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CHICAGO—Josef S. Smolen, MD, professor of internal medicine and chair of the Department of Rheumatology, Vienna General Hospital, Austria, presented the prestigious Paul Klemperer, MD, Memorial Lecture at the 2018 ACR/ARHP Annual Meeting. Dr. Smolen, whose work is frequently cited, created the treat-to-target strategy for rheumatoid arthritis (RA).
Dr. Smolen began by noting a simple examination of the pathology of RA reveals it is an inflammatory disease of the synovial membrane that leads to disability. Unfortunately, researchers still do not know what elicits the disease or which type of T cell is activated in the disease. Instead, most of the knowledge about RA centers on the final stages and the destructive work of the disease.
The realization that cells and cytokines are associated with the damage of RA still leaves unresolved the question of which abnormalities drive the progression of joint damage. The damage is clearly associated with inflammation, which is clinically visible as joint swelling and a higher affected joint count, Dr. Smolen explained. A confounder in this association is that patients with no swollen joints can have a high inflammatory serological response with no progression of joint damage.
Although composite measures of disease activity should include joint counts, Dr. Smolen stated, another important factor drives damage in RA: autoimmunity. Autoimmunity results in the formation of immune complexes that can activate complement and increase the inflammatory response. From this information, Dr. Smolen derived the hypothesis that it may be possible to prevent joint damage by interfering with inflammation and achieving remission.
From this goal, Dr. Smolen explained, stem the questions: How is the progression of joint damage best stopped? Is it possible to achieve early remission and sustained remission? When attempting to answer these questions, rheumatologists discovered even patients who achieved remission shortly before their second year had some disease progression.1 In contrast, patients who were able to achieve an earlier and durable remission were able to halt the progression of joint damage. Further research suggested tumor necrosis factor inhibitors were the most effective drugs for inhibiting joint damage.2
Disease Progression
Typically, RA outcomes are measured by the ACR70 criteria. What rheumatologists began to see, however, was patients could more easily achieve remission than they could meet the ACR70 criteria. This suggested remission was somehow separate from the response to treatment documented by the ACR70. Dr. Smolen explained this difference is probably at least partly due to the way the hand is constructed. The patient with early disease has disability as a result of stiffness or pain from disease activity, and the disability can be fully reversed with treatment. In contrast, a patient with longstanding disease has disability, not from disease activity, but from the damage itself. The disability in this patient is the consequence of joint destruction. So this latter patient will experience permanent disability in the face of clinical remission.
Dr. Smolen explained that a patient with a modified Sharp score of 50 or higher will likely not show much response to treatment because such a patient has physical disability associated with cartilage damage. The treatment goal for patients with RA becomes to stop inflammation as quickly as possible to optimize physical function.