Triple Therapy for Rheumatoid Arthritis

Introduction to Triple Therapy

The American College of Rheumatology recommends triple therapy, consisting of methotrexate, sulfasalazine, and hydroxychloroquine, as a well-established treatment option for patients who have not achieved adequate disease control with methotrexate monotherapy 1, 2

The typical dosing regimen for triple therapy includes methotrexate 15-25 mg weekly, with folic acid supplementation always required to reduce adverse effects 3, 4

The American College of Rheumatology conditionally recommends triple therapy for patients without poor prognostic factors who have not achieved target disease activity after 3-6 months of optimized methotrexate monotherapy 3
The American College of Rheumatology notes that addition of a biologic DMARD or targeted synthetic DMARD is conditionally recommended over triple therapy for patients taking maximally tolerated doses of methotrexate who are not at target 1

For patients with moderate-to-high disease activity on methotrexate monotherapy, ensure methotrexate is optimized to 15-25 mg weekly, and assess for poor prognostic factors before considering triple therapy 3, 4
If poor prognostic factors are present, add biologic DMARD or JAK inhibitor rather than triple therapy 1, 3

Do not add sulfasalazine and hydroxychloroquine before optimizing methotrexate dose to 15-25 mg weekly, and do not forget folic acid supplementation with methotrexate 3, 4
Do not continue triple therapy beyond 6 months if inadequate response, and do not use triple therapy as first-line in patients with poor prognostic factors 1, 3
Do not combine leflunomide with sulfasalazine and hydroxychloroquine due to gastrointestinal complications and lack of benefit over standard triple therapy 5

If a patient on triple therapy wishes to discontinue one DMARD after achieving sustained remission, gradual discontinuation of sulfasalazine is conditionally recommended over gradual discontinuation of hydroxychloroquine 1