SAT0188 Tocilizumab in early rheumatoid arthritis delivers clinical and ultrasound-confirmed rapid and deep remission with abolition of pd – tremera study

Background: Tocilizumab (TCZ) has shown impressive outcomes in early RA (ERA) with clinical remission rates of up to 80%1. The speed and depth of remission of TCZ in treatment-naive ERA have not been specifically evaluated. Objectives: To evaluate the rate and depth of clinical and imaging response and remission, and timing of optimal response in ERA. Methods: A prospective, open-label, RCT of active (DAS28 ≥3.2), new-onset (symptom duration ≤12 months) treatment-naive RA (2010 ACR/EULAR RA classification criteria), randomised 1:1, and treated with either TCZ 8 mg/kg (4-wkly) monotherapy or TCZ 8 mg/kg (4-wkly) and methotrexate (MTX) combination for 48 weeks. Clinical response/remission rates, and patient reported outcomes (PRO) were evaluated at early (wks 4 and 12) timepoints, and wks 24 and 48. High resolution US dominant hand (±other baseline active joints) was performed at baseline, wks 12, 24 and 48. Odds ratios were calculated using Firth logistic regression. Results: 20 pt [16 female; 13 RF+, 15 ACPA+; mean(SD) age 55.25(12) years] were recruited; baseline mean(SD) DAS28-ESR 5.98(1.21), HAQ 1.64(0.67). High-hurdle endpoints: at wk4, 30%, 95% and 35% achieved DAS28-ESR rem, EULAR and ACR50 response respectively; and continued to increase, peaking at wk48 with 67%, 93% and 63% respectively [OR wk4 1.0, 0.3, 0.7 and wk48 1.4, 3.0, 4.0 respectively]. Sustained DAS28-ESR remission (8 successive weeks) was observed in 40%; chisq=0.5, p=0.462; mean (90% CI) time to remission 38.3 (33.2, 43.3) wks. PRO: Baseline median(IQR) VASGH 56.5(29,71.5) improved by wk4 to 24(14,54), maintained wk48 24.5(3.5,46.5); VASDA from 62(54,77.5) to wk4 22(12.5,49.5), further improved by wk48 14.5(3.5,44.5); VASPain from 63.5(42,77) to wk4 19.5(4,53), maintained wk48 17.5(2.5,49.5). Similarly, median(IQR) HAQ at baseline 1.63(1.25,2.13) decreased by wk4 1.13(0.19,2.0) and wk48 0.75(0.19,1.38). Ultrasound: Baseline mean grey scale (GS) and power Doppler (PD) (as well as DAS28-ESR) are shown in the figure below, illustrating rapid reduction by wk4 that continued through the study period to all achieving PD=0 by wk48. Baseline median (IQR) erosions 0 (0, 0) remained unchanged throughout study. Baseline GS and PD appeared to associate with achievement of DAS44ESR remission (p=0.038 and p=0.043 respectively). No meaningful numerical differences between the two treatment arms was recorded. Conclusions: Conclusion TCZ in ERA (both monotherapy and TCZ/MTX combination) was associated with rapid clinical and imaging improvements, strikingly abolishing PD; with sustained remission in almost half the patients. The peak imaging response was noted at 48 weeks. Impressively, rapid PRO improvement was also observed. These data indicate convincing patient-relevant, imaging-determined depth of remission in a new-onset, treatment-naive RA cohort. Reference [1]Bijlsma JWJ, et al. Lancet2016; 388:10042;343–355. Acknowledgements: This was an investigator-initiated study supported by Roche pharmaceuticals. Disclosure of Interest: L. Hunt: None declared, E. Hensor: None declared, K. Naraghi: None declared, R. Wakefield: None declared, P. Emery Grant/research support from: Abbvie, AstraZeneca, Pfizer Ltd, Roche, Consultant for: Abbvie, AstraZeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Sandoz, M. Buch Grant/research support from: Pfizer Ltd, Roche, Consultant for: Abbvie, BMS, Eli Lilly, Pfizer, Roche, Sandoz