Skip to main content
Top

28-03-2017 | Rheumatoid arthritis | Article

Long-Term Maintenance of Certolizumab Pegol Safety and Efficacy, in Combination with Methotrexate and as Monotherapy, in Rheumatoid Arthritis Patients

Journal: Rheumatology and Therapy

Authors: Roy Fleischmann, Ronald F. van Vollenhoven, Jiri Vencovský, Rieke Alten, Owen Davies, Irina Mountian, Marc de Longueville, David Carter, Ernest Choy

Publisher: Springer Healthcare

Abstract

Introduction

The safety and efficacy of certolizumab pegol (CZP) 400 mg every 4 weeks (Q4W) monotherapy (FAST4WARD/NCT00548834) and in combination with methotrexate (MTX) (014/NCT00544154) in active rheumatoid arthritis (RA) has been published previously. This report outlines final long-term outcomes from the open-label extension (OLE) study (015/NCT00160693), which enrolled patients from these randomized controlled trials (RCTs).

Methods

Patients who withdrew from or completed the 24-week 014/FAST4WARD RCTs were enrolled and received CZP 400 mg Q4W with/without MTX. Exposure-adjusted event rates (ER) per 100 patient-years (PYs) of adverse events (AEs) and serious AEs (SAEs) were reported for all patients receiving ≥1 dose of CZP in RCTs or OLE (N = 427) between first CZP dose and up to 24 weeks after last CZP dose or study withdrawal. Efficacy assessments included clinical (ACR20/50/70 response rates, TJC, SJC) and patient-reported outcomes (HAQ-DI, PtGADA, pain, fatigue) to week 304 (5.8 years) in the CZP intent-to-treat population. SDAI and CDAI outcomes were analyzed post hoc. Outcomes for CZP monotherapy and CZP+MTX combination-therapy were compared.

Results

Globally, ERs of AEs and SAEs were 408.1 and 25.2 per 100 PY, respectively. Eleven patients had AEs leading to death (ER 0.6). Improvements in clinical and patient-reported outcomes during the 24-week RCTs were maintained to week 304, and were similar between all subpopulations.

Conclusions

The longest exposure duration to date with CZP 400 mg Q4W treatment confirmed the safety profile observed in previous studies. Initial improvements in signs and symptoms of RA, including PROs, were maintained in both CZP monotherapy and CZP + MTX combination-therapy patients.
Trial registration: ClinicalTrials.gov identifier, NCT00160693.
Funding: UCB Pharma.
Literature
1.
Smolen JS, Landewe R, Breedveld FC, Buch M, Burmester G, Dougados M, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2014;73(3):492–509.CrossRefPubMed
2.
Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh AF, Kremer JM, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012;64(5):625–39.CrossRef
3.
Emery P, Sebba A, Huizinga TW. Biologic and oral disease-modifying antirheumatic drug monotherapy in rheumatoid arthritis. Ann Rheum Dis. 2013;72(12):1897–904.CrossRefPubMedPubMedCentral
4.
Soliman MM, Ashcroft DM, Watson KD, Lunt M, Symmons DPM, Hyrich KL. Impact of concomitant use of DMARDs on the persistence with anti-TNF therapies in patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register. Ann Rheum Dis. 2011;70(4):583–9.CrossRefPubMedPubMedCentral
5.
Mariette X, Gottenberg J-E, Ravaud P, Combe B. Registries in rheumatoid arthritis and autoimmune diseases: data from the French registries. Rheumatology (Oxford). 2011;50(1):222–9.CrossRef
6.
Lee SJ, Chang H, Yazici Y, Greenberg JD, Kremer JM, Kavanaugh A. Utilization trends of tumor necrosis factor inhibitors among patients with rheumatoid arthritis in a United States observational cohort study. J Rheumatol. 2009;36(8):1611–7.CrossRefPubMed
7.
Choy E, McKenna F, Vencovsky J, Valente R, Goel N, Vanlunen B, et al. Certolizumab pegol plus MTX administered every 4 weeks is effective in patients with RA who are partial responders to MTX. Rheumatology (Oxford). 2012;51(7):1226–34.CrossRef
8.
Fleischmann R, Vencovsky J, van Vollenhoven RF, Borenstein D, Box J, Coteur G, et al. Efficacy and safety of certolizumab pegol monotherapy every 4 weeks in patients with rheumatoid arthritis failing previous disease-modifying antirheumatic therapy: the FAST4WARD study. Ann Rheum Dis. 2009;68(6):805–11.CrossRefPubMed
9.
Smolen J, Landewe RB, Mease P, Brzezicki J, Mason D, Luijtens K, et al. Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis: the RAPID 2 study. A randomised controlled trial. Ann Rheum Dis. 2009;68(6):797–804.CrossRefPubMed
10.
Keystone E, Heijde D, Mason D Jr, Landewe R, Vollenhoven RV, Combe B, et al. Certolizumab pegol plus methotrexate is significantly more effective than placebo plus methotrexate in active rheumatoid arthritis: findings of a fifty-two-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis Rheum. 2008;58(11):3319–29.CrossRefPubMed
11.
Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, Goldsmith C, et al. American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum. 1995;38(6):727–35.CrossRefPubMed
12.
Bruce B, Fries JF. The Stanford Health Assessment Questionnaire: dimensions and practical applications. Health Qual Life Outcomes. 2003;1:20.CrossRefPubMedPubMedCentral
13.
Ware JE, Kosinski M. Interpreting SF-36 summary health measures: a response. Qual Life Res. 2001;10(5):405–13 (discussion 15–20).CrossRefPubMed
14.
Khanna D, Pope JE, Khanna PP, Maloney M, Samedi N, Norrie D, et al. The minimally important difference for the fatigue visual analog scale in patients with rheumatoid arthritis followed in an academic clinical practice. J Rheumatol. 2008;35(12):2339–43.CrossRefPubMedPubMedCentral
15.
Prevoo ML, van ‘t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995;38(1):44–8.CrossRefPubMed
16.
Felson DT, Smolen JS, Wells G, Zhang B, van Tuyl LH, Funovits J, et al. American College of Rheumatology/European League Against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Arthritis Rheum. 2011;63(3):573–86.CrossRefPubMedPubMedCentral
17.
Wells GA, Tugwell P, Kraag GR, Baker PR, Groh J, Redelmeier DA. Minimum important difference between patients with rheumatoid arthritis: the patient’s perspective. J Rheumatol. 1993;20(3):557–60.PubMed
18.
Kosinski M, Zhao SZ, Dedhiya S, Osterhaus JT, Ware JE Jr. Determining minimally important changes in generic and disease-specific health-related quality of life questionnaires in clinical trials of rheumatoid arthritis. Arthritis Rheum. 2000;43(7):1478–87.CrossRefPubMed
19.
Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole RM. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001;94(2):149–58.CrossRefPubMed
20.
Strand V, Singh JA. Improved health-related quality of life with effective disease-modifying antirheumatic drugs: evidence from randomized controlled trials. Am J Manag Care. 2007;13(Suppl 9):S237–51.PubMed
21.
Weinblatt ME, Bathon JM, Kremer JM, Fleischmann RM, Schiff MH, Martin RW, et al. Safety and efficacy of etanercept beyond 10 years of therapy in North American patients with early and longstanding rheumatoid arthritis. Arthritis Care Res (Hoboken). 2011;63(3):373–82.
22.
Genovese MC, Schiff M, Luggen M, Le Bars M, Aranda R, Elegbe A, et al. Long-term safety and efficacy of abatacept through 5 years of treatment in patients with rheumatoid arthritis and an inadequate response to tumor necrosis factor inhibitor therapy. J Rheumatol. 2012;39(8):1546–54.CrossRefPubMed
23.
Burmester GR, Matucci-Cerinic M, Mariette X, Navarro-Blasco F, Kary S, Unnebrink K, et al. Safety and effectiveness of adalimumab in patients with rheumatoid arthritis over 5 years of therapy in a phase 3b and subsequent postmarketing observational study. Arthritis Res Ther. 2014;16(1):R24.CrossRefPubMedPubMedCentral
24.
Smolen JS, Kay J, Doyle M, Landewé R, Matteson EL, Gaylis N, et al. Golimumab in patients with active rheumatoid arthritis after treatment with tumor necrosis factor α inhibitors: findings with up to five years of treatment in the multicenter, randomized, double-blind, placebo-controlled, phase 3 GO-AFTER study. Arthritis Res Ther. 2015;17(1):14.CrossRefPubMedPubMedCentral
25.
Keystone E, Landewe R, van Vollenhoven R, Combe B, Strand V, Mease P, et al. Long-term safety and efficacy of certolizumab pegol in combination with methotrexate in the treatment of rheumatoid arthritis: 5-year results from the RAPID 1 trial and open-label extension. Ann Rheum Dis. 2014;73(12):2094–100.CrossRefPubMed
26.
Smolen JS, van Vollenhoven R, Kavanaugh A, Strand V, Vencovsky J, Schiff M, et al. 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. Arthritis Res Ther. 2015;17(1):245.CrossRefPubMedPubMedCentral
27.
Bykerk VP, Cush J, Winthrop K, Calabrese L, Lortholary O, de Longueville M, et al. Update on the safety profile of certolizumab pegol in rheumatoid arthritis: an integrated analysis from clinical trials. Ann Rheum Dis. 2015;74(1):96–103.CrossRefPubMed
28.
van Gestel AM, Prevoo ML, van ‘t Hof MA, van Rijswijk MH, van de Putte LB, van Riel PL. Development and validation of the European League Against Rheumatism response criteria for rheumatoid arthritis. Comparison with the preliminary American College of Rheumatology and the World Health Organization/International League Against Rheumatism Criteria. Arthritis Rheum. 1996;39(1):34–40.CrossRefPubMed
29.
Felson DT, Anderson JJ, Boers M, Bombardier C, Chernoff M, Fried B, et al. The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. The Committee on Outcome Measures in Rheumatoid Arthritis Clinical Trials. Arthritis Rheum. 1993;36(6):729–40.CrossRefPubMed
30.
Kirwan JR, Hewlett SE, Heiberg T, Hughes RA, Carr M, Hehir M, et al. Incorporating the patient perspective into outcome assessment in rheumatoid arthritis—progress at OMERACT 7. J Rheumatol. 2005;32(11):2250–6.PubMed