Therapeutic Agents for Rheumatoid Arthritis
Methotrexate (a), hydroxychloroquine (c), and sulfasalazine (d) are routinely used to treat rheumatoid arthritis, while cyclosporine (b) and hydroxyurea (e) are not standard therapeutic agents for this condition.
Standard DMARDs for Rheumatoid Arthritis
First-Line Therapy
Methotrexate is the preferred first-line conventional synthetic DMARD for treatment-naive patients with active rheumatoid arthritis, based on its superior efficacy and safety profile 1, 2. The 2026 PANLAR guidelines and 2021 ACR guidelines both strongly recommend methotrexate over other conventional synthetic DMARDs 1, 2.
Alternative Conventional Synthetic DMARDs
The following agents are established therapies for rheumatoid arthritis:
Hydroxychloroquine (c): Used therapeutically for RA, though considered less efficacious than methotrexate in the long term 1. It is commonly used in triple therapy combinations (methotrexate + sulfasalazine + hydroxychloroquine) when methotrexate monotherapy is insufficient 1.
Sulfasalazine (d): Another conventional synthetic DMARD used for RA treatment, particularly in combination regimens 1, 2. Like hydroxychloroquine, it is less efficacious than methotrexate but remains a therapeutic option 1.
Leflunomide: Has similar clinical efficacy to methotrexate and is equally effective in slowing radiographic damage, though methotrexate is conditionally preferred due to greater dosing flexibility and lower cost 1, 2.
Agents NOT Routinely Used for Rheumatoid Arthritis
Cyclosporine (b)
Cyclosporine is not a standard therapeutic agent for rheumatoid arthritis and is not mentioned in current major guidelines 1, 2, 3. While it has immunosuppressive properties, it is not part of the conventional DMARD armamentarium for RA management.
Hydroxyurea (e)
Hydroxyurea is not used therapeutically for rheumatoid arthritis. This agent is primarily used for hematologic conditions such as sickle cell disease and certain malignancies. It does not appear in any rheumatoid arthritis treatment guidelines or recommendations 1, 2, 3.
Clinical Algorithm
The current treatment approach follows this hierarchy 1, 2:
- Initial therapy: Start methotrexate as first-line conventional synthetic DMARD
- Inadequate response at 3-6 months: Add triple conventional synthetic therapy (methotrexate + sulfasalazine + hydroxychloroquine) for patients without poor prognostic factors 1
- Persistent inadequate response: Escalate to biologic or targeted synthetic DMARDs 1, 2, 3
Important Caveats
The 2021 ACR guideline strongly recommends methotrexate over hydroxychloroquine or sulfasalazine for DMARD-naive patients with moderate-to-high disease activity, despite very low to low certainty evidence, based on methotrexate's superior disease-modifying properties and long-term tolerability 2. However, both hydroxychloroquine and sulfasalazine remain valid therapeutic options, particularly in combination regimens or when methotrexate is contraindicated.
Answer Summary:
- a) Methotrexate: YES - first-line therapy
- b) Cyclosporine: NO - not a standard RA treatment
- c) Hydroxychloroquine: YES - used therapeutically, especially in combinations
- d) Sulfasalazine: YES - used therapeutically, especially in combinations
- e) Hydroxyurea: NO - not used for RA