POS0591 SARILUMAB ATTENUATES DISEASE ACTIVITY IN SERONEGATIVE RA PATIENTS – PRELIMINARY DATA FROM A NON-INTERVENTIONAL STUDY IN REGULAR CARE IN GERMANY
Authors: H. Burkhardt, H. P. Tony, P. M. Aries, S. Zinke, K. Krueger, J. Ahlers, R. Hecker, I. Albrecht, S. Kalus, O. Bley, P. Sternad, A. D. Holst, N. T. Baerlecken, T. Klopsch, M. Welcker, E. Feist
Journal: Annals of the Rheumatic Diseases (2021)

Background: Although seronegative RA patients often present with substantial disease burden [1], patients are underrepresented in research cohorts or clinical trials. Consequently, less knowledge about this subgroup has been accumulated. Objectives: To describe outcome of seronegative vs. seropositive RA patients treated with sarilumab in regular care in Germany. Methods: The prospective, observational, 24-month single-arm PROSARA study (SARILL08661) is currently running in Germany at 96 sites, aiming to enroll up to 750 RA patients treated with sarilumab. RA patients are prospectively selected at physician’s discretion according to label, and medical history is documented before treatment. This interim analysis included patients with data available up to 24 months. Here we focus on sustained treatment response after 6 and 12 months, respectively. Patients were stratified according to serostatus (RF- AND ACPA- as seronegative or RF+ AND/OR ACPA+ as seropositive). All analyses are descriptive only. Results: To date 473 patients were included in the study, of which 22.2% (n=105) were seronegative and 59.0% (n=279) were seropositive (Table 1). For 89 patients (18.8%) serostatus was not specified. Table 1. Baseline data regarding patient characteristics, prior treatment and disease activity seronegative seropositive patients [n] (%) 105 (22.2) 279 (59.0) patient characteristics Sex female [n] (%) 81 (77.1) 207 (74.2) Age mean [years] (SD) 56.6 (12.5) 59.6 (10.9) BMI mean (SD) [kg/m 2 ] 29.2 (6.7) 28 (6.0) Smoking history current/former [%] 22.1/11.5 25.5/20.4 Time since diagnosis of RA mean [years] (SD) 7.9 (7.6) 11.5 (9.9) prior RA treatment csDMARD [n] (%) 102 (97.1) 273 (97.8) bDMARD (TNFi) [n] (%) 54 (51.4) 167 (59.9) bDMARD (non-TNFi) [n] (%) 32 (30.5) 83 (29.7) tsDMARD (JAKi) [n] (%) 25 (23.8) 57 (20.4) disease activity CRP [mg/l] (SD) 12.9 (30.9) 14.2 (31.0) ESR [mm/h] (SD) 23.7 (20.5) 25.3 (22.4) SJC mean (SD) 5.3 (5.5) 4.6 (4.8) TJC mean (SD) 10.2 (8.2) 7.2 (6.6) HAQ-DI mean (SD) 1.4 (0.7) 1.2 (0.7) DAS28-ESR mean (SD) 5.0 (1.5) 4.6 (1.5) CDAI mean (SD) 27.7 (14.7) 23.0 (12.9) Fatigue [VAS] (SD) 64.0 (25.5) 51.1 (28.1) The mean time since diagnosis of RA was shorter in seronegative than in seropositive patients (7.9±7.6 years vs. 11.5±9.9 years) (Table 1). At baseline, CDAI score was 27.7±14.7 (n=104) and 23.0±12.9 (n=272) in seronegative and seropositive patients, respectively. After 12 months of sarilumab treatment, CDAI improved to 15.6±12.3 (n=38) and 9.1±8.7 (n=101) in seronegative and seropositive, respectively, for patients with post-baseline data available. At that time, remission/low disease activity according to CDAI was reached by 5.3% (n=2/38) / 39.5% (n=15/38) of seronegative patients, respectively and by 26.7% (n=27/101) / 68.3% (n=69/101) of seropositive patients, respectively (Fig. 1A, B). Figure 1. CDAI (A, B) and HAQ-DI (C) outcomes in seronegative and seropositive patients Physical function, assessed by HAQ-DI, was slightly more impaired in seronegative patients (1.4±0.7) than in seropositive patients (1.2±0.7) at baseline. HAQ-DI improved over 12 months to 0.9±0.7 in seropositive patients (n=90) but showed no change in seronegative patients (1.4±0.7; n=37) (Fig. 1C). Safety was consistent with the anticipated profile of IL-6-R-inhibition and no new safety signals occurred. Adverse events and serious adverse events were described in 61.7% and 12.8% of seronegative patients, respectively and in 55.2% and 13.7% of seropositive patients, respectively. Conclusion: Sarilumab treatment ameliorated CDAI in both seronegative (ΔCDAI -17.0±16.5) and seropositive (ΔCDAI -15.4±14.3) patients to the same extent over the course of 12 months, with a higher remission rate in seropositive patients. Functional capacity improved meaningfully in the seropositive cohort but had no significant impact in seronegative patients. The safety profile was consistent with data reported from controlled clinical trials. References: [1]Choi S-T et al. (2018) PLoS ONE 13(4): e0195550. Acknowledgements: We thank Cornelia Kühne (Haldensleben) for substantial contribution to patient recruitment in PROSARA. Disclosure of Interests: Harald Burkhardt Speakers bureau: Sanofi, Pfizer, Roche, Abb- vie, Boehringer Ingelheim, UCB, Eli Lilly, Chugai, Bristol Myer Scribb, Janssen, and Novartis, Consultant of: Sanofi, Pfizer, Roche, Abbvie, Boehringer Ingelheim, UCB, Eli Lilly, Chugai, Bristol Myer Scripps, Janssen, and Novartis, Grant/research support from: Pfizer, Roche, Abbvie, Hans-Peter Tony Consultant of: AbbVie, Astra-Zeneca, BMS, Chugai, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, Peer-Malte Aries Speakers bureau: Abbvie, Biogen, Berlin Chemie, Celgene, GSK, Hexal, Mylan, Novartis, Pfizer, UCB, Consultant of: Abbvie, Celgene, Hexal, Janssen, Medac, Novartis, Pfizer, Sanofi, UCB, Silke Zinke: None declared, Klaus Krueger Speakers bureau: Sanofi, Jonas Ahlers Employee of: Sanofi, Rolf Hecker Employee of: Sanofi, Inka Albrecht Employee of: Sanofi, Stefanie Kalus Consultant of: Sanofi, Oliver Bley Employee of: Sanofi, Patrizia Sternad: None declared, Ann-Dörthe Holst: None declared, Niklas Thomas Baerlecken: None declared, Thilo Klopsch: None declared, Martin Welcker Speakers bureau: Abbvie, Aescu, Amgen, Biogen, Berlin Chemie, Celgene, GSK, Hexal, Mylan, Novartis, Pfizer, UCB, Consultant of: Abbvie, Actelion, Aescu, Amgen, Cel- gene, Hexal, Janssen, Medac, Novartis, Pfizer, Sanofi, UCB, Grant/research support from: Abbvie, Novartis, UCB, Hexal, BMS, Lilly, Roche, Celgene, Sanofi, Eugen Feist Speakers bureau: Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Sanofi, Consultant of: Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Sanofi