Joint damage causes irreversible disability in rheumatoid arthritis (RA) and psoriatic arthritis. This damage relates to clinical disease activity and can be prevented by therapeutic interference with articular inflammation, especially when clinical remission is achieved.
During Monday’s Paul Klemperer, MD Memorial Lecture, From Progression to Remission & Prevention: The New World of Destructive Arthritis, Josef S. Smolen, MD, Emeritus Professor of Internal Medicine at the Medical University of Vienna, discussed the pathways to joint destruction in RA and reviewed evidence supporting the relationship between clinical disease activity and progression of articular damage.
“Rheumatoid arthritis used to be a progressively destructive joint disease leading to severe disability,” Dr. Smolen said. “However, over the last two decades, this has changed dramatically based on insights into the pathogenesis of RA and an increased understanding of the relationships between disease activity, joint damage, and physical disability.”
Those advances, he said, have led to the development of reliable clinical assessment instruments, the advent of new therapies, and the elaboration of treatment strategies.
“Pathogenetically, we now know that certain cytokines, such as TNF and IL-6, drive the inflammatory response, and that bony joint damage is due to activation of osteoclasts which derive from non-classical monocytes,” Dr. Smolen said. “Additionally, we have learned that joint damage is primarily driven by the extent of joint swelling as a clinical surrogate of articular inflammation and that both disease activity and joint damage contribute to disability, with the latter leading to irreversible disability.”
Consequently, he noted, interfering with inflammation by aiming at clinical remission is critical to preventing occurrence or progression of joint damage and optimizing physical function.
“Disease activity can be best assessed by so-called composite indices that comprise joint counts, such as the DAS28, the SDAI, and the CDAI,” he said. “The DAS28, however, does not capture remission sufficiently stringently, while SDAI and CDAI remission criteria do so and constitute the ACR/EULAR index-based remission definition. In remission as defined by SDAI or CDAI, joint damage is halted and physical function maximized.”
Dr. Smolen said that the optimal use of methotrexate, the availability of biological DMARDs, such as those targeting TNF, IL-6, or certain cell-surface molecules, and most recently, Janus kinase (JAK) inhibitors, have allowed rheumatologists to attain excellent outcomes in increasing proportions of RA patients.
“Adhering to the treat-to-target (T2T) strategy, which calls for a clinical improvement of at least 50 percent within three months and attainment of remission or low disease activity within six months or else a change of therapy, has maximized therapeutic success in up to 75 percent of RA patients,” he said. “Still, new therapies are needed for the residual, less-responsive 25 percent of the patients.”
All these aspects are important for the clinician, Dr. Smolen said, since the clinician has to regularly assess the patients’ disease activity using appropriate instruments while making timely therapeutic decisions.
Dr. Smolen said that recent and emerging advances show that it’s possible to reverse RA from a destructive and disabling condition to a non-destructive and non-disabling joint disease and attain a cure-like state.
“Regular assessment of disease activity using an index that comprises joint counts is of utmost importance and adhering to the T2T strategy with decision points at three and six months optimizes therapeutic success,” he said. “Given that we now have many therapies available, such a T2T strategy can be brought into reality for all patients.”