RESEARCH - Survival, comorbidities and joint damage 11 years after the COBRA combination therapy trial in early RA

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Ann Rheum Dis. Published Online First: 17 May 2009. doi:10.1136/ard.2009.108027

BMJ Publishing Group Ltd & European League Against Rheumatism.

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Extended Report

Survival, comorbidities and joint damage 11 years after the COBRA

combination therapy trial in early rheumatoid arthritis

Lilian H D van Tuyl 1*, Maarten Boers 1, Willem F Lems 1, BM

Landewé 2, Huub Han 3, Sjef van der Linden 2, Mart A F J van der Laar

4, Rene Westhovens 5, J Christiaan Van Denderen 6, Marie-Louise

Westedt 7, André J Peeters 8, Piet s 9, Tom W J Huizinga 10, Hans

van den Brink 11, Ben A C Dijkmans 1 and andre E Voskuyl 1

1 VU University Medical Centre, Netherlands

2 University Hospital Maastricht, Netherlands

3 Medical Center Rijnmond Zuid, Netherlands

4 Medisch Spectrum Twente & Universiteit Twente, Netherlands

5 University Hospital Leuven, Belgium

6 Jan van Breemen Instituut, Netherlands

7 Bronovo Hospital, Netherlands

8 Reinier de Graaf Hospital, Netherlands

9 Sint tius Hospital, Netherlands

10 Leiden University Medical Center, Netherlands

11 Medical Center Alkmaar, Netherlands

Abstract

Background: COBRA combination therapy is effective for the treatment

of rheumatoid arthritis (RA), but long term safety is unknown. This

study evaluates survival, comorbidities and joint damage in the

original COBRA trial cohort.

Methods: In the COBRA trial, 155 early RA patients were treated with

sulfasalazine monotherapy (SSZ-group) or a combination of step-down

prednisolone, methotrexate and sulfasalazine (COBRA-group). The

current 11-year follow-up study of the COBRA trial invited all

original patients and performed protocollized scrutiny of clinical

records, questionnaires, physical examination, laboratory and imaging

tests.

Results: 152 out of 155 patients yielded at least partial data. After

mean 11 years follow-up, 18 (12%) patients had died, 6 COBRA patients

and 12 SSZ patients, hazard ratio 0.57 (95%CI: 0.21-1.52). Treatment

for hypertension was significantly more prevalent in the COBRA-group

(P=0.02) with similar trends for diabetes and cataract. Conversely,

hypercholesterolemia, cancer and infection showed a trend in favour of

COBRA. Other comorbidities such as cardiovascular disease and

fractures appeared in similar frequency. Radiographic findings suggest

as a minimum sustained benefit for COBRA therapy, i.e. difference in

joint damage but similar subsequent progression rates after 5 years.

Imputation to compensate for selective dropout suggests increasing

benefit for COBRA, i.e. difference in yearly progression rates similar

to that seen in the first 5 years of follow-up.

Conclusions: After 11 years, initial COBRA combination therapy

resulted in numerically lower mortality and similar prevalence of

comorbidity compared to initial SSZ monotherapy. In addition, lower

progression of joint damage suggests long-term disease modification.

http://ard.bmj.com/cgi/content/abstract/ard.2009.108027v1?papetoc

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