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The Big Surprise: Front End Loading with DMARD Combinations did not Prevent Use of Biologics in ERA

June 8 2016 5:00 PM ET via RheumReports RheumReports

In all RCTs of early rheumatoid arthritis (ERA), treatment with MTX monotherapy only results in 30% remission whereas  MTX in combination with DMARDs yields a 70% remission rate (or a two-fold increase in remission). 

So with that in mind, Dr. Stephanie Gottheil from London, Ontario evaluated data from the Canadian Early Arthritis cohort (CATCH) to determine whether different initial treatment strategies in ERA would differ with respect to the proportion requiring a biologic treatment over time (#OP0179). Patients meeting the ACR criteria from the ERA cohort who had sufficient follow up data and who were not in remission at baseline were included in her analysis. 

Of the more than 1100 patients who were followed, the mean fixed symptom duration was approximately 5 months.  Patients were treated initially with MTX as monotherapy (40%) or in combination with at least one other conventional DMARD (60%), with a mean dose of 20 mg/week. 

Surprisingly, the patients on MTX monotherapy had less biologic use over follow up (17.5% vs. 23.6% on combination therapy). Use of subcutaneous MTX was more likely to prevent the need to escalate treatment to a biologic treatment (approximately 47% reduction in biologic use). In this same cohort, Dr. G. Hazlewood presented CATCH data in 2015 and found that sc MTX was more likely than oral MTX to improve drug survival on MTX. Biologic use was higher in younger patients, steroid users and those with high baseline DAS28. 

So, what is the take home message? There was site heterogeneity so practice variation and treatment may both be important when interpreting the findings in this study (i.e. initial sc MTX monotherapy patients may not need further treatment as often, but certain sites that use this strategy may also use less biologics [confounding by indication], and/or, in order to obtain biologic treatment reimbursement by provincial or private payers in Canada, there needs to be two or more DMARDs used and in general at least one combination of DMARDs, so the initial treatment of combination therapy may be a faster way to obtain a biologic if it is required). 

These data are difficult to reconcile with at least one other report where combination DMARDs prolonged the time to be prescribed a biologic. We don't know if the variation in practice and reimbursement for advanced therapeutics make these results generalizable to other countries. 

Also, since the data are not randomized, there may be confounding by indication:  the highest baseline DAS28 patients received the most treatment and were most likely to require advanced treatment for eventual disease control.


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About the Author

Dr. Janet Pope
Dr. Janet Pope

Dr. Janet Pope is Professor of Medicine at Western University and Division Head of Rheumatology. Dr. Pope's research interests include epidemiologic studies in scleroderma, classification criteria in systemic sclerosis, systemic lupus erythematosus and rheumatoid arthritis.

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