In certain autoimmune diseases, the use of biologics is providing an enormous contribution to disease stabilization and the prevention of complications. Compared to the use of biologics in RA, the use of biologics in SLE has been slower, likely due to the differences in the pathogenesis of the two diseases and the inter-individual variety of manifestations and therapeutic needs in SLE patients.
Despite the relative novelty in the use of biologics in SLE, the field is showing promise, and new investigations are fueled by the encouraging results from recent clinical trials. The hope is to possibly find new drugs that can be partly devoid of the significant side effects that characterize the use of immunosuppressive drugs - widely used in the disease management - while providing effectiveness in inducing disease remission or in reducing disease activity. More specificity of action, a targeted use, and improved efficacy, are the major goals expected for new drugs that might be approved for the treatment of SLE in a near future.
Another consideration is that the critical evaluation of the failures of past clinical trials has been somehow instrumental in improving the design of newer trials. One example is the selection of seropositive SLE patients in the benlysta phase III trials after the negative results of the phase II studies.
Additional aspects improving trial design have included and will include the use of better instruments for the measurement of outcomes, better selection of endpoints, pre-identification of possible responders and subsetting of patients with common characteristics, choice of disease status and duration at enrollment, organ involvement, concomitant therapy, and possibly even consideration on the genetic backgrounds. Timing of response, bioavailability and duration of effects, in addition to best dosing to avoid side effects, should be the additional parameters to take into account. Statistical power has also frequently been a problem due to the clinical diversity of SLE patients, and trials with large numbers of patients may be required to obtain meaningful information. Ultimately, the goal is to find new targeted effective therapies in SLE that may allow a better clinical management, a more favorable prognosis, and an improved quality of life for SLE patients.
- B cells are major targets in the design of new approaches for a better management and therapy of SLE because they produce pathogenic autoantibodies that are implicated in the development of tissue and organ damage.
- Several surface markers expressed by B cells at different stages of their differentiation have been targeted in clinical trials for the modulation of B cell activity in the disease.
- The blockade of B-lymphocyte stimulator (BLyS) in recent clinical trials seems at present to be the most effective novel B cell-targeted approach capable to reduce clinical disease activity in certain subgroups of SLE patients.