Timing of DAS28 in infliximab therapy

D. J. Armstrong and I. N. Bruce

ARC Epidemiology Unit, University of Manchester, and Department of Rheumatology, Manchester Royal Infirmary, Manchester, UK

Correspondence to: D. J. Armstrong, Specialist Registrar, Department of Rheumatology, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK. E-mail: oswald17727{at}hotmail.com

SIR, Durez et al. [1] argue that the clinical judgement of an experienced rheumatologist might be more useful than clinical trial outcome criteria such as ACR20 or DAS28 when assessing response to infliximab at 22 weeks. They report that 34.2% of patients clinically felt to require an increase in dose nevertheless fulfilled the ACR20 criteria, and that in a sub-group of their study in whom DAS28 was performed, 53% of patients who required a dose increase on clinical grounds fulfilled the DAS28 response criteria. In their opinion, in these patients, an ACR20 or DAS28 response underestimates ongoing disease activity.

It would be equally enlightening to analyse the ‘mirror-image’ data, i.e. how many patients failed the ACR20 or DAS28 response at 22 weeks but were nevertheless felt not to require an increase in dose. An assessment performed at 22 weeks, just prior to the fifth dose of infliximab, is a full 8 weeks since the last administration, when some of the beneficial effects may be wearing off. If a patient has had an excellent clinical response for 6 or 7 weeks, but experiences a deterioration in control over the last 7 days, he or she may ‘fail’ a global assessment tool on the day, but nevertheless be felt generally well enough controlled not to require an increase in dose, or to have the drug withdrawn. In this case, it is the timing of the assessment rather than the efficacy of the drug which is the crucial factor. For example, Sidiropoulos et al. [2] report a significant improvement in DAS after increasing the frequency of infliximab infusions from 8-weekly to 6-weekly, in a study in which DAS, EULAR and ACR responses were assessed immediately before the next infusion. Although they naturally suggest that the significant improvement in DAS is related to the increasing dose intensity, after the increase the patients were assessed 6 weeks rather than 8 weeks after the previous infusion.

Information from the Durez et al. study on DAS28 failures who were nevertheless felt to be able to continue on their 8-weekly dose might further strengthen the case that the DAS28 8 weeks after the last infusion is not the ideal tool for measurement of infliximab efficacy. A fair assessment of disease activity and apparent response might require an increase in the frequency of the assessment, rather than necessarily an increase in the frequency of the drug.

I. N. Bruce has received funding support for departmental developments from Wyeth and Abbott Laboratories. D. J. Armstrong has declared no conflicts of interest.

References

  1. Durez P, Van den Bosch F, Corluy L et al. A dose adjustment in patients with rheumatoid arthritis not optimally responding to a standard dose of infliximab of 3 mg/kg every 8 weeks can be effective: a Belgian prospective study. Rheumatology 2005;44:465–8.[Abstract/Free Full Text]
  2. Sidiropoulos P, Bertsias G, Kritikos HD, Kouroumali H, Voudouris K, Boumpas DT. Infliximab treatment for rheumatoid arthritis, with dose titration based on the Disease Activity Score: dose adjustments are common but not always sufficient to assure sustained benefit. Ann Rheum Dis 2004;63:144–8.[Abstract/Free Full Text]
Accepted 8 April 2005





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