SP0079 STRUCTURAL DAMAGE PROGRESSION IN RA – DOES IT STILL MATTER WITH IMPROVED MEDICAL AND NON-MEDICAL TREATMENTS
Authors: Désirée van der Heijde
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> The distinction between symptomatic and disease modifying drugs is based on inhibition of structural damage and preservation of physical function. Radiographs of hands and feet are typically used to assess structural damage in RA. They provide a good representation of overall damage of all joints and bone erosions and joint space narrowing can be assessed reliably. Structural damage is the consequence of inflammation and is related to permanent loss of function and other outcomes important to patients such as work and quality of life. In cohorts of RA patients followed in the eighties of the twentieth century, the average progression rate was about 7 units of the modified Sharp score. This was still the case in the control arms of the RCTs in the nineties and early zeros. However, in recent trials the progression in the control arms is reduced to around 1 unit per year. There are several reasons for this reduced progression observed in clinical trials. First, the duration of placebo is limited to a maximum of 12-16 weeks for ethical reasons. Consequently, there is only restricted time to develop radiographic damage. Second, more frequently an active comparator is used instead of placebo. Third, there is better overall standard of care. Fourth, inclusion of patients with less severe disease in RCTs. Moreover, some speculate that there is a trend to a milder form of RA, however this is hard to proof. For all these reasons, it is essential to enrich the population with patients with a higher chance of showing radiographic progression over the (short) period of the RCT To enhance the probability of proving a reduction in radiographic progression. These factors include ACPA/RF-positivity, erosive disease and elevated CRP. It is frequently asked if a reduction of the mean progression of 1 unit in the control arm to the mean progression of 0.5 unit in the treatment arm is clinically relevant. However, clinical relevance cannot be based on mean progression scores due to the skewness of the progression: many patients do not show progression, while a minority show (major) progression. A reduction in the likelihood of (significant) progression by treatment A over treatment B could already provide more useful information. Moreover, people tend to relate the '1 unit" to the maximum score of 448 units of the scale. Though, it is important to realise that a patient with a score of 50 already has major damage and that RA is a chronic disease with many patients suffering for many years. But true clinical relevance of structural damage needs to be established in observational cohorts over longer follow-up times. Despite the limited radiographic progression in the control arms of RCTs, it was possible to show the disease modifying effect by inhibition of structural damage progression for csDMARDs (mainly MTX), all bDMARDs and tsDMARDs currently on the market. <h3>Disclosure of Interests:</h3> Désirée van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, Union Chimique Belge