POS0594 MEANINGFUL IMPROVEMENT AND WORSENING IN PATIENTS WHO DO NOT ACHIEVE LDA AND SWITCH THERAPY TO A NEW BIOLOGIC OR TARGETED THERAPY: RESULTS FROM THE CORRONA REGISTRY
Authors: J. Curtis, S. Fiore, K. Ford, J. Janak, H. Chang, D. A. Pappas, T. Blachley, K. Emeanuru, V. Bykerk
Journal: Annals of the Rheumatic Diseases (2021)

Background: Guidelines recommend adjusting therapy in patients with rheumatoid arthritis (RA) who fail to reach and sustain low disease activity (LDA) or remission (disease control). Many factors can affect the decision to change therapy, including the potential for improvement as well as the fear of potential worsening or loss of improvement already achieved. Although data exist on response to treatment in patients who switch therapy, data addressing the likelihood of worsening are limited. Objectives: The aim of this analysis was to describe the demographic, clinical characteristics, and change in clinical outcomes in patients on biologic/targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) who had some improvement in clinical disease activity index (CDAI) but did not achieve LDA after ~ 6-12 months of treatment and then switched to a different b/tsDMARD. Methods: This study included adult inadequately responding RA patients from the CORRONA registry who: (1) started a biologic or Janus kinase inhibitor (JAKi) between January 2010 to November 2020 (V1), (2) had any CDAI improvement (i.e., decrease ≥1 unit) but were not in LDA or remission at a subsequent visit (baseline [BL]) occurring 3 to 15 months after V1; (3) had a third visit (follow-up [F/U]) 6 (±3) months after BL with a valid CDAI measure; (4) switched therapy at the BL or between BL and F/U, with the switch occurring at least 3 months prior to the F/U. CDAI &gt;10 and ≤22 was defined as moderate disease activity (MDA) and CDAI &gt;22 was defined as high disease activity (HDA). Two thresholds of change in CDAI (≥6 and ≥12 units) were used to define meaningful improvement and meaningful worsening after the switch. If there was no meaningful improvement or meaningful worsening, this was considered as no meaningful change (-5 to +5 for 6 units change and -11 to +11 for 12 units change). These thresholds for meaningful change were set for all switchers regardless of their pre-switch CDAI value. Descriptive statistics were generated for demographic and clinical characteristics for the switchers at BL, and the change of clinical outcomes was evaluated from BL to F/U. Results: Of the 1,224 patients fulfilling the inclusion criteria, 93 (7.6%) switched therapy and 1,131 (92.4%) did not switch therampy after not achieving an adequate response on the initial b/tsDMARD. At BL, 42.5% and 70.0% of patients had no meaningful improvement to their prior therapy based on ≥6 and ≥12-unit change, respectively; mean (SD) age was 53.1 (14.0) years; duration of RA 10.7 (10.4) years; CDAI 22.2 (10.8); 81.7% were female; 64.5% had MDA, 35.5% had HDA; 21.5 % reported being disabled, 24.7% were current smokers, and 50% were obese. In terms of prior biologic use 57.0%, 22.6%, and 20.4% had been on 1, 2, and 3+, respectively. From BL to F/U, meaningful worsening occurred in 30.1% and 12.9% using a threshold of 6 and 12, respectively, with the remaining patients experiencing meaningful improvement or no meaningful change (Figure 1). Figure 1. Meaningful Worsening, Meaningful Improvement, and No Meaningful Change Based on CDAI Change Thresholds of ≥6 and ≥12 From BL to F/U (N=93) Conclusion: In our analysis, a large proportion of patients who initiated a biologic/JAKi and experienced some improvement but failed to attain LDA or remission, did not switch therapy within approximately a year. This analysis consisted of many patients who did not have a meaningful response to their prior biologic/JAKi, patients who had received multiple prior biologics, and a large portion of patients with poor prognostic factors. Despite this, the proportion of patients with meaningful worsening was low compared with most patients who had either meaningful improvement or no meaningful change. Additional research is warranted to understand the reasons for not switching and whether the likelihood of a meaningful change correlates with prior response, poor prognosis, or other factors. Acknowledgements: Amy Praestgaard (Sanofi) contributed to the statistical analysis for this abstract. Medical writing support for this abstract was provided by Krishna Kammari (Sanofi). Disclosure of Interests: Jeffrey Curtis Grant/research support from: and personal fees from AbbVie, Amgen, BMS, CORRONA, Eli Lily, Janssen, Myriad, Pfizer, Roche, Regeneron, Radius, UCB, outside the submitted work, Stefano Fiore Shareholder of: Sanofi, Employee of: Sanofi. In addition, he has a patent EP 19306553.9; USPTO #s 62/799,698; 62/851,474; 62/935,395 issued, Kerri Ford Shareholder of: Sanofi, Employee of: Sanofi, Judson Janak: None declared, Hong Chang: None declared, Dimitrios A Pappas Employee of: CORRONA LLC. He has previously acted as a consultant for Sanofi, Abbvie, Gtech Roche Hellas, and Novartis. He has an equity interest in CORRONA LLC. and is on the Board of directors of the CORRONA research foundation, Taylor Blachley: None declared, Kelechi Emeanuru: None declared, Vivian Bykerk Grant/research support from: reports grants from Amgen, BMS, UCB, and Novartis were given to institution, that grants from the NIH, PCORI, and CIHR were given to institutions which whom she is affiliated, and that she has received personal fees from Amgen, Gilead, BMS, Pfizer, Sanofi Aventis, Roche, UCB and Regeneron, outside the submitted work.