Optimal responses in disease activity scores to treatment in rheumatoid arthritis: Is a DAS28 reduction of >1.2 sufficient?

Abstract

BackgroundThe overall benefit of intensive treatment strategies in rheumatoid arthritis (RA) remains uncertain. We explored how reductions in disability and improvements in quality of life scores are affected by alternative assessments of reductions in disease activity scores for 28 joints (DAS28) in two trials of intensive treatment strategies in active RA.MethodsOne trial (CARDERA) studied 467 patients with early active RA receiving 24 months of methotrexate monotherapy or steroid and disease-modifying anti-rheumatic drug (DMARD) combinations. The other trial (TACIT) studied 205 patients with established active RA; they received 12 months of treatment with DMARD combinations or biologic agents. We compared changes in the health assessment questionnaire (HAQ) and Euroqol-5D (EQ5D) at trial endpoints in European League Against Rheumatism (EULAR) good and moderate EULAR responders in patients in whom complete endpoint data were available.ResultsIn the CARDERA trial 98 patients (26 %) were good EULAR responders and 160 (32 %) were EULAR moderate responders; comparable data in TACIT were 66 (35 %) and 86 (46 %) patients. The magnitude of change in the HAQ and EQ5D was greater in both trials in EULAR good responders than in EULAR moderate responders. HAQ scores had a difference in of –0.49 (95 % CI –0.66, –0.32) in the CARDERA and –0.31 (95 % CI –0.47, –0.13) in the TACIT trial. With the EQ5D comparable differences were 0.12 (95 % CI 0.04, 0.19) and 0.15 (95 % CI 0.05, 0.25). Both exceeded minimum clinically important differences in HAQ and EQ5D scores.ConclusionsWe conclude that achieving a good EULAR response with DMARDs and biologic agents in active RA results in substantially improved mean HAQ and EQ5D scores. Patients who achieve such responses should continue on treatment. However, continuing such treatment strategies is more challenging when only a moderate EULAR response is achieved. In these patients evidence of additional clinically important benefits in measures such as the HAQ should also be sought.

Defining response to TNF-inhibitors in rheumatoid arthritis: the negative impact of anti-TNF cycling and the need for a personalized medicine approach to identify primary non-responders

“…For non-responders, prolonged anti-TNF treatment is costly and unnecessary and may be associated with potentially harmful side effects such as infusion or injection site reactions, infections, tuberculosis, malignancy, lupus-like syndromes, demyelinating syndromes, and/or the appearance of blocking auto-antibodies [1,3,26]. Hence, long-term treatment is not recommended for patients who do not respond to therapy [6]. Yet, it is common practice for primary non-responders to anti-TNF drugs to receive multiple anti-TNFs for prolonged periods, often years [61].…”

“…The variety of molecular inflammatory pathways activated in RA patients may determine each individual's response to treatment, as recently approved therapies for RA treatment are molecularly targeted. The advent of personalized [3] or precision [4] medicine (PM) for RA will make it possible to determine if an individual will respond to a specific targeted treatment, improving a clinician's ability to "treat-to-target" [5,6], which is the primary goal of RA therapy. Treat-to-target is the foundation of the American College of Rheumatology (ACR) [7] and the European League Against Rheumatism (EULAR) [8], and their current guidelines for RA treatment define the target as achieving either remission or, if remission is not possible, achieving low disease activity (LDA).…”

Entropy Production Associated with Aggregation into Granules in a Subdiffusive Environment

“…The aggregation of segments of hyaluronic acid into granules is an example with biomedical significance. Hyaluronic acid is a biopolymer that is present in large concentration in the synovial fluid [ 2 , 3 ]. In a healthy synovial joint, the synovial fluid reduces friction and absorbs shocks.…”

“…For the synovial fluid to exhibit optimal viscoelasticity, the hyaluronic acid needs to have the right amount of aggregation. Understanding the physics of the growing and shrinking of granules can be important for the understanding and treatment of many types of arthritis [ 3 ].…”

Patients’ conceptions of their own influence on good treatment response to biological therapy in chronic inflammatory arthritis

“…The European League Against Rheumatism classifies good treatment response as DAS28 ≤3.2 with reductions in DAS28 of more than 1.2 points 11. Patients with good treatment response achieve an improvement in physical function and quality of life 12. Despite the fact that many patients respond well to their biological therapies, about one-third are nonresponders 6,13,14…”