RESEARCH - Evidence for differential acquired drug resistance to anti-TNF agents in RA

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Ann Rheum Dis. 2006 Jun;65(6):746-52. Epub 2005 Dec 8.

Evidence for differential acquired drug resistance to anti-tumour necrosis

factor agents in rheumatoid arthritis.

Department of Medicine, Division of Rheumatology, Immunology and Allergy,

Brigham and Women's Hospital, Harvard Medical School, Boston, USA.

afinckh@...

BACKGROUND: Acquired drug resistance or gradual drug failure has been

described with most disease modifying antirheumatic drugs (DMARDs) and is

also starting to be recognised with anti-tumour necrosis factor (anti-TNF)

agents. OBJECTIVE: To study acquired drug resistance to anti-TNF agents in

rheumatoid arthritis (RA). METHODS: Swiss health authorities requested

continuous monitoring of patients receiving biological agents.

Intensification of co-therapy with traditional DMARDs, gradual dose

escalation, and drug discontinuation rates in all patients receiving

infliximab, etanercept, or adalimumab, adjusting for potential confounders,

were analysed. Intensification of DMARD co-therapy and time to

discontinuation of the three anti-TNF agents were analysed using a

proportional hazards models. Dose escalation and evolution of RA disease

activity (DAS28) were analysed using a longitudinal regression model.

RESULTS: 1198 patients contributing 1450 patient-years of anti-TNF treatment

met the inclusion criteria. The rate of intensification of traditional DMARD

co-therapy over time was significantly higher with infliximab (hazards ratio

= 1.73 (99% confidence interval (CI) 1.19 to 2.51)) than with the two other

agents. Infliximab also showed significant dose escalation over time, with

an average dose increase of +12% (99% CI 8% to 16%) after 1 year, and +18%

(99% CI 11% to 25%) after 2 years. No significant differences in

discontinuation rates were seen between the three anti-TNF agents (ANOVA, p

= 0.67). Evolution of disease activity over time indicated a lower

therapeutic response to infliximab (DAS28, p<0.001) compared with

etanercept, after 6 months' treatment.

CONCLUSIONS: In this population, infliximab was associated with a higher

risk of requiring intensification of DMARD co-therapy than the other

anti-TNF agents and a significant dose escalation over time. Analysis of RA

disease activity indicated a reduced therapeutic response to infliximab

after the first 6 months of treatment, suggestive of acquired drug

resistance.

PMID: 16339288

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=abstractplus & db=pubmed & cmd=R\

etrieve & dopt=abstractplus & list_uids=16339288

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