Elisabeth Hjardem, Mikkel Østergaard, Jan Pødenphant, Ulrik Tarp, Lis Smedegaard Andersen, Jette Bing, Elisabeth Peen, Hanne Merete Lindegaard, Vibeke Stevenius Ringsdal, Anne Rødgaard, Jens Skøt, Annette Hansen, Hans Henrik Mogensen, Janne Unkerskov, and Merete Lund Hetland

Do rheumatoid arthritis patients in clinical practice benefit from switching from infliximab to a second tumor necrosis factor alpha inhibitor?
Ann Rheum Dis 2007; 66: 1184-1189 [Abstract] [Full text] [PDF]

p.emery{at}leeds.ac.uk Paul Emery, et al.

We read with interest the article by Hjardem E et al which reported the experiences of switching between TNF-antagonists from the Danish patient registry, DANIBO. We would like to draw the authors’ attention to data published from our group 2 years ago which both highlights some aspects relevant to the current report and which provides some insights into the mechanisms involved. Non-response is seen either as a primary phenomenon i.e. no response at the first point of assessment (usually 12 weeks using standard response criteria) or secondary non-response - loss of an initial demonstrable response. We described primary non-response in detail in a cohort of over 200 patients on infliximab (Buch MH, et al, A&R 05). Furthermore, distinctsub-groups of primary non-response were identified based on the presence or lack of CRP suppression, with the latter group demonstrating significantly high response rates upon switching to etanercept (68% ACR20, 51% ACR50). These observations have been confirmed in a larger cohort (Buch MH et al, Arth Rheum 07). The basis for such contrasting responses has been discussed and explored previously with a representative case suggesting a role for lymphotoxin-alpha, targeted by etanercept but not infliximab (Buch MH et al, ARD 04). We have also recently illustrated that secondary non-response occurs to a significant extent in a cohort of initial infliximab responders (Buch MH et al, Rheum 07). We suggested the kinetics of secondary non-response implies a pharmacokinetic basis for failure and showed that such patients demonstrate a higher response rate to adalimumab (Buch MH et al Arth Rheum abstract 05); probably by overcoming potential HACA issues. Thus the observations by Hjardem E et al have been well-described previously in a more homogeneous cohort and with the benefit of more stringent classification. Furthermore, tailored therapeutic intervention has revealed possible underlying basis for such non-response.