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Certolizumab Pegol: A Review in Inflammatory Autoimmune Diseases

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Abstract

Certolizumab pegol (Cimzia®) is a subcutaneously administered polyethylene glycolylated (PEGylated) antigen-binding fragment of a recombinant human monoclonal antibody that selectively neutralizes TNFα. The drug is indicated for a variety of inflammatory autoimmune diseases, including Crohn’s disease (CD), rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), based on its benefit in these settings in well-designed clinical trials. In these studies, certolizumab pegol (as first- or subsequent-line therapy) reduced the severity of CD when used as an induction or maintenance therapy, and improved the signs/symptoms and slowed the radiographic progression of RA (with or without concomitant methotrexate), PsA and axSpA. Certolizumab pegol is generally well tolerated, with upper respiratory tract infections, rash and urinary tract infections being among the most frequent adverse reactions. Thus, certolizumab pegol is an effective option for the management of these autoimmune diseases.

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References

  1. Disabled World. Autoimmune diseases: types, facts & information. 2016. http://www.disabled-world.com/health/autoimmunediseases/. Accessed 5 July 2016.

  2. National Institute of Arthritis and Musculoskeletal and Skin Diseases. Understanding autoimmune diseases. 2016. http://www.niams.nih.gov/health_info/autoimmune. Accessed 5 July 2016.

  3. Australasian Society of Clinical Immunology and Allergy. Autoimmune diseases. 2016. http://www.allergy.org.au. Accessed 5 July 2016.

  4. UCB. Cimzia® (certolizumab pegol): US prescribing Information. 2016. http://www.fda.gov. Accessed 26 Sep 2016.

  5. UCB Pharma S.A. Cimzia solution for injection: summary of product characteristics. 2016. http://www.ema.europa.eu. Accessed 26 Sep 2016.

  6. Nesbitt A, Fossati G, Bergin M, et al. Mechanism of action of certolizumab pegol (CDP870): in vitro comparison with other anti-tumor necrosis factor alpha agents. Inflamm Bowel Dis. 2007;13(11):1323–32.

    Article  PubMed  Google Scholar 

  7. Ueda N, Tsukamoto H, Mitoma H, et al. The cytotoxic effects of certolizumab pegol and golimumab mediated by transmembrane tumor necrosis factor alpha. Inflamm Bowel Dis. 2013;19(6):1224–31.

    Article  PubMed  Google Scholar 

  8. Dubinsky M, Khanna R, Kosutic G, et al. The relative efficacy of methotrexate and thiopurines in preventing anti-drug antibodies to certolizumab pegol in patients with crohn’s disease [abstract no. P-096]. Inflamm Bowel Dis. 2014;20(Suppl 1):S66.

    Google Scholar 

  9. Sandborn WJ, Schreiber S, Hanauer SB, et al. Reinduction with certolizumab pegol in patients with relapsed Crohn’s disease: results from the PRECiSE 4 Study. Clin Gastroenterol Hepatol. 2010;8(8):696–702.e1.

  10. Sandborn WJ, Lee SD, Randall C, et al. Long-term safety and efficacy of certolizumab pegol in the treatment of Crohn’s disease: 7-year results from the PRECiSE 3 study. Aliment Pharmacol Ther. 2014;40(8):903–16.

    Article  CAS  PubMed  Google Scholar 

  11. Sandborn WJ, Feagan BG, Stoinov S, et al. Certolizumab pegol for the treatment of Crohn’s disease. N Engl J Med. 2007;357(3):228–38.

    Article  CAS  PubMed  Google Scholar 

  12. Schreiber S, Khaliq-Kareemi M, Lawrance IC, et al. Maintenance therapy with certolizumab pegol for Crohn’s disease. N Engl J Med. 2007;357(3):239–50.

    Article  CAS  PubMed  Google Scholar 

  13. Hanauer SB, Panes J, Colombel JF, et al. Clinical trial: impact of prior infliximab therapy on the clinical response to certolizumab pegol maintenance therapy for Crohn’s disease. Aliment Pharmacol Ther. 2010;32(3):384–93.

    Article  CAS  PubMed  Google Scholar 

  14. Schreiber S, Colombel J-F, Bloomfield R, et al. Increased response and remission rates in short-duration Crohn’s disease with subcutaneous certolizumab pegol: an analysis of PRECiSE 2 randomized maintenance trial data. Am J Gastroenterol. 2010;105(7):1574–82.

    Article  CAS  PubMed  Google Scholar 

  15. Schreiber S, Lawrance IC, Thomsen OO, et al. Randomised clinical trial: certolizumab pegol for fistulas in Crohn’s disease—subgroup results from a placebo-controlled study. Aliment Pharmacol Ther. 2011;33(2):185–93.

    Article  CAS  PubMed  Google Scholar 

  16. Feagan BG, Coteur G, Tan S, et al. Clinically meaningful improvement in health-related quality of life in a randomized controlled trial of certolizumab pegol maintenance therapy for Crohn’s disease. Am J Gastroenterol. 2009;104(8):1976–83.

    Article  PubMed  Google Scholar 

  17. Feagan BG, Reilly MC, Gerlier L, et al. Clinical trial: the effects of certolizumab pegol therapy on work productivity in patients with moderate-to-severe Crohn’s disease in the PRECiSE 2 study. Aliment Pharmacol Ther. 2010;31(12):1276–85.

    Article  CAS  PubMed  Google Scholar 

  18. Lichtenstein GR, Thomsen OO, Schreiber S, et al. Continuous therapy with certolizumab pegol maintains remission of patients with Crohn’s disease for up to 18 months. Clin Gastroenterol Hepatol. 2010;8(7):600–9.

    Article  CAS  PubMed  Google Scholar 

  19. Lee SD, Rubin DT, Sandborn WJ, et al. Reinduction with certolizumab pegol in patients with Crohn’s disease experiencing disease exacerbation: 7-year data from the PRECiSE 4 study. Inflamm Bowel Dis. 2016;22(8):1870–80.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Sandborn WJ, Abreu MT, D’Haens G, et al. Certolizumab pegol in patients with moderate to severe Crohn’s disease and secondary failure to infliximab. Clin Gastroenterol Hepatol. 2010;8(8):688–95.e2.

  21. Feagan BG, Sandborn WJ, Wolf DC, et al. Randomised clinical trial: improvement in health outcomes with certolizumab pegol in patients with active Crohn’s disease with prior loss of response to infliximab. Aliment Pharmacol Ther. 2011;33(5):541–50.

    Article  CAS  PubMed  Google Scholar 

  22. US National Institutes of Health. Clinicaltrials.gov identifier NCT00333788. 2016. https://clinicaltrials.gov. Accessed 3 June 2016.

  23. Emery P, Bingham CO 3rd, Burmester GR, et al. Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-naive patients with early, active rheumatoid arthritis with poor prognostic factors: 1-year results from C-EARLY, a randomised, double-blind, placebo-controlled phase III study. Ann Rheum Dis. 2016;. doi:10.1136/annrheumdis-2015-209057.

    PubMed Central  Google Scholar 

  24. Emery P, Bingham C, Burmester G, et al. Improvements in patient-reported outcomes following 52 weeks of treatment with certolizumab pegol in combination with methotrexate in DMARD-naive patients with severe, active and progressive rheumatoid arthritis: results from the C-EARLY randomized, double-blind, controlled phase 3 study [abstract no. PRM143]. Value Health. 2015;18:A707–8.

    Article  CAS  PubMed  Google Scholar 

  25. Keystone E, Heijde DVD, Mason D, et al. Certolizumab pegol plus methotrexate is significantly more effective than placebo plus methotrexate in active rheumatoid arthritis. Arthritis Rheum. 2008;58(11):3319–29.

    Article  CAS  PubMed  Google Scholar 

  26. Smolen J, Landewe RB, Mease P, 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.

    Article  CAS  PubMed  Google Scholar 

  27. Strand V, Smolen JS, van Vollenhoven RF, et al. Certolizumab pegol plus methotrexate provides broad relief from the burden of rheumatoid arthritis: analysis of patient-reported outcomes from the RAPID 2 trial. Ann Rheum Dis. 2011;70(6):996–1002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Strand V, Mease P, Burmester GR, et al. Rapid and sustained improvements in health-related quality of life, fatigue, and other patient-reported outcomes in rheumatoid arthritis patients treated with certolizumab pegol plus methotrexate over 1 year: results from the RAPID 1 randomized controlled trial. Arthritis Res Ther. 2009;11(6):1–12.

    Article  Google Scholar 

  29. Kavanaugh A, Smolen J, Emery P, et al. Effect of certolizumab pegol with methotrexate on home and workplace productivity and social activities in patients with active rheumatoid arthritis. Arthritis Rheum. 2009;61(11):1592–600.

    Article  CAS  PubMed  Google Scholar 

  30. Hazes JM, Taylor P, Strand V, et al. Physical function improvements and relief from fatigue and pain are associated with increased productivity at work and at home in rheumatoid arthritis patients treated with certolizumab pegol. Rheumatology. 2010;49(10):1900–10.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Combe B, Furst DE, Keystone EC, et al. Certolizumab pegol efficacy across methotrexate regimens: a pre-specified analysis of two phase III trials. Arthritis Care Res (Hoboken). 2016;68(3):299–307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Smolen JS, van Vollenhoven R, Kavanaugh A, 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(245).

  33. Keystone E, Landewe R, van Vollenhoven R, 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.

    Article  CAS  PubMed  Google Scholar 

  34. Keystone EC, Combe B, Smolen J, et al. Sustained efficacy of certolizumab pegol added to methotrexate in the treatment of rheumatoid arthritis: 2-year results from the RAPID 1 trial. Rheumatology. 2012;51(9):1628–38.

    Article  CAS  PubMed  Google Scholar 

  35. Van Der Heijde D, Keystone EC, Curtis JR, et al. Timing and magnitude of initial change in disease activity score 28 predicts the likelihood of achieving low disease activity at 1 year in rheumatoid arthritis patients treated with certolizumab pegol: a post-hoc analysis of the RAPID 1 trial. J Rheumatol. 2012;39(7):1326–33.

    Article  PubMed  Google Scholar 

  36. Keystone EC, Curtis JR, Fleischmann RM, et al. Rapid improvement in the signs and symptoms of rheumatoid arthritis following certolizumab pegol treatment predicts better longterm outcomes: post-hoc analysis of a randomized controlled trial. J Rheumatol. 2011;38(6):990–6.

    Article  PubMed  Google Scholar 

  37. Fleischmann R, Vencovsky J, van Vollenhoven RF, 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.

    Article  CAS  PubMed  Google Scholar 

  38. Fleischmann R, Van Vollenhoven R, Vencovsky J, et al. Long-term safety and efficacy of 4-weekly certolizumab pegol monotherapy and combination therapy in rheumatoid arthritis: 5-year results from an open-label extension study [abstract no. FRI0186]. In: Annual EULAR Congress; 2013.

  39. Strand V, Purcaru O, Van Vollenhoven R, et al. Long-term benefits of 4-weekly certolizumab pegol monotherapy and combination therapy on household productivity and social participation in rheumatoid arthritis: 5-year results from an open-label extension study [abstract]. In: Annual EULAR Congress; 2013.

  40. Mease PJ, Fleischmann R, Deodhar AA, et al. Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24-week results of a phase 3 double-blind randomised placebo-controlled study (RAPID-PsA). Ann Rheum Dis. 2014;73(1):48–55.

    Article  CAS  PubMed  Google Scholar 

  41. Van Der Heijde D, Fleischmann R, Wollenhaupt J, et al. Effect of different imputation approaches on the evaluation of radiographic progression in patients with psoriatic arthritis: results of the RAPID-PsA 24-week phase III double-blind randomised placebo-controlled study of certolizumab pegol. Ann Rheum Dis. 2014;73(1):233–7.

    Article  PubMed  Google Scholar 

  42. Gladman D, Fleischmann R, Coteur G, et al. Effect of certolizumab pegol on multiple facets of psoriatic arthritis as reported by patients: 24-week patient-reported outcome results of a phase III, multicenter study. Arthritis Care Res (Hoboken). 2014;66(7):1085–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kavanaugh A, Gladman D, van der Heijde D, et al. Improvements in productivity at paid work and within the household, and increased participation in daily activities after 24 weeks of certolizumab pegol treatment of patients with psoriatic arthritis: results of a phase 3 double-blind randomised placebo-controlled study. Ann Rheum Dis. 2015;74(1):44–51.

    Article  CAS  PubMed  Google Scholar 

  44. Mease P, Deodhar A, Fleischmann R, et al. Effect of certolizumab pegol over 96 weeks in patients with psoriatic arthritis with and without prior antitumour necrosis factor exposure. RMD Open. 2015;1(1):e000119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Landewe R, Braun J, Deodhar A, et al. Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24-week results of a double-blind randomised placebo-controlled phase 3 study. Ann Rheum Dis. 2014;73(1):39–47.

    Article  CAS  PubMed  Google Scholar 

  46. Landewe RBM, Rudwaleit M, Van Der Heijde D, et al. Effect of certolizumab pegol on signs and symptoms of ankylosing spondylitis and non-radiographic axial spondyloarthritis: 24-week results of a double blind randomized placebo-controlled phase 3 axial spondyloarthritis study [abstract no. 777]. Arthritis Rheum. 2012;64(10 Suppl):S336–7.

  47. Van Der Heijde D, Maksymowych WP, Landewe RBM, et al. Effect of certolizumab pegol on inflammation of spine and sacroiliac joints in patients with axial spondyloarthritis: 12 week magnetic resonance imaging results of a phase 3 double blind randomized placebo-controlled study [abstract no. 1705]. Arthritis Rheum. 2012;64(Suppl 10):S730.

    Google Scholar 

  48. Mease PJ, Dougados M, Davies O, et al. Certolizumab pegol rapidly reduces peripheral enthesitis and the incidence of tender and swollen joints in patients with active axial spondyloarthritis, including both ankylosing spondylitis and non-radiographic axial spondyloarthritis [abstract no. SAT0362]. Ann Rheum Dis. 2014;73(Suppl 2):724–5.

    Google Scholar 

  49. Sieper J, Kivitz A, van Tubergen A, et al. Impact of certolizumab pegol on patient-reported outcomes in patients with axial spondyloarthritis. Arthritis Care Res (Hoboken). 2015;67(10):1475–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Van Der Heijde D, Braun J, Rudwaleit M, et al. Clinical responses and improvements in patient-reported outcomes are associated with increased productivity in the workplace and at home in axial spondyloarthritis patients treated with certolizumab pegol [abstract no. THU0202]. Ann Rheum Dis. 2015;74(Suppl 2):268–9.

    Google Scholar 

  51. Rudwaleit M, Rosenbaum JT, Landewe R, et al. Observed incidence of uveitis following certolizumab pegol treatment in patients with axial spondyloarthritis. Arthritis Care Res. 2016;68(6):838–44.

    Article  CAS  Google Scholar 

  52. Sieper J, Landewe R, Rudwaleit M, et al. Effect of certolizumab pegol over ninety-six weeks in patients with axial spondyloarthritis: results from a phase III randomized trial. Arthritis Rheumatol. 2015;67(3):668–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. van Der Heijde D, Dougados M, Landewé R, et al. Certolizumab pegol for the treatment of axial spondyloarthritis: 4-year outcomes from the RAPID-axSpA trial [abstract]. In: Annual EULAR Congress; 2016.

  54. van Der Heijde D, Maksymowych WP, Landewé R, et al. Factors associated with structural damage in the spine, as measured by X-ray, in patients with axial spondyloarthritis treated with certolizumab pegol over 96 weeks [abstract plus poster]. In: Annual EULAR Congress; 2015.

  55. Sieper J, Rudwaleit M, Van Der Heijde D, et al. Long-term safety and efficacy of certolizumab pegol in patients with axial spondyloarthritis: 96-week outcomes of the rapid-axSpA trial [abstract no. P29]. Clin Exp Rheumatol. 2014;32(5):785–6.

    Google Scholar 

  56. Van Der Heijde D, Braun J, Rudwaleit M, et al. Sustained improvements in workplace and household productivity and social participation with certolizumab pegol over 96 weeks in patients with axial spondyloarthritis, including ankylosing spondylitis and non-radiographic axial spondyloarthritis [abstract no. 2560]. Arthritis Rheumatol. 2014;66(S10):S1119.

    Google Scholar 

  57. Braun J, Maksymowych WP, Landewe R, et al. Achievement of remission of inflammation in the spine and sacroiliac joints measured by magnetic resonance imaging (MRI) in patients with axial spondyloarthritis, and associations between MRI and clinical remission, over 96 weeks of treatment with certolizumab pegol [abstract no. OP0171]. Ann Rheum Dis. 2015;74(Suppl 2):134–5.

    Article  Google Scholar 

  58. Bykerk VP, Cush J, Winthrop K, 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.

    Article  CAS  PubMed  Google Scholar 

  59. Loftus EV, Colombel JF, Choi JM, et al. Safety of certolizumab pegol in 2570 crohn’s disease patients with 4378 patients years at risk: integrated data from the global clinical program [abstract no. Sa1139]. Gastroenterology. 2015;148(4 Suppl 1):S237–S8.

  60. Curtis JR, De Longueville M, O’Brien C, et al. Identification of time-dependent risk factors for serious infectious events in rheumatoid arthritis patients treated with certolizumab pegol [abstract no. SAT0149]. Ann Rheum Dis. 2015;74(Suppl 2):705.

    Article  Google Scholar 

  61. Choi J, Ha C, Kosutic G, et al. Incidence of benign and malignant neoplasms in crohn’s disease patients aged <30 years versus 30–64 years treated with certolizumab pegol: results from a pooled safety analysis of 15 studies [abstract no. 1831]. Am J Gastroenterol. 2015;110(Suppl 1):S778.

    Google Scholar 

  62. Gossec L, Smolen JS, Ramiro S, et al. European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update. Ann Rheum Dis. 2016;75(3):499–510.

    Article  CAS  PubMed  Google Scholar 

  63. Braun J, van den Berg R, Baraliakos X, et al. 2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis. 2011;70(6):896–904.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Smolen JS, Landewe R, Breedveld FC, 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.

    Article  CAS  PubMed  Google Scholar 

  65. Terdiman JP, Gruss CB, Heidelbaugh JJ, et al. American Gastroenterological Association Institute guideline on the use of thiopurines, methotrexate, and anti-TNF-alpha biologic drugs for the induction and maintenance of remission in inflammatory Crohn’s disease. Gastroenterology. 2013;145(6):1459–63.

    Article  PubMed  Google Scholar 

  66. Malaviya AP, Ostor AJ. Drug adherence to biologic DMARDS with a special emphasis on the benefits of subcutaneous abatacept. Patient Prefer Adherence. 2012;6:589–96.

    PubMed  PubMed Central  Google Scholar 

  67. Ruderman EM. Overview of safety of non-biologic and biologic DMARDs. Rheumatology. 2012;51 Suppl 6:vi37–43.

  68. Boyman O, Comte D, Spertini F. Adverse reactions to biologic agents and their medical management. Nat Rev Rheumatol. 2014;10(10):612–27.

    Article  CAS  PubMed  Google Scholar 

  69. Sathish JG, Sethu S, Bielsky MC, et al. Challenges and approaches for the development of safer immunomodulatory biologics. Nat Rev Drug Discov. 2013;12(4):306–24.

    Article  CAS  PubMed  Google Scholar 

  70. Maneiro JR, Salgado E, Gomez-Reino JJ. Immunogenicity of monoclonal antibodies against tumor necrosis factor used in chronic immune-mediated inflammatory conditions: systematic review and meta-analysis. JAMA Intern Med. 2013;173(15):1416–28.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

During the peer review process, the manufacturer of certolizumab pegol was offered the opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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    Emma D. Deeks

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Correspondence to Emma D. Deeks.

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The preparation of this review was not supported by any external funding.

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Emma Deeks is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.

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The manuscript was reviewed by: S. Castaneda, Department of Rheumatology, Hospital Universitario la Princesa, Madrid, Spain; R. Caviglia, Gastroenterology and Digestive Endoscopy Department, Chelsea and Westminister Hospital NHS Foundation Trust, Imperial College, London, UK; S. Chohan, Arizona Arthritis and Rheumatology Associates, Phoenix, AZ.

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Deeks, E.D. Certolizumab Pegol: A Review in Inflammatory Autoimmune Diseases. BioDrugs 30, 607–617 (2016). https://doi.org/10.1007/s40259-016-0197-y

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