Disease Activity is the Major Discriminator When Defining Refractory Rheumatoid Arthritis

M Bécède, JS Smolen, D Aletaha.

Medical University of Vienna, Vienna, Austria

Background/Purpose:

Rheumatoid arthritis (RA) is characterised by the presence of a progressively destructive joint inflammation. Even in times of modern therapeutics, a subgroup of patients continues to be refractory to numerous consecutive therapeutic interventions with regards to control of inflammation, joint damage. To date, there exists no definition for refractory RA.

Methods:

To explore different modifications of a definition for refractory RA, we a defined the base case of refractory RA as patients who had experienced ≥3 treatment courses (with at least one biological failure) over a minimum of 18 months since first treatment initiation (to avoid counting treatment courses that were given for a too short period), and the lack of reaching the treatment goal of low disease activity or remission (defined by a Clinical Disease Activity Index, CDAI, >10). We then modified our working definition based on these four variables (disease duration: 12/18/24 months; disease activity: moderate/high; number of treatment courses: ≥3/≥4; different biologic agents: ≥1/≥2.

Results:

From our clinic’s ongoing longitudinal data set we identified 68 refractory patients out of 688 RA outpatients. There was virtually no difference based on modifying disease duration, so we kept our working definition of a minimum disease duration of at least 18 months (n=464; 12 months: n=466; 24 months: n=453). Changing the disease activity component of the definition had a great impact on the identified refractory RA population, by requiring high instead of moderate disease activity (MDA: CDAI >10, n=129 vs. HDA: CDAI >22, n=31). In both, the MDA and the HDA group of patients, we could observe ≥60% of patients, who already experienced at least three treatment courses (MDA, n=82/129; HDA, n=21/31). Above a half in each group qualified as refractory also with the criterion of an addition fourth failed treatment course (MDA, n=64/129; HDA, n=15/31). When further stratifying patients based on the number of failed different biologic DMARDs, we could observe that regardless of the level of disease activity and number of failed treatment courses, most patients experienced at least one or even a second biologic agent (table).

Conclusion:

The level of disease activity is the major discriminator when defining a population of refractory RA. The duration of treatment does not significantly impact the identification of refractory RA. The number of failed treatment courses and insufficient responses to biologic DMARDs further helps characterizing patients with refractory RA. Considerations of the impact of these different characteristics of refractory disease may well inform future criteria for refractory RA.