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Comparative Immunogenicity of TNF Inhibitors: Impact on Clinical Efficacy and Tolerability in the Management of Autoimmune Diseases. A Systematic Review and Meta-Analysis

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Abstract

Background

Tumor necrosis factor (TNF) inhibitors are a mainstay in the treatment of rheumatoid arthritis (RA), as well as in the management of spondyloarthritis (SpA) and inflammatory bowel diseases (IBD). Unfortunately, a portion of patients taking these drugs require escalating doses within the approved label to achieve response, while others lose response altogether. This may be due to the development of antibodies against TNFi agents.

Objectives

Our objective was to examine the immunogenicity of TNF inhibitors (adalimumab, infliximab, etanercept, golimumab, and certolizumab) in RA, SpA, and IBD, and to examine the potential effect of anti-drug antibodies (ADABs) on the loss of clinical response through a systematic literature review and meta-analysis.

Methods

We conducted a comprehensive literature search using three databases (PubMed, Web of Science, and the Cochrane library) to identify studies examining the immunogenicity of TNF inhibitors in autoimmune diseases between 1966 and 31 December 2013. Inclusion criteria required that studies be in English, be randomized controlled trials, observational studies, or case reports involving more than five patients, and that the patients be aged 18 years or older. Studies were excluded if they were strictly genetic with no clinical correlate, if the patients had concomitant cancer within 5 years of the study, or if the patients had a renal disease requiring dialysis. Double extraction was followed by a third extraction if needed. Consensus was reached by discussion when disagreements occurred. Random-effect models were generated for the meta-analysis of 68 studies to estimate the odds ratio (OR) of the ADAB effects on TNF inhibitor response. Regression analysis was used to compare among the drugs and diseases.

Results

A total of 68 studies (14,651 patients) matched the inclusion/exclusion criteria. Overall, the cumulative incidence of ADABs was 12.7 % [95 % confidence interval (CI) 9.5–16.7]. Of the patients using infliximab, 25.3 % (95 % CI 19.5–32.3) developed ADABs compared with 14.1 % (95 % CI 8.6–22.3) using adalimumab, 6.9 % (95 % CI 3.4–13.5) for certolizumab, 3.8 % (95 % CI 2.1–6.6) for golimumab, and 1.2 % (95 % CI 0.4–3.8) for etanercept. ADABs reduced the odds of clinical response by 67 % overall, although most of the data were derived from articles involving infliximab (nine) and adalimumab (eight). The summary effect for infliximab yielded an estimated OR (with ADABs vs. without) of 0.42 (95 % CI 0.30–0.58); the summary effect for adalimumab yielded an estimated OR (as above) of 0.13 (95 % CI 0.08–0.22); and the OR (as above) for golimumab was 0.42 (95 % CI 0.22–0.81). All figures were statistically significant. ADABS decreased response by 27 % in RA and 18 % in SpA, both of which were statistically significant. However, the effect of ADABS on response was not statistically significant for IBD when we only included the studies that reported the duration of exposure in the regression analysis. The use of concomitant immunosuppressives (methotrexate, 6-mercaptopurine, azathioprine, and others) reduced the odds of ADAB formation in all patients by 74 %. The OR for risk with immunosuppressives versus without was 0.26 (95 % CI 0.21–0.32).

Conclusion

ADABs developed in 13 % of patients. All five TNF inhibitors were associated with ADABs, but to varying degrees depending on the specific TNF inhibitor and the disease. ADABs are associated with reduced clinical response and an increased incidence of infusion reactions and injection site reactions. Concomitant use of immunosuppressives can reduce ADAB formation.

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References

  1. Sandborn WJ, et al. Adalimumab for maintenance treatment of Crohn’s disease: results of the CLASSIC II trial. Gut. 2007;56(9):1232–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Yoo DH, et al. A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study. Ann Rheum Dis. 2013;72(10):1613–20.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Lichtenstein GR, et al. Clinical trial: benefits and risks of immunomodulators and maintenance infliximab for IBD-subgroup analyses across four randomized trials. Aliment Pharmacol Ther. 2009;30(3):210–26.

    Article  CAS  PubMed  Google Scholar 

  4. Bartelds GM, et al. Development of antidrug antibodies against adalimumab and association with disease activity and treatment failure during long-term follow-up. JAMA. 2011;305(14):1460–8.

    Article  CAS  PubMed  Google Scholar 

  5. de Vries MK, et al. Immunogenicity does not influence treatment with etanercept in patients with ankylosing spondylitis. Ann Rheum Dis. 2009;68(4):531–5.

    Article  PubMed  Google Scholar 

  6. Radstake TR, et al. Formation of antibodies against infliximab and adalimumab strongly correlates with functional drug levels and clinical responses in rheumatoid arthritis. Ann Rheum Dis. 2009;68(11):1739–45.

    Article  CAS  PubMed  Google Scholar 

  7. Baert F, et al. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn’s disease. N Engl J Med. 2003;348(7):601–8.

    Article  CAS  PubMed  Google Scholar 

  8. Seow CH, et al. Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis. Gut. 2010;59(1):49–54.

    Article  CAS  PubMed  Google Scholar 

  9. Westhovens R, et al. A phase I study assessing the safety, clinical response, and pharmacokinetics of an experimental infliximab formulation for subcutaneous or intramuscular administration in patients with rheumatoid arthritis. J Rheumatol. 2006;33(5):847–53.

    CAS  PubMed  Google Scholar 

  10. Bendtzen K, et al. Individualized monitoring of drug bioavailability and immunogenicity in rheumatoid arthritis patients treated with the tumor necrosis factor alpha inhibitor infliximab. Arthritis Rheum. 2006;54(12):3782–9.

    Article  CAS  PubMed  Google Scholar 

  11. Wolbink GJ, et al. Development of antiinfliximab antibodies and relationship to clinical response in patients with rheumatoid arthritis. Arthritis Rheum. 2006;54(3):711–5.

    Article  PubMed  Google Scholar 

  12. Farrell RJ, et al. Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn’s disease: a randomized controlled trial. Gastroenterology. 2003;124(4):917–24.

    Article  CAS  PubMed  Google Scholar 

  13. Vermeire S, et al. Effectiveness of concomitant immunosuppressive therapy in suppressing the formation of antibodies to infliximab in Crohn’s disease. Gut. 2007;56(9):1226–31.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Imaeda H, et al. Development of a new immunoassay for the accurate determination of anti-infliximab antibodies in inflammatory bowel disease. J Gastroenterol. 2012;47(2):136–43.

    Article  CAS  PubMed  Google Scholar 

  15. Ben-Horin S, et al. The immunogenic part of infliximab is the F(ab’)2, but measuring antibodies to the intact infliximab molecule is more clinically useful. Gut. 2011;60(1):41–8.

    Article  CAS  PubMed  Google Scholar 

  16. Plasencia C, et al. Influence of immunogenicity on the efficacy of longterm treatment of spondyloarthritis with infliximab. Ann Rheum Dis. 2012;71(12):1955–60.

    Article  CAS  PubMed  Google Scholar 

  17. Abe T, et al. A multicenter, double-blind, randomized, placebo controlled trial of infliximab combined with low dose methotrexate in Japanese patients with rheumatoid arthritis. J Rheumatol. 2006;33(1):37–44.

    CAS  PubMed  Google Scholar 

  18. Finckh A, et al. Influence of anti-infliximab antibodies and residual infliximab concentrations on the occurrence of acquired drug resistance to infliximab in rheumatoid arthritis patients. Joint Bone Spine. 2010;77(4):313–8.

    Article  CAS  PubMed  Google Scholar 

  19. de Vries MK, et al. Decreased clinical response to infliximab in ankylosing spondylitis is correlated with anti-infliximab formation. Ann Rheum Dis. 2007;66(9):1252–4.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Steenholdt C, et al. Cut-off levels and diagnostic accuracy of infliximab trough levels and anti-infliximab antibodies in Crohn’s disease. Scand J Gastroenterol. 2011;46(3):310–8.

    Article  CAS  PubMed  Google Scholar 

  21. Van den Bemt BJ, et al. Sustained effect after lowering high-dose infliximab in patients with rheumatoid arthritis: a prospective dose titration study. Ann Rheum Dis. 2008;67(12):1697–701.

    Article  PubMed  Google Scholar 

  22. van der Maas A, et al. Low infliximab serum trough levels and anti-infliximab antibodies are prevalent in rheumatoid arthritis patients treated with infliximab in daily clinical practice: results of an observational cohort study. BMC Musculoskelet Disord. 2012;13:184.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Steenholdt C, et al. Clinical implications of variations in anti-infliximab antibody levels in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2012;18(12):2209–17.

    Article  PubMed  Google Scholar 

  24. Ainsworth MA, et al. Tumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn’s disease. Am J Gastroenterol. 2008;103(4):944–8.

    Article  CAS  PubMed  Google Scholar 

  25. Kremer J, et al. Golimumab, a new human anti-tumor necrosis factor alpha antibody, administered intravenously in patients with active rheumatoid arthritis: forty-eight-week efficacy and safety results of a phase III randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2010;62(4):917–28.

  26. Inman RD, et al. Efficacy and safety of golimumab in patients with ankylosing spondylitis: results of a randomized, double-blind, placebo-controlled, phase III trial. Arthritis Rheum. 2008;58(11):3402–12.

    Article  CAS  PubMed  Google Scholar 

  27. Kavanaugh A, et al. Golimumab, a new human tumor necrosis factor alpha antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: twenty-four-week efficacy and safety results of a randomized, placebo-controlled study. Arthritis Rheum. 2009;60(4):976–86.

    Article  CAS  PubMed  Google Scholar 

  28. Kavanaugh A, et al. Golimumab in psoriatic arthritis: one-year clinical efficacy, radiographic, and safety results from a phase III, randomized, placebo-controlled trial. Arthritis Rheum. 2012;64(8):2504–17.

    Article  CAS  PubMed  Google Scholar 

  29. Keystone EC, et al. Golimumab, a human antibody to tumour necrosis factor alpha given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study. Ann Rheum Dis. 2009;68(6):789–96.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Smolen JS, et al. Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial. Lancet. 2009;374(9685):210–21.

    Article  CAS  PubMed  Google Scholar 

  31. Kay J, et al. Golimumab in patients with active rheumatoid arthritis despite treatment with methotrexate: a randomized, double-blind, placebo-controlled, dose-ranging study. Arthritis Rheum. 2008;58(4):964–75.

    Article  CAS  PubMed  Google Scholar 

  32. Emery P, et al. Golimumab, a human anti-tumor necrosis factor alpha monoclonal antibody, injected subcutaneously every four weeks in methotrexate-naive patients with active rheumatoid arthritis: twenty-four-week results of a phase III, multicenter, randomized, double-blind, placebo-controlled study of golimumab before methotrexate as first-line therapy for early-onset rheumatoid arthritis. Arthritis Rheum. 2009;60(8):2272–83.

    Article  CAS  PubMed  Google Scholar 

  33. Zhuang Y, et al. Golimumab pharmacokinetics after repeated subcutaneous and intravenous administrations in patients with rheumatoid arthritis and the effect of concomitant methotrexate: an open-label, randomized study. Clin Ther. 2012;34(1):77–90.

    Article  CAS  PubMed  Google Scholar 

  34. Tanaka Y, et al. Golimumab in combination with methotrexate in Japanese patients with active rheumatoid arthritis: results of the GO-FORTH study. Ann Rheum Dis. 2012;71(6):817–24.

  35. Weinblatt ME, et al. Intravenous golimumab is effective in patients with active rheumatoid arthritis despite methotrexate therapy with responses as early as week 2: results of the phase 3, randomised, multicentre, double-blind, placebo-controlled GO-FURTHER trial. Ann Rheum Dis. 2013;72(3):381–9.

    Article  CAS  PubMed  Google Scholar 

  36. Dore RK, et al. The immunogenicity, safety, and efficacy of etanercept liquid administered once weekly in patients with rheumatoid arthritis. Clin Exp Rheumatol. 2007;25(1):40–6.

    CAS  PubMed  Google Scholar 

  37. Jamnitski A, et al. Patients non-responding to etanercept obtain lower etanercept concentrations compared with responding patients. Ann Rheum Dis. 2011;71(1):88–91.

    Article  PubMed  Google Scholar 

  38. Mease PJ, et al. Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression. Arthritis Rheum. 2004;50(7):2264–72.

    Article  CAS  PubMed  Google Scholar 

  39. Weinblatt ME, et al. Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum. 2003;48(1):35–45.

    Article  CAS  PubMed  Google Scholar 

  40. Choy E, 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.

    Article  CAS  Google Scholar 

  41. Fleischmann R, 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;6:805–11.

    Article  Google Scholar 

  42. Smolen J, et al. Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis: the RAPID 2 study. A randomised controlled trail. Ann Rheum Dis. 2009;68(6):797–804.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Schreiber S, et al. (2007). Maintenance therapy with certolizumab pegol for Crohn’s disease. N Engl J Med. 2007;357(3):239–50.

  44. Sandborn WJ, 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 

  45. Keystone E, 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.

    Article  CAS  PubMed  Google Scholar 

  46. van Schouwenburg PA, et al. Long-term measurement of anti-adalimumab using pH-shift-anti-idiotype antigen binding test shows predictive value and transient antibody formation. Ann Rheum Dis. 2013;72(10):1680–6.

    Article  PubMed  Google Scholar 

  47. Bartelds GM, et al. Anti-infliximab and anti-adalimumab antibodies in relation to response to adalimumab in infliximab switchers and anti-tumour necrosis factor naive patients: a cohort study. Ann Rheum Dis. 2010;69(5):817–21.

    Article  CAS  PubMed  Google Scholar 

  48. West RL, et al. Immunogenicity negatively influences the outcome of adalimumab treatment in Crohn’s disease. Aliment Pharmacol Ther. 2008;28(9):1122–6.

    Article  CAS  PubMed  Google Scholar 

  49. Karmiris K, et al. Influence of trough serum levels and immunogenicity on long-term outcome of adalimumab therapy in Crohn’s disease. Gastroenterology. 2009;137(5):1628–40.

    Article  CAS  PubMed  Google Scholar 

  50. de Vries MK, et al. Decreased clinical response to adalimumab in ankylosing spondylitis is associated with antibody formation. Ann Rheum Dis. 2009;68(11):1787–8.

    Article  PubMed  Google Scholar 

  51. Bartelds GM, et al. Clinical response to adalimumab: relationship to anti-adalimumab antibodies and serum adalimumab concentrations in rheumatoid arthritis. Ann Rheum Dis. 2007;66(7):921–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. van Kuijk AW, et al. Relationship between the clinical response to adalimumab treatment and serum levels of adalimumab and anti-adalimumab antibodies in patients with psoriatic arthritis. Ann Rheum Dis. 2010;69(3):624–25.

  53. Garcês S, et al. The immunogenicity of anti-TNF therapy in immune-mediated inflammatory diseases: a systematic review of the literature with a meta-analysis. Ann Rheum Dis. 2012;72(12):1947–55.

    Article  PubMed  Google Scholar 

  54. Vincent FB, et al. Antidrug antibodies (ADAb) to tumour necrosis factor (TNF)-specific neutralising agents in chronic inflammatory diseases: a real issue, a clinical perspective. Ann Rheum Dis. 2013;72(2):165–78.

    Article  CAS  PubMed  Google Scholar 

  55. van Schouwenburg PA, et al. A novel method for the detection of antibodies to adalimumab in the presence of drug reveals “hidden” immunogenicity in rheumatoid arthritis patients. J Immunol Methods. 2010;362(1–2):82–8.

    Article  PubMed  Google Scholar 

  56. Atzeni F, et al. Immunogenicity and autoimmunity during anti-TNF therapy. Autoimmun Rev. 2013;12(7):703–8.

    Article  CAS  PubMed  Google Scholar 

  57. Alawadhi A, et al. The effect of neutralizing antibodies on the sustainable efficacy of biologic therapies: what’s in it for African and Middle Eastern rheumatologists. Clin Rheumatol. 2012;31(9):1281–7.

    Article  PubMed  Google Scholar 

  58. Ordas I, et al. Anti-TNF monoclonal antibodies in inflammatory bowel disease: pharmacokinetics-based dosing paradigms. Clin Pharmacol Ther. 2012;91(4):635–46.

    Article  CAS  PubMed  Google Scholar 

  59. Emi Aikawa N, et al. Immunogenicity of anti-TNF-alpha agents in autoimmune diseases. Clin Rev Allergy Immunol. 2010;38(2–3):82–9.

    Article  CAS  PubMed  Google Scholar 

  60. van Schouwenburg PA, et al. Immunogenicity of anti-TNF biologic therapies for rheumatoid arthritis. Nat Rev Rheumatol. 2013;9(3):164–72.

    Article  PubMed  Google Scholar 

  61. Clark M. Antibody humanization: a case of the ‘Emperor’s new clothes’? Immunol Today. 2000;21(8):397–402.

    Article  CAS  PubMed  Google Scholar 

  62. Pendley C, et al. Immunogenicity of therapeutic monoclonal antibodies. Curr Opin Mol Ther. 2003;5(2):172–9.

    CAS  PubMed  Google Scholar 

  63. Bartelds GM, et al. Anti-adalimumab antibodies in rheumatoid arthritis patients are associated with interleukin-10 gene polymorphisms. Arthritis Rheum. 2009;60(8):2541–2.

    Article  CAS  PubMed  Google Scholar 

  64. Goss SL, et al. Adalimumab and methotrexate pharmacokinetics following combination therapy with different methotrexate doses in methotrexate and biologic-naïve rheumatoid arthritis patients: Concerto Study. Arthritis Rheum. 2013;65(Suppl 10):483.

    Google Scholar 

  65. Burmester GR, et al. Efficacy and safety of ascending methotrexate dose in combination with adalimumab: the randomized CONCERTO trial. Ann Rheum Dis. 2014. doi:10.1136/annrheumdis-2013-204769.

    Google Scholar 

  66. Jamnitski A, et al. The presence or absence of antibodies to infliximab or adalimumab determines the outcome of switching to etanercept. Ann Rheum Dis. 2011;70(2):284–8.

    Article  CAS  PubMed  Google Scholar 

  67. Afif W, et al. Clinical utility of measuring infl iximab and human anti-chimeric antibody concentrations in patients with inflammatory bowel disease. Am J Gastroenterol. 2010;105(5):1133–9.

    Article  CAS  PubMed  Google Scholar 

  68. Bender NK, et al. Immunogenicity, efficacy and adverse events of adalimumab in RA patients. Rheumatol Int. 2007;27(3):269–74.

    Article  CAS  PubMed  Google Scholar 

  69. Colombel JF, et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med. 2010;362(15):1383–95.

    Article  CAS  PubMed  Google Scholar 

  70. Ducourau E, et al. Antibodies toward infliximab are associated with low infliximab concentration at treatment initiation and poor infliximab maintenance in rheumatic diseases. Arthritis Res Ther. 2011;13(3):R105.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  71. Hanauer SB, et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn’s disease: the CLASSIC-I trial. Gastroenterology. 2006;130(2):323–33.

    Article  CAS  PubMed  Google Scholar 

  72. Hanauer SB, et al. Incidence and importance of antibody responses to infliximab after maintenance or episodic treatment in Crohn’s disease. Clin Gastroenterol Hepatol. 2004;2(7):542–53.

    Article  CAS  PubMed  Google Scholar 

  73. Haraoui B, et al. Anti-infliximab antibodies in patients with rheumatoid arthritis who require higher doses of infliximab to achieve or maintain a clinical response. J Rheumatol. 2006;33(1):31–6.

    CAS  PubMed  Google Scholar 

  74. Keystone EC, et al. Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheum. 2004;50(5):1400–11.

    Article  CAS  PubMed  Google Scholar 

  75. Keystone EC, et al. Once-weekly administration of 50 mg etanercept in patients with active rheumatoid arthritis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2004;50(2):353–63.

    Article  CAS  PubMed  Google Scholar 

  76. Korswagen LA, et al. Venous and arterial thromboembolic events in adalimumab-treated patients with antiadalimumab antibodies: a case series and cohort study. Arthritis Rheum. 2011;63(4):877–83.

    Article  CAS  PubMed  Google Scholar 

  77. Maini RN, et al. Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum. 1998;41(9):1552–63.

    Article  CAS  PubMed  Google Scholar 

  78. Park W, et al. A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study. Ann Rheum Dis. 2013;72(10):1605–12.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  79. Pascual-Salcedo D, et al. Influence of immunogenicity on the efficacy of long-term treatment with infliximab in rheumatoid arthritis. Rheumatology (Oxford). 2011;50(8):1445–14452.

    Article  CAS  Google Scholar 

  80. Sandborn WJ, et al. Certolizumab pegol for active Crohn’s disease: a placebo-controlled, randomized trial. Clin Gastroenterol Hepatol. 2011;9(8):670–8.e3.

  81. Takeuchi T, et al. Golimumab monotherapy in Japanese patients with active rheumatoid arthritis despite prior treatment with disease-modifying antirheumatic drugs: results of the phase 2/3, multicentre, randomised, double-blind, placebo-controlled GO-MONO study through 24 weeks. Ann Rheum Dis. 2013;72(9):1488–95.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  82. Targan SR, et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn’s disease. Crohn’s Disease cA2 Study Group. N Engl J Med. 1997;337(15):1029–35.

    Article  CAS  PubMed  Google Scholar 

  83. van de Putte LB, et al. Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed. Ann Rheum Dis. 2004;63(5):508–16.

    Article  PubMed Central  PubMed  Google Scholar 

  84. Armijo-Olivo S, et al. Assessment of study quality for systematic reviews: a comparison of the Cochrane Collaboration Risk of Bias Tool and the Effective Public Health Practice Project Quality Assessment Tool: methodological research. J Eval Clin Pract. 2012;18(1):12–8.

    Article  PubMed  Google Scholar 

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Correspondence to Sarah S. Thomas or Daniel E. Furst.

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Sarah Thomas, Nabeel Borazan, Nashla Barroso, Lewei Duan, Sara Taroumian, Benjamin Kretzmann, Ricardo Bardales, David Elashoff, and Sitaram Vangala have no conflicts to declare. Dr. Daniel Furst has received grant/research support from AbbVie, Actelion, Amgen, BMS, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, and UCB and is a consultant for AbbVie, Actelion, Amgen, BMS, Cytori, Janssen, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, and UCB; he is also on the speaker’s bureau (CME only) for AbbVie, Actelion, and UCB.

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S. S Thomas and N. Borazan contributed equally to this work.

Appendices

Appendix 1

(“Arthritis, Rheumatoid”[MeSH Terms] OR (Rheumatoid [all fields] AND arthriti* [all fields]) OR “caplan syndrome” [all fields] OR (“felty syndrome” [all fields] OR “felty’s syndrome” [all fields]) OR (“adult” [all fields] AND (“still disease” [all fields] OR “still’s disease” [all fields])) OR “Crohn Disease”[MeSH Terms] OR (crohn [all fields] OR crohn’s [all fields]) OR ((colitis [all fields] OR enteritis [all fields] OR ileitis [all fields]) AND (regional [all fields] OR granulomatous [all fields])) OR ((regional [all fields] OR terminal [all fields]) AND ileitis [all fields]) OR (“Spondylitis, Ankylosing”[Mesh] OR “ankylosing spondylitis” [all fields] OR “Bechterew Disease” [all fields] OR “Marie Struempell Disease” [all fields] OR “Marie Strumpell Disease” [all fields]) OR (“Arthritis, Psoriatic”[Mesh] OR “psoriatic arthritis”[all fields] OR (psoriasis [all fields] AND arthritis [all fields])) OR (“Colitis, Ulcerative”[Mesh] OR (ulcerative [all fields] AND colitis [all fields]))) AND ((cimzia [all fields] OR certolizumabpegol [all fields] OR cdp870[All Fields] OR certolizumabpegol [Supplementary Concept]) OR (enbrel [all fields] OR etanercept [all fields] OR TNFR-Fc fusion protein [All Fields] OR TNFR-Fc fusion protein [Supplementary Concept]) OR (humira [all fields] OR adalimumab [all fields] OR adalimumab [Supplementary Concept]) OR (remicade [all fields] OR infliximab [all fields] OR infliximab [Supplementary Concept] OR mab ca2 [All Fields] OR monoclonal antibody ca2[All Fields]) OR (simponi [all fields] OR golimumab [all fields] OR golimumab [Supplementary Concept] OR cnto-148[All Fields])) AND (immunogenic* [all fields] OR “antibody formation” [all fields] OR Antibody Formation [MeSH terms] OR “response failure” [all fields] OR bioavailability OR biological availability OR “Biological Availability”[MeSH Terms] OR “drug tolerance”[all fields] OR Drug Tolerance [MeSH Terms] OR “treatment outcome” [all fields] OR Treatment Outcome [MeSH Terms]) AND ((“Randomized Controlled Trial” [ptyp] OR “Controlled Clinical Trial” [ptyp] OR “Multicenter Study” [ptyp] OR “randomized”[tiab] OR “randomised”[tiab] OR “placebo”[tiab] OR “randomly”[tiab] OR “trial”[tiab] OR “randomized controlled trials as topic”[MeSH Terms]OR “random allocation”[MeSH Terms] OR “double-blind method”[MeSH Terms] OR “double-blind”[text word] OR “single-blind method”[MeSH Terms] OR “single-blind” [text word] NOT (“Meta-Analysis” [ptyp]OR “Review” [ptyp] OR “Letter” [ptyp] OR “Editorial” [ptyp])) AND (“1966/01/01”[PDat] : “2012/12/1”[PDat] AND English[lang]) NOT (animals[mh] NOT human[mh])).

Appendix 2: Quality Assessment Tool for Quantitative Studies

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Thomas, S.S., Borazan, N., Barroso, N. et al. Comparative Immunogenicity of TNF Inhibitors: Impact on Clinical Efficacy and Tolerability in the Management of Autoimmune Diseases. A Systematic Review and Meta-Analysis. BioDrugs 29, 241–258 (2015). https://doi.org/10.1007/s40259-015-0134-5

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  • DOI: https://doi.org/10.1007/s40259-015-0134-5

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