5 Questions About DMARDs in RA

Methotrexate is recommended as initial treatment for patients with rheumatoid arthritis (RA). However, treatment strategies can be altered if methotrexate does not meet treatment targets. Available data on the ideal follow-up strategy in daily practice is limited. So, addressing drug efficacy can be difficult due to various, uncontrolled factors.

In a new study¹, Dr Systsje Anne Bergstra, of the department of rheumatology at Leiden University Medical Center in Leiden, The Netherlands, and colleagues sought to compare disease modifying antirheumatic drug (DMARD) treatment regimens in daily practice among patients with newly diagnosed RA who failed initial methotrexate treatment.

The researchers evaluated data on patients found in METEOR, an international, observational registry. Among the patients, 143 received conventional synthetic DMARDs, 278 received conventional synthetic DMARDs plus glucocorticoid, and 89 patients received biological DMARDs plus conventional synthetic DMARDs.

Multinomial regression analysis was used to configure the multiple propensity score for each patient, which expressed the likelihood of treatment with each regimen. Linear mixed model analyses were also performed to analyze treatment responses per category after a maximum follow-up duration of 6 and 12 months.

Results showed that after 6 months, propensity score-adjusted treatment responses yielded a change in Disease Activity Score (DAS) per year of -2.00 if patients received a biologic DMARD; DAS per year of -0.96 if patients received conventional synthetic DMARDs plus glucocorticoid; and DAS per year of -0.73 if patients received conventional synthetic DMARDs only.

After 1 year, change in DAS were −0.91 for biologic DMARD; −0.43 for conventional synthetic DMARDs plus glucocorticoid; and −0.39 for conventional synthetic DMARDs only.

Rheumatology Consultant caught up with Dr Bergstra about her research.

Rheumatology Consultant: How did your study come about?
 

Sytske Anne Bergstra: Methotrexate is the recommended initial treatment for rheumatoid arthritis (RA) patients, but if methotrexate is insufficient to meet the required treatment targets, patients should switch to a different treatment strategy. To date, evidence about the preferred follow-up strategy in daily practice is sparse. At the same time, answering questions about drug efficacy in daily practice data is difficult because several uncontrolled factors can influence the results. Therefore, we wanted to introduce a statistical technique that is not commonly used in rheumatology, but that we think can be helpful to get more reliable answers to the kind of question we wanted to answer.

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RHEUM CON: Why might a patient with RA fail treatment with methotrexate? Is this common?
 

SAB: Methotrexate is recommended and widely used as the drug of first choice in the treatment of RA patients because it is effective, cost-efficient, and it has an acceptable safety profile. Despite its reputation of high effectiveness, 50-75% of patients do not reach a state of low disease activity within 6 months after initial methotrexate. Unfortunately, it is not yet possible to predict which patients will and will not show a good response to methotrexate. Therefore, the effect of therapy is closely monitored and if the desired treatment targets, or at least sufficient improvement, are not met within 3 to 6 months, patients switch to a different treatment.

RHEUM CON: Why do you think patients had a better response to a biological DMARD than a conventional synthetic DMARD?

SAB: It is currently impossible to predict which patients will show a good response to which type of treatment. We found that in daily practice more patients had a good response to a biologic DMARD than to a conventional synthetic DMARD. Ideally, we would be able to predict beforehand which patients would need expensive biologic DMARDs to show a good response, and which patients will show a good response to less expensive conventional synthetic DMARDs. If we would be able to understand why some patients have a better response to some type of medication than others, this would probably help us to predict which treatment would be best for which patient.

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RHEUM CON: Is there another setting where a conventional synthetic DMARD or glucocorticoids would be more effective in this patient population?

SAB: The investigated patient population included newly diagnosed patients who failed their initial treatment with methotrexate monotherapy. In current daily practice, there are also many patients who start treatment with a combination of methotrexate and a glucocorticoid. In those patients, we might have found different results, but it is not possible to know this based on the current analyses.

RHEUM CON: What are the clinical implications of the study and how can a rheumatologist apply this to real-life practice?
 

SAB: Our results showed that in patients who failed initial methotrexate monotherapy, switching to a biologic DMARD showed higher effectiveness than switching to treatment with conventional synthetic DMARDs with or without a glucocorticoid. Rheumatologists can take these results into account when choosing among treatment strategies in patients who fail initial methotrexate monotherapy. However, next to effectiveness, other factors such as cost-effectiveness, patient preferences, and risk of side effects should be taken into account. Therefore, more work needs to be done before we can identify the best treatment for each individual patient.

Reference:

1. Bergstra SA, Winchow LL, Murphy E, et al. How to treat patients with rheumatoid arthritis when methotrexate has failed? The use of a multiple propensity score to adjust for confounding by indication in observational studies. Ann Rheum Dis. 2019;78(1):25-30. https://ard.bmj.com/content/78/1/25.  

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