OP0201 REASONS FOR TREATMENT FAILURE: A COMPARISON BETWEEN “MULTI-REFRACTORY” AND “DIFFICULT-TO-TREAT” RHEUMATOID ARTHRITIS PATIENTS
Authors: G. Maioli, G. Cincinelli, C. Posio, F. Ingegnoli, E. G. Favalli, R. F. Caporali
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Despite incredible progress in rheumatoid arthritis (RA) therapy, a substantial number of patients remain unresponsive to multiple treatments. These include patients who have high disease activity despite the use of two or more biotechnological or synthetic targeted DMARDs (b/tsDMARDs) with different mechanism of action (MOAs), identified as difficult-to-treat (D2T) patients. <h3>Objectives:</h3> The aim of the study is to analyse the clinical characteristics of RA patients who have failed at least two lines of b/tsDMARDs therapy and to understand whether D2T patients differ from multi-refractory patients with regard to the reasons for treatment failure. <h3>Methods:</h3> A retrospective analysis of data from patients with RA treated with b/tsDMARDs included in a single-centre Italian registry was performed. Four categories of patients were identified and analysed: non-refractory, refractory to at least 2 lines of therapy, refractory to drugs with at least 2 different MOAs, and D2T according to the 2021 EULAR definition. Four reasons for discontinuation were identified: primary inefficacy, secondary inefficacy, adverse event or malignancy. Comparison analyses were performed using the chi-squared test for categorical variables and analysis of variance (ANOVA) for continuous variables. <h3>Results:</h3> The study population included 610 patients with RA (83% female, median age [±SD] 59 years [±12.5], median disease duration 17.3 [±11.5] years). Seventy-five percent (458/610) of the patients had never failed first-line therapy. Among the refractory patients (149/610), 104 patients (17%) failed at least 2 drugs with different MOAs and 42 patients (7%) met the EULAR definition of 'difficult-to-treat' patients. Comparative analysis showed that D2T patients were statistically significantly different from the other patient categories in terms of younger age at disease onset (p=0.007) and longer disease duration (p&lt;0.0005). It was also observed that the time from diagnosis to initiation of b/tsDMARDs drug therapy was significantly longer in D2T patients than in patients refractory to at least two MOAs (mean 120.6 [±105.9] months vs. 93.5 [±103.8] months, respectively [p=0.008]). With the exception of a higher prevalence of fibromyalgia in multi-refractory and D2T patients than in non-refractory patients, there were no significant differences in seropositivity, presence of erosions and comorbidities (Table 1). On average, the number of failed drug lines did not differ between the different categories of multi-refractory patients (p=0.249). Regarding the causes of failure, an average of 71.6% of treatments were discontinued due to inefficacy (24.3% primary and 47.3% secondary) and 28.4% due to an adverse event or malignancy, with no statistically significant differences between patient categories (p=0.25) (Table 2). <h3>Conclusion:</h3> Difficult-to-treat patients represent 7% of our cohort and are characterised by earlier disease onset and later initiation of targeted therapy. The main reason for discontinuation of the different therapeutic lines is inefficacy (primary or secondary) of the drug, regardless of the number of drug lines used or the number of MOAs the patient has undergone. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>