Kalle Jyri Aaltonen1, Jaana Tuulikki Joensuu2, Liisa Virkki2, Tuulikki Sokka2, Pasi Aronen2, Heikki Relas2, Heikki Valleala2, Vappu Rantalaiho2, Laura Pirilä2, Kari Puolakka2, Tea Uusitalo2, Marja Blom2, Yrjö Tapio Konttinen2, Dan Nordström2. 1. 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. 2. 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.
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. CONCLUSION: Our results provide some reassurance of the safety of biologic treatments in the treatment of RA.
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. CONCLUSION: Our results provide some reassurance of the safety of biologic treatments in the treatment of RA.
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