Difficult-to-treat RA: are we any closer to predicting who is at risk? Save

It is almost four years since EULAR published its definition of difficult-to-treat (D2T) rheumatoid arthritis (RA) (1). This marked a formal recognition of the group of patients who, despite the advances in pharmacological therapy for RA, remain symptomatic.

The final definition comprised three elements: (1) treatment failure history; (2) characterisation of active/symptomatic disease; and (3) clinical perception. All three criteria need to be present to confirm the state of D2T RA. Points to consider on management of patients with D2T RA came shortly after, encompassing guidance on pharmacological and non-pharmacological interventions as well as a reminder to consider broader concepts such as goal setting, self-efficacy and impact of comorbidities (2, 3).

Given up to 30% of individuals with RA have D2T disease, the ability to identify who is most at risk is desirable for optimal management.

Abstract OP0131 discussed predictors of multiple DMARD treatment failure within the Swedish Quality Rheumatology Register. Included patients were divided into three defined groups: 1) patients followed from RA diagnosis; 2) patients starting a DMARD for the first time; and 3) patients starting a b/tsDMARD for the first time. The first criterion in the EULAR D2T definition was applied to define two outcomes: 1) ‘Definition 1’ was defined as failure of ≥3 b/tsDMARDs; 2) ‘Definition 2’ was defined as failure of ≥2 b/tsDMARDs with different mechanisms of action.

A key strength of this study is its large sample sizes, with a total of 17780 patients in group 1, 18038 in group 2 and 7957 in group 3. In group 1, in the multivariable logistic regression analysis, female gender, younger age, higher HAQ, fatigue, pain and seropositivity at baseline were significantly associated with outcome 1, with similar findings observed for outcome 2. In groups 2 and 3, higher disease activity, no concomitant csDMARD, ongoing treatment with glucocorticoids, but not pain, were significantly associated with outcome 1, with similar observations for outcome 2.

Overall, it was found that approximately 8% of all patients failed ≥3 b/tsDMARDS, with a median time to failure of four years. Furthermore, up to 25% of patients starting their first b/tsDMARD fail two or more b/tsDMARDs within three years. The overall risk of fulfilling the first criterion of the EULAR D2T definition was 2.3% in the first five years following a diagnosis of RA.

This study provides a unique insight into a large group of patients with RA as to the factors which may be associated with recurrent treatment failure. The presence of factors such as fatigue and pain once again bring home the need for a holistic approach to management in RA. This abstract is just one of several focusing on D2T RA at EULAR 2024. This certainly highlights the growing awareness, and perhaps prevalence, of D2T disease. Studies such as this one continue to shed light on the challenges associated with, and potential facilitators for, managing D2T RA.

1.Nagy G, Roodenrijs NM, Welsing PM, Kedves M, Hamar A, Goes MCvd, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. BMJ Publishing Group Ltd; 2021. p. 31-5.

2. Nagy G, Roodenrijs NMT, Welsing PMJ, Kedves M, Hamar A, Goes MCvd, et al. EULAR points to consider for the management of difficult-to-treat rheumatoid arthritis. BMJ Publishing Group Ltd; 2021. p. annrheumdis-2021-220973.

3. Dey M, Rgy Nagy G, Nikiphorou E. Comorbidities and extra-articular manifestations in difficult-to-treat rheumatoid arthritis: different sides of the same coin? : Oxford University Press (OUP); 2022.