibitor Use and the Risk of Incident Hypertension in Patients with Rheumatoid Arthritis: A Retrospective Cohort Study

Rishi J. Desai¹, Daniel H. Solomon², Sebastian Schneeweiss³, Goodarz Danaei⁴, Katherine Liao⁵ and Seoyoung C. Kim⁶, ¹Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, ²Rheumatology, Brigham and Women's Hospital, Boston, MA, ³Division of Pharmacoepidemiology, Brigham and Women's Hospital, Boston, MA, ⁴Harvard School of Public Health, Boston, MA, ⁵Division of Rheumatology, Immunology, and Allergy, Brigham & Women's Hospital, Boston, MA, ⁶Div. of Pharmacoepidemiology and Pharmacoeconomics, Div. of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: hypertension, rheumatoid arthritis (RA) and tumor necrosis factor (TNF)

Session Information

Date: Sunday, November 8, 2015

Title: Epidemiology and Public Health I: RA Comorbidities and Mortality

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: Results from several small studies support the potential blood pressure lowering effect
of tumor necrosis factor (TNF)-a
inhibitors in rheumatoid arthritis (RA) patients. Yet, no study has compared
the effect of TNF-a inhibitors with non-biologic
disease-modifying anti-rheumatic drugs (nbDMARDs) on the development of
incident hypertension in a population-based cohort of RA patients. Therefore,
the objective of this study was to compare the risk of incident hypertension
between initiators of TNF-α inhibitors and initiators of nbDMARDs in a
cohort of RA patients taking methotrexate monotherapy who are free from
cardiovascular diseases or hypertension.

Methods: We conducted a
cohort study using insurance claims data (2001-2012) from the US. We identified
initiators of either TNF-α inhibitors or nbDMARDs. Subsequent exposure to
these agents was measured monthly in a time-varying manner. The outcome of
interest was incident hypertension, defined by a diagnosis and a
prescription for an anti-hypertensive drug. Marginal structural models (MSM)
estimated hazard ratios (HR) adjusted for both baseline and time-varying
confounders. To validate the primary analysis examining TNF-α inhibitors
and hypertension association, we designed a verification analysis to evaluate a
known association between leflunomide and hypertension using similar
methodology.

Results: We identified 4,822
initiations of TNF-α inhibitors and 2,400 of nbDMARDs. Crude incidence
rates of hypertension per 1,000 person-years of follow-up were 36.1 (95%CI
31.8-40.7) for the TNF-α inhibitor group and 41.2 (95%CI 33.0-50.8) for
the nbDMARDs. The crude HR of TNF-α inhibitors versus nbDMARDs for the
risk of incident hypertension was 0.85 (95%CI 0.67-1.09). After adjusting for
both baseline and time-varying covariates in MSM, the HR was 1.01 (95%CI
0.78-1.31). In the verification analysis, the adjusted HR of incident
hypertension was 2.33 (95% CI 1.75-3.09) in leflunomide initiators compared
with methotrexate initiators.

Conclusion: Treatment with
TNF-α inhibitors was not associated with a reduced risk of incident
hypertension compared with nbDMARDs in RA patients.

Table: Incidence rates and relative risks of hypertension in initiators of TNF-alpha inhibitors compared to the initiators of non-biologic DMARDs for RA
	nbDMARDs	TNF-α inhibitors
Hypertension Events	88	258
Follow-up (person-years)	2137	7155
Crude incidence rates/1000 person-years (95% CI)	41.2 (33.0-50.8)	36.1 (31.8-40.7)
Unadjusted HR	1	0.85 (0.67-1.09)
Adjusted HR for only time-fixed covariates*	1	0.94 (0.74-1.25)
Adjusted HR for time-fixed and time-varying covariates using IPTW^† in MSM**	1	1.01 (0.78-1.31)
Abbreviations: CI- Confidence interval, HR- Hazard ratio, IPTW- Inverse probability treatment weights, MSM- Marginal structural models, nbDMARDs- non biologic disease modifying anti-rheumatic drugs, TNF- tumor necrosis factor Time-fixed covariates (measured at initiation of either TNF-inhibitor of non-biologic DMARDs): gender, diabetes, hyperlipidemia, lipid-lowering agent use, anti-diabetic medication use, obesity, smoking, combined comorbidity score. *Time-varying covariates (updated monthly post-initiation of either TNF-inhibitor of non-biologic DMARDs): use of NSAIDs, injectable steroids, cumulative dose of oral steroids, methotrexate use, leflunomide or cyclosporine use, other non-TNF biologic use, hospitalizations, emergency room visits, office visits, and number of distinct drugs, and age (updated every year in the study). †IPTW were truncated at the 1^st percentile (0.53) and 99^th percentile (1.85). Mean (SD) of the weights were 0.97 (0.19) after truncation.

Disclosure: R. J. Desai, None; D. H. Solomon, None; S. Schneeweiss, Novartis Pharmaceutical Corporation, 2,Boehringer Ingelheim, 2; G. Danaei, None; K. Liao, None; S. C. Kim, Pfizer Inc, 2,AstraZeneca, 2,Lilly, 2,Genentech and Biogen IDEC Inc., 2.

To cite this abstract in AMA style:

Desai RJ, Solomon DH, Schneeweiss S, Danaei G, Liao K, Kim SC. Tumor Necrosis Factor-Alpha Inhibitor Use and the Risk of Incident Hypertension in Patients with Rheumatoid Arthritis: A Retrospective Cohort Study [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/tumor-necrosis-factor-alpha-inhibitor-use-and-the-risk-of-incident-hypertension-in-patients-with-rheumatoid-arthritis-a-retrospective-cohort-study/. Accessed .

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