Hydroxychloroquine sulfate (Plaquenil®)
Chloroquine phosphate (Aralen®)
Sulfasalazine (Salazopyrin®, Salazopyrin En-Tabs®)
Sodium aurothiomalate (Myochrysine®)
Sodium aurothioglucose (Solganol®)
Methotrexate sodium (Methotrexate)
Azathioprine (Imuran®)
Cyclophosphamide (Cytoxan®, Procytox®)
Cyclosporine (Neoral®, Sandimmune® IV)

General comments
In patients with RA, a quick referral is key since disease-modifying antirheumatic drugs (DMARDS) should be started early in the disease course to be more effective (deformities and disability develop most rapidly early in the disease). Referral should take place ideally within a month. If the waiting list is too long, a simple phone call is a good way of informing the local rheumatologist about a new patient with RA.

DMARDS are only indicated for chronic inflammatory rheumatic diseases and take weeks if not months before being effective. They are usually supplemented with analgesics and NSAIDs.

Optimal DMARD treatment should have a high degree of disease-modifying capacity, minimal toxicity and allow the patient to continue with the therapy for as long as possible.

Prednisone, a systemic corticosteroid, is useful in controlling inflammation while the DMARD is slowly gaining effectiveness. Prednisone is associated with very serious side effects, e.g. diabetes, hypertension, atherosclerosis, osteoporosis and, therefore, the dosage should be decreased and stopped if possible once the DMARD has taken effect.

Patients taking DMARDS require strict monitoring (visual assessment, blood pressure, serum creatinine, complete blood count, urinalysis, liver function tests) to avoid toxicity.

Drug

• Hydroxychloroquine sulfate (Plaquenil®)
• Chloroquine phosphate (Aralen®, Chloroquine, Novo-Chloroquine)

Dosage used in clinical practice

• Hydroxychloroquine sulfate (Plaquenil®): 200 to 400 mg po/day (in single or divided doses)
• Chloroquine phosphate: 250 mg po/day (single dose)

Dosage according to CPS

• Hydroxycholoroquine sulfate (Plaquenil®):
  • Initial dosage: 400 to 600 mg/day
  • Maintenance dosage at 4 to 12 weeks: 200 to 400 mg/day
• Chloroquine phosphate (Aralen®, Chloroquine, Novo-Chloroquine):
  • Initial dose: 250 mg daily
  • Usual dose: 250 mg daily

Indications

• Degenerative joint disease
• Rheumatoid arthritis
• Seronegative arthritis
• Systemic lupus erythematosus
  

Comments
Hydroxychloroquine appears to be the least toxic of the DMARDS and is substantially less toxic than most NSAIDs.

Results from clinical control and anecdotal studies of hydroxychloroquine in nodal arthritis/inflammatory osteoarthritis of the hands have suggested a role for hydroxycholoroquine. However, hydroxychloroquine has not received approval for this indication. Ongoing randomized controlled trials are underway to test the hypothesis.

Other toxicities associated with the use of chloroquine are nausea and vomiting, retinal toxicity and skin reactions.

Dosage used in clinical practice
1.0 to 1.5 g/day po (in bid or tid divided doses)

Dosage according to CPS

• Week 1: 1 delayed-release tablet in the evening
• Week 2: 1 delayed-release tablet in the morning and 1 delayed-release tablet in the evening
• Week 3: 1 delayed-release tablet in the morning and 2 delayed-release tablets in the evening
• Week 4 and on: 2 delayed-release tablets in the morning and 2 delayed-release tablets in the evening

If no response after two months, dose may be increased to 3 g/day. Some patients may do well with 1.5 g/day.

Indications

• Rheumatoid arthritis
• Seronegative arthritis

Comments
Toxicities associated with sulfasalazine are nausea and vomiting, mucocutaneous reactions, neutropenia and liver abnormities.

Drug

• Sodium aurothiomalate (Myochrysine®)

Dosage used in clinical practice
Induction 25-50 mg IM weekly; maintenance 25-50 mg IM 2-4 weekly

Dosage according to CPS
Sodium aurothiomalate: (Myochrysine®)

• Initial dose:
  • Week 1: 10 mg IM
  • Week 2: 25 mg IM
  • Week 3 and thereafter: 25 to 50 mg IM

• Rheumatoid arthritis
• Seronegative arthritis
  

Comments
Toxicities associated with gold salts include mucocutaneous reactions, nitritoid reactions, thrombocytopenia, nephrotic syndrome, “gold lung” and marrow aplasia.

Dosage used in clinical practice
10 to 30 mg po or IM weekly

Dosage according to CPS

1. Single oral doses of 7.5 mg once a week
2. Divided oral dosages of 2.5 mg at 12-hour intervals for 3 doses given as a course once weekly

Indications

• Rheumatoid arthritis
• Seronegative arthritis
  

Comments
Though the majority of patients with polymyalgia rheumatica respond well to steroids, some remain less steroid responsive. On average, patients will be on steroids for approximately one year and usually no more than two years. Exceptional cases are up to four years. In two recent studies, methotrexate was used as a “steroid-sparing agent.” Methotrexate (12.5 mg IM weekly) was found to reduce the total amount of corticosteroid required to control the disease activity.

Gastrointestinal intolerance is common with methotrexate and is often the reason for it being discontinued.

Methotrexate is associated with teratogenicity; there is no consistent evidence of oncogenicity.

A reduction in the methotrexate dose may be required with renal insufficiency.

Other toxicities associated with methotrexate are nausea and vomiting, mucocutaneous reactions, marrow suppression, pulmonary fibrosis and liver fibrosis.

Dosage used in clinical practice

• 50 to 150 mg po daily (single or divided dosage)

Dosage according to CPS

• Initial dose: 1 mg/kg (50 to 100 mg)/day as a single dose or bid
• Dose increased at 6 to 8 weeks and then increased at 4-week intervals
• Dose increments: 0.5 mg/kg/day up to a maximum of 2.5 mg/kg/day

Indications

• Rheumatoid arthritis
• Seronegative arthritis
  

Comments
Toxicities associated with azathioprine are nausea and vomiting, infections, marrow suppression and possible increased cancer risk.

Dosage used in clinical practice

• 50 to 150 mg po daily (in single or divided doses)
• May be administered in IV bolus in extreme cases

Dosage according to CPS

• No dosage provided for RA

Indications

• Rheumatoid arthritis
• Seronegative arthritis
• Systemic lupus erythematosus
• Connective tissue diseases
  

Comments
Toxicities associated with cyclophosphamide are nausea and vomiting, infections, marrow suppression and possible increased cancer risk.

Dosage used in clinical practice
2 mg/kg/day po (in divided dosage)

Dosage according to CPS

• First 6 weeks: 2.0 mg/kg/day po in 2 divided doses
• Daily dose should not exceed 5 mg/kg/day

Indications

• Rheumatoid arthritis
• Seronegative arthritis

Comments
Toxicities associated with cyclosporine are nausea and vomiting, hypertrichosis, renal dysfunction and possible increased cancer risk.