Selecting Non-Biological DMARDS

 

Methotrexate:

• Many guidelines recommends MTX as the first option because of its ease of administration (i.e., once-weekly dosing) and relatively rapid onset of action
• MTX has the most favourable efficacy/toxicity trade-off.
• An initial trial of methotrexate should last for 3 months.
• Risk of liver toxicity is higher than that observed with use in rheumatoid arthritis. 
• Daily folic acid supplements are required

Sulfasalazine

• MTX and sulfasalazine have similar effects on symptoms, disease activity, functional capacity, and limiting radiographic changes (in patients with RA for less than 3 years).
• Sulfasalazine and leflunomide have been shown to reduce symptoms of peripheral arthritis
• do not impair female fertility and are relatively safe if continuing use is essential in pregnancy; thus, they are especially suitable for female patients who are planning a family

Leflunomide

• MTX and leflunomide (AravaR) have similar effects on symptom response, radiographic change, and functional capacity.
• Sulfasalazine and leflunomide have been shown to reduce symptoms of peripheral arthritis
• Leflunomide may be superior to sulfasalazine for improving functional capacity
• Methotrexate and sulfasalazine are the DMARDs of choice due to their more favourable efficacy and toxicity profiles

Hydroxychloroquine

• hydroxychloroquine (HCQ) and/or sulfasalazine (SSZ) are recommended by Uptodate as the initial disease-modifying antirheumatic drug (DMARD) in most patients with mildly active rheumatoid arthritis (RA), particularly those with minimal or low levels of disease activity and those who are seronegative for rheumatoid factor and anti-cyclic citrullinated peptide (CCP) antibodies.
• do not impair female fertility and are relatively safe if continuing use is essential in pregnancy; thus, they are especially suitable for female patients who are planning a family

Ciclosporin

• Use of ciclosporin is limited due to renal toxicity
• Patients failing to respond to NSAIDs, intra-articular corticosteroid injections, and single-agent DMARDs have experienced joint and skin improvement when treated with ciclosporin combined with methotrexate

Combination

• Combining a biologic with methotrexate works better than using either drug alone
• Combining prednisone with hydroxychloroquine, methotrexate, or sulfasalazine works better than using these synthetic DMARDs alone. It also gives better 2-year radiographic outcomes.
• A triple combination of hydroxychloroquine, methotrexate, and sulfasalazine works better than a two-drug combination (methotrexate with either drug) for people previously on monotherapy.
• Combining sulfasalazine with methotrexate does not work better than monotherapy with either drug alone for people with early RA
• Evidence is insufficient to determine whether combining two biologics works better than monotherapy with a biologic
• Research has not addressed whether combining a corticosteroid with a biologic works better than monotherapy with a biologic
• Corticosteroids have several wellknown side effects. Long-term use of corticosteroids increases the risk of adrenal suppression, osteoporosis, obesity, diabetes, cataracts, and infection

References:

1. Choosing Medications for RHEUMATOID ARTHRITIS Clinician’s Guide. April 2008
2. www.uptodate
3. Disease-Modifying Antirheumatic Drugs for the Management of Rheumatoid Arthritis
4. SIGN: Management of early rheumatoid arthritis A national clinical guideline
5. Drug Therapy for Rheumatoid Arthritis: Comparative Effectiveness. 2007