RESEARCH - Can clinical factors at presentation be used to predict outcome of treatment with MTX in patients with early inflammatory polyarthritis?

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Ann Rheum Dis. Published Online First: 21 February 2008.

doi:10.1136/ard.2008.088237

Copyright © 2008 BMJ Publishing Group Ltd & European League Against

Rheumatism

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Extended Report

Can clinical factors at presentation be used to predict outcome of

treatment with methotrexate in patients with early inflammatory

polyarthritis?

L Hider 1, Alan J Silman 1, Thomson 1, Mark Lunt 1,

Diane Bunn 2 and Deborah Symmons 3*

1 University of Manchester, United Kingdom

2 Norfolk Arthritis Register, United Kingdom

3 ARC Epidemiology Unit, United Kingdom

Abstract

Purpose: Methotrexate (MTX) is the first choice conventional DMARD for

rheumatoid arthritis. However, it is not universally effective,

although to date it is not possible to predict with any accuracy which

patients will respond to treatment. The aim of this analysis was to

examine whether clinical and genetic variables could be used to

predict response to MTX.

Methods: Patients recruited to the Norfolk Arthritis Register (NOAR),

a primary care based inception cohort of patients with inflammatory

polyarthritis, were eligible for this analysis if they were commenced

on MTX as their first DMARD within 3 months of their baseline visit

and had at least 2 year follow up data. Outcome on MTX was defined as

(a) stopped for adverse events ( stopped for inefficacy or 2nd DMARD

added © stopped for other reasons or d) remained on MTX monotherapy.

Multiple logistic regression was used to establish which variables

(including demographics, disease activity and HAQ score) predicted

stopping monotherapy for inefficacy or adverse event (with those

remaining on treatment taken as the referent category). The area under

the Receiver Operating Characteristic curves (AUC ROC), were used to

determine how accurate the model was at predicting outcome.

Results: 309 patients were included in this analysis. At 1 year (2

years), 34 (46) patients had stopped for adverse events and 25 (49)

had either stopped monotherapy for inefficacy or had a 2nd DMARD

added. 231 (188) patients remained on MTX monotherapy. The strongest

predictor of inefficacy at both time points was shared epitope

positivity: OR 5.8 (95%CI 1.3-25.6) at one year, OR 3.0 (95%CI

1.3-7.3) at two years. High HAQ score (OR 1.84 95%CI 1.12-3.01) and

female gender (OR 2.2, 0.92-5.28) were associated with adverse events

on MTX at one year. However even the most optimal combinations of the

factors analysed were only weakly predictive of treatment outcome: AUC

ROC for adverse events 0.68 (95% CI 0.58-0.78) and for inefficacy AUC

ROC 0.71 (95%CI 0.6-0.81).

Conclusion: Within this cohort, routine clinical and laboratory

factors were poor at predicting outcome of treatment with MTX. Given

the major therapeutic advantage to be derived from accurate prediction

of treatment outcome, further studies will need to investigate novel

biological and other markers.

http://ard.bmj.com/cgi/content/abstract/ard.2008.088237v1?papetoc

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