title: Rates of serious infections and malignancies among patients with rheumatoid arthritis receiving either tumor necrosis factor inhibitor or rituximab therapy.
abstract: OBJECTIVE
  Because of the role of tumor necrosis factor (TNF) in host defense, it was hypothesized that its inhibition might lead to an increased risk of malignancies and infections. The objective of our study was to assess the incidence of serious infections leading to hospitalization and malignancies among patients with rheumatoid arthritis (RA) receiving either TNF inhibitor or rituximab (RTX) therapy.
  
  
  METHODS
  The study population was identified from the National Register for Biologic Treatment in Finland and the hospital records of Central Finland Central Hospital for conventional disease-modifying antirheumatic drug (cDMARD) users. Data on infections and malignancies were acquired from national healthcare registers. A Poisson model was used to calculate the adjusted incidence rate ratios (aIRR) and was composed of age, sex, time from diagnosis, year of the beginning of the followup, rheumatoid factor status, Disease Activity Score at 28 joints, Health Assessment Questionnaire, prior malignancy, prior serious infection, prior biologic use, and time-updated use of methotrexate, sulfasalazine, hydroxychloroquine, and oral corticosteroids as confounders.
  
  
  RESULTS
  In total, during the followup of 10,994 patient-years, 92 malignancies and 341 serious infections were included in the analyses. The aIRR of infections compared to cDMARD users were 1.2 (95% CI 0.63-2.3), 0.84 (95% CI 0.53-1.3), 0.98 (95% CI 0.60-1.6), and 1.1 (95% CI 0.59-1.9) for the patients treated with infliximab (IFX), etanercept, adalimumab, and RTX, respectively. The crude rates of malignancies were highest among the users of cDMARD and RTX, and lowest among patients treated with IFX with no differences in aIRR.
  
  
  CONCLUSIONS
  Our results provide some reassurance of the safety of biologic treatments in the treatment of RA.
authors.affiliation: From the University of Helsinki, and the Helsinki University Central Hospital, Helsinki; Jyväskylä Central Hospital, Jyväskylä; Tampere University Hospital, Tampere; Turku University Central Hospital, Turku; South Karelia Central Hospital, Lappeenranta; Kanta-Häme Central Hospital, Hämeenlinna, Finland.K.J. Aaltonen, MSc (pharm); J.T. Joensuu, MSc (pharm); L. Virkki, MSc (pharm); P. Aronen, MSc; M. Blom, PhD, Professor, University of Helsinki; T. Sokka, MD, PhD, Adj. Professor, Jyväskylä Central Hospital; H. Relas, MD, PhD; H. Valleala, MD, PhD, Adj. Professor, Helsinki University Central Hospital; V. Rantalaiho, MD, PhD, Tampere University Hospital; L. Pirilä, MD, PhD, Turku University Central Hospital; K. Puolakka, MD, PhD, Adj. Professor, South Karelia Central Hospital; T. Uusitalo, MD, Kanta-Häme Central Hospital; Y.T. Konttinen, MD, PhD, Professor; D. Nordström, MD, PhD, Adj. Professor, University of Helsinki, and the Helsinki University Central Hospital. kalle.jm.aaltonen@helsinki.fi.
authors.forename: Kalle Jyri
authors.initials: KJ
authors.lastname: Aaltonen
authors.affiliation: From the University of Helsinki, and the Helsinki University Central Hospital, Helsinki; Jyväskylä Central Hospital, Jyväskylä; Tampere University Hospital, Tampere; Turku University Central Hospital, Turku; South Karelia Central Hospital, Lappeenranta; Kanta-Häme Central Hospital, Hämeenlinna, Finland.K.J. Aaltonen, MSc (pharm); J.T. Joensuu, MSc (pharm); L. Virkki, MSc (pharm); P. Aronen, MSc; M. Blom, PhD, Professor, University of Helsinki; T. Sokka, MD, PhD, Adj. Professor, Jyväskylä Central Hospital; H. Relas, MD, PhD; H. Valleala, MD, PhD, Adj. Professor, Helsinki University Central Hospital; V. Rantalaiho, MD, PhD, Tampere University Hospital; L. Pirilä, MD, PhD, Turku University Central Hospital; K. Puolakka, MD, PhD, Adj. Professor, South Karelia Central Hospital; T. Uusitalo, MD, Kanta-Häme Central Hospital; Y.T. Konttinen, MD, PhD, Professor; D. Nordström, MD, PhD, Adj. Professor, University of Helsinki, and the Helsinki University Central Hospital.
authors.forename: Jaana Tuulikki
authors.initials: JT
authors.lastname: Joensuu
authors.affiliation: From the University of Helsinki, and the Helsinki University Central Hospital, Helsinki; Jyväskylä Central Hospital, Jyväskylä; Tampere University Hospital, Tampere; Turku University Central Hospital, Turku; South Karelia Central Hospital, Lappeenranta; Kanta-Häme Central Hospital, Hämeenlinna, Finland.K.J. Aaltonen, MSc (pharm); J.T. Joensuu, MSc (pharm); L. Virkki, MSc (pharm); P. Aronen, MSc; M. Blom, PhD, Professor, University of Helsinki; T. Sokka, MD, PhD, Adj. Professor, Jyväskylä Central Hospital; H. Relas, MD, PhD; H. Valleala, MD, PhD, Adj. Professor, Helsinki University Central Hospital; V. Rantalaiho, MD, PhD, Tampere University Hospital; L. Pirilä, MD, PhD, Turku University Central Hospital; K. Puolakka, MD, PhD, Adj. Professor, South Karelia Central Hospital; T. Uusitalo, MD, Kanta-Häme Central Hospital; Y.T. Konttinen, MD, PhD, Professor; D. Nordström, MD, PhD, Adj. Professor, University of Helsinki, and the Helsinki University Central Hospital.
authors.forename: Liisa
authors.initials: L
authors.lastname: Virkki
authors.affiliation: From the University of Helsinki, and the Helsinki University Central Hospital, Helsinki; Jyväskylä Central Hospital, Jyväskylä; Tampere University Hospital, Tampere; Turku University Central Hospital, Turku; South Karelia Central Hospital, Lappeenranta; Kanta-Häme Central Hospital, Hämeenlinna, Finland.K.J. Aaltonen, MSc (pharm); J.T. Joensuu, MSc (pharm); L. Virkki, MSc (pharm); P. Aronen, MSc; M. Blom, PhD, Professor, University of Helsinki; T. Sokka, MD, PhD, Adj. Professor, Jyväskylä Central Hospital; H. Relas, MD, PhD; H. Valleala, MD, PhD, Adj. Professor, Helsinki University Central Hospital; V. Rantalaiho, MD, PhD, Tampere University Hospital; L. Pirilä, MD, PhD, Turku University Central Hospital; K. Puolakka, MD, PhD, Adj. Professor, South Karelia Central Hospital; T. Uusitalo, MD, Kanta-Häme Central Hospital; Y.T. Konttinen, MD, PhD, Professor; D. Nordström, MD, PhD, Adj. Professor, University of Helsinki, and the Helsinki University Central Hospital.
authors.forename: Tuulikki
authors.initials: T
authors.lastname: Sokka
authors.affiliation: From the University of Helsinki, and the Helsinki University Central Hospital, Helsinki; Jyväskylä Central Hospital, Jyväskylä; Tampere University Hospital, Tampere; Turku University Central Hospital, Turku; South Karelia Central Hospital, Lappeenranta; Kanta-Häme Central Hospital, Hämeenlinna, Finland.K.J. Aaltonen, MSc (pharm); J.T. Joensuu, MSc (pharm); L. Virkki, MSc (pharm); P. Aronen, MSc; M. Blom, PhD, Professor, University of Helsinki; T. Sokka, MD, PhD, Adj. Professor, Jyväskylä Central Hospital; H. Relas, MD, PhD; H. Valleala, MD, PhD, Adj. Professor, Helsinki University Central Hospital; V. Rantalaiho, MD, PhD, Tampere University Hospital; L. Pirilä, MD, PhD, Turku University Central Hospital; K. Puolakka, MD, PhD, Adj. Professor, South Karelia Central Hospital; T. Uusitalo, MD, Kanta-Häme Central Hospital; Y.T. Konttinen, MD, PhD, Professor; D. Nordström, MD, PhD, Adj. Professor, University of Helsinki, and the Helsinki University Central Hospital.
authors.forename: Pasi
authors.initials: P
authors.lastname: Aronen
authors.affiliation: From the University of Helsinki, and the Helsinki University Central Hospital, Helsinki; Jyväskylä Central Hospital, Jyväskylä; Tampere University Hospital, Tampere; Turku University Central Hospital, Turku; South Karelia Central Hospital, Lappeenranta; Kanta-Häme Central Hospital, Hämeenlinna, Finland.K.J. Aaltonen, MSc (pharm); J.T. Joensuu, MSc (pharm); L. Virkki, MSc (pharm); P. Aronen, MSc; M. Blom, PhD, Professor, University of Helsinki; T. Sokka, MD, PhD, Adj. Professor, Jyväskylä Central Hospital; H. Relas, MD, PhD; H. Valleala, MD, PhD, Adj. Professor, Helsinki University Central Hospital; V. Rantalaiho, MD, PhD, Tampere University Hospital; L. Pirilä, MD, PhD, Turku University Central Hospital; K. Puolakka, MD, PhD, Adj. Professor, South Karelia Central Hospital; T. Uusitalo, MD, Kanta-Häme Central Hospital; Y.T. Konttinen, MD, PhD, Professor; D. Nordström, MD, PhD, Adj. Professor, University of Helsinki, and the Helsinki University Central Hospital.
authors.forename: Heikki
authors.initials: H
authors.lastname: Relas
authors.affiliation: From the University of Helsinki, and the Helsinki University Central Hospital, Helsinki; Jyväskylä Central Hospital, Jyväskylä; Tampere University Hospital, Tampere; Turku University Central Hospital, Turku; South Karelia Central Hospital, Lappeenranta; Kanta-Häme Central Hospital, Hämeenlinna, Finland.K.J. Aaltonen, MSc (pharm); J.T. Joensuu, MSc (pharm); L. Virkki, MSc (pharm); P. Aronen, MSc; M. Blom, PhD, Professor, University of Helsinki; T. Sokka, MD, PhD, Adj. Professor, Jyväskylä Central Hospital; H. Relas, MD, PhD; H. Valleala, MD, PhD, Adj. Professor, Helsinki University Central Hospital; V. Rantalaiho, MD, PhD, Tampere University Hospital; L. Pirilä, MD, PhD, Turku University Central Hospital; K. Puolakka, MD, PhD, Adj. Professor, South Karelia Central Hospital; T. Uusitalo, MD, Kanta-Häme Central Hospital; Y.T. Konttinen, MD, PhD, Professor; D. Nordström, MD, PhD, Adj. Professor, University of Helsinki, and the Helsinki University Central Hospital.
authors.forename: Heikki
authors.initials: H
authors.lastname: Valleala
authors.affiliation: From the University of Helsinki, and the Helsinki University Central Hospital, Helsinki; Jyväskylä Central Hospital, Jyväskylä; Tampere University Hospital, Tampere; Turku University Central Hospital, Turku; South Karelia Central Hospital, Lappeenranta; Kanta-Häme Central Hospital, Hämeenlinna, Finland.K.J. Aaltonen, MSc (pharm); J.T. Joensuu, MSc (pharm); L. Virkki, MSc (pharm); P. Aronen, MSc; M. Blom, PhD, Professor, University of Helsinki; T. Sokka, MD, PhD, Adj. Professor, Jyväskylä Central Hospital; H. Relas, MD, PhD; H. Valleala, MD, PhD, Adj. Professor, Helsinki University Central Hospital; V. Rantalaiho, MD, PhD, Tampere University Hospital; L. Pirilä, MD, PhD, Turku University Central Hospital; K. Puolakka, MD, PhD, Adj. Professor, South Karelia Central Hospital; T. Uusitalo, MD, Kanta-Häme Central Hospital; Y.T. Konttinen, MD, PhD, Professor; D. Nordström, MD, PhD, Adj. Professor, University of Helsinki, and the Helsinki University Central Hospital.
authors.forename: Vappu
authors.initials: V
authors.lastname: Rantalaiho
authors.affiliation: From the University of Helsinki, and the Helsinki University Central Hospital, Helsinki; Jyväskylä Central Hospital, Jyväskylä; Tampere University Hospital, Tampere; Turku University Central Hospital, Turku; South Karelia Central Hospital, Lappeenranta; Kanta-Häme Central Hospital, Hämeenlinna, Finland.K.J. Aaltonen, MSc (pharm); J.T. Joensuu, MSc (pharm); L. Virkki, MSc (pharm); P. Aronen, MSc; M. Blom, PhD, Professor, University of Helsinki; T. Sokka, MD, PhD, Adj. Professor, Jyväskylä Central Hospital; H. Relas, MD, PhD; H. Valleala, MD, PhD, Adj. Professor, Helsinki University Central Hospital; V. Rantalaiho, MD, PhD, Tampere University Hospital; L. Pirilä, MD, PhD, Turku University Central Hospital; K. Puolakka, MD, PhD, Adj. Professor, South Karelia Central Hospital; T. Uusitalo, MD, Kanta-Häme Central Hospital; Y.T. Konttinen, MD, PhD, Professor; D. Nordström, MD, PhD, Adj. Professor, University of Helsinki, and the Helsinki University Central Hospital.
authors.forename: Laura
authors.initials: L
authors.lastname: Pirilä
authors.affiliation: From the University of Helsinki, and the Helsinki University Central Hospital, Helsinki; Jyväskylä Central Hospital, Jyväskylä; Tampere University Hospital, Tampere; Turku University Central Hospital, Turku; South Karelia Central Hospital, Lappeenranta; Kanta-Häme Central Hospital, Hämeenlinna, Finland.K.J. Aaltonen, MSc (pharm); J.T. Joensuu, MSc (pharm); L. Virkki, MSc (pharm); P. Aronen, MSc; M. Blom, PhD, Professor, University of Helsinki; T. Sokka, MD, PhD, Adj. Professor, Jyväskylä Central Hospital; H. Relas, MD, PhD; H. Valleala, MD, PhD, Adj. Professor, Helsinki University Central Hospital; V. Rantalaiho, MD, PhD, Tampere University Hospital; L. Pirilä, MD, PhD, Turku University Central Hospital; K. Puolakka, MD, PhD, Adj. Professor, South Karelia Central Hospital; T. Uusitalo, MD, Kanta-Häme Central Hospital; Y.T. Konttinen, MD, PhD, Professor; D. Nordström, MD, PhD, Adj. Professor, University of Helsinki, and the Helsinki University Central Hospital.
authors.forename: Kari
authors.initials: K
authors.lastname: Puolakka
authors.affiliation: From the University of Helsinki, and the Helsinki University Central Hospital, Helsinki; Jyväskylä Central Hospital, Jyväskylä; Tampere University Hospital, Tampere; Turku University Central Hospital, Turku; South Karelia Central Hospital, Lappeenranta; Kanta-Häme Central Hospital, Hämeenlinna, Finland.K.J. Aaltonen, MSc (pharm); J.T. Joensuu, MSc (pharm); L. Virkki, MSc (pharm); P. Aronen, MSc; M. Blom, PhD, Professor, University of Helsinki; T. Sokka, MD, PhD, Adj. Professor, Jyväskylä Central Hospital; H. Relas, MD, PhD; H. Valleala, MD, PhD, Adj. Professor, Helsinki University Central Hospital; V. Rantalaiho, MD, PhD, Tampere University Hospital; L. Pirilä, MD, PhD, Turku University Central Hospital; K. Puolakka, MD, PhD, Adj. Professor, South Karelia Central Hospital; T. Uusitalo, MD, Kanta-Häme Central Hospital; Y.T. Konttinen, MD, PhD, Professor; D. Nordström, MD, PhD, Adj. Professor, University of Helsinki, and the Helsinki University Central Hospital.
authors.forename: Tea
authors.initials: T
authors.lastname: Uusitalo
authors.affiliation: From the University of Helsinki, and the Helsinki University Central Hospital, Helsinki; Jyväskylä Central Hospital, Jyväskylä; Tampere University Hospital, Tampere; Turku University Central Hospital, Turku; South Karelia Central Hospital, Lappeenranta; Kanta-Häme Central Hospital, Hämeenlinna, Finland.K.J. Aaltonen, MSc (pharm); J.T. Joensuu, MSc (pharm); L. Virkki, MSc (pharm); P. Aronen, MSc; M. Blom, PhD, Professor, University of Helsinki; T. Sokka, MD, PhD, Adj. Professor, Jyväskylä Central Hospital; H. Relas, MD, PhD; H. Valleala, MD, PhD, Adj. Professor, Helsinki University Central Hospital; V. Rantalaiho, MD, PhD, Tampere University Hospital; L. Pirilä, MD, PhD, Turku University Central Hospital; K. Puolakka, MD, PhD, Adj. Professor, South Karelia Central Hospital; T. Uusitalo, MD, Kanta-Häme Central Hospital; Y.T. Konttinen, MD, PhD, Professor; D. Nordström, MD, PhD, Adj. Professor, University of Helsinki, and the Helsinki University Central Hospital.
authors.forename: Marja
authors.initials: M
authors.lastname: Blom
authors.affiliation: From the University of Helsinki, and the Helsinki University Central Hospital, Helsinki; Jyväskylä Central Hospital, Jyväskylä; Tampere University Hospital, Tampere; Turku University Central Hospital, Turku; South Karelia Central Hospital, Lappeenranta; Kanta-Häme Central Hospital, Hämeenlinna, Finland.K.J. Aaltonen, MSc (pharm); J.T. Joensuu, MSc (pharm); L. Virkki, MSc (pharm); P. Aronen, MSc; M. Blom, PhD, Professor, University of Helsinki; T. Sokka, MD, PhD, Adj. Professor, Jyväskylä Central Hospital; H. Relas, MD, PhD; H. Valleala, MD, PhD, Adj. Professor, Helsinki University Central Hospital; V. Rantalaiho, MD, PhD, Tampere University Hospital; L. Pirilä, MD, PhD, Turku University Central Hospital; K. Puolakka, MD, PhD, Adj. Professor, South Karelia Central Hospital; T. Uusitalo, MD, Kanta-Häme Central Hospital; Y.T. Konttinen, MD, PhD, Professor; D. Nordström, MD, PhD, Adj. Professor, University of Helsinki, and the Helsinki University Central Hospital.
authors.forename: Yrjö Tapio
authors.initials: YT
authors.lastname: Konttinen
authors.affiliation: From the University of Helsinki, and the Helsinki University Central Hospital, Helsinki; Jyväskylä Central Hospital, Jyväskylä; Tampere University Hospital, Tampere; Turku University Central Hospital, Turku; South Karelia Central Hospital, Lappeenranta; Kanta-Häme Central Hospital, Hämeenlinna, Finland.K.J. Aaltonen, MSc (pharm); J.T. Joensuu, MSc (pharm); L. Virkki, MSc (pharm); P. Aronen, MSc; M. Blom, PhD, Professor, University of Helsinki; T. Sokka, MD, PhD, Adj. Professor, Jyväskylä Central Hospital; H. Relas, MD, PhD; H. Valleala, MD, PhD, Adj. Professor, Helsinki University Central Hospital; V. Rantalaiho, MD, PhD, Tampere University Hospital; L. Pirilä, MD, PhD, Turku University Central Hospital; K. Puolakka, MD, PhD, Adj. Professor, South Karelia Central Hospital; T. Uusitalo, MD, Kanta-Häme Central Hospital; Y.T. Konttinen, MD, PhD, Professor; D. Nordström, MD, PhD, Adj. Professor, University of Helsinki, and the Helsinki University Central Hospital.
authors.forename: Dan
authors.initials: D
authors.lastname: Nordström
mesh_terms: D000068879:Adalimumab / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D000068800:Etanercept / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005387:Finland; D006801:Humans; D015994:Incidence; D007239:Infections / Q000453:epidemiology* / Q000209:etiology; D000069285:Infliximab / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology* / Q000209:etiology; D012042:Registries; D000069283:Rituximab / Q000009:adverse effects* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept
keywords: ANTIBODIES; EPIDEMIOLOGY; INFECTION; MONOCLONAL; NEOPLASMS; RHEUMATOID ARTHRITIS