Combination Therapy With Dmards

COMBINATION THERAPY WITH DMARDS

In a 1998 study, approximately half of North American rheuma-tologists treated moderately aggressive rheumatoid arthritis with combination therapy, and the use of drug combinations is prob-ably much higher now. Combinations of DMARDs can be designed rationally on the basis of complementary mechanisms of action, non-overlapping pharmacokinetics, and non-overlapping toxicities.

When added to methotrexate background therapy, cyclosporine, chloroquine, hydroxychloroquine, leflunomide, infliximab, adali-mumab, rituximab, and etanercept have all shown improved efficacy. In contrast, azathioprine, auranofin, or sulfasalazine plus methotrexate results in no additional therapeutic benefit. Other combinations have occasionally been used, including the combi-nation of intramuscular gold with hydroxychloroquine.

While it might be anticipated that combination therapy could result in more toxicity, this is often not the case. Combination therapy for patients not responding adequately to monotherapy is becoming the rule in the treatment of rheumatoid arthritis.

Indications

Corticosteroids have been used in 60–70% of rheumatoid arthritis patients. Their effects are prompt and dramatic, and they are capable of slowing the appearance of new bone erosions. Corticosteroids may be administered for certain serious extra-articular manifestations of rheumatoid arthritis such as pericardi-tis or eye involvement or during periods of exacerbation. When prednisone is required for long-term therapy, the dosage should not exceed 7.5 mg daily, and gradual reduction of the dose should be encouraged. Alternate-day corticosteroid therapy is usually unsuccessful in rheumatoid arthritis.

Other rheumatic diseases in which the corticosteroids’ potent anti-inflammatory effects may be useful include vasculitis, systemic lupus erythematosus, Wegener’s granulomatosis, psoriatic arthritis, giant cell arteritis, sarcoidosis, and gout.

Intra-articular corticosteroids are often helpful to alleviate pain-ful symptoms and, when successful, are preferable to increasing the dosage of systemic medication.

Adverse Effects

Prolonged use of these drugs leads to serious and disabling toxic effects as described. There is controversy over whether many of these side effects occur at doses below 7.5 mg prednisone equivalent daily, although many experts believe that even 3–5 mg/d can cause these effects in susceptible individuals when this class of drugs is used over prolonged periods.