EU Consensus Statement on Combined Therapy with Methotrexate

(©Tatyana,AdobeStock)

Methotrexate should be continued in most patients with active rheumatoid arthritis when biologic or targeted synthetic therapy is initiated, EU researchers reported in a poster presentation on November 12 at the annual meeting of the American College of Rheumatology in Atlanta.

This is the main message of 10 new consensus statement recommendations for EU rheumatologists made by a panel of Spanish experts and presented by Jesús Tornero, M.D., chief of the Section of Rheumatology at the Hospital Universitario de Guadalajara.  American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) guidelines for rheumatoid arthritis currently recommend adding a biologic to methotrexate when disease activity remains moderate to high. Many patients, however, stop methotrexate when starting these agents.

The Spanish panel reviewed relevant EULAR, ACR, and international guidelines and conducted a systematic literature review to answer questions about combination therapy for rheumatoid arthritis with methotrexate plus a biologic or targeted synthetic.

They restricted searches to English or Spanish-language systematic reviews and meta-analyses with data on efficacy or safety variables in patients with RA on or considering initiating methotrexate plus a biologic or targeted synthetic. The panel included 61 papers in their final review and evaluated evidence quality with Oxford Center for Evidence-based Medicine standards, which they also used to assign evidence level and grade to their final recommendations.

Experts voted yes or no on proposed recommendations, reaching 100% agreement for all but two, which had 91% agreement. Most had a 1b level of evidence (based on a single randomized controlled trial with a narrow confidence interval) and many received an A grade (consistent level 1 studies).

Summarized Recommendations

• For patients with an inadequate response to methotrexate, the panel recommended continuing that drug when adding a TNF inhibitor, abatacept, rituximab, an anti-Il-6 agent, or a JAK inhibitor. 

• Methotrexate dosing in these patients should remain the same when adding a biologic or targeted synthetic, though the panel also recommended it be at least 10 mg a week in those combining methotrexate with a TNF inhibitor.

• The panel recommended giving priority to de-escalating biologics in patients who reach and sustain treatment goals (not including methotrexate dose adjustments or withdrawal in some intolerant patients on IL-6 inhibitors). This is one of two recommendations based on expert opinion, the lowest level evidence.

• Methotrexate should be the first conventional DMARD used when starting a biologic or JAK inhibitor, though other conventional DMARDs can be considered in patients with an intolerance or contraindication to methotrexate. 

• The panel’s final recommendation, also based on expert opinion, advised that combined therapy with methotrexate and a biologic or targeted synthetic should not imply different management of the standard of care for routine patient safety monitoring.

REFERENCE“2386 - Consensus Statement and Recommendations on Methotrexate Use in Combined Therapy with Biological or Targeted Synthetic Disease Modifying Drugs in Patients with Rheumatoid Arthritis,” Jesús Tornero, MD, 9 a.m., Nov 12. American College of Rheumatology 2019 annual meeting, Atlanta.