Biologic Agents in Rheumatoid Arthritis
Over the past 2 decades, considerable advances in the management of rheumatoid arthritis (RA) have been made and good results achieved in increasing numbers of patients. The treatment goal in RA is remission, and a large number of conventional and biologic medications are currently available to reach this aim.
In current practice, upon diagnosis of RA, patients usually are given conventional disease-modifying antirheumatic drugs (DMARDs), sometimes combined with glucocorticoid injections or oral glucocorticoids in low doses; combinations of conventional DMARDs can be considered at an early stage as well. If disease activity is not fully controlled despite optimized conventional DMARDs, treatment with biologic agents is recommended.
Because anti-tumor necrosis factor (TNF) agents were among the earliest biologic agents approved, they are often considered first at this stage. However, the inhibitor of T-cell costimulation abatacept and the interleukin (IL)-6 antagonist tocilizumab are also approved in this setting, and clinical trial data also support the off-label use of rituximab for such patients. In practice, the biologics are usually added to the DMARDs that the patient is on, and the combination of biologics with a DMARD -- particularly methotrexate (MTX) -- has become one of the keystones of antirheumatic therapy.
Several clinical trials have demonstrated that frequent monitoring using a prespecified target will provide better overall results, even though this may also lead to more use of glucocorticoids, and will certainly lead to higher costs compared with 3-monthly follow-up or making treatment choices simply on the basis of clinical impressions. This successful approach of having frequent visits and a clear therapeutic target is referred to as "treat-to-target" and has been supported both by data and by expert groups.
However, when applying treat-to-target and using remission as the target, it has become clear that a significant proportion of patients with RA will need a biologic treatment at some stage after optimized monotherapy or combination therapy with conventional DMARDs has failed. In healthcare settings where no major impediments exist to the use of biologics, up to 50% of patients with RA might end up on biologics, at least among those with moderate or severe disease.
For most patients who have been started on a biologic treatment, it is anticipated that such treatment will have to be continued indefinitely, and because of the high cost of this class of drugs, there is a legitimate long-term health-economic concern. Is there an alternative to simply restricting, on economic grounds, the use of biologics beyond what is medically reasonable? I believe that 2 promising approaches are currently emerging that could help resolve this painful dilemma: induction-maintenance therapy, and dosing-down of biologics.