PO:06:078 | Is difficult-to-treat rheumatoid arthritis less severe in patients with autoantibody-negative disease? retrospective analysis from a monocentric cohort.

Bernardo D'Onofrio¹, Maria Chiara Ditto¹, Francesco Ghellere¹, Giacomo Tanti¹, Salvatore Panaro¹, Enrico Fusaro¹, Simone Parisi¹. | ¹AOU Città della Salute e della Scienza, Torino, Italy.

Abstract

Background. Patients with rheumatoid arthritis (RA) are at higher risk of radiographic progression, joint damage, disability, and extraarticular manifestations when autoantibodies – such as rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) are presents. Moreover, most of RA cohorts report an association between autoantibodies and polyrefractory – or difficult-to-treat (D2T) disease. However, at the moment, no data evaluated whether autoantibody-negative D2T is actually less severe than its seropositive counterpart.

Methods. Data were retrieved from a cohort of RA patients under targeted-therapy [Turin Targeted-Therapies clinic (TTT), n=636], followed from the year 2000 onwards. D2T disease was defined according to the European Alliance of Associations for Rheumatology (EULAR) criteria; patients who interrupted drugs for safety/adverse events were excluded. Time-to-develop the D2T state (defined as the difference between disease onset and the time point when fulfilling the D2T criteria) was stratified for autoantibody status by Mann-Whitney U analysis. Also, disease activity state, joint deformities, extraarticular manifestations, the number of swollen joints on 28 evaluated (SJC28), the number of tender joints on 28 evaluated (TJC28), pain expressed by a visual analogue scale (VAS), the health assessment questionnaire (HAQ), and other patient reported outcomes were evaluated at the D2T time point both in seropositive and -negative patients by multivariate linear logistic regression or Mann-Whitney U test, as appropriate.

Results. From the original cohort, 189/636 (30%) interrupted at least two targeted therapies, and 132/636 (21%) fulfilled EULAR D2T criteria, 100 of them (76%) with seropositive RA. Time-to-achieve the D2T state was significantly shorter in seronegative vs. seropositive patients (mean Rank 58.89 for seronegative vs. 77.04 for seropositive; p=0.024). At the D2T-time point, patients with autoantibody-positive RA had more extraarticular manifestations [OR (95% CI) of 8.64 (1.08-69.04); p=0.042], joint deformities [OR (95% CI) of 2.842 (1.11-7.29); p=0.030], and a higher number of SJC28 (p<0.001), compared to seronegative ones. On the opposite, in face of a similar DAS28 and grade of disability expressed by the HAQ (p=ns), autoantibody-negative RA patients showed higher values of VAS pain (p=0.006), patient global assessment (PGA) (p<0.001), ad morning stiffness (p=0.009).

Conclusions. D2T disease is similarly impactful in autoantibody-positive and -negative patients with RA. Despite a lower number of swollen joints, deformities and extraarticular features, patients with autoantibody-negative D2T RA are burdened by worst patients reported outcomes, suffering from much pain and morning stiffness. Strategies aimed to reduce the symptomatic burden of RA in seronegative patients are urgently needed.

Keywords

• Difficult-to-treat
• Autoantibodies
• Patient-reported outcomes