FRI0138 Treat to target strategy plus certolizumab in comparison to continued, fixed csdmard plus corticosteroids in patients with rheumatoid arthritis and inadequate response to csdmards (REMISSION BY INTRA-ARTICULAR INJECTION PLUS CERTOLIZUMAB, THE RICE STUDY): a multi-centre randomised controlled trial
Authors: R. Mueller, M. Spaeth, C. von Restorff, C. Ackermann, J. von Kempis
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Treatment of rheumatoid arthritis (RA) includes the use of conventional (cs) or targeted synthetic (ts) and biologic disease-modifying anti-rheumatic drugs (DMARDs) and oral or subcutaneous (SC) glucocorticoids (GC). <h3>Objectives</h3> We aimed to test the hypothesis that an improved outcome can be achieved by employing a treat to target (T2T) strategy optimising csDMARD, oral, and SC-GC treatment in parallel to a new onset certolizumab pegol (CZP) in RA patients with an incomplete response to csDMARD as compared to a conventional step up strategy with CZP. <h3>Methods</h3> We designed a randomised controlled trial in four specialised rheumatological units. 43 patients with active RA (≥6 tender,≥6 swollen joints, and ESR ≥20 mm/h or CRP ≥7 mg/L) despite csDMARD treatment for ≥3 months and naïve to biologic DMARDs were randomly allocated either to CZP plus a treat to target strategy (T2T group, n=21) or add on of CZP to a fixed dose of the already established csDMARD with or without established GCs (fixed dose group, n=22). Patients of both groups received 400 mg CZP at week 0, 2, and 4 (loading dose), followed by 200 mg every 2 weeks. The T2T strategy consisted in a step up in, or to, SC-methotrexate (dose: 15≥20≥25 mg/week), followed by leflunomide (20 mg/d) and then by sulfasalazine (2 × 1000 mg/d). In parallel, oral GCs were initiated in the T2T group at 20 mg/d and tapered every 5 days (15–12.5–10–7.5–5–2.5–0 mg/d). The decision to take the next step in the DMARD modification and addition of oral GCs was taken depending on the achievement of LDA (low disease activity: DAS28 &lt;3.2) at the 4-weekly visits. Injections of up to five tender and/or swollen joints with triamcinolone (small joints 10 mg, intermediate 20 mg, and big joints 40 mg; max. 100 mg/visit) was allowed in the T2T group. The primary outcome measure was ACR 50 response after 24 weeks. The analysis was intention-to-treat. <h3>Results</h3> Three patients dropped out during the study (n=2 T2T, n=1 fixed dose). ACR 50 was achieved in 16 out 21 T2T patients (76.2%) as compared to 8 out of 22 fixed dose patients (36.4%; Chi<sup>2</sup>: 5.355, p=0.020). ACR 20 and 70 responses were achieved in 90.5% and 71.4% of the T2T patients and 59.1% and 27.3% of the fixed dose patients, respectively (p=0.045 and p=0.010, resp.). Mean reduction in DAS28 were significantly and HAQ-DI markedly greater in the T2T group than in the fixed dose group (DAS28: −3.9 [SD 1.2] vs. −2.2 [SD 1.5], p&lt;0.0006; HAQ-DI: −0.63 [SD 0.58] vs. 0.20 [SD 0.67], p&lt;0.14). All but five of the T2T patients required only one modification of csDMARD and one additional course of oral GC. 10.2 joints (mean) were infiltrated with triamcinolone in the T2T group (av. dose 14.1 mg/injection). The adverse event rate was similar for both groups (T2T n=51; fixed dose n=55). <h3>Conclusions</h3> Treat to target management with optimisation of csDMARDs, oral and intra-articular glucocorticoids of RA patients in parallel to additional CZP treatment was safe and substantially improves disease activity and the patient related outcome HAQ-DI in comparison to additional CZP to a fixed dose of csDMARDS. <h3>Disclosure of Interest</h3> R. Mueller Grant/research support from: Unlimited grant by UCB pharmaceuticals, M. Spaeth: None declared, C. von Restorff: None declared, C. Ackermann: None declared, J. von Kempis: None declared