Superiority of a Treat-to-Target Strategy over Conventional Treatment with Fixed csDMARD and Corticosteroids: A Multi-Center Randomized Controlled Trial in RA Patients with an Inadequate Response to Conventional Synthetic DMARDs, and New Therapy with Certolizumab Pegol

Ruediger B Mueller; Michael Spaeth; Cord von Restorff; Christoph Ackermann; Hendrik Schulze-Koops; Johannes von Kempis

doi:10.3390/jcm8030302

Superiority of a Treat-to-Target Strategy over Conventional Treatment with Fixed csDMARD and Corticosteroids: A Multi-Center Randomized Controlled Trial in RA Patients with an Inadequate Response to Conventional Synthetic DMARDs, and New Therapy with Certolizumab Pegol

J Clin Med. 2019 Mar 3;8(3):302. doi: 10.3390/jcm8030302.

Authors

Ruediger B Mueller^{1

2

3}, Michael Spaeth⁴, Cord von Restorff⁵, Christoph Ackermann⁶, Hendrik Schulze-Koops⁷, Johannes von Kempis⁸

Affiliations

¹ Division of Rheumatology and Immunology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland. Ruediger.Mueller@ksa.ch.
² Division of Rheumatology and Clinical Immunology, Department of Internal Medicine IV, Ludwig-Maximilians-University Munich, 80336 Munich, Germany. Ruediger.Mueller@ksa.ch.
³ Division of Rheumatology, Medical University Department, Kantonsspital Aarau, CH-5001 Aarau, Switzerland. Ruediger.Mueller@ksa.ch.
⁴ Division of Rheumatology, Spital Linth, 8730 Uznach, Switzerland. michael.spaeth@spital-linth.ch.
⁵ Medical practice, 8708 Männedorf, Switzerland. vonrestorff@hin.ch.
⁶ Medical practice, 9495 Triesen, Liechtenstein. ackermann.c@gmx.net.
⁷ Division of Rheumatology and Clinical Immunology, Department of Internal Medicine IV, Ludwig-Maximilians-University Munich, 80336 Munich, Germany. Hendrik.Schulze-Koops@med.uni-muenchen.de.
⁸ Division of Rheumatology and Immunology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland. johannes.vonKempis@kssg.ch.

Abstract

Background: Treatment of rheumatoid arthritis (RA) includes the use of conventional (cs), biologic (b) disease-modifying anti-rheumatic drugs (DMARDs) and oral, intramuscularly, intravenous, or intraarticular (IA) glucocorticoids (GCs). In this paper, we analysed whether a treat-to-target (T2T) strategy optimizing csDMARD, oral, and IA-GC treatment as an adjunct new therapy to a new certolizumab pegol (CZP) therapy improves the effectivity in RA patients.

Methods: 43 patients with active RA (≥6 tender, ≥6 swollen joints, ESR ≥ 20 mm/h or CRP ≥ 7mg/L) despite csDMARD treatment for ≥ 3 months and naïve to bDMARDs were randomized to CZP (200 mg/2 weeks after loading with 400 mg at weeks 0⁻2⁻4) plus a treat-to-target strategy (T2T, n = 21), or to CZP added to the established csDMARD therapy (fixed regimen, n = 22). The T2T strategy consisted of changing the baseline csDMARD therapy (1) SC-methotrexate (dose: 15 ≥ 20 ≥ 25 mg/week, depending on the initial dose) ≥ leflunomide (20 mg/d) ≥ sulphasalazine (2 × 1000 mg/d) plus (2) oral GCs (prednisolone 20⁻15⁻12.5⁻10⁻7.5⁻5⁻2.5⁻0 mg/d tapered every five days) and (3) injections of ≤5 affected joints with triamcinolone. DMARD modification and an addition of oral GCs were initiated, depending on the achievement of low disease activity (DAS 28 < 3.2). The primary objective was defined as the ACR 50 response at week 24.

Results: ACR 50 was achieved in 76.2% of the T2T, as compared to 36.4% of the fixed regimen patients (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 regimen patients, respectively (p = 0.045 and p = 0.010, respectively). The adverse event rate was similar for both groups (T2T n = 51; fixed regimen n = 55).

Conclusion: Treat-to-target management with the optimization of csDMARDs, oral, and IA-GCs of RA patients in parallel to a newly established CZP treatment was safe and efficacious in comparison to a fixed regimen of csDMARDs background therapy.

Keywords: ACR response; DAS 28; HAQ-DI; certolizumab pegol; csDMARDs; glucocorticoids; intra-articular injections; rheumatoid arthritis; treat-to-target.