Oral meds only? | Arthritis Information

Summary

Early aggressive treatment of rheumatoid arthritis is associated with improved disease control, slower radiological progression and improved functional outcomes. Tumor necrosis factor blocking therapy is effective but there remain concerns about long-term risks. Combining disease-modifying antirheumatic drugs (DMARDs) is a widely used therapeutic alternative; however, there is uncertainty surrounding the most effective regimen. A popular combination is methotrexate plus sulfasalazine, but each of these DMARDs can also be used in combination with other DMARDs and in triple therapy regimens. However, wide variations in study size, design, steroid usage and approaches to combination therapy have made it difficult to form firm conclusions regarding their efficacy. Generally, combination therapy is well tolerated and associated with no significant increase in the rate of adverse events compared with monotherapy. Methotrexate-sulfasalazine, methotrexate-chloroquine, methotrexate- ciclosporin, methotrexate-leflunomide, methotrexate-intramuscular-gold and methotrexate-doxycycline are effective combination regimens. Triple DMARD therapy is better than various DMARD monotherapy and dual therapy regimens. Methotrexate and hydroxychloroquine may have synergistic anti-inflammatory properties. Clinical trial evidence to support the use of other methotrexate and sulfasalazine combinations is often weak or lacking. Further investigation is required to determine the most effective regimen and approach to combination therapy.

Introduction

The principles behind the management of rheumatoid arthritis (RA) continue to evolve as our understanding of the pathophysiological processes that underlie this disease advances. The immune-targeted biologic therapies-especially tumor necrosis factor (TNF) blockers-provide a welcome addition to the rheumatologist's armamentarium. However, the use of both traditional disease-modifying antirheumatic drugs (DMARDs) and TNF blockers needs to be continued indefinitely to sustain clinical benefit. As long-term experience with anti-TNF therapy is limited, the potential long-term risks, particularly of developing lymphomas, remains an issue.^[1] Until these concerns are fully addressed, traditional DMARDs will probably remain the preferred initial treatments for RA.

It is postulated that a 'treatment window' exists in early RA, during which optimal treatment provides a better long-term outcome. Delaying the administration of DMARD therapy reduces the likelihood of patients achieving disease remission,^[2] and is associated with more rapid radiological progression and worse functional outcomes.^[3] Current guidelines, therefore, advocate the early and sustained use of DMARDs in RA; methotrexate and sulfasalazine are the most commonly prescribed.^[4-6]

With the earlier introduction of DMARD therapy, many rheumatologists have suggested the simultaneous use of different DMARDs. Different strategies (Figure 1) favor a step-up (sequential addition of new DMARDs to existing treatment), a step-down (initial use of multiple DMARDs with subsequent withdrawal once remission is achieved) or a parallel approach (simultaneous use of two or more DMARDs); however, there is no consensus regarding either the most effective strategy, or the combination of DMARDs for the treatment of RA.^[7]