PMID- 26353833 OWN - NLM STAT- MEDLINE DCOM- 20160520 LR - 20220408 IS - 1478-6362 (Electronic) IS - 1478-6354 (Print) IS - 1478-6354 (Linking) VI - 17 IP - 1 DP - 2015 Sep 10 TI - Certolizumab pegol plus methotrexate 5-year results from the rheumatoid arthritis prevention of structural damage (RAPID) 2 randomized controlled trial and long-term extension in rheumatoid arthritis patients. PG - 245 LID - 10.1186/s13075-015-0767-2 [doi] LID - 245 AB - INTRODUCTION: As patients with rheumatoid arthritis (RA) receive treatment with anti-tumour necrosis factors over several years, it is important to evaluate their long-term safety and efficacy. The objective of this study was to examine the safety and benefits of certolizumab pegol (CZP)+methotrexate (MTX) treatment for almost 5 years in patients with RA. METHODS: Patients who completed the 24-week Rheumatoid Arthritis Prevention of Structural Damage (RAPID) 2 randomized controlled trial (RCT; NCT00160602), or who were American College of Rheumatology (ACR) 20 non-responders at Week 16, entered the open-label extension (OLE; NCT00160641). After >/=6 months treatment with CZP 400 mg every two weeks (Q2W), dose was reduced to 200 mg Q2W, the approved maintenance dose. Safety data are presented from all patients who received >/=1 dose CZP (Safety population, n=612). Efficacy data are presented to Week 232 for the intent-to-treat (ITT, n=492) and Week 24 CZP RCT Completer (n=342) populations, and through 192 weeks of dose-reduction for the Dose-reduction population (patients whose CZP dose was reduced to 200 mg, n=369). Radiographic progression (modified total Sharp score change from RCT baseline >0.5) to Week 128 is reported for the Week 24 CZP Completers. RESULTS: In the RCT, 619 patients were randomized to CZP+MTX (n=492) or placebo+MTX (n=127). Overall, 567 patients (91.6%) entered the OLE: 447 CZP and 120 placebo patients. Of all randomized patients, 358 (57.8%) were ongoing at Week 232. Annual drop-out rates during the first four years ranged from 8.4-15.0%. Event rates per 100 patient-years were 163.0 for adverse events (AEs) and 15.7 for serious AEs. Nineteen patients (3.1%) had fatal AEs (incidence rate=0.8). Clinical improvements in the RCT were maintained to Week 232 in the CZP Completers: mean Disease Activity Score 28 (Erythrocyte Sedimentation Rate) change from baseline was -3.4 and ACR20/50/70 responses 68.4%/47.1%/25.1% (non-responder imputation). Similar improvements observed in the ITT were maintained following dose-reduction. 73.2% of CZP Completers had no radiographic progression at Week 128. CONCLUSIONS: In patients with active RA despite MTX therapy, CZP was well tolerated, with no new safety signals identified. CZP provided sustained improvements in clinical outcomes for almost 5 years. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00160602 and NCT00160641 . Registered 8 September 2005. FAU - Smolen, Josef S AU - Smolen JS AD - Medical University of Vienna and Hietzing Hospital, Vienna, Austria. josef.smolen@wienkav.at. AD - Department of Medicine, Medical University of Vienna and Hietzing Hospital, Vienna, Austria. josef.smolen@wienkav.at. FAU - van Vollenhoven, Ronald AU - van Vollenhoven R AD - Karolinska Institute, Stockholm, Sweden. ronald.van.vollenhoven@ki.se. FAU - Kavanaugh, Arthur AU - Kavanaugh A AD - UCSD, San Diego, CA, USA. akavanaugh@ucsd.edu. FAU - Strand, Vibeke AU - Strand V AD - Biopharmaceutical Consultant, Portola Valley, CA, USA. vstrand@aol.com. FAU - Vencovsky, Jiri AU - Vencovsky J AD - Rheumatology Institute, Prague, Czech Republic. venc@revma.cz. FAU - Schiff, Michael AU - Schiff M AD - University of Colorado, Denver, CO, USA. michael.schiff@me.com. FAU - Landewe, Robert AU - Landewe R AD - Academic Medical Centre, Amsterdam, Netherlands. landewe@rlandewe.nl. FAU - Haraoui, Boulos AU - Haraoui B AD - Centre Hospitalier de l'Universite de Montreal, Montreal, Canada. bharaoui@videotron.ca. FAU - Arendt, Catherine AU - Arendt C AD - UCB Pharma, Brussels, Belgium. catherine.arendt@ucb.com. FAU - Mountian, Irina AU - Mountian I AD - UCB Pharma, Brussels, Belgium. irina.mountian@ucb.com. FAU - Carter, David AU - Carter D AD - UCB Pharma, Brussels, Belgium. dave-carter01@hotmail.co.uk. FAU - van der Heijde, Desiree AU - van der Heijde D AD - Leiden University, Leiden, Netherlands. mail@dvanderheijde.nl. LA - eng SI - ClinicalTrials.gov/NCT00160602 SI - ClinicalTrials.gov/NCT00160641 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20150910 PL - England TA - Arthritis Res Ther JT - Arthritis research & therapy JID - 101154438 RN - 0 (Antirheumatic Agents) RN - UMD07X179E (Certolizumab Pegol) RN - YL5FZ2Y5U1 (Methotrexate) SB - IM MH - Adult MH - Aged MH - Antirheumatic Agents/adverse effects/therapeutic use MH - Arthritis, Rheumatoid/*drug therapy/*prevention & control MH - Certolizumab Pegol/adverse effects/*therapeutic use MH - Dose-Response Relationship, Drug MH - Drug Administration Schedule MH - Drug Therapy, Combination MH - Female MH - Humans MH - Infections/chemically induced MH - Kaplan-Meier Estimate MH - Male MH - Methotrexate/adverse effects/*therapeutic use MH - Middle Aged MH - Time Factors MH - Treatment Outcome PMC - PMC4565002 EDAT- 2015/09/12 06:00 MHDA- 2016/05/21 06:00 PMCR- 2015/09/10 CRDT- 2015/09/11 06:00 PHST- 2015/03/02 00:00 [received] PHST- 2015/08/25 00:00 [accepted] PHST- 2015/09/11 06:00 [entrez] PHST- 2015/09/12 06:00 [pubmed] PHST- 2016/05/21 06:00 [medline] PHST- 2015/09/10 00:00 [pmc-release] AID - 10.1186/s13075-015-0767-2 [pii] AID - 767 [pii] AID - 10.1186/s13075-015-0767-2 [doi] PST - epublish SO - Arthritis Res Ther. 2015 Sep 10;17(1):245. doi: 10.1186/s13075-015-0767-2.