PMID- 32248829 OWN - NLM STAT- MEDLINE DCOM- 20210118 LR - 20210118 IS - 1745-6215 (Electronic) IS - 1745-6215 (Linking) VI - 21 IP - 1 DP - 2020 Apr 5 TI - Effectiveness of TOcilizumab in comparison to Prednisone In Rheumatoid Arthritis patients with insufficient response to disease-modifying antirheumatic drugs (TOPIRA): study protocol for a pragmatic trial. PG - 313 LID - 10.1186/s13063-020-04260-y [doi] LID - 313 AB - BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, predominantly affecting joints, which is initially treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). In RA patients with insufficient response to csDMARDs, the addition of prednisone or tocilizumab, a biological DMARD (bDMARD), to the medication has been shown to be effective in reducing RA symptoms. However, which of these two treatment strategies has superior effectiveness and safety is unknown. METHODS: In this multicenter, investigator-initiated, open-label, randomized, pragmatic trial, we aim to recruit 120 RA patients meeting the 2010 ACR/EULAR classification criteria for RA, with active disease defined as a Clinical Disease Activity Index (CDAI) > 10 and at least one swollen joint of the 28 assessed. Patients must be on stable treatment with csDMARDs for >/= 8 weeks prior to screening and must have been treated with >/= 2 DMARDs, of which a maximum of one tumor necrosis factor inhibitor (a class of bDMARDs) is allowed. Previous use of other bDMARDs or targeted synthetic DMARDs is not allowed. Patients will be randomized in a 1:1 ratio to receive either tocilizumab (subcutaneously at 162 mg/week) or prednisone (orally at 10 mg/day) as an addition to their current csDMARD therapy. Study visits will be performed at screening; baseline; and months 1, 2, 3, 6, 9, and 12. Study medication will be tapered in case of clinical remission (CDAI 22 at any visit or > 10 at two consecutive visits), patients will switch to the other strategy arm. Primary outcome is a change in CDAI from baseline to 12 months. Secondary outcomes are additional clinical response and quality of life measures, drug retention rate, radiographically detectable progression of joint damage, functional ability, and cost utility. Safety outcomes include tocilizumab-associated adverse events (AEs), glucocorticoid-associated AEs, and serious AEs. DISCUSSION: This will be the first randomized clinical trial comparing addition of oral prednisone or of tocilizumab head to head in RA patients with insufficient response to csDMARD therapy. It will yield important information for clinical rheumatology practice. TRIAL REGISTRATION: This trial was prospectively registered in the Netherlands Trial Register on October 7, 2019 (NL8070). The Netherlands Trial Register contains all items from the World Health Organization Trial Registration Data Set. FAU - van der Leeuw, Matthijs S AU - van der Leeuw MS AD - University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. m.s.vanderleeuw-17@umcutrecht.nl. FAU - Welsing, Paco M J AU - Welsing PMJ AD - University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. FAU - de Hair, Maria J H AU - de Hair MJH AD - University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. FAU - Jacobs, Johannes W G AU - Jacobs JWG AD - University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. FAU - Marijnissen, Anne C A AU - Marijnissen ACA AD - University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. FAU - Linn-Rasker, Suzanne P AU - Linn-Rasker SP AD - Meander Medical Center, Maatweg 3, 3813 TZ, Amersfoort, The Netherlands. FAU - Fodili, Faouzia AU - Fodili F AD - Reumazorg Zuid West Nederland, Streuvelslaan 18, 4707 CH, Roosendaal, The Netherlands. FAU - Bos, Reinhard AU - Bos R AD - Medical Center Leeuwarden, Henri Dunantweg 2, 8934 AD, Leeuwarden, The Netherlands. FAU - Tekstra, Janneke AU - Tekstra J AD - University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. FAU - van Laar, Jacob M AU - van Laar JM AD - University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. LA - eng GR - ML29704/F. Hoffmann-La Roche/ PT - Clinical Trial Protocol PT - Comparative Study PT - Journal Article DEP - 20200405 PL - England TA - Trials JT - Trials JID - 101263253 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antirheumatic Agents) RN - 0 (Biological Products) RN - 0 (Glucocorticoids) RN - I031V2H011 (tocilizumab) RN - VB0R961HZT (Prednisone) SB - IM MH - Antibodies, Monoclonal, Humanized/adverse effects/*therapeutic use MH - Antirheumatic Agents/adverse effects/*therapeutic use MH - Arthritis, Rheumatoid/*drug therapy MH - Biological Products MH - Drug Therapy, Combination MH - Glucocorticoids/adverse effects/*therapeutic use MH - Humans MH - Multicenter Studies as Topic MH - Netherlands MH - Pragmatic Clinical Trials as Topic MH - Prednisone/adverse effects/*therapeutic use MH - Quality of Life MH - Remission Induction MH - Severity of Illness Index MH - Treatment Outcome PMC - PMC7133012 OTO - NOTNLM OT - Rheumatoid arthritis, Tocilizumab, Prednisone, Randomized controlled trial, Insufficient response to csDMARDs COIS- JMvL has received honoraria from Arx Tx, Boehringer, Eli Lilly, Gesyntha, Leadiant, Roche, and Sanofi Genzyme and research grants from Astra Zeneca, Boehringer, MSD, Roche, and Thermofisher. The remaining authors declare that they have no competing interests. EDAT- 2020/04/07 06:00 MHDA- 2021/01/20 06:00 PMCR- 2020/04/05 CRDT- 2020/04/07 06:00 PHST- 2020/02/24 00:00 [received] PHST- 2020/03/15 00:00 [accepted] PHST- 2020/04/07 06:00 [entrez] PHST- 2020/04/07 06:00 [pubmed] PHST- 2021/01/20 06:00 [medline] PHST- 2020/04/05 00:00 [pmc-release] AID - 10.1186/s13063-020-04260-y [pii] AID - 4260 [pii] AID - 10.1186/s13063-020-04260-y [doi] PST - epublish SO - Trials. 2020 Apr 5;21(1):313. doi: 10.1186/s13063-020-04260-y.