Characterisation of a basket trial population for arthritis associated with ana-positive rmds

Abstract Background/Aims Musculoskeletal inflammation is the most common reason for the inclusion of patients in SLE trials or biologic use. It is also common across other ANA-associated diseases, but these patients do not have access to the same therapies as SLE patients despite a seemingly similar problem. Our aims were to test whether (i) patient-reported impact and (ii) immunological profile of MSK inflammation are equivalent across ANA-associated diseases; (iii) identify features that stratify ANA-associated arthritis; (iv) explore the criterion validity of BILAG-MSK in other ANA-associated arthritis. Methods We used cross-sectional analysis of patient-reported outcome measures, antibody, gene expression and flow cytometric data from a study of mixed ANA-associated diseases (DEFINITION). The clinical and immunological implications of legacy diagnosis membership were analysed by comparing QoL measures (SF36, EQ5D-5L, Patient VAS, ICECAP-A, FACIT-F, WPAI and ICECAP-A), gene expression scores (2 IFN Scores, neutrophil, plasmablasts, myeloid and inflammation scores) and flow cytometry using Kruskal Wallis tests. The association between the BILAG MSK domain and physician arthritis VAS was tested for SLE and non-SLE patients. Results Of 300 patients, 215 had current or prior joint or tendon inflammation. Only FACIT-F and EQ5DL-5L showed trends to difference between diseases, being worst in the MCTD group. No other clinical or immunological variable differed between groups (Table 1). However, significant associations were found for non-disease-specific variables; worse EQ5D-5l index scores were associated with chromatin antibody positivity (T-Test, p < 0.001) and non-European ancestry (T-Test, p < 0.05). There was a significant association between BILAG-MSK and physician arthritis VAS in both SLE (Kruskal Wallis Chi-Sq=56.8, p < 0.0001), and non-SLE (Kruskal Wallis Chi-Sq=17.468, p < 0.001) patients. Conclusion Patients with ANA-associated arthritis appear clinically homogenous across legacy diagnoses so performing trials in a basket population appears appropriate and may be more clinically homogenous than populations currently included in SLE trials who have mixed organ involvement. Furthermore, such a basket trial could benefit from an organ-specific outcome measure, which our preliminary analysis of BILAG-MSK suggests would be valid. Predictors of worse symptoms are not specific to individual diseases, including autoantibody profile and ancestry. Disclosure J. Arnold: None. L. Carter: Consultancies; UCB. S. Hassan: None. K. Dutton: None. Z. Wigston: None. S. Dass: Consultancies; Roche, Abbvie, UCB and Chugai. Honoraria; Roche, Abbvie, UCB and Chugai. M. Md Yusof: Consultancies; Aurinia and, UCB. E. Vital: Consultancies; Roche, GSK, AstraZeneca, Aurinia, Lilly, UCB and Novartis. Grants/research support; Roche, AstraZeneca and Sandoz.