Anti-TNF therapy in RA and risk of malignant lymphomas Relative risks and time-trends in the Swedish Biologics Register

Johan Askling ^1*, Eva Baecklund ², Fredrik Granath ¹, Pierre Geborek ³, Michael Fored ⁴, Carin Backlin ², Lennart Bertilsson ⁵, Lars Cöster ⁶, Lennart Jacobsson ⁷, Staffan Lindblad ¹, Jörgen Lysholm ⁸, Solbritt Rantapää-Dahlqvist ⁹, Tore Saxne ¹⁰, Ronald van Vollenhoven ¹, Lars Klareskog ¹ and Nils Feltelius ¹

¹ Karolinska Institutet, Sweden
² Uppsala University, Sweden
³ Lund University, Sweden
⁴ karolinska institutet, Switzerland
⁵ Sahlgrenska Academy, Sweden
⁶ University of Linköping, Sweden
⁷ Malmö University Hospital, Sweden
⁸ Falu County Hospital, Sweden
⁹ Umea University, Sweden
¹⁰ University of Lund, Sweden

^* To whom correspondence should be addressed. E-mail: johan.askling{at}ki.se.

Accepted 23 April 2008

Abstract

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.