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Efficacy and safety profile of intravenous tocilizumab versus intravenous abatacept in treating female Saudi Arabian patients with active moderate-to-severe rheumatoid arthritis

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Abstract

Objectives

To compare the efficacy and safety of tocilizumab with those of abatacept in patients with active rheumatoid arthritis not responding to anti-tumor necrosis factor therapy.

Methods

A prospective, open-label study was carried out on adult females with moderate-to-severe rheumatoid arthritis. Patients were randomly assigned to receive either intravenous tocilizumab or abatacept treatment. History taking, clinical examination, and laboratory evaluation were done at baseline and during a 24-week period of follow-up. Disease activity was calculated using the DAS28-ESR score. The incidence of accompanying adverse events was evaluated and all statistical analyses were performed by InStat.

Results

One hundred thirty-two patients were enrolled and classified randomly into the tocilizumab (n = 68) and abatacept (n = 64) groups. By week 24, the mean DAS28-ESR was significantly reduced in both groups (P < 0.0001) in association with significant reductions in CRP, ESR, and HAQ scores. No significant difference in the incidence rate of adverse effects appeared between both study groups. However, there were marked declines in the hemoglobin levels (P = 0.003) and neutrophil count (P = 0.002) together with significant elevations in systolic blood pressure (P = 0.002), liver enzymes (P = 0.001), total cholesterol (P = 0.001), and high-density lipoproteins (P = 0.002) in the tocilizumab group compared with the abatacept group.

Conclusion

Both intravenous abatacept and tocilizumab significantly decreased the disease activity and improved the physical function in rheumatoid arthritis patients who failed to respond to anti-tumor necrosis factor therapy. Although the efficacy of both drugs was similar, abatacept showed a more promising short-term safety profile since it was associated with less adverse effects and better laboratory outcomes.

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References

  1. Giles J, Bathon JM (2010) Management of rheumatoid arthritis: synovitis. Rheumatology 1:955–963

    Google Scholar 

  2. Emery P, Breedveld FC, Hall S, Durez P, Chang DJ, Robertson D, Singh A, Pedersen RD, Koenig AS, Freundlich B (2008) Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomized, double-blind, parallel treatment trial. Lancet 372:375–382

    Article  CAS  PubMed  Google Scholar 

  3. Finckh A, Simard JF, Gabay C, Guerne PA (2006) Evidence for differential acquired drug resistance to anti-tumor necrosis factor agents in rheumatoid arthritis. Ann Rheum Dis 65:746–752

    Article  CAS  PubMed  Google Scholar 

  4. Du Pan SM, Dehler S, Ciurea A et al (2009) Comparison of drug retention rates and causes of drug discontinuation between anti-tumor necrosis factor agents in rheumatoid arthritis. Arthritis Rheum 61:560–568

    Article  PubMed  Google Scholar 

  5. Buch MH (2010) Sequential use of biologic therapy in rheumatoid arthritis. Curr Opin Rheumatol 22:321–329

    Article  CAS  PubMed  Google Scholar 

  6. Harrold LR, Reed GW, Solomon DH, Curtis JR et al (2016) Comparative effectiveness of abatacept versus tocilizumab in rheumatoid arthritis patients with prior TNFi exposure in the US Corrona registry and Joel M. Kremer 5,6. Arthritis Res Ther 18:280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Moots RJ, Sebba A, Rigby W, Ostor A, Porter-Brown B, Donaldson F, Dimonaco S, Rubbert-Roth A, van Vollenhoven R, Genovese MC (2017) Effect of tocilizumab on neutrophils in adult patients with rheumatoid arthritis: pooled analysis of data from phase 3 and 4 clinical trials. Rheumatology 56:541–549

    Article  CAS  PubMed  Google Scholar 

  8. Nishimoto N, Terao K, Mima T, Nakahara H, Takagi N, Kakehi T (2008) Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease. Blood 112:3959–3964

    Article  CAS  PubMed  Google Scholar 

  9. Smolen JS, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, Alecock E, Woodworth T, Alten R (2008) Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double blind, placebo-controlled, randomized trial. Lancet 371:987–997

    Article  CAS  PubMed  Google Scholar 

  10. Nishimoto N, Hashimoto J, Miyasaka N et al (2007) Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor—evidence of clinical and radiographic benefit from an X-ray reader-blinded randomized controlled trial of tocilizumab. Ann Rheum Dis 6:1162–1167

    Article  CAS  Google Scholar 

  11. Nishimoto N, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Azuma J (2009) Long-term safety and efficacy of tocilizumab, an anti-IL-6 receptor monoclonal antibody, in monotherapy, in patients with rheumatoid arthritis (the STREAM study): evidence of safety and efficacy in a 5-year extension study. Ann Rheum Dis 68:1580–1584

    Article  CAS  PubMed  Google Scholar 

  12. Bluestone J, St. Clair E, Turka L (2006) CTLA4Ig: bridging the basic immunology with clinical application. Immunity 24:233–238

    Article  CAS  PubMed  Google Scholar 

  13. Cron RQ (2005) A signal achievement in the treatment of arthritis [editorial]. Arthritis Rheum 52:2229–2232

    Article  CAS  PubMed  Google Scholar 

  14. Langford CA, Cuthbertson D, Ytterberg SR, Khalidi N, Monach PA, Carette S, Seo P, Moreland LW, Weisman M, Koening CL, Sreih AG, Spiera R, McAlear C, Warrington KJ, Pagnoux C, McKinnon K, Forbess LJ, Hoffman GS, Borchin R, Krischer JP, Merkel PA, Vasculitis Clinical Research Consortium (2017) A randomized, double-blind trial of abatacept (CTLA-4Ig) for the treatment of Takayasu arteritis. Arthritis Rheumatol 69(4):846–853

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO III, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JMW, Hobbs K, Huizinga TWJ, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Ménard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovský J, Wolfe F, Hawker G (2010) Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 62:2569–2581

    Article  Google Scholar 

  16. Sakpal TV (2010) Sample size estimation in clinical trial. Perspect Clin Res 1(2):67–69

    PubMed  PubMed Central  Google Scholar 

  17. Prevoo ML, van’t Hof MA, Kuper HH et al (1995) 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 38(1):44–48

    Article  CAS  PubMed  Google Scholar 

  18. Kubo S, Nakayamada S, Nakano K et al (2015) Comparison of the efficacies of abatacept and tocilizumab in patients with rheumatoid arthritis by propensity score matching. Ann Rheum Dis. https://doi.org/10.1136/annrheumdis-207784

  19. Pascart T, Philippe P, Drumez E, Deprez X, Cortet B, Duhamel A, Houvenagel E, Flipo RM (2016) Comparative efficacy of tocilizumab, abatacept and rituximab after non-TNF inhibitor failure: results from a multicenter study. Int J Rheum Dis 19(11):1093–1102

    Article  CAS  PubMed  Google Scholar 

  20. Jones G, Ding C (2010) Tocilizumab: a review of its safety and efficacy in rheumatoid arthritis. Clin Med Insights Arthritis Musculoskelet Disord 3:81–89

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. King-Konert C, von Hinüber U, Richter C et al (2016) ROUTINE—a prospective, multicenter, non-interventional, observational study to evaluate the safety and effectiveness of intravenous tocilizumab for the treatment of active rheumatoid arthritis in daily practice in Germany. Rheumatology 55:624–635

    Article  CAS  Google Scholar 

  22. Schiff M, Poncet C, Le Bars M (2010) Efficacy and safety of abatacept therapy for rheumatoid arthritis in routine clinical practice. Int J Clin Rheumatol 5(5):581–591

    Article  CAS  Google Scholar 

  23. Leffers HC, Ostergaard M, Glintborg B, Krogh NS et al (2011) Efficacy of abatacept and tocilizumab in patients with rheumatoid arthritis treated in clinical practice: results from the nationwide Danish DANBIO registry. Ann Rheum Dis 70(7):1216–1222

    Article  CAS  PubMed  Google Scholar 

  24. Hirabara S, Takahashi N, Fukaya N, Hiroyuki H et al (2014) Clinical efficacy of abatacept, tocilizumab, and etanercept in Japanese rheumatoid arthritis patients with inadequate response to anti-TNF monoclonal antibodies. Clin Rheumatol 33:1247–1254

    Article  PubMed  PubMed Central  Google Scholar 

  25. Emery P, Keystone E, Tony HP, Cantagrel A, van Vollenhoven R, Sanchez A, Alecock E, Lee J, Kremer J (2008) IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicenter randomized placebo-controlled trial. Ann Rheum Dis 67(11):1516–1523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Genovese MC, Schiff M, Luggen M, Becker JC et al (2008) Efficacy and safety of the selective co-stimulation modulator abatacept following 2 years of treatment in patients with rheumatoid arthritis and an inadequate response to anti-tumour necrosis factor therapy. Ann Rheum Dis 67(4):547–554

    Article  CAS  PubMed  Google Scholar 

  27. Schiff M, Pritchard C, Huffstutter JE, Rodriguez-Valverde V, Durez P, Zhou X, Li T, Bahrt K, Kelly S, le Bars M, Genovese MC (2009) The 6-month safety and efficacy of abatacept in patients with rheumatoid arthritis who underwent a washout after anti-tumour necrosis factor therapy or were directly switched to abatacept: the ARRIVE trial. Ann Rheum Dis 68:1708–1714

    Article  CAS  PubMed  Google Scholar 

  28. Westhovens R, Kremer JM, Emery P, Russell AS, Alten R, Barré E, Dougados M (2014) Long-term safety and efficacy of abatacept in patients with rheumatoid arthritis and an inadequate response to methotrexate: a 7-year extended study. Clin Exp Rheumatol 32:553–562

    PubMed  Google Scholar 

  29. Gottenberg JE, Morel J, Constantin A et al (2016) Long-term registry data in 4498 patients with rheumatoid arthritis indicate a similar safety but a different drug retention between abatacept, rituximab and tocilizumab. Arthr Rheumatol. 68(Suppl 10):2550–2553

    Google Scholar 

  30. Gottenberg JE, Morel J, Constantin A et al (2016) Similar rates of death, serious infections, cancers, major cardiovascular events in patients treated with abatacept, rituximab and tocilizumab: long-term registry data in 4498 patients with rheumatoid arthritis. Arthr Rheumatol 68(Suppl 10):3536–3537

    Google Scholar 

  31. Jones G, Sebba A, Gu J, Lowenstein MB, Calvo A, Gomez-Reino JJ, Siri DA, Tomsic M, Alecock E, Woodworth T, Genovese MC (2010) Comparison of TCZ monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis 69:88–96

    Article  CAS  PubMed  Google Scholar 

  32. Choy E, Sattar N (2009) Interpreting lipid levels in the context of high-grade inflammatory states with a focus on rheumatoid arthritis: a challenge to conventional cardiovascular risk actions. Ann Rheum Dis 68:460–469

    Article  CAS  PubMed  Google Scholar 

  33. Kremer JM, van Vollenhoven RF, Ridley DJ et al (2008) Relationship between patient characteristics and the development of serious infections in patients receiving tocilizumab: results from long-term extension studies with a follow-up duration of 1.5 years. Arthritis Rheum 58:S783–S784

    Google Scholar 

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Authors and Affiliations

  1. Physical Medicine, Rheumatology and Rehabilitation Department, Tanta University, El-Giesh Street, Tanta, 31111, Egypt

    Samah Hamdy Elmedany

  2. Physical Medicine, Rheumatology and Rehabilitation Department, Suez Canal University, Ismailia, Egypt

    Aly Elsayed Mohamed

  3. Rheumatology & Rehabilitation Department, Faculty of Medicine, Zagazig University, University Street, Zagazig, 44519, Egypt

    Sahar Mahfouz Abdel Galil

  4. Medicine Department, College of Medicine, Umm Al-Qura University, El-Abdia, Makkah province, 21955, Saudi Arabia

    Sahar Mahfouz Abdel Galil

Authors
  1. Samah Hamdy Elmedany
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  2. Aly Elsayed Mohamed
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  3. Sahar Mahfouz Abdel Galil
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Correspondence to Sahar Mahfouz Abdel Galil.

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Ethical approval

Our study was approved according to the local ethical committee inside all hospitals that participated in this study. All selected patients have given written informed consents, before being enrolled in the study.

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Elmedany, S.H., Mohamed, A.E. & Galil, S.M.A. Efficacy and safety profile of intravenous tocilizumab versus intravenous abatacept in treating female Saudi Arabian patients with active moderate-to-severe rheumatoid arthritis. Clin Rheumatol 38, 2109–2117 (2019). https://doi.org/10.1007/s10067-019-04508-2

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  • DOI: https://doi.org/10.1007/s10067-019-04508-2

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