title: Tumor Necrosis Factor-α Inhibitor Use and the Risk of Incident Hypertension in Patients with Rheumatoid Arthritis.
abstract: OBJECTIVE
  To compare the risk of incident hypertension between initiators of tumor necrosis factor (TNF)-α inhibitors and initiators of nonbiologic disease modifying antirheumatic drugs (hereafter referred to as nonbiologics) in rheumatoid arthritis patients taking methotrexate monotherapy.
  
  
  METHODS
  We conducted a cohort study using insurance claims data (2001-2012) from the US. We identified initiators of use of either TNF-α inhibitors or nonbiologics. 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 antihypertensive drug. Marginal structural models estimated hazard ratios (HRs) adjusted for both baseline and time-varying confounders. To validate the primary analysis, we designed a verification analysis to evaluate a known association between leflunomide (a nonbiologic disease modifying agent) and hypertension.
  
  
  RESULTS
  We identified 4,822 initiations of TNF-α inhibitor use and 2,400 of nonbiologic use. Crude incidence rates of hypertension per 1,000 person-years of follow-up were 36 (95% CI [confidence interval]: 32, 41) for the TNF-α inhibitor group and 42 (95% CI: 34, 51) for the nonbiologics group. The crude HR of TNF-α inhibitors versus nonbiologics for the risk of incident hypertension was 0.85 (95% CI: 0.67, 1.1). After adjusting for both baseline and time-varying covariates using marginal structural models, the HR was 0.95 (95% CI: 0.74, 1.2). In the verification analysis, the adjusted HR of incident hypertension was 2.3 (95% CI: 1.7, 3.0) in leflunomide initiators compared with methotrexate initiators.
  
  
  CONCLUSIONS
  Treatment with TNF-α inhibitors was not associated with a reduced risk of incident hypertension compared with nonbiologics in rheumatoid arthritis patients.See Video Abstract at http://links.lww.com/EDE/B36.
authors.affiliation: From the aDivision of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital & Harvard Medical School, Boston, MA; bDivision of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA; and cDepartment of Global Health and Population, Harvard School of Public Health, Boston, MA.
authors.forename: Rishi J
authors.initials: RJ
authors.lastname: Desai
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Solomon
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schneeweiss
authors.forename: Goodarz
authors.initials: G
authors.lastname: Danaei
authors.forename: Katherine P
authors.initials: KP
authors.lastname: Liao
authors.forename: Seoyoung C
authors.initials: SC
authors.lastname: Kim
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001379:Azathioprine / Q000627:therapeutic use; D000068582:Certolizumab Pegol / Q000627:therapeutic use; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000627:therapeutic use; D000068800:Etanercept / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use; D006973:Hypertension / Q000453:epidemiology*; D015994:Incidence; D000069285:Infliximab / Q000627:therapeutic use; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D008911:Minocycline / Q000627:therapeutic use; D010396:Penicillamine / Q000627:therapeutic use; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D012460:Sulfasalazine / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D012460:Sulfasalazine; D006886:Hydroxychloroquine; D003520:Cyclophosphamide; C529000:golimumab; D000069285:Infliximab; D000068879:Adalimumab; D008911:Minocycline; D010396:Penicillamine; D001379:Azathioprine; D000068800:Etanercept; D000068582:Certolizumab Pegol; D008727:Methotrexate