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Anti-TNF therapy in RA and risk of malignant lymphomas Relative risks and time-trends in the Swedish Biologics Register
  1. Johan Askling (johan.askling{at}
  1. Karolinska Institutet, Sweden
    1. Eva Baecklund
    1. Uppsala University, Sweden
      1. Fredrik Granath
      1. Karolinska Institutet, Sweden
        1. Pierre Geborek
        1. Lund University, Sweden
          1. Michael Fored
          1. karolinska institutet, Switzerland
            1. Carin Backlin
            1. Uppsala University, Sweden
              1. Lennart Bertilsson
              1. Sahlgrenska Academy, Sweden
                1. Lars Cöster
                1. University of Linköping, Sweden
                  1. Lennart Jacobsson
                  1. Malmö University Hospital, Sweden
                    1. Staffan Lindblad
                    1. Karolinska Institutet, Sweden
                      1. Jörgen Lysholm
                      1. Falu County Hospital, Sweden
                        1. Solbritt Rantapää-Dahlqvist
                        1. Umea University, Sweden
                          1. Tore Saxne
                          1. University of Lund, Sweden
                            1. Ronald van Vollenhoven
                            1. Karolinska Institutet, Sweden
                              1. Lars Klareskog
                              1. Karolinska Institutet, Sweden
                                1. Nils Feltelius
                                1. Karolinska Institutet, Sweden


                                  Background: TNF-antagonists have proven effective as treatment against RA, but the unresolved issue of whether use of anti-TNF therapy increases the already elevated lymphoma risk in RA remains a concern.

                                  Methods: Using the Swedish Biologics Register (ARTIS), the Swedish Cancer Register, pre-existing RA-cohorts, and cross-linkage with other national health- and census-registers, we assembled a national RA cohort (n=67,743), and identified those patients who started anti-TNF therapy from 1998 through July 2006 (n=6,604); we also assembled a general population comparator (n=471,024), and assessed and compared the incidence of lymphomas from 1999 through December 31st 2006 in these individuals.

                                  Results: Among the 6,604 anti-TNF treated RA-patients, 26 malignant lymphomas were observed during 26,981 person-years of follow-up, which corresponded to a relative risk of 1.35 (0.82-2.11) versus anti-TNF naïve RA subjects (336 lymphomas during 365,026 person-years), and 2.72 (95% CI 1.82-4.08) versus the general population comparator (1,568 lymphomas during 3,355,849 person-years). RA-patients starting anti-TNF therapy 1998-2001 accounted for the entire increase in lymphoma risk versus the two comparators. By contrast, relative risks did not vary significantly by time since first treatment start or with accumulated duration of treatment, nor with type of anti-TNF agent.

                                  Conclusion: Overall and as used in routine care against RA, TNF-antagonists are not associated with any major further increase of the already elevated lymphoma occurrence in RA. Changes in selection of patients for treatment may influence the observed risk.

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